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Background: The World Health Organization is considering substituting Xpert MTB/RIF (Xpert) with Xpert MTB/RIF Ultra (Ultra) for tuberculosis (TB) diagnosis, but supportive evidence is scarce, particularly among people more likely (presumptive) to have paucibacillary pulmonary TB (PTB). Methods: During January-July 2018, presumptive PTB patients visiting TB Screening and Treatment Centres of Dhaka for routine chest X-ray (CXR) and conventional Xpert were enrolled. Sputum specimens were additionally tested with microscopy, culture, and Ultra. Specimens with “Trace call” by Ultra (Ultra-trace) were retested. Yield and diagnostic accuracy using various approaches to Ultra-trace and concordance of Ultra with bacteriological-positive PTB were assessed. Results: Altogether, 1,083 participants (104 ‘Xpert-positive’; 979 ‘Xpert-negative and CXR-suggestive’) were enrolled. All Xpert-positives and 900 (92%) Xpert-negatives were concordant with Ultra, however, seventy-nine (8.1%) Xpert-negative specimens tested positive with Ultra; 37 (46.8%) were categorically positives, and 42 (53.2%) were Ultra-trace. Sixteen of the 42 were retested, of whom eight (50.1%) Ultra-trace turned categorically positive, leading to 45 (4.6%) additionally detected by Ultra. Ultra sensitivity and specificity were 93.9% and 94.6%, and it additionally detected 5.4% more TB patients with a concordance of 94.6% (kappa, □=0.78) compared to any bacteriologically positive specimen (microscopy, culture, or Xpert). Conclusion: Ultra exhibited improved detection and accuracy among Xpert-negatives in a cohort with a high likelihood of PTB.

Background The World Health Organization recommends the Xpert MTB/RIF Ultra assay for diagnosing pulmonary tuberculosis (PTB) in children. Though stool is a potential alternative to respiratory specimens among children, the diagnostic performance of Xpert Ultra on stool is unknown. Thus, we assessed the diagnostic performance of Xpert Ultra on stool to diagnose PTB in children. Methods We conducted a cross-sectional study among consecutively recruited children (, Xpert Ultra may be used on stool, an easy-to-obtain specimen, for childhood pulmonary tuberculosis diagnosis. Future studies with follow-up and clinical evolution are needed to provide insight on management of children with trace call.

Highlights • Japanese encephalitis (JE) is largely preventable through vaccination. • Several JE vaccines prequalified by World Health Organization are available. • Hospital-based surveillance were conducted in Bangladesh to describe JE epidemiology. • JE cases were identified each year, among all age groups, and from a widespread geographical area. • Routine childhood immunization program or mass vaccination need to be examined., Background Japanese encephalitis (JE) virus is recognized as a major cause of encephalitis in Bangladesh. The World Health Organization (WHO) recommends human immunization as the most effective means to control JE. Several WHO-prequalified vaccines are available to prevent JE but no vaccination program has been implemented in Bangladesh. Methods We conducted hospital-based surveillance for acute meningitis-encephalitis syndrome (AMES) to describe JE epidemiology and help inform policy decisions about possible immunization strategies for Bangladesh. Results During 2007–2016, a total of 6543 AMES patients were identified at four tertiary hospitals. Of the 6525 patients tested, 548 (8%) were classified as JE cases. These 548 patients resided in 36 (56%) out of 64 districts of Bangladesh, with the highest proportion of JE cases among AMES patients (12% and 7%) presenting at two hospitals in the northwestern part of the country. The median age of JE cases was 30 years, and 193 (35%) were aged ≤15 years. The majority of JE cases (80%) were identified from July through November. Conclusions Surveillance results suggest that JE continues to be an important cause of meningo-encephalitis in Bangladesh. Immunization strategies including JE vaccine introduction into the routine childhood immunization program or mass vaccination in certain age groups or geographic areas need to be examined, taking into consideration the cost-effectiveness ratio of the approach and potential for decreasing disease burden.

Our changing climate is already affecting the transmission of vector borne diseases such as dengue fever. This issue presents a significant public health concern for some nations, such as Bangladesh, which already experience regular seasonal outbreaks of dengue fever under present day conditions. To provide guidance for proactive public health planning to potentially mitigate future infections, we explore the impact of climate change on dengue infections by calculating the change in vectorial capacity of Aedes aegypti mosquito at a seasonal level for all regions in Bangladesh under two scenarios for future atmospheric greenhouse gas concentrations. For each of the four climate models used, and for both scenarios, our analysis reveals that the annual vectorial capacity remains at a level that would enable potential dengue epidemic transmission in all regions in Bangladesh. We found a slight decline in vectorial capacity in half of the regions examined during the last two decades of the 21st Century for the lower-concentration scenario, with a pronounced decline in vectorial capacity in all geographic regions beginning in 2060 for the higher-concentration scenario. The likely reason is that in many regions, warming is leading to sub-optimal mosquito breeding temperatures. However, seasonal differences in vectorial capacity dissipates as the climate warms, to the point that there is almost no observable seasonality for the higher-concentration scenario during the last two decades of this century. This finding suggests there is the potential for the dengue season to extend all year, with outbreaks occurring at any time. Consequently, disease surveillance and control activities would need to be geographically and temporally adapted to mitigate dengue epidemic risk in response to climate change.

In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method’s sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.

Background In recent non-pandemic periods, tuberculosis (TB) has been the leading killer worldwide from a single infectious disease. Patients with DM are three times more likely to develop active TB and poor treatment outcomes. Single glycemic measurements at TB diagnosis may inaccurately diagnose or mischaracterize DM severity. Data are limited regarding glycemic dynamics from TB diagnosis through treatment. Methods Prospective study of glycemia dynamics in response to TB treatment measured glycosylated haemoglobin (HbA1c) in patients presenting to TB screening centres in Bangladesh to determine the prevalence and risk factors of hyperglycemia before and at TB treatment completion. Results 429 adults with active TB disease were enrolled and divided into groups based on history of DM and initial HbA1c range: normoglycemia, prediabetes, and DM. DM was diagnosed in 37%. At treatment completion,14(6%) patients from the normoglycemia and prediabetes groups had HbA1c>6.5%, thus increasing the prevalence of DM to 39%. The number needed to screen to diagnose one new case of DM at TB diagnosis was 5.7 and 16 at treatment completion in the groups without DM. Weight gain>5% at treatment completion significantly increased the risk of hyperglycemia in the groups without DM at TB diagnosis (95% CI 1.23–26.04, p Conclusion HbA1c testing prior to and at TB treatment completion found a high prevalence of prediabetes and DM, including a proportion found at treatment completion and commonly in people with a higher percentage of weight gain. Further longitudinal research is needed to understand the effects of TB disease and treatment on insulin resistance and DM complications.

Background In Bangladesh, about 80% of healthcare is provided by the private sector. Although free diagnosis and care is offered in the public sector, only half of the estimated number of people with tuberculosis are diagnosed, treated, and notified to the national program. Private sector engagement strategies often have been small scale and time limited. We evaluated a Social Enterprise Model combining external funding and income generation at three tuberculosis screening centres across the Dhaka Metropolitan Area for diagnosing and treating tuberculosis. Methods and findings The model established three tuberculosis screening centres across Dhaka Metropolitan Area that carried the icddr,b brand and offered free Xpert MTB/RIF tests to patients visiting the screening centres for subsidized, digital chest radiographs from April 2014 to December 2017. A network of private and public health care providers, and community recommendation was formed for patient referral. No financial incentives were offered to physicians for referrals. Revenues from radiography were used to support screening centres’ operation. Tuberculosis patients could choose to receive treatment from the private or public sector. Between 2014 and 2017, 1,032 private facilities networked with 8,466 private providers were mapped within the Dhaka Metropolitan Area. 64, 031 patients with TB symptoms were referred by the private providers, public sector and community residents to the three screening centres with 80% coming from private providers. 4,270 private providers made at least one referral. Overall, 10,288 pulmonary and extra-pulmonary tuberculosis cases were detected and 7,695 were bacteriologically positive by Xpert, corresponding to 28% of the total notifications in Dhaka Metropolitan Area. Conclusion The model established a network of private providers who referred individuals with presumptive tuberculosis without financial incentives to icddr,b’s screening centres, facilitating a quarter of total tuberculosis notifications in Dhaka Metropolitan Area. Scaling up this approach may enhance national and international tuberculosis response.

Background Data are scarce regarding the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients in Bangladesh. This study was undertaken to estimate the number needed to screen (NNS) to identify a case of DM among those with TB symptoms and those with confirmed TB disease, and to identify factors predicting treatment outcomes of TB patients with and without DM. Methods Persons attending public–private model screening centres in urban Dhaka for the evaluation of TB were offered free blood glucose testing in addition to computer-aided chest X-ray and sputum Xpert MTB/RIF. Results Among 7647 people evaluated for both TB and DM, the NNS was 35 (95% confidence interval (CI) 31–40) to diagnose one new case of DM; among those diagnosed with TB, the NNS was 21 (95% CI 17–29). Among those with diagnosed TB, patients with DM were more likely to have cavitation on chest X-ray compared to those without DM (31% vs 22%). Treatment failure (odds ratio (OR) 18.9, 95% CI 5.43–65.9) and death (OR 2.08, 95% CI 1.11–3.90) were more common among TB patients with DM than among TB patients without DM. DM was the most important predictor of a poor treatment outcome in the classification analysis for TB patients aged 39 years and above. Conclusions A considerable burden of DM was found among patients accessing TB diagnostics through a public–private model in urban Bangladesh, and DM was associated with advanced TB disease and a high rate of poor treatment outcome.

In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death. We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes. From December’2014 to September’2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females—12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth. This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups., Author summary In the absence of reliable surveillance data on the burden of hepatitis E in endemic countries, we conducted a hospital-based acute jaundice surveillance study over a two and a half year period in six tertiary hospitals in Bangladesh. The study confirms that HEV infections occur throughout the year, and is a major (34%) cause of acute jaundice in tertiary hospitals in Bangladesh. Three-quarters of the acute hepatitis E cases were male, and HEV infection was higher among patients residing in urban areas than patients in rural areas (41% vs 32%). The overall case fatality rate of acute HEV infections in hospitals was 5%, but was higher among pregnant women (12%). Hepatitis E patients who died were more likely to have co-infection with HAV or HBV than the HEV infected patients who did not die. Fifteen percent of HEV infected mothers had miscarriage/stillbirth. Of the children who were born alive, 19% died, all within one week of birth. Considering the high burden of hepatitis E among hospitalized acute jaundice patients, Bangladesh could take control measures to reduce this risk including improvements in water quality, sanitation and hygiene practices and the introduction of hepatitis E vaccine in high-risk areas.

Serostudies are needed to answer generalizable questions on disease risk. However, recruitment is usually biased by age or location. We present a nationally-representative study for dengue from 70 communities in Bangladesh. We collected data on risk factors, trapped mosquitoes and tested serum for IgG. Out of 5866 individuals, 24% had evidence of historic infection, ranging from 3% in the north to >80% in Dhaka. Being male (aOR:1.8, [95%CI:1.5–2.0]) and recent travel (aOR:1.3, [1.1–1.8]) were linked to seropositivity. We estimate that 40 million [34.3–47.2] people have been infected nationally, with 2.4 million ([1.3–4.5]) annual infections. Had we visited only 20 communities, seropositivity estimates would have ranged from 13% to 37%, highlighting the lack of representativeness generated by small numbers of communities. Our findings have implications for both the design of serosurveys and tackling dengue in Bangladesh., eLife digest Dengue is a mosquito-borne virus that infects millions of people each year. Often the countries most affected by the virus, such as Bangladesh, do not have the resources needed to tackle the disease. For resources sent to these countries to have the greatest impact, it is important to know which areas are most affected, and which subsets of the population are most at risk. A way to gather this information is to test for dengue virus antibodies a protein produced by the immune system in response to the infection in the blood of individuals. However, previous efforts to use these tests to understand dengue risk in communities have generally only been done in single locations, typically a major city, and the findings of these tests are unlikely to be applicable to the wider population. Now, Salje et al. have visited 70 different communities from all around Bangladesh and used these tests on blood samples collected from over 5,000 individuals from a range of age-groups. From these measurements it was estimated that an average 2.4 million people are infected with dengue each year in Bangladesh, with major cities, such as Dhaka, experiencing more concentrated levels. The exposure to dengue outside major cities was much lower, and men, who tend to travel more, were found to be at greater risk of infection. Salje et al. also showed that using a small number of communities to estimate national levels of infection led to misleading results. This highlights the danger of using information collected from a limited number of places to represent the effects of a disease on the wider population. Public health agencies in Bangladesh will be able to use this information to tackle dengue more effectively, focusing on the areas and the populations most affected by the disease. In addition, the design and analytical approaches used in this study could be applied to other countries, and to different diseases.

Background Dengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka. Methodology/Principal findings Considering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with DENV seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables. Conclusions/Significance Our study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversion among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease., Author summary Similar to many other tropical regions of the world, dengue is a major public health problem in Bangladesh where Aedes aegypti mosquitoes are the main vector. Through this serological survey, we present data on the magnitude (measured in proportions) of seroprevalence and seroconversion within 12 selected wards in the city of Dhaka, Bangladesh. In 2012 the observed dengue seroprevalence was 93% among individuals tested during post-monsoon with a seroconversion rate between pre- and post-monsoon periods of 57.7%. This finding suggests that dengue virus (DENV) circulated in the city during the observation period. Past exposure to dengue virus was highly associated with age, possession of indoor potted plants, types of mosquito control measures used, and human movement and attendance in mass gatherings, while the extent of dengue seroprevalence were not associated with the socioeconomic status of the study participants. Our findings suggest that household utilities and water management or storage practices and recognition and elimination of mosquito development sites and participation in mass gatherings are important factors that affect exposure to dengue. Intervention strategies should therefore target these factors for effective prevention and control of dengue infection.