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1 Eaton 2005 February 2010 February 2010 Emerging Zoonoses: Nipah and Hendra viruses Emerging Emerging Zoonoses Zoonoses: : Nipah and Hendra viruses Nipah and Hendra viruses Pierre E. Rollin, MD Special Pathogens Branch Centers for Disease Control and Prevention Pierre E. Rollin, MD Pierre E. Rollin, MD Special Pathogens Branch Special Pathogens Branch Centers for Disease Control and Prevention Centers for Disease Control and Prevention Eaton 2005 February 2010 February 2010 Histogram of the phosphoprotein gene of members of the subfamily Paramyxovirinae Histogram of the phosphoprotein gene of members of the subfamily Paramyxovirinae HPIV-1 Sendai HPIV-3 CDV PDV RPV Measles DMV NDV Goose paramyxovirus HPIV-4b HPIV-4a Tioman Menangle HPIV-2 SV5 Mumps Nipah-UMCC1 Nipah-Malaysia Nipah-P. hypomelanus* Nipah-Bangladesh Hendra Tupaia Mossman Salem 100 changes Eaton 2005 February 2010 February 2010 Hendra and Nipah viruses Hendra and Nipah viruses Hendra and Nipah viruses History of previous outbreaks Reservoirs of viruses Clinical features in human Diagnosis and Treatment Transmission and Epidemiology Disease in horses and pigs Prevention and Control History of previous outbreaks History of previous outbreaks Reservoirs of viruses Reservoirs of viruses Clinical features in human Clinical features in human Diagnosis and Treatment Diagnosis and Treatment Transmission and Epidemiology Transmission and Epidemiology Disease in horses and pigs Disease in horses and pigs Prevention and Control Prevention and Control

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Page 1: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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February 2010February 2010

Emerging Zoonoses: Nipah and Hendra viruses

Emerging Emerging ZoonosesZoonoses: : Nipah and Hendra virusesNipah and Hendra viruses

Pierre E. Rollin, MDSpecial Pathogens Branch

Centers for Disease Control and Prevention

Pierre E. Rollin, MDPierre E. Rollin, MDSpecial Pathogens BranchSpecial Pathogens Branch

Centers for Disease Control and PreventionCenters for Disease Control and Prevention

Eaton 2005

February 2010February 2010

Histogram of the phosphoprotein gene of members of the subfamily Paramyxovirinae

Histogram of the phosphoprotein gene of members of the subfamily Paramyxovirinae

HPIV-1Sendai

HPIV-3CDVPDVRPV

MeaslesDMV

NDVGoose paramyxovirus

HPIV-4bHPIV-4a

TiomanMenangle

HPIV-2SV5

Mumps

Nipah-UMCC1Nipah-MalaysiaNipah-P. hypomelanus*

Nipah-BangladeshHendra

TupaiaMossman

Salem

100 changes

Eaton 2005

February 2010February 2010

Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

Page 2: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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History of Hendra outbreaks -1994 outbreak

History of Hendra outbreaks History of Hendra outbreaks --1994 outbreak1994 outbreak

Eaton 2005

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History of Hendra outbreaks -1995 Mackay

History of Hendra outbreaks History of Hendra outbreaks --1995 Mackay1995 Mackay

• In 1995, a 36yo farmer died of severe encephalitis in Mackay, Queensland.

• Two horses died a year before of unknown infection (one of pneumonia, the other of acute neurological illness) retrospectively Hendra-confirmed.

• He had assist at their post-mortem examination and had retrospective serologic evidence of Hendra infection at that time.

•• In 1995, a 36yo farmer died of severe In 1995, a 36yo farmer died of severe encephalitis in Mackay, Queensland.encephalitis in Mackay, Queensland.

•• Two horses died a year before of unknown Two horses died a year before of unknown infection (one of pneumonia, the other of acute infection (one of pneumonia, the other of acute neurological illness) retrospectively Hendraneurological illness) retrospectively Hendra--confirmed.confirmed.

•• He had assist at their postHe had assist at their post--mortem examination mortem examination and had retrospective serologic evidence of and had retrospective serologic evidence of Hendra infection at that time.Hendra infection at that time.

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History of Hendra outbreaksHistory of Hendra outbreaksHistory of Hendra outbreaksHORSE HUMAN

Mackay 2 1* August 1994Brisbane (Hendra) 20 2* September 1994Cairns (Trinity Beach) 1 - January 1999Cairns (Gordonvale) 1 1 October 2004Townsville 1 - December 2004Peachester 1 - June 2006Murwillimbah 1 - October 2006Peachester 1 - June 2007Cairns (Clifton Beach) 1 - July 2007Brisbane (Redlands) 5 2* June 2008Proserpine 3 - July 2008Cawarral 4 1* July 2009Bowen 2 - Aug 2009

43 7 (4 deaths)

HORSE HUMANMackay 2 1* August 1994Brisbane (Hendra) 20 2* September 1994Cairns (Trinity Beach) 1 - January 1999Cairns (Gordonvale) 1 1 October 2004Townsville 1 - December 2004Peachester 1 - June 2006Murwillimbah 1 - October 2006Peachester 1 - June 2007Cairns (Clifton Beach) 1 - July 2007Brisbane (Redlands) 5 2* June 2008Proserpine 3 - July 2008Cawarral 4 1* July 2009Bowen 2 - Aug 2009

43 7 (4 deaths)

Page 3: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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History of Hendra

outbreaks, Australia

History of History of Hendra Hendra

outbreaks, outbreaks, AustraliaAustralia

Eaton 2005

February 2010February 2010

History of Nipah outbreaks -Malaysia - 1999

History of Nipah outbreaks History of Nipah outbreaks --Malaysia Malaysia -- 19991999

Outbreak of viral encephalitis in Malaysia:• Disease in humans (mostly pig farmers) with cases described as

beginning in October 1998• Parallel disease in pigs, but not initially reported nor well described• Japanese encephalitis diagnosed as the etiology of the disease in

humans and pigs• March 1999. CSF from patients from Negeri Sembelan: yields

cytopathic agent. EM--paramyxovirus like morphology on thin section. 12/13 patients positive by Hendra IgM capture. IHC on frozen brain positive for Hendra

• RT-PCR is positive with degenerate paramyxovirus P-protein primers, sequence is Hendra-like but distinct

Outbreak of viral encephalitis in Malaysia:Outbreak of viral encephalitis in Malaysia:•• Disease in humans (mostly pig farmers) with cases described as Disease in humans (mostly pig farmers) with cases described as

beginning in October 1998beginning in October 1998•• Parallel disease in pigs, but not initially reported nor well deParallel disease in pigs, but not initially reported nor well describedscribed•• Japanese encephalitis diagnosed as the etiology of the disease iJapanese encephalitis diagnosed as the etiology of the disease in n

humans humans and pigsand pigs•• March 1999. CSF from patients from March 1999. CSF from patients from NegeriNegeri SembelanSembelan: yields : yields

cytopathiccytopathic agent. EMagent. EM----paramyxovirusparamyxovirus like morphology on thin section. like morphology on thin section. 12/13 patients positive by Hendra IgM capture. IHC on frozen bra12/13 patients positive by Hendra IgM capture. IHC on frozen brain in positive for Hendrapositive for Hendra

•• RTRT--PCR is positive with degenerate PCR is positive with degenerate paramyxovirusparamyxovirus PP--protein primers, protein primers, sequence is Hendrasequence is Hendra--like but distinct like but distinct

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History of Nipah outbreaksHistory of Nipah outbreaksHistory of Nipah outbreaks

• In 1999, Singapore’s importation of infected pigs from Malaysia. 22 human cases and one death. Of these, 12 (54±6%) were symptomatic; 9 presented with encephalitis, 2 with pneumonia and 1 with both encephalitis and pneumonia. Stopped with pig import ban from Malaysia.

• Since 2001, 10 outbreaks in Bangladesh, 2 in West Bengal, India.

• Since discovery, 480 human cases including 251 deaths

•• In 1999, SingaporeIn 1999, Singapore’’s importation of infected pigs from s importation of infected pigs from Malaysia. 22 human cases and one death. Malaysia. 22 human cases and one death. Of these, 12 (54±6%) were symptomatic; 9 presented with encephalitis, 2 with pneumonia and 1 with both encephalitis and pneumonia. Stopped with pig import ban from Malaysia.Stopped with pig import ban from Malaysia.

•• Since 2001, 10 outbreaks in Bangladesh, 2 in West Bengal, Since 2001, 10 outbreaks in Bangladesh, 2 in West Bengal, India.India.

•• Since discovery, 480 human cases including 251 deathsSince discovery, 480 human cases including 251 deaths

Page 4: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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History of Nipah

Outbreaks, Bangladesh

and India

History of History of Nipah Nipah

Outbreaks, Outbreaks, Bangladesh Bangladesh

and Indiaand India

Eaton 2005

February 2010February 2010

Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

Eaton 2005

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Reservoirs of virusesHendra

Reservoirs of virusesReservoirs of virusesHendraHendra

• fruit bats identified as the natural host in 1996.

• antibodies in all 4 species (20-50%).

• antibodies across the geographic range.

• no attributed clinical disease in flying foxes.

• antibodies in archive samples.

• fruit bats identified as the natural host in 1996.

• antibodies in all 4 species (20-50%).

• antibodies across the geographic range.

• no attributed clinical disease in flying foxes.

• antibodies in archive samples.

Page 5: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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Reservoirs of virusesNipah Malaysia

Reservoirs of virusesReservoirs of virusesNipahNipah MalaysiaMalaysia

Total of ~310 batsKB Chua has isolated

Nipah virus from Pteropus hypomalenus

Total of ~310 batsTotal of ~310 batsKB Chua has isolated KB Chua has isolated

Nipah virus from Nipah virus from PteropusPteropus hypomalenushypomalenus

Species # Tested Nipah SNT Pos

Pteropus vampyrus 57 (28) 5Pteropus hypomalenus 42 10Cynopterus brachyolitis 74 0Cynopterus horsfieldi 9 0Rousettus amplexicaudatus 16 0Eonycteris spelaea 74 0Macroglosus sobrinus 4 0Balionycterus maculata 4 0Megaerops ecaudatus 1 0

Scotophuilus kuhli 58 0*Rhinolophus spp. 7 0Taphozous melanopogon 7 0Hippeosiderus bicolor 1 0

* Toxic

Eaton 2005

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Eaton 2005

February 2010February 2010

Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

Page 6: Emerging Zoonoses: Nipah and Hendra viruses - · PDF fileNipah and Hendra viruses Emerging Zoonoses: Pierre E. Rollin, MD ... Nipah virus from PteropusPteropus hypomalenushypomalenus

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Clinical features - HendraClinical features Clinical features -- HendraHendra

• All have unprotected contact with infected horses

• Incubation period 5-14 days• All cases symptomatic (4/7 died)• All start with “flu-like” syndrome: fever,

headache, myalgias, sore-throat, dry cough• Neurological manifestations indicative of bad

prognosis• Multi-organ failure and death

•• All have unprotected contact with infected All have unprotected contact with infected horseshorses

•• Incubation period 5Incubation period 5--14 days14 days•• All cases symptomatic (4/7 died)All cases symptomatic (4/7 died)•• All start with All start with ““fluflu--likelike”” syndrome: fever, syndrome: fever,

headache, headache, myalgiasmyalgias, sore, sore--throat, dry coughthroat, dry cough•• Neurological manifestations indicative of bad Neurological manifestations indicative of bad

prognosisprognosis•• MultiMulti--organ failure and deathorgan failure and death

Eaton 2005

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Clinical features - HendraClinical features Clinical features -- HendraHendra

Mild case in a veterinarian (Hanna et al. Med J Aust 2006;562-4)

– Extensive exposure to horse’s blood & body fluids during necropsy on horse with acute febrile illness with respiratory and pre-terminal neurological manifestations

– Onset 7 days later: febrile illness with cough, pharyngitis, cervical lymphadenopathy

– Recovered ~8 days later

– Seroconversion to HeV on day 14 of illness

– No clinical evidence of relapse

Mild case in a veterinarian (Hanna et al. Med J Aust 2006;562-4)

– Extensive exposure to horse’s blood & body fluids during necropsy on horse with acute febrile illness with respiratory and pre-terminal neurological manifestations

– Onset 7 days later: febrile illness with cough, pharyngitis, cervical lymphadenopathy

– Recovered ~8 days later

– Seroconversion to HeV on day 14 of illness

– No clinical evidence of relapse

Eaton 2005

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Clinical features - HendraClinical features Clinical features -- HendraHendra

33-year-old equine veterinarian (Playford et al. Emerg Infect DIs 2009 (in press)) Performed necropsy and nasal cavity lavage on infected horses (16 and 9 days previously)

Day 2 illness: Presented with “flu-like” illness, fevers, mild neutropenia & thrombocytopeniaNPA/serum: RT-PCR-positive for HeV; – NPA: RT-PCR-negative for respiratory viruses

Days 3-4: Afebrile/improvedDay 5: Drowsy, confused, ptosis, ataxia, dysarthria

MRI: multifocal pontine & cortical lesionsDWI: hyperintense foci c/w infarctionCSF: Leukocytes <5×106/L, protein 600 mg/L, HeV RT-PCRpositiveEEG: Bilateral slow wave activityCommenced on iv Ribavirin (30 mg/kg, then 15 mg/kg q6h)

Days 6-31: Progressive neurological deterioration: Generalised partial tonic-clonic seizure (day 10); Ventilated (day 11); Ribavirin ceased because of haemolytic anaemia (day 16); Sluggish reactive pupils, minimal responsiveness off sedation despite seizure control (day 19 on)MRIs: Innumerable widespread multifocal lesions on T2 FLAIR; lesions c/w infarction on DWIEEGs: absent stable rhythm, periodic sharp waves, severe diffuse encephalopathy

Day 31: Death

33-year-old equine veterinarian (Playford et al. Emerg Infect DIs 2009 (in press)) Performed necropsy and nasal cavity lavage on infected horses (16 and 9 days previously)

Day 2 illness: Presented with “flu-like” illness, fevers, mild neutropenia & thrombocytopeniaNPA/serum: RT-PCR-positive for HeV; – NPA: RT-PCR-negative for respiratory viruses

Days 3-4: Afebrile/improvedDay 5: Drowsy, confused, ptosis, ataxia, dysarthria

MRI: multifocal pontine & cortical lesionsDWI: hyperintense foci c/w infarctionCSF: Leukocytes <5×106/L, protein 600 mg/L, HeV RT-PCRpositiveEEG: Bilateral slow wave activityCommenced on iv Ribavirin (30 mg/kg, then 15 mg/kg q6h)

Days 6-31: Progressive neurological deterioration: Generalised partial tonic-clonic seizure (day 10); Ventilated (day 11); Ribavirin ceased because of haemolytic anaemia (day 16); Sluggish reactive pupils, minimal responsiveness off sedation despite seizure control (day 19 on)MRIs: Innumerable widespread multifocal lesions on T2 FLAIR; lesions c/w infarction on DWIEEGs: absent stable rhythm, periodic sharp waves, severe diffuse encephalopathy

Day 31: Death

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Clinical features - HendraClinical features Clinical features -- HendraHendra

Day 5Day 5

Day 18Day 18

Day 25Day 25

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Clinical features – Nipah Malaysia

Clinical features Clinical features –– Nipah Nipah MalaysiaMalaysia

• Febrile illness - 4-7 days duration• Early respiratory signs?• Headache, drowsiness, slurred speech, loss of

cognition, coma• Neurological signs suggest mid-brain, pons

lesions• Pathology: diffuse focal lesions of CNS• Mortality ~36%of those hospitalized (105/285)• There were subclinical infections

•• Febrile illness Febrile illness -- 44--7 days duration7 days duration•• Early respiratory signs?Early respiratory signs?•• Headache, drowsiness, slurred speech, loss of Headache, drowsiness, slurred speech, loss of

cognition, comacognition, coma•• Neurological signs suggest midNeurological signs suggest mid--brain, brain, ponspons

lesionslesions•• Pathology: diffuse focal lesions of CNSPathology: diffuse focal lesions of CNS•• Mortality ~36%of those hospitalized (105/285)Mortality ~36%of those hospitalized (105/285)•• There were subclinical infectionsThere were subclinical infections

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Admission Laboratory Values Admission Laboratory Values

Test Median Range (NormalRange)

WBC (x1000/mm3) 5.2 1.2 – 14.7 (4.5-11.0)

Platelet (x1000/mm3) 141 8 - 357 (150-400)

Creatinine (mg/dL) 0.9 0.4- 5.0 (0.7-1.5)

CSF WBC (# /cu mm) 2 0-1250 (0-10)

CSF protein (mg/dL) 67 15 - 335 (15-45)

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Clinical features of Nipah virus encephalitisGoh et al NEJM 2000;342:1229

Clinical features of Nipah virus encephalitisGoh et al NEJM 2000;342:1229

Clinical features at presentation (n=94)

Fever 97%Headache 65%Dizziness 36%Vomiting 27%Reduced consciousness 21%Nonproductive cough 14%Myalgia 12%Focal neurological signs 10%

Clinical features at presentation (n=94)

Fever 97%Headache 65%Dizziness 36%Vomiting 27%Reduced consciousness 21%Nonproductive cough 14%Myalgia 12%Focal neurological signs 10%

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Clinical features of Nipah virus encephalitisGoh et al NEJM 2000;342:1229

Clinical features of Nipah virus encephalitisGoh et al NEJM 2000;342:1229

Neurological characteristics (n=94)

Absent or reduced reflexes 56%Impaired consciousness 55%Abnormal pupils 52%Tachycardia 39%Abnormal doll’s eye reflex 38%Segmental myoclonus 32%Meningism 28%Seizures 23%Nystagmus 16%Cerebellar signs 9%

Neurological characteristics (n=94)

Absent or reduced reflexes 56%Impaired consciousness 55%Abnormal pupils 52%Tachycardia 39%Abnormal doll’s eye reflex 38%Segmental myoclonus 32%Meningism 28%Seizures 23%Nystagmus 16%Cerebellar signs 9%

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Factors associated with prognosisGoh et al. NJEM 2000;342:1229

Factors associated with prognosisGoh et al. NJEM 2000;342:1229

FACTOR DEATH SURVIVAL P VALUE(N=30) (N=64)

Mean age — yr 40.9 35.2 0.02Vomiting — no. (%) 12 (40) 13 (20) 0.04Mean lowest Glasgow Coma scores 6.8 12.8 0.005Segmental myoclonus — no. (%) 20 (67) 10 (16) <0.001Abnormal doll’s-eye reflex — no. (%) 26 (87) 10 (16) <0.001Abnormal pupils — no. (%) 29 (97) 20 (31) <0.001Hypertension — no. (%) 23 (77) 14 (22) <0.001Tachycardia — no. (%) 28 (93) 8 (12) <0.001Absent or reduced reflexes — no. (%) 22 (73) 31 (48) 0.02Seizures — no. (%) 12 (40) 10 (16) 0.01Mean AST level at admission — U/liter 87 34.4 0.001Mean ALT level at admission — U/liter 94.2 53.6 0.006Mean platelet count at admission 151,000 197,000 0.005— per mm3

FACTOR DEATH SURVIVAL P VALUE(N=30) (N=64)

Mean age — yr 40.9 35.2 0.02Vomiting — no. (%) 12 (40) 13 (20) 0.04Mean lowest Glasgow Coma scores 6.8 12.8 0.005Segmental myoclonus — no. (%) 20 (67) 10 (16) <0.001Abnormal doll’s-eye reflex — no. (%) 26 (87) 10 (16) <0.001Abnormal pupils — no. (%) 29 (97) 20 (31) <0.001Hypertension — no. (%) 23 (77) 14 (22) <0.001Tachycardia — no. (%) 28 (93) 8 (12) <0.001Absent or reduced reflexes — no. (%) 22 (73) 31 (48) 0.02Seizures — no. (%) 12 (40) 10 (16) 0.01Mean AST level at admission — U/liter 87 34.4 0.001Mean ALT level at admission — U/liter 94.2 53.6 0.006Mean platelet count at admission 151,000 197,000 0.005— per mm3

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Relapsed and late-onset Nipah encephalitisChong et al Neurol J Southeast Asia 2003;

8: 109

Relapsed and late-onset Nipah encephalitisChong et al Neurol J Southeast Asia 2003;

8: 109

Relapsed encephalitis was seen in 15 (9%) of acute encephalitis survivors

Late-onset encephalitis was seen in 10 (3.4%) of those with previous non-encephalitic or asymptomatic Nipah infection

Mean duration from initial infection: 13 months (up to 4 ½ years)

3/25 patients had a second neurological episode

Relapsed encephalitis was seen in 15 (9%) of acute encephalitis survivors

Late-onset encephalitis was seen in 10 (3.4%) of those with previous non-encephalitic or asymptomatic Nipah infection

Mean duration from initial infection: 13 months (up to 4 ½ years)

3/25 patients had a second neurological episode

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Immunohistochemistry - NipahImmunohistochemistryImmunohistochemistry -- NipahNipah

A B

C

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Long-term neurological and functional outcome in Nipah virus infection Sejvar JJ et al. Ann Neurol 2007

Long-term neurological and functional outcome in Nipah virus infection Sejvar JJ et al. Ann Neurol 2007

Of the survivors of acute Nipah infection in Bangladesh# 21/22 had disabling fatigue, with medium duration

of 5 months;# 3 patients continued to have profound fatigue 2

years after infection# >50% of those <16 years had Behavioral

abnormalities

Of the survivors of acute Nipah infection in Bangladesh# 21/22 had disabling fatigue, with medium duration

of 5 months;# 3 patients continued to have profound fatigue 2

years after infection# >50% of those <16 years had Behavioral

abnormalities

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Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

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Laboratory diagnosis“BSL-4 agent”

Laboratory diagnosisLaboratory diagnosis““BSLBSL--4 agent4 agent””

Sample PCR Isolation IHC AntibodyN/T Swab +* +* ND NDUrine +* +* ND NDBlood +/- - ND +CSF + + ND +Tissues + + + ND

* Positivity decrease when Ab appears

SampleSample PCRPCR IsolationIsolation IHCIHC AntibodyAntibodyN/T SwabN/T Swab +*+* +*+* NDND NDNDUrineUrine +*+* +*+* NDND NDNDBloodBlood +/+/-- -- NDND ++CSFCSF ++ ++ NDND ++TissuesTissues ++ ++ ++ NDND

* Positivity decrease when * Positivity decrease when AbAb appearsappears

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Treatment Potential prophylactic/therapeutic modalities

Treatment Treatment Potential prophylactic/therapeutic modalities

– Ribavirin Nipah/Hendra– Chloroquine– Passive immunotherapy

– Ribavirin Nipah/Hendra– Chloroquine– Passive immunotherapy

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Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

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Risk of spillover from batsRisk of spillover from bats

Probability of spillover from any given colony depends on• the proportion of susceptible flying foxes,• the colony size,• the presence of infection..

plus• the number and density of horses,• the number and density of flying foxes,• management of the horses,• the virus strain/virus dose/route of infection?

Probability of spillover from any given colony depends on• the proportion of susceptible flying foxes,• the colony size,• the presence of infection..

plus• the number and density of horses,• the number and density of flying foxes,• management of the horses,• the virus strain/virus dose/route of infection?

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0

kilometers1 2

Nipah CaseIndex Case

Pig Farm

SepangSepang

Bukit Bukit PelandukPelanduk

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0

2

4

6

8

10

12

14

16

01-09

-98

01-10

-98

01-11

-98

01-12

-98

01-01

-99

01-02

-99

01-03

-99

01-04

-99

01-05

-99

Date of Onset

Ipoh (n=32)Ipoh (n=32)

SikamatSikamat (n=7)(n=7) SgSg BulohBuloh (n=7)(n=7)

Bukit Bukit PelandokPelandok (n=212)(n=212)SepangSepang (n=13)(n=13)

Nipah confirmedNipah suspected

# of

Cas

es

Cases of Encephalitis in MalaysiaCases of Encephalitis in MalaysiaSeptember 1998 to May 1999September 1998 to May 1999

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National Swine SurveillanceNational Swine SurveillanceNational Swine Surveillance

• Limited period (90 days)• All premises sampled

• Based on high morbidity data• 15 sows• 2 samples (at least 21 days apart)

• Abattoir sampling• Active disease discovery• Human case discovery• Cull infected premises

•• Limited period (90 days)Limited period (90 days)•• All premises sampledAll premises sampled

•• Based on high morbidity dataBased on high morbidity data•• 15 sows15 sows•• 2 samples (at least 21 days apart)2 samples (at least 21 days apart)

•• Abattoir samplingAbattoir sampling•• Active disease discoveryActive disease discovery•• Human case discoveryHuman case discovery•• Cull infected premisesCull infected premises

Eaton 2005

February 2010February 2010

Results of Phase II Nat. Swine Surveillance

Results of Phase II Nat. Results of Phase II Nat. Swine SurveillanceSwine Surveillance

A total of 889 farms were tested

50 farms were found to have evidence of Nipah infection by the prearranged criteria

Farms culled

A total of 889 farms were testedA total of 889 farms were tested

50 farms were found to have 50 farms were found to have evidence of Nipah infection evidence of Nipah infection by the prearranged criteriaby the prearranged criteria

Farms culled Farms culled

Eaton 2005

February 2010February 2010

Epidemiology Nipah MalaysiaEpidemiology Nipah MalaysiaEpidemiology Nipah Malaysia

• Spread• Movement of infected swine

• Transmission in swine:• Very transmissible in modern husbandry

setting: crowding• Virus maintenance in swine

• Continuous transmission? • Persistent infections?

•• SpreadSpread•• Movement of infected swineMovement of infected swine

•• Transmission in swine:Transmission in swine:•• Very transmissible in modern husbandry Very transmissible in modern husbandry

setting: crowdingsetting: crowding•• Virus maintenance in swineVirus maintenance in swine

•• Continuous transmission? Continuous transmission? •• Persistent infections?Persistent infections?

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Eaton 2005

February 2010February 2010

Investigations Nipah MalaysiaInvestigations Nipah MalaysiaInvestigations Nipah Malaysia

• Risk factors:• Direct live infected pig contact• Non-encephalitic/non-clinical infections

• Virus molecular epidemiology• Pigs and human cases: identical sequence

• Nosocomial infections? No• Natural reservoir? • Other species:

• Dogs, cats, horses: but non-spreading• Rodents, birds, insectivores: none or very low

•• Risk factors:Risk factors:•• Direct live infected pig contactDirect live infected pig contact•• NonNon--encephalitic/nonencephalitic/non--clinical infectionsclinical infections

•• Virus molecular epidemiologyVirus molecular epidemiology•• Pigs and human cases: identical sequencePigs and human cases: identical sequence

•• Nosocomial infections? NoNosocomial infections? No•• Natural reservoir? Natural reservoir? •• Other species:Other species:

•• Dogs, cats, horses: but nonDogs, cats, horses: but non--spreadingspreading•• Rodents, birds, insectivores: none or very lowRodents, birds, insectivores: none or very low

Eaton 2005

February 2010February 2010

Risk factors & transmission of Nipah in Bangladesh

Risk factors & transmission of Nipah in Bangladesh

Rahman et al, 2009

Eaton 2005

February 2010February 2010

Bangladesh EpidemiologyBangladesh EpidemiologyBangladesh Epidemiology

Person to person transmission5 of 11 clusters, involved ranging from 1 to 5 generationsStudy conducted to reduce the risk of Nipah virus

transmission• Nipah virus isolated from saliva and urine• Nipah infection associated with close contact of patients• Hand washing is protective

Superspreaders

Palm sap transmissionUnderstand date palm sap collection• Explore existing techniques to interrupt bats in

accessing date palm sap

Person to person transmission5 of 11 clusters, involved ranging from 1 to 5 generationsStudy conducted to reduce the risk of Nipah virus

transmission• Nipah virus isolated from saliva and urine• Nipah infection associated with close contact of patients• Hand washing is protective

Superspreaders

Palm sap transmissionUnderstand date palm sap collection• Explore existing techniques to interrupt bats in

accessing date palm sap

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Eaton 2005

February 2010February 2010

Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

Eaton 2005

February 2010February 2010

Hendra disease in horsesHendra disease in horsesHendra disease in horses

Respiratory HeVPeracute or acute illnessFrothy nasal dischargeFacial oedemaBody temperature > 40 CElevated heart rate (>90 beats/minute)

Neurological HeV (seen recently in Australia)Mild focal neurological signs, including

muscle twitchingAtaxiaHead tilt, facial nerve paralysisElevated body temperatureNeurological signs may resolve

Respiratory Respiratory HeVHeVPeracutePeracute or acute illnessor acute illnessFrothy nasal dischargeFrothy nasal dischargeFacial Facial oedemaoedemaBody temperature > 40 CBody temperature > 40 CElevated heart rate (>90 beats/minute)Elevated heart rate (>90 beats/minute)

Neurological Neurological HeVHeV (seen recently in Australia)(seen recently in Australia)Mild focal neurological signs, including Mild focal neurological signs, including

muscle twitchingmuscle twitchingAtaxiaAtaxiaHead tilt, facial nerve paralysisHead tilt, facial nerve paralysisElevated body temperatureElevated body temperatureNeurological signs may resolveNeurological signs may resolve

Eaton 2005

February 2010February 2010

Nipah disease in swineNipah disease in swineNipah disease in swine

• Febrile respiratory disease predominates• Labored or forced breathing• “One-mile” cough

• CNS disease much rarer than in man• Sudden death/neurological disease in sows

and boars, some abortions reported• Mortality 1-3%, morbidity: ~100%• Post-mortem changes primarily in lung, some

CNS

•• Febrile respiratory disease predominatesFebrile respiratory disease predominates•• Labored or forced breathingLabored or forced breathing•• ““OneOne--milemile”” coughcough

•• CNS disease much rarer than in manCNS disease much rarer than in man•• Sudden death/neurological disease in sows Sudden death/neurological disease in sows

and boars, some abortions reportedand boars, some abortions reported•• Mortality 1Mortality 1--3%, morbidity: ~100%3%, morbidity: ~100%•• PostPost--mortem changes primarily in lung, some mortem changes primarily in lung, some

CNSCNS

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Eaton 2005

February 2010February 2010

Hendra and Nipah virusesHendra and Nipah virusesHendra and Nipah viruses

• History of previous outbreaks• Reservoirs of viruses• Clinical features in human• Diagnosis and Treatment• Transmission and Epidemiology• Disease in horses and pigs• Prevention and Control

•• History of previous outbreaksHistory of previous outbreaks•• Reservoirs of virusesReservoirs of viruses•• Clinical features in humanClinical features in human•• Diagnosis and TreatmentDiagnosis and Treatment•• Transmission and EpidemiologyTransmission and Epidemiology•• Disease in horses and pigsDisease in horses and pigs•• Prevention and ControlPrevention and Control

Eaton 2005

February 2010February 2010

1. Control in domestic animals1. Control in domestic animals

● Routine cleaning & disinfection of pig farm/horse stable isexpected to be effective in preventing infection

● Reducing the risk of bat-to-domestic animal transmission:bat proof buildings, bat exclusion strategy, fruit tree removal…

● Outbreak suspected:Quarantine animal premises± euthanasia or culling of infected animal(s)Restrict/ ban animals movements

● Establish active animal health surveillance system for early warning for veterinary and human public health authorities.

● Routine cleaning & disinfection of pig farm/horse stable isexpected to be effective in preventing infection

● Reducing the risk of bat-to-domestic animal transmission:bat proof buildings, bat exclusion strategy, fruit tree removal…

● Outbreak suspected:Quarantine animal premises± euthanasia or culling of infected animal(s)Restrict/ ban animals movements

● Establish active animal health surveillance system for early warning for veterinary and human public health authorities.

Eaton 2005

February 2010February 2010

2. Reducing risk of infection in people

2. Reducing risk of infection in people

● Reduce risk of bats-to-human transmission:Protect collection process of date palm juice (bamboo)Wash & peel fruits thoroughly

● Reduce risk of human-to-human transmission:Avoid or minimize physical contact with ill patientHand hygiene + use of personal protective equipment (PPE)

● Reduce risk of domestic animal-to-human transmission:Avoid or minimize contact with ill or dead pig, horseHand hygiene + use of personal protective equipment (PPE)Particularly important in veterinary practices (care, necropsies)

● Reduce risk of bats-to-human transmission:Protect collection process of date palm juice (bamboo)Wash & peel fruits thoroughly

● Reduce risk of human-to-human transmission:Avoid or minimize physical contact with ill patientHand hygiene + use of personal protective equipment (PPE)

● Reduce risk of domestic animal-to-human transmission:Avoid or minimize contact with ill or dead pig, horseHand hygiene + use of personal protective equipment (PPE)Particularly important in veterinary practices (care, necropsies)

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Eaton 2005

February 2010February 2010

Social Mobilization and Communication

Social Mobilization and Communication

● Prevention: what should be the key messages:Exposure to bats,Exposure to sick animals,Home care,Funerals?

● Guidelines/trainings for specialized categoriesHealth care workersVeterinariansFarmersWildlife experts

● Prevention: what should be the key messages:Exposure to bats,Exposure to sick animals,Home care,Funerals?

● Guidelines/trainings for specialized categoriesHealth care workersVeterinariansFarmersWildlife experts