M. Rahman

Nipah virus outbreak with person-to-person transmission in a district of Bangladesh, 2007

In February 2007 an outbreak of Nipah virus (NiV) encephalitis in Thakurgaon District of northwest Bangladesh affected seven people, three of whom died. All subsequent cases developed illness 7-14 days after close physical contact with the index case while he was ill. Cases were more likely than controls to have been in the same room (100% vs. 9.5%, OR undefined, P<0.001) and to have touched him (83% vs. 0%, OR undefined, P<0.001). Although the source of infection for the index case was not identified, 50% of Pteropus bats sampled from near the outbreak area 1 month after the outbreak had antibodies to NiV confirming the presence of the virus in the area. The outbreak was spread by person-to-person transmission. Risk of NiV infection in family caregivers highlights the need for infection control practices to limit transmission of potentially infectious body secretions.

Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial

BACKGROUNDnInfluenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh.nnnMETHODSnWe undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010. Patients with a positive rapid influenza test identified by surveillance of households in Kamalapur, Bangladesh were randomly allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5 days. Randomisation lists for individuals enrolled less than 48 h and 48 h or longer since illness onset were generated with permuted blocks of variable length between two and eight. Participants and study staff were masked to treatment group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days later, and were visited daily to record symptoms. All specimens were tested for influenza with reverse-transcriptase PCR, and if the result was positive, we isolated the virus. The primary endpoints were duration of clinical illness and viral shedding in patients treated less than and more than 48 h since illness onset and the frequency of oseltamivir resistance during treatment. Analyses were intention to treat unless otherwise specified. This trial is registered with ClinicalTrials.gov, number NCT00707941.nnnFINDINGSnOverall, 1190 people with a median age of 5 years (IQR 2-9) were enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or longer since symptom onset. 592 participants were assigned to placebo and 598 to oseltamivir. The median duration of symptoms was shorter in the oseltamivir group (3 days, IQR 1-5) than in the placebo group (4 days, 1-6; p=0.01). When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups (oseltamivir 3 days [IQR 2-5], placebo 3 days [1-5]; p=0.04). The median duration of symptoms was reduced by 1 day in the group given oseltamivir who were enrolled less than 48 h since symptom onset compared with those given placebo, but this difference was not significant. In those with all swab specimens (n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo 374 [66%] vs oseltamivir 321 [56%]; difference 15.2%, 95% CI 9.5-20.8, p=0.0004), 4 (241 [43%] vs 174 [30%]; difference 30.2%, 95% CI 24.6-35.8, p<0.0001), and 7 (68 [12%] vs 36 [6%]; difference 47.5%, 95% CI 44.2-50.8, p=0.0009). In participants enrolled 48 h or longer since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2 and 4, but not day 7. In participants enrolled less than 48 h since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2, 4, and 7. The emergency of resistance to oseltamivir during treatment was rare overall (<1%) and in influenza A H1N1pdm09 viruses (3.9%).nnnINTERPRETATIONnOseltamivir treatment resulted in a modest reduction in the duration of symptoms and virus shedding in people with uncomplicated influenza infections, even when treatment was started 48 h or longer after illness onset.nnnFUNDINGnCenters for Disease Control and Prevention (in agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).

Bangladesh moves from being a low-prevalence nation for HIV to one with a concentrated epidemic in injecting drug users

Bangladesh has been conducting annual serological surveillance for HIV and syphilis since 1998 among most at-risk populations including sex workers, males having sex with males, injecting drug users (IDUs) and heroin smokers. During the seventh round conducted between January and June 2006, 10,368 people were sampled and the overall HIV prevalence was 0.9%. The highest HIV rate was recorded in male IDUs from the capital city Dhaka (7%), and the rates have risen significantly over the rounds (P < 0.001). In Dhaka, most of the HIV-positive IDUs (10.5%) were localized in one neighbourhood, while in the remaining neighbourhoods 1% were positive (P < 0.001). In all other groups, HIV prevalence was P < 0.001). Bangladesh has to act urgently to prevent escalation of the epidemic.

Identification and Epidemiology of a Rare HoBi‐Like Pestivirus Strain in Bangladesh

The genus pestivirus of the family flaviviridae consists of four recognized species: bovine viral diarrhoea virus 1 (BVDV-1), bovine viral diarrhoea virus 2 (BVDV-2), classical swine fever virus and border disease virus. A new putative pestivirus species tentatively named as either HoBi-like pestivirus or BVDV-3 has recently been identified in Brazil, Italy and Thailand. Despite reports of serological evidence of BVDV in Bangladesh, the types of the virus circulating in cattle have not been identified. We conducted surveillance in cattle from May 2009 to August 2010 in three government veterinary hospitals to characterize BVDV in cattle of Bangladesh. We tested serum for BVDV using an antigen-capture ELISA. Of 638 cattle samples, 3% (16/638) tested positive for BVDV antigen. The ELISA-positive samples were selected for further molecular detection and characterization of BVDV. Molecular analysis of the partial 5 untranslated region (UTR) nucleotide sequences of BVDV-positive samples identified the rare HoBi-like pestivirus or BVDV-3 virus circulating in cattle of Bangladesh. The identification of this rare HoBi-like pestivirus or BVDV-3 strain in Bangladesh warrants further surveillance to evaluate its impact on livestock production.

Evolving epidemiology of Nipah virus infection in Bangladesh: evidence from outbreaks during 2010–2011

Drinking raw date palm sap is the primary route of Nipah virus (NiV) transmission from bats to people in Bangladesh; subsequent person-to-person transmission is common. During December 2010 to March 2011, we investigated NiV epidemiology by interviewing cases using structured questionnaires, in-depth interviews, and group discussions to collect clinical and exposure histories. We conducted a case-control study to identify risk factors for transmission. We identified 43 cases; 23 were laboratory-confirmed and 20 probable. Thirty-eight (88%) cases died. Drinking raw date palm sap and contact with an infected person were major risk factors; one healthcare worker was infected and for another case transmission apparently occurred through contact with a corpse. In absence of these risk factors, apparent routes of transmission included drinking fermented date palm sap. For the first time, a case was detected in eastern Bangladesh. Identification of new epidemiological characteristics emphasizes the importance of continued NiV surveillance and case investigation.

Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

&NA; Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June–July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north‐eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza‐like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real‐time RT‐PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small‐scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza‐like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate diagnostic testing and detect novel influenza strains.

An outbreak of hepatitis E in an urban area of Bangladesh

We investigated an outbreak of jaundice in urban Bangladesh in 2010 to examine the cause and risk factors and assess the diagnostic utility of commercial assays. We classified municipal residents reporting jaundice during the preceding 4 weeks as probable hepatitis E cases and their neighbours without jaundice in the previous 6 months as probable controls. We tested the sera collected from probable cases and probable controls for IgM anti‐hepatitis E virus (HEV), and the IgM‐negative sera for IgG anti‐HEV using a commercial assay locally. We retested the IgM‐positive sera for both IgM and IgG anti‐HEV using another assay at the Centre for Disease Control and Prevention (CDC), USA. Probable cases positive for IgM anti‐HEV were confirmed cases; probable controls negative for both IgM and IgG anti‐HEV were confirmed controls. We explored the local water supply and sanitation infrastructure and tested for bacterial concentration of water samples. Probable cases were more likely than probable controls to drink tap water (adjusted odds ratio: 3.4; 95% CI: 1.2–9.2). Fifty‐eight percentage (36/62) of the case sera were IgM anti‐HEV positive; and 75% of the IgM‐positive samples were confirmed positive on retesting with another assay at CDC. Compared to confirmed controls, cases confirmed using either or both assays also identified drinking tap water as the risk factor. Two tap water samples had detectable thermotolerant coliforms. Research exploring decentralized water treatment technologies for sustainable safe water might prevent HEV transmission in resource‐poor cities. Detection of serological markers in a majority of probable cases implied that available diagnostic assays could adequately identify HEV infection during outbreaks.

Effects of oseltamivir treatment of index patients with influenza on secondary household illness in an urban setting in Bangladesh: secondary analysis of a randomised, placebo-controlled trial

BACKGROUNDnAntiviral drugs are a proposed medical intervention to reduce household transmission of influenza viruses. In a previously described randomised, placebo-controlled trial in Dhaka, Bangladesh, we showed that oseltamivir treatment of index patients was able to reduce influenza symptom duration and virus shedding. In a further analysis that is part of the same study, we aimed to assess efficacy of oseltamivir to reduce secondary household illnesses in the same cohort.nnnMETHODSnIn this double-blind oseltamivir efficacy trial, we identified index patients aged older than 1 year through surveillance of households in Dhaka, Bangladesh. We randomly allocated eligible patients (1:1) to receive oseltamivir or placebo twice-daily for 5 days, and we stratified them by enrolment 48 h versus 48-120 h since illness onset. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days after enrolment and were visited daily by a research assistant to record symptoms, both in index patients and in household members. For this part of the study, household members were asked to give respiratory specimens for influenza PCR testing. Our primary outcomes were household secondary illness and PCR-confirmed influenza virus infection, assessed in household members of all randomly allocated index patients. This trial is registered with ClinicalTrials.gov, number NCT00707941.nnnFINDINGSnFrom May 11, 2008, to Dec 31, 2010, we enrolled 1190 index patients with 4694 household members. 592 patients were allocated to placebo (2292 household members) and 598 to oseltamivir (2402 household members). Household secondary illness was lower in the oseltamivir group (196 [8%] influenza cases) than in the placebo group (233 [10%]; odds ratio [OR] 0·77, 95% CI 0·60-0·98, p=0·031). PCR-confirmed influenza virus infection did not differ between the placebo (103 [5%]) and oseltamivir groups (92 [4%]; 0·84, 0·59-1·19, p=0·319); however, only 243 (57%) of ill household members gave a specimen for analysis.nnnINTERPRETATIONnIn a crowded, low income setting, oseltamivir treatment of index patients resulted in a small reduction of secondary influenza in their households. Even this slight reduction, in the setting of widespread antiviral use during a community influenza outbreak, might result in reductions in overall disease burden.nnnFUNDINGnCenters for Disease Control and Prevention (in an agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).

Integrated cluster- and case-based surveillance for detecting stage III zoonotic pathogens: an example of Nipah virus surveillance in Bangladesh

SUMMARY This paper explores the utility of cluster- and case-based surveillance established in government hospitals in Bangladesh to detect Nipah virus, a stage III zoonotic pathogen. Physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. Physicians collected blood samples from the clustered cases. As part of case-based surveillance, blood was collected from all listed meningo-encephalitis cases in three hospitals during the Nipah season (January–March). An investigation team visited clustered cases’ communities to collect epidemiological information and blood from the living cases. We tested serum using Nipah-specific IgM ELISA. Up to September 2011, in 5887 listed cases, we identified 62 clusters comprising 176 encephalitis cases. We collected blood from 127 of these cases. In 10 clusters, we identified a total of 62 Nipah cases: 18 laboratory-confirmed and 34 probable. We identified person-to-person transmission of Nipah virus in four clusters. From case-based surveillance, we identified 23 (4%) Nipah cases. Faced with thousands of encephalitis cases, integrated cluster surveillance allows targeted deployment of investigative resources to detect outbreaks by stage III zoonotic pathogens in resource-limited settings.

Serological evidence of hepatitis E virus infection in pigs and jaundice among pig handlers in Bangladesh

Hepatitis E virus (HEV) is the most common cause of viral hepatitis in humans. Pigs may act as a reservoir of HEV, and pig handlers were frequently identified with a higher prevalence of antibodies to HEV. The objectives of this study were to identify evidence of HEV infection in pigs and compare the history of jaundice between pig handlers and people not exposed to pigs and pork. Blood and faecal samples were collected from 100 pigs derived from three slaughterhouses in the Gazipur district of Bangladesh from January to June, 2011. We also interviewed 200 pig handlers and 250 non‐exposed people who did not eat pork or handled pigs in the past 2 years. We tested the pig sera for HEV‐specific antibodies using a competitive ELISA and pig faecal samples for HEV RNA using real‐time RT‐PCR. Of 100 pig sera, 82% (n = 82) had detectable antibody against HEV. Of the 200 pig handlers, 28% (56/200) demonstrated jaundice within the past 2 years, whereas only 17% (43/250) of controls had a history of jaundice (p < .05). Compared to non‐exposed people, those who slaughtered pigs (31% versus 15%, p < .001), reared pigs (37% versus 20%, p < .001), butchered pigs (35% versus 19%, p < .001) or involved in pork transportation (28% versus 13%, p < .001) were more likely to be affected with jaundice in the preceding 2 years. In multivariate logistic regression analysis, exposure to pigs (odds ratio [OR]: 2.2, 95% CI: 1.2–3.9) and age (OR: 0.97, 95% CI: 0.95–0.99) was significantly associated with jaundice in the past 2 years. Pigs in Bangladesh demonstrated evidence of HEV infection, and a history of jaundice was significantly more frequent in pig handlers. Identifying and genotyping HEV in pigs and pig handlers may provide further evidence of the pigs role in zoonotic HEV transmission in Bangladesh.