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11
SPECIA L EDITION ON
CLINICA L VIROLOGY
ISSUE2 | ISSN: VOLUME II | JAN 2020
INFECTION CONTROLTRENDS
NEWSLETTER
Publication of Infection Control Academy of India
1st
Ever
PG
Diploma in
Infection
Prevention &
Control in India
2
FROM EDITORS
Dear Colleague,
Hope the New Year and the new decade has started well for you and your
dear ones.
On behalf of IFCAI, ICT Newsletter, and The IPC News teams wish "Infection
Preventionists (IP)" around the world and their families a very happy,
healthy and prosperous 2020.
ICT Newsletter launched in 2018 as IFCAI broader mission to create the
capacity of IP's in India and other LRC. We aim to improve healthcare by
reducing the risk of infection . The team at Academy is thankful to all its
members, associates, volunteers, supporters and readers of its publications
from all over the world for constant feedback, support and encouragement.
IFCAI publishing seeks to address the information problem in infection
Prevention and Control (IPC) by creating an open vehicle and being a vibrant
discussion forum. We envisage an open, democratic and inclusive forum that
brings together and addresses a large number of aspirants and practitioners
of IPC. We wish to deliver content relevant for all IPC stakeholders including
policymakers, NGO's, Governments specifically in LRC.
Past year had been quite eventful we could see a lot of activity: we forged
relations with professional IP associations abroad, we broadened our reach
within India, our publishing activity has seen multi-fold increase through
digital strategies etc. While all this is satisfying, the most memorable event
happened towards fag end of 2019: the much awaited PG diploma in
Infection Prevention and Control was notified by University of Hyderabad in
collaboration with Infection Control Academy. First ever such course to be
offered by a university in Asia, Africa, ME and other developing nations will
remain a historic milestone in our journey towards "preventing all
preventable infections withing healthcare".
The edition which is now in your hands is brought with a focus on emerging
and re-emerging Viral Infections. As you would have noticed the design,
navigation and blend of offline/online elements are introduced in this edition
for pleasurable reading experience. I am sure like earlier editions this will
also find a special place among your upskilling resources. We would
appreciate your feedback enabling us to constantly work on improvements.
Please send your comments, suggestions, views to secretariat@ifcai.in
At the turn of the decade, ICT Newsletter is rededicating itself to the mission
of spreading IPC knowledge and shall look forward to the much deeper and
meaningful collaboration. On behalf of the entire team wishing all again a
Very Happy 2020.
Dr Ranga Reddy Burri
Dr TV Rao
Dr Sukanya
Dr Srinivas Hiresave
Dr Shamanna
3
ISSUE2 VOLUMEII | JAN 2020
EDITORIAL TEAM
Dr. Ranga Reddy Burri is Health policy enthusiast focused on public health awareness, education and
training. Dr. Reddy is Physician, Public Health specialist & Social Entrepreneur with interest in business
verticals of high social impact. He graduated from Minsk Government Medical Institute, Belarus with
MD (Physician) degree; subsequently he did his PG Diploma in management from Pondicherry
University and Advanced Management from IESE, Barcelona, Spain with specialization in Strategy &
Business Development.
Dr. Reddy is the founder trustee of Infection Control Academy of India (IFCAI). The organization is a
result of his leadership skills, knowledge and experience gained from working in both domestic and
international MNCs. Yet, the Academy?s most valuable strength lies in the strong sense of empathy for
humans and their health imparted by Dr. Reddy and his colleague trustees. His current responsibility
includes leading Sanmed Healthcare, a startup with world class manufacturing capabilities in external
preparations. He supports several non-profit organizations in the capacity of adviser including Neelam
Rajasekhar Reddy Research Center for Social Progress, e-learning center of Hyderabad Central
University & Indian Institute of Public Health. His flair for entrepreneurship has led him to mentor
through imparting knowledge to NGO?s, startups & micro-small enterprises.
Dr. Ranga Reddy
President IFCAI and
Chief Editor ?Infection Control
Trends?
Email: dr.rangareddy@ifcai.in
Dr. T.V. Rao is a former Professor of Microbiology, Alumni of Andhra Medical College, Visakhapatnam
(Andhra Pradesh, India). His experiences in Zambia showed him how people lose their lives to
infections and how the lack of resources was a great challenge that practically forced patients to be
treated blindly.
His association with scientific microbiologists at ICMR (NICED Calcutta) taught him how all that we do is
not necessarily right and why it is essential to involve oneself in diagnostic laboratory conditions and
even bedside medicine.
His observation includes the seamless working of Darwin?s Theory in relation to microbes and how
they pose real challenges. He also believes it is time to rethink one?s role as Medical and Clinical
Microbiologists, especially during a time where it is necessary to understand that Antibiotics are not
magic bullets but soft weapons to destroy the progress of medicine. Dr. Rao has created content that
helps many in developing countries with a global following of 5 million.
Dr. T. V. Rao
Former Professor of Microbiology
Author, Mentor and Advisor
Editor ?Infection Control Trends?
Email: doctortvrao@gmail.com
Dr H Srinivasa has Academic career of more than 3 decades in teaching clinical microbiology for
MBBS, MD, BSc nursing at St. Johns Medical college: superannuated at the same institution
Bangalore in 2015.Subsequently Career as a Free Lance Consultant Microbiologist & Infection Control.
NABL assessor as well Actively involved in Infection Control Groups in several Fora with Dr Ranga
Reddy , Dr TV Rao which Is his current passion ,disseminating, sharing , and learning newer aspects of
Inf disease diagnosis and Control.
Dr. H Srinivasa
MD Medical Microbiology (AIIMS,
New Delhi 1981)
Editor ?Infection Control Trends?
4
ISSUE2 VOLUMEII | JAN 2020
Dr Sukanya Graduated from Bangalore Medical College (BMC) with MBBSand passed out as a rank
holder in MD Microbiology from Madras Medical College (MMC). Awarded PGDID-Infectious Diseases
by Medvarsity in collaboration with University of NSW, Sydney-Australia in 2017. Certified Infection
Control Consultant by the CBIC (APIC) in 2018. Over 13 years of experience in Laboratory Diagnostics,
Hospital Acquired Infection Prevention and Control, Good Antibiotic Prescription Practices, Infectious
Diseases Management, Research and Teaching. Was a Consultant Clinical Microbiologist, Infection
Control Officer, and Convener of Antibiotic Prescription Practices at Fortis Hospitals, BG Road,
Bangalore for over 9 years and formerly an Assistant Professor at M.S. Ramaiah Medical College and
Hospital, Bangalore for around 4years. Currently - Consultant for Mediknit ,Singapore which is a
healthcare start-up focused on learning and education for medical professionals and Associated with
the Care Institute of Health Sciences, Hyderabad for training programmes on Infection Control and
Prevention. Invited speaker in over 30 conferences, forums, and training programs Accolades for
outstanding contributions in JCI and NABH, NABL accreditations. Instrumental in leading the
organisation (Fortis) to win the prestigious AHMA Gold award APSIC Silver award for CSSD and the
CAHOCON awards Published several research articles and clinical case studies in peer-reviewed
national and international journals.
Dr. Sukanya Rengaswamy
MD, PGDID, CIC,
Technical Editor ?Infection Control
Trends?
Dr B.R. Shamanna completed his medical education from Karnataka Medical College, Hubli, and his
Doctoral studies (MD) in Community Medicine from the All India Institute of Medical Sciences, New
Delhi. He also holds a double Diplomate of the National Board in Maternal & Child Health as well as in
Social & Preventive Medicine. He completed his M.Sc. from University College London with distinction
in Community Eye Health. He served as a Senior Research Officer in the International Council for
Control of Iodine Deficiency Disorders (ICCIDD), a WHO-PAMM-UNICEF Organization and later as a
Senior Resident & Medical Officer, Primary Health Centre in Haryana. He is a visiting faculty to the
Masters in Public Health Eyecare at the London School of Hygiene and Tropical Medicine and an
Adjunct Faculty with the Public Health Foundation of India. He is on the ethics committee of the
Fernandez Hospital for Mother and Child in Hyderabad, Piramal Swasthya Management and Research
Institute and the L.V. Prasad Eye institute, Hyderabad and was instrumental in helping Indian Institute
of Public Health, Hyderabad institute its own IEC. Most recently he completed a prestigious fellowship
program and is designated as a PHLEADER through a NIH supported Public Health Leadership
Academy of Implementation Sciences at Emory University, Atlanta, Georgia, and USA. His interests are
Health & Welfare economics, Disability Inclusive Development, Education and teaching methods,
Implementation Research in Health Sciences, and Alternative opinions and Politics in Health Care. He
currently co-ordinates and helps deliver the Ph.D. Programme in Health Sciences from the University
of Hyderabad
Dr. Shamanna
School of Medical Sciences,
University of Hyderabad
Editor ?Infection Control Trends?
5
ISSUE2 VOLUMEII | JAN 2020
INDEX
VIRAL INFECTION IN ICU:A CONCISE REVIEW DR. MASOOD MOHAMMED 6
VIRAL INFECTION IN PEDIATRICS DR M VISHNUVARDHAN
REDDY
26
OLD AND NEW VACCINESFOR THE PREVENTION OF VIRAL
INFECTIONS
DR. RENU AVULA 34
QUIZ 40
AN ATTEMPT TO UNDERSTAND PATHOGENETIC MECHANISMSOF
HUMAN VIRAL DISEASES
DR H.SRINIVASA 50
ERADICATION OF SMALL POX ?-CAN IT RE-EMERGE?CAN WE
SUCCEED WITH OTHER VIRAL INFECTIONS
DR.T.V.RAO 54
ACADEMIC COMMUNICATION IN VIROLOGY DR.T.V.RAO 57
INFECTION CONTROL PRACTICESIN THE ERA OF EMERGING
VIRAL INFECTIONS
DR. UMABALA
PAMIDIMUKKALA
60
VACCINE HESITANCY: HEALTH AND ECONOMIC IMPACT DR RANGA REDDY BURRI 73
UPDATESIN VIROLOGY COMPILED BY DR SUKANYA RENGASWAMY 78
ANSWERSFOR QUIZ 80
INSTRUCTIONSFOR AUTHORS 81
6
Int roduct ion:
Since Reed et al discovered yellow fever as the first viral human illness in 1901, many
viral pathogens and associated disease have been identified. Though most of the viral
infections are being treated in an outpatient clinic few cases among them get admitted to the
hospital and very few to intensive care unit (ICU). Thanks to recent diagnostic studies which not
only detect them rapidly but also are easy to perform and universally and easily available at an
affordable cost. Because of the availability of these rapid diagnostic tests prevalence of viral
infection has been increasing both in community as well in hospitals(1). Few of these viruses
like Avian Influenza A H7N9 and a novel corona virus, Middle East Respiratory syndrome corona
Virus (MERS-coV) are associated with high morbidity and mortality(2, 3). In this review we are
going to discuss about the characteristics of virus in general and discuss some common viral
infections which lead to ICU admission and also those infections which are ICU acquired in a
syndromic approach and their management.
Charact erist ics of viruses: (Fig 1)
Viruses are tiny (20 to 300 nm) living forms that reproduce inside the cell of a
living host. They consist of DNA or RNA (genetic material) based on which they are classified,
which is contained in a capsid, a polymer of capsomere made of one or two viral protein
molecules. The genetic material and capsid are called nucleocapsid which have a specific
symmetry, either icosahedral, helical (helical symmetry is formed only by RNA viruses) or
complex. capsid contains either DNA or RNA but never both.
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Viral Infect ion in ICU: A Concise Review
Dr. Masood Mohammed MD, MRCP (UK), EDIC, FFICM (UK)
Avian Influenza AH7N9 and a novel
corona virus, Middle East Respiratory
syndrome corona Virus(MERS-coV) are
associated with high morbidity and
mortality
7
Most of the viruses don?t have a membrane and are called as naked or non-enveloped, which are
enveloped in a host origin lipid bi-layer into which viral proteins are anchored.
Though the enveloped viruses have an advantage of genome protection they are sensitive
to lipid solvent and can be dissolved by detergent unlike viruses (non-enveloped/naked) with
protein nucleocapsid exteriors which may be resistant to detergent.
Viruses are classified based on nucleic acid composition, nucleocapsid size and
symmetry, and presence or absence of an envelope. Broadly they are divided into either RNA or
DNA viruses (both of them can be single stranded or double stranded i.e. ssRNA, dsRNA, ssDNA
or dsDNA). Viruses unlike other living organisms lack organelles and ribosomes, so they need
host cell in order to replicate. Depending on the genetic material they have their method of
replication differs and involves steps like adsorption, uncoating of the virus, synthesis of viral
structures, and release of virus particles by budding or cell lysis. They may harm the host cell
during this process in the form of chronic or latent infection, induction of oncogenes and to cell
death.
RNA viruses:
Except very few ( Reovirus and Birnavirus) most of the RNA viruses are single stranded. The
ssRNA genome is sub-classified as positive (+) stranded ( can be translated into protein by host
cell) or negative (-) stranded which by RNA-dependent RNA polymerase converted to + strand
before translating proteins. Though the retrovirus possess + ssRNA strand it doesn?t translate
proteins unless it is converted to dsDNA by reverse transcriptase a unique viral enzyme present
only in retro viruses.
DNA Viruses:
Most of the viral DNA genome are double stranded except Parvovirus. They must undergo
transcription to mRNA before translating into proteins.
RNA Viruses and human disease:
Othomyxoviridae: (Influenza A,B and C): Most of the viruses in this group have predilection to
glycoprotein receptors in upper respiratory tract. They are pleomorphic with ssRNA viruses with
a helical nucleocapsid. Influenza A,Band Cbelong to this family.
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
8
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Influenza virus has two types of glycoprotein spikes on their envelop with haemagglutinin
activity (HA) neuraminidase activity (NA). HA spike attaches to the epithelial cells of upper
respiratory tract (URT) and provide cellular entry route for the Influenza. NA spikes helps in entry
as well as replication and release of the virus.
All the three types of Influenza (A,B, and C) have many stains due to antigenic differences in HA
and NA spikes. Pandemics occur due to antigenic shift ( major changes in the glycoproteins due to
assortment of genes between different viruses)and seasonal epidemics are due to antigenic drift(
minor changes in glycoproteins). Major pandemics in history are 1918 (H1N1), 1957 (H2N2), 1968
(H3N2) and 2009 (H1N1).
Diagnosis is by detection of viral RNA by reverse transcription followed by Polymerase Chain
Reaction (RT?PCR) and is considered as the gold standard diagnostic method for detecting
influenza viruses and can be carried out on the nose and throat swabs, nasopharyngeal, tracheal
aspirates or bronchial washings. Neuraminidase inhibitors (NAIs) (Oseltamivir, Laminavir,
Zanamivir and Peramivir) are the treatment of choice for severe cases.
Paramyxoviridae: (Respiratory syncytial virus (RSV), human metapneumovirus, Measles virus, mumps
virus, Hendra virus, Nipah virusand Newcastle disease virus)
These ss RNA have many features similar to Orthomyxoviridae with few exceptions like one
glycoprotein for HA/NA (instead of two spikes) and causes host cells to form syncytia
(multinucleated giant cells) with the help of fusion protein. Respiratory syncytial virus (RSV), human
metapneumovirus, Measles virus, mumps virus, Hendra virus, Nipah virus and Newcastle disease virus
are the recognized pathogens affecting humans belong to this group.
Diagnosis is by detection of viral RNA by RT?PCR from URT and lower respiratory tract (LRT) for
most of these viruses along with clinical grounds.
Management of these cases in ICU is supportive, however, in immunocompromised patients
aerolized Ribavirin is of benefit.
Coronaviridae: Usually coronaviruses cause insignificant URT infections, However, few
coronaviruses include the severe acute respiratory syndrome coronavirus(SARS- CoV) and MERS- CoV
cause high mortality.
Infection is best confirmed by detecting the viral genome by RT?PCR in URT or LRT specimens.
9
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Treatment is largely supportive with no specific antiviral therapy.
Retroviridae:
Two genera of human interest.
1) Lentivirus: (Lenti ? Slow)
? Human immunodeficiency virus1 & 2 ( HIV 1 & 2)
2) Human T- lymphotropic virus ? bovine leukemic virus group
? HTLV-BV- Human T-cell leukaemia virus1 & 2 ( HTLV 1 & 2)
The virion has cone-shaped, icosahedral core, containing the major capsid protein CA (p24). It
contains reverse transcriptase, integrase and protease enzymes.
Diagnosis is based on detection of anti-HIV IgG antibodies. An enzyme-linked immunosorbent
assay (ELISA) is cheap and simple to perform. A western blot analysis may be used to confirm a
positive result. In acute seroconversion, the antibody response may not mount for up to 12
weeks. HIV RNA measurement and detection of p24 antigen may be useful. HIV infections lead to
opportunistic infection by affecting CD4 T- lymphocytes.
Treatment: Typical highly active anti-retroviral therapy (HAART) regimen include combination of
three anti-retroviral therapy (ART) include two nucleoside reverse transcriptase inhibitor (NRTI)
and one Protease Inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) or fusion
inhibitors (FI).
DNA viruses and human disease:
Adenoviruse:
They are naked ds DNA viruses with more than fifty immunologically different types. They cause
respiratory, gastrointestinal, neurological and eye symptoms.
Diagnosis is by PCR of bronchoalveolar lavage (BAL), liver, cerebrospinal fluid (CSF), or faecal
samples. Viral load is useful in starting empirical therapy with Cidofovir in immunocompromised
patients.
Treatment is reduction of immunosuppressive therapy and starting Cidofovir. Ribavirin can also
be used with no evidence of virologic clearance.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
HerpesViridae:
They are subdivided into alpha, beta, and gamma.
1) Alpha-herpes viruses : Herpes Simplex virus(HSV) 1 and 2 and Varicella Zoster Virus (VZV)
causes ballooning of the cells and the formation of multi- nucleated giant cells - form
vesicles between the epidermal and dermal layers of skin and mucosal surfaces.
Alpha-HSVs can invade and replicate in the CNSand establish latency in dorsal root ganglia.
2) Beta-HSVs group: Cytomegalo virus (CMV), Human Herpes virus (HHV) 6 and 7 have an
affinity for lymphocytes and monocytes and cause infected cells to become enlarged
(cytomegaly).
3) Gamma HSVs group: Epstein Bar virus (EBV) and HHV-8 are also lymphotropic and have
oncogenic potential. Patients with compromised cell-mediated immune systems can
present with severe herpes virus infections.
Diagnosis: HIV1 is diagnosed by PCR from CSF or LRT specimens and VZVcan be diagnosed
clinically but confirmed by VZV PCR from vesicular fluid. CMV IgM indicates acute infection,
IgG stays lifelong. CMV PCR from blood and body fluids can also be used. To confirm CMV
end ? organ disease CMV detection in damaged tissues is required. EBV is characterized by
atypical mononuclear cells in peripheral smear, when they are visible infectious
mononucleosis (IM) is often suspected. Heterophile antibody or EBV IgM in blood can
confirm virologic diagnosis.
Treatment: Acyclovir, Valaciclovir and Ganciclovir are the antivirals used for HSV1, VZV and
CMV respectively. Apart from the above Varicella Zoster immunoglobulin for pregnant and
immunocompromised patients within 10 days of exposure to VZV. Intravenous Foscarnet
for CMV and corticosteroids for EBV infected patients with significant neurological
involvement, haemolysis or thrombocytopenia are the treatment options.
Viral Syndromes in ICU:
To make a diagnosis of viral infection based on clinical signs and symptoms is difficult. A
combination of clinical syndromes and specific laboratory tests guide to diagnosing and
treat these viral infections.
Here we are going to discuss various viral infections of adults in ICU based on the organ
involved with syndrome wise approach and treatment.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Respirat ory Infect ions:
In recent years because of availability of new diagnostic tools like PCR it has been noticed
that viruses as the causative agent for pneumonia are on rise and causally associated with
16 ? 49% patients admitted with respiratory failure and/or LRTI to ICU(4, 5). They were
found both in Community Acquired pneumonia (CAP) and Nosocomial pneumonias.
Pandemic 2009 influenza virus, SARS avian influenza and endemic middle east corona viruses
can cause severe CAP leading to acute respiratory distress syndrome (ARDS) and high
mortality and morbidity(6).
Community Acquired pneumonia:
Though bacteria are the common cause of severe community acquired pneumonia,
approximately 3 to 10% of these cases are due to viruses(7-13). In a recent metanalysis The
pooled proportion of patients with viral infection was 24.5% with common viruses being
Influenza viruses (8%), corona virus (3.3%) and respiratory syncytial virus (2.2 %)(14). With the
availability of new diagnostic tools (PCR), it has been observed there is a raise in detection
of viruses like human metapneumovirus and adenovirus(15, 16). Clinically these viruses cause
varied symptoms from simple flu-like symptoms or atypical pneumonia presentation in
immunocompetent patient to severe lobar or bilateral pneumonia leading to ARDS in
immunocompromised patients(17-20).
Nosocomial Pneumonia:
Contrary to the belief that nosocomial pneumonias are due to bacteria, it has been
reported that that virus pneumonia can be nosocomial acquired, especially in
immunocompromised individuals(21, 22). In a recent study 34% of the 134 health care
associated pneumonia (HCAP) patients had at least one respiratory virus recovered, the
most frequent being rhinovirus, parainfluenza virus, human Metapneumovirus and influenza
virus(23).
Ventilate Associated Pneumonia (VAP): It is very difficult to correlate the viral positivity in LRT
samples to VAP in ventilated patients as most of them are colonized. It is not unusual to see
HSV bronchopneumonitis in immunosuppressants, with ARDS, after surgery or burn
victims. However, in a French study among 201 ventilated non-immunocompromised
patients though BAL was positive for HSV in 64% patients and only 21% (42 patients) were
found to have HSV Broncho pneumonitis(24). Among 42 of 201 patients 19 (9.4%) had
combined HSV and bacterial VAP, whereas the remaining 23 (11.4%) had only HSV Broncho
pneumonitis.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Though the mechanical ventilation (MV) duration was prolonged in HSV
bronchopneumonitis patients mortality was the same between two groups. In spite of
several data argue in favour of HSV pathogenicity its exact significance is still open to
debate.
Similar to HSV reactivation of CMV in immunocompetent patients without lung involvement
was observed with very few patients developing CMV pneumonitis especially those who are
on prolonged MV. Mimi virus a large virus is also been attributed to cause VAP in
immunocompetent patients. There is no doubt that mortality of patients with HSV and CMV
viremia and pneumonia is high, the significance of isolation of these viruses in LRT of
immunocompetent ventilated patients is not clear.
Treatment of Viral respiratory infections:
For Influenza, vaccination remains the most effective measure, especially for the high risk
and elderly(25). Neuraminidase inhibitors (oseltamivir or zanamivir) are recommended for
severe disease presentation, (severe pneumonia, requiring mechanical ventilation) or
patients at high risk for complications e.g. immunocompromised individuals and in all
suspect cases in areas endemic for a strain with high mortality (avian influenza strain).
Oseltamivir was used at a dose of 75 mg twice daily. Some use 150 mg twice daily which is
safe and well tolerated, have been used to treat Influenza B, some influenza A strains with
reduced susceptibility and CNS involvement. But overall supportive evidence is lacking and
risk of antiviral resistance may emerge(26).
Few novel antivirals have been used in special cases. Among them a single dose
intravenous Peramivir which was approved by United states Food and Drug Administration
(USFDA) for a short period to treat hospitalized patients with 2009 H1N1 pandemic influenza
and a single inhaled dose of Laminavir for oseltamivir resistant seasonal influenza virus(27).
Favipiravir used to inhibit a variety of influenza viruses, including highly pathogenic avian
influenza H5N1 viruses. Apart from the above entry inhibitors, terminase and helicase
enzyme inhibitors, translation inhibitors and nucleoside analogues such as cidofovir are
used as an off-label(28). Combination antivirals as used in HBV,HCV and HIV infections was
not established to treat these respiratory viral infection. In a randomized controlled study of
oseltamivir-zanamivir combination efficacy for seasonal influenza was established, but
clinical antagonism was observed in another study(29, 30).
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Other therapies:
Corticosteroids: In patients with severe influenza and septic shock low dose systemic
steroids can be used. However, some don?t prefer them as few RCT showed corticosteroids
may be associated with delayed clearance of viruses from(31, 32).
Plasma & Immunoglobulin: A favourable response was observed with Immunoglobulins and
convalescent plasma in patients with severe avian influenza A (H5N1) and H1N1 pandemic
2009 in a RCT and few case series(33-35). Need more RCTs before generalizing these
treatment options.
Cent ral Nervous syst em Infect ions:
Inflammation of meninges and brain parenchyma due to viruses infecting CNS is one of the
cause of meningitis and encephalitis respectively. The presence of normal brain function
distinguishes meningitis from encephalitis. It is not uncommon to see meningitis and
encephalitis in the same patient and the distinction between these two is difficult so the
term meningoencephalitis often used. These patients may develop seizures, coma and
respiratory failure needing mechanical ventilation secondary to aspiration due to low GCS,
atelectasis and neuromuscular weakness needing ICU admission and care. Other than
meningoencephalitis Guillain-Barre? syndrome (GBS) Reyes syndrome, sub-acute sclerosing
panencephalitis, postinfectious acute disseminated encephalomyelitis (ADEM) are other
conditions secondary to viral infections affecting CNSneeding ICU admission.
The true incidence of these infections is difficult because many cases are unidentified
despite the availability of advanced molecular techniques like PCR. HSV 1 causes >50% of
cases followed by VZV(36). A Swedish study revealed 2.2 cases of HSV encephalitis per
million persons(37). Enterovirus (coxsackievirus A and B, echovirus, and enterovirus) are
collectively the third most common cause, while arboviruses [Japanese Encephalitis Virus
(JEV), West Nile virus ( WNV), Murray Valley encephalitis virus (MVEV)] are very common in
certain geographic regions. Rabies, measles and mumps are very rare causes of
encephalitis.
Lumbar puncture and CSF analysis should be performed after CT brain (to rule out any
significant brain tissue shift, evidence of raised intracranial pressure (ICP) and send for PCR
for DNA of HSV-1, HSV-2, VZV, and enterovirus, (which constitute for about 90% of viral
encephalitis).
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
An MRI scan is helpful in confirming the diagnosis of encephalitis and some characteristic
findings like temporal lobe involvement in HSV, basal ganglion and thalamus involvement in
Flavivirus and acute disseminated encephalomyelitis (ADEM) and other post-infectious
encephalitis. Continuous EEG monitoring is helpful in patients with persistently altered
consciousness to exclude intermittent non-convulsive seizures or non-convulsive status
epilepticus.
Management:
Apart from the ABCDE management in ICU, antivirals are the mainstay of treatment. Early
administration of high dose of acyclovir should be administered for 14 ? 21 days. This
reduces mortality from 70% (without treatment) to < 20% ( with acyclovir)(36). Use of
corticosteroids in viral encephalitis is lacking from RCT, so should not be used routinely
except in VZV encephalitis, post- infectious encephalitis and with significant cerebral
edema(36). For VZV encephalitis Acyclovir for 3 weeks., for CMV combination of Foscarnet
and Ganciclovir and for Influenza encephalitis Oseltamavir is recommended. Though no
antivirals are recommended for enteroviruses, pleconaril (an inhibitor of viral replication)
may be used in patients with severe Enterovirus infections.
Shock:
Shock due to viral infections could be due to involvement of myocardium ( cardiogenic
shock), due to hemorrhagic fever ( distributive shock), due to liver failure secondary to viral
hepatitis and pancreatitis (hypovolaemic/distributive shock) and adrenal insufficiency.
Viral Myocarditis: Several viruses (Influenza, Adenovirus, Parvovirus, RSV, CMV, HIV-1, hepatitis
Aand Cviruses) vaccinia virus cause viral myocarditis including Coxsackie Aand B.
Except few who have persistent cardiac dysfunction whose one year mortality was 20%
most of the remaining do recover. Some of them who have severe left ventricular
dysfunction may require Left Ventricular Assist Device (LVAD) until myocardial function
recovers or cardiac transplantation is available.
Treatment: General supportive measures to treat the consequences of heart disease
[treatment of Heart failure (HF), treat of arrhythmia's and in selected cases
anti-coagulation]. Refractory HF in spite of optimum medical therapy need mechanical
circulatory support like LVAD or transplant.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
The role of antivirals like ribavirin or interferon alfa is uncertain, though they reduce
severity and mortality in murine myocarditis and a case report of alpha interferon in
patients with enterovirus-proven myocarditis(38-41). Immunosuppressive therapy along
with steroids and immunomodulatory effect of IV IgG have tried in viral myocarditis, but
their role was controversial since a metanalysis did not reduce mortality(42, 43).
Haemorrhagic fever and dist ribut ive shock:
Hemorrhagic fever (HF)is caused by RNA viruses, Flaviviruses (Yellow fever, Dengue HF),
Arenaviruses (South American HF-Junin; Lassa Fever), Bunyaviruses (Rift valley fever,
Chrimean Congo HF-CCHF), HF with renal syndrome, Hantavirus, Filoviruses (Ebola, Marburg).
They are transmitted by arthropod and rodents. Common in Indian subcontinent is Dengue
virus transmitted by Aedes aegypti and Aedes albopictus. Apart from involving organs leading
to hepatitis, nephropathy, encephalopathy, Disseminated intravascular coagulopathy (DIC)
and even multi-organ failure. The characteristic feature of hemorrhagic fever is capillary
leak due to increased vascular permeability. Outcome depends on the severity of the
disease and serotype of the virus. It has a wide range of case fatality rate (1% to 90%)(27)
Treatment:
As there is no specific antivirals for most of these viruses general intensive care supportive
treatment, support of organs and blood product transfusion is the main stay of
management. Passive transfer of antibodies (convalescent plasma, IVIG) may be of value in
Bunyaviruses [45], Junin virus [42], Lassa virus [43], Hantavirus HF. Case reports of plasma
exchange for severe dengue have been reported as a last resort with some success(44).
Antivirals like ribavirin and interferon can be used for Lassa virus(45).
Liver failure and dist ribut ive shock:
Common viruses that cause liver failure are Hepatitis group (A,B,C,D,E and G), Herpes group
(HSV, VZV, CMV and EBV), Influenza virus and Adeno virus. They usually present with fatigue,
anorexia, lethargy, jaundice, ascites, respiratory insufficiency, acute kidney injury, hepatic
encephalopathy and coma.
Treatment:
Largely supportive management. Patients who progress from grade 1 encephalopathy to
grade 2 or those who presented with grade 3 or 4 are managed in ICU. Haemodynamic
instability is common in these patients due to low systemic vascular resistance and
intravascular
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
depletion, so most of them require fluid resuscitation initially with normal saline, those
who remain hypotensive noradrenaline is the vasopressor of choice. Prophylactic
administration of fresh frozen plasma (FFP) is not recommended for patients with high INR
as it is not going to influence mortality and interfere with assessments of liver function(46).
Patients who are seriously ill need to be transferred to a transplant centre without delay.
Pancreat it is and dist ribut ive shock:
Mumps is the most common virus associated with pancreatitis, other viruses are Coxsackie
B, HSV, VZV, CMV, EBV, adenovirus, Influenza and Para influenza viruses.
Treatment: Supportive treatment as for any pancreatitis due to other aetiology. Fluid
resuscitation and pain management are the main cornerstones of the treatment. Antivirals
should be started for specific viral infections( Acyclovir for VZV, Oseltamavir for Influenza
virus and Pleconaril for severe enterovirusinfections).
Human Immunodefficiency Virus (HIV):
It itself is a separate review, so we are discussing it very briefly. There are number of
reasons with which HIV infected patients admitted to ICU, HIV related or non-HIV related.
Acquired respiratory failure is the most common cause for ICU admission and most
common pathogen is pneumocystis jirovecii pneumoniae followed by bacterial
pneumonia(47). Other causes are sepsis and CNS related conditions (meningitis, Sub-acute
encephalitis, Herpes simplex encephalitis, multi-focal leukoencephalopathy and
seizures)(48). CD4 count and RNA levels are predictors of long term mortality after ICU
discharge and need for MV, RRT, disease severity sore (APACHE II) and receipt of
vasopressors are the predictors of mortality in ICU(49, 50).
Treatment:
Patients who are on ART at the time of ICU admission should stop or continue HAART is a
big debate. Two observational studies suggested that ART may improve outcomes in
critically ill ICU patients (10,27). Limitations are development of resistance due to poor oral
absorption in critically ill patients as most of the ART are oral except Zidovidine and
Enfuvrtide. Start ART within 14 days after starting treatment to opportunistic infections.
Inpatients with cryptococcal infection start ART after 2 -8 wk of anti-fungal treatment to
prevent immune reconstitution inflammatory syndrome (IRIS). Treat OI as per the specific
organism.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Legend: Table
Syndrome Common Virus Treatment
RESPIRATORY FAILURE: CAP: Influenza A and B, RSV A and B,
coronavirus, Severe Acute Respiratory
Syndrome (SARS), Middle East
Respiratory Syndrome coronavirus,
Adenovirus, cytomegalovirus, Varicella,
HSV, Parainfluenza 1-4,
Metapneumovirus, measles especially
in immunocompromised patients
VAP: HSV, CMV, Mimi virus
ARDS: Influenza virus, Hantavirus
[Hantavirus pulmonary syndrome
(HPS)], varicella, herpes simplex virus,
SARS, MERS-CoV
Supportive: Adequate oxygen
delivery
Antivirals:
Neuraminidase inhibitors (NAIs)
(Oselt amivir, Zanamivir, peramivir,
Laninamivir).
For resistant influenza viruses may
consider combination therapy of NAI
with ribavirin and/ or novel antivirals
such as Favipiravir.
Ribavirin for RSVin
immunocompromised patients and
children and may also be considered
for other viruses such as in SARSor
MERS-CoV - lopinavir in combination
regimens has also been used
Acyclovir for VZV pneumonitis
Ganciclovir for CMV pneumonitis in
solid organ transplant patients appears
to reduce morbidity .
Cort icost eroids: For influenza, SARS
and VZV pneumonitis to reduce
inflammatory tissue injury in severe
pneumonia
Immunot herapies: Palivizumab is
approved for high-risk pediatric
patients with RSV infection ; IVIG for
certain respiratory viruses including
influenza and GBS, plasma exchange
for GBS. Combinations of ganciclovir
wit h immuno- globulin or
cyt omegalovirus immunoglobulin
may be of value in patients with bone
marrow transplants and CMV
pneumonitis
Others: Vitamin A for severe measles.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Neurological syndromes:
Encephalitis, meningitis,
meningoencephalitis, myelitis,
polyradiculo-neuropathy,
Guillain-Barre? syndrome (GBS) Reyes
syndrome, subacute sclerosing
panencephalitis, postinfectious acute
disseminated encephalomyelitis (ADEM)
HSV, VZV, Enteroviruses (Enterovirus
71, Coxsackie, Echovirus, poliovirus: as a
group, enteroviruses)
Arboviruses (JEV, WNV, TBEV, MVEV,
LCEV, SLEV, EEEV: the most common
pathogens to cause encephalitis that is
restricted to certain geographic
regions)
Influenza (4-19%) of patients with
severe or fatal H1N1 reported
neurologic complications .
West Nile virus, CMV, mumps, measles,
rubella, rabies, JC virus (PML), acute HIV
infection)
Supportive:
Treatment of neurologic (eg, cerebral
edema, high intracranial pressure, and
seizures) and systemic (eg, hypoxemia,
low cerebral perfusion pressure, and
fever) complications
Antivirals:
Acyclovir: For HSV, VZV improves
mortality and reduces subsequent
cognitive impairment
Ganciclovir: CMV encephalitis
Foscarnet: HHV-6, combination
therapy with foscarnet and ganciclovir is
recommended for CMV encephalitis
Oseltamivir: Severe influenza
Pleconaril: severe Enterovirus
infections
Corticosteroids: Complicated HSV
encephalitis (data based on
retrospective studies), VZV encephalitis
(for inflammatory vasculopathy),
uncomplicated zoster (variable results),
severe influenza, WNV (case report)
[33], postinfectious encephalitis
Immunotherapies: Either intravenous
immune globulin or plasma exchange
for patients with postinfectious
encephalitis who fail corticosteroid
treatment.
Others: Vitamin A for severe measles
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Virus relat ed shock :
Cardiogenic shock Myocarditis :
Distributive shock-Hemorrhagic fever
Hypovolemic/distributive shock in the
setting of acute liver failure secondary
to viral hepatitis
Enteroviruses (Enterovirus 71,
Coxsackie viruses group A and B,
Echovirus), Influenza, Adenovirus,
Parvovirus, RSV, CMV, HIV-1, hepatitis A
and C viruses, vaccinia virus (after
smallpox vaccine)
Arenaviruses (South American
HF-Junin; Lassa Fever), Bunyaviruses
(Rift valley fever, Chrimean Congo
HF-CCHF), HF with renal syndrome,
Hantavirus, Filoviruses (Ebola, Marburg),
Flaviviruses (Yellow fever, Dengue HF)
Hepatitis A, B, C, D, E, G, herpes group
(CMV, HSV and Epstein Barr virus),
adenovirus and influenza virus
Support ive :
Ant ivirals:
Rifampin: For RSV myocarditis [
Pleconaril: severe Enterovirus infections
Oseltamivir: Severe influenza
ART: HIV-1
Corticosteroids: do not reduce
mortality (data based on small RCT of
poor quality)
Immunotherapies: IVIG (data based on
in vitro data, case series, limited RCT)
[38-40]. Combination therapy of IVIG
with rifampin has been described in
case series.
Others: Mechanical ventricular assist
devices until resolution or cardiac
transplantation is available, novel
therapies e.g pleconaril
Support ive: Adequate oxygen delivery,
blood products.
Passive transfer of antibodies (plasma,
IVIG) may be of value in Bunyaviruses,
Junin virus ,Lassa virus, Hantavirus HF,
Flaviviruses (Yellow fever, Dengue HF)
Antivirals: Ribavirin for CCHF, Lassa
virus, Hantavirus HF.
Ribavirin plus interferon may be
considered for Lassa virus.
Support ive: Hemodynamic
management, ventilation, prevention
and treatment of hemorrhage, dialysis,
therapy of co-existent sepsis and
electrolyte disturbance, and
management of intracranial pressure
Ort hot opic liver t ransplant at ion
Ant ivirals (may be used for acute flare
up of chronic viral hepatitis e.g. in
immunocompromised patients.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Courtesy: Modified and reproduced from Kelesidis et al. BMC Infectious Diseases 2014, 14:321
http://www.biomedcentral.com/1471-2334/14/321
Preventive Strategy:
It is well known that some of these viruses are transmittable via droplet and airborne (respiratory)
and some by contacting blood and body fluids (Hepatitis B, C, HIV etc,.). Use of nebulizers, open
suctioning of respiratory secretions, the use of Bi-PAP, outdated ventilation systems in addition to
unawareness, inadequate training and non-compliant to local infection control policies all lead to
spread of viral infections in the ICU setting and health care professionals are at high risk. Vaccines
are not adequate in preventing spread of these infections in ICU. So health care providers, family
members and visitors of the patient must follow strict isolation precautions. Judicious use of
disinfectants is one of the solutions as they are highly active against some viruses.
Hypovolemic/distributive shock in the
setting of acute pancreatitis
Mumps (the most common virus
associated with pancreatitis,
occurring even in the absence of
parotitis), Enteroviruses
(Coxsackie B), cytomegalovirus,
varicella zoster, HSV-1, Epstein-
Barr virus, influenza A,
Parainfluenza, adenovirus,
measles. In fulminant hepatic
failure due to hepatitis A (HAV)
or hepatitis E(HEV) pancreatitis
occurs in up to 34% of the cases.
Supportive
Antivirals
Oseltamivir: Severe influenza
Pleconaril: severe Enterovirus
infections Acyclovir: VZV
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Conclusion:
Viral infections in ICU patients are increasingly identified in recent past especially due to easy
availability and low cost of diagnostic tools. They play an important role even in
immunocompetent patients in outcome. Most of them are community acquired, however, few of
them are nosocomial. Though most of these infections are self-limiting some of them are life
threatening and leading to worse outcome. Unfortunately except supportive therapy specific
anti-retroviral therapy is available for only very few. Therefore it is very crucial to recognize them
at earliest and treat them appropriately. We need more robust studies which aid in confirming the
role of these viruses in critically ill patients.
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Viral Infect ion in Pediat rics
Dr M Vishnuvardhan Reddy,Neonat ologist , Apollo Cradle
MOTHER TO CHILD TRANSMISSION OF VIRAL INFECTIONS
Viral infections of the fetus and new born are common problems in neonatal practice
and are under recognized. So, however identification of the viral infections are important
since anti-viral agents are available for most of the common viral infections.
Vertically transmitted infections of fetus and neonates are divided into three distinct
categories by transmission modes,
Congenit al infect ions: Are those infections which are acquired in-utero.
Perinat al infect ions: Are those acquired during intra-partum (labour and delivery).
Post nat al infect ions: Are those acquired after birth within the first one month of life.
PRENATAL PERINATAL/INTRAPARTUM POSTNATAL
CMV HSV RSV
Zika virus HIV Enteroviruses
Varicella Hepatitis B/C Rotavirus
Parvo virus B19 Adeno Virus Adenovirus
Rubella Enteroviruses Hepatitis B/C
Hepatitis B/C CMV CMV
Influenza
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Relative importance of neonatal viral infections related to timing of acquisition of infections.
Viruses are listed in declining relative order of importance relative to prenatal, perinatal and
postnatal periods.
General approach t o diagnosis:
Clinical features commonly associated with congenital viral infections in neonates:
- Intra uterine growth restriction
- Non immune hydrops fetalis
- Echogenic bowel
- Hepatosplenomegaly
- Jaundice
- Haemolytic anaemia
- Purpura, ecchymosis, petechia
- Skeletal defects
- Microcephaly and hydrocephaly
- Intracranial calcification
- Neuronal migration defects
- Pneumonitis
- Myocarditis
- Cardiac defects
- Chorioretinitis
- Cataract Glaucoma .
MOTHER TO CHILD TRANSMISSION OF HEPATITISB
India has a prevalence rate of 2-7% for HBsAg seropositivity, whereas the prevalence in
pregnant women is between 0.9-11.2%. MCTC of Hepatitis B virus is the most common cause of
chronic hepatitis B infection. Transmission can occur in utero, at birth (most common) or after
birth.
Fact ors associat ed wit h high rat e of MTCT
- High maternal serum HBV DNA level >2,00,000 IU/ml
- HBeAg positivity in mother
- Duration of 1st stage of labour >9 hours
- Premature rupture of membranes and threatened preterm labour
- Prior child with passive active immune-prophylaxis failure
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Prevent ion of mat ernal t o child t ransmission of Hepat it is B
All infants within 12 hrs of birth HepB vaccine + HIBG
MOTHER TO CHILD TRANSMISSION OF HIV
Parent-to-child transmission of HIV is a major route of new HIV infections in children.
Children born to women living with HIV acquire HIV infection from their mother, either during
pregnancy, labour/delivery or through breast feeding which is largely preventable with
appropriate intervention, by providing Anti-retroviral therapy (ART) to mothers and
Anti-Retroviral (ARV) prophylaxis to infants. A total of 61,000 lakh children (0 to 14 years) are
estimated to be living with HIV in India.
Ant epart um
Antiviral drugs ? treatment should be started 6-8 weeks before delivery. Tenofovir is
preferred
Int rapart um
Elective LSCSshould be performed before the onset of labour or before the rupture of
membranes
Post part um
Management of baby born to Hbsg positive mother
B wt >2 kg B wt < 2 kg
Subsequent vaccine doses at 1-2 months
and 6 months of of age
Required vaccines at birth, 1, 2 and 6
months (total 4 doses)
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Risk of HIV transmission from Mother to Child with ARV interventions :
Source: Anti retroviral drugs for treating pregnant women and preventing HIV infection in
infants: Towards universal access, Recommendations for public health approach ? 2006
version ? WHO.
PPTCT: Int ervent ions during pregnancy:
- Primary prevention of HIV in childbearing women
- Provide HIV information to ALL pregnant women
- Antenatal visits are opportunity for PPTCT
- Prevention of unwanted pregnancies in HIV-positive women
- Prevention of PTCT through ART
- Safe obstetric practices
ARV INTERVENTION
RISK OF HIV TRANSMISSION FROM
MOTHER TO CHILD
No ARV; breastfeeding 30-45%
No ARV; No breastfeeding 20-25%
Short course with one ARV; breastfeeding 15-25%
Short course with one ARV; No breastfeeding 10-15%
Short course with two ARVs; breastfeeding 5%
3 ARVs (ART) with breastfeeding 2%
3 ARVs (ART) with No breastfeeding 1%
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PPTCT: Int ervent ions during labour and delivery:
- Minimize vaginal examinations
- Avoid prolonged labour; consider oxytocin to shorten labour
- Avoid artificial rupture of membranes
- Early cord clamping after it stops pulsating and after giving the mother oxytocin
- Use non-invasive foetal monitoring
Avoid invasive procedures
Avoid routine episiotomy / support perineu
Minimise the use of forceps or vacuum extractors.
Use of ART can reduce risk of PTCT better and with lesser risk than a C-section
ART regimens in pregnant and breastfeeding with HIV
Pregnant women presenting in active labour :
TARGET POPULATION DRUG REGIMEN
Pregnant and breastfeeding women with HIV
(ART Naïve / ?Not-already?receiving ART)
TDF + 3TC + EFV
Pregnant and breastfeeding women with HIV
already receiving ART
The same ART regimen must be continued
ART regimen for pregnant women having
prior exposure to NNRTI for PPTCT
TDF + 3TC and LPV/r
MATERNAL STATUS INTRA-PARTUM POST-PARTUM
Presenting in active
labour, no prior AR
Initiate TDF (300 mg)
+ 3TC (300 mg) + EFV
(600 mg)
Continue TDF (300 mg)
+ 3TC (300 mg) + EFV
(600 mg)
Nevirapine prophylaxis for breastfeeding infant should be for
12 weeks, as mother did not receive any ART during ante-natal
period
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
ARV Prophylaxis for Infant:
The infant should be started on Nevirapine. The duration of NVP prophylaxis will depend on the
duration of ART that has been given to the mother during her ante-natal period.
- Infants should be started on daily NVP prophylaxis at their first encounter with the health
services
- Daily infant NVP prophylaxis can be started even if more than 72 hours have passed since
birth and should continue; during this period the mother should be linked to appropriate ART
services.
Duration of daily infant NVP prophylaxis will depend on ?how long the mother was on lifelong ART
[for a minimum of 4 weeks or not]?
- The duration of NVP given to infant is a minimum of 6 weeks, regardless of whether the
infant is exclusively breast fed or exclusive replacement fed
- 6 week-Nevirapine prophylaxis should be increased to 12 weeks, if ART to the mother has
been started in late pregnancy, during or after delivery and she has not been on ART for an
adequate period as to be effective to achieve optimal viral suppression (which is at least 4
weeks)
- The recommendation on extended Nevirapine duration (12 weeks) applies to infants of
breast-feeding women only and not to those on exclusive replacement feeding
- Infants of women with prior exposure to NVP should get syrup Zidovudine (AZT) in place of
syrup Nevirapine Recommended ARV Prophylaxis for HIV Exposed Infants
HIV Exposed Infants of HIV-2 infected mother :
Start syrup AZT in place of NVP syrup, immediately after birth till 6 weeks of age.
Specific Interventions during Infancy:
- Observe for signs and symptoms of HIV infection
- All HIV exposed infants should receive co-trimoxazole at 6 weeks of age
- Follow standard immunization schedule
- Routine well baby visits
- Early Infant Diagnosis: DNA PCR test o 18-month visit for HIV antibody testing
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
MOTHER TO CHILD TRANSMISSION OF CMV
CMV infection is the most common congenital viral infection within birth prevalence of
about 0.5%. Majority of congenital infections are asymptomatic. 5-20% of infants born to
mother with primary CMV infection are symptomatic. Asymptomatic infants are at a risk of
long term neurodevelopmental morbidities, but the risk is such lesser than symptomatic
infants. The most common complication is congenital hearing loss.
Classification of CMV infection in pregnant women :
Primary ? if initial acquisition of virus (seroconversion from negative to positive) occurs
during pregnancy.
Non primary - if maternal antibody to CMV was present before conception due to
reactivation of latent virus or re-infection with new strain.
Vertical transmission via mother to fetus and new born is most common with primary
maternal infection.
Routes of transmission :
- trans placental
- ascending infection from maternal genital tract infection (rare)
- intrapartum through ingestion or aspiration of Cervico-vaginal secretions during
delivery
- postnatal transmission occurs through breastfeeding
Prevent ion :
The Centers for Disease Control and Prevention (CDC) recommends that
(i) pregnant women practice hand washing with soap and water after contact with diapers
or oral secretions; do not share food, utensils, toothbrushes, and pacifiers with children
and avoid saliva when kissing a child.
(ii) pregnant women who develop a mononucleosis-like illness during pregnancy should be
evaluated for CMV infection and counseled about risks to the unborn child.
(iii) antibody testing can confirm prior CMV infection.
(iv) the benefits of breastfeeding outweigh the minimal risk of acquiring CMV.
(v) there is no need to screen for CMV or exclude CMV-excreting children from schools or
institutions.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Immunizat ion :
Passive immunization with hyperimmune anti-CMV immunoglobulin and active
immunization with a live-attenuated CMV vaccine represent attractive therapies for
prophylaxis against congenital CMV infections. However, data from clinical trials have not
shown adequate efficacy of either of these approaches with current passive and active
vaccine products.
Breast milk feeding :
Breast milk is a common source for postnatal CMV infection in the new born, symptomatic
infection is rare in term infants. However, there may be insufficient transplacental IgG to
provide adequate protection in preterm infants. For mothers of extremely premature and
low birth weight infants known to be CMV seropositive, freezing breast milk will reduce
the titer of CMV but will not eliminate active virus.
Environment al rest rict ions :
Day care centers and hospitals are potential high-risk environments for acquiring CMV
infection. Good hand-washing technique should be suggested to pregnant women with
children in day care settings and with children attending day care, especially if the women
are known to be seronegative.
Transfusion product rest rict ions :
The risk of transfusion-acquired CMV infection in the neonate has been almost eliminated
by the use of CMV antibody-negative donors, by freezing packed red blood cells (PRBCs) in
glycerol, or by removing the white blood cells.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Vaccine is an immune biological substance designed to produce specific protection
against a given disease. The development of vaccines has been one of the most
important contributions of immunology to medicine and public health. It was initiated
about 200 years ago by Edward Jenner, with the inoculation of the fortuitously
cross-protective cow-pox discharge, for prevention of smallpox infection. The major
breakthrough, occurring a hundred years later, was the preparation by Pasteur, of
rabies vaccine, which is based on intentional attenuation of the pathogen. This paved
the way for the development of a whole sequence of viral vaccines.
The IAP Advisory Committee on Vaccines and Immunization Practices (ACVIP) has
recently reviewed and revised the recommended immunization schedules for children
aged 0 through 18 years to ensure that the schedule reflects recommendations based
on recent evidence for licensed vaccines in the country. The recommended vaccines for
viral diseases include, vaccines for Measles, Flu, Polio, Hepatitis-B, Mumps, Rota virus.
Most of these vaccines are live-attenuated or inactivated and are developed by earlier
methods like, passage in live animals or eggs. More recent vaccines have been
developed because of the advent of new technologies, particularly cell culture and
molecular biology. Recent technological advances in gene delivery and expression,
nanoparticles, protein manufacturing, and adjuvants have created the potential for new
vaccine platforms that may provide solutions for vaccines against viral pathogens for
which no interventions currently exist.
Old t ype of vaccines:
a. Live, at t enuat ed vaccines:
- These vaccines contain a version of the living virus or bacteria that has been
weakened so that it does not cause serious disease in people with healthy
immune systems live, attenuated vaccines are the closest thing to a natural
infection
- Examples: measles, mumps, and rubella vaccine (MMR) and varicella
(chickenpox) vaccine.
b. Inact ivat ed Vaccine:
- The virus is made inactive during the process of vaccine preparation
- Examples: Inactivated polio vaccine
OLD AND NEW VACCINESFOR THE PREVENTION OF
VIRAL INFECTIONS
Dr. Renu Avula,Professor of Microbiology,Kurnool Medical college,AP,India.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Newer t ypes of vaccines:
Viral vect or t echnology: Here the choice antigen is expressed in the context of an active
heterologous viral infection, which stimulates the full gamut of innate immune responses
required for the development of adaptive humoral and T cell mediated immunity. In this
type of vaccine the characteristics, type and intensity of immune response, as well as
safety considerations and manufacturing techniques are determined predominantly by
the vector and not the pathogen. The applications of this technology include,
a) Replicat ion compet ent approach in which Replication competent but attenuated virus
vectors (RHS) deliver heterologous antigen targets resulting in the induction of cellular and
humoral responses. Their complement of genes enables a full round of replication and
assembly of progeny virus which can amplify and spread the vaccine effect to susceptible
cells. While these platforms are based on highly attenuated viral backgrounds, replication
competence may lead to the development of mutations and reversion to virulence.
Chimeri Vax? -JE for Japanese Encephalitis has been developed by Sanofi Pasteur (Lyon,
France)
It has certain advantages like, 1) Development of good humoral and T cell responses 2)
Several platforms available. 3) Simple production via virus culture. The drawback of this
technology is reduced expression or loss of heterologous antigens or in some case
reversion to virulence.
b) Replicat ion defect ive approaches where Replication defective vectors support
effective cellular entry and a single round of expression of the target gene/ antigen; they
result in effective induction of cellular and humoral responses. They are unable to
generate new infectious progeny and are considered safer than replication competent
vectors
Modified Vaccinia Virus Ankara (MVA) is licensed as third generation vaccinia type vaccine
against small pox. Developing stages: Ebola virus, MERSCoV and Zika virus
This method has the advantage of development of good humoral and T cell responses.
Virus like part icles:
The virus like particles (VLP) acts as vaccine candidates and they present highly antigenic
structures to the immune system. They lack a viral genome, potentially yielding safer
vaccines, as there is no viral sequence that can revert to virulence. They induce strong B
cell responses in the absence of adjuvants by efficiently cross-linking specific receptors on
B cells, and they can also trigger T cell-mediated responses.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
VLP-based vaccines for human papilloma virus (HPV), hepatitis B virus (HBV) and hepatitis E
virus (HEV) have been licensed and are commercially available worldwide. Under clinical
development, including those directed against Norwalk virus, Ebola and Marburg viruses
and hepatitis C virus. VLP vaccines combine many of the immunogenic advantages of
whole-virus vaccines with the safety advantages of recombinant subunit vaccines. These are
safe and are good inducers of humoral and Tcell responses but the production costs may
be high and require multiple steps.
Nucleic acid vaccines:
DNA vaccines have emerged as a safer alternative to standard live and inactivated vaccines
for treating human and animal infections. They exhibit several advantages over traditional
strategies in terms of safety, stability, ease of manufacturing and immunogenicity. They
offer potential advantages for vaccination against emerging viruses, in that plasmids
expressing a viral antigen can be produced rapidly. Antigen is expressed in vivo and induces
both humoral and cell-mediated immune responses. Additionally, large quantities of DNA
can be produced in a short time at reduced cost, and DNA preparations are more stable
than other types of vaccines, which are desirable properties for a vaccine that may be used
in remote areas.
DNA vaccines are considered safe. The main limitation in the development of DNA vaccines
is their intrinsic low immunogenicity. Work to improve this limitation has focused on
optimizing delivery approaches with the use of gene guns, or electroporation ; targeting
immune effector cells; and the use of potent adjuvants. DNA vaccines are also frequently
used in combination with other vaccine platforms in heterologous prime-boost strategies.
A DNA vaccine is currently licensed to immunize against West Nile virus and has undergone
Phase I clinical trials in humans. DNA vaccines have also been evaluated as candidates
against many emerging viruses, including EBOV, RVFV , Dengue virus and CHIKV. These are
safe but induce lower levels of immune responses.
Synt het ic pept ides:
Synthetic peptide-based epitope-vaccines (EVs) make use of short antigen-derived peptide
fragments that can be presented either to T cells or B cells. EVs offer several advantages
over other forms of vaccines, particularly with regard to safety, ease of production, storage
and distribution, without cold chain issues.
They also offer the opportunity to vaccinate against several pathogens or multiple epitopes
from the same pathogen. Drawbacks include poor immunogenicity and the restriction of
the approach to patients of a given tissue type [human leucocyte antigen (HLA) haplotype]
and, as such, they need to be tailored to accommodate the natural variation in HLA genes.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
Recently, bioinformatics tools have been developed to identify putative CD4+ T cell
epitopes, mapped to the surface glycoproteins of the emerging viruses LASV, NipV and
Hendra.
This approach represents an interesting and novel strategy that shows promise for
vaccination and which could also address immunity in particular target populations. This
method has the advantage in ease of production and storage but has uncertain
immunogenicity linked to target populations.
Fut ure perspect ives:
The future perspectives in development of vaccines include, Self-disseminating wild-life
reservoir vaccines, which aim to immunologically contain emerging viruses within their
non-human reservoir hosts, offer an alternative to the conventional vaccine approach. They
are designed to exploit the ability of replicating virus-based vectors to spread through
animal host populations, so avoiding the need for direct inoculation of every animal. In this
way, vaccination of a limited number of initiator animals is used for the introduction of the
vaccine into a target population. The vaccine is engineered to express target antigens from
the emerging pathogen of interest, so its transmission from vaccinated to non-vaccinated
animals will result in the co-ordinated spread of specific immunity for the emerging
pathogen throughout the targeted animal population. A study targeting the human
pathogen Sin Nombre orthohantavirus (SNV) in its rodent reservoir ? the deer mouse
(Peromyscus maniculatus) ? proved effective. This approach used an engineered
cytomegalovirus (CMV) vector which causes a benign but transmissible infection in the host,
expressing the SNV envelope glycoprotein G1. A similar approach is also being developed to
interrupt zoonotic transmission of Ebola virus.
The following is a list of vaccines incorporating novel vaccine preparation methodologies
being available in the market and being used to specifically address the growing threat of
new and emerging disease.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
DISEASE VACCINE
Dengue - Dengue vaccine available is
CYDTDV (Dengvaxia®), a live
attenuated (recombinant)
tetravalent vaccine.
Hepatitis A - Inactivated or live attenuated
hepatitis A virus vaccines
Hepatitis E - Recombinant vaccine based on
genotype 1 capsid protein
Japanese Encephalitis - Inactivated Vero cell-derived
vaccines
- live attenuated vaccines
- live recombinant (chimeric)
vaccines.
Polio - Orally administered, live
attenuated polio vaccine (OPV)
- Inactivated poliovirus vaccine (IPV)
Rabies - Modern cell-culture or
embryonated-egg vaccine.
Tick borne Encephalitis - Inactivated vaccine.
Yellow fever - Live attenuated.
Influenza - Inactivated influenza vaccine [IIV]
- Recombinant influenza vaccine
[RIV]
- Live attenuated influenza vaccine
(LAIV)
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
References:
1. Vaccine-preventable diseases and vaccines :INTERNATIONAL TRAVEL AND HEALTH -
CHAPTER 6
2. www.cdc.gov/vaccines
3. Vaccines for emerging pathogens: from research to the clinic. Clinical and Experimental
Immunology 2019, 196: 155-156.
4. HLA-E: exploiting pathogen-host interactions for vaccine development. Clinical and
Experimental Immunology 2019, 196: 167-177.
5. Novel approaches for the design, delivery and administration of vaccine technologies.
Clinical and Experimental Immunology 2019, 196: 189-204.
6. Mucosal vaccines and technology. Clinical and Experimental Immunology 2019, 196:
205-214.
7. Vaccines for emerging pathogens: prospects for licensure. Clinical and Experimental
Immunology 2019, doi: 10.1111/cei.13284
8. Emerging viruses and current strategies for vaccine intervention. Clinical and Experimental
Immunology Review Article doi: 10.1111/cei.13295.
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
1. What is the most common cause of asept ic meningit is of viral etiology?
a. Enteroviruses
b. Herpesviruses
c. Arboviruses
d. Retroviruses
e. Orthomyxoviruses
2. All of the following picornaviruses are resistant to the acidity of the stomach except:
a. Coxsackievirus A
b. Coxsackievirus B
c. Echo virus
d. Poliovirus
e. Rhinovirus
3. Which one of the following infection routes is most often involved in the neonatal
transmission of hepatitis B virus (HBV)?
a. Blood transfusion
b. Fetal contact with infected blood during childbirth
c. Ingestion of the virus via maternal breast milk
d. Transmission of the virus from hospital personnel during childbirth
e. Transplacental transmission of the virus
4. Protection against influenza A virus in a nonimmune individual can be achieved
through the administration of a drug that interferes with
a. Viral endonuclease activity
b. binding of host messenger RNA (mRNA) caps by the viral P1 protein
c. Synthesis of viral progeny RNA
d. Uncoating of nucleic acid
e. Viral adsorption and penetration
QUIZ CLICK HERE FOR LIVE QUIZ
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
5. The finding of large, multinucleated, clumps of cells in the bronchial secretions of a 2
year old girl with acute bronchopneumonia suggests that this infection is caused by
a. Bordetella pertusis
b. Epstein-Barr virus
c. Mycoplasma hominis
d. Rhinovirus
e. Respiratory syncytial virus (RSV)
6. In a chronic carrier of hepatitis B virus (HBV), which positive test is most indicative of
high infectivity?
a. Hepatitis B Surface Antigen (HbsAg)
b. Hepatitis B Core Antigen (HbcAg)
c. Hepatitis B e Antigen (HbeAg)
d. Anti-HBsAg
e. Anti-HBeAg
7. A retrovirus is found in a high proportion of laboratory animals of a given species. Most
viremic animals are asymptomatic, but others develop a fatal wasting syndrome, and a
few develop leukemia and other tumors after long periods of latency. The virus in
question most likely lacks which one of the following genes?
a. gag
b. pol
c. env
d. onc
8. A sexually active 22 year old college student presents to the local clinic with a localized
vesicular eruption on the shaft of his penis. A scraping of the base of one of the vesicles is
positive for Tzanck cells. The patient mentions that he had a similar eruption in the same
area 2 months earlier. The reappearance of this eruption may be explained by:
a. Cell mediated immunity (CMI) deficiency in the patient
b. A prolonged period of viremia following the initial infection
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
c. A second infection with a similar virus with a different serotype
d. failure of the patient to comply with therapy prescribed at the initial episode
e. reactivation of a latent infection.
9. Influenza vaccine is targeted towards 'at risk' groups in the UK. Which of the following
are classified as 'at risk' (choose three)?
a) Very young under 2 years old
b) Elderly persons over 65 years
c) The obese of any age
d) Teenagers
10. Combination chemotherapy (HAART) is now used to treat patients with HIV because of
which two factors?
a) Drug resistant mutants arise too quickly with monotherapy
b) This is cheaper than consecutive treatments with monotherapy
c) There is synergism between anti HIV drugs working at different stages of the life cycle
d) HAART is also active versus HTLV-1 and HTLV-II
11. What disease do herpes viruses not cause?
a) Infantile paralysis
b) Encephalitis
c) Sexually transmitted disease
d) Cancer
12. The range of disease caused by the Parvovirus family is wide but identify the
exception from the following:
a) Aplastic crisis in anaemia patients
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
b) Fifth disease at 'Slapped cheek' syndrome
c) Foetal infection with teratogenicity
d)Severe pneumonia
13. How are herpes infections controlled?
a) Chemotherapy
b) Vaccines
c) Hygiene and social distancing
d) No method
14. How is the parvovirus family targeted to reduce disease?
a) Transfusion blood is screened
b) Vaccine has been developed
c) A range of new antivirals
d) Social distancing
15. There are 57 serotypes of adenovirus currently recognised. Which has the most
important clinical impact?
a) Diarrhoea
b) Eye infections
c) Respiratory tract infections
d) Haemorrhagic cystitis
16. When was smallpox eradicated from the world?
a) In 1977 following a WHO campaign
b) In 2000
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
c) Is not yet eradicated
d) In 1796 after Jenner's first vaccine
17. The vaccine used to eradicate smallpox originated as:
a) Live smallpox
b) Live cowpox
c) A genetic recombinant
d) Killed whole virus
18. Which areas of the world are rabies free?
a) USA
b) Norway
c) EU
d) Island nations, UK, NZ and Australia
19. The main animal host varies from continent to continent. Where are two regions
where dogs are important carriers?
a) USA
b) Europe
c) Iran/Middle East/Afghanistan
d) Asia
20. Which disease do polyomaviruses predominantly cause?
a) Tumours
b) Brain pathology
c) No disease at all
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
d) Kidney infections
21. How are rotaviruses predominately identified from clinical samples?
a) Electron microscopy
b) RT PCR
c) Antibody tests
d) Laboratory diagnosis not required
22. Where in the body do oncogenic HPVs especially replicate?
a) Brain
b) Liver
c) Cervix
d) Larynx
23. Which of the following HPV viruses are known to cause cervical cancer?
a) Viruses of all 5 clades
b) Types 14, 16, 18, 31, 45
c) None are oncogenic per se
d) Types 1-180
24. What is the biggest risk factor for infection with Ebola?
a) Working in a category IV laboratory
b) Attending a funeral of a victim outside
c) Nursing a patient at home
d) Attending football matches or large gatherings
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
25. How can the spread of filoviruses be restricted?
a) New antivirals
b) New humanised monoclonal antibodies
c) Hygiene and social distancing
d) New vaccines
26. Nipah is a zoonotic paramyxovirus; where did it originate?
a) Originating in pigs
b) Originating in bats
c) Coming from humans
d) Coming from horses
27. Which member of the paramyxovirus family can cause very serious croup?
a) Measles
b) Meta pneumo virus
c) Hendra
d) Respiratory syncytial virus (RSV)
28. Antivirals can be used prophylactically or therapeutically in persons in which of the
following circumstances?
a) If administered within 4 days of clinical signs
b) If used within 48 hours of first clinical signs
c) Used for the obese
d) Used in children under the age of 2 years where high virus spread is noted
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29. Most pandemics have arisen from influenza viruses from which of the following
animals?
a) Pigs
b) Wild birds
c) Bats
d) Humans
e) Whales
30. The treatment of hepatitis C has been revolutionised most recently by which of the
following?
a) The use of interferon
b) A new vaccine
c) Monoclonal antibodies
d) Direct-acting Antivirals such as daclatasvir and sofosbuvir
31. Many virus infections result in immune pathology, this is caused predominantly by
which of the following?
a) A cytokine storm
b) Antibody mediated reactions
c) A response of killer T cells (CD-8)
d) A decline in function of the immune system
32. What is the most common way for a virus to kill a cell?
a) Dissolves the cellular membrane
b) Induces apoptosis via caspases
c) Fragments cellular DNA
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d) Totally blocks cellular transcription
33. Poliovirus can most easily become more virulent by which of the following processes?
a) Mutation of the RNA genome at only a few positions
b) Recombining with another enterovirus
c) Altering its protein coat
d) Multiple nucleotide deletions and substitutions
34. Of the following factors, which are the most important factors for virus spread and
infection?
a) Age
b) Sex
c) Genetic factors
d) Economic status
e) Travel
35. Chikungunya has spread widely from Asia and Africa into the Caribbean in recent years.
This has been mainly facilitated by:
a) Mutation in the virus allowing replication in the mosquito Aedesalbopictus
b) Air Travel
c) Climate change
d) Poor mosquito control and the absence of DTT
36. MERShas four special characteristics and here we have one exception - which is it?
a) Spread by faecal oral route
b) Aerosol droplet transmission
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INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
c) Reservoir in bats
d) A conduit to humans via camels
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Int roduct ion
Bacterial infections corner limelight in most of discussions in academic fora.
Few obvious reasons are that they are dominant causes of sepsis be it local or systemic in the
community, the ability to cause serious illness, morbidity and mortality unless treated early
and last but not the least antimicrobial resistance. However now it appears that viruses are
equally if not more important in causation of human suffering and inflicting many deaths.
Considering the re-emergence of viruses thought under control eg measles and emergence of
new viruses HIV in recent past, more recently H1N1 among many new respiratory viruses, it is
clear we don't know much about how viruses surprise a healthy person by inflicting sickness.
The ability to cause chronic disease is also a feature of some viruses.
Association of new and old viruses with disease syndromes previously thought as bacterial or
idiopathic are also becoming evident. One of the main reason was in many conditions viruses
were not investigated due to lack of facilities for lab diagnosis. However, the scenario is
rapidly changing making us compulsorily revisit Human -virus interactions and their outcome.
This article attempts to bring home to ICT group in simple language the global advances in
pathogenesis and lab diagnosis of human viral infections
Pat hogenet ic mechanisms of Viruses.
Virus is t ot ally different in morphology, biology, t ypes of disease caused.
Table present s comparison of salient feat ures of t wo mechanisms of Viral disease
AN ATTEMPT TO UNDERSTAND PATHOGENETIC
MECHANISMSOF HUMAN VIRAL DISEASES
Dr H.Srinivasa, MD Microbiology AIIMS,New Delhi
FEATURE BACTERIA VIRUS
Size Larger- in micromet ers Larger- in
micromet ers
Morphology Complex , Cell wall
encloses Cell
membrane which
int urn cont ains
cyt oplasm having
nucleus
Relat ively simpler-
Prot ein shell
cont aining nucleic
acid, some have
out er envelope
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Nucleic acid
Have both DNA and RNAHave either DNA or RNA-
thus classified as DNA or
RNA
Mult iplicat ion By Binary fission By replicat ion inside host
cells- copies formed like
xerox using t emplat e
nucleic acid ,each lat er
covered by prot ein
Int erferon Generally not
produced
Generally produced by
infect ed host cells
Ant ibiot ics
Antibacterial
compounds act on
bacteria- may be narrow
spectrum or broad
spectrum Exception:
Drug resistant bacteria
Ant i viral compounds act
but only on limit ed
groups of viruses: viruses
also develop drug
resist ance
Act ion of disinfect ant s General Purpose
disinfect ant s-
suscept ible
Only high level
disinfect ant s act
Bact eriophages These are viruses but
Act on bact eria- only
t o limit ed genera
Do not act
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An encounter with virus do not necessarily cause disease in humans. Why is it so? In fact
may a times there will not be any symptoms in humans even though virus is present in the
body. This is called asymptomatic infection. However the same virus in another individual
may not only multiply but also cause symptoms that is the disease. In fact asymptomatic
infections are more common and outnumber symptomatic infections especially in
outbreaks. Outbreaks of influenza is a classic example. This concept is caused as iceberg
concept of infection. Iceberg in Ocean, though floats, on careful observation it's actually 90
percent underwater and only 10 percent is visible. Visible portion is compared to
symptomatic group and rest , that is huge 90 percent is compared to asymptomatic group.
If we further divide asymptomatic, a few may have mild symptoms, also in symptomatic
group some will be having severe symptoms and invariably very sick and bed ridden.
Genetics of virus
Virus are endowed with certain unique features, which make humans easy prey.
They are:
1 Target only special molecules of host called as receptors once bound, find easy entry in to
cell eg HIV
2 Multiplication rate is fast
3 Many virus being inside host cells evade immune response
4 Some even do not allow host cell to produce IF, even if IF is produced which normally
suppress viral spread from cell to cell. The viral infected may be refractory to IF eg influenza
A ,Dengue
5 Viruses are notorious for frequent genetic changes. Thus, an altered virus is less
recognizable to host immune system. Major change in genetic code result in all most a new
virus not recognizable by immune system. The genetic changes are mutation,
recombination.
6 Generally human Virus cause human disease and animals will have its own spectrum of
viruses. Some human viruses have in addition animals as reservoir, in some other cases
viruses in animals change their characteristic and become endowed with the ability to
cause human infections.
7 Groups of viruses associated with chronicity eg. hepatitis viruses b,c slow viruses ...
Viroids.. prions, viruses normally cause asymptomatic infection but can cause severe
disease in immune-compromised states,
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8 Certain viruses like CMV, EBV normally latent in body may cause serious infection in post
organ transplant.
Are viruses always bad, are there any good viruses...Virologists used say less pathogenic
viruses interfere with growth of pathogenic viruses. Recent data summarized as advances in
this issue by Dr Sukanya suggests it may indeed be so, there may be normal resident
viruses
Further understanding required in viral pathogenesis globally.
Even so called vaccine preventable viruses like measles, rubella, chicken pox are
resurfacing. Also we are facing Viral infections becoming more with atypical or severe
population immunity levels, reduced uptake of vaccine under nutrition. Nutrition.. role of
vitamins vitamin deficiency A, D predispose to viral infections.the latter may lead to further
escalation of vitamin deficiency there by setting a chain reaction Which in turn leads to
more severe , protracted infections. Vitamin C is another powerful antioxidant protection
against respiratory viruses rhino viruses, influenza viruses A Further provision of bed rest so
that convalescence can occur convalescence...needs to be stressed close family members of
the index case. These measures may curtail protracted illness which burdens the family
emotionally and economically. Mixed bacterial and viral infections also pose a major
challenge, As bacterial infection may be diagnosed but not viral. However with the
availability of Real time PCR, Multiplex PCR it is becoming evident that there are sub groups
of Mixed infections which may present atypically. Thus the current situation demands more
re-education of ICT Professionals and debates and discussions, so that best treatment
protocols are used to manage viral infections.
54
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
With the introduction of the worldwide campaign to eradicate Smallpox by WHO in 1967,
the disease was totally eradicated in 1977, and in 1980 the world health authorities
declared the world is free from Smallpox in 1980. Smallpox is caused by a DNA type virus
with Variola major producing classical Smallpox and Variola minor producing Alastrim, a
less serious disease. And the last death from the disease occurred due to a laboratory
accident in England in 1978 (World Health Organization.)
LAST KNOWN CASE OF SMALLPOX - So far, the only known victim is Janet Parker, 40, a
medical photographer. She developed a fever and a rash in early August, but two weeks
passed before her illness was diagnosed as variola major, the severe form of smallpox.
ARE WE IMMUNE TO SMALLPOX TODAY? Many of our older population were vaccinated in
our childhood and none of the younger got vaccinated, however, the Immunity after
vaccination only lasts for 3?5 years? Does it just mean? Today No-one is immune, Next
question?Is it hypothetical it would spread fast as the flu, and kill like the Black Death in the
Middle Ages?It would be biblical thinking or reality?
SCIENCE WILL NEVER STOPS FOR SEARCH ON REEMERGING INFECTIONS - Smallpox
under consideration to think further it can be a Possibility ?- Can it re-emerge. The Centres
for Disease Control and Prevention is now running tests on the six forgotten vials of
smallpox that were recently discovered in an unsecured laboratory, to see if any live virus
remains in them. Stray cases of Varicella (not Variola which causes Smallpox) Monkeypox,
Parapoxviruses and aggressive forms of drug reaction can be mistaken as the outbreak of
Smallpox The present question Smallpox can it re-emerge after more than three decades of
silence, the hypothetical answer is very, very, remote as there is no known animals
harbouring the virus or vector went into hibernation. Even in the crisis of re-emerging/or
the surfacing of the mutated virus can be easily controlled, as we learned a lot of lessons
with SARS/INFLUENZA, And Smallpox is less contagious in the spread, as it requires close
contact between face to face and patients with a rash is infectious, and easily Diagnosed
with growing awareness in the better-communicated world and increasing awareness of
re-emerging infectious diseases. . Millions of doses of Vaccine for Smallpox in stock and are
available at the click of a mouse,
WHO STORES THE SMALLPOX VACCINE STRAINS - Already WHO has recommended that
only five centers in the entire world, including the CDC in Atlanta, be allowed to store strains
of the virus for research purposes?
ERADICATION OF SMALLPOX? - CAN IT RE-EMERGE?
CAN WE SUCCEED WITH OTHER VIRAL INFECTIONS?
Dr.T.V.Rao MD Former Professor of Microbiology,Andhra Medical College
55
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
SEARCH FOR NEW METHODS TO DIAGNOSE POX VIRUSES -Research continues to Make
Better Tests, CDC also is conducting research to develop better lab tests to detect pox-like
viruses more accurately because this would help diagnose smallpox in patients, in time of
re-emergence of Smallpox.
OUR SUCCESS ON CONTROL OF OTHER VIRAL INFECTIONS WITH VACCINATION -
Another important preventive measure is immunizing people against viruses. This involves
giving people vaccines that stimulate the immune system to make antibodies, proteins that
target a specific germ. Vaccines to prevent Hepatitis B, polio, mumps, measles, rubella
(German measles), and chickenpox are usually given to babies and young children. Vaccines
also can prevent influenza and Hepatitis A. vaccines are useful only against certain kinds of
viruses. The search for vaccination in Viral unending game as influenza viruses change in
minor ways every few years and in a major way about every ten years, so a flu vaccine is
useful for only a year or two and we have to create a renewed vaccine. Increasing costs to
the patients and public health.
WHAT WHO THINKS ON POST ERADICATION OF SMALLPOX After the eradication of
smallpox had been confirmed by the WHA in 1980, WHO commenced a five-year program
to implement the post-eradication policies adopted by the World Health Assembly in
resolution WHA33.4. This program had been recommended by the Global Commission for
the Certification of Smallpox Eradication and was designed both to allay the fears that
smallpox might recur and provide full documentation of the effort.
CAN WE ERADICATE MANY OTHER VIRAL INFECTIONS? Obviously one cannot avoid all
viruses, as someone around us suffers from a viral infection. There tends to be a
mini-epidemic of colds at the start of every school term as every virus acquired is shared
around! However, eradication of viral diseases is not a straightforward process. Indeed,
there are viral diseases that appear impossible to eradicate due to certain characteristics of
the causative virus. However, eradication of viral diseases becomes difficult due to certain
characteristics of the causative virus as happens with Herpes simplex virus resides latently
in neurons, from where infection can reactivate. One cannot identify latently infected
individuals clinically but they have the potential to become infective when the virus
reactivates. In spite of many efforts, some viruses continuous to be a challenge and
vaccination and preventive measure are essential as in Influenza. This explains why
individuals can be reinfected with influenza and why the content of the seasonal vaccine
must be altered annually.
56
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
WE ARE BACK TO BASICS IN PREVENTION AND CONTROL OF VIRAL INFECTIONS -
Hygiene sanitation, Vaccines, the first steps in preventing the spread of viral infections, The
great step remains with the practice of good hygiene. This means washing the hands often
and eating only food that has been prepared properly. It also means building and
maintaining facilities for getting rid of sewage safely and for providing clean drinking water.
References Source of Information
1 Medicine: Living Disease Monday, Sept. 18, 1978, TIMEmagazine
2 Viral Infections ? human diseases Forum Updates 2018
3 Emergencies preparedness, the response by WHO on Post elimination of Smallpox 2016
4 Current Resources on Smallpox CDC updates
57
INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
ZIKA VIRUS- EMERGING VIRAL INFECTION AN UPDATE
Its name comes from the Zika Forest of Uganda, where the virus was first isolated in 1947.
Zika virus is related to the dengue, yellow fever, Japanese encephalitis, and West Nile
viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from
Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the
Americas, leading to the 2015?16 Zika virus epidemic. Zika virus is a single-stranded RNA
virus of the Flaviviridae family, genus Flavivirus.
TRANSMISSION - Zika virus is transmitted to humans primarily through the bite of an
infected Aedes species mosquito. The mosquito vectors typically breed in domestic
water-holding containers; they are aggressive daytime biters and feed both indoors and
outdoors near dwellings. Nonhuman and human primates are likely the main reservoirs of
the virus, and anthroponotic (human-to-vector-to-human) transmission occurs during
outbreaks.
EPIDEMIOLOGY Out breaks of Zika have occurred in areas of Africa, Southeast Asia, the
Pacific Islands, and the Americas. Because the Aedes species mosquitoes that spread Zika
virus are found throughout the world, it is likely that outbreaks will spread to new countries.
In December 2015, Puerto Rico reported its first confirmed Zika virus case. Locally
transmitted Zika has not been reported elsewhere in the United States, but cases of Zika
have been reported in returning travelers the most common symptoms of Zika virus
disease are fever, rash, joint pain, and conjunctivitis (red eyes). The illness is usually mild
with symptoms lasting from several days to a week. Severe disease requiring hospitalization
is uncommon.
Diagnosis wit h Specific t est s are suggest ed by FDA
Specific Test s
FDA has issued Emergency Use Authorizations external icon for multiple NAAT assays to
diagnose Zika virus infection. Various Zika virus NAATs can be used on serum, plasma,
whole blood, cerebrospinal fluid, urine, or amniotic fluid. FDA has cleared one enzyme
immunoassay to detect Zika virus IgM antibodies in serum and currently has issued
Emergency Use Authorizations external icon for other IgM antibody assays to diagnose Zika
virus infection.
ACADEMIC COMMUNICATION IN VIROLOGY
Dr.T.V.Rao MD Former Professor of Microbiology,Andhra Medical College
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Ict newsletter january 2020

  • 1. 11 SPECIA L EDITION ON CLINICA L VIROLOGY ISSUE2 | ISSN: VOLUME II | JAN 2020 INFECTION CONTROLTRENDS NEWSLETTER Publication of Infection Control Academy of India 1st Ever PG Diploma in Infection Prevention & Control in India
  • 2. 2 FROM EDITORS Dear Colleague, Hope the New Year and the new decade has started well for you and your dear ones. On behalf of IFCAI, ICT Newsletter, and The IPC News teams wish "Infection Preventionists (IP)" around the world and their families a very happy, healthy and prosperous 2020. ICT Newsletter launched in 2018 as IFCAI broader mission to create the capacity of IP's in India and other LRC. We aim to improve healthcare by reducing the risk of infection . The team at Academy is thankful to all its members, associates, volunteers, supporters and readers of its publications from all over the world for constant feedback, support and encouragement. IFCAI publishing seeks to address the information problem in infection Prevention and Control (IPC) by creating an open vehicle and being a vibrant discussion forum. We envisage an open, democratic and inclusive forum that brings together and addresses a large number of aspirants and practitioners of IPC. We wish to deliver content relevant for all IPC stakeholders including policymakers, NGO's, Governments specifically in LRC. Past year had been quite eventful we could see a lot of activity: we forged relations with professional IP associations abroad, we broadened our reach within India, our publishing activity has seen multi-fold increase through digital strategies etc. While all this is satisfying, the most memorable event happened towards fag end of 2019: the much awaited PG diploma in Infection Prevention and Control was notified by University of Hyderabad in collaboration with Infection Control Academy. First ever such course to be offered by a university in Asia, Africa, ME and other developing nations will remain a historic milestone in our journey towards "preventing all preventable infections withing healthcare". The edition which is now in your hands is brought with a focus on emerging and re-emerging Viral Infections. As you would have noticed the design, navigation and blend of offline/online elements are introduced in this edition for pleasurable reading experience. I am sure like earlier editions this will also find a special place among your upskilling resources. We would appreciate your feedback enabling us to constantly work on improvements. Please send your comments, suggestions, views to secretariat@ifcai.in At the turn of the decade, ICT Newsletter is rededicating itself to the mission of spreading IPC knowledge and shall look forward to the much deeper and meaningful collaboration. On behalf of the entire team wishing all again a Very Happy 2020. Dr Ranga Reddy Burri Dr TV Rao Dr Sukanya Dr Srinivas Hiresave Dr Shamanna
  • 3. 3 ISSUE2 VOLUMEII | JAN 2020 EDITORIAL TEAM Dr. Ranga Reddy Burri is Health policy enthusiast focused on public health awareness, education and training. Dr. Reddy is Physician, Public Health specialist & Social Entrepreneur with interest in business verticals of high social impact. He graduated from Minsk Government Medical Institute, Belarus with MD (Physician) degree; subsequently he did his PG Diploma in management from Pondicherry University and Advanced Management from IESE, Barcelona, Spain with specialization in Strategy & Business Development. Dr. Reddy is the founder trustee of Infection Control Academy of India (IFCAI). The organization is a result of his leadership skills, knowledge and experience gained from working in both domestic and international MNCs. Yet, the Academy?s most valuable strength lies in the strong sense of empathy for humans and their health imparted by Dr. Reddy and his colleague trustees. His current responsibility includes leading Sanmed Healthcare, a startup with world class manufacturing capabilities in external preparations. He supports several non-profit organizations in the capacity of adviser including Neelam Rajasekhar Reddy Research Center for Social Progress, e-learning center of Hyderabad Central University & Indian Institute of Public Health. His flair for entrepreneurship has led him to mentor through imparting knowledge to NGO?s, startups & micro-small enterprises. Dr. Ranga Reddy President IFCAI and Chief Editor ?Infection Control Trends? Email: dr.rangareddy@ifcai.in Dr. T.V. Rao is a former Professor of Microbiology, Alumni of Andhra Medical College, Visakhapatnam (Andhra Pradesh, India). His experiences in Zambia showed him how people lose their lives to infections and how the lack of resources was a great challenge that practically forced patients to be treated blindly. His association with scientific microbiologists at ICMR (NICED Calcutta) taught him how all that we do is not necessarily right and why it is essential to involve oneself in diagnostic laboratory conditions and even bedside medicine. His observation includes the seamless working of Darwin?s Theory in relation to microbes and how they pose real challenges. He also believes it is time to rethink one?s role as Medical and Clinical Microbiologists, especially during a time where it is necessary to understand that Antibiotics are not magic bullets but soft weapons to destroy the progress of medicine. Dr. Rao has created content that helps many in developing countries with a global following of 5 million. Dr. T. V. Rao Former Professor of Microbiology Author, Mentor and Advisor Editor ?Infection Control Trends? Email: doctortvrao@gmail.com Dr H Srinivasa has Academic career of more than 3 decades in teaching clinical microbiology for MBBS, MD, BSc nursing at St. Johns Medical college: superannuated at the same institution Bangalore in 2015.Subsequently Career as a Free Lance Consultant Microbiologist & Infection Control. NABL assessor as well Actively involved in Infection Control Groups in several Fora with Dr Ranga Reddy , Dr TV Rao which Is his current passion ,disseminating, sharing , and learning newer aspects of Inf disease diagnosis and Control. Dr. H Srinivasa MD Medical Microbiology (AIIMS, New Delhi 1981) Editor ?Infection Control Trends?
  • 4. 4 ISSUE2 VOLUMEII | JAN 2020 Dr Sukanya Graduated from Bangalore Medical College (BMC) with MBBSand passed out as a rank holder in MD Microbiology from Madras Medical College (MMC). Awarded PGDID-Infectious Diseases by Medvarsity in collaboration with University of NSW, Sydney-Australia in 2017. Certified Infection Control Consultant by the CBIC (APIC) in 2018. Over 13 years of experience in Laboratory Diagnostics, Hospital Acquired Infection Prevention and Control, Good Antibiotic Prescription Practices, Infectious Diseases Management, Research and Teaching. Was a Consultant Clinical Microbiologist, Infection Control Officer, and Convener of Antibiotic Prescription Practices at Fortis Hospitals, BG Road, Bangalore for over 9 years and formerly an Assistant Professor at M.S. Ramaiah Medical College and Hospital, Bangalore for around 4years. Currently - Consultant for Mediknit ,Singapore which is a healthcare start-up focused on learning and education for medical professionals and Associated with the Care Institute of Health Sciences, Hyderabad for training programmes on Infection Control and Prevention. Invited speaker in over 30 conferences, forums, and training programs Accolades for outstanding contributions in JCI and NABH, NABL accreditations. Instrumental in leading the organisation (Fortis) to win the prestigious AHMA Gold award APSIC Silver award for CSSD and the CAHOCON awards Published several research articles and clinical case studies in peer-reviewed national and international journals. Dr. Sukanya Rengaswamy MD, PGDID, CIC, Technical Editor ?Infection Control Trends? Dr B.R. Shamanna completed his medical education from Karnataka Medical College, Hubli, and his Doctoral studies (MD) in Community Medicine from the All India Institute of Medical Sciences, New Delhi. He also holds a double Diplomate of the National Board in Maternal & Child Health as well as in Social & Preventive Medicine. He completed his M.Sc. from University College London with distinction in Community Eye Health. He served as a Senior Research Officer in the International Council for Control of Iodine Deficiency Disorders (ICCIDD), a WHO-PAMM-UNICEF Organization and later as a Senior Resident & Medical Officer, Primary Health Centre in Haryana. He is a visiting faculty to the Masters in Public Health Eyecare at the London School of Hygiene and Tropical Medicine and an Adjunct Faculty with the Public Health Foundation of India. He is on the ethics committee of the Fernandez Hospital for Mother and Child in Hyderabad, Piramal Swasthya Management and Research Institute and the L.V. Prasad Eye institute, Hyderabad and was instrumental in helping Indian Institute of Public Health, Hyderabad institute its own IEC. Most recently he completed a prestigious fellowship program and is designated as a PHLEADER through a NIH supported Public Health Leadership Academy of Implementation Sciences at Emory University, Atlanta, Georgia, and USA. His interests are Health & Welfare economics, Disability Inclusive Development, Education and teaching methods, Implementation Research in Health Sciences, and Alternative opinions and Politics in Health Care. He currently co-ordinates and helps deliver the Ph.D. Programme in Health Sciences from the University of Hyderabad Dr. Shamanna School of Medical Sciences, University of Hyderabad Editor ?Infection Control Trends?
  • 5. 5 ISSUE2 VOLUMEII | JAN 2020 INDEX VIRAL INFECTION IN ICU:A CONCISE REVIEW DR. MASOOD MOHAMMED 6 VIRAL INFECTION IN PEDIATRICS DR M VISHNUVARDHAN REDDY 26 OLD AND NEW VACCINESFOR THE PREVENTION OF VIRAL INFECTIONS DR. RENU AVULA 34 QUIZ 40 AN ATTEMPT TO UNDERSTAND PATHOGENETIC MECHANISMSOF HUMAN VIRAL DISEASES DR H.SRINIVASA 50 ERADICATION OF SMALL POX ?-CAN IT RE-EMERGE?CAN WE SUCCEED WITH OTHER VIRAL INFECTIONS DR.T.V.RAO 54 ACADEMIC COMMUNICATION IN VIROLOGY DR.T.V.RAO 57 INFECTION CONTROL PRACTICESIN THE ERA OF EMERGING VIRAL INFECTIONS DR. UMABALA PAMIDIMUKKALA 60 VACCINE HESITANCY: HEALTH AND ECONOMIC IMPACT DR RANGA REDDY BURRI 73 UPDATESIN VIROLOGY COMPILED BY DR SUKANYA RENGASWAMY 78 ANSWERSFOR QUIZ 80 INSTRUCTIONSFOR AUTHORS 81
  • 6. 6 Int roduct ion: Since Reed et al discovered yellow fever as the first viral human illness in 1901, many viral pathogens and associated disease have been identified. Though most of the viral infections are being treated in an outpatient clinic few cases among them get admitted to the hospital and very few to intensive care unit (ICU). Thanks to recent diagnostic studies which not only detect them rapidly but also are easy to perform and universally and easily available at an affordable cost. Because of the availability of these rapid diagnostic tests prevalence of viral infection has been increasing both in community as well in hospitals(1). Few of these viruses like Avian Influenza A H7N9 and a novel corona virus, Middle East Respiratory syndrome corona Virus (MERS-coV) are associated with high morbidity and mortality(2, 3). In this review we are going to discuss about the characteristics of virus in general and discuss some common viral infections which lead to ICU admission and also those infections which are ICU acquired in a syndromic approach and their management. Charact erist ics of viruses: (Fig 1) Viruses are tiny (20 to 300 nm) living forms that reproduce inside the cell of a living host. They consist of DNA or RNA (genetic material) based on which they are classified, which is contained in a capsid, a polymer of capsomere made of one or two viral protein molecules. The genetic material and capsid are called nucleocapsid which have a specific symmetry, either icosahedral, helical (helical symmetry is formed only by RNA viruses) or complex. capsid contains either DNA or RNA but never both. INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Viral Infect ion in ICU: A Concise Review Dr. Masood Mohammed MD, MRCP (UK), EDIC, FFICM (UK) Avian Influenza AH7N9 and a novel corona virus, Middle East Respiratory syndrome corona Virus(MERS-coV) are associated with high morbidity and mortality
  • 7. 7 Most of the viruses don?t have a membrane and are called as naked or non-enveloped, which are enveloped in a host origin lipid bi-layer into which viral proteins are anchored. Though the enveloped viruses have an advantage of genome protection they are sensitive to lipid solvent and can be dissolved by detergent unlike viruses (non-enveloped/naked) with protein nucleocapsid exteriors which may be resistant to detergent. Viruses are classified based on nucleic acid composition, nucleocapsid size and symmetry, and presence or absence of an envelope. Broadly they are divided into either RNA or DNA viruses (both of them can be single stranded or double stranded i.e. ssRNA, dsRNA, ssDNA or dsDNA). Viruses unlike other living organisms lack organelles and ribosomes, so they need host cell in order to replicate. Depending on the genetic material they have their method of replication differs and involves steps like adsorption, uncoating of the virus, synthesis of viral structures, and release of virus particles by budding or cell lysis. They may harm the host cell during this process in the form of chronic or latent infection, induction of oncogenes and to cell death. RNA viruses: Except very few ( Reovirus and Birnavirus) most of the RNA viruses are single stranded. The ssRNA genome is sub-classified as positive (+) stranded ( can be translated into protein by host cell) or negative (-) stranded which by RNA-dependent RNA polymerase converted to + strand before translating proteins. Though the retrovirus possess + ssRNA strand it doesn?t translate proteins unless it is converted to dsDNA by reverse transcriptase a unique viral enzyme present only in retro viruses. DNA Viruses: Most of the viral DNA genome are double stranded except Parvovirus. They must undergo transcription to mRNA before translating into proteins. RNA Viruses and human disease: Othomyxoviridae: (Influenza A,B and C): Most of the viruses in this group have predilection to glycoprotein receptors in upper respiratory tract. They are pleomorphic with ssRNA viruses with a helical nucleocapsid. Influenza A,Band Cbelong to this family. INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020
  • 8. 8 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Influenza virus has two types of glycoprotein spikes on their envelop with haemagglutinin activity (HA) neuraminidase activity (NA). HA spike attaches to the epithelial cells of upper respiratory tract (URT) and provide cellular entry route for the Influenza. NA spikes helps in entry as well as replication and release of the virus. All the three types of Influenza (A,B, and C) have many stains due to antigenic differences in HA and NA spikes. Pandemics occur due to antigenic shift ( major changes in the glycoproteins due to assortment of genes between different viruses)and seasonal epidemics are due to antigenic drift( minor changes in glycoproteins). Major pandemics in history are 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 2009 (H1N1). Diagnosis is by detection of viral RNA by reverse transcription followed by Polymerase Chain Reaction (RT?PCR) and is considered as the gold standard diagnostic method for detecting influenza viruses and can be carried out on the nose and throat swabs, nasopharyngeal, tracheal aspirates or bronchial washings. Neuraminidase inhibitors (NAIs) (Oseltamivir, Laminavir, Zanamivir and Peramivir) are the treatment of choice for severe cases. Paramyxoviridae: (Respiratory syncytial virus (RSV), human metapneumovirus, Measles virus, mumps virus, Hendra virus, Nipah virusand Newcastle disease virus) These ss RNA have many features similar to Orthomyxoviridae with few exceptions like one glycoprotein for HA/NA (instead of two spikes) and causes host cells to form syncytia (multinucleated giant cells) with the help of fusion protein. Respiratory syncytial virus (RSV), human metapneumovirus, Measles virus, mumps virus, Hendra virus, Nipah virus and Newcastle disease virus are the recognized pathogens affecting humans belong to this group. Diagnosis is by detection of viral RNA by RT?PCR from URT and lower respiratory tract (LRT) for most of these viruses along with clinical grounds. Management of these cases in ICU is supportive, however, in immunocompromised patients aerolized Ribavirin is of benefit. Coronaviridae: Usually coronaviruses cause insignificant URT infections, However, few coronaviruses include the severe acute respiratory syndrome coronavirus(SARS- CoV) and MERS- CoV cause high mortality. Infection is best confirmed by detecting the viral genome by RT?PCR in URT or LRT specimens.
  • 9. 9 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Treatment is largely supportive with no specific antiviral therapy. Retroviridae: Two genera of human interest. 1) Lentivirus: (Lenti ? Slow) ? Human immunodeficiency virus1 & 2 ( HIV 1 & 2) 2) Human T- lymphotropic virus ? bovine leukemic virus group ? HTLV-BV- Human T-cell leukaemia virus1 & 2 ( HTLV 1 & 2) The virion has cone-shaped, icosahedral core, containing the major capsid protein CA (p24). It contains reverse transcriptase, integrase and protease enzymes. Diagnosis is based on detection of anti-HIV IgG antibodies. An enzyme-linked immunosorbent assay (ELISA) is cheap and simple to perform. A western blot analysis may be used to confirm a positive result. In acute seroconversion, the antibody response may not mount for up to 12 weeks. HIV RNA measurement and detection of p24 antigen may be useful. HIV infections lead to opportunistic infection by affecting CD4 T- lymphocytes. Treatment: Typical highly active anti-retroviral therapy (HAART) regimen include combination of three anti-retroviral therapy (ART) include two nucleoside reverse transcriptase inhibitor (NRTI) and one Protease Inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) or fusion inhibitors (FI). DNA viruses and human disease: Adenoviruse: They are naked ds DNA viruses with more than fifty immunologically different types. They cause respiratory, gastrointestinal, neurological and eye symptoms. Diagnosis is by PCR of bronchoalveolar lavage (BAL), liver, cerebrospinal fluid (CSF), or faecal samples. Viral load is useful in starting empirical therapy with Cidofovir in immunocompromised patients. Treatment is reduction of immunosuppressive therapy and starting Cidofovir. Ribavirin can also be used with no evidence of virologic clearance.
  • 10. 10 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 HerpesViridae: They are subdivided into alpha, beta, and gamma. 1) Alpha-herpes viruses : Herpes Simplex virus(HSV) 1 and 2 and Varicella Zoster Virus (VZV) causes ballooning of the cells and the formation of multi- nucleated giant cells - form vesicles between the epidermal and dermal layers of skin and mucosal surfaces. Alpha-HSVs can invade and replicate in the CNSand establish latency in dorsal root ganglia. 2) Beta-HSVs group: Cytomegalo virus (CMV), Human Herpes virus (HHV) 6 and 7 have an affinity for lymphocytes and monocytes and cause infected cells to become enlarged (cytomegaly). 3) Gamma HSVs group: Epstein Bar virus (EBV) and HHV-8 are also lymphotropic and have oncogenic potential. Patients with compromised cell-mediated immune systems can present with severe herpes virus infections. Diagnosis: HIV1 is diagnosed by PCR from CSF or LRT specimens and VZVcan be diagnosed clinically but confirmed by VZV PCR from vesicular fluid. CMV IgM indicates acute infection, IgG stays lifelong. CMV PCR from blood and body fluids can also be used. To confirm CMV end ? organ disease CMV detection in damaged tissues is required. EBV is characterized by atypical mononuclear cells in peripheral smear, when they are visible infectious mononucleosis (IM) is often suspected. Heterophile antibody or EBV IgM in blood can confirm virologic diagnosis. Treatment: Acyclovir, Valaciclovir and Ganciclovir are the antivirals used for HSV1, VZV and CMV respectively. Apart from the above Varicella Zoster immunoglobulin for pregnant and immunocompromised patients within 10 days of exposure to VZV. Intravenous Foscarnet for CMV and corticosteroids for EBV infected patients with significant neurological involvement, haemolysis or thrombocytopenia are the treatment options. Viral Syndromes in ICU: To make a diagnosis of viral infection based on clinical signs and symptoms is difficult. A combination of clinical syndromes and specific laboratory tests guide to diagnosing and treat these viral infections. Here we are going to discuss various viral infections of adults in ICU based on the organ involved with syndrome wise approach and treatment.
  • 11. 11 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Respirat ory Infect ions: In recent years because of availability of new diagnostic tools like PCR it has been noticed that viruses as the causative agent for pneumonia are on rise and causally associated with 16 ? 49% patients admitted with respiratory failure and/or LRTI to ICU(4, 5). They were found both in Community Acquired pneumonia (CAP) and Nosocomial pneumonias. Pandemic 2009 influenza virus, SARS avian influenza and endemic middle east corona viruses can cause severe CAP leading to acute respiratory distress syndrome (ARDS) and high mortality and morbidity(6). Community Acquired pneumonia: Though bacteria are the common cause of severe community acquired pneumonia, approximately 3 to 10% of these cases are due to viruses(7-13). In a recent metanalysis The pooled proportion of patients with viral infection was 24.5% with common viruses being Influenza viruses (8%), corona virus (3.3%) and respiratory syncytial virus (2.2 %)(14). With the availability of new diagnostic tools (PCR), it has been observed there is a raise in detection of viruses like human metapneumovirus and adenovirus(15, 16). Clinically these viruses cause varied symptoms from simple flu-like symptoms or atypical pneumonia presentation in immunocompetent patient to severe lobar or bilateral pneumonia leading to ARDS in immunocompromised patients(17-20). Nosocomial Pneumonia: Contrary to the belief that nosocomial pneumonias are due to bacteria, it has been reported that that virus pneumonia can be nosocomial acquired, especially in immunocompromised individuals(21, 22). In a recent study 34% of the 134 health care associated pneumonia (HCAP) patients had at least one respiratory virus recovered, the most frequent being rhinovirus, parainfluenza virus, human Metapneumovirus and influenza virus(23). Ventilate Associated Pneumonia (VAP): It is very difficult to correlate the viral positivity in LRT samples to VAP in ventilated patients as most of them are colonized. It is not unusual to see HSV bronchopneumonitis in immunosuppressants, with ARDS, after surgery or burn victims. However, in a French study among 201 ventilated non-immunocompromised patients though BAL was positive for HSV in 64% patients and only 21% (42 patients) were found to have HSV Broncho pneumonitis(24). Among 42 of 201 patients 19 (9.4%) had combined HSV and bacterial VAP, whereas the remaining 23 (11.4%) had only HSV Broncho pneumonitis.
  • 12. 12 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Though the mechanical ventilation (MV) duration was prolonged in HSV bronchopneumonitis patients mortality was the same between two groups. In spite of several data argue in favour of HSV pathogenicity its exact significance is still open to debate. Similar to HSV reactivation of CMV in immunocompetent patients without lung involvement was observed with very few patients developing CMV pneumonitis especially those who are on prolonged MV. Mimi virus a large virus is also been attributed to cause VAP in immunocompetent patients. There is no doubt that mortality of patients with HSV and CMV viremia and pneumonia is high, the significance of isolation of these viruses in LRT of immunocompetent ventilated patients is not clear. Treatment of Viral respiratory infections: For Influenza, vaccination remains the most effective measure, especially for the high risk and elderly(25). Neuraminidase inhibitors (oseltamivir or zanamivir) are recommended for severe disease presentation, (severe pneumonia, requiring mechanical ventilation) or patients at high risk for complications e.g. immunocompromised individuals and in all suspect cases in areas endemic for a strain with high mortality (avian influenza strain). Oseltamivir was used at a dose of 75 mg twice daily. Some use 150 mg twice daily which is safe and well tolerated, have been used to treat Influenza B, some influenza A strains with reduced susceptibility and CNS involvement. But overall supportive evidence is lacking and risk of antiviral resistance may emerge(26). Few novel antivirals have been used in special cases. Among them a single dose intravenous Peramivir which was approved by United states Food and Drug Administration (USFDA) for a short period to treat hospitalized patients with 2009 H1N1 pandemic influenza and a single inhaled dose of Laminavir for oseltamivir resistant seasonal influenza virus(27). Favipiravir used to inhibit a variety of influenza viruses, including highly pathogenic avian influenza H5N1 viruses. Apart from the above entry inhibitors, terminase and helicase enzyme inhibitors, translation inhibitors and nucleoside analogues such as cidofovir are used as an off-label(28). Combination antivirals as used in HBV,HCV and HIV infections was not established to treat these respiratory viral infection. In a randomized controlled study of oseltamivir-zanamivir combination efficacy for seasonal influenza was established, but clinical antagonism was observed in another study(29, 30).
  • 13. 13 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Other therapies: Corticosteroids: In patients with severe influenza and septic shock low dose systemic steroids can be used. However, some don?t prefer them as few RCT showed corticosteroids may be associated with delayed clearance of viruses from(31, 32). Plasma & Immunoglobulin: A favourable response was observed with Immunoglobulins and convalescent plasma in patients with severe avian influenza A (H5N1) and H1N1 pandemic 2009 in a RCT and few case series(33-35). Need more RCTs before generalizing these treatment options. Cent ral Nervous syst em Infect ions: Inflammation of meninges and brain parenchyma due to viruses infecting CNS is one of the cause of meningitis and encephalitis respectively. The presence of normal brain function distinguishes meningitis from encephalitis. It is not uncommon to see meningitis and encephalitis in the same patient and the distinction between these two is difficult so the term meningoencephalitis often used. These patients may develop seizures, coma and respiratory failure needing mechanical ventilation secondary to aspiration due to low GCS, atelectasis and neuromuscular weakness needing ICU admission and care. Other than meningoencephalitis Guillain-Barre? syndrome (GBS) Reyes syndrome, sub-acute sclerosing panencephalitis, postinfectious acute disseminated encephalomyelitis (ADEM) are other conditions secondary to viral infections affecting CNSneeding ICU admission. The true incidence of these infections is difficult because many cases are unidentified despite the availability of advanced molecular techniques like PCR. HSV 1 causes >50% of cases followed by VZV(36). A Swedish study revealed 2.2 cases of HSV encephalitis per million persons(37). Enterovirus (coxsackievirus A and B, echovirus, and enterovirus) are collectively the third most common cause, while arboviruses [Japanese Encephalitis Virus (JEV), West Nile virus ( WNV), Murray Valley encephalitis virus (MVEV)] are very common in certain geographic regions. Rabies, measles and mumps are very rare causes of encephalitis. Lumbar puncture and CSF analysis should be performed after CT brain (to rule out any significant brain tissue shift, evidence of raised intracranial pressure (ICP) and send for PCR for DNA of HSV-1, HSV-2, VZV, and enterovirus, (which constitute for about 90% of viral encephalitis).
  • 14. 14 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 An MRI scan is helpful in confirming the diagnosis of encephalitis and some characteristic findings like temporal lobe involvement in HSV, basal ganglion and thalamus involvement in Flavivirus and acute disseminated encephalomyelitis (ADEM) and other post-infectious encephalitis. Continuous EEG monitoring is helpful in patients with persistently altered consciousness to exclude intermittent non-convulsive seizures or non-convulsive status epilepticus. Management: Apart from the ABCDE management in ICU, antivirals are the mainstay of treatment. Early administration of high dose of acyclovir should be administered for 14 ? 21 days. This reduces mortality from 70% (without treatment) to < 20% ( with acyclovir)(36). Use of corticosteroids in viral encephalitis is lacking from RCT, so should not be used routinely except in VZV encephalitis, post- infectious encephalitis and with significant cerebral edema(36). For VZV encephalitis Acyclovir for 3 weeks., for CMV combination of Foscarnet and Ganciclovir and for Influenza encephalitis Oseltamavir is recommended. Though no antivirals are recommended for enteroviruses, pleconaril (an inhibitor of viral replication) may be used in patients with severe Enterovirus infections. Shock: Shock due to viral infections could be due to involvement of myocardium ( cardiogenic shock), due to hemorrhagic fever ( distributive shock), due to liver failure secondary to viral hepatitis and pancreatitis (hypovolaemic/distributive shock) and adrenal insufficiency. Viral Myocarditis: Several viruses (Influenza, Adenovirus, Parvovirus, RSV, CMV, HIV-1, hepatitis Aand Cviruses) vaccinia virus cause viral myocarditis including Coxsackie Aand B. Except few who have persistent cardiac dysfunction whose one year mortality was 20% most of the remaining do recover. Some of them who have severe left ventricular dysfunction may require Left Ventricular Assist Device (LVAD) until myocardial function recovers or cardiac transplantation is available. Treatment: General supportive measures to treat the consequences of heart disease [treatment of Heart failure (HF), treat of arrhythmia's and in selected cases anti-coagulation]. Refractory HF in spite of optimum medical therapy need mechanical circulatory support like LVAD or transplant.
  • 15. 15 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 The role of antivirals like ribavirin or interferon alfa is uncertain, though they reduce severity and mortality in murine myocarditis and a case report of alpha interferon in patients with enterovirus-proven myocarditis(38-41). Immunosuppressive therapy along with steroids and immunomodulatory effect of IV IgG have tried in viral myocarditis, but their role was controversial since a metanalysis did not reduce mortality(42, 43). Haemorrhagic fever and dist ribut ive shock: Hemorrhagic fever (HF)is caused by RNA viruses, Flaviviruses (Yellow fever, Dengue HF), Arenaviruses (South American HF-Junin; Lassa Fever), Bunyaviruses (Rift valley fever, Chrimean Congo HF-CCHF), HF with renal syndrome, Hantavirus, Filoviruses (Ebola, Marburg). They are transmitted by arthropod and rodents. Common in Indian subcontinent is Dengue virus transmitted by Aedes aegypti and Aedes albopictus. Apart from involving organs leading to hepatitis, nephropathy, encephalopathy, Disseminated intravascular coagulopathy (DIC) and even multi-organ failure. The characteristic feature of hemorrhagic fever is capillary leak due to increased vascular permeability. Outcome depends on the severity of the disease and serotype of the virus. It has a wide range of case fatality rate (1% to 90%)(27) Treatment: As there is no specific antivirals for most of these viruses general intensive care supportive treatment, support of organs and blood product transfusion is the main stay of management. Passive transfer of antibodies (convalescent plasma, IVIG) may be of value in Bunyaviruses [45], Junin virus [42], Lassa virus [43], Hantavirus HF. Case reports of plasma exchange for severe dengue have been reported as a last resort with some success(44). Antivirals like ribavirin and interferon can be used for Lassa virus(45). Liver failure and dist ribut ive shock: Common viruses that cause liver failure are Hepatitis group (A,B,C,D,E and G), Herpes group (HSV, VZV, CMV and EBV), Influenza virus and Adeno virus. They usually present with fatigue, anorexia, lethargy, jaundice, ascites, respiratory insufficiency, acute kidney injury, hepatic encephalopathy and coma. Treatment: Largely supportive management. Patients who progress from grade 1 encephalopathy to grade 2 or those who presented with grade 3 or 4 are managed in ICU. Haemodynamic instability is common in these patients due to low systemic vascular resistance and intravascular
  • 16. 16 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 depletion, so most of them require fluid resuscitation initially with normal saline, those who remain hypotensive noradrenaline is the vasopressor of choice. Prophylactic administration of fresh frozen plasma (FFP) is not recommended for patients with high INR as it is not going to influence mortality and interfere with assessments of liver function(46). Patients who are seriously ill need to be transferred to a transplant centre without delay. Pancreat it is and dist ribut ive shock: Mumps is the most common virus associated with pancreatitis, other viruses are Coxsackie B, HSV, VZV, CMV, EBV, adenovirus, Influenza and Para influenza viruses. Treatment: Supportive treatment as for any pancreatitis due to other aetiology. Fluid resuscitation and pain management are the main cornerstones of the treatment. Antivirals should be started for specific viral infections( Acyclovir for VZV, Oseltamavir for Influenza virus and Pleconaril for severe enterovirusinfections). Human Immunodefficiency Virus (HIV): It itself is a separate review, so we are discussing it very briefly. There are number of reasons with which HIV infected patients admitted to ICU, HIV related or non-HIV related. Acquired respiratory failure is the most common cause for ICU admission and most common pathogen is pneumocystis jirovecii pneumoniae followed by bacterial pneumonia(47). Other causes are sepsis and CNS related conditions (meningitis, Sub-acute encephalitis, Herpes simplex encephalitis, multi-focal leukoencephalopathy and seizures)(48). CD4 count and RNA levels are predictors of long term mortality after ICU discharge and need for MV, RRT, disease severity sore (APACHE II) and receipt of vasopressors are the predictors of mortality in ICU(49, 50). Treatment: Patients who are on ART at the time of ICU admission should stop or continue HAART is a big debate. Two observational studies suggested that ART may improve outcomes in critically ill ICU patients (10,27). Limitations are development of resistance due to poor oral absorption in critically ill patients as most of the ART are oral except Zidovidine and Enfuvrtide. Start ART within 14 days after starting treatment to opportunistic infections. Inpatients with cryptococcal infection start ART after 2 -8 wk of anti-fungal treatment to prevent immune reconstitution inflammatory syndrome (IRIS). Treat OI as per the specific organism.
  • 17. 17 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Legend: Table Syndrome Common Virus Treatment RESPIRATORY FAILURE: CAP: Influenza A and B, RSV A and B, coronavirus, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome coronavirus, Adenovirus, cytomegalovirus, Varicella, HSV, Parainfluenza 1-4, Metapneumovirus, measles especially in immunocompromised patients VAP: HSV, CMV, Mimi virus ARDS: Influenza virus, Hantavirus [Hantavirus pulmonary syndrome (HPS)], varicella, herpes simplex virus, SARS, MERS-CoV Supportive: Adequate oxygen delivery Antivirals: Neuraminidase inhibitors (NAIs) (Oselt amivir, Zanamivir, peramivir, Laninamivir). For resistant influenza viruses may consider combination therapy of NAI with ribavirin and/ or novel antivirals such as Favipiravir. Ribavirin for RSVin immunocompromised patients and children and may also be considered for other viruses such as in SARSor MERS-CoV - lopinavir in combination regimens has also been used Acyclovir for VZV pneumonitis Ganciclovir for CMV pneumonitis in solid organ transplant patients appears to reduce morbidity . Cort icost eroids: For influenza, SARS and VZV pneumonitis to reduce inflammatory tissue injury in severe pneumonia Immunot herapies: Palivizumab is approved for high-risk pediatric patients with RSV infection ; IVIG for certain respiratory viruses including influenza and GBS, plasma exchange for GBS. Combinations of ganciclovir wit h immuno- globulin or cyt omegalovirus immunoglobulin may be of value in patients with bone marrow transplants and CMV pneumonitis Others: Vitamin A for severe measles.
  • 18. 18 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Neurological syndromes: Encephalitis, meningitis, meningoencephalitis, myelitis, polyradiculo-neuropathy, Guillain-Barre? syndrome (GBS) Reyes syndrome, subacute sclerosing panencephalitis, postinfectious acute disseminated encephalomyelitis (ADEM) HSV, VZV, Enteroviruses (Enterovirus 71, Coxsackie, Echovirus, poliovirus: as a group, enteroviruses) Arboviruses (JEV, WNV, TBEV, MVEV, LCEV, SLEV, EEEV: the most common pathogens to cause encephalitis that is restricted to certain geographic regions) Influenza (4-19%) of patients with severe or fatal H1N1 reported neurologic complications . West Nile virus, CMV, mumps, measles, rubella, rabies, JC virus (PML), acute HIV infection) Supportive: Treatment of neurologic (eg, cerebral edema, high intracranial pressure, and seizures) and systemic (eg, hypoxemia, low cerebral perfusion pressure, and fever) complications Antivirals: Acyclovir: For HSV, VZV improves mortality and reduces subsequent cognitive impairment Ganciclovir: CMV encephalitis Foscarnet: HHV-6, combination therapy with foscarnet and ganciclovir is recommended for CMV encephalitis Oseltamivir: Severe influenza Pleconaril: severe Enterovirus infections Corticosteroids: Complicated HSV encephalitis (data based on retrospective studies), VZV encephalitis (for inflammatory vasculopathy), uncomplicated zoster (variable results), severe influenza, WNV (case report) [33], postinfectious encephalitis Immunotherapies: Either intravenous immune globulin or plasma exchange for patients with postinfectious encephalitis who fail corticosteroid treatment. Others: Vitamin A for severe measles
  • 19. 19 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Virus relat ed shock : Cardiogenic shock Myocarditis : Distributive shock-Hemorrhagic fever Hypovolemic/distributive shock in the setting of acute liver failure secondary to viral hepatitis Enteroviruses (Enterovirus 71, Coxsackie viruses group A and B, Echovirus), Influenza, Adenovirus, Parvovirus, RSV, CMV, HIV-1, hepatitis A and C viruses, vaccinia virus (after smallpox vaccine) Arenaviruses (South American HF-Junin; Lassa Fever), Bunyaviruses (Rift valley fever, Chrimean Congo HF-CCHF), HF with renal syndrome, Hantavirus, Filoviruses (Ebola, Marburg), Flaviviruses (Yellow fever, Dengue HF) Hepatitis A, B, C, D, E, G, herpes group (CMV, HSV and Epstein Barr virus), adenovirus and influenza virus Support ive : Ant ivirals: Rifampin: For RSV myocarditis [ Pleconaril: severe Enterovirus infections Oseltamivir: Severe influenza ART: HIV-1 Corticosteroids: do not reduce mortality (data based on small RCT of poor quality) Immunotherapies: IVIG (data based on in vitro data, case series, limited RCT) [38-40]. Combination therapy of IVIG with rifampin has been described in case series. Others: Mechanical ventricular assist devices until resolution or cardiac transplantation is available, novel therapies e.g pleconaril Support ive: Adequate oxygen delivery, blood products. Passive transfer of antibodies (plasma, IVIG) may be of value in Bunyaviruses, Junin virus ,Lassa virus, Hantavirus HF, Flaviviruses (Yellow fever, Dengue HF) Antivirals: Ribavirin for CCHF, Lassa virus, Hantavirus HF. Ribavirin plus interferon may be considered for Lassa virus. Support ive: Hemodynamic management, ventilation, prevention and treatment of hemorrhage, dialysis, therapy of co-existent sepsis and electrolyte disturbance, and management of intracranial pressure Ort hot opic liver t ransplant at ion Ant ivirals (may be used for acute flare up of chronic viral hepatitis e.g. in immunocompromised patients.
  • 20. 20 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Courtesy: Modified and reproduced from Kelesidis et al. BMC Infectious Diseases 2014, 14:321 http://www.biomedcentral.com/1471-2334/14/321 Preventive Strategy: It is well known that some of these viruses are transmittable via droplet and airborne (respiratory) and some by contacting blood and body fluids (Hepatitis B, C, HIV etc,.). Use of nebulizers, open suctioning of respiratory secretions, the use of Bi-PAP, outdated ventilation systems in addition to unawareness, inadequate training and non-compliant to local infection control policies all lead to spread of viral infections in the ICU setting and health care professionals are at high risk. Vaccines are not adequate in preventing spread of these infections in ICU. So health care providers, family members and visitors of the patient must follow strict isolation precautions. Judicious use of disinfectants is one of the solutions as they are highly active against some viruses. Hypovolemic/distributive shock in the setting of acute pancreatitis Mumps (the most common virus associated with pancreatitis, occurring even in the absence of parotitis), Enteroviruses (Coxsackie B), cytomegalovirus, varicella zoster, HSV-1, Epstein- Barr virus, influenza A, Parainfluenza, adenovirus, measles. In fulminant hepatic failure due to hepatitis A (HAV) or hepatitis E(HEV) pancreatitis occurs in up to 34% of the cases. Supportive Antivirals Oseltamivir: Severe influenza Pleconaril: severe Enterovirus infections Acyclovir: VZV
  • 21. 21 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Conclusion: Viral infections in ICU patients are increasingly identified in recent past especially due to easy availability and low cost of diagnostic tools. They play an important role even in immunocompetent patients in outcome. Most of them are community acquired, however, few of them are nosocomial. Though most of these infections are self-limiting some of them are life threatening and leading to worse outcome. Unfortunately except supportive therapy specific anti-retroviral therapy is available for only very few. Therefore it is very crucial to recognize them at earliest and treat them appropriately. We need more robust studies which aid in confirming the role of these viruses in critically ill patients. References: 1. Luyt CE. Virus diseases in ICU patients: a long time underestimated; but be aware of overestimation. Intensive Care Med. 2006;32(7):968-70. 2. Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med. 2003;349(25):2431-41. 3. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, et al. Avian influenza A (H5N1) infection in humans. N Engl JMed. 2005;353(13):1374-85. 4. Nguyen C, Kaku S, Tutera D, Kuschner WG, Barr J. Viral Respiratory Infections of Adults in the Intensive Care Unit. JIntensive Care Med. 2016;31(7):427-41. 5. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377(9773):1264-75.
  • 22. 22 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 6. Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DA, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013;369(5):407-16. 7. Greenberg SB. Viral pneumonia. Infect Dis Clin North Am. 1991;5(3):603-21. 8. Rello J, Diaz E. Pneumonia in the intensive care unit. Critical care medicine. 2003;31(10):2544-51. 9. Moine P, Vercken JB, Chevret S, Chastang C, Gajdos P. Severe community-acquired pneumonia. Etiology, epidemiology, and prognosis factors. French Study Group for Community-Acquired Pneumonia in the Intensive Care Unit. Chest. 1994;105(5):1487-95. 10. de Roux A, Marcos MA, Garcia E, Mensa J, Ewig S, Lode H, et al. Viral community-acquired pneumonia in nonimmunocompromised adults. Chest. 2004;125(4):1343-51. 11. Diaz A, Barria P, Niederman M, Restrepo MI, Dreyse J, Fuentes G, et al. Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens. Chest. 2007;131(3):779-87. 12. Woodhead M. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir JSuppl. 2002;36:20s-7s. 13. Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008;63(1):42-8. 14. Burk M, El-Kersh K, Saad M, Wiemken T, Ramirez J, Cavallazzi R. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis. Eur Respir Rev. 2016;25(140):178-88. 15. Spaeder MC, Custer JW, Bembea MM, Aganga DO, Song X, Scafidi S. A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus. Pediatr Crit Care Med. 2013;14(3):268-72. 16. Spaeder MC. Severe adenoviral respiratory infection in children. Intensive care medicine. 2013;39(6):1157-8. 17. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl JMed. 2003;348(20):1986-94. 18. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004;363(9409):617-9.
  • 23. 23 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 19. Writing Committee of the WHOCoCAoPI, Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl JMed. 2010;362(18):1708-19. 20. Chan PK, Chan MC, Cheung JL, Lee N, Leung TF, Yeung AC, et al. Influenza B lineage circulation and hospitalization rates in a subtropical city, Hong Kong, 2000-2010. Clin Infect Dis. 2013;56(5):677-84. 21. Aitken C, Jeffries DJ. Nosocomial spread of viral disease. Clin Microbiol Rev. 2001;14(3):528-46. 22. Horcajada JP, Pumarola T, Martinez JA, Tapias G, Bayas JM, de la Prada M, et al. A nosocomial outbreak of influenza during a period without influenza epidemic activity. Eur Respir J. 2003;21(2):303-7. 23. Choi SH, Hong SB, Ko GB, Lee Y, Park HJ, Park SY, et al. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med. 2012;186(4):325-32. 24. Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, et al. Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am JRespir Crit Care Med. 2007;175(9):935-42. 25. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl JMed. 2007;357(14):1373-81. 26. Centers for Disease C, Prevention. Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients - Seattle, Washington, 2009. MMWR Morb Mortal Wkly Rep. 2009;58(32):893-6. 27. De Clercq E. Antivirals: past, present and future. Biochem Pharmacol. 2013;85(6):727-44. 28. De Clercq E. A cutting-edge view on the current state of antiviral drug development. Med Res Rev. 2013;33(6):1249-77. 29. Duval X, van der Werf S, Blanchon T, Mosnier A, Bouscambert-Duchamp M, Tibi A, et al. Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial. PLoSMed. 2010;7(11):e1000362. 30. Tarbet EB, Vollmer AH, Hurst BL, Barnard DL, Furuta Y, Smee DF. In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus. Arch Virol. 2014;159(6):1279-91.
  • 24. 24 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 31. Gustafson LM, Proud D, Hendley JO, Hayden FG, Gwaltney JM, Jr. Oral prednisone therapy in experimental rhinovirus infections. JAllergy Clin Immunol. 1996;97(4):1009-14. 32. Buckingham SC, Jafri HS, Bush AJ, Carubelli CM, Sheeran P, Hardy RD, et al. A randomized, double-blind, placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome. JInfect Dis. 2002;185(9):1222-8. 33. Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013;144(2):464-73. 34. Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl JMed. 2007;357(14):1450-1. 35. Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52(4):447-56. 36. Kramer AH. Viral encephalitis in the ICU. Critical care clinics. 2013;29(3):621-49. 37. Hjalmarsson A, Blomqvist P, Skoldenberg B. Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality. Clin Infect Dis. 2007;45(7):875-80. 38. Kishimoto C, Crumpacker CS, Abelmann WH. Ribavirin treatment of murine coxsackievirus B3 myocarditis with analyses of lymphocyte subsets. JAm Coll Cardiol. 1988;12(5):1334-41. 39. Kishimoto C, Crumpacker CS, Abelmann WH. Prevention of murine coxsackie B3 viral myocarditis and associated lymphoid organ atrophy with recombinant human leucocyte interferon alpha A/D. Cardiovasc Res. 1988;22(10):732-8. 40. Matsumori A, Tomioka N, Kawai C. Protective effect of recombinant alpha interferon on coxsackievirus B3 myocarditis in mice. Am Heart J. 1988;115(6):1229-32. 41. Daliento L, Calabrese F, Tona F, Caforio AL, Tarsia G, Angelini A, et al. Successful treatment of enterovirus-induced myocarditis with interferon-alpha. JHeart Lung Transplant. 2003;22(2):214-7. 42. Chen HS, Wang W, Wu SN, Liu JP. Corticosteroids for viral myocarditis. Cochrane Database Syst Rev. 2013(10):CD004471.
  • 25. 25 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 43. Robinson JL, Hartling L, Crumley E, Vandermeer B, Klassen TP. A systematic review of intravenous gamma globulin for therapy of acute myocarditis. BMC Cardiovasc Disord. 2005;5(1):12. 44. Margabandhu S, Ranjit S, Jayakumar I, Sundaramoorthy C, Janarthanan M, Reddy J, et al. Therapeutic plasma exchange for pediatric nonrenal disease indications and outcomes: A single-center experience. Asian JTransfus Sci. 2018;12(2):127-35. 45. De Clercq E. Yet another ten stories on antiviral drug discovery (part D): paradigms, paradoxes, and paraductions. Med Res Rev. 2010;30(4):667-707. 46. Gazzard BG, Henderson JM, Williams R. Early changes in coagulation following a paracetamol overdose and a controlled trial of fresh frozen plasma therapy. Gut. 1975;16(8):617-20. 47. Sarkar P, Rasheed HF. Clinical review: Respiratory failure in HIV-infected patients--a changing picture. Critical care. 2013;17(3):228. 48. Morris A, Creasman J, Turner J, Luce JM, Wachter RM, Huang L. Intensive care of human immunodeficiency virus-infected patients during the era of highly active antiretroviral therapy. Am JRespir Crit Care Med. 2002;166(3):262-7. 49. Casalino E, Wolff M, Ravaud P, Choquet C, Bruneel F, Regnier B. Impact of HAART advent on admission patterns and survival in HIV-infected patients admitted to an intensive care unit. AIDS. 2004;18(10):1429-33. 50. Narasimhan M, Posner AJ, DePalo VA, Mayo PH, Rosen MJ. Intensive care in patients with HIV infection in the era of highly active antiretroviral therapy. Chest. 2004;125(5):1800-4.
  • 26. 26 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Viral Infect ion in Pediat rics Dr M Vishnuvardhan Reddy,Neonat ologist , Apollo Cradle MOTHER TO CHILD TRANSMISSION OF VIRAL INFECTIONS Viral infections of the fetus and new born are common problems in neonatal practice and are under recognized. So, however identification of the viral infections are important since anti-viral agents are available for most of the common viral infections. Vertically transmitted infections of fetus and neonates are divided into three distinct categories by transmission modes, Congenit al infect ions: Are those infections which are acquired in-utero. Perinat al infect ions: Are those acquired during intra-partum (labour and delivery). Post nat al infect ions: Are those acquired after birth within the first one month of life. PRENATAL PERINATAL/INTRAPARTUM POSTNATAL CMV HSV RSV Zika virus HIV Enteroviruses Varicella Hepatitis B/C Rotavirus Parvo virus B19 Adeno Virus Adenovirus Rubella Enteroviruses Hepatitis B/C Hepatitis B/C CMV CMV Influenza
  • 27. 27 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Relative importance of neonatal viral infections related to timing of acquisition of infections. Viruses are listed in declining relative order of importance relative to prenatal, perinatal and postnatal periods. General approach t o diagnosis: Clinical features commonly associated with congenital viral infections in neonates: - Intra uterine growth restriction - Non immune hydrops fetalis - Echogenic bowel - Hepatosplenomegaly - Jaundice - Haemolytic anaemia - Purpura, ecchymosis, petechia - Skeletal defects - Microcephaly and hydrocephaly - Intracranial calcification - Neuronal migration defects - Pneumonitis - Myocarditis - Cardiac defects - Chorioretinitis - Cataract Glaucoma . MOTHER TO CHILD TRANSMISSION OF HEPATITISB India has a prevalence rate of 2-7% for HBsAg seropositivity, whereas the prevalence in pregnant women is between 0.9-11.2%. MCTC of Hepatitis B virus is the most common cause of chronic hepatitis B infection. Transmission can occur in utero, at birth (most common) or after birth. Fact ors associat ed wit h high rat e of MTCT - High maternal serum HBV DNA level >2,00,000 IU/ml - HBeAg positivity in mother - Duration of 1st stage of labour >9 hours - Premature rupture of membranes and threatened preterm labour - Prior child with passive active immune-prophylaxis failure
  • 28. 28 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Prevent ion of mat ernal t o child t ransmission of Hepat it is B All infants within 12 hrs of birth HepB vaccine + HIBG MOTHER TO CHILD TRANSMISSION OF HIV Parent-to-child transmission of HIV is a major route of new HIV infections in children. Children born to women living with HIV acquire HIV infection from their mother, either during pregnancy, labour/delivery or through breast feeding which is largely preventable with appropriate intervention, by providing Anti-retroviral therapy (ART) to mothers and Anti-Retroviral (ARV) prophylaxis to infants. A total of 61,000 lakh children (0 to 14 years) are estimated to be living with HIV in India. Ant epart um Antiviral drugs ? treatment should be started 6-8 weeks before delivery. Tenofovir is preferred Int rapart um Elective LSCSshould be performed before the onset of labour or before the rupture of membranes Post part um Management of baby born to Hbsg positive mother B wt >2 kg B wt < 2 kg Subsequent vaccine doses at 1-2 months and 6 months of of age Required vaccines at birth, 1, 2 and 6 months (total 4 doses)
  • 29. 29 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Risk of HIV transmission from Mother to Child with ARV interventions : Source: Anti retroviral drugs for treating pregnant women and preventing HIV infection in infants: Towards universal access, Recommendations for public health approach ? 2006 version ? WHO. PPTCT: Int ervent ions during pregnancy: - Primary prevention of HIV in childbearing women - Provide HIV information to ALL pregnant women - Antenatal visits are opportunity for PPTCT - Prevention of unwanted pregnancies in HIV-positive women - Prevention of PTCT through ART - Safe obstetric practices ARV INTERVENTION RISK OF HIV TRANSMISSION FROM MOTHER TO CHILD No ARV; breastfeeding 30-45% No ARV; No breastfeeding 20-25% Short course with one ARV; breastfeeding 15-25% Short course with one ARV; No breastfeeding 10-15% Short course with two ARVs; breastfeeding 5% 3 ARVs (ART) with breastfeeding 2% 3 ARVs (ART) with No breastfeeding 1%
  • 30. 30 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 PPTCT: Int ervent ions during labour and delivery: - Minimize vaginal examinations - Avoid prolonged labour; consider oxytocin to shorten labour - Avoid artificial rupture of membranes - Early cord clamping after it stops pulsating and after giving the mother oxytocin - Use non-invasive foetal monitoring Avoid invasive procedures Avoid routine episiotomy / support perineu Minimise the use of forceps or vacuum extractors. Use of ART can reduce risk of PTCT better and with lesser risk than a C-section ART regimens in pregnant and breastfeeding with HIV Pregnant women presenting in active labour : TARGET POPULATION DRUG REGIMEN Pregnant and breastfeeding women with HIV (ART Naïve / ?Not-already?receiving ART) TDF + 3TC + EFV Pregnant and breastfeeding women with HIV already receiving ART The same ART regimen must be continued ART regimen for pregnant women having prior exposure to NNRTI for PPTCT TDF + 3TC and LPV/r MATERNAL STATUS INTRA-PARTUM POST-PARTUM Presenting in active labour, no prior AR Initiate TDF (300 mg) + 3TC (300 mg) + EFV (600 mg) Continue TDF (300 mg) + 3TC (300 mg) + EFV (600 mg) Nevirapine prophylaxis for breastfeeding infant should be for 12 weeks, as mother did not receive any ART during ante-natal period
  • 31. 31 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 ARV Prophylaxis for Infant: The infant should be started on Nevirapine. The duration of NVP prophylaxis will depend on the duration of ART that has been given to the mother during her ante-natal period. - Infants should be started on daily NVP prophylaxis at their first encounter with the health services - Daily infant NVP prophylaxis can be started even if more than 72 hours have passed since birth and should continue; during this period the mother should be linked to appropriate ART services. Duration of daily infant NVP prophylaxis will depend on ?how long the mother was on lifelong ART [for a minimum of 4 weeks or not]? - The duration of NVP given to infant is a minimum of 6 weeks, regardless of whether the infant is exclusively breast fed or exclusive replacement fed - 6 week-Nevirapine prophylaxis should be increased to 12 weeks, if ART to the mother has been started in late pregnancy, during or after delivery and she has not been on ART for an adequate period as to be effective to achieve optimal viral suppression (which is at least 4 weeks) - The recommendation on extended Nevirapine duration (12 weeks) applies to infants of breast-feeding women only and not to those on exclusive replacement feeding - Infants of women with prior exposure to NVP should get syrup Zidovudine (AZT) in place of syrup Nevirapine Recommended ARV Prophylaxis for HIV Exposed Infants HIV Exposed Infants of HIV-2 infected mother : Start syrup AZT in place of NVP syrup, immediately after birth till 6 weeks of age. Specific Interventions during Infancy: - Observe for signs and symptoms of HIV infection - All HIV exposed infants should receive co-trimoxazole at 6 weeks of age - Follow standard immunization schedule - Routine well baby visits - Early Infant Diagnosis: DNA PCR test o 18-month visit for HIV antibody testing
  • 32. 32 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 MOTHER TO CHILD TRANSMISSION OF CMV CMV infection is the most common congenital viral infection within birth prevalence of about 0.5%. Majority of congenital infections are asymptomatic. 5-20% of infants born to mother with primary CMV infection are symptomatic. Asymptomatic infants are at a risk of long term neurodevelopmental morbidities, but the risk is such lesser than symptomatic infants. The most common complication is congenital hearing loss. Classification of CMV infection in pregnant women : Primary ? if initial acquisition of virus (seroconversion from negative to positive) occurs during pregnancy. Non primary - if maternal antibody to CMV was present before conception due to reactivation of latent virus or re-infection with new strain. Vertical transmission via mother to fetus and new born is most common with primary maternal infection. Routes of transmission : - trans placental - ascending infection from maternal genital tract infection (rare) - intrapartum through ingestion or aspiration of Cervico-vaginal secretions during delivery - postnatal transmission occurs through breastfeeding Prevent ion : The Centers for Disease Control and Prevention (CDC) recommends that (i) pregnant women practice hand washing with soap and water after contact with diapers or oral secretions; do not share food, utensils, toothbrushes, and pacifiers with children and avoid saliva when kissing a child. (ii) pregnant women who develop a mononucleosis-like illness during pregnancy should be evaluated for CMV infection and counseled about risks to the unborn child. (iii) antibody testing can confirm prior CMV infection. (iv) the benefits of breastfeeding outweigh the minimal risk of acquiring CMV. (v) there is no need to screen for CMV or exclude CMV-excreting children from schools or institutions.
  • 33. 33 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Immunizat ion : Passive immunization with hyperimmune anti-CMV immunoglobulin and active immunization with a live-attenuated CMV vaccine represent attractive therapies for prophylaxis against congenital CMV infections. However, data from clinical trials have not shown adequate efficacy of either of these approaches with current passive and active vaccine products. Breast milk feeding : Breast milk is a common source for postnatal CMV infection in the new born, symptomatic infection is rare in term infants. However, there may be insufficient transplacental IgG to provide adequate protection in preterm infants. For mothers of extremely premature and low birth weight infants known to be CMV seropositive, freezing breast milk will reduce the titer of CMV but will not eliminate active virus. Environment al rest rict ions : Day care centers and hospitals are potential high-risk environments for acquiring CMV infection. Good hand-washing technique should be suggested to pregnant women with children in day care settings and with children attending day care, especially if the women are known to be seronegative. Transfusion product rest rict ions : The risk of transfusion-acquired CMV infection in the neonate has been almost eliminated by the use of CMV antibody-negative donors, by freezing packed red blood cells (PRBCs) in glycerol, or by removing the white blood cells.
  • 34. 34 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Vaccine is an immune biological substance designed to produce specific protection against a given disease. The development of vaccines has been one of the most important contributions of immunology to medicine and public health. It was initiated about 200 years ago by Edward Jenner, with the inoculation of the fortuitously cross-protective cow-pox discharge, for prevention of smallpox infection. The major breakthrough, occurring a hundred years later, was the preparation by Pasteur, of rabies vaccine, which is based on intentional attenuation of the pathogen. This paved the way for the development of a whole sequence of viral vaccines. The IAP Advisory Committee on Vaccines and Immunization Practices (ACVIP) has recently reviewed and revised the recommended immunization schedules for children aged 0 through 18 years to ensure that the schedule reflects recommendations based on recent evidence for licensed vaccines in the country. The recommended vaccines for viral diseases include, vaccines for Measles, Flu, Polio, Hepatitis-B, Mumps, Rota virus. Most of these vaccines are live-attenuated or inactivated and are developed by earlier methods like, passage in live animals or eggs. More recent vaccines have been developed because of the advent of new technologies, particularly cell culture and molecular biology. Recent technological advances in gene delivery and expression, nanoparticles, protein manufacturing, and adjuvants have created the potential for new vaccine platforms that may provide solutions for vaccines against viral pathogens for which no interventions currently exist. Old t ype of vaccines: a. Live, at t enuat ed vaccines: - These vaccines contain a version of the living virus or bacteria that has been weakened so that it does not cause serious disease in people with healthy immune systems live, attenuated vaccines are the closest thing to a natural infection - Examples: measles, mumps, and rubella vaccine (MMR) and varicella (chickenpox) vaccine. b. Inact ivat ed Vaccine: - The virus is made inactive during the process of vaccine preparation - Examples: Inactivated polio vaccine OLD AND NEW VACCINESFOR THE PREVENTION OF VIRAL INFECTIONS Dr. Renu Avula,Professor of Microbiology,Kurnool Medical college,AP,India.
  • 35. 35 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Newer t ypes of vaccines: Viral vect or t echnology: Here the choice antigen is expressed in the context of an active heterologous viral infection, which stimulates the full gamut of innate immune responses required for the development of adaptive humoral and T cell mediated immunity. In this type of vaccine the characteristics, type and intensity of immune response, as well as safety considerations and manufacturing techniques are determined predominantly by the vector and not the pathogen. The applications of this technology include, a) Replicat ion compet ent approach in which Replication competent but attenuated virus vectors (RHS) deliver heterologous antigen targets resulting in the induction of cellular and humoral responses. Their complement of genes enables a full round of replication and assembly of progeny virus which can amplify and spread the vaccine effect to susceptible cells. While these platforms are based on highly attenuated viral backgrounds, replication competence may lead to the development of mutations and reversion to virulence. Chimeri Vax? -JE for Japanese Encephalitis has been developed by Sanofi Pasteur (Lyon, France) It has certain advantages like, 1) Development of good humoral and T cell responses 2) Several platforms available. 3) Simple production via virus culture. The drawback of this technology is reduced expression or loss of heterologous antigens or in some case reversion to virulence. b) Replicat ion defect ive approaches where Replication defective vectors support effective cellular entry and a single round of expression of the target gene/ antigen; they result in effective induction of cellular and humoral responses. They are unable to generate new infectious progeny and are considered safer than replication competent vectors Modified Vaccinia Virus Ankara (MVA) is licensed as third generation vaccinia type vaccine against small pox. Developing stages: Ebola virus, MERSCoV and Zika virus This method has the advantage of development of good humoral and T cell responses. Virus like part icles: The virus like particles (VLP) acts as vaccine candidates and they present highly antigenic structures to the immune system. They lack a viral genome, potentially yielding safer vaccines, as there is no viral sequence that can revert to virulence. They induce strong B cell responses in the absence of adjuvants by efficiently cross-linking specific receptors on B cells, and they can also trigger T cell-mediated responses.
  • 36. 36 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 VLP-based vaccines for human papilloma virus (HPV), hepatitis B virus (HBV) and hepatitis E virus (HEV) have been licensed and are commercially available worldwide. Under clinical development, including those directed against Norwalk virus, Ebola and Marburg viruses and hepatitis C virus. VLP vaccines combine many of the immunogenic advantages of whole-virus vaccines with the safety advantages of recombinant subunit vaccines. These are safe and are good inducers of humoral and Tcell responses but the production costs may be high and require multiple steps. Nucleic acid vaccines: DNA vaccines have emerged as a safer alternative to standard live and inactivated vaccines for treating human and animal infections. They exhibit several advantages over traditional strategies in terms of safety, stability, ease of manufacturing and immunogenicity. They offer potential advantages for vaccination against emerging viruses, in that plasmids expressing a viral antigen can be produced rapidly. Antigen is expressed in vivo and induces both humoral and cell-mediated immune responses. Additionally, large quantities of DNA can be produced in a short time at reduced cost, and DNA preparations are more stable than other types of vaccines, which are desirable properties for a vaccine that may be used in remote areas. DNA vaccines are considered safe. The main limitation in the development of DNA vaccines is their intrinsic low immunogenicity. Work to improve this limitation has focused on optimizing delivery approaches with the use of gene guns, or electroporation ; targeting immune effector cells; and the use of potent adjuvants. DNA vaccines are also frequently used in combination with other vaccine platforms in heterologous prime-boost strategies. A DNA vaccine is currently licensed to immunize against West Nile virus and has undergone Phase I clinical trials in humans. DNA vaccines have also been evaluated as candidates against many emerging viruses, including EBOV, RVFV , Dengue virus and CHIKV. These are safe but induce lower levels of immune responses. Synt het ic pept ides: Synthetic peptide-based epitope-vaccines (EVs) make use of short antigen-derived peptide fragments that can be presented either to T cells or B cells. EVs offer several advantages over other forms of vaccines, particularly with regard to safety, ease of production, storage and distribution, without cold chain issues. They also offer the opportunity to vaccinate against several pathogens or multiple epitopes from the same pathogen. Drawbacks include poor immunogenicity and the restriction of the approach to patients of a given tissue type [human leucocyte antigen (HLA) haplotype] and, as such, they need to be tailored to accommodate the natural variation in HLA genes.
  • 37. 37 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Recently, bioinformatics tools have been developed to identify putative CD4+ T cell epitopes, mapped to the surface glycoproteins of the emerging viruses LASV, NipV and Hendra. This approach represents an interesting and novel strategy that shows promise for vaccination and which could also address immunity in particular target populations. This method has the advantage in ease of production and storage but has uncertain immunogenicity linked to target populations. Fut ure perspect ives: The future perspectives in development of vaccines include, Self-disseminating wild-life reservoir vaccines, which aim to immunologically contain emerging viruses within their non-human reservoir hosts, offer an alternative to the conventional vaccine approach. They are designed to exploit the ability of replicating virus-based vectors to spread through animal host populations, so avoiding the need for direct inoculation of every animal. In this way, vaccination of a limited number of initiator animals is used for the introduction of the vaccine into a target population. The vaccine is engineered to express target antigens from the emerging pathogen of interest, so its transmission from vaccinated to non-vaccinated animals will result in the co-ordinated spread of specific immunity for the emerging pathogen throughout the targeted animal population. A study targeting the human pathogen Sin Nombre orthohantavirus (SNV) in its rodent reservoir ? the deer mouse (Peromyscus maniculatus) ? proved effective. This approach used an engineered cytomegalovirus (CMV) vector which causes a benign but transmissible infection in the host, expressing the SNV envelope glycoprotein G1. A similar approach is also being developed to interrupt zoonotic transmission of Ebola virus. The following is a list of vaccines incorporating novel vaccine preparation methodologies being available in the market and being used to specifically address the growing threat of new and emerging disease.
  • 38. 38 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 DISEASE VACCINE Dengue - Dengue vaccine available is CYDTDV (Dengvaxia®), a live attenuated (recombinant) tetravalent vaccine. Hepatitis A - Inactivated or live attenuated hepatitis A virus vaccines Hepatitis E - Recombinant vaccine based on genotype 1 capsid protein Japanese Encephalitis - Inactivated Vero cell-derived vaccines - live attenuated vaccines - live recombinant (chimeric) vaccines. Polio - Orally administered, live attenuated polio vaccine (OPV) - Inactivated poliovirus vaccine (IPV) Rabies - Modern cell-culture or embryonated-egg vaccine. Tick borne Encephalitis - Inactivated vaccine. Yellow fever - Live attenuated. Influenza - Inactivated influenza vaccine [IIV] - Recombinant influenza vaccine [RIV] - Live attenuated influenza vaccine (LAIV)
  • 39. 39 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 References: 1. Vaccine-preventable diseases and vaccines :INTERNATIONAL TRAVEL AND HEALTH - CHAPTER 6 2. www.cdc.gov/vaccines 3. Vaccines for emerging pathogens: from research to the clinic. Clinical and Experimental Immunology 2019, 196: 155-156. 4. HLA-E: exploiting pathogen-host interactions for vaccine development. Clinical and Experimental Immunology 2019, 196: 167-177. 5. Novel approaches for the design, delivery and administration of vaccine technologies. Clinical and Experimental Immunology 2019, 196: 189-204. 6. Mucosal vaccines and technology. Clinical and Experimental Immunology 2019, 196: 205-214. 7. Vaccines for emerging pathogens: prospects for licensure. Clinical and Experimental Immunology 2019, doi: 10.1111/cei.13284 8. Emerging viruses and current strategies for vaccine intervention. Clinical and Experimental Immunology Review Article doi: 10.1111/cei.13295.
  • 40. 40 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 1. What is the most common cause of asept ic meningit is of viral etiology? a. Enteroviruses b. Herpesviruses c. Arboviruses d. Retroviruses e. Orthomyxoviruses 2. All of the following picornaviruses are resistant to the acidity of the stomach except: a. Coxsackievirus A b. Coxsackievirus B c. Echo virus d. Poliovirus e. Rhinovirus 3. Which one of the following infection routes is most often involved in the neonatal transmission of hepatitis B virus (HBV)? a. Blood transfusion b. Fetal contact with infected blood during childbirth c. Ingestion of the virus via maternal breast milk d. Transmission of the virus from hospital personnel during childbirth e. Transplacental transmission of the virus 4. Protection against influenza A virus in a nonimmune individual can be achieved through the administration of a drug that interferes with a. Viral endonuclease activity b. binding of host messenger RNA (mRNA) caps by the viral P1 protein c. Synthesis of viral progeny RNA d. Uncoating of nucleic acid e. Viral adsorption and penetration QUIZ CLICK HERE FOR LIVE QUIZ
  • 41. 41 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 5. The finding of large, multinucleated, clumps of cells in the bronchial secretions of a 2 year old girl with acute bronchopneumonia suggests that this infection is caused by a. Bordetella pertusis b. Epstein-Barr virus c. Mycoplasma hominis d. Rhinovirus e. Respiratory syncytial virus (RSV) 6. In a chronic carrier of hepatitis B virus (HBV), which positive test is most indicative of high infectivity? a. Hepatitis B Surface Antigen (HbsAg) b. Hepatitis B Core Antigen (HbcAg) c. Hepatitis B e Antigen (HbeAg) d. Anti-HBsAg e. Anti-HBeAg 7. A retrovirus is found in a high proportion of laboratory animals of a given species. Most viremic animals are asymptomatic, but others develop a fatal wasting syndrome, and a few develop leukemia and other tumors after long periods of latency. The virus in question most likely lacks which one of the following genes? a. gag b. pol c. env d. onc 8. A sexually active 22 year old college student presents to the local clinic with a localized vesicular eruption on the shaft of his penis. A scraping of the base of one of the vesicles is positive for Tzanck cells. The patient mentions that he had a similar eruption in the same area 2 months earlier. The reappearance of this eruption may be explained by: a. Cell mediated immunity (CMI) deficiency in the patient b. A prolonged period of viremia following the initial infection
  • 42. 42 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 c. A second infection with a similar virus with a different serotype d. failure of the patient to comply with therapy prescribed at the initial episode e. reactivation of a latent infection. 9. Influenza vaccine is targeted towards 'at risk' groups in the UK. Which of the following are classified as 'at risk' (choose three)? a) Very young under 2 years old b) Elderly persons over 65 years c) The obese of any age d) Teenagers 10. Combination chemotherapy (HAART) is now used to treat patients with HIV because of which two factors? a) Drug resistant mutants arise too quickly with monotherapy b) This is cheaper than consecutive treatments with monotherapy c) There is synergism between anti HIV drugs working at different stages of the life cycle d) HAART is also active versus HTLV-1 and HTLV-II 11. What disease do herpes viruses not cause? a) Infantile paralysis b) Encephalitis c) Sexually transmitted disease d) Cancer 12. The range of disease caused by the Parvovirus family is wide but identify the exception from the following: a) Aplastic crisis in anaemia patients
  • 43. 43 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 b) Fifth disease at 'Slapped cheek' syndrome c) Foetal infection with teratogenicity d)Severe pneumonia 13. How are herpes infections controlled? a) Chemotherapy b) Vaccines c) Hygiene and social distancing d) No method 14. How is the parvovirus family targeted to reduce disease? a) Transfusion blood is screened b) Vaccine has been developed c) A range of new antivirals d) Social distancing 15. There are 57 serotypes of adenovirus currently recognised. Which has the most important clinical impact? a) Diarrhoea b) Eye infections c) Respiratory tract infections d) Haemorrhagic cystitis 16. When was smallpox eradicated from the world? a) In 1977 following a WHO campaign b) In 2000
  • 44. 44 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 c) Is not yet eradicated d) In 1796 after Jenner's first vaccine 17. The vaccine used to eradicate smallpox originated as: a) Live smallpox b) Live cowpox c) A genetic recombinant d) Killed whole virus 18. Which areas of the world are rabies free? a) USA b) Norway c) EU d) Island nations, UK, NZ and Australia 19. The main animal host varies from continent to continent. Where are two regions where dogs are important carriers? a) USA b) Europe c) Iran/Middle East/Afghanistan d) Asia 20. Which disease do polyomaviruses predominantly cause? a) Tumours b) Brain pathology c) No disease at all
  • 45. 45 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 d) Kidney infections 21. How are rotaviruses predominately identified from clinical samples? a) Electron microscopy b) RT PCR c) Antibody tests d) Laboratory diagnosis not required 22. Where in the body do oncogenic HPVs especially replicate? a) Brain b) Liver c) Cervix d) Larynx 23. Which of the following HPV viruses are known to cause cervical cancer? a) Viruses of all 5 clades b) Types 14, 16, 18, 31, 45 c) None are oncogenic per se d) Types 1-180 24. What is the biggest risk factor for infection with Ebola? a) Working in a category IV laboratory b) Attending a funeral of a victim outside c) Nursing a patient at home d) Attending football matches or large gatherings
  • 46. 46 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 25. How can the spread of filoviruses be restricted? a) New antivirals b) New humanised monoclonal antibodies c) Hygiene and social distancing d) New vaccines 26. Nipah is a zoonotic paramyxovirus; where did it originate? a) Originating in pigs b) Originating in bats c) Coming from humans d) Coming from horses 27. Which member of the paramyxovirus family can cause very serious croup? a) Measles b) Meta pneumo virus c) Hendra d) Respiratory syncytial virus (RSV) 28. Antivirals can be used prophylactically or therapeutically in persons in which of the following circumstances? a) If administered within 4 days of clinical signs b) If used within 48 hours of first clinical signs c) Used for the obese d) Used in children under the age of 2 years where high virus spread is noted
  • 47. 47 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 29. Most pandemics have arisen from influenza viruses from which of the following animals? a) Pigs b) Wild birds c) Bats d) Humans e) Whales 30. The treatment of hepatitis C has been revolutionised most recently by which of the following? a) The use of interferon b) A new vaccine c) Monoclonal antibodies d) Direct-acting Antivirals such as daclatasvir and sofosbuvir 31. Many virus infections result in immune pathology, this is caused predominantly by which of the following? a) A cytokine storm b) Antibody mediated reactions c) A response of killer T cells (CD-8) d) A decline in function of the immune system 32. What is the most common way for a virus to kill a cell? a) Dissolves the cellular membrane b) Induces apoptosis via caspases c) Fragments cellular DNA
  • 48. 48 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 d) Totally blocks cellular transcription 33. Poliovirus can most easily become more virulent by which of the following processes? a) Mutation of the RNA genome at only a few positions b) Recombining with another enterovirus c) Altering its protein coat d) Multiple nucleotide deletions and substitutions 34. Of the following factors, which are the most important factors for virus spread and infection? a) Age b) Sex c) Genetic factors d) Economic status e) Travel 35. Chikungunya has spread widely from Asia and Africa into the Caribbean in recent years. This has been mainly facilitated by: a) Mutation in the virus allowing replication in the mosquito Aedesalbopictus b) Air Travel c) Climate change d) Poor mosquito control and the absence of DTT 36. MERShas four special characteristics and here we have one exception - which is it? a) Spread by faecal oral route b) Aerosol droplet transmission
  • 49. 49 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 c) Reservoir in bats d) A conduit to humans via camels
  • 50. 50 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Int roduct ion Bacterial infections corner limelight in most of discussions in academic fora. Few obvious reasons are that they are dominant causes of sepsis be it local or systemic in the community, the ability to cause serious illness, morbidity and mortality unless treated early and last but not the least antimicrobial resistance. However now it appears that viruses are equally if not more important in causation of human suffering and inflicting many deaths. Considering the re-emergence of viruses thought under control eg measles and emergence of new viruses HIV in recent past, more recently H1N1 among many new respiratory viruses, it is clear we don't know much about how viruses surprise a healthy person by inflicting sickness. The ability to cause chronic disease is also a feature of some viruses. Association of new and old viruses with disease syndromes previously thought as bacterial or idiopathic are also becoming evident. One of the main reason was in many conditions viruses were not investigated due to lack of facilities for lab diagnosis. However, the scenario is rapidly changing making us compulsorily revisit Human -virus interactions and their outcome. This article attempts to bring home to ICT group in simple language the global advances in pathogenesis and lab diagnosis of human viral infections Pat hogenet ic mechanisms of Viruses. Virus is t ot ally different in morphology, biology, t ypes of disease caused. Table present s comparison of salient feat ures of t wo mechanisms of Viral disease AN ATTEMPT TO UNDERSTAND PATHOGENETIC MECHANISMSOF HUMAN VIRAL DISEASES Dr H.Srinivasa, MD Microbiology AIIMS,New Delhi FEATURE BACTERIA VIRUS Size Larger- in micromet ers Larger- in micromet ers Morphology Complex , Cell wall encloses Cell membrane which int urn cont ains cyt oplasm having nucleus Relat ively simpler- Prot ein shell cont aining nucleic acid, some have out er envelope
  • 51. 51 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 Nucleic acid Have both DNA and RNAHave either DNA or RNA- thus classified as DNA or RNA Mult iplicat ion By Binary fission By replicat ion inside host cells- copies formed like xerox using t emplat e nucleic acid ,each lat er covered by prot ein Int erferon Generally not produced Generally produced by infect ed host cells Ant ibiot ics Antibacterial compounds act on bacteria- may be narrow spectrum or broad spectrum Exception: Drug resistant bacteria Ant i viral compounds act but only on limit ed groups of viruses: viruses also develop drug resist ance Act ion of disinfect ant s General Purpose disinfect ant s- suscept ible Only high level disinfect ant s act Bact eriophages These are viruses but Act on bact eria- only t o limit ed genera Do not act
  • 52. 52 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 An encounter with virus do not necessarily cause disease in humans. Why is it so? In fact may a times there will not be any symptoms in humans even though virus is present in the body. This is called asymptomatic infection. However the same virus in another individual may not only multiply but also cause symptoms that is the disease. In fact asymptomatic infections are more common and outnumber symptomatic infections especially in outbreaks. Outbreaks of influenza is a classic example. This concept is caused as iceberg concept of infection. Iceberg in Ocean, though floats, on careful observation it's actually 90 percent underwater and only 10 percent is visible. Visible portion is compared to symptomatic group and rest , that is huge 90 percent is compared to asymptomatic group. If we further divide asymptomatic, a few may have mild symptoms, also in symptomatic group some will be having severe symptoms and invariably very sick and bed ridden. Genetics of virus Virus are endowed with certain unique features, which make humans easy prey. They are: 1 Target only special molecules of host called as receptors once bound, find easy entry in to cell eg HIV 2 Multiplication rate is fast 3 Many virus being inside host cells evade immune response 4 Some even do not allow host cell to produce IF, even if IF is produced which normally suppress viral spread from cell to cell. The viral infected may be refractory to IF eg influenza A ,Dengue 5 Viruses are notorious for frequent genetic changes. Thus, an altered virus is less recognizable to host immune system. Major change in genetic code result in all most a new virus not recognizable by immune system. The genetic changes are mutation, recombination. 6 Generally human Virus cause human disease and animals will have its own spectrum of viruses. Some human viruses have in addition animals as reservoir, in some other cases viruses in animals change their characteristic and become endowed with the ability to cause human infections. 7 Groups of viruses associated with chronicity eg. hepatitis viruses b,c slow viruses ... Viroids.. prions, viruses normally cause asymptomatic infection but can cause severe disease in immune-compromised states,
  • 53. 53 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 8 Certain viruses like CMV, EBV normally latent in body may cause serious infection in post organ transplant. Are viruses always bad, are there any good viruses...Virologists used say less pathogenic viruses interfere with growth of pathogenic viruses. Recent data summarized as advances in this issue by Dr Sukanya suggests it may indeed be so, there may be normal resident viruses Further understanding required in viral pathogenesis globally. Even so called vaccine preventable viruses like measles, rubella, chicken pox are resurfacing. Also we are facing Viral infections becoming more with atypical or severe population immunity levels, reduced uptake of vaccine under nutrition. Nutrition.. role of vitamins vitamin deficiency A, D predispose to viral infections.the latter may lead to further escalation of vitamin deficiency there by setting a chain reaction Which in turn leads to more severe , protracted infections. Vitamin C is another powerful antioxidant protection against respiratory viruses rhino viruses, influenza viruses A Further provision of bed rest so that convalescence can occur convalescence...needs to be stressed close family members of the index case. These measures may curtail protracted illness which burdens the family emotionally and economically. Mixed bacterial and viral infections also pose a major challenge, As bacterial infection may be diagnosed but not viral. However with the availability of Real time PCR, Multiplex PCR it is becoming evident that there are sub groups of Mixed infections which may present atypically. Thus the current situation demands more re-education of ICT Professionals and debates and discussions, so that best treatment protocols are used to manage viral infections.
  • 54. 54 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 With the introduction of the worldwide campaign to eradicate Smallpox by WHO in 1967, the disease was totally eradicated in 1977, and in 1980 the world health authorities declared the world is free from Smallpox in 1980. Smallpox is caused by a DNA type virus with Variola major producing classical Smallpox and Variola minor producing Alastrim, a less serious disease. And the last death from the disease occurred due to a laboratory accident in England in 1978 (World Health Organization.) LAST KNOWN CASE OF SMALLPOX - So far, the only known victim is Janet Parker, 40, a medical photographer. She developed a fever and a rash in early August, but two weeks passed before her illness was diagnosed as variola major, the severe form of smallpox. ARE WE IMMUNE TO SMALLPOX TODAY? Many of our older population were vaccinated in our childhood and none of the younger got vaccinated, however, the Immunity after vaccination only lasts for 3?5 years? Does it just mean? Today No-one is immune, Next question?Is it hypothetical it would spread fast as the flu, and kill like the Black Death in the Middle Ages?It would be biblical thinking or reality? SCIENCE WILL NEVER STOPS FOR SEARCH ON REEMERGING INFECTIONS - Smallpox under consideration to think further it can be a Possibility ?- Can it re-emerge. The Centres for Disease Control and Prevention is now running tests on the six forgotten vials of smallpox that were recently discovered in an unsecured laboratory, to see if any live virus remains in them. Stray cases of Varicella (not Variola which causes Smallpox) Monkeypox, Parapoxviruses and aggressive forms of drug reaction can be mistaken as the outbreak of Smallpox The present question Smallpox can it re-emerge after more than three decades of silence, the hypothetical answer is very, very, remote as there is no known animals harbouring the virus or vector went into hibernation. Even in the crisis of re-emerging/or the surfacing of the mutated virus can be easily controlled, as we learned a lot of lessons with SARS/INFLUENZA, And Smallpox is less contagious in the spread, as it requires close contact between face to face and patients with a rash is infectious, and easily Diagnosed with growing awareness in the better-communicated world and increasing awareness of re-emerging infectious diseases. . Millions of doses of Vaccine for Smallpox in stock and are available at the click of a mouse, WHO STORES THE SMALLPOX VACCINE STRAINS - Already WHO has recommended that only five centers in the entire world, including the CDC in Atlanta, be allowed to store strains of the virus for research purposes? ERADICATION OF SMALLPOX? - CAN IT RE-EMERGE? CAN WE SUCCEED WITH OTHER VIRAL INFECTIONS? Dr.T.V.Rao MD Former Professor of Microbiology,Andhra Medical College
  • 55. 55 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 SEARCH FOR NEW METHODS TO DIAGNOSE POX VIRUSES -Research continues to Make Better Tests, CDC also is conducting research to develop better lab tests to detect pox-like viruses more accurately because this would help diagnose smallpox in patients, in time of re-emergence of Smallpox. OUR SUCCESS ON CONTROL OF OTHER VIRAL INFECTIONS WITH VACCINATION - Another important preventive measure is immunizing people against viruses. This involves giving people vaccines that stimulate the immune system to make antibodies, proteins that target a specific germ. Vaccines to prevent Hepatitis B, polio, mumps, measles, rubella (German measles), and chickenpox are usually given to babies and young children. Vaccines also can prevent influenza and Hepatitis A. vaccines are useful only against certain kinds of viruses. The search for vaccination in Viral unending game as influenza viruses change in minor ways every few years and in a major way about every ten years, so a flu vaccine is useful for only a year or two and we have to create a renewed vaccine. Increasing costs to the patients and public health. WHAT WHO THINKS ON POST ERADICATION OF SMALLPOX After the eradication of smallpox had been confirmed by the WHA in 1980, WHO commenced a five-year program to implement the post-eradication policies adopted by the World Health Assembly in resolution WHA33.4. This program had been recommended by the Global Commission for the Certification of Smallpox Eradication and was designed both to allay the fears that smallpox might recur and provide full documentation of the effort. CAN WE ERADICATE MANY OTHER VIRAL INFECTIONS? Obviously one cannot avoid all viruses, as someone around us suffers from a viral infection. There tends to be a mini-epidemic of colds at the start of every school term as every virus acquired is shared around! However, eradication of viral diseases is not a straightforward process. Indeed, there are viral diseases that appear impossible to eradicate due to certain characteristics of the causative virus. However, eradication of viral diseases becomes difficult due to certain characteristics of the causative virus as happens with Herpes simplex virus resides latently in neurons, from where infection can reactivate. One cannot identify latently infected individuals clinically but they have the potential to become infective when the virus reactivates. In spite of many efforts, some viruses continuous to be a challenge and vaccination and preventive measure are essential as in Influenza. This explains why individuals can be reinfected with influenza and why the content of the seasonal vaccine must be altered annually.
  • 56. 56 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 WE ARE BACK TO BASICS IN PREVENTION AND CONTROL OF VIRAL INFECTIONS - Hygiene sanitation, Vaccines, the first steps in preventing the spread of viral infections, The great step remains with the practice of good hygiene. This means washing the hands often and eating only food that has been prepared properly. It also means building and maintaining facilities for getting rid of sewage safely and for providing clean drinking water. References Source of Information 1 Medicine: Living Disease Monday, Sept. 18, 1978, TIMEmagazine 2 Viral Infections ? human diseases Forum Updates 2018 3 Emergencies preparedness, the response by WHO on Post elimination of Smallpox 2016 4 Current Resources on Smallpox CDC updates
  • 57. 57 INFECTION CONTROL TRENDS VOL II | ISSUE1 | JAN 2020 ZIKA VIRUS- EMERGING VIRAL INFECTION AN UPDATE Its name comes from the Zika Forest of Uganda, where the virus was first isolated in 1947. Zika virus is related to the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015?16 Zika virus epidemic. Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. TRANSMISSION - Zika virus is transmitted to humans primarily through the bite of an infected Aedes species mosquito. The mosquito vectors typically breed in domestic water-holding containers; they are aggressive daytime biters and feed both indoors and outdoors near dwellings. Nonhuman and human primates are likely the main reservoirs of the virus, and anthroponotic (human-to-vector-to-human) transmission occurs during outbreaks. EPIDEMIOLOGY Out breaks of Zika have occurred in areas of Africa, Southeast Asia, the Pacific Islands, and the Americas. Because the Aedes species mosquitoes that spread Zika virus are found throughout the world, it is likely that outbreaks will spread to new countries. In December 2015, Puerto Rico reported its first confirmed Zika virus case. Locally transmitted Zika has not been reported elsewhere in the United States, but cases of Zika have been reported in returning travelers the most common symptoms of Zika virus disease are fever, rash, joint pain, and conjunctivitis (red eyes). The illness is usually mild with symptoms lasting from several days to a week. Severe disease requiring hospitalization is uncommon. Diagnosis wit h Specific t est s are suggest ed by FDA Specific Test s FDA has issued Emergency Use Authorizations external icon for multiple NAAT assays to diagnose Zika virus infection. Various Zika virus NAATs can be used on serum, plasma, whole blood, cerebrospinal fluid, urine, or amniotic fluid. FDA has cleared one enzyme immunoassay to detect Zika virus IgM antibodies in serum and currently has issued Emergency Use Authorizations external icon for other IgM antibody assays to diagnose Zika virus infection. ACADEMIC COMMUNICATION IN VIROLOGY Dr.T.V.Rao MD Former Professor of Microbiology,Andhra Medical College