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MARYAM JAMILAH BINTI ABDUL HAMID082013100002IMS BANGALORE
Definition of viral haemorrhagic fever
Exanthematous fever
Mosquito borne diseases
A general term for a severe illness, sometimes
associated with bleeding, that may be caused by a
number of viruses (WHO)
Arbovirus
ArenavirusFilovirus
Herpes
virusParamyxovirusPoxvirus
Togaviridae
Rhabdoviridae
Reoviridae
Bunyaviridae
Flaviviridae
1) ARBOVIRUSo Togaviridae
Alfavirus
Rubivirus
o Flaviviridae
Mosquito borne diseases
Tick born fevers
o Bunyaviridae
Hantavirus
o Reoviridae
o Rhabdoviridae
2) POXVIRUSo Small pox (variola)
3) HERPES VIRUSo Chicken pox (HHV-3)
4) PARAMYXOVIRUSo Measles (Measles virus)
5) FILOVIRUSo Marburg virus
o Ebola virus
6) ARENAVIRUSESo Lassa fever
o South America haemorrhagic
fever
fever with skin eruption
POXVIRUS
Small pox (variola)
HERPES VIRUS
Chicken pox (HHV-3)
PARAMYXOVIRUS
Measles (Measles virus)
Family: PoxviridaeSubfamily: ChordopoxvirinaeGenus: OrthopoxvirusVirus: VariolaMorphology Enveloped DNA virus, Largest animal virus
(300x200x100 nm) Brick shaped Complex virus Nucleocapsids not symmetry V.S: biconcave double stranded DNA core surrounded
by double layered membrane
SMALL POX (Variola)
Major scourge of humankind for at least 3000 years
Global eradication in 1980
Pathogenesis
Causative virus: poxvirus, IP: 7-17 days
Host: human
Forms: florid (fatal) in India –variola major
alastrim (non-fatal) in Latin America
–variola minor
Mode of transmission:◦ Contact by skin lesion
◦ Respiratory tract
Clinical Manifestation
Fever
Overall discomfort
Headache
Severe fatigue
Severe back pain
Vomiting
Centrifugal vesicles
Lab diagnosis
Light microscope
- Inclusion bodies: Guarnieri bodies
Culture
- CAM in chick embryo
- Tissue culture (monkey kidney, HeLa, chick embryo cells)
- CPE >48 hr
- Rounding up of individual cells
Prophylaxis
Prophylaxis
Vaccinia virus is used for small pox vaccination
-artificial virus, similar properties with variola virus
-broad host range; rabbit & mice
-may evolved from cowpox or smallpox
-cause localised skin infection
-vector for development of recombinant vaccines
Eradication is achieved because:-
No subclinical infection or carrier state
An effective vaccine
No animal reservoir
Aggressive surveillance-containment measure
The only lab which stores variola virusWHO Collaboration Centre, Atlanta, USA
Koltsovo, Russian Federation
Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Virus: Varicella-zoster virus (DNA virus)
Life long latent infections
Morphology
100-200 nm diameter
Icosahedral capsid (162 capsomers)
Linear double strand DNA
Lipid envelope containing peplomers
Tegument (between capsid & envelope)
Multiply in the nuclei of infected cells
Intranuclear inclusion bodies: Cowdry Type A
& peplomers
CHICKEN POX (Varicella-zoster virus)
Commonest childhood exanthemata
Primary infection in non-immune individual when
immunity falls to ineffective level
Mode of transmission:
◦ Direct contact on skin lesion
◦ Inhalation by droplets from respiratory secretion & saliva
Pathogenesis
Virus passes across surface epithelium in the
respiratory tract (no symptoms & detectable
lesion)
IP: 7-23 days
May cross placenta and causing viraemia in
pregnant woman
May infect the foetus congenital malformation
Clinical Manifestation
Vesicular rash on the trunk
Progress through macule, papule, vesicle, pustule
and scab
Centripetal distribution
Low grade fever
Pruritis at the side of exanthemata
More intense in adult
Complication
Varicella pneumonia (common)
Viral encephalitis & haemorrhagic varicella (rare)
Lab diagnosis:-
Direct
Microscopy◦ Tzanck smear
◦ Cowdry Type A intranuclear
inclusion bodies
Culture◦ Human fibroblast
◦ HeLa cells
◦ Human amnion
◦ CPE: syncytium formation slower than in HSV
Direct fluorescent antibody
Indirect
Specific antisera
(distinguish from HSV-1 & HSV-2)
Treatment
Acyclovir
Prophylaxis
Varicella vaccine from Oka strain
Family: Paramyxovirus
Genus: Morbillivirus
Virus: Measles virus
Origin: Human
Morphology
Spherical enveloped
120-250 nm diameter
Envelope consists of lipoprotein membrane &
covered by projections
Peplomers:◦ H (haemagglutinin)
◦ F (fusion protein)
Inner surface of the envelope covered by matrix
(M) protein
Tightly coiled helical nucleocapsid
Contains a single stranded negative sense RNA
genome and RNA-dependent RNA polymerase
MEASLES
Highly infectious childhood disease
Self limiting
Once infected, life long immunity
Pathogenesis
Mode of transmission: respiratory secretions
IP: 10-12 days
Inhalation of measles virus
Epithelial surface (skin, mouth, respiratory tract, conjunctiva)
Secondary viraemia
Reticuloendothelial system & multiply
Invades bloodstream (primary viraemia)
Virus multiples in lymphoid tissue of respiratory track
Koplik’s spots (buccal mucosa),
widespread maculopapular rash (1st
at neck) –hypersensitivity type IV to
viral antigens
Rashes fade (a week)
Recover by 10-14 days
Complication
Otitis media
Bronchopneumonia
Croup
Giant cell pneumonia
Post-measles encephalitis
Subacute sclerosing panencephalitis (SSPE)
Lab diagnosis
Most cases clinically diagnose but differential diagnosis need
lab study
Samples collection: nasal secretion, throat washing, blood,
nasopharyngeal swab, conjunctiva
Direct
Microscopy
Multinucleated giant cells from nasal secretion (Giemsa
stained) –even before rash appears
Warthin finkeldey bodies; Intranuclear & intracytoplasmic
inclusion bodies (7-10 days)
Immunofluorescene; virus particle in exfoliated respiratory cells –
nasal secretion
Isolation
Virus can be isolate after 2 days appearance of rash
Virus can be obtained from urine after few more days
Cultured in primary human embryo kidney, monkey
kidney or human amnion cells
CPE: Intranuclear & intracytoplasmic inclusion bodies
(7-10 days)
Immunofluorescene staining: monoclonal antibodies
Serology
Serum is collected
ELISA: Measles specific Ig M antibody
Confirmatory test (1-2 weeks after onset of rash)
Haemagglutination inhibition (HI)
Complement fixation test (CFT)
Neutralisation tests on acute & convalescent sera
-4 fold rise in titre
High titre measles antibody in CSF SSPE
Epidemiology
Natural host is man
Monkeys acquire infection from man
Maximum incidence in 1-5 y/o child
Patients are infective 3 days before symptoms
manifest and till rash desquamates
Virus enter through respiratory tract & conjunctiva
Endemic throughout the world
Epidemics in later winter and early spring
Prophylaxis
Active immunisation Edmonston strain-live attenuated vaccine at age 9 months old-passage through human kidney,amnion cellcultures, chick embryo culture
-cause febrile rash
Schwartz & Moraten strain-safe but effective only in children15 months old
Edmonston-Zagreb strain-passage in human diploid cells-produce seroconversion even in infant 4-6 months-one dose by subcutaneous
MMR vaccine (Measles, Mumps, Rubella)
-administered in 12 to 15 months old child
-subcutaneous injection
-lasting >20 years
-However, may not induce adequated antibody
response in young babies who possess maternal
antibodies
Sabin
-live attenuated vaccine
-by intranasal aerosal
-induces good antibody response irrespective of the presence of maternal antibodies
Passive immunisation
Pooled sera containing antibody against
measles virus
To: children with immunodeficiency, pregnant
women
ARBOVIRUS
Togaviridae (alphavirus)
Chikungunya
Flaviviridae (flavivirus)
Dengue
Yellow fever
Family: Togaviridae
Genus: Alphavirus
Virus: Chikungunya virus
Africa, Europe, Asia, India and Pacific Oceans
Once infected, he or she is likely to be protected from
future infections
Morphology
Enveloped RNA virus
60-70 nm in diameter
Icosahedral capsid
Single strand positive sense RNA
Pathogenesis
Vector: Aedes aegypti & Aedes albopictus
Primary host: human
1. Bite of blood sucking mosquitoes
2. Virus multiplies in local lymph nodes
3. Variemia
4. May involve target organs leading to rash, arthritis,
hepatitis, nephritis and encephalitis
5. Capillary endothelium is involved
Clinical Manifestation
(3-7 days after bitten by infected mosquito)
Fever
Crippling joint pains (doubled-up)
Lymphadenopathy
Conjunctivitis
Rash
Lab diagnosis
Sample collection
Blood
Virus isolation
Tissue culture
• Vero, BHK-21 & mosquito cell lines
• Growth identified by immunofluorescence, haemagglutination inhibition, complement fixation, ELISA or neutralisation
Insect vectors & reservoir animal
Serology
ELISA
-serotype specific IgM antibody (within 1-3 days
after onset of illness)
-4 fold rise or more in antibody titre
CFT
Haemagglutination inhibition test or neutralisation
test
Treatment
There is no medicine to treat chikungunya virus
infection or disease.
Decrease the symptoms:
◦ Get plenty of rest
◦ Drink fluids to prevent dehydration
◦ Take medicines, such as ibuprofen, naproxen,
acetaminophen, or paracetamol, to relieve fever and
pain.
Prophylaxis
No vaccine exists to prevent chikungunya virus
infection or disease
Prevent chikungunya virus infection by avoiding
mosquito bites
The mosquitoes that spread the chikungunya virus
bite mostly during the daytime
Family: Flaviviridae
Genus: Flavivirus
Virus: Yellow fever virus
‘Yellow quarantine flag’
Tropical and subtropical areas in South America
and Africa
Illness ranges in severity from a self-limited febrile
illness to severe liver disease with bleeding
Morphology
Envelope RNA virus
Spherical 40-50 nm in
diameter
Single stranded positive
sense RNA
Inner viral core surrounded
by lipid envelope which is
covered with glycoprotein
peplomers & matrix or
membrane protein
Pathogenesis (IP: 3-6 days)
2 forms it can occurs; urban cycle & forest or
sylvatic cycle
Urban cycle
Reservoir & definitive host :Man
Vector: Aedes aegypti mosquito
Forest or sylvatic cycle
Reservoir: wild monkeys
Vectors: forest mosquitoes
Aedes africanus (Africa)
Haemagogus spegazzinii (S.America)
-Human infected when trespass into the forest or
when monkeys raid villages
Clinical Manifestation
Fever with chills
Headache
Myalgia
Vomiting
Severe jaundice (extensive destruction of liver)
Death 20-50% in severe cases
Lab diagnosis
Sample collection
Blood, liver biopsy
Virus isolation
Tissue culture
• Vero, BHK-21 & mosquito cell lines
• Growth identified by immunofluorescence, haemagglutination inhibition, complement fixation, ELISA or neutralisation
Insect vectors & reservoir animal
Serology
ELISA
-serotype specific IgM antibody (within 1-3 days
after onset of illness)
-4 fold rise or more in antibody titre
CFT
Haemagglutination inhibition test or neutralisation
test
Treatment
There is no specific treatment for yellow fever
Prophylaxis
17 D vaccine
French neurotropic vaccine (Dakar)
Steps to prevent yellow fever virus infection
include using insect repellent, wearing protective
clothing, and getting vaccinated
Family: Flaviviridae
Genus: Flavivirus
Virus: Dengue virus
Also known as ‘break-bone fever’
Asia, the Caribbean, the Pacific, West Africa, India
(East coast)
Morphology
Similar to yellow fever
Pathogenesis
4 serotypes; DEN 1, DEN 2, DEN 3, DEN 4
Vector: Aedes aegypti
1) Classical dengue fever
2) Dengue haemorrhagic fever
3) Dengue shock syndrome
Usually affects older children & adults
Bite from the infected mosquito enters the blood
stream
Biphasic fever (saddle back), headache, pain in
muscles & bones
IP: 5-8 days
Maculopapular rash appears on 3rd or 4th day
Febrile illness lasts for about 10 days
Complete recovery and rarely fatal
More serious form; Hyperimmune response
Mostly confined among children 5-10 y/o in area
where multiple dengue viruses cause disease
Seen in patients previously infected with dengue
virus
On reinfection with a different serotype, antibody
formed against the first virus reacts with the
second serotype virus forming immune complexes
(virus-antibody complex)
Symptoms like those of dengue fever but
associated with haemorrhagic rash,
thrombocytopenia & shock
Clinical Manifestation
Fever of sudden onset
Headache
Retrobulbar pain
Conjunctival infection
Pain in the back & joints
Lymphadenopathy
Maculopapular rash
Lab diagnosis
Specimens
Antibody & antigen detection: serum
Isolation of virus and PCR: serum, plasma, whole
blood (washed buffy coat), autopsy tissue,
mosquitoes collected in nature
Haematological diagnosis
Thrombocytopenia (1 lakh or less per mm3)
Haemoconcentration (>20% rise in haematocrit)
Microbiological diagnosis
Serology plays important role
Detect antibody
ELISA
–Ig M (5 days after onset & persist 1-3 months)
–Ig G (later than Ig M), 4 folds rise titre in paired
sera taken at an interval of 10 days *confirmatory
Strip of immunochromatographic test (rapid test)
–Ig M
Detection of NS1 antigen
Immunochromatographic test (Rapid test)
1st day of fever before antibodies appear
It takes 15 minutes
Isolation of virus
Inoculate virus into mosquitoes, mosquitoes cell
lines (C6/36 or AP-61 cells), or suckling mice
Further identification by fluorescent antibody test
Polymerase Chain Reaction (PCR)
Viral RNA can be detected in clinical specimens by
reverse transcriptase polymerase chain reaction
(RTPCR)
Viral genomic can be detected
Treatment
Symptomatic treatment
If severe, infuse platelets to reduce the haemorrhagic
manifestation
Prophylaxis
No effective vaccine available
Elimination of the mosquitoes (Aedes aegypti)
To avoid DHF/DSS in immunised persons, a live
attenuated vaccine containing all serotypes
(clinical trials)
Topics covered are:
Exanthematous fever
◦ Smallpox, chickenpox, measles
Mosquito borne diseases
◦ Chikungunya, yellow fever, dengue
Mim’s Medical Microbiology, 5th edition
Textbook of Microbiology, Baveja, 4th edition
Internet
www.cdc.gov
