Pharm Mlacha virology 2.pdf

PHARMACEUTICAL
MICROBIOLOGY
PST 05103
⚕
NTA Level 5 Semester 1
BY
PHARM MLACHA JO. jp214479@Gmail.com

Rabies
28
BY PHARM MLACHA JO. 2

LearningTasks
By the end of this session students are
expected to be able to:
Describe causative agent, transmission,
signs and symptoms of rabies
Describe treatment, prevention and
control of rabies

Causes andTransmission of Rabies
Rabies is an acute viral infection of the central
nervous system that affects all mammal.
Rabies is caused by the Rabies virus infects the
central nervous system, ultimately causing disease in
the brain and death.
Rabies virus is a neurotropic virus that belongs to
the genus lyssavirus of the family Rhabdoviridae
Rabies virus is a rod- or bullet-shaped, single-stranded,
negative-sense, unsegmented, enveloped RNA virus
Rabies is transmitted to man by a bite wound from
an infected animal via infected secretions, usually
saliva.

Life Cycle of Rabbies

 Cycle
◦ After inoculation, rabies virus may enter the
peripheral nervous system directly and
migrates to the brain or may replicate in
muscle tissue, remaining sequestered at or
near the entry site during incubation, prior to
central nervous system invasion and
replication.
◦ It then spreads centrifugally to numerous
other organs.

Signs and Symptoms of Rabies
Rabies infection has five general stages in humans:
incubation, prodrome, acute neurologic period, coma,
and death.
The incubation period is exceptionally variable, ranging
from fewer than 10 days to longer than 2 years, but is
usually 1–3 months.
Early or prodromal clinical features of the disease are
non-specific and include
Fever, general malaise and fatigue
Respiratory system features (sore throat, cough, and dyspnea),
gastrointestinal system features (anorexia, dysphagia, nausea,
vomiting, abdominal pain, and diarrhea)
Central nervous systems (headache, vertigo, anxiety, apprehension,
irritability, and nervousness

◦ The late features of the disease are:
 Excessive motor activity and agitation, confusion,
hallucinations, excessive salivation, convulsions, priapism,
increased libido, hydrophobia, insomnia, nightmares and
depression
Death is considered as invariable outcome.

Treatment, Prevention and Control of
Rabies
Treatment of rabies include;
◦ Local wound therapy
 The bite wound is thoroughly washed with water and soap for 15 minutes
 Then washed with 0% Povidone iodine to prevent secondary bacterial infection
◦ To prevent or treat bacterial infection antibiotics are used;
 Amoxycillin with clavulanic acid, Ciprofloxacin , Clindamycin,
Trimothoprime/sulphamethoxazole
◦ Passive immunization
 Anti-rabies human immunoglobulin on day 0
 40 IU/kg body weight for Equine (ERIG)
 20 IU/kg body weight for Human (HRIG
 Parenterally and the other half injected into and around the wound
◦ Active immunization
 Human Diploid CellVaccine (HDCV)
 Tetanus toxoid vaccine

 Administer antirabies vaccines
◦ 0.2ml (ID) in divided doses of 0.1 ml on deltoid
on one hand and another 0.1ml on the deltoid of
the second hand on days 0, 3, 14 and 28
◦ 1 ml (IM) on deltoid muscle for days 0, 3,7,14, and
28
 Note 1: Children are given the same doses
but vaccine should be administered on the
lateral part of the thigh
 Note 2: The World Health Organization
recommends ID route of vaccination
administration because it is cost effective.

Prevention and control
Animal rabies is prevented by vaccinating
susceptible species, particularly dogs and cats.
This reduces transmission to humans
Human rabies is best prevented by avoiding
exposures to the disease
 If exposure occurs, postexposure prophylaxis is
necessary and should be initiated promptly.
 Postexposure prophylaxis consists of the
combination of local wound cleansing, human rabies
immune globulin (HRIG) and rabies vaccine.

Key Points
 Rabies is a fatal viral infection that attacks the central
nervous and respiratory systems of mammals,
including humans.
 It is caused by a bite from an infected animal via
secretions usually saliva. Human infection can be from
rabid dogs, bats and other animals.
 The disease attacks the central nervous system
causing non-specific illness which later develop to
severe neurological dysfunction and death
 Rabies is best prevented than treated by avoiding
exposure to the virus through vaccination of animals
and in case exposure occurs immediate institution of
post exposure prophylaxis.

Evaluation
What is rabbies?
What are the signs and symptoms of
rabbies?
What are the medicines used in the
treatment of rabies?

Viral Haemorrhagic Fevers
29

LearningTasks
Describe causative agents, transmission,
signs and symptoms ofViral haemorrhagic
fevers
control ofViral haemorrhagic fever

Introduction to Haemorrhagic
Fevers
Viral haemorrhagic fevers (VHFs) are a
group of illnesses caused by several distinct
families of viruses
Common features ofVHFs;
They affect many organs
They damage the blood vessels
They affect the body's ability to regulate
itself
SomeVHFs cause mild disease, but some,
like Ebola or Marburg, cause severe disease
and death

VHFs are caused by viruses of five distinct
families;Arenaviridae, Bunyaviridae, Filoviridae,
Flaviviridae, and Paramyxoviridae
These five families share the following features;
They are all RNA viruses, and are all covered, or
enveloped, in a fatty (lipid) coating
Their survival is dependent on an animal or insect
host, called the natural reservoir
Humans are not the natural reservoir for any of
these viruses
Humans are infected when they come into
contact with infected hosts
However, with some viruses, after the accidental transmission
from the host, humans can transmit the virus to one another

Human cases or outbreaks of haemorrhagic
fevers caused by these viruses occur
sporadically and irregularly; occurrence of
outbreaks cannot be easily predicted
With a few noteworthy exceptions, there is
no cure or established drug treatment for
VHFs
The viruses are geographically restricted to
the areas where their host species live
 Lassa fever is limited to rural areas ofWest Africa where
rats and mice carry the virus

EBOLA
 Ebola Hemorrhagic fever (Ebola HF) is a
severe often fatal disease in humans and
non-humans (monkeys, gorillas and
chimpanzees).
 It caused by ebola virus of the family
Filoviridae.
 Transmission
◦ Researchers have hypothesized that the first
patient becomes infected through contact
with an infected animal.

Ebola Haemorrhagic Fever
Cause andTransmission
Ebola is an acute viral infection caused by
Ebolavirus, a filovirus that causes haemorrhage,
multiple organ failure, and high mortality rates
Primary transmission is from animal to human,
through contact with an infected animal or its
product
Secondary transmission is from person to person
through:
Broken skin, mucous membrane or exchange of bodily fluids
or ingestion, inhalation and injection of infectious material
Breast feeding
 Sexual contact
The disease can spread rapidly within the health care setting.

 After the first case-patient in an outbreak setting is
infected, the virus can be transmitted in several ways:
◦ Direct contact with blood or other secretions of an
infected person (blood, secretions, organs or other bodily
fluids)
◦ Exposure to Ebola virus through contact with objects, such
as needles, that has been contaminated with infected
secretions
◦ Nosocomial transmission i.e. exposure to the virus has
occurred when health care workers treated individuals
with Ebola HF
◦ Burial ceremonies where mourners have direct contact
with the body of the deceased person
◦ Through handling of infected chimpanzees, gorillas, and
forest antelopes- both dead and alive

Signs and Symptoms
Incubation period is 2 to 20 days
High grade fever
Head ache
Body ache
Abdominal pain, nausea, vomiting and diarrhoea
Photophobia, conjunctival injection, jaundice, and
lymphadenopathy
Upper respiratory symptoms (cough, chest pain,
pharyngitis)
Haemorrhagic symptoms (unexplained bleeding)
CNS symptoms (Delirium, stupor, and coma)
A maculopapular rash, primarily on the trunk,
begins around day 5

Treatment and Prevention
Non-PharmacologicalTreatment
There is no specific treatment for Haemorrhagic Fever
 Supportive therapy includes
Mechanical ventilation, renal dialysis, and anti-seizure therapy
may be required
Management of complications symptomatically
Maintaining Oxygen status and blood pressure
Pharmacological Treatment
Paracetamol
Treat for any complicating infection and co-morbid
condition  B:
Oxygen and management of hypoglycaemia if present
Fluid and electrolyte balance
Sodium Lactate Compound (Ringers Lactate)
NS intravenously if patient cannot take fluids orally

Prevention
Strictly isolation and handling of patients
 Wearing of completely body covering protective
gears when handling patients
 Special and strictly handling of the dead

Marburg Haemorrhagic Fever
 Marburg is severe type of haemorrhagic fever which affects
both animals and humans
 It is caused by the Marburg virus and it is related to Ebola
virus and a parent type belongs to viral haemorrhagic fevers
of Filoviridae family
 Transmission
Spread of the virus between humans has occurred in a setting of
close contact, often in a hospital
Droplets of body fluids, or direct contact with persons,
equipment, or other objects contaminated with infectious blood
or tissues are all highly suspect as sources of disease
Transmission through infected semen can occur up to seven
weeks after clinical recovery
Transmission does not occur during the incubation period

Signs and Symptoms
Incubation period is between 3-9 days
All age groups are susceptible but most case
to adults
Signs and symptoms occur in two phases:
Phase One
Sudden onset of fever, chills, headache and myalgia
Phase Two
 Maculopapular rashes,Trunk rash, Nausea,Vomiting, Sore throat,
Abdominal pain, Diarrheal, Jaundice, Pancreas inflammation, Severe
weight loss
 Liver failure, Massive haemorrhage (all orifices), Multi-organ
dysfunction, Delirium, Shock, and Death

There is no specific treatment, cure, or
vaccine for Marburg Haemorrhagic fever
Supportive hospital therapy:
Fluid and Electrolyte balancing
Oxygen
Blood transfusion and clotting factors
Treatment of complicating infections
Prevention
Isolation of patients
Wearing protective gears when attend patients or
dead bodies

RiftValley Fever
 This is a viral zoonosis that is primarily spread amongst
animals by the bite of infected mosquitoes, transmitting the
RiftValley virus
 Aedes mosquitoes are the main vector biting animals
 Transmission to human is mainly by direct or indirect contact
with blood or organs of infected animals through;
 Handling of animal tissue during slaughtering or butchering
 Assisting with animal births, conducting veterinary
procedures
 Direct inoculation e.g. via wound from infected knife or
through contact with broken skin or through inhalation of
aerosols produced during the slaughter of an infected animal
 Bite of an infected mosquito

 Human become viraemic; capable of infecting
mosquitoes shortly before onset of fever
and for the first 3–5 days of illness. Once
infected, mosquitoes remain so for life.
 Incubation period is between 2-6 days. Signs
and symptoms are Influenza like illnesses:
sudden onset of fevers, headache, myalgia,
backache neck stiffness photophobia,
vomiting and Clinical jaundice
 Meningoencephalitis and haemorrgic fever
syndrome follow thereafter.

There is no any established course of
treatment of this disease.
Most of human cases are relatively mild
and of short duration so will not require
any specific treatment
Prevention
Mosquito control
Wearing proactive gears when handling
animals or their fluids

Dengue Haemorrhagic Fever
 Dengue fever is transmitted by the bite of an
Aedes aegypti mosquito infected with a dengue
virus.
 The mosquito becomes infected when it bites a
person with dengue virus in their blood.
 Dengue does not spread directly from
person to person.
 It is only spread through the bite of an infected
mosquito.
 This type of mosquito breeds in clean water and
has a flight range of only 100 – 200 metres and
likes to bite in the afternoon unlike the anopheles
mosquito which bites in the night.

Signs and Symptoms
 Symptoms usually begin three (3)days and lasts up to fourteen
(14)days after infection.
 Clinical features of the disease can be divided into three groups
and this forms the basis of the standard case definition;
 Dengue Febrile Illness (DF):
 Retro-orbital or ocular pain, headache, rash, myalgia, arthralgia
 Haemorrhagic manifestations (epistaxis, gum bleeding; blood in vomitus, urine,
stool; or vaginal bleeding
 Anorexia, nausea, abdominal pain, and persistent vomiting may also occur
 Dengue Haemorrhagic Fever (DHF)
 Persistent high grade fever lasting from 2-7 days
 Spontaneous bleeding
 Retro-orbital pain
 Joint, muscle and abdominal pain
 Macular or confluent blanching rash (noted during recovery period)
 Thrombocytopenia (>100,000 cells per mm3)
Sometimes symptoms are mild and can be mistaken for those of the flu or
another viral infection.

Dengue Shock Syndrome (DSS)
 Circulatory failure as evidenced by rapid and weak
pulse and narrow pulse pressure (<20mm Hg)
 Age-specific hypotension and cold, clammy skin and
restlessness
No specific treatment is available for
Dengue fever
 Supportive Treatment
 Paracetamol
 Fluids (Ringers lactate, NS)
 Blood transfusion and clotting factors
 Oxygen and management of hypoglycaemia if present

 Prevention
◦ Do not allow empty vessels, coconut shells, plastic
containers, flower pots, tires etc to collect rain
water in them
◦ Cover your over tanks to prevent mosquitoes
breeding in fresh water
◦ Screen your homes with wire mesh
◦ Wear full clothing – long sleeves
◦ Apply mosquito repellents
Note: True community participation is key. Integrated
vector management (IVM) is the strategic approach to
vector control promoted by WHO and includes
control of the vectors of dengue

Yellow Fever
 Yellow fever is an acute viral infection that is
transmitted to human through a bite of infected
mosquito-predominantly Aedes mosquitoes.
 It is caused by a virus that belongs to Flavivirus.
 Though many cases of yellow fever are mild and self-
limiting, the disease can also be a life threatening
causing hemorrhagic fever and hepatitis.
 Incubation period of 2-6 days and human become
viremic - capable of infecting mosquitoes, shortly
before onset of fever and for the first 3–5 days of
illness.
 Once infected, mosquitoes remain so for life
The disease can be life threatening causing
haemorrhagic fever and hepatitis

 Treatment, prevention and control
◦ No specific anti-viral treatment, supportive therapies
are recommended.
◦ Prevention and Control involve mosquito control and
provision of yellow fever vaccine.
 Indication forYellow fever vaccine:
◦ persons ≥ 9 months of age
 Planning travel to or residence in an endemic area
 Planning travel to a country with an entry requirement
◦ Needs to be given ≥ 10 days prior to arrival in
endemic area
◦ Revaccination at 10 year intervals

Key Points
VHFs are caused by RNA viruses of five
distinct families;Arenaviridae,
Bunyaviridae, Filoviridae, Flaviviridae, and
Paramyxoviridae
VHFs affect many organs, damage the
blood vessels and affect the body's ability
to regulate itself
There is not specific treatment for the
VHFs

Evaluation
What is aVHF?
How areVHS acquired by humans?
What is the treatment ofVHFs?

HIV and AIDS
30

LearningTasks
Describe causative agents, transmission,
signs and symptoms of HIV and AIDS
control of HIV and AIDS

HIV/AIDS
 AIDS (Acquired immune Deficiency
Syndrome)
~Is a set of symptoms (syndrome) caused by
HIV virus.
◦ The illness was first described in 1981, and HIV-1 was
isolated by the end of 1983.
◦ Since then, AIDS has become a worldwide epidemic,
expanding in scope and magnitude as HIV infections
have affected different populations and geographic
regions.
◦ Millions are now infected worldwide.

HIV (Retrovirus)
 AIDS is caused by a Human Immunodeficiency virus
(HIV) which infect CD4 cells of immune system.
 HIV is an enveloped RNA-containing virus belonging to
the family Retroviridae.
 It is:-
◦ Spherical
◦ Single strand (ss) RNA, positive-sense.
◦ Reverse transcriptase, RT (RNA-dependent DNA
polymerase) Enzyme.
 Very few viruses have this enzyme
 Retroviruses replicate backwards, hence the prefix ‘retro’ in their
name. RNA is transcribed from DNA, but retroviruses are capable of
transcribing DNA from RNA by use of the RT

 There are two distinct types of human
AIDS viruses:
◦ HIV-1 and
◦ HIV-2
 In Tanzania, HIV infection is caused by HIV-1
subtype.
 The common HIV-1 subtypes in Tanzania are A, C,
D, and their recombinants.There is no HIV-2
subtype infection has been reported to date.

HIV Transmission
 HIV infection is acquired through:
◦ Unprotected sexual intercourse with an
infected partner;
◦ Exposure to infected blood and blood products;
or
◦ Transmission from an infected mother to the
unborn child :-
In the uterus,
During delivery, or
From breast milk

 More than 90% of adults in sub-Saharan Africa
acquire HIV infection through unprotected sexual
intercourse with infected partners.
 Transmission of HIV through body fluids other than
blood and genital secretions such as cerebrospinal
fluid, pleural fluid and amniotic fluids are also
possible.
◦ However, unless blood is visibly present, saliva, sputum,
sweat, tears, faeces, nasal secretions, urine, and vomits
carry a very low risk of transmission of HIV2

 Interaction between the viral envelope proteins
(gp120) and receptors on the cell membrane is
critical for the HIV to enter and infect the host
cell.
◦ High concentrations of the CD4 molecule and co-
receptors have been detected on the surface of
T-lymphocytes and macrophages.
◦ Other cells that have been found to have CD4
molecules on their surface include the Langerhans
cells (found in the skin) and the microglial cells of the
brain.

◦ Following entry of the HIV into a susceptible host
cell using the enzyme reverse transcriptase, the viral
genome copies itself from RNA to DNA genetic
material.
◦ The viral DNA copy enters the nucleus of the host
cell and becomes intimately incorporated into the host
cell’s own DNA using the enzyme integrase.
◦ The virus thus becomes a permanent part of an
infected person’s nuclear proteins.
◦ There follows a latent period during which the provirus
in the infected nucleus waits for an external stimulus to
start reproducing

Signs and Symptoms of HIV/AIDS
HIV is associated with three presentations;
Asymptomatic infection
Acute infection with symptoms
May include fever, sweats, myalgia or arthralgia, sore throat,
lymphadenopathy, nausea, vomiting, diarrhea, persistent
headaches, rash and generalized pruritus
Acquired immune deficiency syndrome (AIDS)
Characterized by progressive immune deficiency accompanied
by a wide range of opportunistic infections, neoplasms, and
neurologic abnormalities, including progressive dementia and
peripheral neuropathy.
Most patients, however, present with symptoms
due to opportunistic infections e.g. tuberculosis,
candidiasis or pyogenic infections.

Diseases Associated by HIV
 Main effect of HIV in the human is that it weakens
the immune system hence rendering it incapable
of fighting against disease.
 HIV does not cause one disease condition but
associated with a group diseases and conditions.
 HIV can also directly affect other organs of the
body such as brain, heart, kidney and skin.

 Example of diseases associated with HIV can be
grouped as follows:
◦ Viral infections;
 e.g. herpes virus infections and reactivation diseases.
◦ Bacterial infections;
 E.g. Mycobacteria species, Salmonella, Shigella, Staphylococcal and
Streptococcal.
◦ Fungal infection;
 Candida spp, Cryptococcus spp, Pneumocystis spp,
◦ Parasitic infections,
 Toxoplasmosis, Strongyloidiasis
◦ Malignant conditions (Cancer)
 E.g. Kaposi’s sarcoma, Cervical cancer (HPV), Lymphoma.

HIV Management
 The management of HIV includes
treatment of the associated infections or
conditions and specific treatment to
control the HIV.
 Most drugs used in HIV target the
enzymes used in the viral replication cycle
where by the treatment involves
simultaneous use of more than one drug
of different classes.

 Drugs used to treat/control HIV can be divided
into classes as follows:
◦ Nucleoside Reverse Transcriptase Inhibitors (NRTI’s)
 Eg. Lamivudine(3TC), Zidovudine (AZT/ZDV), Emtricitabine
(FTC),Tenofovir (TDF), Didanosine (ddl),Abacavir (ABC)
◦ Non-Nucleoside Reverse Transcriptase Inhibitors
(NNRTI’s)
 Eg. Efavirenz, Nevirapine
◦ Protease Inhibitors (PI’s)
 Lopinavir (LPV), Ritonavir (RTV),Atanazavir (ATV), Saquinavir
(SQV)

Integrase strand transfer inhibitors (INSTI)/
Integrase inhibitors
 Dolutegravir (DTG).Raltegravir
Fusion inhibitors
 Enfuvirtide
Chemokine receptor inhibitors/CCR5 inhibitors
 Maraviroc

Prevention and control of HIV/AIDS
Safe sex practices e.g. use of condoms
Post exposure prophylaxis for people at risk
e.g. medical staff
Prevention of mother-to-child transmission
Avoid sharing skin piercing instruments e.g.
needles
Avoid drug abuse

 Key Points
 HIV is the virus that cause AIDS
 A person may have HIV but not AIDS
 AIDS occur when the body’s immune system is
weakened by the virus so that the body cannot
defend against infectious pathogens.
 Treatment of HIV/AIDS involves the use of
antiretroviral drugs which lower viral load and
improve the immunity and quality of life in HIV/AIDS
patients
 Prevention of HIV transmission involves wide aspects
of behavioural changes, post exposure prophylaxis
and prevention of mother-to-child transmission

Evaluation
What is the difference between HIV and
AIDS?
How is HIV transmitted?
What are the classes of medications used
for treatment of HIV/AIDS?

QUESTION
What are the regimes (including drug name, dose
and dose schedule) of antiretroviral drugs used;
◦ In treatment of adults and adolescents without
tuberculosis
◦ In treatment of adults and adolescents with
tuberculosis
◦ In pregnancy
◦ Drug abusers
◦ For post-exposure prophylaxis of medical staff
◦ For prevention of mother-to-child transmission
◦ In prophylaxis of babies born from infected mothers

END
ALLTHE BEST
BY
PHARM MLACHA JO.

Pharm Mlacha virology 2.pdf

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