Arup Dutta

Malaria incidence and prevalence on Pemba Island before the onset of the successful control intervention on the Zanzibar Archipelago

BackgroundMalaria incidence has been reported to decrease substantially in parts of sub-Saharan Africa, including the Zanzibar Archipelago in East Africa. A cohort study with an intensive follow-up on Pemba Island just before the onset of the highly successful malaria control intervention was conducted. The reported estimates of parasite prevalence and incidence can serve as a robust baseline to evaluate the effect size of the successful interventions and the potential contribution of quality controls and other factors associated with research studies in the decreased estimate of transmission.MethodsIn a rural clinic, two successive cohorts of 537 children total aged 2-23 months were followed for six months each with an intensive visitation schedule of bi-weekly follow-up. Robust estimates of incidence and prevalence according to four different malaria definitions were obtained.ResultsMalaria incidence and prevalence placed Pemba Island in a hyperendemic rather than holoendemic setting for the years 2003-2005. Overall parasite prevalence was estimated to be 39% - with monthly estimates varying between 30% and 50%. Incidence of malaria varied between 2.3 and 3.8 malaria episodes per year based on a diagnosis of fever and various microscopy-based parasite thresholds and between 4.8 and 5.7 based on a diagnosis of fever and 100 parasites/microliter analogous to detection by rapid diagnostic tests. Both parasite densities and malaria incidence increased with age and rainy season. Malaria incidence also varied substantially between the individual villages within the study area.ConclusionsPemba Island was previously considered holo-endemic for Malaria. The data suggest that the transmission situation on Pemba Island was significantly lower in 2003-2005 suggesting a hyper-endemic or meso-endemic transmission environment. The figures were obtained just before the onset of the highly successful malaria control intervention by impregnated bed nets and IRS on the Zanzibar Archipelago and provide robust estimates of the malaria transmission situation prior to the control programme. Together with other published data, the results suggest that malaria transmission had started to decrease before the onset of the control programme. The local heterogeneity in malaria incidence highlights the importance of a micro-epidemiological approach in the context of malaria control and elimination.

Efficiency of red cell distribution width in identification of children aged 1-3 years with iron deficiency anemia against traditional hematological markers

BackgroundCurrent strategy to identify iron deficiency anemia relies on markers involving high costs. Reports have suggested red cell distribution width (RDW) as a potential screening test for identifying iron deficiency anemia (IDA) but studies in pediatric populations are lacking. Our study elucidates the discriminative ability of RDW for detecting IDA among young children.Methods2091 blood reports of children aged 1–3xa0years from an urban low socio-economic population of Delhi were analyzed to evaluate the sensitivity of RDW in discriminating IDA using receiver’s operating characteristic curve. Hemoglobin and RDW were estimated using coulter, zinc protoporphyrin with AVIV fluorometer and serum ferritin by enzyme linked immunosorbent assay.ResultsA total of 1026 samples were classified as iron deficient anemia using gold standard. As a marker of overall efficiency, area under the curve for RDW was 0.83 (95% CI, 0.81- 0.84; p <u20090.001). Sensitivity of RDW at cut-off of 18% to detect iron deficiency anemia was 76.5% and specificity 73.1% yielding a positive predictive value of 73% and negative predictive value of 76%. At a cut-off of RDW 16.4%, the sensitivity was 94% and at a cut-off of 21%, the specificity was 95%. Combination of hemoglobin ≤10xa0g/dL and RDW >15%, yielded a sensitivity of 99% and specificity of 90%. These data suggest that simple coulter analysis estimating hemoglobin and RDW can be used for identification of children in need for iron therapy.ConclusionsIn India and similar settings, RDW >15% with hemoglobin ≤10.0xa0g/dL identifies iron deficient anemic children without need for iron status markers which could help reduce cost of management especially in poor settings.Trial registrationClinicaltrials.gov NCT00255385.

Delivery, immediate newborn and cord care practices in Pemba Tanzania: a qualitative study of community, hospital staff and community level care providers for knowledge, attitudes, belief systems and practices

BackgroundDeaths during the neonatal period account for almost two-thirds of all deaths in the first year of life and 40 percent of deaths before the age of five. Most of these deaths could be prevented through proven cost-effective interventions. Although there are some recent data from sub-Saharan Africa, but there is paucity of qualitative data from Zanzibar and cord care practices data from most of East Africa. We undertook a qualitative study in Pemba Island as a pilot to explore the attitudes, beliefs and practices of the community and health workers related to delivery, newborn and cord care with the potential to inform the main chlorhexidine (CHX) trial.Methods80 in-depth interviews (IDI) and 11 focus group discussions (FGD) involving mothers, grandmothers, fathers, traditional birth attendants and other health service providers from the community were undertaken. All IDIs and FGDs were audio taped, transcribed and analyzed using ATLAS ti 6.2.ResultsPoor transportation, cost of delivery at hospitals, overcrowding and ill treatment by hospital staff are some of the obstacles for achieving higher institutional delivery. TBAs and health professionals understand the need of using sterilized equipments to reduce risk of infection to both mothers and their babies during delivery. Despite this knowledge, use of gloves during delivery and hand washing before delivery were seldom reported. Early initiation of breastfeeding and feeding colostrum was almost universal. Hospital personnel and trained TBAs understood the importance of keeping babies warm after birth and delayed baby’s first bath. The importance of cord care was well recognized in the community. Nearly all TBAs counseled the mothers to protect the cord from dust, flies and mosquitoes or any other kind of infections by covering it with cloth. There was consensus among respondents that CHX liquid cord cleansing could be successfully implemented in the community with appropriate education and awareness.ConclusionThe willingness of community in accepting a CHX cord care practice was very high; the only requirement was that a MCH worker needs to do and demonstrate the use to the mother.Trial registrationClinicalTrials.gov: NCT01528852

Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial

BACKGROUNDnIn low-income countries, including the east African region, a third of neonatal deaths are due to infections. A substantial proportion of these have been attributed to sepsis, which can result from umbilical cord infections. Evidence from Asia suggests that chlorhexidine application to the neonatal umbilical cord reduces mortality, but no data from Africa are available. We aimed to assess the effect of umbilical cord cleansing with 4% chlorhexidine solution on neonatal mortality and omphalitis in rural settings of sub-Saharan Africa.nnnMETHODSnWe did a community-based randomised controlled trial on Pemba Island, Zanzibar, Tanzania. All eligible babies (aged 1 h to 48 h, without congenital malformations) from hospital-based and community-based deliveries on Pemba Island were enrolled. Participants were randomly assigned to either 4% free chlorhexidine for cord care or to dry cord care using a computer-generated random sequence. For babies allocated to the chlorhexidine group, mothers or caretakers were advised to apply the solution to the cord every day until 3 days after the cord had dropped off. Cord stumps were examined for redness, pus, swelling, and foul odour on day 0, 1, 4, 10, and 28. The primary outcome for this study was mortality until day 28 on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, number NCT01528852.nnnFINDINGSnBetween May 19, 2011, and Aug 31, 2014, 36u2008911 newborn babies were enrolled into the chlorhexidine (n=18u2008015) and dry cord care study (n=18u2008896) groups. 17u2008468 (96·9%) of 18u2008015 neonates in the chlorhexidine group were available for complete follow-up (28 days) compared with 18u2008384 (97·3%) of 18u2008896 neonates in the dry cord care group. Mortality rate in the chlorhexidine group (10·5 deaths per 1000 livebirths) was not significantly lower than that in the dry cord care group (11·7 per 1000 livebirths; relative risk 0·90, 0·74-1·09; p=0·27).nnnINTERPRETATIONnOur findings do not support the use of chlorhexidine for reduction of neonatal mortality in this east African setting, which might not justify a change in the WHO policy. To inform global policy, a detailed meta-analysis and pooled analysis needs to be undertaken using data from both African and Asian settings.nnnFUNDINGnBill & Melinda Gates Foundation.

Neonatal mortality within 24 hours of birth in six low-and lower-middle-income countries

Abstract Objective To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries. Methods We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality. Findings Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality. Conclusion Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings.

Effect of Iron/Folic Acid Supplementation on the Outcome of Malaria Episodes Treated with Sulfadoxine-Pyrimethamine

Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.

4 Trials of Improved Practices - A Pilot Study Evaluating the Acceptability and Preferences for a Chlorhexidine Cord Care Intervention

Background Chlorhexidine, a broad-spectrum topical antiseptic with strong residual activity, has a potential to reduce infections during the neonatal period. However, the challenge remains what would be the best mode to deliver the intervention. As a part of formative research, we evaluated three possible modes of chlorhexidine delivery i.e. 100ml bottle with cotton swab, 10ml single use dropper bottle and 3g single application squeeze tube containing gel, as an umbilical cord care intervention using Trials for Improved Practices (TIPS) methodology in preparation for a large double-blind randomized controlled trial evaluating the impact of chlorhexidine. in Pemba, Tanzania. Methods 204 mother-newborn pairs were enrolled from hospital and community setting. Three different modes of application of intervention were tested (3 days for each preparation) in a cross over design. Mothers (on day 10), MCH, TBA and hospital staff was interviewed about their experience and feedback of their preference among the three delivery modes. Convenient and preference scores were calculated based on their feedback. Results 97% mothers applied intervention for all 9 days. 10ml dropper bottle (49.7%) was rated as most convenient by the mothers, gel tube (32.2%) and 100ml bottle (19.8%). Mothers opted 10ml dropper bottle (44.6%) as their first choice over the 100ml bottle (21.5%) or gel tube (33.9%). MCH/hospital staff’s choice was to use gel tube (84%) or 10ml dropper bottle (82%). Conclusions Overall acceptability was high, in terms of convenience and preference 10ml dropper bottle was a winner. Based on their choice the 10ml dropper bottle was selected for RCT.

Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study

Summary Background Modelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa. Methods In this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach. Findings We identified 278u2008186 pregnancies and 263u2008563 births across the study sites, with outcomes ascertained for 269u2008630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100u2008000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100u2008000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa). Interpretation These results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era. Funding Bill & Melinda Gates Foundation.

Understanding biological mechanisms underlying adverse birth outcomes in developing countries: protocol for a prospective cohort (AMANHI bio–banking) study

Objectives The AMANHI study aims to seek for biomarkers as predictors of important pregnancy–related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available. Methods AMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8–19 weeks of gestation) for population–based follow–up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field workers will collect very detailed phenotypic and epidemiological data from the pregnant woman and her family at scheduled home visits during pregnancy (enrolment, 24–28 weeks, 32–36 weeks & 38+ weeks) and postpartum (days 0–6 or 42–60). Trained phlebotomists will collect maternal and umbilical blood samples, centrifuge and obtain aliquots of serum, plasma and the buffy coat for storage. They will also measure HbA1C and collect a dried spot sample of whole blood. Maternal urine samples will also be collected and stored, alongside placenta, umbilical cord tissue and membrane samples, which will both be frozen and prepared for histology examination. Maternal and newborn stool (for microbiota) as well as paternal and newborn saliva samples (for DNA extraction) will also be collected. All samples will be stored at –80°C in the biobank in each of the three sites. These samples will be linked to numerous epidemiological and phenotypic data with unique study identification numbers. Importance of the study AMANHI biobank proves that biobanking is feasible to implement in LMICs, but recognises that biobank creation is only the first step in addressing current global challenges.

Development and validation of a simplified algorithm for neonatal gestational age assessment – protocol for the Alliance for Maternal Newborn Health Improvement (AMANHI) prospective cohort study

Objective The objective of the Alliance for Maternal and Newborn Health Improvement (AMANHI) gestational age study is to develop and validate a programmatically feasible and simple approach to accurately assess gestational age of babies after they are born. The study will provide accurate, population–based rates of preterm birth in different settings and quantify the risks of neonatal mortality and morbidity by gestational age and birth weight in five South Asian and sub–Saharan African sites. Methods This study used on–going population–based cohort studies to recruit pregnant women early in pregnancy (<20 weeks) for a dating ultrasound scan. Implementation is harmonised across sites in Ghana, Tanzania, Zambia, Bangladesh and Pakistan with uniform protocols and standard operating procedures. Women whose pregnancies are confirmed to be between 8 to 19 completed weeks of gestation are enrolled into the study. These women are followed up to collect socio–demographic and morbidity data during the pregnancy. When they deliver, trained research assistants visit women within 72 hours to assess the baby for gestational maturity. They assess for neuromuscular and physical characteristics selected from the Ballard and Dubowitz maturation assessment scales. They also measure newborn anthropometry and assess feeding maturity of the babies. Computer machine learning techniques will be used to identify the most parsimonious group of signs that correctly predict gestational age compared to the early ultrasound date (the gold standard). This gestational age will be used to categorize babies into term, late preterm and early preterm groups. Further, the ultrasound–based gestational age will be used to calculate population–based rates of preterm birth. Importance of the study The AMANHI gestational age study will make substantial contribution to improve identification of preterm babies by frontline health workers in low– and middle– income countries using simple evaluations. The study will provide accurate preterm birth estimates. This new information will be crucial to planning and delivery of interventions for improving preterm birth outcomes, particularly in South Asia and sub–Saharan Africa.