Publications

Development of microneedle array patches (MAPs) for potential use in immunization is ongoing, but the cost of manufacturing is expected to be higher than that of existing needle-and-syringe vial systems. The potential benefits of MAPs in reaching previously unvaccinated populations have been touted, but affordability, especially in low- and middle-income countries, remains an open question. In this study, we quantify the expected impact on operational costs of switching to MAPs for immunization for measles-rubella, human papilloma virus, and typhoid in both routine and campaign-based delivery modes. We endeavor to make a comprehensive estimate, including the costs of labor, syringes, waste management (i.e., sharps and trash), wastage (unused vaccine), freight and in-country cold chain transportation. We examined five potential use cases and our results show that in total, operational cost savings from a switch to MAPs are expected to range from a low of $0.24 per dose delivered (HPV, 1-dose vial, campaign) up to $0.61 per dose delivered (MR, 10-dose vial, routine). Excluding the allocated cost of labor, the estimated range of cost savings are $0.18 and $0.43, respectively. Confidence intervals are wide, due to the uncertainty in the assumptions, but in all five use cases tested, there was at least an 87 % probability of savings. These results show that operational savings from a switch to MAPs may offset at least part of the expected incremental manufacturing costs, which will make the transition more viable in settings with limited budget space. With this in mind, development agencies should continue to invest in MAPs technology and, if the product does come to market, use this evidence as part of total value of vaccines assessments and to inform investment strategies for implementation of vaccine MAPs, including alignment with policy makers.

Central to the ongoing debate surrounding rights-based family planning measures is the need for a woman-centered paradigm. Despite this debate, in the 30 years since the 1994 International Conference on Population and Development, widely used family planning measures have evolved relatively slowly. In this paper, we describe the utilization of an understudied family planning indicator—women’s expressed intention to use (ITU) contraceptives—and explore its implications for developing metrics, tracking program impact, and mechanistic understanding. We leverage Performance Monitoring for Action program data in ten geographies and assess, (1) cross-sectionally, the extent to which ITU captures demand and concords with ‘unmet need’ and (2) longitudinally, the extent to which women actualize their ITU over time. We demonstrate that the utilization of ITU more accurately identifies women who have demand and who are (un) able to actualize their ITU. We also discuss the limitations of the current ITU metric, making recommendations for data efforts to improve and include ITU as routinely reported family planning indicators.

Contraceptive intention is an important woman-centered indicator for family planning. Yet, few studies have examined the determinants of women or couples actualizing their contraceptive intentions. We leverage panel data from the Performance Monitoring for Action (PMA) survey in Ethiopia to examine these dynamics among a pregnancy cohort, over the first year postpartum. Using cluster analysis on intent-to-use trajectories, we find distinct patterns across wealth categories, education levels, and regions. Additionally, we find that receiving family planning counseling in both antenatal and postnatal care visits led to a higher likelihood of intending to use. However, counseling did not increase the odds of actualization. We argue that examining actualization through model-based approaches like cluster analysis generates better insight into woman-centered contraceptive demand and provides stronger evidence for strengthening postpartum family planning interventions, than quantifying contraceptive use alone. Modeling postpartum actualization trajectories can shed light on the barriers to women’s and couple’s reproductive autonomy and inform future investments in both upstream development of better contraceptive methods and downstream implementation.

In 2020, the WHO launched its first global strategy to accelerate the elimination of cervical cancer, outlining an ambitious set of targets for countries to achieve over the next decade. At the same time, new tools, technologies, and strategies are in the pipeline that may improve screening performance, expand the reach of prophylactic vaccines, and prevent the acquisition, persistence and progression of oncogenic HPV. Detailed mechanistic modelling can help identify the combinations of current and future strategies to combat cervical cancer. Open-source modelling tools are needed to shift the capacity for such evaluations in-country. Here, we introduce the Human papillomavirus simulator (HPVsim), a new open-source software package for creating flexible agent-based models parameterised with country-specific vital dynamics, structured sexual networks, and co-transmitting HPV genotypes. HPVsim includes a novel methodology for modelling cervical disease progression, designed to be readily adaptable to new forms of screening. The software itself is implemented in Python, has built-in tools for simulating commonly-used interventions, includes a comprehensive set of tests and documentation, and runs quickly (seconds to minutes) on a laptop. Performance is greatly enhanced by HPVsim’s multiscale modelling functionality. HPVsim is open source under the MIT License and available via both the Python Package Index (via pip install) and GitHub (hpvsim.org).

Access to medical treatment for fever is essential to prevent morbidity and mortality in individuals and to prevent transmission of communicable febrile illness in communities. Quantification of the rates at which treatment is accessed is critical for health system planning and a prerequisite for disease burden estimates. In this study, national data on the proportion of children under five years old with fever who were taken for medical treatment were collected from all available countries in Africa, Latin America, and Asia (n = 91). We used generalised additive mixed models to estimate 30-year trends in the treatment-seeking rates across the majority of countries in these regions (n = 151). Our results show that the proportions of febrile children brought for medical treatment increased steadily over the last 30 years, with the greatest increases occurring in areas where rates had originally been lowest, which includes Latin America and Caribbean, North Africa and the Middle East (51 and 50% increase, respectively), and Sub-Saharan Africa (23% increase). Overall, the aggregated and population-weighted estimate of children with fever taken for treatment at any type of facility rose from 61% (59–64 95% CI) in 1990 to 71% (69–72 95% CI) in 2020. The overall population-weighted average for fraction of treatment in the public sector was largely unchanged during the study period: 49% (42–58 95% CI) sought care at public facilities in 1990 and 47% (44–52 95% CI) in 2020. Overall, the findings indicate that improvements in access to care have been made where they were most needed, but that despite rapid initial gains, progress can plateau without substantial investment. In 2020 there remained significant gaps in care utilisation that must be factored in when developing control strategies and deriving disease burden estimates.

The behavioral and biological underpinnings of family planning (FP) unfold on an individual level, across a full reproductive lifecourse, and within a complex system of social and structural constraints. Yet, much of the existing FP modeling landscape hasfocused solely on macro- or population-level dynamics of family planning. There is a need for an individual-based approach toprovide a deeper understanding of how family planning is intertwined with individuals’lives and health at the micro-level, whichcan contribute to more effective, person-centered design of both contraceptive technologies and programmatic interventions. Thisarticle introduces the Family Planning Simulator (FPsim), a data-driven, agent-based model of family planning, which explicitlymodels individual heterogeneity in biology and behavior over the life course. Agents in FPsim can experience a wide range of life-course events, such as increases in fecundability (and primary infertility), sexual debut, contraceptive choice, postpartum familyplanning, abortion, miscarriage, stillbirth, infant mortality, and maternal mortality. The core components of the model—fecundability and contraceptive choice, are represented individually and probabilistically, following age-specific patterns observedin demographic data and prospective cohort studies. Once calibrated to a setting leveraging multiple sources of data, FPsim can beused to build hypothetical scenarios and interrogate counterfactual research questions about the use, non-use, and/or efficacy offamily planning programs and contraceptive methods. To our knowledge, FPsim is the first open-source, individual-level, woman-centered model of family planning.

Importance
The MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial demonstrated that mass azithromycin administration reduced mortality by 18% among children aged 1 to 59 months in Niger. The identification of high-risk subgroups to target with this intervention could reduce the risk of antimicrobial resistance.

Objective
To evaluate whether distance to the nearest primary health center modifies the effect of azithromycin administration to children aged 1 to 59 months on child mortality.

Design, Setting, and Participants
The MORDOR cluster randomized trial was conducted from December 1, 2014, to July 31, 2017; this post hoc secondary analysis was conducted in 2023 among 594 clusters (communities or grappes) in the Boboye and Loga departments in Niger. All children aged 1 to 59 months in eligible communities were evaluated.

Interventions
Biannual (twice-yearly) administration of a single dose of oral azithromycin or matching placebo over 2 years.

Main Outcomes and Measures
A population-based census was used to monitor mortality and person-time at risk (trial primary outcome). Community distance to a primary health center was calculated as kilometers between the center of each community and the nearest health center. Negative binomial regression was used to evaluate the interaction between distance and the effect of azithromycin on the incidence of all-cause mortality among children aged 1 to 59 months.

Results
Between December 1, 2014, and July 31, 2017, a total of 594 communities were enrolled, with 76 092 children (mean [SD] age, 31 [2] months; 39 022 [51.3%] male) included at baseline, for a mean (SD) of 128 (91) children per community. Median (IQR) distance to the nearest primary health center was 5.0 (3.2-7.1) km. Over 2 years, 145 693 person-years at risk were monitored and 3615 deaths were recorded. Overall, mortality rates were 27.5 deaths (95% CI, 26.2-28.7 deaths) per 1000 person-years at risk in the placebo arm and 22.5 deaths (95% CI, 21.4-23.5 deaths) per 1000 person-years at risk in the azithromycin arm. For each kilometer increase in distance in the placebo arm, mortality increased by 5% (adjusted incidence rate ratio, 1.05; 95% CI, 1.03-1.07; P < .001). The effect of azithromycin on mortality varied significantly by distance (interaction P = .02). Mortality reduction with azithromycin compared with placebo was 0% at 0 km from the health center (95% CI, −19% to 17%), 4% at 1 km (95% CI, −12% to 17%), 16% at 5 km (95% CI, 7% to 23%), and 28% at 10 km (95% CI, 17% to 38%).

Conclusions and Relevance
In this secondary analysis of a cluster randomized trial of mass azithromycin administration for child mortality, children younger than 5 years who lived farthest from health facilities appeared to benefit the most from azithromycin administration. These findings may help guide the allocation of resources to ensure that those with the least access to existing health resources are prioritized in program implementation.

Women’s empowerment and contraceptive use are critical to achieving gender equality. The positive association between more empowered women and higher rates of contraceptive use has been well-established by cross-sectional research. However, there remains a gap in understanding the longitudinal relationship between contraceptive adoption and changes to women’s empowerment. This study represents a novel approach to understanding the relationship between contraceptive adoption and women’s empowerment longitudinally, at the individual level. To the authors’ knowledge, this is the first attempt to measure the relationship between contraceptive adoption and women’s empowerment using more than one wave of panel data. We leverage the longitudinal design of the Urban Reproductive Health Initiative data to code empowerment items by change over time (e.g., more empowered, no change, less empowered). We use sparse principal component analysis to establish empowerment change domains and calculate individual scores standardized by country-level averages. We estimate mixed effects models on these change domains, to investigate the link between contraceptive adoption and empowerment. We find common themes in empowerment across contexts—but contraceptive adoption has both positive and negative effects on those domains, and this varies across context. We discuss the need for cohort studies to examine this relationship.

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.

Introduction Anaemia is a major cause of morbidity and mortality among children in sub-Saharan Africa. Anaemia has many aetiologies best addressed by different treatments, so regional studies of the aetiology of anaemia may be required.

Methods We analysed data from Nigeria’s 2018 Demographic and Health Survey (DHS) to study predictors of anaemia among children ages 6-59m. We computed the fraction of anaemia at different degrees of severity attributable to malaria and sickle cell disease (SCD) using a regression model adjusting for demographic and socioeconomic risk factors. We also estimated the contribution of the risk factors to haemoglobin concentration.

Results We found that 63.7% (95% CI: 58.3-69.4) of semi-severe anaemia (<80 g/L) was attributable to malaria compared to 12.4% (95% CI: 11.1-13.7) of mild-to-severe (adjusted haemoglobin concentration <110 g/L) and 29.6% (95% CI: 29.6-31.8) of moderate-to-severe (<100 g/L) anaemia and that SCD contributed 0.6% (95%CI: 0.4-0.9), 1.3% (95% CI: 1.0-1.7), and 7.3% (95%CI: 5.3-9.4) mild-to-severe, moderate-to-severe, and semi-severe anaemia, respectively. Sickle trait was protective against anaemia and was associated with higher haemoglobin concentration compared to children with normal haemoglobin (HbAA) among malaria-positive but not malaria-negative children.

Conclusion This approach used offers a new tool to estimate the contribution of malaria to anaemia in many settings using widely available DHS data. The fraction of anaemia among young children in Nigeria attributable to malaria and SCD is higher at more severe levels of anaemia. Prevention of malaria and SCD and timely treatment of affected individuals would reduce cases of severe anaemia.