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Research Detail

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M. Jahangir Hossain
International Centre for Diarrhoeal Disease Research

Emily S. Gurley
International Centre for Diarrhoeal Disease Research

Joel M. Montgomery
Centers for Disease Control and Prevention, Atlanta, Georgia

Michael Bell
Centers for Disease Control and Prevention, Atlanta, Georgia

Darin S. Carroll
Centers for Disease Control and Prevention, Atlanta, Georgia

Vincent P. Hsu
Centers for Disease Control and Prevention, Atlanta, Georgia

P. Formenty
Centers for Disease Control and Prevention, Atlanta, Georgia; and 5 World Health Organization, Geneva, Switzerland

A. Croisier
Centers for Disease Control and Prevention, Atlanta, Georgia; and 5 World Health Organization, Geneva, Switzerland

E. Bertherat
Centers for Disease Control and Prevention, Atlanta, Georgia; and 5 World Health Organization, Geneva, Switzerland

M. A. Faiz
Dhaka Medical College Hospital, Dhaka

Abul Kalam Azad
Institute of Epidemiology, Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh, Bangladesh

Rafiqul Islam
Institute of Epidemiology, Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh, Bangladesh

M. Abdur Rahim Molla
Institute of Epidemiology, Disease Control and Research, Ministry of Health and Family Welfare, Government of Bangladesh, Bangladesh

Thomas G. Ksiazek
Centers for Disease Control and Prevention, Atlanta, Georgia

Paul A. Rota
Centers for Disease Control and Prevention, Atlanta, Georgia

James A. Comer
Centers for Disease Control and Prevention, Atlanta, Georgia

Pierre E. Rollin
Centers for Disease Control and Prevention, Atlanta, Georgia

Stephen P. Luby
International Centre for Diarrhoeal Disease Research

Robert F. Breiman
International Centre for Diarrhoeal Disease Research

Background. In Bangladesh, 4 outbreaks of Nipah virus infection were identified during the period 2001– 2004. Methods. We characterized the clinical features of Nipah virus-infected individuals affected by these outbreaks. We classified patients as having confirmed cases of Nipah virus infection if they had antibodies reactive with Nipah virus antigen. Patients were considered to have probable cases of Nipah virus infection if they had symptoms consistent with Nipah virus infection during the same time and in the same community as patients with confirmed cases. Results. We identified 92 patients with Nipah virus infection, 67 (73%) of whom died. Although all age groups were affected, 2 outbreaks principally affected young persons (median age, 12 years); 62% of the affected persons were male. Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms; clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak. Among those who died, death occurred a median of 6 days (range, 2–36 days) after the onset of illness. Patients who died were more likely than survivors to have a temperature 1370C, altered mental status, difficulty breathing, and abnormal plantar reflexes. Among patients with Nipah virus infection who had well-defined exposure to another patient infected with Nipah virus, the median incubation period was 9 days (range, 6–11 days). Conclusions. Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems. Clinical characteristics of Nipah virus infection in Bangladesh, including a severe respiratory component, appear distinct from clinical characteristics reported during earlier outbreaks in other countries.

  Nipah Virus, Infection, Bangladesh
  In Bangladesh
  00-00-2001
  00-00-2004
  Risk Management in Agriculture
  Nipah virus

Hypothetically, a single strain of Nipah virus could result in a narrower range of clinical presentations than those found during epidemics associated with genetically diverse strains. Thus, Nipah virus illnesses occurring in Bangladesh potentially provide insight into broader clinical manifestations of Nipah virus infection. We describe the clinical presentation of 92 Nipah virus–infected patients identified during the first 4 outbreaks in Bangladesh during the period 2001–2004.

We investigated cases of Nipah virus infection from 4 outbreaks in the following regions: Meherpur District (from April through May 2001), Naogaon District (in January 2003), Rajbari (Goalanda subdistrict) and 7 other northwestern districts (from January through April 2004), and Faridpur District (from February through April 2004). The investigations for the first and second outbreaks, in Mehepur and Naogaon, took place after the outbreaks occurred. Because of increased awareness of Nipah virus among health officials, the third and fourth outbreaks, in Rajbari and Faridpur, were reported to authorities and investigated while the outbreaks were ongoing. Therefore, the case definitions and case detection methods differed slightly because of differences in the timing of investigations.

Outbreaks of Nipah virus infection in Meherpur and Naogaon. The investigation of the Meherpur outbreak was conducted 2 years after the outbreak, and the investigation of the Naogaon outbreak was performed 2 months after the outbreak. Patients with suspected cases of Nipah virus infection were persons residing in the outbreak areas who experienced fever with either headache or altered mental status during the time of the outbreak. Field research assistants identified patients with suspected cases during house–to-house case-finding efforts. Study physicians collected illness histories from either patients with suspected cases or their caregivers (when the patients were minors or decedents) using a standardized case report form. We also collected information from hospital records, if available. A 5-mL blood specimen was collected from each living patient with a suspected case, and the serum was transported to the International Centre for Diarrhoeal Disease Research, Bangladesh (Dhaka), on ice for storage at 70C. Serum samples were then shipped to the Centers for Disease Control and Prevention (Atlanta, GA) for Nipah virus serologic testing. Patients with suspected cases of Nipah virus infection who survived and had evidence of the infection, demonstrated by the presence of either IgM or IgG antibodies, were considered to have laboratory-confirmed cases. Patients with suspected cases who died during the outbreak, experienced fever with altered mental status, and were linked to patients with laboratory-confirmed cases by place of residence and timing of symptom onset were considered to have had probable cases of Nipah virus infection.

Outbreaks of Nipah virus infection in Rajbari and Faridpur. The Rajbari and Faridpur cases were investigated while the outbreaks were ongoing. A similar definition for a suspected case (fever and headache or altered mental status) was used during these investigations. However, because many severely ill patients with suspected cases also presented with respiratory symptoms, patients with a history of cough and fever were also considered to have suspected cases. Patients with suspected cases of Nipah virus infection were identified by house-to-house and hospital visits in the affected area. Physicians working with the investigation team collected illness histories from patients with suspected cases or their caregivers (when the patients were minors, decedents, or unable to provide personal histories because of altered mental status) using a standardized case report form. They verified clinical information by physical examination of the surviving patients (when possible) and by reviewing hospital records (when available). Case-finding efforts were expanded to 7 northwestern districts from January through April 2004. Tertiary care hospitals in the region were visited, and all patients hospitalized with fever and altered mental status during this period were investigated. We identified 19 additional cases of Nipah virus infection during this effort; some were clustered, and some were isolated. We included these 19 cases with the cases identified in Rajbari District for this report, because the cases were identified beginning with the Rajbari outbreak in January. We obtained acute serum samples from all living patients with suspected Nipah virus infection and convalescent serum samples at least 10 days after onset of illness from patients surviving acute illness. In addition to blood samples, we obtained throat swab, urine, and when possible, CSF samples from hospitalized patients with altered mental status. Serum and CSF samples were assayed for the presence or absence of Nipah virus–specific IgM and IgG antibodies, as described elsewhere. CSF and throat swab specimens were tested for presence of Nipah virus RNA by RT-PCR using a primer set to detect the nucleocapsid gene, as described elsewhere [7]. Attempts were also made to isolate virus from CSF, throat swab, and urine specimens by placing 100 uL of specimen in cell culture, according to methods described elsewhere. The samples were transported and stored in the same manner as in the first 2 outbreaks.

Patients with suspected cases who had evidence of Nipah virus infection, demonstrated by the presence of Nipah virus IgM antibodies or by isolation of Nipah virus, were considered to have laboratory-confirmed cases. Although other laboratory tests were performed, they were not considered to be reliable enough to use for the case definition. Patients with probable cases were those who had fever with altered mental status or breathing difficulty and whose cases were part of a cluster of laboratory-confirmed cases in the outbreak region; adequate specimens (including convalescent-phase specimens) for detection of Nipah virus antibodies could not be obtained from these patients because of fatal outcomes. Those with specimens (including convalescent-phase serum specimens) shown to be Nipah virus negative using all Nipah virus tests were considered to not be infected with Nipah virus.

Statistical analysis. Clinical findings were contrasted between patients with fatal outcomes and patients who survived. Pearson’s x2 test or Fisher’s exact test and univariate logistic regression were performed to determine ORs. Normally distributed continuous variables were analyzed using Student’s t test, and nonnormally distributed continuous variables were analyzed using the Mann-Whitney U test. Associations were considered to be statistically significant at . Stata, version P ! .05 8.0 (Stata), was used for statistical analysis. 

  Clinical Presentation of Nipah Virus • CID 2008:46 (1 April) • 977
  
Funding Source:
1.   Budget:  
  

The findings of our investigation suggest that Nipah virus infections occurred in all age groups and that fever, altered mental status, cough, and respiratory symptoms were the most common symptoms among those infected in Bangladesh. Severe neurologic manifestations are consistently the most substantial and severe components of Nipah virus infection. Severe chronic sequelae occur in many survivors, adding to the significant public health burden of Nipah virus–associated disease. Future priorities should include ongoing surveillance and investigation of outbreaks of Nipah virus infection, identification and evaluation of strategies to prevent Nipah virus transmission, and improvement of clinical management of cases in resource-poor settings

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