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EMERGING VIRAL DISEASES IN
KERALA
ARBOVIRUSES:
Dengue
Chikungunya
Kyasanur Forest Disease
Japanese encephalitis
 West Nile virus
Robovirus
 Hantavirus
Hepatitis E
Influenza (H1N1)
Measles
Viral Diarrhoea
Hand Foot and Mouth Disease
01/09/15 4
Chikungunya…..
It is a viral fever caused by an Alpha virus
-Epidemiology:
-Mode of transmission-Through bites from
Aedes aegypti mosquitoes.
-During June 2007,out breaks were reported
from Pattanamthitta,Kottayam & Alappuzha
districts of south Kerala.
Morphology
 Spherical enveloped virus.
 Size: 50-70 nm diameter.
 Genome is a molecule of single stranded
RNA.
 Replication – is in the host cell cytoplasm
and released by budding.
01/09/15 6
-
1. Fever-typically’ biphasic’
2.Petechial or maculopapular rashes-involving
limbs and trunks.
3.Joint pain-Patient lies “doubled up”due to
severe joint pains
4.Lymphadenopathy
5.Conjunctivitis
Symptoms:
 Incubation period – 5 days (3-7 days).
Diagnosis
 Serodiagnosis is the main approach.
 ELISA for IgM or IgG antibodies in paired
serum sample.
 PCR- detects viral RNA.
01/09/15 8
Continuation….
Treatment:
-No specific treatment.
-No vaccine currently available.
Preventive measures:
-Protect against any contact with disease
carrying mosquitoes,using insect repellents.
Flavivirus
Mosquito borne group:
1. Japanese encephalitis virus.
2. Dengue virus.
3. Yellow fever virus.
Tick borne group:
1. Kayasanur forest disease
01/09/15 10
Japanese encephalitis…
 Principal vector: Culex mosquito
 Clinical manifestations:
 Incubation period: 5-15 days.
 Abrupt onset with fever,head ache and
vomiting.
 Signs of encephalitis with nuchal rigidity.
 Convulsions.
 Altered sensorium.
 Coma.
 Mortality rates in some epidemics has been
upto 50%.
 Convalesence takes many weeks.
 Large majority of infections are
asymptomatic.
01/09/15 12
Clinical findings:
 Neutrophil leucocytosis.
 normal or raised sugar.
 Slightly raised protein in CSF.
 Reservoir host:Herons.
 Amplifier host:Pigs.
 Preventive measures:
 Mosquito control
 Locating piggeries away from the human
dwellings.
01/09/15 13
Immunization programme…
-A formalin inactivated mouse brain vaccine
using the Nakayama strain.
- Beijing-3 strain - inactivated
-JE strain SA14-14-2 – a live attenuated
vaccine.
- IC51 – Australian – Vero cell -
Whole cell – formalin inactivated
West Nile Virus
Reported in Kerala in May 2011
WNV infection is primarily maintained in
nature in a cycle between birds and
mosquitoes (usually Culex).
 Transmitted during blood meals by
mosquitoes to man and horses (dead end
hosts)
 Cases of man-man transmission after solid
organ transplantation or blood transfusions
WNV infection is usually asymptomatic or results in a
non-specific viral fever.
 Fewer than 1% of the cases develop neuroinvasive WNV
infection, often a non-specific meningoencephalitis
Acute flaccid paralysis can occur
Reversible paralysis
 Hepatitis, pancreatitis, myocarditis, nephritis, optic
neuritis and cardiac dysrhythmias and hemorrhagic fever
with coagulopathy
 Rash
Laboratory Diagnosis
 Virus is rapidly cleared from blood within 2 days of onset of illness.
Hence, PCR and real-time PCR are positive only for 2-3 days
 The main stay of diagnosis of WNV encephalitis is antibody
detection in serum or CSF
 The high level of cross reactivity between WNV and JEV makes
the differentiation by IgM capture ELISA difficult.
 Demonstration of significantly high level of virus specific
neutralizing antibodies
 Fourfold rise in titer in the patient serum/CSF by micro-
neuralization assay or plaque reduction neutralization test assay
Treatment
Supportive measures
01/09/15 18
Dengue fever…
-Another term-Break-bone fever.
-Causative agent –Dengue virus
- types-4 types DEN 1-4.
- More than 7000 cases in kerala in 2016 and 13
deaths
-Clinical manifestations-
-Incubation period-3-14 days.
-Symptoms:
a)Sudden onset of fever with headache.
b)Retrobulbar pain
c)Conjunctival injection
01/09/15 19
Continuation…
d)Pain in the back and limbs(Break-bone
fever).
e)Lymphadenopathy
f)Maculopapular rash
-Fever is typically biphasic & last for 5-7
days.
-Most serious forms:
-Dengue hemorrhagic fever (hemorrhagic
manifestations)
-Dengue Shock syndrome.(Shock).
Pathogenesis
 Primary dengue infection- when a person
is infected with dengue for the first time.
 Secondary dengue infection- months to
years later a severe form of dengue illness
appears due to infection with another
serotype.
 Infection leads to formation of neutralizing
and non-neutralizing antibodies.
 Neutralizing antibodies- protective against
infecting serotype and other serotypes.
 Non-neutralizing antibodies- protective
against only other serotypes.
01/09/15 22
Continuation…
-Vector-Aedes aegypti mosquitoes.
Laboratory diagnosis:
-Demonstration of antibody by ELISA.
-Strip immunochromatographic test for IgM
is available for rapid diagnosis.
- RT-PCR , real time PCR for viral RNA
Control:
-Vector control.
-No vaccine is currently available in India.
01/09/15 23
Tick-borne hemorrhagic fever
1.Kyasanur Forest Disease (KFD)
-Hemorrhagic fever that occurs in
Karnataka state.
- In 2015, 102 cases and 11 deaths in kerala
- In 2016, 9 cases
 Reservoir host-Forest birds and mammals.
 Vector – ticks ( Haemophysalis spinigera).
 Mode of transmission-Bite of ticks
 In monkeys it causes fatal disease.
Clinical manifestations in humans
-Incubation period 3-8 days.
-Sudden onset with fever,headache,conjunctivitis
and severe prostration.
-Some cases develop hemorrhages.
- Neurological manifestations - headache, neck
stiffness, altered sensorium, seizures, visual
deficits
Diagnosis
 RT-PCR within 5 days of onset
 After 5 days, IgM antibody detection by
ELISA.
Vaccine
 A formalin inactivated chick embryo
vaccine has been developed at Haffkine
institute Mumbai.
01/09/15 27
Hantavirus:
Family Bunyaviridae
Causes Haemorrhagic Fever with Renal
Syndrome (HFRS)
Causes Hantavirus Pulmonary
Sundrome
Inhalation of aerosolised rodent
secretions, urine or faeces containing
virus
Hantavirus
- Single stranded RNA virus, negative sense
- 120- 160 nm , enveloped
HFRS:
- Incubation period- 1 to 2 weeks
- Prodromal symptoms- fever, fatigue,
myalgia
- Followed by hypotension, oliguria, renal
failure, proteinuria
Hantavirus Pulmonary
Syndrome
Prodromal symptoms- fever, cough,
myalgia, headache, lethargy
 Dyspnoea, acute respiratory failure,
pulmonary edema
Mortality about 40%
Laboratory Diagnosis
- IgG ELISA demonstrating fourfold rise in
titre in paired sera
- IgM ELISA
- RT-PCR
Treatment
No cure or vaccine available
Supportive treatment – dialysis,
mechanical ventilation
Ribavirin
Rodent control measures
Hepatitis E
 Positive-sense RNA virus
 Hepevirus
 4 genotypes
 Feco-oral transmission through water/
food
 After monsoon
Reservoir : pigs, boar, chicken, deer
- HEV is the commonest cause of viral hepatitis in
this area
- No vaccine available in India
- Self-limiting illness
- 4 genotypes – 1and 2 in humans, 3 and 4 also in
animals. Only one serotype.
- Mortality less than 1%
- In pregnancy, more than 25%
Clinical features
• Incubation period – 2 to 6 weeks
• Acute infection- jaundice, dark urine,
fatigue, nausea, vomiting and abdominal
pain.
• Fulminant hepatitis – 1% -4%
• Greater in pregnancy
Laboratory diagnosis
- Stool, serum samples
- ELISA for IgM in serum
- HEV RNA by RT-PCR in serum or stool
- Prevention by improved sanitation
Hand, foot and Mouth Disease
01/09/15
-Occurs mainly in children. Can occur in
adults
- Oral and pharyngeal ulceration and rashes
of palms and soles, gluteal region.
-fever
-Coxsackie virus A16, enterovirus 71 mainly
- Occasionally by Coxsackievirus A4-A7,
A9, A10, B1-B3, and B5
- Mostly self-limiting
- Enterovirus 71 may be associated with
neurological complications
- Aseptic meningitis, encephalitis, rarely
flaccid paralysis
Transmission
- Transmitted by nasopharyngeal secretions
by direct contact, or by fecal-oral
transmission.
Laboratory diagnosis
-RT-PCR for viral RNA from throat swab or
from stool samples
- Mostly clinical diagnosis
- No vaccine available in India
-Handwashing, quarantine of affected
children
Influenza (H1N1)
- Pandemic in 2009
-Genetic reassortment of influenza strains in
pigs – 1 human, 2 swine, 1 avian
Symptoms
Fever > 100 deg F,
- Upper respiratory symptoms
- Cough
- Sore throat.
- Head ache, bodyache, fatigue, diarrhea and
vomiting
Category- A,B&C
Category A- mild fever plus cough / sore
throat with or without body ache,
headache, diarrhoea and vomiting
Category-B (Bi) Category-A plus high grade
fever and severe sore throat
(Bii)
 Pregnant women
 Lung/ heart / liver/ kidney / neurological
disease, blood disorders/
Category C
· Breathlessness, chest pain, drowsiness, fall
in blood pressure, haemoptysis, cyanosis
· Children with red flag signs:
. Somnolence, high/persistent fever, inability
to feed well, convulsions, respiratory
distress
· Worsening of underlying chronic
conditions.
H1N1 Testing
Cat- A- No testing needed
Cat-B- No testing for Category-B (i) and (ii)
Cat-C- Test may be needed, but do not wait
for test results
Specimen required - 1 throat swab and 1
nasal swab, using Dacron swab, and
immersed in Viral Transport Medium tube,
refrigerated at 2-8 deg C .
Testing centres
3 authorized testing centres for Kerala,
1. Rajiv Gandhi Centre for Biotechnology,
Thiruvananthapuram,
2.Virology Division, KMC Hospital,
Manipal, Karnataka State.
3. NIV Unit, Medical College, Alappuzha
Management:
No Oseltamivir
--Symptomatic treatment
--Good supportive measures
 Plenty of warm nourishing oral fluids,
 Good food intake
 Complete rest
--Monitor progress and reassess at 24 to 48 hours.
Self isolation at home, and telephone follow up for the next
2-3 days
--Any suggestion of deterioration/ failure to improve?--
report in person stat
Category-B
(Bi) Home isolation
---Oseltamivir to be started
(Bii) Start Oseltamivir immediately
--Self isolation at home, and telephone
follow up for the next 2-3 days
--Any suggestion of deterioration/ failure to
improve?- report in person stat
Category C

Hospitalization stat

Start Oseltamivir immediately, without
waiting for test results

Intensive supportive management is
usually necessary.
H1N1 in Pregnancy (Ante natal and early
Post natal)

Pregnancy is an extreme high risk
category
Oseltamivir dosage schedule

For weight <15kg - 30 mg BD for 5 days

15-23kg - 45 mg BD for 5 days

24-<40kg -60 mg BD for 5 days

>40kg -75 mg BD for 5 days
Chemoprophylaxis
For those with high risk Eg. pregnancy/
diabetes/ Asthma/immunosuppressed/
- Start OD dose Oseltamivir x 10 days
Vaccines
-Inactivated vaccines
- Live attenuated cold adapted vaccines
Inactivated vaccines
- Grown in allantoic cavity of embryonated
egg
- Protectiveness 50-80%. Lasts up to 1 year
-Administered im/sc
3 types
- Whole virus
- Subvirion
- Surface antigen – NA,HA
Live attenuated vaccines
- Trivalent vaccine – 2 circulating type A
and a type B
- Cold adapted – grow at 33 deg C but not at
37 deg C
- Given as intranasal spray
- Do not infect lower respiratory tract
- Not given in pregnancy and high risk
groups
01/09/15 54
THANK YOUTHANK YOU
ALLALL

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Emerging viral dseaes

  • 2. ARBOVIRUSES: Dengue Chikungunya Kyasanur Forest Disease Japanese encephalitis  West Nile virus Robovirus  Hantavirus
  • 3. Hepatitis E Influenza (H1N1) Measles Viral Diarrhoea Hand Foot and Mouth Disease
  • 4. 01/09/15 4 Chikungunya….. It is a viral fever caused by an Alpha virus -Epidemiology: -Mode of transmission-Through bites from Aedes aegypti mosquitoes. -During June 2007,out breaks were reported from Pattanamthitta,Kottayam & Alappuzha districts of south Kerala.
  • 5. Morphology  Spherical enveloped virus.  Size: 50-70 nm diameter.  Genome is a molecule of single stranded RNA.  Replication – is in the host cell cytoplasm and released by budding.
  • 6. 01/09/15 6 - 1. Fever-typically’ biphasic’ 2.Petechial or maculopapular rashes-involving limbs and trunks. 3.Joint pain-Patient lies “doubled up”due to severe joint pains 4.Lymphadenopathy 5.Conjunctivitis Symptoms:  Incubation period – 5 days (3-7 days).
  • 7. Diagnosis  Serodiagnosis is the main approach.  ELISA for IgM or IgG antibodies in paired serum sample.  PCR- detects viral RNA.
  • 8. 01/09/15 8 Continuation…. Treatment: -No specific treatment. -No vaccine currently available. Preventive measures: -Protect against any contact with disease carrying mosquitoes,using insect repellents.
  • 9. Flavivirus Mosquito borne group: 1. Japanese encephalitis virus. 2. Dengue virus. 3. Yellow fever virus. Tick borne group: 1. Kayasanur forest disease
  • 10. 01/09/15 10 Japanese encephalitis…  Principal vector: Culex mosquito  Clinical manifestations:  Incubation period: 5-15 days.  Abrupt onset with fever,head ache and vomiting.  Signs of encephalitis with nuchal rigidity.  Convulsions.  Altered sensorium.  Coma.
  • 11.  Mortality rates in some epidemics has been upto 50%.  Convalesence takes many weeks.  Large majority of infections are asymptomatic.
  • 12. 01/09/15 12 Clinical findings:  Neutrophil leucocytosis.  normal or raised sugar.  Slightly raised protein in CSF.  Reservoir host:Herons.  Amplifier host:Pigs.  Preventive measures:  Mosquito control  Locating piggeries away from the human dwellings.
  • 13. 01/09/15 13 Immunization programme… -A formalin inactivated mouse brain vaccine using the Nakayama strain. - Beijing-3 strain - inactivated -JE strain SA14-14-2 – a live attenuated vaccine. - IC51 – Australian – Vero cell - Whole cell – formalin inactivated
  • 14. West Nile Virus Reported in Kerala in May 2011 WNV infection is primarily maintained in nature in a cycle between birds and mosquitoes (usually Culex).  Transmitted during blood meals by mosquitoes to man and horses (dead end hosts)  Cases of man-man transmission after solid organ transplantation or blood transfusions
  • 15. WNV infection is usually asymptomatic or results in a non-specific viral fever.  Fewer than 1% of the cases develop neuroinvasive WNV infection, often a non-specific meningoencephalitis Acute flaccid paralysis can occur Reversible paralysis  Hepatitis, pancreatitis, myocarditis, nephritis, optic neuritis and cardiac dysrhythmias and hemorrhagic fever with coagulopathy  Rash
  • 16. Laboratory Diagnosis  Virus is rapidly cleared from blood within 2 days of onset of illness. Hence, PCR and real-time PCR are positive only for 2-3 days  The main stay of diagnosis of WNV encephalitis is antibody detection in serum or CSF  The high level of cross reactivity between WNV and JEV makes the differentiation by IgM capture ELISA difficult.  Demonstration of significantly high level of virus specific neutralizing antibodies  Fourfold rise in titer in the patient serum/CSF by micro- neuralization assay or plaque reduction neutralization test assay
  • 18. 01/09/15 18 Dengue fever… -Another term-Break-bone fever. -Causative agent –Dengue virus - types-4 types DEN 1-4. - More than 7000 cases in kerala in 2016 and 13 deaths -Clinical manifestations- -Incubation period-3-14 days. -Symptoms: a)Sudden onset of fever with headache. b)Retrobulbar pain c)Conjunctival injection
  • 19. 01/09/15 19 Continuation… d)Pain in the back and limbs(Break-bone fever). e)Lymphadenopathy f)Maculopapular rash -Fever is typically biphasic & last for 5-7 days. -Most serious forms: -Dengue hemorrhagic fever (hemorrhagic manifestations) -Dengue Shock syndrome.(Shock).
  • 20. Pathogenesis  Primary dengue infection- when a person is infected with dengue for the first time.  Secondary dengue infection- months to years later a severe form of dengue illness appears due to infection with another serotype.  Infection leads to formation of neutralizing and non-neutralizing antibodies.
  • 21.  Neutralizing antibodies- protective against infecting serotype and other serotypes.  Non-neutralizing antibodies- protective against only other serotypes.
  • 22. 01/09/15 22 Continuation… -Vector-Aedes aegypti mosquitoes. Laboratory diagnosis: -Demonstration of antibody by ELISA. -Strip immunochromatographic test for IgM is available for rapid diagnosis. - RT-PCR , real time PCR for viral RNA Control: -Vector control. -No vaccine is currently available in India.
  • 23. 01/09/15 23 Tick-borne hemorrhagic fever 1.Kyasanur Forest Disease (KFD) -Hemorrhagic fever that occurs in Karnataka state. - In 2015, 102 cases and 11 deaths in kerala - In 2016, 9 cases
  • 24.  Reservoir host-Forest birds and mammals.  Vector – ticks ( Haemophysalis spinigera).  Mode of transmission-Bite of ticks  In monkeys it causes fatal disease. Clinical manifestations in humans -Incubation period 3-8 days. -Sudden onset with fever,headache,conjunctivitis and severe prostration. -Some cases develop hemorrhages. - Neurological manifestations - headache, neck stiffness, altered sensorium, seizures, visual deficits
  • 25. Diagnosis  RT-PCR within 5 days of onset  After 5 days, IgM antibody detection by ELISA.
  • 26. Vaccine  A formalin inactivated chick embryo vaccine has been developed at Haffkine institute Mumbai.
  • 27. 01/09/15 27 Hantavirus: Family Bunyaviridae Causes Haemorrhagic Fever with Renal Syndrome (HFRS) Causes Hantavirus Pulmonary Sundrome Inhalation of aerosolised rodent secretions, urine or faeces containing virus
  • 28. Hantavirus - Single stranded RNA virus, negative sense - 120- 160 nm , enveloped HFRS: - Incubation period- 1 to 2 weeks - Prodromal symptoms- fever, fatigue, myalgia - Followed by hypotension, oliguria, renal failure, proteinuria
  • 29. Hantavirus Pulmonary Syndrome Prodromal symptoms- fever, cough, myalgia, headache, lethargy  Dyspnoea, acute respiratory failure, pulmonary edema Mortality about 40%
  • 30. Laboratory Diagnosis - IgG ELISA demonstrating fourfold rise in titre in paired sera - IgM ELISA - RT-PCR
  • 31. Treatment No cure or vaccine available Supportive treatment – dialysis, mechanical ventilation Ribavirin Rodent control measures
  • 32. Hepatitis E  Positive-sense RNA virus  Hepevirus  4 genotypes  Feco-oral transmission through water/ food  After monsoon Reservoir : pigs, boar, chicken, deer
  • 33. - HEV is the commonest cause of viral hepatitis in this area - No vaccine available in India - Self-limiting illness - 4 genotypes – 1and 2 in humans, 3 and 4 also in animals. Only one serotype. - Mortality less than 1% - In pregnancy, more than 25%
  • 34. Clinical features • Incubation period – 2 to 6 weeks • Acute infection- jaundice, dark urine, fatigue, nausea, vomiting and abdominal pain. • Fulminant hepatitis – 1% -4% • Greater in pregnancy
  • 35. Laboratory diagnosis - Stool, serum samples - ELISA for IgM in serum - HEV RNA by RT-PCR in serum or stool - Prevention by improved sanitation
  • 36. Hand, foot and Mouth Disease 01/09/15 -Occurs mainly in children. Can occur in adults - Oral and pharyngeal ulceration and rashes of palms and soles, gluteal region. -fever -Coxsackie virus A16, enterovirus 71 mainly - Occasionally by Coxsackievirus A4-A7, A9, A10, B1-B3, and B5
  • 37. - Mostly self-limiting - Enterovirus 71 may be associated with neurological complications - Aseptic meningitis, encephalitis, rarely flaccid paralysis
  • 38. Transmission - Transmitted by nasopharyngeal secretions by direct contact, or by fecal-oral transmission.
  • 39. Laboratory diagnosis -RT-PCR for viral RNA from throat swab or from stool samples - Mostly clinical diagnosis - No vaccine available in India -Handwashing, quarantine of affected children
  • 40. Influenza (H1N1) - Pandemic in 2009 -Genetic reassortment of influenza strains in pigs – 1 human, 2 swine, 1 avian
  • 41. Symptoms Fever > 100 deg F, - Upper respiratory symptoms - Cough - Sore throat. - Head ache, bodyache, fatigue, diarrhea and vomiting
  • 42. Category- A,B&C Category A- mild fever plus cough / sore throat with or without body ache, headache, diarrhoea and vomiting Category-B (Bi) Category-A plus high grade fever and severe sore throat (Bii)  Pregnant women  Lung/ heart / liver/ kidney / neurological disease, blood disorders/
  • 43. Category C · Breathlessness, chest pain, drowsiness, fall in blood pressure, haemoptysis, cyanosis · Children with red flag signs: . Somnolence, high/persistent fever, inability to feed well, convulsions, respiratory distress · Worsening of underlying chronic conditions.
  • 44. H1N1 Testing Cat- A- No testing needed Cat-B- No testing for Category-B (i) and (ii) Cat-C- Test may be needed, but do not wait for test results Specimen required - 1 throat swab and 1 nasal swab, using Dacron swab, and immersed in Viral Transport Medium tube, refrigerated at 2-8 deg C .
  • 45. Testing centres 3 authorized testing centres for Kerala, 1. Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 2.Virology Division, KMC Hospital, Manipal, Karnataka State. 3. NIV Unit, Medical College, Alappuzha
  • 46. Management: No Oseltamivir --Symptomatic treatment --Good supportive measures  Plenty of warm nourishing oral fluids,  Good food intake  Complete rest --Monitor progress and reassess at 24 to 48 hours. Self isolation at home, and telephone follow up for the next 2-3 days --Any suggestion of deterioration/ failure to improve?-- report in person stat
  • 47. Category-B (Bi) Home isolation ---Oseltamivir to be started (Bii) Start Oseltamivir immediately --Self isolation at home, and telephone follow up for the next 2-3 days --Any suggestion of deterioration/ failure to improve?- report in person stat
  • 48. Category C  Hospitalization stat  Start Oseltamivir immediately, without waiting for test results  Intensive supportive management is usually necessary. H1N1 in Pregnancy (Ante natal and early Post natal)  Pregnancy is an extreme high risk category
  • 49. Oseltamivir dosage schedule  For weight <15kg - 30 mg BD for 5 days  15-23kg - 45 mg BD for 5 days  24-<40kg -60 mg BD for 5 days  >40kg -75 mg BD for 5 days
  • 50. Chemoprophylaxis For those with high risk Eg. pregnancy/ diabetes/ Asthma/immunosuppressed/ - Start OD dose Oseltamivir x 10 days
  • 51. Vaccines -Inactivated vaccines - Live attenuated cold adapted vaccines
  • 52. Inactivated vaccines - Grown in allantoic cavity of embryonated egg - Protectiveness 50-80%. Lasts up to 1 year -Administered im/sc 3 types - Whole virus - Subvirion - Surface antigen – NA,HA
  • 53. Live attenuated vaccines - Trivalent vaccine – 2 circulating type A and a type B - Cold adapted – grow at 33 deg C but not at 37 deg C - Given as intranasal spray - Do not infect lower respiratory tract - Not given in pregnancy and high risk groups