Review

Nipah virus outbreaks in Bangladesh: a deadly infectious disease

Mahmudur Rahmana, Apurba Chakrabortya

Abstract: During 2001-2011, multidisciplinary teams from the Institute of Epidemiology, Disease Control and Research (IEDCR) and International Centre for Diarrhoeal Disease Research, Bangladesh(icddr,b) identified sporadic cases and 11 outbreaks of Nipah . Three outbreaks were detected through sentinel surveillance; others were identified through event-based surveillance. A total of 196 cases of Nipah encephalitis, in outbreaks, clusters and as isolated cases were detected from 20 districts of Bangladesh; out of them 150 (77%) cases died. Drinking raw date palm sap and contact with a case were identified as the major risk factors for acquiring the disease. Combination of surveillance systems and multidisciplinary outbreak investigations can be an effective strategy not only for detection of emerging infectious diseases but also for identification of novel characteristics and risk factors for these diseases in resource- poor settings.

Keywords: , outbreak, surveillance, transmission, communicable disease, Bangladesh.

Introduction through outbreak investigations during 2001- 2011. Nipah is a recently detected viral zoonotic disease caused by Nipah virus originating from a new genus - the Henipa virus.1, 2 Pteropus Methods bats are the zoonotic host of the virus and We reviewed IEDCR strategies and guidelines pigs are the likely amplifying host.2, 3 The from its records to explore the mechanism for virus was first identified in Nipah village of detection of Nipah cases and clusters. We also in 1998,2, 4 since then three other reviewed the method of hospital-based Nipah countries have reported human cases of Nipah surveillance jointly conducted by IEDCR and virus infection, including Bangladesh.5-7 The the International Centre for Diarrhoeal Disease Institute of Epidemiology, Disease Control and Research, Bangladesh (icddr,b). Outbreak Research (IEDCR), a government mandated investigation reports were studied to identify institute, conducted disease surveillance and the sources of information through which outbreak investigations for Nipah encephalitis these outbreaks were detected. The Nipah in Bangladesh. We present a review of the surveillance database was used to describe methods used for detecting these cases and the demographic and clinical characteristics of their novel characteristics and risk factors the identified Nipah cases. Published reports

a Institute of Epidemiology, Disease Control and Research, Mohakhali, Dhaka-1212, Bangladesh. Correspondence to Mahmudur Rahman (email: [email protected])

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on Nipah encephalitis in Bangladesh and brain pathology manifested by altered mental unpublished outbreak investigation reports status or new onset of or neurological were reviewed to identify the risk factors for deficit. Any cluster of encephalitis cases, Nipah encephalitis in Bangladesh. defined by two encephalitis cases within 21 days of each other and within half an hour Results walking distance from each other, identified through the sentinel hospitals are investigated To detect disease outbreaks, IEDCR conducts by a trained team of epidemiologists from both ‘event-based surveillance’ and ‘surveillance IEDCR and icddr,b. for specific disease or conditions’. Up to April 2010, as part of the event-based surveillance, As part of the cluster investigation the IEDCR conducted unstructured monitoring of IEDCR and icddr,b team conducts search for newspapers and television channels for reports encephalitis cases in the community adjacent of suspected disease outbreaks. In April 2010, to the cluster and carries out epidemiological IEDCR started a more structured surveillance research to identify risk factors. In case of of suspected disease outbreak reports in outbreaks of encephalitis that are detected 10 national newspapers and eight national through event-based surveillance or sentinel television channels. Any reported cluster or surveillance, a team of epidemiologists, outbreak of known illness and even report veterinarians and anthropologists conduct of a single death from unknown disease is outbreak investigations. These investigations captured through this surveillance method. In include identification of alive or deceased addition to the media surveillance, IEDCR has human cases suspected of having Nipah two hotline numbers for healthcare providers encepahlitis, identification of possible animal to report disease outbreaks. Through district sources of the infection, assessment of and sub-district rapid response teams, IEDCR environmental contamination, and study of verifies the existence of any outbreak and possible behavioural factors contributing to conducts investigation. the outbreak and case control study to identify possible risk factors. For each case of Nipah To identify outbreaks of encephalitis encephalitis, four age-matched neighbourhood through enhanced surveillance networks and controls are selected for case control study. to identify risk factors for transmission of Exposure histories of both cases and controls Nipah encephalitis, IEDCR in collaboration within 30 days prior to the onset of illness are with the International Centre for Diarrhoeal collected. Disease Research, Bangladesh (icddr,b) has been conducting surveillance for Nipah In case of any encephalitis cluster or encephalitis in Bangladesh since 2006. outbreak, investigation teams collect blood Initially, this surveillance programme started from the suspected encephalitis cases and in 10 hospitals. Currently, the surveillance is samples are sent to IEDCR. Initially, samples functioning in five hospitals in northwestern were sent to Centers for Disease Control and central Bangladesh. Clinicians of sentinel and Prevention, USA (CDC) for testing. Later hospitals identify and list all encephalitis cases in 2007, a Nipah laboratory was set up at presenting in the surveillance hospitals. A IEDCR for safe specimen handling and testing. case of encephalitis is defined as any person Virologists of IEDCR conduct enzyme-linked with history of acute onset of or axillary immunosorbent assay to identify IgM and IgG temperature of >38.50C and evidence of acute antibodies against Nipah virus.

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In Bangladesh, Nipah outbreak was first days). In the course of illness, 123 (63%) confirmed in 2003, when a team from Centers Nipah encephalitis cases developed acute for Disease Control and Prevention, Atlanta, respiratory distress syndrome (Table 1). USA (CDC), icddr,b and the Government of Drinking raw date palm sap collected during Bangladesh retrospectively investigated two winter months, which is a delicacy in rural outbreaks of suspected encephalitis with human Bangladesh, was first identified as a risk factor deaths which had occurred in for Nipah infection in an outbreak in Tangail in in 2001 and in Naogaon in 2003.7 Including 2005.8 This has also been identified as a risk these two, 11 outbreaks of Nipah encephalitis factor in three more outbreaks so far. Several have been detected in Bangladesh since sporadic cases have also reported history of 2001. Five of these outbreaks were detected drinking raw date palm sap within 30 days from newspaper reports of human deaths before the onset of illness. Close contacts with from unknown illness, three were reported a sick person or his/her secretions and contact by sentinel hospitals, one was reported from with sick animals were the other two risk a private hospital and others were reported factors identified through case control studies by the civil surgeon of a district. During this in different outbreak investigations (Table 2). period, 196 cases of Nipah encephalitis were detected from 20 districts of Bangladesh in Pteropus bats were found to be positive outbreaks, clusters and as isolated cases; out for Nipah antibodies in different outbreak of these 150 (77%) cases died. areas.7 A zoonotic investigation team of icddr,b identified the way bats contaminate the shaved The Nipah cases were mostly distributed surface of the date palm trees (from where the in the northwestern and central part of sap is collected) using infrared camera.9 Bangladesh. Outbreaks occurred during December to May, which coincides with the winter season in Bangladesh. Cases were Discussion distributed in all age groups. Median age was A combination of an ‘event-based’ and 25 years (range: 0.5-75 years) and 124 (63%) ‘sentinel’ surveillance system has been cases were males. Median duration from onset a successful strategy in Bangladesh for of illness to death was six days (range: 1-47 detecting recurrent outbreaks of Nipah

Table 1: Clinical characteristics of Nipah cases in Bangladesh Clinical characteristic Number (%) Fever 196 (100) Altered mental status 169 (86) Sever weakness/lethargy 142 (72) Headache 131 (67) Acute respiratory distress syndrome 123 (63) Cough 108 (55) Vomiting 105 (54) Myalgia 81 (41) Convulsions 59 (30)

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Table 2: Risk factors identified through case control studies in Nipah outbreaks of Bangladesh Year District Risk factors Odds 95% p Ratio Confidence Interval 2001 Meherpur Contact with a sick cow7 7.9 2.2 - 27.7 -

Caring or living with a case7 4.8 1.23 - 18.8 -

2003 Naogaon Close proximity with pig herds10 6.1 1.3 - 27.8 0.007 2004 Rajbari Climbing trees13 8.2 1.25 - ∞ - Contact with Nipah patient13 21.4 2.78 - 966.1 - 2004 Faridpur Touching a Nipah patient14 5.6 1.79 - 17.24 0.003 2005 Tangail Drinking raw date palm juice8 7.9 1.6 - 38 <0.01 2007 Thakurgaon Remaining in the same room with Undefined - <0.001 Nipah patient16 2007 Kushtia Physical contact with a Nipah Undefined - <0.001 patient15 2008 Manikganj and Drinking raw date palm juice 18 2.2 - ∞ <0.005 Rajbari 2010 Faridpur Drinking raw date palm juice - - - 2011 Lalmonirhat Drinking raw date palm juice 17 4 - 70 ≤0.001

encephalitis. Multidisciplinary collaborative based surveillance system with a sentinel investigation of the outbreaks identified the surveillance system for encephalitis has clinical characteristics, risk factors and mode possibly increased the likelihood of identifying of transmission of this highly fatal zoonotic Nipah cases in Bangladesh in comparison to disease. some other countries in the region, which lack a strong surveillance for encephalitis. Over 50 species of Pteropus bats, the natural reservoir of Nipah virus, live in South While more than 95% of the Nipah cases in and South-East Asian countries.10 After Malaysia had a history of contact with pigs,11 the large outbreak of Nipah encephalitis in only one of the 11 Bangladeshi outbreaks a in Malaysia, only three outbreaks have close proximity to pig herds was identified as been reported from countries other than a risk factor. Identification of the drinking of Bangladesh, one in Singapore and two raw date palm sap, a unique cultural practice in India.5, 6 Therefore, it is important to in rural Bangladesh12 and possibly in the know whether specific environmental or neighbouring Indian states, as a risk factor for host factors are responsible for recurrent acquiring Nipah infection in Bangladesh and the transmission of Nipah virus to humans in validation of the plausibility of contamination Bangladesh or whether virus detections are of date palm sap with Nipah virus from the result of an efficient surveillance system. Pteropus bats through separate zoonotic Although Bangladesh, like many other low- investigation highlights the importance of a income countries, lacks an integrated disease multidisciplinary approach in investigating surveillance system, the combination of event- outbreaks of zoonotic diseases.9

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Nipah outbreaks in Bangladesh have 4. Goh KJ, Tan CT, Chew NK, et al. Clinical features presented some features distinctly different of Nipah virus encephalitis among pig farmers in than the outbreak in Malaysia. In Bangladesh, Malaysia. N Engl J Med. 2000;342:1229-35. a higher proportion of Nipah cases suffered 5. Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah- from respiratory symptoms than in Malaysia.4 virus infection among abattoir workers in Singapore. Lancet. 1999;354:1253-6. Also, the case fatality ratio was higher in Bangladesh, which may be related to the lack 6. Harit AK, Ichhpujani RL, Gupta S, et al. Nipah/Hendra of access of Bangladeshi cases to intensive virus outbreak in Siliguri, West Bengal, India in 2001. Indian J Med Res. 2006;123:553-60. care facilities.4 Like in other diseases caused by paramyxoviruses, such as measles, 7. Hsu VP, Hossain MJ, Parashar UD, et al. Nipah virus encephalitis reemergence, Bangladesh. Emerg Infect mumps, respiratory syncytial virus infection, Dis. 2004;10:2082-7. parainfluenza, person-to-person transmission was a common mode of transmission in 8. Luby SP, Rahman M, Hossain MJ, et al. Foodborne transmission of Nipah virus, Bangladesh. Emerg Bangladeshi Nipah cases, but this mode Infect Dis. 2006;12:1888-94. of transmission was not common in Nipah 9. Khan MS, Hossain J, Gurley ES, Nahar N, Sultana R encephalitis cases in Malaysia. Therefore, and Luby SP. Use of infrared camera to understand future investigations should focus on exploring bats’ access to date palm sap: implications for the reasons for variable presentation and preventing Nipah virus transmission. Ecohealth. different modes of transmission of Nipah virus 2010;7:517-25.

in different settings. 10. Luby SP, Gurley ES and Hossain MJ. Transmission of human infection with Nipah virus. Clin Infect Dis. To conclude, Nipah encephalitis, a fatal 2009;49:1743-8. zoonotic disease, recurrently claims lives in Bangladesh following the initial reports of 11. Parashar UD, Sunn LM, Ong F, et al. Case-control study of risk factors for human infection with a new outbreaks in other countries. A combination of zoonotic paramyxovirus, Nipah virus, during a 1998- event-based and sentinel surveillance systems 1999 outbreak of severe encephalitis in Malaysia. J is an innovative strategy to detect encephalitis Infect Dis. 2000;181:1755-9.

outbreaks which has been successful in 12. Rahman MA, Hossain MJ, Sultana S, et al. Date Palm detecting Nipah outbreaks in Bangladesh. Sap Linked to Nipah Virus Outbreak in Bangladesh, Multidisciplinary outbreak investigations 2008. Vector Borne Zoonotic Dis. 2012;12(1):65- can be an important tool in exploring novel 72. characteristics and risk factors of emerging 13. Montgomery JM, Hossain MJ, Gurley E, et al. Risk infectious zoonotic diseases in resource-poor factors for Nipah virus encephalitis in Bangladesh. settings. Emerg Infect Dis. 2008;14:1526-32. 14. Gurley ES, Montgomery JM, Hossain MJ, et al. Person- References to-person transmission of Nipah virus in a Bangladeshi community. Emerg Infect Dis. 2007;13:1031-7.

1. Chua KB. Nipah virus outbreak in Malaysia. J Clin 15. Homaira N, Rahman M, Hossain MJ, et al. Cluster of Virol. 2003;26:265-75. Nipah virus infection, Kushtia District, Bangladesh, 2. Chua KB, Bellini WJ, Rota PA, et al. Nipah virus: a 2007. PLoS One. 2010;5:e13570. recently emergent deadly paramyxovirus. Science. 16. Homaira N, Rahman M, Hossain MJ, et al. Nipah 2000;288:1432-5. virus outbreak with person-to-person transmission 3. Epstein JH, Field HE, Luby S, Pulliam JR and Daszak in a district of Bangladesh, 2007. Epidemiol Infect; P. Nipah virus: impact, origins, and causes of 138:1630-6. emergence. Curr Infect Dis Rep. 2006;8:59-65.

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