DR. ROOPAM JAIN PROFESSOR & HEAD, DEPT. OF PATHOLOGY & BLOOD BANK

1. INFECTIOUS DISEASE -
Human Viruses & Viral Diseases
DR. ROOPAM JAIN
PROFESSOR & HEAD,
DEPT. OF PATHOLOGY & BLOOD BANK

2. Selected Human Viruses &
Viral Diseases

5. Mechanisms
by which
viruses cause
injury to cells

6. DISEASES CAUSED BY VIRUSES

7. VIRAL HAEMORRHAGIC FEVERS
• common features of causing haemorrhages, shock & sometimes
death.
• arthropod-borne (or arbo) viruses
• Classified - 4 groups:
1. Mosquito-borne (e.g. yellow fever, dengue fever, Rift Valley fever)
2. Tick-borne (e.g. Crimean haemorrhagic fever, Kyasanur Forest
disease)
3. Zoonotic (e.g. Korean haemorrhagic fever, Lassa fever)
4. Marburg virus disease & Ebola virus disease by unknown route.
• Mosquito-borne viral haemorrhagic fevers in which Aedes aegypti
mosquitoes are vectors.
• Two important examples of Aedes mosquito-borne viral
haemorrhagic fevers are yellow fever and dengue fever.

8. YELLOW FEVER
• Oldest known viral haemorrhagic fever
• restricted to some regions of Africa and South America.
• Monkeys carry the virus without suffering from illness and the
virus is transmitted from them to humans by Aedes aegypti as
vector.
Clinical features:
• Sudden onset of high fever, & chills,
• myalgia,
• headache,
• jaundice,
• hepatic failure,
• renal failure,
• bleeding disorders
• hypotension.

9. YELLOW FEVER
MORPHOLOGIC FEATURES
Liver. The characteristic changes include:
i) midzonal necrosis;
ii) Councilman bodies; and
iii) microvesicular fat.
Kidneys. The kidneys show the following changes:
i) coagulative necrosis of proximal tubules;
ii) accumulation of fat in the tubular epithelium; and
iii) haemorrhages.

10. DENGUE HAEMORRHAGIC FEVER
(DHF)
• The word dengue is derived from African word ‘denga’ meaning
fever with haemorrhages.
• Dengue is caused by virus transmitted by bites of mosquito Aedes
aegypti.
• DHF was first described in 1953 when it struck Philippines.
• regularly reported from tropics and subtropics—South East Asia,
Latin America

11. • Dengue occurs in two forms:
1. Dengue fever or break-bone fever in an uncomplicated
way is a self-limited febrile illness affecting muscles and
joints with severe back pain due to myalgia (and hence
the name ‘breakbone’ fever).
2. Dengue haemorrhagic fever (DHF), on the other hand, is
a severe and potentially fatal form of acute febrile illness
characterised by cutaneous and intestinal haemorrhages
d/t thrombocytopenia, haemoconcentration,
Hypovolaemic shock and neurologic disturbances.

12. • DHF is most common in children under 15 years of age.
• There are 4 types of dengue viruses
• These visruses infect blood monocytes, lymphocytes and
endothelial cells.
• If patient is treated appropriately at this stage, there is rapid and
dramatic recovery.
• But in untreated cases, dengue shock syndrome develops and
death occurs.

13. MORPHOLOGIC FEATURES :
i) Focal haemorrhages and congestion
ii) Increased vascular permeability resulting in oedema in different
organs
iii) Coagulopathy with thrombocytopenia
iv) Haemoconcentration.

14. Diagnosis of DHF:
1. Serologic testing for detection of antibodies
2. Detection of virus by immunofluorescence method & monoclonal
antibodies
3. Rapid methods such as reverse transcriptase-PCR and fluorogenic-
ELISA.

15. • Main abnormalities in investigations in DHF are as under:
i) Leucopenia with relative lymphocytosis,
ii) Thrombocytopenia
iii) Elevated haematocrit due to haemoconcentration
iv) X-ray chest showing bilateral pleural effusion
v) Deranged liver function tests (elevated transaminases,
hypoalbuminaemia and reversed A:G ratio)
vi) Prolonged coagulation tests (PT, APTT and TT)

16. • At autopsy:
i) Brain: Intracranial haemorrhages, cerebral oedema, dengue
encephalitis.
ii) Liver: Enlarged; necrosis of hepatocytes and Kupffer cells, Reye’s
syndrome in children.
iii) Kidneys: Petechial haemorrhages and features of renal failure.
iv) Muscles and joints: Perivascular mononuclear cell infiltrate.

17. CHIKUNGUNYA VIRUS
INFECTION
• The word chikungunya means “that which bends up”
• Primarily a disease in nonhuman primates but the
infection is transmitted to humans by A. aegypti
mosquito.

18. CHIKUNGUNYA VIRUS INFECTION
Clinically, the disease is characterised by
• abrupt onset of fever,
• severe arthralgia
• migratory polyarthritis affecting small joints,
• chills,
• headache,
• anorexia, nausea, abdominal pain,
• rash,
• Petechiae,
• ocular symptoms such as photophobia.
”

19. • Major laboratory findings
• leucopenia,
• mild thrombocytopenia,
• elevated transaminaseS
• raised CRP.

20. INFLUENZA VIRUS INFECTIONS
• Important and common form of communicable disease.
• General clinical features range from a mild afebrile illness
similar to common cold by appearance of sudden fever,
headache, myalgia, malaise, chills and respiratory tract
manifestations such as cough, soar throat to a more severe
form of acute respiratory illness and lymphadenopathy.
• Sometimes with alarming morbidity and mortality in the
world.
• Seasonal flu vaccine is administered to population at high
risk in developed countries.

21. ETIOLOGIC AGENT
• Influenza virus is a single-stranded RNA virus belonging to
coronaviruses.
• Depending upon its antigenic characteristics of the
nucleoprotein and matrix, 3 distinct types are known: A, B & C.
• Influenza type A is responsible for most serious and severe forms
of outbreaks in human beings while types B and C cause a milder
form of illness.
Type A influenza virus is further subtyped based on its 2 viral
surface features:
• Haemagglutinin (H) H antigen elicits host immune response by
antibodies and determines the future protection against
influenza A viruses.
• Neuraminidase (N) Antibody response against N antigen limits
the spread of viral infection and is responsible for reduction of
infection.

22. • Subtypes of influenza A viruses are designated by denoting
serial subtype numbers of H and N antigens as H1N1, H2N2
etc.
• Influenza A viruses infect human beings, birds, pigs & horses.
• Major antigenic variation in H or N antigens is called antigenic
shift while minor variation is termed antigenic drift.
• In general, population at high risk are immunosuppressed
patients, elderly individuals and infants.
• Two of the known subtypes of influenza A viruses which have
affected the human beings in recent times are as under:
 ”
Avian influenza virus A/H5N1 commonly called “bird flu”.
 ”
Swine influenza virus A/H1N1 commonly called “swine flu”.

23. BIRD FLU (INFLUENZA A/H5N1)
• H5N1 subtype of the influenza type A virus
infection causes severe acute respiratory
syndrome (SARS) which is the human form of bird
flu or avian influenza with having similar
symptomatology.
• Every year, there have been outbreaks in poultry
birds in different parts of the world resulting in
slaughtering of millions of infected chickens every
year.
• Every year there have been seasonal outbreaks in
the human form of the disease in high winter.

24. PATHOGENESIS
• SARS is caused by influenza type A/H5N1 respiratory
virus, also called SARS-associated coronaviruses (SARS-
CoV).
• Humans acquire infection through contaminated nasal,
respiratory and faecal material from infected birds.
• An individual who has human flu and also gets infected
with bird flu, then the hybrid virus so produced is
highly contagious and causes lethal disease.
• Humans do not have immune protection against avian
viruses.

25. LABORATORY DIAGNOSIS :
1. Almost normal-to-low TLC with lymphopaenia in about
half the cases, mostly due to fall in CD4+ T cells.
2. Thrombocytopenia.
3. Elevated liver enzymes: aminotransferases, creatine
kinase and LDH.
4. Virus isolation by reverse transcriptase-PCR on
respiratory sample, plasma, urine or stool.
5. Tissue culture.
6. Detection of serum antibodies by ELISA or
immunofluorescence

26. CLINICOPATHOLOGICAL FEATURES
• Disease begins with influenza-like features such
as fever, cough, dyspnoea, sore throat, muscle
aches and eye infection.
• Patient develops viral pneumonia evident on X-
ray chest and acute respiratory distress (hence
the term SARS), and terminally kidney failure.
• Currently vaccine is yet being developed, the
available measures are directed at prevention of
infection such as by culling (killing of the infected
poultry birds) and isolation of infected case.

27. SWINE FLU (INFLUENZA A/H1N1)
• H1N1 influenza type A flu which appeared last in 1977-78
as a mild form of pandemic reappeared in April 2009 as an
outbreak in Mexico but is rapidly spreading elsewhere.
PATHOGENESIS
• H1N1 influenza type A virus is primarily an infection in pigs
with low mortality in them.
• Human beings acquire infection by direct contact with
infected pigs.
• Further transmission of H1N1 flu occurs by person-to-
person contact such as by coughing, sneezing etc but it is
not known to occur from eating pork.

28. CLINICAL FEATURES
• The disease has the usual flu-like clinical features,
but additionally one-third of cases have been
found to have diarrhoea and vomiting.
• Since human beings do not have immune
protection by antibody response against H1N1
influenza type A and the usual seasonal flu
vaccine does not provide protection against
H1N1, personal hygiene and prophylaxis remain
the mainstay of further spread of disease.

29. VARICELLA ZOSTER VIRUS INFECTION
• Member of herpes virus family and causes
chickenpox (varicella) in non-immune
individuals and herpes zoster (shingles) in
those who had chickenpox in the past.

30. Varicella or chickenpox
• An acute vesicular exanthem occurring in non-immune
persons, especially children.
• Condition begins as an infection of the nasopharynx.
• On entering the blood stream, viraemia is accompanied
by onset of fever, malaise and anorexia.
• Maculopapular skin rash, usually on the upper trunk
and face, develops in a day or two.
• Followed by formation of vesicles which rupture and
heal with formation of scabs.
• A few cases may develop complications which include
pneumonia, hepatitis, encephalitis, carditis, orchitis,
arthritis, and haemorrhages

31. Herpes zoster or shingles
• It is a recurrent, painful, vesicular eruption caused by
reactivation of dormant varicella zoster virus in an
individual who had chickenpox in the earlier years.
• The condition is infectious and spreads to children.
• The virus during the latent period resides in the dorsal
root spinal ganglia or in the cranial nerve ganglia.
• Vesicles in shingles are seen in one or more of the
sensory dermatomes and along the peripheral nerves.
• Lesions are particularly painful.

32. HERPES SIMPLEX VIRUS INFECTION
• Two of the herpes simplex viruses (HSV)—type 1 and 2, cause ‘fever
blisters’ and herpes genitalis respectively.
• HSV-1 causes vesicular lesions on the skin, lips and mucous
membranes.
• The infection spreads by close contact.
• Severe in immunodeficient patients and neonates.
• Complications such as meningoencephalitis and
keratoconjunctivitis.
• Various stimuli such as fever, stress and respiratory infection
reactivate latent virus lying in the ganglia and result in recurrent
attacks of blisters.
• HSV-2 causes herpes genitalis characterised by vesicular and
necrotising lesions on the cervix, vagina and vulva.

33. RABIES
• Fatal form of encephalitis in humans caused by rabies virus.
• Virus is transmitted by the bite of infected carnivores e.g. dog,
wolf, fox and bats.
• The virus spreads from the contaminated saliva of these animals.
• The organism enters a peripheral nerve and then travels to the
spinal cord and brain.
• A latent period of 10 days to 3 months may elapse between the bite
and onset of symptoms.
• Virus localises at the brainstem, it produces classical symptoms of
difficulty in swallowing and painful spasm of the throat termed
hydrophobia.
• Clinical features like irritability, seizure and delirium point towards
viral encephalopathy.
• Death occurs within a period of a few weeks.
• Microscopically, neurons of the brainstem show characteristic Negri
bodies which are intracytoplasmic, deeply eosinophilic inclusions.