Lessons from the pandemic: new best practices in selecting molecular diagnostics for point-of-care testing of infectious diseases in sub-Saharan Africa

Introduction: Point-of-care molecular diagnostics offer solutions to the limited diagnostic availability and accessibility in resource-limited settings. During the COVID-19 pandemic, molecular diagnostics became essential tools for accurate detection and monitoring of SARS-CoV-2. The unprecedented demand for molecular diagnostics presented challenges and catalyzed innovations which may provide lessons for the future selection of point-of-care molecular diagnostics. Areas Covered: We searched PubMed from January 2020 to August 2023 to identify lessons learned from the COVID-19 pandemic which may impact the selection of point-of-care molecular diagnostics for future use in sub-Saharan Africa. We evaluated this in the context of REASSURED criteria (Real-time connectivity; Ease of specimen collection; Affordable; Sensitive; Specific; User-friendly; Rapid and robust; Equipment free; and Deliverable to users at the point of need) for point-of-care diagnostics for resource-limited settings. Expert Opinion: The diagnostic challenges and successes during the COVID-19 pandemic affirmed the importance of the REASSURED criteria but demonstrated that these are not sufficient to ensure new diagnostics will be appropriate for public health emergencies. Capacity for rapid scale-up of diagnostic testing and transferability of assays, data, and technology are also important, resulting in updated REST-ASSURED criteria. Few diagnostics will meet all criteria, and trade-offs between criteria will need to be context-specific

Neonatal and child mortality data in retrospective population-based surveys compared with prospective demographic surveillance: EN-INDEPTH study.

BACKGROUND: Global mortality estimates remain heavily dependent on household surveys in low- and middle-income countries, where most under-five deaths occur. Few studies have assessed the accuracy of mortality data or determinants of capturing births in surveys. METHODS: The Every Newborn-INDEPTH study (EN-INDEPTH) included a large, multi-country survey of women aged 15-49 interviewed about livebirths and their survival status in five Health and Demographic Surveillance Systems (HDSSs). The HDSSs undertake regular household visits to register births and deaths for a given population. We analysed EN-INDEPTH survey data to assess background factors associated with not recalling a complete date-of-birth. We calculated Kaplan-Meier survival estimates for both survey and HDSS data and describe age-at-death distributions during the past 5 years for children born to the same women. We assessed the proportion of HDSS-births that could be matched on month-of-birth to survey-births and used regression models to identify factors associated with matching. RESULTS: 69,176 women interviewed in the survey reported 109,817 births and 3064 deaths in children under 5 years in the 5 years prior to the survey. In the HDSS data, the same women had 83,768 registered births and 2335 under-five deaths in the same period. A complete date-of-birth was not reported for 1-7% of survey-births. Birthdates were less likely to be complete for dead children and children born to women of higher parity or with little/no education. Distributions of reported age-at-death indicated heaping at full weeks (neonatal period) and at 12 months. Heaping was more pronounced in the survey data. Survey estimates of under-five mortality rates were similar to HDSS estimates of under-five mortality in two of five sites, higher in the survey in two sites (15%, 41%) and lower (24%) in one site. The proportion of HDSS-births matched to survey-births ranged from 51 to 89% across HDSSs and births of children who had died were less likely to be matched. CONCLUSIONS: Mortality estimates in the survey and HDSS were not markedly different for most sites. However, neither source is a "gold standard" and both sources miss some events. Research is required to improve capture and accuracy to better track newborn and child survival targets

Stillbirth maternity care measurement and associated factors in population-based surveys: EN-INDEPTH study.

BACKGROUND: Household surveys remain important sources of maternal and child health data, but until now, standard surveys such as Demographic and Health Surveys (DHS) have not collected information on maternity care for women who have experienced a stillbirth. Thus, nationally representative data are lacking to inform programmes to address the millions of stillbirths which occur annually. METHODS: The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with additional questions on pregnancy losses (FBH+) or full pregnancy history (FPH). A sub-sample, including all women reporting a recent stillbirth or neonatal death, was asked additional maternity care questions. These were evaluated using descriptive measures. Associations between stillbirth and maternal socio-demographic characteristics, babies' characteristics and maternity care use were assessed using a weighted logistic regression model for women in the FBH+ group. RESULTS: A total of 15,591 women reporting a birth since 1 January 2012 answered maternity care questions. Completeness was very high (> 99%), with similar proportions of responses for both live and stillbirths. Amongst the 14,991 births in the FBH+ group, poorer wealth status, higher parity, large perceived baby size-at-birth, preterm or post-term birth, birth in a government hospital compared to other locations and vaginal birth were associated with increased risk of stillbirth after adjusting for potential confounding factors. Regarding association with reported postnatal care, women with a stillbirth were more likely to report hospital stays of > 1 day. However, women with a stillbirth were less likely to report having received a postnatal check compared to those with a live birth. CONCLUSIONS: Women who had experienced stillbirth were able to respond to questions about pregnancy and birth, and we found no reason to omit questions to these women in household surveys. Our analysis identified several potentially modifiable factors associated with stillbirth, adding to the evidence-base for policy and action in low- and middle-income contexts. Including these questions in DHS-8 would lead to increased availability of population-level data to inform action to end preventable stillbirths

Stillbirth outcome capture and classification in population-based surveys: EN-INDEPTH study.

BACKGROUND: Household surveys remain important sources of stillbirth data, but omission and misclassification are common. Classifying adverse pregnancy outcomes as stillbirths requires accurate reporting of vital status at birth and gestational age or birthweight for every pregnancy. Further categorisation, e.g. by sex, or timing (intrapartum/antepartum) improves data to understand and prevent stillbirth. METHODS: We undertook a cross-sectional population-based survey of women of reproductive age in five health and demographic surveillance system sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with pregnancy loss questions (FBH+) or a full pregnancy history (FPH). A sub-sample across both groups were asked additional stillbirth questions. Questions were evaluated using descriptive measures. Using an interpretative paradigm and phenomenology methodology, focus group discussions with women exploring barriers to reporting birthweight for stillbirths were conducted. Thematic analysis was guided by an a priori codebook. RESULTS: Overall 69,176 women reported 98,483 livebirths (FBH+) and 102,873 pregnancies (FPH). Additional questions were asked for 1453 stillbirths, 1528 neonatal deaths and 12,620 surviving children born in the 5 years prior to the survey. Completeness was high (> 99%) for existing FBH+/FPH questions on signs of life at birth and gestational age (months). Discordant responses in signs of life at birth between different questions were common; nearly one-quarter classified as stillbirths on FBH+/FPH were reported born alive on additional questions. Availability of information on gestational age (weeks) (58.1%) and birthweight (13.2%) was low amongst stillbirths, and heaping was common. Most women (93.9%) were able to report the sex of their stillborn baby. Response completeness for stillbirth timing (18.3-95.1%) and estimated proportion intrapartum (15.6-90.0%) varied by question and site. Congenital malformations were reported in 3.1% stillbirths. Perceived value in weighing a stillborn baby varied and barriers to weighing at birth a nd knowing birthweight were common. CONCLUSIONS: Improving stillbirth data in surveys will require investment in improving the measurement of vital status, gestational age and birthweight by healthcare providers, communication of these with women, and overcoming reporting barriers. Given the large burden and effect on families, improved data must be made available to end preventable stillbirths

“Every Newborn-INDEPTH” (EN-INDEPTH) study protocol for a randomised comparison of household survey modules for measuring stillbirths and neonatal deaths in five Health and Demographic Surveillance sites

Background: Under-five and maternal mortality were halved in the Millennium Development Goals (MDG) era, with slower reductions for 2.6 million neonatal deaths and 2.6 million stillbirths. The Every Newborn Action Plan aims to accelerate progress towards national targets, and includes an ambitious Measurement Improvement Roadmap. Population-based household surveys, notably Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys, are major sources of population-level data on child mortality in countries with weaker civil registration and vital statistics systems, where over two-thirds of global child deaths occur. To estimate neonatal/child mortality and pregnancy outcomes (stillbirths, miscarriages, birthweight, gestational age) the most common direct methods are: (1) the standard DHS-7 with Full Birth History with additional questions on pregnancy losses in the past 5 years (FBH+) or (2) a Full Pregnancy History (FPH). No direct comparison of these two methods has been undertaken, although descriptive analyses suggest that the FBH+ may underestimate mortality rates particularly for stillbirths. Methods: This is the protocol paper for the Every Newborn-INDEPTH study (INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health Every Newborn, Every Newborn Action Plan), aiming to undertake a randomised comparison of FBH+ and FPH to measure pregnancy outcomes in a household survey in five selected INDEPTH Network sites in Africa and South Asia (Bandim in urban and rural Guinea-Bissau; Dabat in Ethiopia; IgangaMayuge in Uganda; Kintampo in Ghana; Matlab in Bangladesh). The survey will reach >68 000 pregnancies to assess if there is ≥15% difference in stillbirth rates. Additional questions will capture birthweight, gestational age, birth/death certification, termination of pregnancy and fertility intentions. The World Bank's Survey Solutions platform will be tailored for data collection, including recording paradata to evaluate timing. A mixed methods assessment of barriers and enablers to reporting of pregnancy and adverse pregnancy outcomes will be undertaken. Conclusions: This large-scale study is the first randomised comparison of these two methods to capture pregnancy outcomes. Results are expected to inform the evidence base for survey methodology, especially in DHS, regarding capture of stillbirths and other outcomes, notably neonatal deaths, abortions (spontaneous and induced), birthweight and gestational age. In addition, this study will inform strategies to improve health and demographic surveillance capture of neonatal/child mortality and pregnancy outcomes.Children’s Investment Fund Foundation (CIFF

Paradata analyses to inform population-based survey capture of pregnancy outcomes: EN-INDEPTH study

Background: Paradata are (timestamped) records tracking the process of (electronic) data collection. We analysed paradata from a large household survey of questions capturing pregnancy outcomes to assess performance (timing and correction processes). We examined how paradata can be used to inform and improve questionnaire design and survey implementation in nationally representative household surveys, the major source for maternal and newborn health data worldwide. Methods: The EN-INDEPTH cross-sectional population-based survey of women of reproductive age in five Health and Demographic Surveillance System sites (in Bangladesh, Guinea-Bissau, Ethiopia, Ghana, and Uganda) randomly compared two modules to capture pregnancy outcomes: full pregnancy history (FPH) and the standard DHS-7 full birth history (FBH+). We used paradata related to answers recorded on tablets using the Survey Solutions platform. We evaluated the difference in paradata entries between the two reproductive modules and assessed which question characteristics (type, nature, structure) affect answer correction rates, using regression analyses. We also proposed and tested a new classification of answer correction types. Results: We analysed 3.6 million timestamped entries from 65,768 interviews. 83.7% of all interviews had at least one corrected answer to a question. Of 3.3 million analysed questions, 7.5% had at least one correction. Among corrected questions, the median number of corrections was one, regardless of question characteristics. We classified answer corrections into eight types (no correction, impulsive, flat (simple), zigzag, flat zigzag, missing after correction, missing after flat (zigzag) correction, missing/incomplete). 84.6% of all corrections were judged not to be problematic with a flat (simple) mistake correction. Question characteristics were important predictors of probability to make answer corrections, even after adjusting for respondent’s characteristics and location, with interviewer clustering accounted as a fixed effect. Answer correction patterns and types were similar between FPH and FBH+, as well as the overall response duration. Avoiding corrections has the potential to reduce interview duration and reproductive module completion by 0.4 min. Conclusions: The use of questionnaire paradata has the potential to improve measurement and the resultant quality of electronic data. Identifying sections or specific questions with multiple corrections sheds light on typically hidden challenges in the survey’s content, process, and administration, allowing for earlier real-time intervention (e.g.,, questionnaire content revision or additional staff training). Given the size and complexity of paradata, additional time, data management, and programming skills are required to realise its potential. Keywords: Survey, Paradata, Neonatal, Newborn, Answer correction type, Survey desig

Randomised comparison of two household survey modules for measuring stillbirths and neonatal deaths in five countries: the Every Newborn-INDEPTH study.

BACKGROUND: An estimated 5·1 million stillbirths and neonatal deaths occur annually. Household surveys, most notably the Demographic and Health Survey (DHS), run in more than 90 countries and are the main data source from the highest burden regions, but data-quality concerns remain. We aimed to compare two questionnaires: a full birth history module with additional questions on pregnancy losses (FBH+; the current DHS standard) and a full pregnancy history module (FPH), which collects information on all livebirths, stillbirths, miscarriages, and neonatal deaths. METHODS: Women residing in five Health and Demographic Surveillance System sites within the INDEPTH Network (Bandim in Guinea-Bissau, Dabat in Ethiopia, IgangaMayuge in Uganda, Matlab in Bangladesh, and Kintampo in Ghana) were randomly assigned (individually) to be interviewed using either FBH+ or FPH between July 28, 2017, and Aug 13, 2018. The primary outcomes were stillbirths and neonatal deaths in the 5 years before the survey interview (measured by stillbirth rate [SBR] and neonatal mortality rate [NMR]) and mean time taken to complete the maternity history section of the questionnaire. We also assessed between-site heterogeneity. This study is registered with the Research Registry, 4720. FINDINGS: 69 176 women were allocated to be interviewed by either FBH+ (n=34 805) or FPH (n=34 371). The mean time taken to complete FPH (10·5 min) was longer than for FBH+ (9·1 min; p<0·0001). Using FPH, the estimated SBR was 17·4 per 1000 total births, 21% (95% CI -10 to 62) higher than with FBH+ (15·2 per 1000 total births; p=0·20) in the 5 years preceding the survey interview. There was strong evidence of between-site heterogeneity (I2=80·9%; p<0·0001), with SBR higher for FPH than for FBH+ in four of five sites. The estimated NMR did not differ between modules (FPH 25·1 per 1000 livebirths vs FBH+ 25·4 per 1000 livebirths), with no evidence of between-site heterogeneity (I2=0·7%; p=0·40). INTERPRETATION: FPH takes an average of 1·4 min longer to complete than does FBH+, but has the potential to increase reporting of stillbirths in high burden contexts. The between-site heterogeneity we found might reflect variations in interviewer training and survey implementation, emphasising the importance of interviewer skills, training, and consistent implementation in data quality. FUNDING: Children's Investment Fund Foundation