Generation of Full-Length Class I Human Leukocyte Antigen Gene Consensus Sequences for Novel Allele Characterization.

BACKGROUND: Routine, high-resolution human leukocyte antigen (HLA) genotyping by next generation sequencing within clinical immunogenetics laboratories can now provide the full-length gene sequence characterization of fully phased HLA alleles. This powerful technique provides insights into HLA variation beyond the traditionally characterized antigen recognition domain, providing sequence annotation across the entire gene including untranslated and intronic regions and may be used to characterize novel alleles from massively parallel sequencing runs. METHODS: We evaluated the utility of the Omixon Holotype HLA assay to generate credible, fully phased full-length gene consensus sequences for 50 individuals at major histocompatibility complex, class I, A (HLA-A), HLA-B, and HLA-C loci (300 genotyped alleles in total) to identify and characterize novel class I HLA alleles using our downstream analytical pipeline. RESULTS: Our analysis revealed that 7.7% (23/300) of genotyped class I HLA alleles contain novel polymorphisms. Interestingly, all of the novel alleles identified by our analysis were found to harbor sequence variations within intronic regions of the respective locus. In total our analysis identified 17 unique novel class I HLA alleles from 23 of the 300 genotyped alleles and generated full-length gene sequence annotations for 9 previously incompletely annotated HLA class I allele sequences derived from 14 of the 300 genotyped alleles. CONCLUSIONS: The demonstrated utility of the Omixon Holotype HLA assay in combination with our downstream analytical framework to generate fully phased, full-length gene consensus sequences for the identification and characterization of novel HLA alleles, facilitates the study of HLA polymorphism beyond the antigen recognition domain in human health and disease.

Prevalence and factors associated with caesarean section in four Hard-to-Reach areas of Bangladesh: Findings from a cross-sectional survey.

BACKGROUND: Caesarean section (C-section) is a major obstetric life-saving intervention for the prevention of pregnancy and childbirth related complications. Globally C-section is increasing, as well as in Bangladesh. This study identifies the prevalence of C-section and socio-economic and health care seeking related determinants of C-section among women living in hard-to-reach (HtR) areas in Bangladesh. METHODS: A cross-sectional survey was conducted using a structured questionnaire between August and December 2017 at four distinct types of HtR areas of Bangladesh, namely coastal, hilly, haor (wetland), and char areas (shallow land-mass rising out of a river). Total 2,768 women of 15-49 years of age and who had delivery within one year prior to data collection were interviewed. For the analysis of determinants of C- section, the explanatory variables were maternal age, educational status of women and their husbands, women's religion, employment status and access to mobile phone, wealth index of the household, distance to the nearest health facility from the household, the number of ANC visits and presence of complications during pregnancy and the last childbirth. Logistic regression model was run among 850 women, who had facility delivery. Variables found significantly associated with the outcome (C-section) in bivariate analysis were included in the multivariable logistic model. A p-value <0.05 was considered as statistically significant in the analyses. RESULTS: Of the 2,768 women included in the study, 13% had C-sections. The mean (±SD) age of respondents was 25.4 (± 0.1) years. The adjusted prevalence of C-section was 13.1 times higher among women who had their delivery in private facilities than women who delivered in public facilities (Adjusted Odds Ratio, AOR: 13.1; 95% CI 8.6-19.9; p-value: <0.001). Women from haor area and coastal area had 4.7 times (AOR: 4.7; 95% CI 2.4-9.4; p value: <0.001) and 6.8 times (AOR: 6.8; 95% CI 3.6-12.8; p value: <0.001) more chance of having C-section, respectively, than women living in char area. Among women who reported complications during the last childbirth, the AOR of C-section was 3.6 times higher than those who did not report any complication (AOR: 3.6; 95% CI 2.4-5.4; p value: <0.001). CONCLUSIONS: The study identifies that the prevalence of C-sections in four HtR areas of Bangladesh in substantially below the national average, although, the prevalence was higher in coastal areas than three other HtR regions. Both public and private health services for C-section should be made available and accessible in remote HtR areas for women with pregnancy complications. Establishment of an accreditation system for regulating private hospitals are needed to ensure rational use of the procedure.

The Effect of a Club in Making Differences in Knowledge, Attitude, and Practices on Family Planning Among Married Adolescent Girls in Urban Slums in Bangladesh.

Early marriage and childbearing have led to Bangladesh having the highest adolescent fertility rate in the Asia Pacific region. Adolescent pregnancy is correlated with pregnancy-related complications, preterm delivery, delivery of low-birth weight babies, and spousal violence. A quasi-experimental study was conducted in four urban slums (two intervention and two control areas) of Dhaka from July 2014 to August 2016 to assess the effectiveness of a married adolescent girls club (MAG club) in reducing the unmet need for family planning (FP) among married girls between the ages of 14 and 19 (n = 1601, 799 in intervention and 802 in control areas). The percentages of the targeted population using any modern method of contraception were significantly higher among respondents in the intervention areas than those in the control areas (72.6% versus 63.5%). The unmet need for FP was significantly lower among respondents in the intervention areas than that of the control areas (16.2% versus 20.7%). The MAG club was a well-received strategy to provide comprehensive information on FP, which in turn helped improve contraceptive method practices and reduced the unmet need for FP among married adolescent girls in urban slums in Bangladesh. The government could leverage its existing resources to expand the MAG Club model in rural parts of the country to achieve the targets outlined in its Adolescent Reproductive Health Strategy.

Quality of care during childbirth at public health facilities in Bangladesh: a cross-sectional study using WHO/UNICEF 'Every Mother Every Newborn (EMEN)' standards.

BACKGROUND: This manuscript presents findings from a baseline assessment of health facilities in Bangladesh prior to the implementation of the 'Every Mother Every Newborn Quality Improvement' initiative. METHODOLOGY: A cross-sectional survey was conducted between June and August 2016 in 15 government health facilities. Structural readiness was assessed by observing the physical environment, the availability of essential drugs and equipment, and the functionality of the referral system. Structured interviews were conducted with care providers and facility managers on human resource availability and training in the maternal and newborn care. Observation of births, reviews of patient records and exit interviews with women who were discharged from the selected health facilities were used to assess the provision and experience of care. RESULTS: Only six (40%) facilities assessed had designated maternity wards and 11 had newborn care corners. There were stock-outs of emergency drugs including magnesium sulfate and oxytocin in nearly all facilities. Two-thirds of the positions for medical officers was vacant in district hospitals and half of the positions for nurses was vacant in subdistrict facilities. Only 60 (45%) healthcare providers interviewed received training on newborn complication management. No health facility used partograph for labour monitoring. Blood pressure was not measured in half (48%) and urine protein in 99% of pregnant women. Only 27% of babies were placed skin to skin with their mothers. Most mothers (97%) said that they were satisfied with the care received, however, only 46% intended on returning to the same facility for future deliveries. CONCLUSIONS: Systematic implementation of quality standards to mitigate these gaps in service readiness, provision and experience of care is the next step to accelerate the country's progress in reducing the maternal and neonatal deaths.

Bangladesh: a success case in combating childhood diarrhoea.

BACKGROUND: Bangladesh had a large reduction in childhood deaths due to diarrhoeal disease in recent decades. This paper explores the preventive, promotive, curative and contextual drivers that helped Bangladesh achieve this exemplary success. METHODS: Primary and secondary data collection approaches were used to document trends in reduction of Diarrhoea Specific Mortality Rate (DSMR) between 1980 and 2015, understand what policies and programmes played key roles, and estimate the contribution of specific interventions that were implemented during the period. Data acquisition involved relevant document reviews and in-depth interviews with key stake-holders. A systematic search of literature was undertaken to explore socio-economic, aetiological, behavioural, and nutritional drivers of diarrhoeal disease reduction in Bangladesh. Finally, we used LiST (Lives Saved Tool) to model the contributions of the relevant interventions during three time periods (1980-2015, 1980-2000 and 2000-2015), and to project the number of lives saved in 2030 (compared to 2015) if these interventions were implemented at near universal coverage (90%). RESULTS: The factors which likely had the most impact on DSMR were the coordinated efforts of the Government of Bangladesh (GoB) with non-government organizations (NGOs) and the private sector that enabled swift implementation, at scale, of interventions like oral rehydration solution (ORS) and zinc, promotion of breastfeeding, handwashing and sanitary latrines (WASH), as well as improvements in female education and nutrition. Compared to 1980, we found ORS and reduction in stunting prevalence had the greatest impact on DSMR, saving roughly 70 000 lives combined in 2015. Until 2000, ORS had a higher contribution to DSMR reduction than reduction in stunting prevalence. This proportionate contribution was reversed during 2000-2015. At near universal coverage (90%) of combined direct diarrhoeal disease, nutrition and WASH interventions, we project that an additional 5356 deaths due to diarrhoea could be averted in 2030. CONCLUSION: Bangladesh's achievement in reduction of DSMR highlights the important role of an enabling policy environment that fostered coordinated efforts of the public and private sectors and NGOs for maximal impact. To maintain this momentum, evidence-based interventions should be scaled up at universal coverage.