Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh.

BACKGROUND: We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development. METHODS: Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate (SSG), miltefosine (MF), paromomycin intramuscular injection (PMIM), liposomal amphotericin B [AmBisome (AMB)] in a single dose (SDAMB) and in multidose (MDAMB), and combination therapies by AMB+PMIM, AMB+MF, and PMIM+MF. Follow up period was 4 years after treatment. Cohorts were prospective except SSG (retrospective) and MF (partially retrospective). We compared incidence proportion and rate in 100-person-4year of PKDL and VLR by treatment regimens using univariate and multivariate analysis. FINDINGS: 974 of 984 enrolled participants completed the study. Overall incidence proportion for PKDL and VLR was 12.3% (95% CI, 10.4%-14.5%) and 7.0% (95% CI, 5.6%-8.8%) respectively. The incidence rate (95% CI) of PKDL and VLR was 14.0 (8.6-22.7) and 7.6 (4.1-14.7) accordingly. SSG cohort had the lowest incidence rate of PKDL at 3.0 (1.3-7.3) and VLR at 1.8 (0.6-5.6), followed by MDAMB at 8.2 (4.3-15.7) for PKDL and at 2.7 (0.9-8.4) for VLR. INTERPRETATION: Development of PKDL and VLR is related with treatment regimens for VL. SSG and MDAMB resulted in less incidence of PKDL and VLR compared to other treatment regimens. MDAMB should be considered for VL as a first step for prevention of PKDL and VLR since SSG is highly toxic and not recommended for VL.

Molecular characterization and drug susceptibility profile of Mycobacterium tuberculosis isolates from Northeast Bangladesh.

Tuberculosis (TB) remains a major public health problem worldwide including in Bangladesh. Molecular epidemiological tools provide genotyping profiles of Mycobacterium tuberculosis (M. tuberculosis) strains that can give insight into the transmission of TB in a specific region. The objective of the study was to identify the genetic diversity and drug susceptibility profile of M. tuberculosis strains circulating in the northeast Bangladesh. A total of 244 smear-positive sputum specimens were collected from two referral hospitals in Mymensingh and Netrakona districts. The isolated strains were genotyped by deletion analysis, spoligotyping, and MIRU-VNTR typing. We also analyzed the distributions of drug susceptibility pattern and demographic data among different genotypes. All isolates were identified as M. tuberculosis and among them 167 strains (68.44%) were 'ancestral' and the remaining 77 (31.56%) were 'modern' type. Spoligotyping analysis yielded 119 distinct patterns, among them, 86 isolates had unique patterns and the remaining 158 were grouped into 33 distinct clusters containing 2 to 18 isolates. The predominant spoligotypes belong to the EAI lineage strains, comprising 66 (27.04%) isolates followed by Beijing (7.38%), T1 (6.15%), CAS1-Delhi (5.33), LAM9 (3.28%), MANU-2 and X2. MIRU-VNTR analysis revealed 167 isolates (68%) had unique patterns, whereas 77 (32%) were grouped into 26 clusters and the rate of recent transmission was 20.9%, suggesting that the majority of TB cases in this region are caused by the reactivation of previous TB infections rather than recent transmission. About 136 (55.7%) isolates were sensitive to four anti-TB drugs, 69 (28.3%) were resistant to one or more (except rifampicin and isoniazid combination) drugs and 39 (15.9%) were MDR. In conclusion, our study provides a first insight into molecular characterization and drug resistance profile of M. tuberculosis strains in northeast Bangladesh which will ultimately contribute to the national TB control program.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

INTRODUCTION: Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. MATERIAL AND METHODS: We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. RESULTS: Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. CONCLUSIONS: In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.

Household-level risk factors for influenza among young children in Dhaka, Bangladesh: a case-control study.

OBJECTIVES: To identify household-level factors associated with influenza among young children in a crowded community in Dhaka, Bangladesh. METHODS: We conducted a case-control study using existing active surveillance for respiratory illness. Cases were children aged 12-59 months with laboratory-confirmed influenza. Controls were children frequency-matched by age group with no respiratory illness in the prior 6 months. We interviewed caregivers and observed household handwashing behaviour. Soap consumption was estimated by summing weight differences of three bars of soap sequentially left in each household. We measured concentrations of airborne particulate matter <2.5 µg in diameter (PM2.5) in a subset of households. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: We enrolled 145 cases and 341 controls between March 2009 and April 2010. Case and control household members were observed to wash hands with similar frequency during a 5-h period (mean, 0.64 events vs. 0.63, P = 0.87), and similar daily soap consumption per capita (mean 2.92 grams vs. 2.93, P = 0.92). Case households were more likely than controls to have crowded (≥4 persons) sleeping areas (aOR = 1.67, CI: 1.06-2.63) and cross-ventilated cooking spaces (aOR = 1.75, CI: 1.16-2.63). Case and control households had similar median 24-h geometric mean PM2.5 concentrations in the cooking (69.2 vs. 69.6 µg/m(3), P = 0.45) and sleeping (65.4 vs. 67.4 µg/m(3), P = 0.19) spaces. CONCLUSIONS: Handwashing with soap was practiced infrequently and was not associated with paediatric influenza in this community. Interventions aimed at crowded households may reduce influenza incidence in young children.