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NIPAH VIRUS INFECTION
IN CHILDREN
Speaker- Dr CHAYANIKA MISHRA
Paediatrician
INTRODUCTION:
• Nipah Virus (NiV) is a negative sense,
single stranded, enveloped RNA virus.
• Zoonotic virus
• Family – Paramyxoviridae
• Genus - Henipavirus
• It is a BSL-4 pathogen.
• The name "Nipah" refers to the place, Sungai
Nipah (literally 'nipah river') in Malaysia, the
source of the human case from which Nipah
virus was first isolated.
TRANSMISSION
Current outbreak in Kerala:
 This is the 4th outbreak.
 6 positive, 2 died rest 4 recovered.
EPIDEMIOLOGY
NIPAH VIRUS IN INDIA
Time Place Total no case Death Fatality Rate(%)
2001 Siliguri, West Bengal 66 45 68.2
2007 Nadia, West Bengal 5 5 100
2018 Kozhikode and
Malappuram, Kerala
18 17 94.4
2019 Kochi, Kerala 1 0 0
2021 Kozhikode, Kerala 1 1 100
2023 (Ongoing) Kozhikode, Kerala 6 2 33.33
2018 Outbreak
 The samples were tested at the Manipal Institute of Virology & National Institute of Virology, Pune.
 To fight the outbreak, M 102.4-a human monoclonal antibody for which clinical trials are still going
on, was imported from Australia.
 Lini Puthussery, a 28 year old nurse at the Perambra Taluk hospital who fell victim to Nipah virus
(who treated the index patient before diagnosis) awarded the "Best Nurse in Public Service Award“.
NIPAH VIRUS IN SILIGURI, INDIA
Chadha, M. S., Comer, J. A., Lowe, L., Rota, P. A., Rollin, P. E.,
Bellini, W. J., Ksiazek, T. G., & Mishra, A. (2006). Nipah virus-
associated encephalitis outbreak, Siliguri, India. Emerging
infectious diseases, 12(2), 235–240.
• Based on the case definition, 66 cases of encephalitis
were identified, and the case-fatality ratio was
≈74%.
• The outcome of 61 cases was known; the remaining
5 patients were discharged from the hospital against
medical advice.
• All patients were >15 years of age; the male-to-
female ratio was 1.4:1.
• Forty-five (75%) of the 60 patients had a history of
hospital exposure, i.e., they were members of the
hospital staff or had attended to or visited patients
in the hospital.
• The outbreak began at a single hospital, and cases
were subsequently detected at 3 other hospitals.
• No definitive information about the possible index
case exists.
• No neck rigidity or cranial nerve involvement was observed in the 16 patients who were examined. Pupils were bilaterally dilated
and reactive to light. Deep tendon reflexes were diminished or absent. Abnormal plantar reflexes (extensor plantar response)
were elicited in 11 patients.
• Patients were normotensive at admission but became hypertensive before death.
• NiV-specific IgM and IgG were detected in 9 of 17 serum samples; 1 sample was positive for IgG and negative for IgM. RT-PCR
assays detected RNA from the N gene of NiV in 4 urine samples from NiV antibody–positive patients and in 1 urine sample from a
NiV antibody–negative patient.
• Death occurred within 1 week of onset of disease in 10 patients (62.5%), within 2 weeks in 5 (32.8%) patients, and on day 30
after onset for 2 patients.
• Before the outbreak, the staff did not routinely use personal protective equipment or barrier nursing methods. Use of surgical
masks was minimal on wards, except in the intensive-care units. Certain universal precautions, such as hand washing and use of
gloves, were partially adhered to when staff were carrying out invasive procedures.
Clinical features Percentage
Fever 100
Headache & myalgia 57
Vomiting 19
Altered sensorium (Confusion to coma) 97
Respiratory symptoms (tachypnea to acute
respiratory distress)
51
involuntary movements or convulsions 43
PATHOGENESIS
• Viral antigen in bronchiole & alveoli
• Cytokines- IL, G-CSF by swollen epithelium
• ARDS like disorder
• Virus enter into endothelium & blood stream
• Enter into CNS – choroid plexus & olfactory bulb
• Target organs- Respiratory, digestive, excretory, brain
RISK FACTORS
• Nipah virus can remain viable for a few days in few fruit juices or mango fruits, and at least 7 days
in palm milk.
• Bats act as a breeding ground for many dangerous viruses, including Nipah, rabies, and Marburg
viruses. Such viruses are not associated with any major pathological changes within the bat
population.
• Transmission of NiV occurs by eating contaminated food. Risks include contact, touch,
breastfeeding, or exposure to an infected person, thereby making it easier to come in contact with a
droplet of NiV infection.
• More recently, experimental studies with aerosolized NiV in Syrian hamsters have found that NiV
droplets (aerosol distribution) may cause NiV transmission during close contact. Drinking fresh
palm milk is a very common method, and the use of Tari (ripe palm juice) is a powerful way to
transmit the virus.
SIGNS AND SYMPTOMS
• The incubation period is believed to range from 4 to 14 days. However, an incubation
period as long as 45 days has been reported.
• Asymptomatic infection to acute respiratory infection and fatal encephalitis.
• Approximately 20% of patients are left with residual neurological consequences such as
seizure disorder and personality changes.
• A small number of people who recover subsequently relapse or develop delayed onset
encephalitis.
Initial symptoms Neurological Respiratory
Fever Drowsiness, disorientation Cough
Headache Cerebellar Symptoms Atypical pneumonia
Myalgia Brainstem dysfunction Shortness of breath
Vomiting Seizures ARDS
Sore throat Coma
• Respiratory symptoms account for half to two-thirds of the cases during epidemics in
Bangladesh and India.
• This may be the reason of higher frequency of human-to-human transmission
confirmed in Bangladesh and India compared to the epidemics in Malaysia and
Singapore.
• In Bangladesh and India, genetically similar strains caused a significantly higher
number of deaths, although this was also partly related to the low quality of
healthcare in these countries and the incidence of new virus outbreaks.
• However, the 2018 NiV outbreak in Kerala was characterized by significantly higher
mortality than in Siliguri and the occurrence of heart muscle dysfunction in
patients–a symptom that had not been reported in previous epidemics.
• The mean disease duration
from symptom onset to death
was 16 days in Malaysia and
only 4–6 days in Bangladesh
and India.
Out of the NiV strains responsible for causing disease in humans tested so far, there
are two main strains characterized–
Malaysian strain (NiV-MY) and NiV Bangladesh (NiVBD).
DIFFERENTIAL DIAGNOSIS
• Any disease presenting with fever and encephalitis, and/or ARDS, but epidemiology,
travel history, and ongoing outbreaks help differentiate the diagnosis.
 Japanese encephalitis
 Measles
 Rabies
 Dengue encephalitis
 Cerebral malaria
 Scrub typhus
 Leptospirosis
 Herpes encephalitis
 Bacterial meningitis
DIAGNOSIS
• During early stages of the illness- RT-PCR from throat and nasal swabs, cerebrospinal fluid, urine, and
blood.
• Later in the course of illness and after recovery- Testing for antibodies (IgM and IgG) is conducted using
ELISA.
• Virus isolation (Cell culture) in Vero cells, producing cytopathic effects
(characterized by syncytia formation and cell death, and an ensuing vasculitis)
within 3 days, is used to confirm new NiV foci.
TREATMENT
• There are currently no drugs or vaccines specific for Nipah virus infection although WHO has identified
Nipah as a priority disease for the WHO Research and Development Blueprint.
• Supportive care, including rest, hydration, and symptomatic treatment.
• Maintenance of airway patency, prophylaxis of venous thrombosis, and maintenance of fluid and
electrolyte balance & broad-spectrum antibiotics. Mechanical ventilation is used in severe
respiratory symptoms.
• Immunotherapeutic treatments (monoclonal antibody therapies) that are currently under development- m102.4 has completed
phase 1 clinical trials.
• Ribavirin was used to treat a small number of patients in the initial Malaysian NiV outbreak and Acyclovir used in
Singapore, but its efficacy is unclear.
PREVENTION
• In areas where Nipah virus (NiV) outbreaks have occurred (Bangladesh, Malaysia, India, and Singapore), people should:
1. Practice handwashing regularly with soap and water
2. Avoid contact with sick bats or pigs
3. Avoid areas where bats are known to roost
4. Avoid eating or drinking products that could be contaminated by bats, such as raw date palm sap, raw fruit, or fruit that is found on
the ground
5. Avoid contact with the blood or body fluids of any person known to be infected with NiV
• Because NiV can be spread from person-to-person, standard infection control practices and proper barrier nursing techniques are
important in preventing hospital-acquired infections (nosocomial transmission) in settings where a patient has confirmed or suspected
NiV infection.
VACCINES
• Clinical trials with vaccines to protect against NiV are limited due to the lack of new large
viral outbreaks.
• The effectiveness of potential preparations is tested in animal models. To date, research has
included over 10 vaccines based on viral vectors, mRNA, recombinant protein subunits, or
virus-like particles (Broder et al., 2016; Amaya and Broder, 2020).
• The most studied so far is the subunit vaccine based on soluble recombinant Hendra G-
glycoprotein (HeV-sG), also inducing a cross-immune response against NiV. It has been
proven to be completely effective in protecting against NiV MY, NiV BD, and HeV in horses,
cats, ferrets, and non-human primates, while it did not show effectiveness in pigs (Mungall
et al., 2006; McEachern et al., 2008; Bossart et al., 2012; Pallister et al., 2013; Middleton et
al., 2014; Mire et al., 2014).
• The only vaccine officially approved and registered by the Australian Pesticides and
Veterinary Medicines Authority (APVMA) vaccine is Equivac produced by Zoetis, Inc. It is
used in the prophylactic treatment of horses (Aditi and Shariff, 2019; Ambat et al., 2019;
Ochani et al., 20).
NIPAH VIRUS–PANDEMIC POTENTIAL
• Rapid and effective transmission of the pathogen from person to person, especially in the
absence of immunity in exposed people. This route of NiV transmission was confirmed to
be extremely important during the epidemics in Bangladesh and India.
• Taking into account the risk associated with the appearance of a certain percentage of
subclinical cases(according to WHO, the incubation period for NiV in extreme cases may
last 45 days), the rank of NiV as a potential source of another global epidemic increases.
• The high mortality characteristic of NiV is a factor that can limit the spread of a virus
that does not infect another due to the death of the host.
• RNA viruses, due to their commonly observed high rate of nucleotide substitutions, poor
ability to correct mutation errors, and the resulting adaptability to new hosts, are
regarded as extremely dangerous and require close supervision.
• The detection of henipaviruses in bats in China and West Africa may suggest that the
diseases they cause will also appear outside of Asia and Australia.
NIPAH-An emmerging Epidemic in India.pptx

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NIPAH-An emmerging Epidemic in India.pptx

  • 1. NIPAH VIRUS INFECTION IN CHILDREN Speaker- Dr CHAYANIKA MISHRA Paediatrician
  • 2. INTRODUCTION: • Nipah Virus (NiV) is a negative sense, single stranded, enveloped RNA virus. • Zoonotic virus • Family – Paramyxoviridae • Genus - Henipavirus • It is a BSL-4 pathogen. • The name "Nipah" refers to the place, Sungai Nipah (literally 'nipah river') in Malaysia, the source of the human case from which Nipah virus was first isolated.
  • 4. Current outbreak in Kerala:  This is the 4th outbreak.  6 positive, 2 died rest 4 recovered. EPIDEMIOLOGY
  • 5. NIPAH VIRUS IN INDIA Time Place Total no case Death Fatality Rate(%) 2001 Siliguri, West Bengal 66 45 68.2 2007 Nadia, West Bengal 5 5 100 2018 Kozhikode and Malappuram, Kerala 18 17 94.4 2019 Kochi, Kerala 1 0 0 2021 Kozhikode, Kerala 1 1 100 2023 (Ongoing) Kozhikode, Kerala 6 2 33.33 2018 Outbreak  The samples were tested at the Manipal Institute of Virology & National Institute of Virology, Pune.  To fight the outbreak, M 102.4-a human monoclonal antibody for which clinical trials are still going on, was imported from Australia.  Lini Puthussery, a 28 year old nurse at the Perambra Taluk hospital who fell victim to Nipah virus (who treated the index patient before diagnosis) awarded the "Best Nurse in Public Service Award“.
  • 6. NIPAH VIRUS IN SILIGURI, INDIA Chadha, M. S., Comer, J. A., Lowe, L., Rota, P. A., Rollin, P. E., Bellini, W. J., Ksiazek, T. G., & Mishra, A. (2006). Nipah virus- associated encephalitis outbreak, Siliguri, India. Emerging infectious diseases, 12(2), 235–240. • Based on the case definition, 66 cases of encephalitis were identified, and the case-fatality ratio was ≈74%. • The outcome of 61 cases was known; the remaining 5 patients were discharged from the hospital against medical advice. • All patients were >15 years of age; the male-to- female ratio was 1.4:1. • Forty-five (75%) of the 60 patients had a history of hospital exposure, i.e., they were members of the hospital staff or had attended to or visited patients in the hospital. • The outbreak began at a single hospital, and cases were subsequently detected at 3 other hospitals. • No definitive information about the possible index case exists.
  • 7. • No neck rigidity or cranial nerve involvement was observed in the 16 patients who were examined. Pupils were bilaterally dilated and reactive to light. Deep tendon reflexes were diminished or absent. Abnormal plantar reflexes (extensor plantar response) were elicited in 11 patients. • Patients were normotensive at admission but became hypertensive before death. • NiV-specific IgM and IgG were detected in 9 of 17 serum samples; 1 sample was positive for IgG and negative for IgM. RT-PCR assays detected RNA from the N gene of NiV in 4 urine samples from NiV antibody–positive patients and in 1 urine sample from a NiV antibody–negative patient. • Death occurred within 1 week of onset of disease in 10 patients (62.5%), within 2 weeks in 5 (32.8%) patients, and on day 30 after onset for 2 patients. • Before the outbreak, the staff did not routinely use personal protective equipment or barrier nursing methods. Use of surgical masks was minimal on wards, except in the intensive-care units. Certain universal precautions, such as hand washing and use of gloves, were partially adhered to when staff were carrying out invasive procedures. Clinical features Percentage Fever 100 Headache & myalgia 57 Vomiting 19 Altered sensorium (Confusion to coma) 97 Respiratory symptoms (tachypnea to acute respiratory distress) 51 involuntary movements or convulsions 43
  • 8. PATHOGENESIS • Viral antigen in bronchiole & alveoli • Cytokines- IL, G-CSF by swollen epithelium • ARDS like disorder • Virus enter into endothelium & blood stream • Enter into CNS – choroid plexus & olfactory bulb • Target organs- Respiratory, digestive, excretory, brain
  • 9.
  • 10. RISK FACTORS • Nipah virus can remain viable for a few days in few fruit juices or mango fruits, and at least 7 days in palm milk. • Bats act as a breeding ground for many dangerous viruses, including Nipah, rabies, and Marburg viruses. Such viruses are not associated with any major pathological changes within the bat population. • Transmission of NiV occurs by eating contaminated food. Risks include contact, touch, breastfeeding, or exposure to an infected person, thereby making it easier to come in contact with a droplet of NiV infection. • More recently, experimental studies with aerosolized NiV in Syrian hamsters have found that NiV droplets (aerosol distribution) may cause NiV transmission during close contact. Drinking fresh palm milk is a very common method, and the use of Tari (ripe palm juice) is a powerful way to transmit the virus.
  • 11. SIGNS AND SYMPTOMS • The incubation period is believed to range from 4 to 14 days. However, an incubation period as long as 45 days has been reported. • Asymptomatic infection to acute respiratory infection and fatal encephalitis. • Approximately 20% of patients are left with residual neurological consequences such as seizure disorder and personality changes. • A small number of people who recover subsequently relapse or develop delayed onset encephalitis. Initial symptoms Neurological Respiratory Fever Drowsiness, disorientation Cough Headache Cerebellar Symptoms Atypical pneumonia Myalgia Brainstem dysfunction Shortness of breath Vomiting Seizures ARDS Sore throat Coma
  • 12. • Respiratory symptoms account for half to two-thirds of the cases during epidemics in Bangladesh and India. • This may be the reason of higher frequency of human-to-human transmission confirmed in Bangladesh and India compared to the epidemics in Malaysia and Singapore. • In Bangladesh and India, genetically similar strains caused a significantly higher number of deaths, although this was also partly related to the low quality of healthcare in these countries and the incidence of new virus outbreaks. • However, the 2018 NiV outbreak in Kerala was characterized by significantly higher mortality than in Siliguri and the occurrence of heart muscle dysfunction in patients–a symptom that had not been reported in previous epidemics.
  • 13. • The mean disease duration from symptom onset to death was 16 days in Malaysia and only 4–6 days in Bangladesh and India. Out of the NiV strains responsible for causing disease in humans tested so far, there are two main strains characterized– Malaysian strain (NiV-MY) and NiV Bangladesh (NiVBD).
  • 14. DIFFERENTIAL DIAGNOSIS • Any disease presenting with fever and encephalitis, and/or ARDS, but epidemiology, travel history, and ongoing outbreaks help differentiate the diagnosis.  Japanese encephalitis  Measles  Rabies  Dengue encephalitis  Cerebral malaria  Scrub typhus  Leptospirosis  Herpes encephalitis  Bacterial meningitis
  • 15. DIAGNOSIS • During early stages of the illness- RT-PCR from throat and nasal swabs, cerebrospinal fluid, urine, and blood. • Later in the course of illness and after recovery- Testing for antibodies (IgM and IgG) is conducted using ELISA. • Virus isolation (Cell culture) in Vero cells, producing cytopathic effects (characterized by syncytia formation and cell death, and an ensuing vasculitis) within 3 days, is used to confirm new NiV foci.
  • 16. TREATMENT • There are currently no drugs or vaccines specific for Nipah virus infection although WHO has identified Nipah as a priority disease for the WHO Research and Development Blueprint. • Supportive care, including rest, hydration, and symptomatic treatment. • Maintenance of airway patency, prophylaxis of venous thrombosis, and maintenance of fluid and electrolyte balance & broad-spectrum antibiotics. Mechanical ventilation is used in severe respiratory symptoms. • Immunotherapeutic treatments (monoclonal antibody therapies) that are currently under development- m102.4 has completed phase 1 clinical trials. • Ribavirin was used to treat a small number of patients in the initial Malaysian NiV outbreak and Acyclovir used in Singapore, but its efficacy is unclear.
  • 17. PREVENTION • In areas where Nipah virus (NiV) outbreaks have occurred (Bangladesh, Malaysia, India, and Singapore), people should: 1. Practice handwashing regularly with soap and water 2. Avoid contact with sick bats or pigs 3. Avoid areas where bats are known to roost 4. Avoid eating or drinking products that could be contaminated by bats, such as raw date palm sap, raw fruit, or fruit that is found on the ground 5. Avoid contact with the blood or body fluids of any person known to be infected with NiV • Because NiV can be spread from person-to-person, standard infection control practices and proper barrier nursing techniques are important in preventing hospital-acquired infections (nosocomial transmission) in settings where a patient has confirmed or suspected NiV infection.
  • 18. VACCINES • Clinical trials with vaccines to protect against NiV are limited due to the lack of new large viral outbreaks. • The effectiveness of potential preparations is tested in animal models. To date, research has included over 10 vaccines based on viral vectors, mRNA, recombinant protein subunits, or virus-like particles (Broder et al., 2016; Amaya and Broder, 2020). • The most studied so far is the subunit vaccine based on soluble recombinant Hendra G- glycoprotein (HeV-sG), also inducing a cross-immune response against NiV. It has been proven to be completely effective in protecting against NiV MY, NiV BD, and HeV in horses, cats, ferrets, and non-human primates, while it did not show effectiveness in pigs (Mungall et al., 2006; McEachern et al., 2008; Bossart et al., 2012; Pallister et al., 2013; Middleton et al., 2014; Mire et al., 2014). • The only vaccine officially approved and registered by the Australian Pesticides and Veterinary Medicines Authority (APVMA) vaccine is Equivac produced by Zoetis, Inc. It is used in the prophylactic treatment of horses (Aditi and Shariff, 2019; Ambat et al., 2019; Ochani et al., 20).
  • 19. NIPAH VIRUS–PANDEMIC POTENTIAL • Rapid and effective transmission of the pathogen from person to person, especially in the absence of immunity in exposed people. This route of NiV transmission was confirmed to be extremely important during the epidemics in Bangladesh and India. • Taking into account the risk associated with the appearance of a certain percentage of subclinical cases(according to WHO, the incubation period for NiV in extreme cases may last 45 days), the rank of NiV as a potential source of another global epidemic increases. • The high mortality characteristic of NiV is a factor that can limit the spread of a virus that does not infect another due to the death of the host. • RNA viruses, due to their commonly observed high rate of nucleotide substitutions, poor ability to correct mutation errors, and the resulting adaptability to new hosts, are regarded as extremely dangerous and require close supervision. • The detection of henipaviruses in bats in China and West Africa may suggest that the diseases they cause will also appear outside of Asia and Australia.