Nipah outbreaks in Bangladesh - Historical

[Ronan Kelly]

Nipah outbreak in Faridpur District,Bangladesh, 2010Nipah outbreak in Faridpur District,Bangladesh, 2010

Physicians at Faridpur Medical College Hospital recognized a cluster of encephalitis cases within Faridpur District in January 2010. A subsequent feld investigation suggested that the initial cases acquired Nipah through drinking raw date palm sap and subsequent transmission occurred through person-to-person contact. In March 2010, one of the hospital physicians who cared for two Nipah patients died from Nipah encephalitis. To prevent further outbreaks of Nipah virus, people in the ?Nipah belt? should be warned about the risk of drinking fresh date palm sap. Practical steps to interrupt contamination of date palm sap should be introduced, and protective measures to reduce patient to caregiver transmission undertaken.



Eight outbreaks of Nipah encephalitis have been recognized in Bangladesh from 2001 to 2008 (1,2). The Institute for Epidemiology Disease Control and Research (IEDCR) of the Government of Bangladesh, in collaboration with ICDDR,B, established 10 Nipah surveillance sites beginning in February 2006 in hospitals located in the region where prior Nipah outbreaks were recognized (Figure 1). The objective of the surveillance is to identify outbreaks of encephalitis and to characterize the conditions and risk factors for transmission of the responsible viruses. Each of the six active site submits a monthly report to IEDCR and ICDDR,B on the number of meningo-encephalitic cases, while the four passive sites only report if they suspect a high number of encephalitis cases.



Senior physicians and paediatricians of corresponding active surveillance hospitals are the focal persons and each hospital has a designated Nipah surveillance study physician. The active surveillance sites maintain a registry throughout the year of patients who fulfil the enrollment criteria based on encephalitis and/or pulmonary presentation (3). The encephalitic presentation includes fever with evidence of acute brain pathology, i.e. altered mental status, new onset of seizures, or a new neurological deficit. Respiratory presentation includes acute onset <7 days of symptoms with fever, severe shortness of breath and chest radiograph with diffuse infiltrates.

To cost effectively focus scarce public health surveillance resources, active surveillance focuses on identifying clusters of patients with meningo-encephalitis. We define a cluster as two or more persons living within a 30 minute walk of each other who develop similar symptoms within 21 days of each other. Surveillance physicians keep a detailed address of each case in the registry that they match cases with using distance and time. They also ask individual patients or attendants about recent deaths in their community or any other cases with similar symptoms not yet reported. When active surveillance identifies a cluster they report it to IEDCR and ICDDR,B and we promptly conduct an epidemiological investigation in the community to search for more cases of meningo-encephalitis syndrome and to collect additional samples to try to identify the aetiology of the disease.

To identify all hospital reported cases that occur during the usual Nipah season from January to March, we collected blood and cerebrospinal fluid samples at three active surveillance sites, Faridpur, Rajshahi and Rangpur Medical College Hospitals, which admit the largest number of acute meningo-encephalitis cases. We tested these samples for anti-Nipah IgM by ELISA at IEDCR and ICDDR,B virology laboratory in Dhaka to confirm both clusters and isolated cases.

In December 2009, an experienced surveillance officer from Rajbari Sadar Hospital reported a suspected Nipah encephalitis case and referred the patient to Faridpur Medical College Hospital, where a blood sample was collected that was found positive for IgM antibody against Nipah virus. We then initiated sample collection from each meningo-encephalitis case from Faridpur surveillance hospital. In total, from December 2009 to March 2010, we enrolled 331 cases from the six active surveillance sites. Among them 293 (89%) cases were from Faridpur, Rajshahi and Rangpur Medical College Hospitals. Fifty seven percent of cases (167) were under 15 years of age (Table 1). No Nipah cases were confirmed by laboratory testing from Rangpur and Rajshahi Medical College Hospitals. We found twelve anti-Nipah IgM positive cases at Faridpur Medical College Hospital: two of them were part of a cluster, and the remainder were isolated cases from a widespread geographic area in and around Faridpur district (Figure 1).



During this same period, we investigated seven meningo-encephalitis clusters: one from Rangpur; and three each from Rajshahi and Faridpur. In Rangpur and in Rajshahi we could not find any exposure history, or epidemiological links between cases of these clusters and each case was anti-Nipah IgM negative.

In Faridpur, the first cluster consisted of two cases, both of which had fever, with features of brain pathology, but both of whom tested anti-Nipah IgM negative. The second Faridpur cluster involved two cases who also had fever with features of brain pathology, but with no epidemiological link between them. One Nipah antibody negative case survived, but a Nipah antibody positive case, who collected date palm sap and had a history of drinking raw date palm sap, died. The third Faridpur cluster was reported to IEDCR and ICDDR,B on 14 January 2010, and consisted of eight cases. We defined probable cases as people with fever and altered mental status or new onset of seizures or respiratory distress. Confirmed Nipah cases were serum anti-Nipah IgM antibody positive. The index case was a 45 year old male from Bhanga sub-district who died after being admitted to the hospital. Another 40-year old female case, who was a neighbour of the index case, presented with vomiting, headache, convulsion, altered mental status, and loss of consciousness, and died at home. Both of them were probable cases. Two other cases from the 40-year old female?s family, 10 and 11 year old girls, who were admitted in hospital with a clinical diagnosis of encephalitis, died. One girl was found anti-Nipah IgM positive. The other girl was a probable Nipah case.

After one week, the study physician from Fardipur Medical College Hospital reported another upsurge of cases from the same sub-district. The investigation team identified two more probable and two more confirmed Nipah encephalitis cases. These four cases were all between 32 and 60 years of age; three of the four died.

We observed two generations of Nipah transmission in this large cluster. The male index case had a history of drinking raw date palm sap with other family members and his house was under a bat roost. He had no physical contact with subsequent cases of the first generation. The subsequent three cases had onset of illness on a same day (Figure 2). All three cases were from a single family, living about 250 meters away from a bat roost, who drank raw date palm sap together during the previous week. After another seven days, three other persons who had a history of close physical contact with the index case became sick. All of them died. None of them had a history of drinking raw date palm sap within the last one month. The last case of the cluster, the wife of the index case, was the only survivor. She had reported drinking raw date palm sap and had contact with the index case.

As part of Nipah surveillance, we also investigated all isolated laboratory confirmed Nipah positive cases. Among the nine cases identified between December 2009 to April 2010, one case was an intern doctor, who had very recently joined the paediatric department of Fardipur Medical College Hospital. He performed several physical examinations, without any personal protective equipment, on two young girls, aged 5 and 7 years old, who had been admitted to the hospital with encephalitis. One of these two children died, and the doctor died after six days. All three were Nipah antibody positive. The overall case fatality rate of Nipah encephalitis cases was 88% (15/17).




Reported by: Faridpur Medical College Hospital, Faridpur; Institute of Epidemiology Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh; Programme of Infectious Diseases and Vaccine Sciences, ICDDR,B

Supported by: Institute of Epidemiology Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh; The Centers for Disease Control and Prevention, Atlanta, USA and the U.S. National Institutes of Health Division of Microbiology and Infectious Diseases, International Collaborations in Infectious Disease Opportunity Pool, Consortium of Conservative Medicine and Wild Life Trust.

Comments This large Nipah outbreak, across a wide geographic area in Faridpur district in 2010, suggests repeated introduction of the virus from its wildlife reservoir in Pteropus bats into people. Two of the infected persons subsequently transmitted the virus to caregivers, including a physician.

Previous outbreak investigations in Bangladesh provide compelling evidence of person-to-person transmission of Nipah infection (4). However, the infection and death of a physician who cared for Nipah patients was the first reported nosocomial transmission of Nipah virus in Bangladesh. Repeated episodes of person-to-person transmission of Nipah virus emphasize the importance of interrupting viral transmission through body fluids, both at household level and at healthcare facilities.
Several protective interventions to prevent person-to-person transmission should be prioritized through the development of appropriate, culturally sensitive health messages for the caregiver focusing on frequent hand washing, avoiding sharing of food and bed, and maintaining a three feet distance while caring for patients (two hands length). Also prompt isolation of patients with meningo-encephalitis syndrome during the Nipah virus season and implementation of basic infection control measures can reduce the risk to hospital staff and patients (5). As the laboratory diagnosis for Nipah virus is not available during initial evaluation of patients with meningo-encephalitis syndrome, health care workers should routinely practice basic infection control measures with every patient. Novice physicians should receive specific training on personal protective measures before beginning hospital duties.

References
Luby SP, Gurley ES, Hossain MJ. Transmission of human infection with Nipah virus. Clin Infect Dis 2009;49:1743-8.
ICDDR,B. Outbreaks of Nipah virus in Rajbari and Manikgonj, February 2008. Health Sci Bul 2008;6:12-3.
Hossain MJ, Gurley ES, Montgomery JM, Bell M, Carroll DS, Hsu VP, et al. Clinical presentation of Nipah virus infection in Bangladesh. Clin Infect Dis 2008;46:977-84.
Gurley ES, Montgomery JM, Hossain MJ, Bell M, Azad AK, Islam MR, et al. Person-to-person transmission of Nipah virus within a Bangladeshi Community. Emerg infect dis 2007;13:1031-7.
Chadha MS, Comer JA, Lowe L, Rota PA, Rollin PE, Belline WJ, et al. Nipah virus-associated encephalitis

http://www.icddrb.org/publication.cfm?classificationID=0&pubID=10930

[Ronan Kelly]

Re: Nipah outbreaks in Bangladesh - Historical

Nipah Virus Outbreak from Date Palm JuiceNipah Virus Outbreak from Date Palm Juice
We investigated an outbreak of encephalitis that affected 12 persons in Basail Upazila of Tangail District, in January 2005. Eleven persons (92%) died. Serum was available from three; two had IgM antibodies against Nipah/Hendra virus by capture enzyme immunoassay. Cases were significantly more likely than controls to drink raw date palm juice (64% among cases versus 18% among controls, odds ratio [OR] 7.9, P=0.01). Fruit bats (Pteropus giganteus) are a nuisance to date palm juice collectors because the bats drink from the clay pots used to collect the juice at night. This investigation identified another route whereby Nipah virus moves from P. giganteus to humans in Bangladesh.


Four outbreaks of Nipah virus have been recognized in central and west Bangladesh between 2001 and 2004 (1,2,3). Each outbreak occurred between January and May. These outbreaks have been associated with different exposures. In the first outbreak in Meherpur in 2001 Nipah cases were significantly more likely to have contact with a sick cow and an ill person’s secretions compared to controls (1). In the Naogaon outbreak in 2003, cases were more likely than controls to have had contact with a herd of pigs that had passed through the area prior to the outbreak (4). In Goalando in 2004, Nipah cases were significantly more likely to have climbed trees where bats may have been and to have contact with ill persons compared to controls (J Montgomery, Personal communication). In Faridpur in 2004, contact with ill persons was the primary risk for human Nipah disease (3).


P. giganteus fruit bats appear to be the wildlife reservoir for Nipah virus in Bangladesh. In the Naogaon investigation, two of 19 P. giganteus specimens had antibody against Nipah virus. None of 31 other animals tested had Nipah antibodies (1). A larger animal study in Goalando also found that P. giganteus was the only species with antibodies to Nipah virus (Darin Carrol, personal communication).


On January 11, 2005 government health workers in Tangail District reported that eight previously healthy persons from Basail Upazila had died within the preceding week from an illness characterized by fever and mental status changes. The Institute for Epidemiology, Disease Control and Research (IEDCR) of the government of Bangladesh immediately launched an investigation, and five days later invited ICDDR,B: Centre for Health and Population Research, to assist. The objectives of the investigation were to determine the cause of the outbreak, identify risk factors for developing illness and develop strategies for prevention.


The study team defined a case of outbreak associated encephalitis as a person who lived or travelled in Habla Union, Basail Upazila, Tangail district, Bangladesh and developed fever with the new onset of seizures or altered mental status between 15 December 2004 and 31 January 2005.


An anthropology team conducted in-depth interviews with the families of each case-patient. The objectives were to explore potentially relevant exposures, to assist in framing questions for the case-control questionnaire within the context of activities, understanding and language of local residents and, because most of the cases had died, to identify appropriate proxy respondents.


Based on the findings from the in-depth study, a standardized, closed ended questionnaire was developed. Trained interviewers administered the questionnaire to each case or his/her proxy(ies). Controls were identified by visiting the next closest house to the case, confirming that no one in the house met the case definition, identifying the household resident closest in age to the case, and then seeking consent to administer the questionnaire. Proxy respondents were identified for each case-patient who had died or was unable to respond for him/herself.


Serum samples were shipped on dry ice to the Centers for Disease Control and Prevention and tested with an immunoglobulin M capture enzyme immunoassay (EIA) for detection of Nipah/Hendra IgM antibodies and an indirect EIA for Nipah/Hendra IgG antibodies.


Twelve persons met the outbreak associated encephalitis case definition. Among cases the most common accompanying symptom was unconsciousness (Table 1). Their median age was 16 years (range 5-85); seven (58%) were male. Eleven (92%) of the persons who met the case definition died. Death occurred a median of four days (range 2-9) after the first reported symptom of illness. The onset of illness for all of the cases occurred within two weeks of each other (Figure 1).



Serum was collected from three people who met the outbreak associated encephalitis case definition. Two cases had IgM antibodies against Nipah/Hendra by capture enzyme immunoassay.


Interviewers enrolled 11 cases who met the encephalitis outbreak case definition and 33 matched controls. One case was excluded because appropriate proxy respondents with thorough knowledge of his exposures could not be identified. Proxy respondents were used for all case interviewers, and for six (17%) of control interviews.





The only exposure that was significantly associated with illness was drinking raw date palm juice (64% among cases versus 18% among controls, odds ratio [OR] 7.9, P=0.01). Of the 13 persons who reported consuming date palm juice, 11 knew from where the juice had been harvested. Ten (91%) reported that the juice was harvested from a single village.





Date palm juice collectors explained that at the outset of the season, a cut is made at the top of the tree to create an opening where the tap is placed. In the evening, a clay pot is positioned under the tap so that it can catch the dripping palm juice. Palm juice collectors climb the tree early in the morning to gather the palm juice just before distribution. Fresh date palm juice is sold early in the morning. If it is held more than a few hours it ferments and loses its sweet taste. Date palm tree owners view fruit bats as a nuisance because the bats frequently drink the palm juice directly from the tap or the clay pot. Signs of bat excrement on the outside of the clay pot or floating in the juice are common.


Reported by: Institute for Epidemiology Disease Control and Research, Ministry of Health and Family
Welfare, Government of Bangladesh; Clinical Sciences Division and Health Systems
and Infectious Diseases Division, ICDDR,B


Supported by: Institute for Epidemiology Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh; World Health Organization; The Centers for Disease Control and Prevention, Atlanta, USA and USAID, Dhaka Bangladesh


Comment


This is the fifth Nipah outbreak in five years that has been identified in the same region of Bangladesh. Each outbreak occurred between January and April. P. giganteus is widely distributed throughout Bangladesh (5). The reason the outbreaks are occurring in this region at this time of year may be related to increased Nipah virus shedding at the time of P. giganteus pregnancy and parturition and/or P. giganteus’ attraction to particular natural or agricultural foods that are seasonally available in this region.


Date palm juice was the likely vehicle of transmission for most of the Nipah infections in this particular outbreak. Moreover, date palm juice is a biologically plausible transmission route. Drinking fresh, raw date palm juice was the sole exposure significantly associated with illness. Nipah virus is shed from the saliva and urine of bats (6). Because fresh date palm juice is sold and consumed within a few hours of collection, even a virus that does not persist long outside of its host, might be able to survive in sufficient numbers for transmission. Indeed, the majority of the outbreak could have resulted from a single contamination of one pot of date palm juice by a single P. giganteus.


Fresh date palm juice is a national delicacy that is enjoyed by millions of Bangladeshis each winter. Apparently, the vast majority of servings of fresh date palm juice are safe to drink. However, this investigation illustrates that at least occasionally, the juice contains a sufficient dose of Nipah virus to be fatal to humans. Further research to define how frequently this occurs is important. Persons who want to avoid ingesting Nipah from this route, should avoid drinking raw date palm juice. Low cost interventions to restrict access of fruit bats to date palm taps and pots and so make fresh date palm juice safer should be developed and evaluated.


This outbreak provides further evidence that Nipah virus infection in humans is a seasonal disease in Bangladesh that results from interaction between P. giganteus fruit bats and humans. The different modes of transmission identified in outbreaks illustrate that there are several routes of viral spread to humans from fruit bats. Further investigations should continue to look for alternative routes and devise preventive strategies.
Reference
1. Hsu VP, Hossain MJ, Parashar UD, Ali MM, Ksiazek TG, Kuzmin I et al. Nipah virus encephalitis reemergence, Bangladesh. Emerg Infect Dis 2004 Dec;10(12):2082-7.
2. Nipah encephalitis outbreak over wide area of western Bangladesh, 2004. Health Science Bull 2004 Mar;2(1):7-11.
3. Person-to-person transmission of Nipah virus during outbreak in Faridpur District, 2004. Health Science Bull 2004 Jun;2(2):5-9.
4. Outbreaks of encephalitis due to Nipah/Hendra-like viruses, Western Bangladesh. Health Science Bull 2003 Dec;1(5):1-6.
5. Bates PJJ, Harrison D. Bats of the Indian Subcontinent. Sevenoaks: Harrison Zoological Museum, 1997.
6. Wacharapluesadee S, Lumlertdacha B, Boongird K, Wanghongsa S, Chanhome L, Rollin P et al. Bat Nipah virus, Thailand. Emerg Infect Dis 2005 Dec;11(12):1949-1951.

http://www.icddrb.org/publication.cfm?classificationID=0&pubID=6590

[Ronan Kelly]

Re: Nipah outbreaks in Bangladesh - Historical

Person-to-person transmission of Nipah virus during outbreak in Faridpur District, 2004

From 19 February to 16 April 2004, 36 residents of Faridpur district, Bangladesh became ill with Nipah virus encephalitis; 27 died—this was the second outbreak of Nipah virus encephalitis during 2004. Unlike previous Nipah virus outbreaks, the epidemiologic evidence from this latest outbreak supports person-to-person transmission. At least six patients developed acute respiratory distress syndrome (ARDS), not previously documented as a common feature of Nipah virus infection. Efforts continue to characterize risk factors for infection, enhance infection control measures in hospitals, and understand community beliefs about the virus in order to develop effective prevention messages.


On 5 April 2004 ICDDR,B and the Institute of Epidemiology and Disease Control (IEDCR) were alerted to six cases of lethal encephalitis which had occurred during the previous few weeks among family members and others living within a distinct geographic area in Faridpur district. An investigation began on 6 April at the request of the Ministry of Health and Family Welfare. The team was later joined by scientists from the Centers for Disease Control and Prevention-- Atlanta (CDC), Health Canada, and from Malaysia.


Nipah virus was determined to be the cause of the outbreak through evaluation of sera and other clinical material collected from patients with fever and mental status changes. As a result of surveillance and epidemiologic investigations, ultimately 36 residents of Faridpur District were identified with Nipah-associated illness, including an early case with onset of illness on 19 February (Figure 1); 27 (75%) patients died. Most cases were in adults; four (11%) were ≤15 years old. In addition to fever and mental status abnormalities, (including unconsciousness), cough, respiratory difficulty, headache, and vomiting occurred commonly. Chest radiographs were done in six patients; all showed bilateral infiltrates consistent with acute respiratory distress syndrome (ARDS) (Figure 2).


A laboratory confirmed case was defined by evidence of acute infection demonstrated by the presence of IgM antibodies to Nipah viruses in serum or CSF. A probable case was defined as a patient with fever and mental status changes, who lived or worked in the same village as a confirmed case. Serum specimens were obtained from 27 of 36 cases; 23 were laboratory confirmed. Four of the 27 had undetectable anti-Nipah virus antibody levels. These samples were collected early in the course of illness, perhaps before IgM seroconversion. These patients were categorized as probable cases, as they died before a subsequent sample could be collected for confirmation. An additional nine cases who were linked epidemiologically to laboratory confirmed Nipah cases died before diagnostic specimens were collected, and they were also designated as probable cases (total number of probable cases=13). Nipah virus RNA was also detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in throat swabs collected from several patients during this investigation.


The preliminary epidemiologic evidence clearly indicates that Nipah virus was primarily spread from person-to-person during this outbreak, perhaps through large droplet transmission. Patients lived in seven different villages, but were clustered in households and families. Prior to their illness onset, 33 of 36 (92%) cases had close contact with at least one person with confirmed or probable Nipah virus infection. Two people (Patients B and C) developed symptoms of Nipah infection seven and 11 days, respectively, after having close contact with their dying brother (Patient A); they also died. Patient A’s daughter (Patient D) and her husband (Patient E) became ill six and eight days after a visit to see Patient A late in his illness, and they also died. Patient A became ill on 19 March (Figure 1) and likely transmitted the virus to many other friends and family. Another patient (Patient F) was linked to a variety of subsequent cases. A man who supported Patient F while walking to a different residence during his illness and a rickshaw driver who transported Patient F to a hospital became sick 9 and 10 days, respectively, following one-time exposures; both died. Patient F was initially cared for at his father’s house some distance from Patient F’s home; patient F’s father, and a sister-in law (both of whom cared for patient F) also became severely ill. Patient F and his father died.





Figure 2: Radiographs from two paients with Nipah encephalitis


The research agenda and investigative strategies developed during this outbreak were based upon the evidence of person-to-person transmission and the need for a long-term approach to prevent and control Nipah virus infection in Bangladesh. Investigation and public health activities included: 1) infection control and patient isolation enhancement; 2) supportive care of patients within local hospitals; 3) a cohort study to determine specific types of behaviours and exposures that may have carried a high risk of transmission of illness; 4) collection and testing of specimens from Indian flying foxes (Pteropus giganteus); 5) assessment of environmental surfaces for presence of virus; 6) and behavioural research to characterize perceptions of Nipah-associated illness and healthcare seeking behaviours in the community. The findings of the behavioural research will be used for devising effective health communication strategies and messages.


Reported by: Institute of Epidemiology and Disease Control Research (IEDCR), Faridpur Medical College Hospital, Dhaka Medical College Hospital, Ministry of Health and Family Welfare; Faridpur General Hospital; World Health Organization (WHO); Health Canada; Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC, USA; Laboratory Sciences Division, Public Health Sciences Division, Clinical Sciences Division, and Health Systems and Infectious Diseases Division, ICDDR,B.


Supported by:Centers for Disease Control and Prevention (CDC), Atlanta, USA; Health Canada, Winnepeg, Canada; Canadian International Development Agency (CIDA), Dhaka; United States Agency for International Development (USAID), Dhaka


Comment


This is the fourth recognized outbreak of Nipah virus encephalitis in Bangladesh, and the second during 2004 (1). The findings of this report suggest that this outbreak was novel in two important ways. First, person-to-person transmission appears to have been the primary mode of spread. Previous outbreaks have been linked to animal sources and person-to-person transmission, while not ruled out, has not previously been clearly documented. (1-3) Second, ARDS occurred in a substantial number of cases during this outbreak, which has not been previously reported as a major symptom of Nipah-associated illness.


Documentation of person-to-person transmission of Nipah virus heightens the need for community containment and rapid isolation/hospitalization of suspect Nipah virus infected patients. Furthermore, appropriate infection control practices, isolation procedures and environmental hygiene within hospitals, are essential. While many cases became infected through caring for family and friends, there were no documented cases of Nipah infection among healthcare workers. There are several possible explanations for the lack of Nipah virus infection among healthcare workers. In the setting of this outbreak, family members, acting as patient attendants, generally had much closer contact with patients than that experienced by healthcare workers. In addition, many patients with Nipah-associated illness did not seek treatment in local hospitals or were hospitalized for very brief periods, limiting the potential for exposure to healthcare workers. Continuing efforts will focus on disseminating infection control protocols to healthcare facilities and developing effective prevention messages for the community, which will address minimizing risk of environmental and human transmission.


Transmission of Nipah virus to humans during this outbreak appears to have been bimodal. Fruit bats continue to be the only identified reservoir for the virus (1-4). During this outbreak, it appears that introduction of the virus into human(s) was followed by person-to-person transmission. Three cases had no known contact with a sick patient before onset of illness and two of these had no known association with other cases. These cases may have been infected through exposure to bat saliva, urine, or faeces, while subsequent cases were infected via exposure to infectious human secretions. During the time of the Faridpur outbreak another active Nipah infection was confirmed in a patient from Rajbari District- the focal point for the previous outbreak in January and February (1). In addition to the two outbreaks documented this year in Bangladesh, isolated, sporadically occurring cases continue to be identified (1).


Nipah-associated illness has emerged as a significant public health problem. While pneumonia, tuberculosis, malaria, and dengue have a much greater public health impact in Bangladesh, the sudden occurrence of several Nipah virus outbreaks with high case fatality rates have had a devastating and frightening impact on families and villages. It appears that there is a zone for epidemic (and perhaps endemic) Nipah virus transmission in western Bangladesh that may be referred to as a “Nipah Belt.??� Sustained, long term research is needed to characterize the reservoir of the virus and mechanisms for both animal-to-animal and animal-to-human transmission (in particular fruit bat mating and movement patterns, and viral shedding); understand the climatologic and other environmental factors linked to transmission; and to define viral epitopes potentially linked to virulence and transmission. Finally, appropriate infection control practices, hospital hygiene and heightened community awareness about this pathogen and the illness it causes, including how the probability of infection can be minimized, are greatly needed.


References


1. Nipah encephalitis outbreak over wide area of western Bangladesh, 2004. Health Sci Bull 2004;2(1):7-11.


2. Outbreak of encephalitis due to Nipah/Hendra-like viruses, western Bangladesh, Health Sci Bull 2003;1(5):1-6.


3. Yob JM, Field H, Rashdi AM, Morrissy C, van der Heide B, Rota P et al. Nipah virus infection in bats (order Chiroptera ) in peninsular Malaysia. Emerg Infect Dis 2001;7(3):439-41.


4. Olson JG, Rupprecht C, Rollin PE, An US, Niezgoda M, Clemins T et al. Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia. Emerg Infect Dis 2002;8(9):987-8.

http://www.icddrb.org/publication.cfm?classificationID=0&pubID=5252

[Ronan Kelly]

Re: Nipah outbreaks in Bangladesh - Historical

Nipah Encephalitis Outbreak Over Wide Area of Western Bangladesh, 2004Nipah Encephalitis Outbreak Over Wide Area of Western Bangladesh, 2004
During January and February 2004, an outbreak of Nipah encephalitis occurred. Twenty-nine laboratory confirmed or probable cases were identified; 22 patients died. While most cases occurred within Goalanda in Rajbari District, Nipah associated illness was also identified Joypurhat, Naogaon, Natore, Faridpur, Gopalganj, Manikganj, and Dhaka Districts. There was no clear evidence of person-to-person transmission during this outbreak. Fruit bats (Pteropus giganteus) appear to be the principal reservoir for the virus; ongoing studies have the objective of defining the modes of transmission.


During 12-17 January 2004, twelve residents of two contiguous villages in Goalanda, Rajbari District developed febrile illnesses progressing to coma; ten of these illnesses resulted in death. All but two of the patients were between the ages of seven and 15 years and eight were male. The patients lived in close proximity to each other, including three brothers who lived in one house and two brothers in another house, as well as a mother and toddler. Following notification about the cluster on 21 January, ICDDR,B and the Institute of Epidemiology and Disease Control Research (IEDCR) began a joint investigation on January 22 at the request of the MoHFW. Staff from the Centers for Disease Control and Prevention, Atlanta and from the World Health Organization, Geneva, arrived on 4 February to assist in the investigation.


Testing clinical specimens from these patients (serum specimens, cerebrospinal fluids (CSF)) for IgG and IgM antibodies and throat swabs and CSF for culturable virus and presence of Nipah virus RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) have demonstrated that Nipah virus is the cause of this outbreak.

The investigation team is focusing on defining the magnitude and geographic scope of infection with Nipah viruses during this outbreak, and on identifying reservoirs of the virus and sources of transmission. Civil surgeons in a variety of surrounding districts were contacted and asked to report similar cases, defined as fever associated with mental status change (including disorientation, delirium or coma). When possible, specimens from these cases were collected for laboratory testing to document infection with Nipah virus—many patients died before specimens could be obtained. A laboratory confirmed case was defined as a patient with evidence of acute infection demonstrated by the presence of IgM antibodies to Nipah viruses in serum or CSF. A probable case was defined as a patient with fever and mental status changes living near a confirmed case. The investigation also included collection and testing for Nipah virus infection from a variety of animals in areas with reported cases. Both human and animal specimens were sent to CDC in Atlanta for testing for evidence of Nipah infection.


Through 5 April 2004, 29 cases were identified through active case detection, including 14 laboratory confirmed cases; 22 (76%) died. While many were from Goalanda in Rajbari District, confirmed cases were also identified from as far as 150 kilometers away in Joypurhat, Naogaon, Natore, Faridpur, Gopalganj, Manikganj, and Dhaka Districts (Figure 1). Disease onset of most identified cases in these other areas was simultaneous or within a few weeks of that of the cases in Rajbari District (Figure 2). No information is available to link the two cases occurring in March in Natore and Dhaka with the other cases described in this report. No illnesses were identified among health care workers in facilities where cases were managed.

Figure 1: Location of residences for several clusters of cases






The investigation is ongoing and includes a case-control study to evaluate risk factors for infection, which may be helpful in characterizing how infection occurred, and a Nipah virus antibody prevalence study among 266 residents of Goalanda to determine the scope of current and previous virus transmission and the spectrum of clinical involvement following infection with Nipah virus (to evaluate whether milder illness or asymptomatic infection occurred). Over 450 animals, including bats, fowl, pigs, horses, goats, cows, rodents, shrews, cats and dogs were sampled and their specimens will be tested for evidence of Nipah infection over the coming weeks. Preliminary studies confirm that fruit bats (pteropus giganteus ) of the genus Pteropus have evidence of Nipah virus infection.


Reported by: Institute of Epidemiology and Disease Control Research, Dhaka Medical College Hospital, Rajshahi Medical College Hospital, Faridpur Medical College Hospital, Directorate General of Health Services, Ministry of Health & Family Welfare (MoHFW), Bangladesh; World Health Organization, Dhaka and Geneva; Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC-Atlanta, USA; Clinical Sciences Division, Laboratory Sciences Division and Health Systems and Infectious Diseases Division, ICDDR,B, Dhaka, Bangladesh

Supported by: Centers for Disease Control and Prevention, USA; World Health Organization
Comment

This is the third recognized outbreak of encephalitis in Bangladesh due to Nipah or Nipah-like viruses (1). Clinical materials from this outbreak investigation have allowed the isolation and genetic characterization of the causative agent, a strain of Nipah virus closely related but distinguishable from the virus that had caused a large outbreak of encephalitis in Malaysia in 1998-1999 (2). Diagnoses during the previous outbreaks were based on serological tests which made it impossible to define the precise identity of the etiologic agent; however, the isolation and characterization of Nipah viruses during the current outbreak increases the likelihood that the Nipah virus identified from patients is responsible for all three outbreaks. This suggests that there is a zone of periodic transmission of Nipah viruses from their reservoir hosts to man in western Bangladesh, and that this may result in clusters of human encephalitis.

Bats (fruit bats genus pteropus ) continue to be suspected to be the main reservoir for Nipah viruses (3-5). The ongoing investigation will attempt to define whether transmission occurred directly from bats to humans (perhaps via bat secretions or excrement or through ingesting fruits which had been contaminated by an infected bat) or whether other animals are involved in amplifying virus and transmitting to humans. The predominance of young boys within the Goalanda cluster suggests that a specific type of activity may have resulted in exposure to the virus; further epidemiologic studies combined with animal surveys may provide some suggestions as to the mode(s) of transmission. As in the previous Nipah virus outbreaks in Bangladesh, pigs did not appear to play a central role in maintenance and transmission of Nipah virus to man as occurred with the first outbreak of Nipah encephalitis in Malaysia and Singapore (6). Limited person-to-person transmission cannot be ruled out in this outbreak since several of the cases occurred within the same households but also shared common environmental exposures.

The occurrence of three outbreaks of Nipah encephalitis since 2001 raises questions about potential prevention and control strategies. The outbreaks have had devastating effects upon the villages where they have occurred. Current therapy for Nipah infection is supportive—with careful fluid management and respiratory care. Ribavirin, a very expensive antiviral therapeutic, has been said to improve outcomes (7). However, in vitro and laboratory animal studies have found the drug to have no effect on replication of the virus or disease outcome (Rollin, CDC, unpublished data). Prevention strategies await more information on mode of transmission, and may involve interventions that reduce the likelihood of direct exposure to Pteropus secretions, urine or faeces.


Added Note:
A new outbreak of Nipah virus encephalitis in Faridpur District is currently under investigation. As of April 25, 2004, 33 cases have been identified with 24 deaths. In contrast with previous outbreaks, there is evidence that person-to-person transmission may be responsible for many of the cases, and several patients have acute respiratory distress syndrome. The focus of the current efforts involving the MoHFW, WHO, ICDDR,B and CDC is on restricting transmission of the virus in the community and in hospitals, and on further characterizing how disease is being transmitted, defining the magnitude of the problem, identifying persistent animal reservoirs of the virus, and determining the genetic diversity of Nipah virus in Bangladesh. Updated information will be available in future issues of the HSB, and may be posted on the ICDDR,B website at www.icddrb.org.



References

Outbreaks of encephalitis due to Nipah/Hendra-like viruses, western Bangladesh. Health Sci Bull 2003;1(5):1-6.
Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK et al . Nipah virus: a recently emergent deadly paramyxovirus. Science 2000;288(5470):1432-5.
Chua KB, Koh CL, Hooi PS, Wee KF, Khong JH, Chua BH et al . Isolation of Nipah virus from Malaysian Island flying-foxes. Microbes Infect 2002;4(2):145-51.
Yob JM, Field H, Rashdi AM, Morrissy C, van der Heide B, Rota P et al . Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. Emerg Infect Dis 2001;7(3):439-41.
Olson JG, Rupprecht C, Rollin PE, An US, Niezgoda M, Clemins T et al. Antibodies to Nipah-like virus in bats (Pteropus lylei ), Cambodia. Emerg Infect Dis 2002;8(9):987-8.
Parashar UD, Sunn LM, Ong F, Mounts AW, Arif MT, Ksiazek TG et al . Case-control study of risk factors for human infection with a new zoonotic Paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia. J Infect Dis 2000;181(5):1755-9.
Chong HT, Kamarulzaman A, Tan CT, Goh KJ, Thayaparan T, Kunjapan SR, et al . Treatment of acute Nipah encephalitis with ribavirin. Annals of Neurology. 2001;49(6):810-3.

http://www.icddrb.org/publication.cfm?classificationID=0&pubID=5144

[Ronan Kelly]

Re: Nipah outbreaks in Bangladesh - Historical

Outbreaks of Encephalitis Due to Nipah/Hendra-like Viruses, Western Bangladesh
Two outbreaks of encephalitis, both caused by Nipah/Hendra-like viruses, occurred in separate areas in western Bangladesh in 2001 and 2003. Both outbreaks occurred over brief periods and had high case-fatality ratios. In contrast to previous experience with Hendra and Nipah viruses in which no human-to-human transmission had occurred in Australia, Malaysia and Singapore, epidemiologic characteristics of the outbreak in Bangladesh suggested the possibility of person-to-person transmission. Exposure to animals may have contributed to disease transmission to humans during the outbreaks but nevertheless, the ultimate source of the virus is its zoonotic reservoir.


Between 26 April and 26 May 2001, 9 deaths occurred among people with febrile illnesses and neurologic symptoms in Chandpur village of Meherpur district, 17 km from the border with India; 7 deaths occurred among people within the same family who lived within the same home or whose homes were adjacent to each other. The mean age was 40 years (range 32-60 years); 6 were males. During the same time interval, 18 other residents of the village were reported to have a similar illness and survived.

An investigation led by the Director General of Health Services (DGHS) in May 2001 was followed by a second investigation from 26 May to 1 June 2001 by a team that included staff from DGHS, the World Health Organization (WHO), and ICDDR,B. Results of antibody testing by enzyme-linked immunoassay (ELISA) done at the Centers for Disease Control and Prevention (CDC) in the United States suggested that at least 2 people in the Chandpur outbreak were infected with Nipah/Hendra-like viruses.

Between 11 and 28 January 2003, another outbreak of severe illness including features of encephalitis was reported affecting at least 17 residents (range 4-42 years) of Chalksita and Biljoania villages (located 45 km north-east of Rajshahi) in Naogaon district; 8 people died.


In February 2003, an investigative team from ICDDR,B and CDC-Atlanta visited Chandpur to learn more about the scope and risk factors for the first outbreak. Upon concluding studies in Chandpur, the team visited Naogaon District with the objective of defining the etiology and scope of the second outbreak.


The team collected specimens of blood from 119 residents of Chandpur and 89 residents of Chalksita and Biljoania villages who reportedly had been ill and recovered and those who were contacts (family members, close acquaintances, and neighbours of cases) of residents who had died, during either of the outbreaks. Sera were not available from any of the patients who died during the outbreaks.


Four people from Chandpur had evidence of antibodies (by ELISA) to Nipah antigen; all 4 had been ill during the outbreak period and were relatives of patients who died. Similarly, in Chalksita and Biljoania, 4 residents were found to have antibodies reactive with Nipah virus antigen; all 4 had been ill and had contact with patients who died. No health care workers were identified with illness during the outbreak periods.


A case of Nipah/Hendra-like virus infection was defined as a resident of one of the villages where the outbreaks occurred, who died during the outbreak periods, or who had measurable antibodies to Nipah virus antigen. A total of 13 cases (including 9 deaths) were identified from the first outbreak (Figure 1) and 12 cases (including 8 deaths) were identified from the second outbreak (Figure 2).





In Meherpur, the first case became ill on 20 April 2001 and this was followed by 11 cases through 8 May 2001 and one additional case occurred on May 20 (Figure 1). Median duration from onset of fever to death was 6 (range 3-9) days. In Naogaon, the first case occurred on 11 January and was quickly followed by a cluster of 7 cases; a second cluster of 4 cases began 10 daysafter the last case in the first cluster (Figure 2).


Fever, headache, and altered consciousness were the most common symptoms (Table 1). Cases in the Naogaon outbreak were more likely than non-cases to have had contact with a herd of pigs that had passed through the villages (Table 2). In the Meherpur outbreak, cases were more likely than non-cases to report contact with a cow during the two weeks before illness. Close contact with ill people in the Meherpur outbreak, including contact with patient secretions, was reported much more commonly in cases than in non-cases.


Table 1: Clinical characteristics of confirmed encephalitis cases by district


Meherpur (n=13)
Naogaon (n=12)

Symptoms
n (%)
n (%)

Fever
13 (100)
12 (100)

Headache
8 (62)
10 (83)

Altered level of consciousness
13 (100)
10 (83)

Dizziness
n/a
4 (33)

Seizures
3 (23)
3 (25)

Cough
10 (77)
6 (50)

Difficulty in breathing
9 (69)
7 (58)

Bleeding (nose, mouth, cough/sputum)
3 (23)
4 (33)

Vomiting
7 (54)
6 (50)

Diarrhoea
2 (15)
1 (8)

Focal weakness
n/a
2 (12)

Median (range) duration of onset of illness to death
6 (3-9)
4 (2-7)


n/a = Not applicable



Sera were collected from a variety of animals with the goal of identifying the source of the virus for these outbreaks. Antibodies reactive with Nipah virus antigens were found in 2 of 44 Pteropus giganteus bats tested, while none were found in the remaining animals tested including 2 other species of bats, pigs, rodents, shrews, pigeons, and dogs in areas near case-households.



Reported by: Division of Viral and Rickettsial Disease, National Center for Infectious Diseases, Centers for Disease Control and Prevention, USA; Health Systems and Infectious Diseases Division and Clinical Sciences Division, ICDDR,B


Supported by: Centers for Disease Control and Prevention, USA

Comment


Findings of this report suggest that Nipah/Hendra-like viruses were the etiological agents of both outbreaks. Because diagnoses were dependent on serologic tests in both outbreaks, the precise etiological agent is not known and may be due to a pathogen that cross-reacts with Nipah virus antigens in antibody assays.


Hendra and Nipah virus-associated illness was first recognized during outbreaks in Australia in 1994 and an epidemic in Malaysia and Singapore in 1998-1999 (1,2); 105 of 276 patients with laboratory-confirmed Nipah virus in Malaysia and Singapore died with viral encephalitis. Close contact with sick pigs was highly associated with human illness (3-5) but a few patients had no direct contact with pigs (3). No person-to-person transmission was shown (6).


The reservoir for Hendra and Nipah viruses are bats of the genus Pteropus. In Australia, horses have been the domestic link to human infections, while in Malaysia and Singapore pigs were clearly the linking animal host. Antibodies to Nipah viruses were identified in other animals (dogs, cats and horses) (7-9), but transmission from these animals to humans was not documented. Subsequent studies in Cambodia have also showed that evidence of infection (antibodies) with Nipah/Hendra-like viruses can be found in apparently healthy bats (10). No cases of human illness due to Nipah viruses were identified following the mass culling of >1 million pigs in Malaysia.


In contrast to the Australia, and the Malaysia/Singapore outbreaks, no clear source of transmission was identified for either of the outbreaks in Bangladesh summarized within this report. Because of the clustering of cases among family members and neighbours, the secondary peaks of cases following a period of no illnesses, and an epidemiologic suggestion of increased risk for illness among people who had exposure to secretions of other sick patients, person-to-person transmission cannot be ruled out. However, absence of illness among health care workers creates some uncertainty about this possibility. Increased risk of illness following exposure to pigs in one outbreak and a sick cow in the other raise the potential of animal-to-human transmission but this possibility cannot be validated with the limited data available.


Systematic surveillance for encephalitis is not routinely done in Bangladesh. It is possible that other outbreaks and sporadic cases of Nipah/Hendra-like virus encephalitis have occurred or will occur. More information will be needed to define the magnitude of the problem and to identify strategies to prevent illness and deaths. ICDDR,B is currently collaborating with Rajshahi Medical College Hospital, Mymensingh Medical College Hospital, and Dhaka Medical College Hospital in conducting hospital-based surveillance to define the epidemiology and etiologies of encephalitis in Bangladesh. This surveillance project may help to determine the role of Nipah/Hendra-like viruses in sporadically occurring disease and identify appropriate and optimal approaches to management and prevention of this serious disease syndrome.

References
Murray K, Selleck P, Hooper P, Hyatt A, Gould A, Gleeson L et al. A morbillivirus that caused fatal disease in horses and humans. Science 1995;268:94-97
Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK et al. Nipah virus: a recently emergent deadly paramyxovirus. Science 2000;288(5470):1432-1435
Parashar UD, Sunn LM, Ong F, Mounts AW, Arif MT, Ksiazek TG et al. Case control study of risk factors for human infection with a new zoonotic Paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia. J Infect Dis 2000;181(5):1755-9
Tan KS, Tan CT, Goh KJ. Epidemiological aspects of Nipah virus infection. Neurol J Southeast Asia 1999;4:77-81
Lam SK and Chua KB. Nipah virus encephalitis outbreak in Malaysia. Clinical Infectious Diseases 2002;34(suppl 2):S48-51
Tan CT, Tan KS. Nosocomial transmissibility of Nipah virus. J Infect Dis 2001;184:1367
Hooper PT, Williamson MM. Hendra and Nipah virus infections. Vet Clin North Am Equine Pract 2000;16:597-603
Chua KB, Koh CL, Hooi PS, Wee KF, Khong JH, Chua BH et al. Isolation of Nipah virus from Malaysian island flying-foxes. Microbes Infect 2002;4(2):145-51
Yob JM, Field H, Rashdi AM, Morrissy C, van der Heide B, Rota P et al. Nipah virus infection in bats (order Chiropetra) in peninsular Malaysia. Emerg Infect Dis 2001;7(3):439-41
Olson JG, Rupprecht C, Rollin PE, An US, Niezgoda M, Clemins T et al. Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia. Emerg Infect Dis 2002;8(9):987-8

http://www.icddrb.org/publication.cfm?classificationID=0&pubID=4673