Viral Diseases Notes

Viral Diseases

Viral diseases are the most common cause of human illness. However, many of the viralinfections remain asymptomatic while others produce viral disease.

Another peculiar feature of viral infection is that a single etiologic agent may produce different diseases in the same host depending upon host’s immune response and age at infection for example, Varicella-zoster virus is causative for chickenpox as well as herpes zoster.

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Viruses are essentially intracellular parasites. Depending upon their nucleic acid genomic composition, they may be single-stranded or double-stranded, RNA or DNA viruses.

A list of common viruses and diseases caused by them is given in Table.

Oncogenic viruses A few common and important viral diseases are described below.

Viral Haemorrhagic Fevers

Viral haemorrhagic fevers are a group of acute viral infections which have common features of causing haemorrhages, shock and sometimes death.

• Viruses causing haemorrhagic fevers were earlier called arthropod-borne (or arbo) viruses since their transmission to humans was considered to be from arthropods.
• However, now it is known that all such viruses are not transmitted by arthropod vectors alone and hence such haemorrhagic

Fevers are classified according to the routes of transmission and other epidemiologic features into 4 groups:

1.  Mosquito-borne (for example, Yellow fever, Dengue fever, Rift Valley fever)
2. Tick-borne (for example, Crimean haemorrhagic fever, Kyasanur Forest disease)
3. Zoonotic (for example,  Korean haemorrhagic fever, Lassa fever)
4.  Marburg virus disease and Ebola virus disease by an unknown route.

Of these, mosquito-borne viral haemorrhagic fevers in which Aedes aegypti mosquitoes are vectors, are the most common problem the world over, especially in developing countries.

Important examples of Aedes mosquito-borne viral haemorrhagic fevers are yellow fever, dengue fever and chikungunya, which are discussed below.

Diseases caused by viruses:

Yellow Fever

Yellow fever is the 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 a vector.

Yellow fever is characterised by the following clinical features:

1. Sudden onset of high fever
2. Chills
3. Myalgia
4. Headache
5. Jaundice
6. Hepatic failure
7. Renal failure
8. Bleeding disorders and
9. Hypotension.

Morphologic Features:

Major pathologic changes are seen in the liver and kidneys.

• Liver The characteristic changes include:
  • Midzonal necrosis
  • Councilman bodies, and
  • Microvesicular fat.
• Kidneys The kidneys show the following changes:
  • Coagulative necrosis of proximal tubules
  • Accumulation of fat in the tubular epithelium, and
  • Haemorrhages.

Patients tend to recover without sequelae; the death rate is less than 5%, and death results from hepatic or renal failure and petechial haemorrhages in the brain.

Dengue Haemorrhagic Fever (Dhf)

The word dengue is derived from the African word ‘denga’ meaning fever with haemorrhages. Dengue is caused by a virus transmitted by bites of the mosquito Aedes aegypti;

• The transmission is highest during and after the rainy season when mosquitos are numerous.
• DHF was first described in 1953 when it struck the Philippines. Since then, DHF has been regularly reported from tropics and subtropics—South East Asia, Latin America and the Pacific Islands.
• Since 1996, cases have been seen every year in North India in the post-monsoon rain period.

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 due to thrombocytopenia, haemoconcentration, hypovolaemic shock and neurologic disturbances. DHF is most common in children under 15 years of age.

There are 4 types of dengue viruses and all of them produce similar clinical syndrome.

• These viruses infect blood monocytes, lymphocytes and endothelial cells. This initiates complement activation and consumptive coagulopathy including thrombocytopenia.
• The entire process takes place rapidly and may evolve over a few hours. If the patient is treated appropriately at this stage, there is rapid and dramatic recovery. But in untreated cases, dengue shock syndrome develops and death occurs.

Morphologic Features:

• The predominant organ changes in DHF are due to the following:
  • Focal haemorrhages and congestion
  • Increased vascular permeability resulting in oedema in different organs
  • Coagulopathy with thrombocytopenia
  • Haemoconcentration.
• Diagnosis of DHF is confirmed by the following tests:
  • Serologic testing for the detection of antibodies
  • Detection of the virus by immunofluorescence method and monoclonal antibodies
  • Rapid methods such as reverse transcriptase-PCR and fluorogenic-ELISA.
• The main abnormalities in investigations of DHF are as under:
  • Leucopenia with relative lymphocytosis, sometimes with atypical lymphocytes
  • Thrombocytopenia
  • Elevated haematocrit due to haemoconcentration
  • X-ray chest showing bilateral pleural effusion
  • Deranged liver function tests (elevated transaminases, hypoalbuminaemia and reversed A: G ratio)
  • Prolonged coagulation tests (prothrombin time, activated partial thromboplastin time and thrombin time)
• At autopsy: The predominant organ changes observed are as follows:
  • Brain Intracranial haemorrhages, cerebral oedema, dengue encephalitis.
  • Liver Enlarged; necrosis of hepatocytes and Kupffer cells, Reye’s syndrome in children.
  • Kidneys Petechial haemorrhages and features of renal failure.
  • Muscles and joints Perivascular mononuclear cell infiltrate.

Chikungunya Virus Infection

The word chikungunya means “that which bends up” and is derived from the language in Africa where this viral disease was first found in human beings. Chikungunya virus infection is primarily a disease in nonhuman primates but the infection is transmitted to humans by A.aegypti mosquito.

The disease is endemic in parts of Africa and Asia and occurs sporadically elsewhere.

• Clinically, the disease is characterised by abrupt onset of fever, severe arthralgia (producing bending posture of the patient due to pain and hence the name), migratory polyarthritis affecting small joints, chills, headache, anorexia, nausea, abdominal pain, rash, petechiae and ocular symptoms such as photophobia.
• Major laboratory findings include leucopenia, mild thrombocytopenia, elevated transaminases and raised CRP.

Influenza Virus Infections

Influenza virus infection is an important and common form of communicable disease, especially prevalent as a seasonal infection in developed countries.

Its general clinical features range from a mild afebrile illness similar to the common cold by the appearance of:

1. Sudden fever
2. Headache
3. Myalgia
4. Malaise
5. Chills and
6. Respiratory tract Manifestations such as cough
7. Soar throat to a more severe form of acute respiratory illness and lymphadenopathy.

Various forms of influenza virus infections have occurred as an outbreak at different times, sometimes with alarming morbidity and mortality in the world. The seasonal flu vaccine is administered to the population at high risk in developed countries.

Etiologic Agent:

• The influenza virus is a single-stranded RNA virus belonging to coronaviruses. Depending upon the antigenic characteristics of the nucleoprotein and matrix, 3 distinct types are known: A, B and C.
• Out of these, influenza type A is responsible for most 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:

1. Haemagglutinin (H): H antigen elicits host immune response by antibodies and determines the future protection against influenza A viruses.  There are 16 distinct H subtypes of type A influenza viruses.
2. Neuraminidase (N):
   • Antibody response against N antigen limits the spread of viral infection and is responsible for the reduction of infection. N antigen of influenza A exists in 9 subtypes.
   • Thus, the 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 and horses. Given a high antigenic variation in H and N components, influenza A viruses are responsible for many known epidemics and pandemics in history and in present times.
   • Major antigenic variation in H or N antigens is called antigenic shift while minor variation is termed antigenic drift.
   • In general, populations at high risk are immunosuppressed patients, elderly individuals and infants.

Two of the known subtypes of influenza A viruses which have affected human beings in recent times are as under:

• Avian influenza virus A/H5N1 is commonly called “bird flu”.
• Swine influenza virus A/H1N1 is commonly called “swine flu”. These two entities are briefly discussed below.

Bird Flu ((Influenza A/H5n1)

The 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 similar symptomatology.

• Every year, there have been outbreaks in poultry birds in different parts of the world resulting in the slaughtering of millions of infected chickens. The human outbreak of the disease called SARS reemerged in December 2003 in southern China, Hong Kong and
• Vietnam and then spread to other countries in Asia, Europe and America. Since then, every year there have been seasonal outbreaks in the human form of the disease in high winter and has so far affected 15 countries and taken a toll of over 250 lives.
• Its rapidly downhill and fatal clinical course and apprehension of a pandemic have sent alarm bells all over the world for quarantine.

Pathogenesis:

Sars is caused by influenza type A/H5N1 respiratory virus, also called SARS-associated coronaviruses (SARS-CoV). Though it is not fatal for wild birds, it can kill poultry birds and people.

• 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.
• No person-to-person transmission has been reported so far but epidemiologists fear that if it did occur it will be a global epidemic. Humans do not have immune protection against avian viruses.

Laboratory Diagnosis:

The following abnormalities in laboratory tests are noted:

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

Clinicopathological Features:

Typically, the disease begins with influenza-like features such as fever, cough, dyspnoea, sore throat, muscle aches and eye infection.

• Soon, the patient develops viral pneumonia evident on X-ray chest acute respiratory distress (hence the term SARS), and terminal kidney failure.
• There is apprehension of an epidemic of SARS if the avian virus mutates and gains the ability to cause person-to-person infection.
• Since currently vaccine is yet to be developed, the available measures are directed at the prevention of infection such as culling (killing of the infected poultry birds) and isolation of infected cases.

Swine Flu (Influenza A/H1n1)

H1N1 influenza type A flu which appeared as a mild form of pandemic in 1977-78 and reappeared in April 2009 as an outbreak in Mexico but has spread elsewhere globally. Given the rising number of cases and high mortality attributed to swine flu, the WHO has sounded worldwide alert of a pandemic.

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.
• However, further transmission of H1N1 flu occurs through person-to-person contact such as by coughing, sneezing etc but it is not known to occur from eating pork.

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 protect against H1N1, personal hygiene and prophylaxis remain the mainstay of further spread of the disease.

Varicella Zoster Virus Infection

Varicella zoster virus is a 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.

Varicella or chickenpox:

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

Herpes zoster or shingles:

• It is a recurrent, painful, vesicular eruption caused by the reactivation of dormant varicella-zoster virus in an individual who had chickenpox in earlier years.
• The condition is infectious and spreads to children.
• The virus during the latent period resides in the dorsal root spinal ganglia or the cranial nerve ganglia.
• On reactivation, the virus spreads from the ganglia to the sensory nerves and peripheral nerves.
• Unlike chickenpox, the vesicles in shingles are seen in one or more of the sensory dermatomes and along the peripheral nerves.
• The lesions are particularly painful as compared with painless eruptions in chickenpox.

Herpes Simplex Virus Infection

Two of the herpes simplex viruses (HSV)—type 1 and 2, cause ‘fever blisters’ and herpes genitalis respectively.

HSV-1:

• HSV-1 causes vesicular lesions on the skin, lips and mucous membranes. The infection spreads by close contact.
• The condition is particularly severe in immunodeficient patients and neonates while milder attacks of infection cause fever blisters on lips, oral mucosa and skin.
• Severe cases may develop 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:

• HSV-2 causes herpes genitalis characterised by vesicular and necrotising lesions on the cervix, vagina and vulva.
• Like HSV-1 infection, lesions caused by HSV-2 are also recurrent and develop in non-immune individuals.
• Latency of HSV-2 infection is similar to HSV-1 and the organisms are reactivated by stimuli such as menstruation and sexual intercourse.

Rabies

Rabies is a fatal form of encephalitis in humans caused by rabies virus.

The virus is transmitted into the human body by the bite of infected carnivores, for example, Dogs, 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.
• Since the virus localises at the brainstem, it produces classical symptoms of difficulty in swallowing and painful spasms of the throat termed hydrophobia.
• Other clinical features such as 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.

Polio

Poliomyelitis is caused by poliovirus which is an enterovirus, so named because of its ability of multiply in the gastrointestinal tract.

• The infection occurs by ingestion (faecal-oral route) and the organisms infect the epithelial cells in the mucosa of the gastrointestinal tract, submucosal lymphoid tissue of the tonsils and Peyer’s patches.
• While infected patients may remain asymptomatic, about 5% of cases develop viraemia manifested by fever, malaise sore throat, myalgia and headache.
• In a small proportion of patients, aseptic meningitis may occur and present with paralytic polio.
• Given the risk of the development of polio from the live polio vaccine, it has been replaced with inactivated oral polio vaccine since 2000.
• The WHO had resolved to eradicate polio globally by the year 2000 which has largely succeeded:
• However, isolated cases have continued to appear in
  • Nigeria
  • India
  • Pakistan
  • Afghanistan and
  • Somalia.
• Diagnosis of infection with enterovirus is established by isolation of the organism from the throat, CSF, serum or other body fluids, and confirmed by culture or PCR.
• Serologic diagnosis is less helpful due to many serotypes and the lack of a specific antigen.

Viral Diseases:

• Mosquito-borne viral haemorrhagic fevers in which Aedes aegypti mosquitoes are vectors, are the most common problem the world over, especially in developing countries, and include yellow fever, dengue fever, and chikungunya.
• Chikungunya is primarily a disease in nonhuman primates but the infection is transmitted to humans by A.aegypti mosquito.
• Influenza virus infection is an important and common form of communicable disease, especially prevalent as a seasonal infection in developed countries.
• Two of the known subtypes of influenza A viruses which have affected mankind in recent times are avian influenza virus A/H5N1 commonly called “bird flu” and swine influenza virus A/H1N1 commonly called “swine flu”.
• Varicella zoster virus is a member of the herpes virus family and causes chickenpox (varicella) in non-immune individuals and herpes zoster (shingles) in those who had chickenpox in the past.
• Two of the herpes simplex viruses (HSV)—type 1 and 2, cause ‘fever blisters’ and herpes genitalis.
• Rabies is a fatal form of encephalitis in humans caused by rabies virus. Poliomyelitis is caused by polio enterovirus which may present with viraemia and paralytic polio