Community-based asthma assessment in young children: adaptations for a multicentre longitudinal study in South Asia.

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan. Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the 'Aetiology of Neonatal Infection in South Asia (ANISA)' study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a 'Child Card' to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels. Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges. Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children's respiratory outcomes in future translational research studies.

Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.

BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings. METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed. RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002). CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

BACKGROUND: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. METHODS: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. RESULTS: Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). CONCLUSIONS: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.

Systematic review (protocol) of clinical effectiveness and models of care of low-resource pulmonary rehabilitation.

More than half of the people with chronic respiratory diseases (CRDs) live in low- and middle-income countries (LMICs). The increasing disability, reduced productivity, associated anxiety and depression from CRDs result in social isolation and economic hardship for patients and their families. Pulmonary rehabilitation (PR) is a guideline-recommended multidisciplinary and multifaceted intervention that improves the physical and psychological condition of people with CRD. However, PR services are underprovided and uptake is poor in LMICs, especially in low-resourced setting. We aim to systematically assess the effectiveness, applicable components and mode of delivery of PR. We will search MEDLINE, EMBASE, CABI, AMED and CENTRAL from January 1990 using a PICOS search strategy (Population: adults with CRD (including chronic obstructive pulmonary disease, post-tuberculosis, remodelled asthma); Intervention: PR; Comparator: usual care; Outcomes: functional exercise capacity and Health-Related Quality-of-Life; Setting: low-resource settings). Two reviewers will independently screen titles/abstracts and full texts for eligibility and extract data from included papers. We will use the Cochrane Risk-of-Bias tool, rating the quality of evidence using GRADE. We will use narrative synthesis to answer our three objectives: What is the effectiveness of PR in low-resource settings? What components are used in effective studies? What models of service delivery are used? This systematic review will inform the potential impact and practical models of low-resource PR for the betterment of patients with CRDs to improve their substantial health-care burden and address poor quality of life.

Usability Testing of a Reusable Pulse Oximeter Probe Developed for Health-Care Workers Caring for Children < 5 Years Old in Low-Resource Settings.

Hypoxemia measured by pulse oximetry predicts child pneumonia mortality in low-resource settings (LRS). Existing pediatric oximeter probes are prohibitively expensive and/or difficult to use, limiting LRS implementation. Using a human-centered design, we developed a low-cost, reusable pediatric oximeter probe for LRS health-care workers (HCWs). Here, we report probe usability testing. Fifty-one HCWs from Malawi, Bangladesh, and the United Kingdom participated, and seven experts provided reference measurements. Health-care workers and experts measured the peripheral arterial oxyhemoglobin saturation (SpO2) independently in < 5 year olds. Health-care worker measurements were classed as successful if recorded in 5 minutes (or shorter) and physiologically appropriate for the child, using expert measurements as the reference. All expert measurements were considered successful if obtained in < 5 minutes. We analyzed the proportion of successful SpO2 measurements obtained in < 1, < 2, and < 5 minutes and used multivariable logistic regression to predict < 1 minute successful measurements. We conducted four testing rounds with probe modifications between rounds, and obtained 1,307 SpO2 readings. Overall, 67% (876) of measurements were successful and achieved in < 1 minute, 81% (1,059) < 2 minutes, and 90% (1,181) < 5 minutes. Compared with neonates, increasing age (infant adjusted odds ratio [aOR]; 1.87, 95% confidence interval [CI]: 1.16, 3.02; toddler aOR: 4.33, 95% CI: 2.36, 7.97; child aOR; 3.90, 95% CI: 1.73, 8.81) and being asleep versus being calm (aOR; 3.53, 95% CI: 1.89, 6.58), were associated with < 1 minute successful measurements. In conclusion, we designed a novel, reusable pediatric oximetry probe that was effectively used by LRS HCWs on children. This probe may be suitable for LRS implementation.

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh.

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh's national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia .  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

Factors associated with delay in care-seeking for fatal neonatal illness in the Sylhet district of Bangladesh: results from a verbal and social autopsy study.

BACKGROUND: We conducted a social and verbal autopsy study to determine cultural-, social- and health system-related factors that were associated with the delay in formal care seeking in Sylhet district, Bangladesh. METHODS: Verbal and social autopsy interviews were conducted with mothers who experienced a neonatal death between October 2007 and May 2011. We fitted a semi-parametric regression model of the cumulative incidence of seeking formal care first, accounting for competing events of death or seeking informal care first. RESULTS: Three hundred and thirty-one neonatal deaths were included in the analysis and of these, 91(27.5%) sought formal care first; 26 (7.9%) sought informal care first; 59 (17.8%) sought informal care only, and 155 (46.8%) did not seek any type of care. There was lower cumulative incidence of seeking formal care first for preterm neonates (sub-hazard ratio SHR 0.61, P = 0.025), and those who delivered at home (SHR 0.52, P = 0.010); and higher cumulative incidence for those who reported less than normal activity (SHR 1.95, P = 0.048). The main barriers to seeking formal care reported by 165 mothers included cost (n = 98, 59.4%), believing the neonate was going to die anyway (n = 29, 17.7%), and believing traditional care was more appropriate (n = 26, 15.8%). CONCLUSIONS: The majority of neonates died before formal care could be sought, but formal care was more likely to be sought than informal care. There were economic and social belief barriers to care-seeking. There is a need for programs that educate caregivers about well-recognized danger signs requiring timely care-seeking, particularly for preterm neonates and those who deliver at home.

The Effect of Integrating Family Planning with a Maternal and Newborn Health Program on Postpartum Contraceptive Use and Optimal Birth Spacing in Rural Bangladesh.

Meeting postpartum contraceptive need remains a major challenge in developing countries, where the majority of women deliver at home. Using a quasi-experimental trial design, we examine the effect of integrating family planning (FP) with a community-based maternal and newborn health (MNH) program on improving postpartum contraceptive use and reducing short birth intervals <24 months. In this two-arm trial, community health workers (CHWs) provided integrated FP counseling and services during home visits along with their outreach MNH activities in the intervention arm, but provided only MNH services in the control arm. The contraceptive prevalence rate (CPR) in the intervention arm was 15 percent higher than in the control arm at 12 months, and the difference in CPRs remained statistically significant throughout the 24 months of observation. The short birth interval of less than 24 months was significantly lower in the intervention arm. The study demonstrates that it is feasible and effective to integrate FP services into a community-based MNH care program for improving postpartum contraceptive use and lengthening birth intervals.

Local understandings and current barriers to optimal birth intervals among recently delivered women in Sylhet District, Bangladesh.

BACKGROUND: Sylhet Division in Bangladesh has the highest proportion of births spaced less than 36 months (46.5%) in Bangladesh. METHODS: Formative research was conducted on current fertility-related practices in order to explore how to integrate the promotion of healthy fertility practices into a package of maternal and neonatal care interventions. In-depth interviews, focus group discussions and other qualitative methods were utilized with recently delivered women, their families, community health workers and community leaders in Sylhet Division. RESULTS: Mothers of young children generally understood the benefits of both healthy timing and spacing of pregnancies. However, a variety of factors prevent these desired behaviours from becoming actualized, including the roles of women in the provision of children/grandchildren, local understandings of modern contraceptive methods, perceived side effects, lack of communication regarding healthy fertility practices between partners and extended family members, and limited female autonomy. CONCLUSIONS: In order to increase families' ability to achieve optimal birth intervals, we propose the promotion and integration of healthy fertility practices into antenatal and newborn care interventions, focusing on providing biomedically correct and culturally appropriate information on modern contraceptive methods to the entire family, while simultaneously encouraging open spousal and family communication patterns regarding timing and spacing of pregnancy.