Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings.

Brucellosis is a zoonotic disease, caused by some species within the Brucella genus. The primary and secondary objectives of this cross-sectional study were to determine the seroprevalence of Brucella antibodies in humans and cows and identify risk factors for exposure to Brucella spp. among people in Shahjadpur sub-district, Bangladesh. Twenty-five villages were randomly selected from the 303 milk-producing villages in the sub-district. We randomly selected 5% of the total households from each village. At each household, we collected demographic information and history of potential exposure to Brucella spp. in humans. In addition, we collected serum from household participants and serum and milk from cattle and tested to detect antibodies to Brucella sp. Univariate analysis was performed to detect associations between seropositivity and demographics, risk factors, and behaviors in households. We enrolled 647 households, 1313 humans, and 698 cows. Brucella antibodies were detected in sera from 27 household participants (2.1%, 95% confidence interval [95%CI]: 1.2-2.9%). Eleven (1.6%, 95%CI 0.6-2.4%) cows had detectable Brucella antibodies in either milk or serum. About half (53%) of the 698 cows exhibited more than one reproductive problem within the past year; of these, seven (2%) had Brucella antibodies. Households with seropositive individuals more frequently reported owning cattle (78% vs. 32%, P < 0.001). Despite a low prevalence of Brucella seropositivity in the study, the public health importance of brucellosis cannot be ruled out. Further studies would help define Brucella prevalence and risk factors in this region and nationally.

BACKGROUND: Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. METHODS: During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. RESULTS: Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. CONCLUSIONS: Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

BACKGROUND: Tuberculosis (TB) has been an important public health concern in Bangladesh. The most common cause of human TB is Mycobacterium tuberculosis, while bovine TB is caused by Mycobacterium bovis. OBJECTIVE: The objective of this study was to determine the frequency of TB in individuals with occupational exposure to cattle and to detect Mycobacterium bovis among cattle in slaughterhouses in Bangladesh. METHODS: Between August and September 2015, an observational study was conducted in two government chest disease hospitals, one cattle market, and two slaughterhouses. Sputum samples were collected from individuals who met the criteria for suspected TB and had been exposed to cattle. Tissue samples were collected from cattle that had low body condition score(s). Both humans and cattle samples were screened for acid-fast bacilli (AFB) by Ziehl-Neelsen (Z-N) staining and cultured for Mycobacterium tuberculosis complex (MTC). Region of difference (RD) 9-based polymerase chain reaction (PCR) was also performed to identify Mycobacterium spp. We also conducted Spoligotyping to identify the specific strain of Mycobacterium spp. RESULTS: Sputum was collected from a total of 412 humans. The median age of human participants was 35 (IQR: 25-50) years. Twenty-five (6%) human sputum specimens were positive for AFB, and 44 (11%) were positive for MTC by subsequent culture. All (N = 44) culture-positive isolates were confirmed as Mycobacterium tuberculosis by RD9 PCR. Besides, 10% of cattle workers were infected with Mycobacterium tuberculosis in the cattle market. Of all TB (caused by Mycobacterium tuberculosis) infected individuals, 6.8% of individuals were resistant to one or two anti-TB drugs. The majority of the sampled cattle (67%) were indigenous breeds. No Mycobacterium bovis was detected in cattle. CONCLUSIONS: We did not detect any TB cases caused by Mycobacterium bovis in humans during the study. However, we detected TB cases caused by Mycobacterium tuberculosis in all humans, including cattle market workers.

Bats, rodents and monkeys are reservoirs for emerging zoonotic infections. We sought to describe the frequency of human exposure to these animals and the seasonal and geographic variation of these exposures in Bangladesh. During 2013-2016, we conducted a cross-sectional survey in a nationally representative sample of 10,002 households from 1001 randomly selected communities. We interviewed household members about exposures to bats, rodents and monkeys, including a key human-bat interface-raw date palm sap consumption. Respondents reported observing rodents (90%), bats (52%) and monkeys (2%) in or around their households, although fewer reported direct contact. The presence of monkeys around the household was reported more often in Sylhet division (7%) compared to other divisions. Households in Khulna (17%) and Rajshahi (13%) were more likely to report drinking date palm sap than in other divisions (1.5-5.6%). Date palm sap was mostly consumed during winter with higher frequencies in January (16%) and February (12%) than in other months (0-5.6%). There was a decreasing trend in drinking sap over the three years. Overall, we observed substantial geographic and seasonal patterns in human exposure to animals that could be sources of zoonotic disease. These findings could facilitate targeting emerging zoonoses surveillance, research and prevention efforts to areas and seasons with the highest levels of exposure.

BACKGROUND: Rotavirus is a common cause of severe acute gastroenteritis among young children. Estimation of the economic burden would provide informed decision about investment on prevention strategies (e.g., vaccine and/or behavior change), which has been a potential policy discussion in Bangladesh for several years. METHODS: We estimated the societal costs of children <5 years for hospitalization from rotavirus gastroenteritis (RVGE) and incidences of catastrophic health expenditure. A total of 360 children with stool specimens positive for rotavirus were included in this study from 6 tertiary hospitals (3 public and 3 private). We interviewed the caregiver of the patient and hospital staff to collect cost from patient and health facility perspectives. We estimated the economic cost considering 2015 as the reference year. RESULTS: The total societal per-patient costs to treat RVGE in the public hospital were 126 USD (95% CI: 116-136) and total household costs were 161 USD (95% CI: 145-177) in private facilities. Direct costs constituted 38.1% of total household costs. The out-of-pocket payments for RVGE hospitalization was 23% of monthly income and 76% of households faced catastrophic healthcare expenditures due to this expense. The estimated total annual household treatment cost for the country was 10 million USD. CONCLUSIONS: A substantial economic burden of RVGE in Bangladesh was observed in this study. Any prevention of RVGE through cost-effective vaccination or/and behavioural change would contribute to substantial economic benefits to Bangladesh.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

Vaccines against Japanese encephalitis (JE) have been available for decades. Currently, most JE-endemic countries have vaccination programs for their at-risk populations. Even so, JE remains the leading recognized cause of viral encephalitis in Asia. In 2018, the U.S. Centers for Disease Control and Prevention and PATH co-convened a group of independent experts to review JE prevention and control successes, identify remaining scientific and operational issues that need to be addressed, discuss opportunities to further strengthen JE vaccination programs, and identify strategies and solutions to ensure sustainability of JE control during the next decade. This paper summarizes the key discussion points and recommendations to sustain and expand JE control.

Influenza vaccination is a key public health intervention for pandemic influenza as it can limit the burden of disease, especially in high-risk groups, minimize social disruption and reduce economic impact. (1) In the event of an influenza pandemic, large-scale production, distribution and administration of pandemic vaccines in the shortest time possible is required. In addition, monitoring vaccine effectiveness, coverage and adverse events following immunization (AEFI) is important. Since seasonal influenza vaccination programmes require annual planning in each of these areas, establishing and strengthening annual influenza programmes will contribute to pandemic preparedness. (2) This paper presents efforts made in the World Health Organization (WHO) Western Pacific Region to improve seasonal influenza vaccination and pandemic preparedness.

BACKGROUND: Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). METHODS: Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. FINDINGS: 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32.9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38.0% (95% CI 4.8-73.4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23.0% (0.7-57.7) of admissions for acute gastroenteritis, showing a 39.6% (35.4-43.8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26.4% (15.0-37.8) in the Eastern Mediterranean Region to 55.2% (43.0-67.4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. INTERPRETATION: A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. FUNDING: The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

BACKGROUND: Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3+0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonisation and invasive disease in children aged <5 years. METHODS: Six colonisation surveys were done between January 2014 and January 2018 in children attending the outpatient department of a non-governmental paediatric hospital in Siem Reap. Nasopharyngeal swabs were analysed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012 - December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonisation data were modelled to estimate vaccine effectiveness (VE). RESULTS: Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, vaccine effectiveness (VE) estimates for colonisation were 16.6% (95% CI 10.6-21.8) for all pneumococci and 39.2% (26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (17.7-33.0) decrease in multi-drug resistant pneumococcal colonisation. IPD incidence was estimated to have declined by 26.4% (14.4-35.8) by 2018, with a decrease of 36.3% (23.8-46.9) for VT IPD and an increase of 101.4% (62.0-145.4) for non-vaccine serotype IPD. CONCLUSIONS: Following PCV13 introduction into the Cambodian immunisation schedule there have been declines in VT pneumococcal colonisation and disease in children aged <5 years. Modelling of dominant serotype colonisation data produced plausible vaccine effectiveness estimates.

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.

Intussusception is the invagination of one segment of the bowel into a distal segment, characterized by symptoms of bloody stool, vomiting, and abdominal pain. Previous studies have found regional differences in incidence but the etiology of most intussusception cases is unknown. Rotavirus vaccines were associated with a slightly of increased risk of intussusception in post-licensure evaluations in high- and middle-income countries, but not in low income African countries. To describe the baseline epidemiology of intussusception in young children prior to rotavirus vaccine implementation, active sentinel hospital surveillance for intussusception in children<2years of age was conducted in 4 low income Asian countries (Bangladesh, Nepal, Pakistan and Vietnam). Over a 24-month period, 15 sites enrolled 1,415 intussusception cases, of which 70% were enrolled in Vietnam. Overall, 61% of cases were male and 1% (n=16) died, ranging from 8% in Pakistan to 0% in Vietnam. The median age of cases enrolled ranged from 6months in Bangladesh and Pakistan to 12months in Vietnam. The proportion of cases receiving surgical management was 100% in Bangladesh, 88% in Pakistan, 61% in Nepal, and 1% in Vietnam. The high proportion of males and median age of cases around 6months of age found in this regional surveillance network are consistent with previous descriptions of the epidemiology of intussusception in these countries and elsewhere. Differences in management and the fatality rate of cases between the countries likely reflect differences in access to healthcare and availability of diagnostic modalities. These baseline data will be useful for post-rotavirus vaccine introduction safety monitoring.

INTRODUCTION: In preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. METHODS: We enrolled and collected fresh stool from every fourth child<5years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. RESULTS: We found that 64% (4832/7562) of children<5years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were <12months of age. The most common strains were G1P[8] (43%), G12P[8] (15%) and G9P[8] (9%); 11% of children had mixed infection.G3P[8], which has not been reported in Bangladesh since 2001, was documented for the first time in our surveillance system. CONCLUSIONS: The high burden of rotavirus-associated hospitalizations highlights the potential value of rotavirus vaccination in Bangladesh. Continued surveillance is important for monitoring the impact of vaccination as well as monitoring evolving genotypes.

A prospective, multicentre study was conducted in four sentinel surveillance hospitals to assess the trend and epidemiology of acute diarrhea caused by Rotavirus in Vietnam. During the period 2012-2015, a total 8,889 children under 5years of age were enrolled in the surveillance, and 8689 stool samples were collected. Of these cases, Rotavirus was most common pathogen 46.7% (4054 cases); in which 26.6% (1117) rotavirus-positive stool samples were evaluated to identify genotypes. The proportion of rotavirus positive specimens decreased annually from 54.7% in 2012 to 36.6% in 2015. Rotavirus was detected year-round, but most rotavirus gastroenteritis cases (77.1%) occurred between December and May, corresponding to the rotavirus seasonality. It is found that the peaks varied by regions. Rotavirus positivities varied between the youngest and oldest age, but children 6-11months old (38.8%) and 12-23months old (38.4%) counted for most cases. A significant higher number of diarrhea within 24hours (8.3 times, 95%CI: 8.1-8.4 times) and higher proportion of severe dehydration (12.9%) in Rotavirus positive group than that in Rotavirus negative group (7.7 times, 95%CI: 7.6-7.9 times; and 9.7%, respectively). A downtrend of prevalence of G1P[8] was observed from 82% in 2013 to 15% in 2015. However, G2P[4] was found in 5% of samples in 2012, 9% in 2013, 36% in 2014, and 28% in 2015. Rotavirus infection is the most important cause of acute diarrhea among hospitalized children in Vietnam, and a rotavirus vaccination program for children may significantly reduce this disease.

BACKGROUND: Each year, approximately 1,066 Cambodian children under five years old die of diarrhea, and 51% of these deaths are due to rotavirus gastroenteritis. Quantifying childhood hospitalizations caused by severe rotavirus infections is also important in demonstrating disease burden caused by this virus. The objective of this study is to update and confirm the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children using seven years of continuous active, prospective surveillance from 2010 to 2016. We also characterize the circulating rotavirus genotypic strains during this period. METHODS: Active surveillance for rotavirus gastroenteritis was conducted from January 2010 through December 2016 at a national hospital in Phnom Penh, Cambodia. Children <60months of age who were hospitalized for acute gastroenteritis (AGE) were consented and enrolled. Information on gender, age, clinical characteristics, and month of onset were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus antigen, and genotyping was performed on rotavirus test-positive specimens to characterize predominant rotavirus strains during the surveillance period. RESULTS: Of 7007 children enrolled with AGE and having specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The majority of rotavirus hospitalizations occurred in children younger than two years old (92%). Year-round rotavirus transmission was observed, with seasonal peaks during the cooler, dry months between November and May. Genotypic trends in rotavirus were observed over the surveillance period; the predominant rotavirus strains changed from G1P[8] (2010-2012), to G2P[4] (2013-2014), the emergence of genotype G8P[8] in 2015, and G3P[8] in 2016. CONCLUSIONS: Rotavirus is the leading cause of severe acute gastroenteritis hospitalizations in Cambodian children under five years old, with 50% of such hospitalizations attributable to rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2years of age. Changes in the predominant rotavirus strains occurred over time among these unvaccinated children. This information is important to understand and prioritize the current potential impacts upon child health that could be achieved through the introduction of rotavirus vaccines in Cambodia.

INTRODUCTION: Rotavirus vaccines have significantly decreased the burden of diarrheal diseases in countries that have introduced them into their immunization programs. In some studies, there has been a small association between rotavirus vaccines and intussusception in post-marketing surveillance, highlighting the importance of tracking incidence before and after vaccine introduction. The objective of this study was to describe the epidemiology of intussusception among Bangladeshi children pre-vaccine introduction. METHODS: We conducted active, hospital-based surveillance for intussusception at 7 tertiary care hospitals with pediatric surgical facilities during July 2012 to September 2016. Hospitalized children under 2years of age were identified according to Brighton Collaboration level 1 criteria for intussusception. The frequency and proportion of intussusception among overall surgical admissions, as well as the demographic and clinical information of the cases is described. RESULTS: Overall 153 cases of intussusception among children <2years-old were identified at participating sites over the enrolment period, confirmed by Level 1 Brighton criteria. These cases represented 2% of all surgical admissions under 2years of age. One hundred twelve cases (73%) were male; the median age was 7months; and the median duration of hospitalization was 7days. One hundred forty-six (95%) children with intussusception required surgery, and 11 (7%) died. CONCLUSIONS: Confirmed cases of intussusception represented nearly 2% of pediatric surgical admissions at tertiary referral centers in Bangladesh during the study period and 7% of children with intussusception died. Given the high burden of rotavirus disease in Bangladesh, vaccine introduction is warranted, however, further studies after introduction of rotavirus vaccine are necessary to determine any association between vaccine and intussusception in this setting.

Recurrent outbreaks of acute encephalitis syndrome (AES) among children in lychee growing areas in Asia highlight the need to better understand the etiology and the context. We conducted a mixed-methods study to identify risk factors for disease, and behaviors and practices around lychee cultivation in an AES outbreak community in northern Bangladesh in 2012. The outbreak affected 14 children; 13 died. The major symptoms included unconsciousness, convulsion, excessive sweating, and frothy discharge. The median time from illness onset to unconsciousness was 2.5 hours. The outbreak corresponded with lychee harvesting season. Multiple pesticides including some banned in Bangladesh were frequently used in the orchards. Visiting a lychee orchard within 24 hours before onset (age-adjusted odds ratio [aOR] = 11.6 [1.02-109.8]) and 3 days (aOR = 7.2 [1.4-37.6]), and family members working in a lychee orchard (aOR = 7.2 [1.7-29.4]) and visiting any garden while pesticides were being applied (aOR = 4.9 [1.0-19.4]) in 3 days preceding illness onset were associated with illness in nearby village analysis. In neighborhood analysis, visiting an orchard that used pesticides (aOR = 8.4 [1.4-49.9]) within 3 days preceding illness onset was associated with illness. Eating lychees was not associated with illness in the case-control study. The outbreak was linked to lychee orchard exposures where agrochemicals were routinely used, but not to consumption of lychees. Lack of acute specimens was a major limitation. Future studies should target collection of environmental and food samples, acute specimens, and rigorous assessment of community use of pesticides to determine etiology.

Background We assessed programmatic adaptations and infants' uptake of inactivated poliovirus vaccine (IPV) after its introduction into the routine immunization schedule in Bangladesh. Methods Using convenience and probability sampling, we selected 23 health facilities, 36 vaccinators, and 336 caregivers, within 5 districts and 3 city corporations. We collected data during August-October 2015 by conducting interviews, reviewing vaccination records, and observing activities. Results Knowledge about IPV was high among vaccinators (94%). No problems with IPV storage, transport, or waste disposal were detected, but shortages were reported in 20 health facilities (87%). Wastage per 5-dose vaccine vial was above the recommended 30% in 20 health facilities (87%); all were related to providing <5 doses per open vial. Among eligible infants, 87% and 86% received the third dose of pentavalent and oral poliovirus vaccine, respectively, but only 65% received IPV at the same visit. Among 73 infants not vaccinated with IPV, 58% of caregivers reported that vaccine was unavailable. Conclusions Bangladesh successfully introduced IPV, but shortages related to insufficient global supply and high vaccine wastage in small outreach immunization sessions might reduce its impact on population immunity. Minimizing wastage and use of a 2-dose fractional-IPV schedule could extend IPV immunization to more children.

Hepatitis B is highly endemic in the Republic of Kiribati, while the coverage of timely birth dose vaccination, the primary method shown to prevent mother-to-child transmission of hepatitis B virus, was only 66% in 2014. Children born at home are especially at high risk, as they have limited access to timely birth dose (i.e. within 24 h) vaccination. To improve birth dose coverage, a project to improve linkages between village health volunteers and health workers and educate pregnant women on hepatitis B vaccination was carried out in 16 communities with low birth dose coverage in Kiribati from November 2014 to May 2015. After project completion, the coverage of timely birth dose administration increased significantly both in the densely populated capital region of South Tarawa (from 89% to 95%, p=0.001) and the Outer Islands (from 57% to 83%, p<0.001). The coverage of timely birth dose administration among infants born at home increased significantly from 70% to 84% in South Tarawa (p=0.001) and from 49% to 75% in the Outer Islands (p<0.001). Timely birth dose was associated with being born in a hospital, being born during the study period and caregivers having developed an antenatal birth dose plan. The project demonstrates a successful model for improving hepatitis B vaccine birth dose coverage that could be adopted in other areas in Kiribati as well as other similar settings.

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to successful TB control. The 2010-2011 Bangladesh Drug Resistance Survey (DRS) showed MDR-TB prevalence to be 7% overall, 1.4% in new and 28.5% in previously treated patients. We aimed to determine the rate of MDR-TB in selected sentinel sites in Bangladesh. METHODS: Fourteen hospitals from the seven divisions in Bangladesh were selected as sentinel surveillance sites. Newly registered TB patients were systematically enrolled from August 2011 to December 2014. Sputum specimens were processed for culture and drug susceptibility testing by the proportion method using Lowenstein-Jensen medium. RESULTS: Specimens from 1906 (84%) of 2270 enrolled patients were analysed. Isolates from 61 (3.2%) were identified as having MDR-TB. The proportion of MDR-TB was 2.3% among new and 13.8% among previously treated TB patients (P < 0.001). The overall proportion of MDR-TB was 3.2%:3.5% in males and 2.3% in females; by age, the MDR-TB rate was highest (5.2%) in those aged ≥65 years. CONCLUSIONS: The high proportion of MDR-TB among new patients found in this sentinel surveillance significantly differs from that reported in the DRS. While the sentinel surveillance sites were not designed to be nationally representative, it is worrying to observe a higher number of MDR-TB cases among new patients.

BACKGROUND: In anticipation of introduction of a rotavirus vaccine into the national immunization program of Bangladesh, active hospital-based surveillance was initiated to provide pre-vaccine baseline data on rotavirus disease. METHODS: Children 5 years of age and younger admitted with acute gastroenteritis (AGE) (≥3 watery or looser-than-normal stools or ≥1 episode of forceful vomiting) at 7 hospitals throughout Bangladesh were identified. Clinical information and stool specimens were collected from every 4th patient. Specimens were tested for rotavirus antigen by enzyme immunoassays; 25% of detected rotaviruses were genotyped. RESULTS: From July 2012-June 2015, rotavirus was detected in 2,432 (64%) of 3,783 children hospitalized for AGE. Eight enrolled children died, including 4 (50%) who were rotavirus positive. Rotavirus was detected year-round in Bangladesh with peak detection rates of >80% during November-February. Most (86%) rotavirus AGE cases were 6-23 months of age. Sixty-nine percent of children with rotavirus had severe disease (Vesikari score ≥11). Among 543 strains genotyped, G1P[8] (31%) and G12P[8] (29%) were the most common. CONCLUSIONS: Rotavirus is a major cause of morbidity in Bangladeshi children, accounting for nearly two-thirds of AGE hospitalizations. These data highlight the potential value of rotavirus vaccination in Bangladesh, and will be key for future measurement of vaccine impact.

INTRODUCTION: Inactivated poliovirus vaccine (IPV) introduction and phased oral poliovirus vaccine (OPV) cessation are essential for eradication of polio. METHODS: Healthy 6-week old infants in Bangladesh were randomized to one of five study arms: receipt of trivalent OPV (tOPV) or bivalent OPV (bOPV) at ages 6, 10 and 14 weeks, intramuscular IPV or intradermal one-fifth fractional dose IPV (f-IPV) at ages 6 and 14 weeks, or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks (f-IPV/bOPV). All participants received tOPV at age 18 weeks. RESULTS: Of 975 infants randomized, 95% (922) completed follow-up. Type 1 seroconversion after 3 doses at 6, 10 and 14 weeks was higher with bOPV compared with tOPV (99% vs 94%, p=0.019). Seroconversions to types 1 and 3 after 2 IPV doses at ages 6 and 14 weeks were no different than after 3 doses of tOPV or bOPV at ages 6, 10 and 14 weeks. A priming response, seroconversion 1 week after IPV at 14 weeks among those who did not seroconvert after IPV at 6 weeks, was observed against poliovirus types 1, 2 and 3 in 91%, 84% and 97%, respectively. Compared with IPV, f-IPV failed non-inferiority tests for seroconversion with 1 or 2 doses and priming after 1 dose. DISCUSSION: The findings demonstrate considerable priming with IPV at age 6 weeks, comparable immunogenicity of tOPV and bOPV, and inferior immunogenicity of one-fifth f-IPV compared with IPV. If IPV induced priming at age 6 weeks is similar to that at age 14 weeks, IPV could be administered at a younger age and possibly with a higher coverage.

OBJECTIVE: Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013 we sought to evaluate program performance. METHODS: In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT program over six months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the program. RESULTS: Chart review was performed on 77 patients. Sputum smears and cultures were done, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS: The cPMDT program in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the program is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritized. This article is protected by copyright. All rights reserved.

BACKGROUND: The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules. METHODS: We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh. We recruited healthy infants aged 6 weeks at 42 immunisation clinics and randomly assigned them (with blocks of 15, three per group) to receive a short three-dose schedule of bOPV (bOPV short) or mOPV1 (mOPV1 short) with the first dose given at age 6 weeks, the second at age 8 weeks, and the third at age 10 weeks; or to a standard three-dose schedule of bOPV (bOPV standard) or mOPV1 (mOPV1 standard) or trivalent OPV (tOPV standard) with the first dose given at age 6 weeks, the second at 10 weeks, and the third at age 14 weeks. The primary outcome was the proportion of infants with antibody seroconversion for type 1, type 2, and type 3 polioviruses. The primary, modified intention-to-treat analysis included all patients who had testable serum samples before and after receiving at least one OPV dose. We used a 10% margin to establish non-inferiority for bOPV groups versus mOPV1 groups in seroconversion for type 1 poliovirus, and for bOPV1 short versus bOPV1 standard for types 1 and 3. This trial is registered at ClinicalTrials.gov, number NCT01633216, and is closed to new participants. FINDINGS: Between May 13, 2012, and Jan 21, 2013, we randomly assigned 1000 infants to our study groups. 927 completed all study visits and were included in the primary analysis. Seroconversion for type-1 poliovirus was recorded in 183 (98%, 95% CI 95-100) of 186 infants given bOPV short, 179 (97%, 94-99) of 184 given bOPV standard, 180 (96%, 92-98) of 188 given mOPV short, 178 (99%, 97-100) of 179 given mOPV1 standard, and 175 (92%, 87-96) of 190 given tOPV standard. Seroconversion for type 2 was noted in 16 infants (9%, 5-14) on bOPV short, 29 (16%, 11-22) on bOPV standard, 19 (10%, 7-15) on mOPV short, 33 (18%, 13-25) on mOPV1 standard, and 182 (96%, 92-98) on tOPV standard. Seroconversion for type 3 was noted in 175 infants (94%, 90-97) on bOPV short, 176 (96%, 92-98) on bOPV standard, 18 (10%, 6-15) on mOPV short, 25 (14%, 10-20) on mOPV1 standard, and 167 (88%, 83-92) on tOPV standard. The short schedules for mOPV1 and bOPV elicited a non-inferior antibody response compared with the bOPV standard schedule. 104 adverse events were reported in 100 infants during follow up. 36 of these events needed admission to hospital (32 were pneumonia, two were vomiting or feeding disorders, one was septicaemia, and one was diarrhoea with severe malnutrition). One of the infants admitted to hospital for pneumonia died 5 days after admission. No adverse event was attributed to the vaccines. INTERPRETATION: Our trial showed that three doses of mOPV1 or bOPV with a short schedule of 2 week intervals between doses induces an immune response similar to that obtained with the standard schedule of giving doses at 4 week intervals. These findings support the use of these vaccines in campaigns done at short intervals to rapidly increase population immunity against polioviruses to control outbreaks or prevent transmission in high-risk areas. FUNDING: Centers for Disease Control and Prevention and UNICEF.

BACKGROUND: Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. METHODS: The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). RESULTS: A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. CONCLUSIONS: Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

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.

BACKGROUND: Bacterial sexually transmitted infections may facilitate HIV transmission. Bacterial sexually transmitted infection testing is recommended for sexually active HIV-infected patients annually and more frequently for those at elevated sexual risk. We estimated percentages of HIV-infected patients in the United States receiving at least one syphilis, gonorrhea, or chlamydia test, and repeat (≥2 tests, ≥3 months apart) tests for any of these sexually transmitted infections from mid-2008 through mid-2010. DESIGN: The Medical Monitoring Project collects behavioral and clinical characteristics of HIV-infected adults receiving medical care in the United States using nationally representative sampling. METHODS: Sexual activity included self-reported oral, vaginal, or anal sex in the past 12 months. Participants reporting more than 1 sexual partner or illicit drug use before/during sex in the past year were classified as having elevated sexual risk. Among participants with only 1 sex partner and no drug use before/during sex, those reporting consistent condom use were classified as low risk; those reporting sex without a condom (or for whom this was unknown) were classified as at elevated sexual risk only if they considered their sex partner to be a casual partner, or if their partner was HIV-negative or partner HIV status was unknown. Bacterial sexually transmitted infection testing was ascertained through medical record abstraction. RESULTS: Among sexually active patients, 55% were tested at least once in 12 months for syphilis, whereas 23% and 24% received at least one gonorrhea and chlamydia test, respectively. Syphilis testing did not vary by sex/sexual orientation. Receipt of at least 3 CD4+ T-lymphocyte cell counts and/or HIV viral load tests in 12 months was associated with syphilis testing in men who have sex with men (MSM), men who have sex with women only, and women. Chlamydia testing was significantly higher in sexually active women (30%) compared with men who have sex with women only (19%), but not compared with MSM (22%). Forty-six percent of MSM were at elevated sexual risk; 26% of these MSM received repeat syphilis testing, whereas repeat testing for gonorrhea and chlamydia was only 7% for each infection. CONCLUSIONS: Bacterial sexually transmitted infection testing among sexually active HIV-infected patients was low, particularly for those at elevated sexual risk. Patient encounters in which CD4+ T-lymphocyte cell counts and/or HIV viral load testing occurs present opportunities for increased bacterial sexually transmitted infection testing.

BACKGROUND: Predictors of death in hospitalized HIV-infected patients have not been previously reported in Bangladesh. OBJECTIVE: The primary aim of this study was to determine predictors of death among hospitalized HIV-infected patients at a large urban hospital in Bangladesh. METHODS: A study was conducted in the HIV in-patient unit (Jagori Ward) of icddr,b's Dhaka Hospital. Characteristics of patients who died during hospitalization were compared to those of patients discharged from the ward. Bivariate analysis was performed to determine associations between potential risk factors and death. Multivariable logistic regression was used to identify factors independently associated with death. RESULTS: Of 293 patients admitted to the Jagori Ward, 57 died during hospitalization. Most hospitalized patients (67%) were male and the median age was 35 (interquartile range: 2-65) years. Overall, 153 (52%) patients were diagnosed with HIV within 6 months of hospitalization. The most common presumptive opportunistic infections (OIs) identified were tuberculosis (32%), oesophageal candidiasis (9%), Pneumocystis jirovecii pneumonia (PJP) (8%), and histoplasmosis (7%). On multivariable analysis, independent predictors of mortality were CD4 count ≤200 cells/mm3 (adjusted odds ratio [aOR]: 16.6, 95% confidence interval [CI]: 3.7-74.4), PJP (aOR: 18.5, 95% CI: 4.68-73.3), oesophageal candidiasis (aOR: 27.5, 95% CI: 5.5-136.9), malignancy (aOR:15.2, 95% CI: 2.3-99.4), and bacteriuria (aOR:7.9, 95% CI: 1.2-50.5). Being on antiretroviral therapy prior to hospitalization (aOR: 0.2, 95% CI: 0.06-0.5) was associated with decreased mortality. CONCLUSION: This study showed that most patients who died during hospitalization on the Jagori Ward had HIV-related illnesses which could have been averted with earlier diagnosis of HIV and proper management of OIs. It is prudent to develop a national HIV screening programme to facilitate early identification of HIV.