An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully.

BACKGROUND We evaluated the immunogenicity of the pentavalent rotavirus vaccine (PRV) in two GAVI-eligible Asian countries, Bangladesh and Vietnam, nested in a larger randomized, double-blind, placebo-controlled efficacy trial conducted over a two-year period from 2007 through 2009. METHODS 2036 infants were randomly assigned, in a 1:1 ratio, to receive three oral doses of PRV or placebo approximately at 6, 10, and 14 weeks of age. Concomitant use of EPI vaccines, including oral poliovirus vaccine (OPV) and diphtheria-tetanus-whole cell pertussis (DTwP) vaccine, was encouraged in accordance to the local EPI schedule. A total of 303 infants were evaluated for immunogenicity and blood samples were collected before the first dose (pD1) and approximately 14 days following the third dose (PD3). The seroresponse rates (≥3-fold rise from pD1 to PD3) and geometric mean titers (GMTs) were measured for anti-rotavirus immunoglobulin A (IgA) and serum neutralizing antibody (SNA) to human rotavirus serotypes G1, G2, G3, G4, and P1A[8], respectively. RESULTS Nearly 88% of the subjects showed a ≥3-fold increase in serum anti-rotavirus IgA response in the analysis of the two countries combined. When analyzed separately, the IgA response was lower in Bangladeshi children (78.1%[95% CI: 66.0, 87.5]) than in Vietnamese children (97.0%[95% CI: 89.6, 99.6]), with a PD3 GMT of 29.1 (units/mL) and 158.5 (units/mL), respectively. In the combined population, the SNA responses to the individual serotypes tested ranged from 10 (G3) to 50 (G1) percentage points lower than the responses shown in the developed countries. However, the SNA response to G3 in Vietnamese subjects was 37.3%(95% CI: 25.8, 50.0), which was similar to the G3 response rate in developed countries. CONCLUSIONS Three oral doses of PRV were immunogenic in two GAVI-eligible Asian countries: Bangladesh and Vietnam. The GMTs of both the serum anti-rotavirus IgA and SNA responses were generally higher in Vietnamese than in Bangladeshi children. The SNA responses varied by individual serotypes and were lower than the results from developed countries. The clinical significance of these observations is not understood because an immune correlate of protection has not been established.

OBJECTIVE To estimate influenza-associated mortality in Bangladesh in 2009. METHODS In four hospitals in Bangladesh, respiratory samples were collected twice a month throughout 2009 from inpatients aged < 5 years with severe pneumonia and from older inpatients with severe acute respiratory infection. The samples were tested for influenza virus ribonucleic acid (RNA) using polymerase chain reaction. The deaths in 2009 in five randomly selected unions (the smallest administrative units in Bangladesh) in each hospital's catchment area were then investigated using formal records and informal group discussions. The deaths of those who had reportedly died within 14 days of suddenly developing fever with cough and/or a sore throat were assumed to be influenza-associated. The rate of such deaths in 2009 in each of the catchment areas was then estimated from the number of apparently influenza-associated deaths in the sampled unions, the proportion of the sampled inpatients in the local hospital who tested positive for influenza virus RNA, and the estimated number of residents of the sampled unions. FINDINGS Of the 2500 people known to have died in 2009 in all 20 study unions, 346 (14%) reportedly had fever with cough and/or sore throat within 14 days of their deaths. The estimated mean annual influenza-associated mortality in these unions was 11 per 100 000 population: 1.5, 4.0 and 125 deaths per 100 000 among those aged < 5, 5-59 and > 59 years, respectively. CONCLUSION The highest burden of influenza-associated mortality in Bangladesh in 2009 was among the elderly.

BACKGROUND Pneumonia is the leading cause of childhood death in Bangladesh. We conducted a longitudinal study to estimate the incidence of virus-associated pneumonia in children aged <2 years in a low-income urban community in Dhaka, Bangladesh. METHODS We followed a cohort of children for two years. We collected nasal washes when children presented with respiratory symptoms. Study physicians diagnosed children with cough and age-specific tachypnea and positive lung findings as pneumonia case-patients. We tested respiratory samples for respiratory syncytial virus (RSV), rhinoviruses, human metapneumovirus (HMPV), influenza viruses, human parainfluenza viruses (HPIV 1, 2, 3), and adenoviruses using real-time reverse transcription polymerase chain reaction assays. RESULTS Between April 2009-March 2011, we followed 515 children for 730 child-years. We identified a total of 378 pneumonia episodes, 77% of the episodes were associated with a respiratory viral pathogen. The overall incidence of pneumonia associated with a respiratory virus infection was 40/100 child-years. The annual incidence of pneumonia/100 child-years associated with a specific respiratory virus in children aged <2years was 12.5 for RSV, 6 for rhinoviruses, 6 for HMPV, 4 for influenza viruses, 3 for HPIV and 2 for adenoviruses. CONCLUSION Young children in Dhaka are at high risk of childhood pneumonia and the majority of these episodes are associated with viral pathogens. Developing effective low-cost strategies for prevention are a high priority.

OBJECTIVE To determine how much influenza contributes to severe acute respiratory illness (SARI), a leading cause of death in children, among people of all ages in Bangladesh. METHODS Physicians obtained nasal and throat swabs to test for influenza virus from patients who were hospitalized within 7 days of the onset of severe acute respiratory infection (SARI) or who consulted as outpatients for influenza-like illness (ILI). A community health care utilization survey was conducted to determine the proportion of hospital catchment area residents who sought care at study hospitals and calculate the incidence of influenza using this denominator. FINDINGS The estimated incidence of SARI associated with influenza in children < 5 years old was 6.7 (95% confidence interval, CI: 0-18.3); 4.4 (95% CI: 0-13.4) and 6.5 per 1000 person-years (95% CI: 0-8.3/1000) during the 2008, 2009 and 2010 influenza seasons, respectively. The incidence of SARI in people aged ≥ 5 years was 1.1 (95% CI: 0.4-2.0) and 1.3 (95% CI: 0.5-2.2) per 10,000 person-years during 2009 and 2010, respectively. The incidence of medically attended, laboratory-confirmed seasonal influenza in outpatients with ILI was 10 (95% CI: 8-14), 6.6 (95% CI: 5-9) and 17 per 100 person-years (95% CI: 13-22) during the 2008, 2009 and 2010 influenza seasons, respectively. CONCLUSION Influenza-like illness is a frequent cause of consultation in the outpatient setting in Bangladesh. Children aged less than  5 years are hospitalized for influenza in greater proportions than children in other age groups.

To explore Bangladesh's ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June-July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.

Rotavirus strain diversity in Bangladesh has been explored since 1985 and as seen in other parts of the world, rotaviruses have shown tremendous strain diversity overtime. Rotavirus antigen was detected in stool specimens using a solid-phase sandwich-type enzyme immunoassay. A multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed for rotavirus G and P genotypes. This current study was carried out between 2006 and 2009 during which time 1,607 (23%) of 7,058 fecal specimens tested positive for group A rotaviruses with the highest incidence rate being observed in winter each year. Genotyping of rotaviruses showed a sharp decline in G2P[4] between 2008 and 2009 with a gradual increase in G1 and G9 strains. Since the Government of Bangladesh is planning to include rotavirus vaccine in the national immunization program, these data on rotavirus strain diversity should be taken into consideration for vaccine strain selection.

AIMS To provide an overview of the availability of pharmaceutical opioids and the evidence on the extent of diversion and injection in South Asia. METHODS This paper reviews existing peer-reviewed and 'grey' literature on the extramedical use and injection of pharmaceutical opioids in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. RESULTS Reports indicate that prescribing for all types of pain is inadequate. There is a paucity of empirical data across South Asia regarding the mechanisms and extent of the diversion and misuse of pharmaceutical opioids, although the problem is widely acknowledged. India is believed to account for significant large-scale diversion within the region and further afield through poor regulation of licit opioid production and pharmacies. A recent decline in use of natural opiates has been accompanied by an increase in pharmaceutical opioid misuse and increasingly, injection, particularly in Bangladesh, India, Nepal and Pakistan. The medications are typically buprenorphine preparations and/or other lower potency opioids, such as codeine, nalbuphine and dextropropoxyphene. Opioid substitution treatment and needle-syringe programs are available in some countries, but better coverage is needed. Studies identify a lack of comprehensive knowledge regarding HIV and high prevalence of risk behaviours among at-risk populations in the region. CONCLUSIONS It is imperative for the region to rapidly facilitate access to opioids for the treatment of pain and opioid dependence, ensuring effective systems that maintain quality care, regulate and monitor retail pharmacies, and minimise diversion. Prevention of HIV among people who inject pharmaceutical opioids is essential.

Despite the known presence of rotavirus-associated diarrhoea in Bangladesh, its prevalence, including records of hospitalization in rural health facilities, is largely unknown. In a systematic surveillance undertaken in two government-run rural health facilities, 457 children, aged less than five years, having acute watery diarrhoea, were studied between August 2005 and July 2007 to determine the prevalence of rotavirus. Due to limited financial support, the surveillance of rotavirus was included as an addendum to an ongoing study for cholera in the same area. Rotavirus infection was detected in 114 (25%) and Vibrio cholerae in 63 (14%) children. Neither rotavirus nor V cholerae was detected in 280 (61%) samples; these were termed 'non-rotavirus and non-cholera' diarrhoea. Both rotavirus and cholera were detected in all groups of patients (<5 years). The highest proportion (41%; 47/114) of rotavirus was in the age-group of 6-11 months. In children aged less than 18 months, the proportion (67%; 76/114) of rotavirus was significantly (p < 0.001) higher than that of cholera (16%; 10/63). By contrast, the proportion (84%; 53/63) of cholera was significantly (p < 0.001) higher than that of rotavirus (33%; 38/114) in the age-group of 18-59 months. During the study period, 528 children were hospitalized for various illnesses. Thirty-eight percent (202/528) of the hospitalizations were due to acute watery diarrhoea, and 62% were due to non-diarrhoeal illnesses. Rotavirus accounted for 34% of hospitalizations due to diarrhoea. Severe dehydration was detected in 16%(74/457) of the children. The proportion (51%; 32/63) of severe dehydration among V cholerae-infected children was significantly higher (p < 0.001) compared to the proportion (16%; 18/114) of rotavirus-infected children. The study revealed that 12-14% of the hospitalizations in rural Bangladesh in this age-group were due to rotavirus infection, which has not been previously documented.

Strategic information is fundamental to the formulation and delivery of effective HIV programmes, but generating that information is a complex process, for which most countries in south and south-east Asia lack capacity and supporting structures. Although most countries in this region have made tremendous strides in collecting relevant data, advances in the ability to translate that data into strategic information and evidence for action, have not kept pace. To overcome these shortcomings, this paper presents a comprehensive approach to collecting strategic information and building the capacity to use it effectively, which is based on experience in the successful use of data in different countries in south and south-east Asia. The system recommended here requires that staff and resources carry out four major functions: implement an early alert and response system allowing for the timely collection, synthesis and use of information to respond quickly to emerging epidemics; carefully analyze data to develop policy scenarios and resource projections to guide decision-making; periodically evaluate the impact of the current response and make recommendations to improve it; and engage policy-makers in ways that proactively promote improvements to current programmes based on evidence. At present, countries in this region are carrying out these functions in an ad-hoc and uncoordinated manner, if at all. The establishment and resourcing of structures dedicated to fulfilling these functions in an organized and coordinated manner are required to counteract the formidable barriers and challenges that inhibit the use of Asia's wealth of data for maximum benefit.