Impact of integrated community-facility interventions model on neonatal mortality in rural Bangladesh- a quasi-experimental study.

BACKGROUND: Neonatal mortality remains unacceptably high in many countries. WHO recommends that all newborns be assessed during the postnatal period and should seek prompt medical care if there is any danger sign. However, in many developing countries, only a small proportion of women receive postnatal care. Also, the quality of care in public health facilities is sub-optimal. METHODS: We designed an intervention package that included community health worker-assisted pregnancy and birth surveillance, post-natal visits to assess newborns on the first, third, seventh and twenty-eighth days of birth, referral for facility-based care, and establishing a newborn stabilization unit at the first level referral health facility. We did a quasi-experimental, propensity-score matched, controlled study in the Sylhet region of Bangladesh. We used a cross-sectional survey method at baseline and endline to measure the effect of our intervention. We considered two indicators for the primary outcome-(a) all-cause neonatal mortality rate and (b) case fatality of severe illness. Secondary outcomes were the proportion of neonates with signs and symptoms of severe illness who sought care in a hospital or a medically qualified provider. RESULTS: Our sample size was 9,940 live births (4,257 at baseline, 5,683 at end line). Our intervention was significantly associated with a 39% reduction (aRR = 0.61, 95% CI: 0.40-0.93; p = 0.046) in the risk of neonatal mortality and 45% reduction (aRR = 0.55, 95% CI: 0.35-0.86; p = 0.001) in the risk of case fatality of severe illness among newborns in rural Bangladesh. The intervention significantly increased the care-seeking for severe illness at the first-level referral facility (DID 36.6%; 95% CI % 27.98 to 45.22; p<0.001). INTERPRETATION: Our integrated community-facility interventions model resulted in early identification of severely sick neonates, early care seeking and improved treatment. The interventions led to a significant reduction in all-cause neonatal mortality and case fatality from severe illness.

Gauging the skin resident Leishmania parasites through a loop mediated isothermal amplification (LAMP) assay in post-kala-azar dermal leishmaniasis.

Despite the availability of highly sensitive polymerase chain reaction (PCR)-based methods, the dearth of remotely deployable diagnostic tools circumvents the early and accurate detection of individuals with post-kala-azar dermal leishmaniasis (PKDL). Here, we evaluate a design-locked loop-mediated isothermal amplification (LAMP) assay to diagnose PKDL. A total of 76 snip-skin samples collected from individuals with probable PKDL (clinical presentation and a positive rK39 rapid diagnostic test (RDT)) were assessed by microscopy, qPCR, and LAMP. An equal number of age and sex-matched healthy controls were included to determine the specificity of the LAMP assay. The LAMP assay with a Qiagen DNA extraction (Q-LAMP) showed a promising sensitivity of 72.37% (95% CI: 60.91-82.01%) for identifying the PKDL cases. LAMP assay sensitivity declined when the DNA was extracted using a boil-spin method. Q-qPCR showed 68.42% (56.75-78.61%) sensitivity, comparable to LAMP and with an excellent agreement, whereas the microscopy exhibited a weak sensitivity of 39.47% (28.44-51.35%). When microscopy and/or qPCR were considered the gold standard, Q-LAMP exhibited an elevated sensitivity of 89.7% (95% CI: 78.83-96.11%) for detection of PKDL cases and Bayesian latent class modeling substantiated the excellent sensitivity of the assay. All healthy controls were found to be negative. Notwithstanding the optimum efficiency of the LAMP assay towards the detection of PKDL cases, further optimization of the boil-spin method is warranted to permit remote use of the assay.

Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study.

INTRODUCTION: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care. METHODS AND ANALYSIS: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies. ETHICS AND DISSEMINATION: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings. TRIAL REGISTRATION NUMBER: NCT04285021.

Evidence-based diagnostic algorithm for visceral leishmaniasis in Bangladesh.

Evidence-based diagnostic algorithm is highly recommended for the visceral leishmaniasis (VL). This cross-sectional study was performed in Bangladesh to evaluate VL diagnostic tools including serology, buffy coat smear microscopy for LD body and various DNA-based techniques using buffy coat in 100 confirmed VL cases and 100 controls. The performance of tools against spleen smear (gold standard) was evaluated using kappa coefficient. Diagnostic precision and other inherent indicators were considered for index scoring (IS) of performance of tools using factor analysis. A diagnostic algorithm was formulated based on the IS and availability of the tools at different health care facilities of Bangladesh. A high level of agreement (kappa ≥  0.80) was observed for all the diagnostic tools. The highest kappa coefficients were found for rK39 RDT and rK39 ELISA (0.95), followed by ssuRNA-PCR (0.94), Buffy coat smear (0.93), rK28 ELISA (0.92), rK28 RDT (0.89), LAMP (0.89), Mini-exon PCR (0.86), ITS1 (0.85), and ITS2 PCR (0.80). rK39 RDT was found to be the best diagnostic test (IS: 1.7) followed by rK28 RDT (IS: 1.5), buffy coat smear microscopy (IS: 0.5), rK39 & rK28 ELISA (IS: 0.3), ssuRNA-PCR (IS: -0.7) and LAMP, Mini-exon, ITS1, & ITS2 PCR (IS: -0.9). rK39 RDT has been proposed as the best option for primary health care facilities, while buffy coat smear microscopy was found to be a good adjunct for confirmation of serology-positive cases and proposed for secondary and tertiary facilities. ssuRNA-PCR or LAMP can be an alternate confirmation tool only applicable to the tertiary facilities.

An Association between Rainy Days with Clinical Dengue Fever in Dhaka, Bangladesh: Findings from a Hospital Based Study.

BACKGROUND: Dengue, a febrile illness, is caused by a Flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Climate influences the ecology of the vectors. We aimed to identify the influence of climatic variability on the occurrence of clinical dengue requiring hospitalization in Zone-5, a high incidence area of Dhaka City Corporation (DCC), Bangladesh. METHODS AND FINDINGS: We retrospectively identified clinical dengue cases hospitalized from Zone-5 of DCC between 2005 and 2009. We extracted records of the four major catchment hospitals of the study area. The Bangladesh Meteorological Department (BMD) provided data on temperature, rainfall, and humidity of DCC for the study period. We used autoregressive integrated moving average (ARIMA) models for the number of monthly dengue hospitalizations. We also modeled all the climatic variables using Poisson regression. During our study period, dengue occurred throughout the year in Zone-5 of DCC. The median number of hospitalized dengue cases was 9 per month. Dengue incidence increased sharply from June, and reached its peak in August. One additional rainy day per month increased dengue cases in the succeeding month by 6% (RR = 1.06, 95% CI: 1.04-1.09). CONCLUSIONS: Dengue is transmitted throughout the year in Zone-5 of DCC, with seasonal variation in incidence. The number of rainy days per month is significantly associated with dengue incidence in the subsequent month. Our study suggests the initiation of campaigns in DCC for controlling dengue and other Aedes mosquito borne diseases, including Chikunguniya from the month of May each year. BMD rainfall data may be used to determine campaign timing.

Home Fortification of Rice With Lime: A Novel Potential Way to Reduce Calcium Deficiency in Bangladesh.

BACKGROUND: In order to improve calcium status, fortified rice should have acceptable organoleptic properties of that food. OBJECTIVE: We aimed to assess whether home fortification of rice with slaked lime can increase calcium content of rice and whether this fortified rice is well tolerated in a nutritionally at-risk population. METHODS: This experimental study measured the calcium content of rice cooked with different concentration of lime and assessed the acceptability of fortified rice among 400 women and children. Each participant received fortified rice with one of five concentrations of lime (0, 2.5, 5, 7.5 or 10 gm per 500 gm of rice), with or without additional foods (lentil soup or fried green papaya). All participants were asked to score the organoleptic qualities on a hedonic scale. RESULTS: Analysis showed that rice calcium content increased in a dose- response manner with increased lime during cooking (76.03, 205.58, 427.55, 614.29 and 811.23 mg/kg for given lime concentrations). Acceptability of the meal was greater when additional foods were served with rice at all lime concentrations. In both groups, the 7.5M arm reported highest overall acceptability (children, 6.25; women 6.10). This study found significant association between overall acceptability (different concentrations of lime mixed rice; with/without additional foods) and between groups (women vs. children) (p value = < 0.001) where-as no association was found within groups. CONCLUSIONS: Lime-fortified rice can be feasible considering the calcium uptake of rice and organoleptic character. Further research on bioavailability can establish a solid foundation that will support design of an effective intervention to reduce calcium deficiency in this population.

Evaluation of Real-time PCR for Diagnosis of Post-Kala-azar Dermal Leishmaniasis in Endemic Foci of Bangladesh.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a sequel to visceral leishmaniasis (VL), which is found in VL-endemic countries including Bangladesh. Because of these enigmatic cases, the success of the National Kala-azar Elimination Program is under threat. To date, diagnostic methods for PKDL cases in endemic regions have been limited to clinical examination and rK39 test or microscopy, and a suitable and accurate alternative method is needed. In this study, we investigated the application of real-time polymerase chain reaction (PCR) as a potential method for diagnosis of PKDL in comparison with microscopy. METHODS: Ninety-one suspected macular PKDL cases from Mymensingh district, Bangladesh, were enrolled in the study after diagnosis by clinical examination and an rK39 strip test. All of them responded after completion of the treatment with miltefosine. During enrollment, a skin biopsy was done for each patient, and both microscopy and real-time PCR were performed for detection and quantification of Leishmania donovan body (LDB) and LD DNA, respectively. RESULTS: Real-time PCR detected 83 cases among all suspected PKDL patients, with an encouraging sensitivity of 91.2% (83.4%-96.1%), whereas microscopy showed 50.6% (39.9%-61.2%) sensitivity. Among all suspected PKDL cases, 42 cases were positive in both microscopy and qPCR, whereas 41 cases were detected as positive through qPCR only. CONCLUSIONS: This study provides evidence that real-time PCR is a promising tool for diagnosis of PKDL in endemic regions. In addition to diagnosis, the quantitative ability of this method could be further exploited for after-treatment prognosis and cure assessment of PKDL cases.

Post-Kala-Azar Dermal Leishmaniasis Without Previous History of Visceral Leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) without previous visceral leishmaniasis (VL) is a rare dermatological manifestation of Leishmania infection. To date, most of the reported cases neither showed parasitological confirmation nor explained the outcome of treatment. Herein, we report three confirmed cases that were were successfully cured after miltefosine treatment.

Validation of an anti-measles virus-specific IgG assay with oral fluid samples for immunization surveillance in Bangladesh.

Immune marker surveys may be used as substitutes or in conjunction with traditional surveys to monitor immunization program performance. This study assessed the validity and reliability of the Microimmune anti-measles virus-specific IgG ELISA with oral fluid samples (OF-ELISA) among a random sample of children ages 12-16 months in Bangladesh. Up to two oral fluid samples and one serum sample were analyzed for the presence of protective levels of anti-measles IgG antibodies. Results from the OF-ELISA were compared to the Enzygnost anti-measles IgG ELISA with serum and multivariate logistic regression models were developed to identify risk factors for false negative oral fluid results. Anti-measles IgG antibodies were measured in 330 paired oral fluid and serum samples. Immune marker prevalence of measles IgG antibodies was significantly higher in serum (88.1%, 95% CI: [84.1, 91.5]) than oral fluid (56.1% [50.2, 61.5]). Sensitivity (60.2% [54.1, 66.0]) and specificity (75.7% [58.8, 88.2]) of the OF-ELISA were lower than expected, but sensitivity significantly improved for individuals with higher anti-measles IgG in serum. False negative oral fluid results were associated with month of sample collection and variability between data collectors and assay procedures. Due to poor performance, caution should be exercised when using oral fluid samples to assess population immunity to measles virus, especially in highly vaccinated populations.

Causes of neonatal and maternal deaths in Dhaka slums: implications for service delivery.

BACKGROUND: Bangladesh has about 5.7 million people living in urban slums that are characterized by adverse living conditions, poor access to healthcare services and health outcomes. In an attempt to ensure safe maternal, neonatal and child health services in the slums BRAC started a programme, MANOSHI, in 2007. This paper reports the causes of maternal and neonatal deaths in slums and discusses the implications of those deaths for Maternal Neonatal and Child Health service delivery. METHODS: Slums in three areas of Dhaka city were selected purposively. Data on causes of deaths were collected during 2008-2009 using verbal autopsy form. Two trained physicians independently assigned the cause of deaths. RESULTS: A total of 260 newborn and 38 maternal deaths were identified between 2008 and 2009. The majority (75%) of neonatal deaths occurred during 0-7 days. The main causes of deaths were birth asphyxia (42%), sepsis (20%) and birth trauma (7%). Post partum hemorrhage (37%) and eclampsia (16%) were the major direct causes and hepatic failure due to viral hepatitis was the most prevalent indirect cause (11%) of maternal deaths. CONCLUSION: Delivery at a health facility with child assessment within a day of delivery and appropriate treatment could reduce neonatal deaths. Maternal mortality is unlikely to reduce without delivering at facilities with basic Emergency Obstetric Care (EOC) and arrangements for timely referral to EOC. There is a need for a comprehensive package of services that includes control of infectious diseases during pregnancy, EOC and adequate after delivery care.