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Enveloped, ss positive stranded RNA virus
6 major genotypes-do not affect development of chronic complications. May affect response to treatment (Poor response in genotype 1)
Mode of infection-predominantly parenteral (via percutaneous exposures to blood)
Prevalence is highest in IVDU( ~ 80%), transfusion recipients/ chronic hemodialysis patients, persons who engage in high-risk sexual practices.
Can be transmitted vertically (< HBV)
Principal age-15-29 yrs
Insidious onset. Usually mild disease with mild elevation of liver enzymes.
Fulminant disease is rare.
Despite mild nature of disease, 70-90 % of cases progress to chronic liver disease (often asympto-matic, but histologic evaluation shows chronic active hepatitis)
20-50% develop cirrhosis
Of these 5-25% develop HCC
Extrahepatic complications due to circulating immune complexes may manifest as mixed cryoglobulinemia and glomerulonepritis
40% of chronic liver disease in hospitals is HCV-related
End-stage liver disease associated with HCV is the most frequent indication for liver transplanta-tionQ
EIA can detect antibodies (appear in 8-9 weeks after infection) against core, envelope and NS3 and NS4 (non-structural).
Serology cannot differentiate acute/chronic or resolved infections
RT-PCR can detect presence of circulating RNA and are useful in monitoring antiviral therapy
A single infection with any of the 5 hepatitis causing viruses confers homologous but not heterologous immunity.
An exception is HCV, where reinfections can occur.
HBV-HCV co-infections can occur as they have the same mode of transmissionQ.
A patient suffering from HCV may become infected with HBV at a later stage and vice-versa.
Treatment-IFN-alpha of proven benefit. Only 25% show a sustained response, rest may relapse after cessation of therapy.
Combination of IFN with ribavirin if given may give a sustained response in 50%
Orthotopic liver transplantation is treatment for ESHD.
Spherical 40-50 nm
ss , positive sense RNA
Flavivirus- arthropod borne
Hepaci virus- Non arthropod borne
St. Louis encephalitis
Murray valley encephalitis
West Nile Virus
Russian spring summer encephalitis
Dengue Hemorrhagic fever
Omsk Hemorrhagic fever
Kyasanur forest disease
Most widespread of all arboviruses (2nd-Chikun
Antigenically related to yellow fever virus
Infection with one serotype confers life-long immunity to that serotype but no cross immunity
Transmission mainly occurs in tropics, ie. Between 35 degree north and south latitudes
Vector- Aedes aegypti
These mosquitoes breed around human dwellings in uncovered water storage containers, vases, flower dishes, cans, etc.
They shelter indoors and are day biters.
Break-bone fever/saddle back fever
Frontal headache, retro orbital pain, bodyaches, joint pains, rash with intense pruritis
DF is generally self limiting(3-7 days)
DHF- Usually seen in children less than 15 yrsQ
Most common cause- DEN 2
Main pathogenesis- TCP, coagulation system malfunction and increased vascular permeability
Leukopenia, TCP, elevated AST levels
Serological diagnosis- Capture IgM and IgG ELISAQ, ICT or IFAT.
Heterologous reactions with other cocirculating flaviviruses are often seen due to cross reactions. Neutralization tests like plaque reduction assays are more specific, though time consuming and expensive.
Serotype-Specific Neutralization test can be used to differentiate the 4 serotypes
Monitoring pulse, BP, urine output
Whole blood, platelet or fresh frozen plasma if significant hemorrhage
No vaccine is available yet, as it is difficult because a vaccine must provide protection against all 4 serotypes; otherwise recipients may be at increased risk for DHF.
A tetravalent vaccine using molecular attenuation is being clinically evaluated.
Most important cause of epidemic viral encephalitis in the world.
Occurs in Korea, Japan, SEA and India
Season- June to October
In 2005-2006, large outbreaks in Northern India
Vector- Culex tritaeniorhyncus and Culex vishnui which breed in rice fields**
Amplifier host pigs and water birds
More than 90% of infections are asymptomatic and provide protective immunity.
Cases occur primarily in children 2-10 yrs of age.
Severe encephalitis leading frequently to coma
CFR is as high as 25-50%.
Neurologic complications like seizures, CN palsies, motor deficits may persist for 5 yrs.
Vaccines for JE
Inactivated mouse brain vaccine- WHO approved
Based on Nakayama and Beijing 1 strain
Produced in CRI Kasauli
Given S/C -3 doses -0, 7 30/14
Cell culture derived live attenuated –SA-14-14-2 strain grown in BHK 21 cell lines; highly effective even with a single dose. Given to several children during the 2006 epidemic in India
Inactivated vaccine in Vero cell line-being developed with the same vaccine strain.
Chimeric yellow fever 17 D JE vaccine
Not reported from AsiaQ.
Seen in tropical America and Africa
Vector in urban cycle- Aedes aegypti
Vector in sylvatic cycle- A. haemagogous
Virus multiplies in Kupffer cellsQ
Torres bodies in infected liver cells.
Councilman bodies are eosinophilic masses formed due to hyalinized necrosed cells
Infection may be asymptomatic- upto 50%. Milder disease in infants.
Stage of infection-Fever, HA, facial flushing, chills, myalgias and bradycardia (Faget’s sign) with leukopenia
Stage of intoxication-N, V, Jaundice, hemorrhagic manifestations, like petechiae, epistaxis, hematemesis. Albuminuria helps in differentiating from other causes of viral hepatitis
Hypotension, shock and metabolic acidosis.
Death occurs in 7-10 d. mortality rate-20%
If patient survives- no long term sequelae.
Diagnosis is done by-IgM antibody by ELISA in a single sample provides a presumptive diagnosis with confirmation by a 4-fold rise in neutralising antibody between acute and convalescent phase serum samples.
Supportive treatment with oxygen, fluids, fresh frozen plasma and vasopressors
Surviving patients develop neutralizing antibodies which give life long protection.
Live attenuated 17 D vaccine was developed by Theiler in 1937. nobel prize in 1951
now is prepared in eggs and lyophilized.
Single dose (S/C) give protection for at least 10 yrs or possibly lifelong. It is contraindicated in pregnancy, in HIV and less than 9 months
The virulent strain of the virus is called- Asibi strain which was attenuated by serial passage in cell culture to give rise to the 17 D strain
Tick borne flavivirus closely related to RSSE
Vector – Tick: Haemaphysalis spinigera
Reservoir- Rodent and squirrels
Amplifier host – Monkeys( fatal disease)
Season- January to June . Subsides with onset of monsoon
First isolated- Shimoga district in Karnataka (1957)
Fever, myalgia, severe prostration, LNAP, HSM, hemorrhages of skin/ mucosa/ viscera
Formaline inactivated tissue culture vaccine being produced at Shimoga.
West Nile fever virus-occurs in Europe, Middle East, Africa, Russia and South West Africa.
It is a member of Japanese B E antigenic complex
I antigenic type.
Appeared for the first time in USA in 1999 and caused the largest arbovirus ME in the Western hemisphere in 2002. This epidemic also documented transmission by organ transplantation, blood transfusion and breast feeding.
Vector- mainly Culex
Most common reservoir- birds (crows, sparrows, jays)
Humans are dead end hosts as they have insufficient viremia to infect feeding mosquitoes
St Louis E virus is the most common cause of epidemic E in N. America
Vector –Culex sp.
related to Japanese encephalitis virus
ILH virus is very closely related to the Japanese encephalitis virus complex
Central and South America
Vector-several genera of mosquitoes-culex, Ochlerotatus,Psorophora, Haemagogus.
symptoms ranging from subclinical to severe febrile disease.
In mild cases, patients often report gastrointestinal or respiratory symptoms lasting ≈1 week.
In severe cases, either the central nervous or cardiac system can be affected
Enterovirus- Polio virus 1-3
Coxsackie A 1-24
Coxsackie B 1-6
Echo virus 1-34
Hepatovirus /HAV-enterovirus 72
27 nm ssRNA non-enveloped virus
Only one serotypeQ
Can survive chlorinationQ
Feco-oral route of transmission, more often a person to person spread
Incubation period-2-6 wks
Multiplies in the intestinal epithelium and reaches the liver by hematogenous route
Shed in the feces in the late IP and prodromeQ
No virus in stool during jaundice
No chronic stage/extrahepatic manifestation
M/c cause of hepatitis in children.Q
90% of Indian population is seropositive
Diagnosis on the basis of serology-IgM ELISAQ
Vaccine- formaline inactivated( on human diploid cells) which provides immunity for 20 yrs
First isolated from the feces of children with paralytic polio in the village of Coxsackie in New York
Able to infect suckling but not adult mice
Based on pathological changes produced in suckling miceQ, two grps A and B
Grp A viruses- 24 types
Grp B viruses- 6 types
Respiratory tract infection
Herpangina (vesicular stomatitis)
Hand , foot and mouth disease
Acute hemorrhagic conjunctivitis
Post viral fatigue syndrome
Acute hemorrhagic conjunctivitis- A/c Apollo conjunctivitis: Enterovirus type 70, Cox A 24Q
HFMD- Cox A 16, Cox B 1-3(Benign)
HFMD- Enterovirus 71 (epidemic with serious complications)
Non enveloped, ss RNA virus
Stable at acid pH, heat labile.
Can survive chlorination.
Does not survive freeze drying well**
Three types based on neutralization tests
Type 1- Epidemics
Type 2- Endemic infections
Type 3- Occasionally causes epidemics
2 major antigens- C and D.
D ag is type specific
Anti-D antibody is protective
Natural infection only occurs in humans
Lab animals- Monkeys, chimpanzees. Only primates have receptor for the virus. Transgenic mice developed which carry PVR.
Tissue culture-only primate cell line which have PVR. Primary monkey kidney cell cultures, Hela, Hep-2
L20B (murine cell line with PVR)
Spread through feco-oral route and inhalation of droplets
90-95% of infection- Asymptomatic
4-8% have minor illness
1-2% non paralytic polio
Death occurs due to respiratory failure
No permanent carriers. Carriage maximum upto 3-4 months- Virus shed in feces & throat secretionQ
Earliest change- Degeneration of Nissl bodies (chromatolysis)
Maximum damage to anterior horns of spinal cord- flaccid paralysisQ
M/c muscle involved-Quadriceps
M/c muscle affected in hand- Opponens policis
Type 2 eliminated in 1999
Bivalent polio vaccine launched in India- Jan 2010
M/c type causing VAPP-type 3
Non-enveloped, positive stranded ssRNA
Human caliciviruses including Norwalk virus which cause GE
Hepatitis E virus
Spherical non-enveloped, ss RNA virus
Also called epidemic NANB/enteric NANB
Only one serotype
Mode of transmission-fecal contamination of water
Mild and self limited.
No carrier/chronic hepatitis/cirrhosis
Severe disease with high mortality(10-20%) in pregnant womenQ
Diagnosis-IgM and IgG anti-HEV antibodies by ELISA
PCR/IEM to detect virus in stool
Rodent borne viruses
Segmented, negative sense, ssRNA genome - 2 segments: large and small
Enveloped with glycoprotein peplomers
Sand-sprinkled appearance on EM-incorporation of host cell ribosomes during viral assembly
Inapparent infection in rodents->urine/feces
Human infection through skin or aerosols
Type species-LCMV which is a natural parasite of mice. Human infection is asymptomatic, occasionally may develop influenza like illness or meningitis
Arena viruses causing South American/New World hemorrhagic feversQ
genus Nairovirus. 80-120 nm. Enveloped
The genome is circular, ambisense RNA in three parts - Small (S), Middle (M) and Large (L).
The L segment encodes the RNA polymerase;
the M segment encodes the envelope proteins
the S segment encodes the nucleocapsid protein
Vector-hyalloma ticks- a variety of hard ticks.
Main reservoir-hares, hedgehogs, rodents
Ticks carry the virus to domestic animal stock. Sheep, goats and cattle develop high titers of virus in blood, but tend not to fall ill.
Clinical disease is commonly severe in infected humans, with a 30% mortality rate.
also called Phlebotomus fever
Mild disease occurring in mediterranean countries, Russia, India, Pakistan, Brazil, panama and Trinidad.
P.papatasii-endemic between 20 and 45 degrees latitude. Very small size. Common just above ground. Transovarial transmission occurs. Primarily feeds at night. Itchy papules at the site of bite for upto 5 d
IP-3-6 days; HA, N, V, F, photophobia, stiffness of neck and back, abdominal pain and leukopenia.
Total recovery. No specific treatment
RIFT VALLEY FEVER
Animal reservoir-sheep, cattle and goats.
Reported primarily from Africa
Mild febrile illness with total recovery.
Belong to the Bunyaviridae family of viruses
Rodent borne via bites/inhalation of feces
3 segments-L, M and S. Negative sense single-stranded
Hemorrhagic fever with renal syndrome (HFRS)
Hantavirus pulmonary syndrome . Also known as House Mouse Flu.
While the primary replication site is not clear, in both HFRS and HPS, the main effect is in the blood vessels
Hantavirus has an IP of 2–4 weeks in humans, before symptoms of infection occur. These symptoms can be split into five phases:
The symptoms in HPS area similar to HFRS, include tachycardia and tachypnea. Such conditions can lead to a cardiopulmonary phase, where cardiovascular shock can occur
HFRS includes diseases such as Korean hemorrhagic fever, epidemic hemorrhagic fever, and nephropathia epidemica.
The viruses that cause HFRS include Hantaan, Dobrava, Saaremaa, Seoul, and Puumala
An interstitial nephritis with generalized hemorrhage; CFR-5-35%. Especially reported from Korea.
Intravenous ribavirin, an antiviral drug, has been shown to decrease illness and death associated with HFRS if used very early in the disease.
Symptoms of HFRS usually develop within 1 to 2 weeks after exposure, but in rare cases, they may take up to 8 weeks to develop.
Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Individuals may have flushing of the face, inflammation or redness of the eyes, or a rash.
Later symptoms can include low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload.
The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul, Saaremaa, and Puumala virus infections are usually more moderate.
Complete recovery can take weeks or months
Ebola virus is a-
Long filamentous or odd shaped forms
Marburg virus-about 790 nm long
Ebola- 970 nm
Both antigenically distinct
ss, non segmented, negative sense RNA genome
Highly virulent- BSL IV pathogens
Transmitted to man from primates by aerosols/direct contact with blood/organs or tissues
Cause hemorrhagic diseases Qassociated with high mortality rates
Secondary spread between humans occurs
4 subtypes of Ebola v- Zaire, Sudan, Reston, Ivory Coast
Belong to the family Reoviridae
Spherical virions, non enveloped, segmentedQ (10-12) ds RNA: a unique feature
Double walled viruses with an appearance of wheel
Commonest cause of GE in children less than two years.
Usually does not cause diarrhea in individuals more than 5 yrs; most likely due to development of virus-neutralising antibodies, not due to decreased receptor expression.
3 types of particles are seen
Complete - Double shelled about 70 nm
Incomplete - Single shelled, 60 nm, rough surface
Empty particles without RNA core
Divided into six serogroups (A-E). All infect animals.
M/c group causing human disease- A(less often B/C)
Lab diagnosis- Antigen detection in feces-LA/PHA/ELISAQ
Detection of virus- EM/IEM/PCR
ss RNA, spherical, enveloped
Fringe of surface projections (peplomers ), resembling the solar corona
Second most common cause of common cold after rhinoviruses Q
First isolated on organ cultures of human embryonic trachea.
SARS- Corona virus type 4Q
Genus- Lyssa virusQ
Bullet shaped, enveloped, ss RNA, negative senseQ
180 x 75 nm, one end rounded/conical and the other planar/concave
The envelope carries glycoprotein spikes which mediate the binding of virus to acetyl choline receptors and induces protective antibodies**
All mammals are susceptible to rabiesQ
Street virus- Rabies virus isolated from natural human/animal infection. Long IP
Fixed virus- After several intracerebral passage in rabbits. Short IP . Used for vaccine production*.
Can be grown in chick embryos- yolk sacQ
Tissue culture- Human diploid cell, chick embryo, vero cell
Rabies- no viremia
Caused by the bite of rabid dogs/ animals
Untreated 50% develop rabies
Virus multiplies locally for 2-3 days , penetrates the nerve endings and travels up in the axoplasm up the spinal cord to the brain
Following multiplication in brain, it spreads centrifugally to various parts of the body including the salivary glands
Virus is always present in the cornea and facial skinQ
I.P is variable(1-3 months)
In the spinal cord posterior horns are most affected
In the brain, limbic system is more affected
Characteristic histopathological feature is intracytoplasmic inclusion body .
Negri bodies are composed of rabies virus embedded in a finely fibrillar matrix found only in neural tissue. Most abundant in cerebellum and hippocampusQ
Stained by Seller’s stain
Demonstration of rabies virus antigen by IFQ in corneal smears/skin biopsy/ saliva and brain post mortem
Negri bodies in the brain biopsy- may be absent in 20%
Tissue culture- WI 38, BHK 21- Detection by IF
Post exposure Prophylaxis
Antirabic serum-ERIG and HRIG. Provides passive immunity in the form of readymade antibodies which bind with the rabies virus.
Should be administered prior to vaccine, half around the wound and half I/m
3. Immunity by vaccine takes two weeks to develop
Two main categories-
Neural vaccines are suspensions of nervous tissue of animals infected with fixed rabies V. Associated with serious risk of neural complications
Earliest - Pasteur’s vaccine
Semple vaccine- 5% suspension of sheep brain infected with fixed virus, phenol inactivated
Fermi /BPL vaccine
Infant mouse brain vaccine- To decrease the allergenic component
Non neural vaccines
3 types- Egg, tissue culture, subunit
Egg vaccines- Live attenuated chick embryo vaccines Flury and Kelev- low egg passage(40-50) and high egg passage(180). No longer used
Tissue culture vaccines-
Ist generation-human diploid cell vaccine grown in WI-38/MRC-5
IInd generation-Purified chick embryo vaccine and purified vero cell vaccineQ
Essen schedule (i/m) -0,3,7,14,28,90
Oxford regime (8-0-4-0-1-1)and Thai regime (2-2-2-0-2)- i/d.
Subunit vaccine- cloned and recombinant surface glycoprotein. Experimental stagesQ
Enveloped RNA viruses
Negative sense RNA
Adsorb onto mucoprotein receptors on respiratory epithelium and RBC’s
Paramyxo –non-segmented linear genome
Influenza virus- segmented(8) negative strand ssRNA;
3 types; A, B and C
A-pandemicsQ and epidemics
Type specific antigens are the RNP agQ and M (matrix) ag of the membrane layer of envelope
Strain/subtype specific antigens are H (16) and N (9)Q
Protective ab’s –antihaemagglutinin mainly
Mixed with a suspension of RBC’s, virus is absorbed onto mucoprotein receptors and links together adjacent cells-> Haemagglutination.
Produced by HA peplomers projecting from the envelope- triangular in cross section
Elution-HA is followed after a time by reversal due to enzyme NA (mushroom shaped peplomers) that destroys the cell receptor
Type A and B agglutinate RBC’s of fowls, g.pigs, humans over 0 C to 37 C
Type C agglutinate RBC’s of fowls only, at 4 C
HA and elution used for purifying influenza viruses
Hemadsorption-red cell adsorbed onto the surface of tissue culture cells in which influenza virus is multiplying
Antigenic variations-the internal RNP and M protein are stable
Variations are seen in surface antigens, H and N
Antigenic shift- abrupt genetic recombinationQ only seen with type A. results in a novel strain unrelated to predecessor strain. Occurs after 10-15 yrs Q
Antigenic drift- gradual sequential change due to mutation due to selection pressure by population immunityQ. Only seen with A and B. occurs every 2-3 yrs(A)/4-5 yrs(B)
No antigenic variations demonstrated in type C
As an aerosol, small doses can initiate infection
Site of viral infection- ciliated cells of RT
Most infections are asymptomatic
Mild coryza to fulminating pneumonia
M/C complication- pneumoniaQ(secondary)
GI symptoms-gastric flu. Type B can present as an abdominal emergency
Reye’s syndrome-due to Type BQ
Best specimen for diagnosis-nasopharyngeal secretionsQ
Diagnosis- IFAT (ag detection) and RT-PCR (viral RNA)
Culture in amniotic cavity of 11-13 day old chick eggs.
Type A and B can adapt to growing well in allantoic cavity after few egg passages
Culture in primary monkey kidney cell lines detected by haemadsorption/ IF
Serology-CFT and HAI with RNP ag of type A, B and C
Genus- Rubula virus- Parainfl V 2, 4a, 4b, mumps
Genus-Parainfluenza virus- Parainfl V 1 and 3
Genus- Morbilli virus- Measles
Non-segmented linear, negative sense ss RNAQ
Lipid envelope has 2 trans membrane glycoprotein spikes- HN and F proteins
HN proteins is responsible for adsorption of virus to the host cell
F protein responsible for fusion of the envelope with host cell
Transmitted by respiratory secretions
I.P 12-25 days.Q
1/3rd are asymptomatic
Non suppurative enlargement of the parotid glandsQ.
U/l or B/L
Meningo-encephalitis which resolves without sequelae. May have residual deafness
Epididymo orchitisQ seen in a third of male patients- Usually unilateral. Rarely B/L
Less common complications are arthritis, oophritis, nephritis, thyroidits, pancreatitis, myocarditis
Diagnosis- IF of saliva/urine/CSF.
Vaccine- Jeryl-Lynn strain (live attenuated)/Urabe strain
120-250 nm roughly spherical
Helical nucleocapsid H protein and F protein
H protein does not have neuraminidase activity
I.P 1-2 weeks
Spread by respiratory secretions
Prodrome followed by Koplic spots in buccal mucosa followed by red maculopapular rash which first appears on the forehead and spreads downwards. Rash stains brown before it desquamates.
Lab diagnosis-Demonstration of multinucleated giant cells in Giemsa stained smears of nasal secretions.
CPE(syncytium formation) takes 5-7 days. IF can be done.
Measles vaccine- Edmonsten Zagreb strain attenuated by passage in human diploid cells. Vaccine is contraindicated in untreated TB, pregnancy and ID
LAV has been developed which can be given as an intranasal aerosol
Otitis media/pneumonia due to secondary bacterial infection
Cervical adenitis (multinucleate giant cells called Warthin-Finkeldey cells)
Giant cell pneumonia in patients with CMI**
Gastroenteritis which may be life threatening in infants.
Worsening of TB
Precipitation of labour
*Acute postinfectious encephalitis- 1 in 1000. Immune mediated not due to viral invasion. Cerebral or cerebellar
SSPE -1 in 1 lakh occurs 5-15 yrs after an attack of measles. Thought to be due to a complex interaction of host immune response to a defective virus. High level of antibodies in CSF**
RSV is different in not possessing HA/NAQ
F protein brings about fusion.
The infection is rarely asymptomatic.
**Peak age 6weeks- 6 months
50% of cases of bronchiolitis and 25% of pneumonia in 1st few months of life
Otitis media and other URTI in older children and adults.
In immunocompromised it can cause pneumonia
Antigen detection by IF and tissue culture
Infection via respiratory tract secretions
Responsible for 10% of RTIs needing hospitalization
Croup or LTB is most frequently due to type 1 and 2 .
Type 3 causes LRTI- Bronchitis, bronchiolitis and pneumonia
Type 4 causes minor respiratory infections
ssRNA, replicates in host cell cytoplasm
Word Toga-means mantle/cloak in roman; refers to the viral envelope.
Earlier called group A arboviruses
32 species-13 cause human disease; all are mosquito borne.
all the medically important alphaviruses were grouped into two clades, the Semliki Forest clade, including CHIK, O’nyong-nyong, and Ross River viruses, and the Sindbis-equine encephalitis clade, including Sindbis, VEE, WEE, and EEE viruses.
For identification of different species, neutralization test is more specific than HAI/CFT.
Eastern, Western and Venezuelan equine encephalitis viruses cause encephalitis in horses and man;
Several species of Culex and Anopheles are vectors and wild birds are the reservoir.
Inactivated vaccines against EEE and WEE are available for limited human use. Both formalin-inactivated and live, attenuated vaccines to prevent VEE infection are in limited use in humans.
the principal enzootic vector for EEE is the mosquito Culiseta melanura which is highly ornithophilic.
Infection of avian species may result in death in some cases and may be without apparent consequence in others. In either case, it results in viremia of sufficient magnitude and frequency to maintain a reservoir of infected mosquitoes
Horses and humans develop only low or undetectable levels of viremia. Therefore, these hosts do not serve as reservoirs for further virus spread.
The WEE viruses are distributed primarily in the Americas
The vector is Culex tarsalis
Case-to-infection ratio ranges from less than 1 : 1000 in older adults to nearly 1 : 1 in infants. Thus, encephalitis is most frequent in infants younger than 1 year. However, encephalitis is most severe in older adults
Case-fatality rates are 3% to 4%
CDC criteria for the diagnosis of an arboviral encephalitis require the presence of an acute febrile illness with encephalitis during a time when virus transmission is likely plus one of the following criteria: (1) greater than fourfold increase in viral antibody titer between acute and convalescent sera; (2) virus isolation from CSF, blood, or tissue in suckling mice or embryunated eggs; or (3) IgM positive to the virus in CSF.
VEE virus infections in South America and Central America have been associated with tens of thousands of both equine and human cases.
Equines play an important role in maintenance because they develop high-titer viremia and are thus likely to transmit infection to mosquitoes.
At least 10 mosquito species, including Culex, Aedes, Mansonia, Psorophora, and Deinocerites, have been identified as probable epidemic vectors
Chikungunya virus-1st isolated in Tanzania in 1952-native word for the disease meaning “to walk bent over,” in reference to the crippling arthritic manifestations of the disease
Vector-Aedes aegypti and Aedes albopinctus; no animal reservoir.
First appeared in India in 1963 causing extensive epidemics in Calcutta, Madras, etc.
Fever, crippling joint pains favoring small joints, LNAP and conjunctivitis, uveitis; a maculopapular rash is common; some show hemorrhagic manifestations
No vaccine available.
A live, attenuated vaccine to prevent CHIK fever (strain TSI-GSD-218) has been shown to be safe in volunteers at the level of phase II clinical trials
O’nyong-nyong virus-confined to Africa. Related closely to Chikungunya. Similar disease; transmitted by Anopheles.
Mayaro virus causes a similar disease in West Indies and South America. Haemagogus mosquito
Semliki Forest virus-Aedes. Isolated in Uganda; not associated with any human disease.
Sindbis virus-Culex. Febrile illness in Africa. In India antibodies in human sera but not associated with any disease.
Ross river virus-epidemic polyarthritis in Australia. It is the most common and most widespread arboviral disease in Australia.
German measles/ 3 day measles/3rd disease
Family- Togaviridae; Genus- Rubivirus
Enveloped spherical ss RNA
Hemagglutinin peplomers which agglutinate goose, pigeon and human RBCs at 4 C
Cytopathic effects are readily observed in the rabbit kidney cell line RK-13 and in primary African green monkey cells.
Mild exanthematus disease+fever + LNAP
German measles/ 3 day measles
Hemagglutinin peplomers which agglutinate goose, pigeon and 1 DAY OLD CHICK RBC’S
Mild exanthematus disease + LNAP
Rubella in pregnant women is teratogenic
Rubella virus is spread in droplets shed from respiratory secretions of infected persons. Patients are most contagious while the rash is erupting, but they may shed virus from the throat from 10 days before until 15 days after the onset of the rash. Patients with subclinical cases of illness may also transmit the infection to others.
Infants with congenital rubella shed large quantities of virus from body secretions for many months and therefore may transmit the infection to those who care for them, despite high titers of neutralizing antibody which is unexplainable
After an attack of rubella, lifelong protection against the disease develops in most persons
Rubella reinfections have been documented by detection of a significant boost in rubella antibody titers in naturally immune persons after reexposure to the virus. Most reinfections are asymptomatic. Viremia is rare
Rubella reinfection occurring months or years after the receipt of rubella vaccine has also been observed. Detectable only serologically. No viremia mostly. Are more common in vaccinees than naturally immune..
The incubation period for rubella ranges from 12 to 23 days (average, 18 days).
As in measles, a primary and a secondary viremia are believed to accompany rubella
As in measles, the rubella rash appears as immunity develops and the virus disappears from the blood, suggesting that the rash is immunologically mediated
The major clinical manifestations of postnatal rubella are adenopathy, which may last several weeks, and rash.
The lymph nodes involved include the posterior auricular, posterior cervical, and suboccipital chains.
The rash of rubella begins on the face and moves down centrifugally to the trunk and extremities. It is maculopapular but not confluent.
An enanthem consisting of petechial lesions on the soft palate (Forschheimer's spots) has been described for rubella, but this enanthem is not diagnostic of rubella.
On occasion, splenomegaly also occurs
The laboratory diagnosis of postnatal rubella is most conveniently made serologically-ELISA or latex agglutination for specific IgM or observation of a significant (>4-fold) rise in rubella-specific immunoglobulin G (IgG) antibody titer between the acute and convalescent serum specimens drawn 2-3 weeks apart
The younger the fetus when infected, the more severe the illness. Usually due to a primary infection in pregnancy.
During the first 2 months of gestation, 65% to 85% chance of being affected, with an outcome of multiple congenital defects/spontaneous abortion/ both
Rubella during the third month of fetal life has been associated with a 30% to 35% chance of developing a single defect, such as deafness or CHD.
Fetal infection during the fourth month carries a 10% risk for a single congenital defect.
Occasionally, fetal damage (deafness alone) is seen if rubella occurs up to the 20th week of gestation
The most common manifestations are deafness, (M/C) cataract or glaucoma, congenital heart disease (PDA and PS), and mental retardation.
Others-microcephaly, glaucoma, myopia, retinopathy, inguinal hernia, cryptorchidism
Diabetes mellitus in late childhood has also been observed 50 times more frequently in children who had congenital rubella than in normal children
Congenital rubella infection has been diagnosed by the following tests or procedures: placental biopsy at 12 weeks and demonstration of rubella antigen with monoclonal antibody, cordocentesis and detection of RNA by in situ hybridization/ PCR
Congenital rubella in infants and children is diagnosed by viral isolation or by serologic testing.
In contrast to postnatal infection, viral isolation is the preferred technique in congenital rubella syndrome because rubella serology may be difficult to interpret in view of transplacental passage of rubella-specific maternal IgG antibody. In addition, rubella-specific IgM antibody may not be detectable at the time of evaluation.
Specimens used for viral isolation in congenital rubella include nasopharyngeal swab, urine, cerebrospinal fluid, and buffy coat of the blood
Vaccine- Strain RA 27/3Q grown in human diploid cell culture(LAV)**
C/I-Pregnancy and ID
A/c subacute spongiform viral encephalopathies
Nobel prize to Stanley Prusiner in 1997
Neuro degenerative disorders due to transmission of unique proteinaceous particles which are pathogenic isoforms of a prion protein normally present in the neuronal cell membrane
Normal prion protein is protease sensitive, soluble, rich in alpha helices-PRPsen
Direct exposure to an abnormal form (protease resistant, insoluble, beta sheets) causes the misfolding of the normal protein
Transmission related to prolonged intimate exposure, diet, mutation, familial, iatrogenic (through dural grafts/hormone injections /corneal transplant/contaminated instruments)
Highly resistant to gamma radiation, dry heat, UV light, ETO, plasma, aldehydes.
Inactivated by 25% sodium hypochlorite, 90% phenol, ether, acetone, autoclaving at 135-138 C for 18 min, strong detergents like 10% SDS and guanidine thiocyanate.
Chronic progressive disease that is uniformly fatal
No inflammatory/immune response is seen in the host- prions are non-antigenic
The etiologic agent is recoverable from other organs
Disease only seen in nervous system
Neuronal degeneration and spongiform changes
Amyloid plaques may be seen
Familial fatal insomnia and
Animal- Scrapie, mink encephalopathy, BSE, Feline encephalopathy, wasting disease of deer and elk
Retro viruses- Denotes that information in the form of RNA is transcribed into DNA in the host cell due to the presence of an enzyme RNA- Dependent DNA polymerase
Oncovirinae HTLV 1 and HTLV 2
Lentivirinae-HIV1,HIV2, SIV, FIV
HTLV-1- First of the retroviruses isolated in 1980.
Causes HTLV-1 associated myelopathy or TSP characterized by motor and sensory deficits, incontinence and impotence
and adult T cell leukemia
HIV 1- Genetically close to SIVCPZ
HIV 2 closely related to SIVMAC
HIV 1 vs HIV 2: vpu vs vpx
HIV 1 isolated in 1983- Luc Montagnier
First case in India of HIV 1- 1986
HIV 2 first isolated in 1986.
In India HIV 2 first reported in 1991
HIV 2- less virulent, less infectious, restricted to West Africa
Subtypes of HIV1
On the basis of gag and env gene-3 groups
The M group been divided into 10 subtypes/ clades-A to K
Group O-outlier only seen in West Africa
Group N- New-distinct from M and O
6 Subtypes of HIV-2
Prevalence in India- 0.5-1%
M/C mode of transmission in India-heterosexual
M/c subtype of HIV-1 seen in India-C
M/c subtype seen in the West-B
Most prevalent form in the world-A
Spherical, enveloped, 80-100 nm ss RNA, linear, positive sense
Genome is diploid- Composed of two identical ss RNA
Reverse transcriptase enzyme is associated with the viral RNA
The genome of HIV contains 3 structural genes-
1. env gene–> gp 160-> gp120 and gp 41
gp 120- surface spikes, is the major envelope antigen associated with maximum antigenic variability.
Binds to CD4 and coreceptors on T lymphocytes and determines lymphocyte/ macrophage tropism
Chemokine receptors serve as co-receptors.
CCR-5 is the predominant coreceptor for macrophage-tropic strains
CXCR-4 is the predominant coreceptor for lymphocyte-tropic strains
gp 41- Is the transmembrane anchoring protein responsible for fusion of virus with host cell.
The binding of gp-120 to CD-4 and coreceptor cause transformational change in the viral envelope, activating gp-41 fusion peptide and triggering membrane fusion
2. gag gene- codes for the core and shell. Expressed as a precursor protein, p55 which is cleaved into p15,p18 (shell protein), p24 (major core protein)
3. pol gene- Code for the reverse transcriptase, protease, and endonuclease
Sequences of gag and pol genes are highly conserved
Efficiency of transmission:
Blood transfusion 90-95%
Intravenous drug abuse: 0.5-1%
Needle stick: 0.3-0.5%
CD4 Opportunistic Infections
400 Herpes Zoster
300 Oral candidiasis
200 PCP, esophageal
50 Crypto, PML
pmally present in the neuronal cell membrane
Causes HTLV-1 associated myelopathy or TSP charac