Program for Appropriate Technology in Health

ABSTRACT Background Severe Plasmodium falciparum malaria is a leading cause of death in sub-Saharan Africa, with most deaths occurring in children younger than five years of age. The RTS,S/AS01 E (RTS,S) malaria vaccine delivered seasonally with Seasonal Malaria Chemoprevention (SMC) led to a two-third reduction in severe malaria and malaria deaths compared with either intervention given alone. The aim of this study was to assess the seasonal distribution and clinical presentation of children admitted in hospital with severe malaria who received RTS,S with or without SMC, and whether seasonal vaccination with RTS,S affected their distribution and clinical presentation. Methods We conducted a secondary ad-hoc analysis of hospital admissions in children aged 5 to 17 months of age when enrolled in the RTS,S + SMC trial in April 2017 in Houndé, Burkina Faso, and Bougouni, Mali, and who were followed until they reached five years of age. Results Three hundred and thirtythirty-seven serious adverse events were reported during the trial with 222 (65.9%) in Burkina Faso and 115 (34.1%) in Mali, and 48.1% (162/337) were due to severe malaria. The mean age of children with severe malaria was 2.9 years; 79.0% (128/162) of the cases occurred in children aged 3 years or less and 21.0% (34/162) in those aged 4 to 5 years. The most common presentation was severe anemia reported in 50% (81/162) of children, followed by repeated convulsions 25.3%, (41/162), prostration 11.1%, (18/162), hyperparasitaemia 8.0%, (13/162) and cerebral malaria 6.2%, (10/162). Severe malaria anemia was a more frequent form of severe malaria in children in the SMC alone arm 62.1%, (36/58) and lower in children in the SMC+ RTS,S arm 37.1%, (13/35), p=0.048. There was no significant difference in frequency of other clinical presentations between the study arms. Most severe malaria cases, 85.8% (139/162) occurred during the transmission season (July to December). Conclusions Severe anaemia was the most common presentation of severe malaria and was most frequent in the SMC alone arm. Children aged 3 years or less were the most affected and almost all the cases occurred between July and December. Trial registration ClinicalTrials.gov , NCT04319380

Malaria parasite transmission remains a barrier to elimination since asymptomatic individuals sustain the infectious reservoir. Transmission-blocking vaccine (TBV) candidates targeting Plasmodium falciparum (Pf) gametocyte surface proteins Pfs230 and Pfs48/45 have shown promise in clinical trials. Several vaccine candidates have been developed for these antigens, yet it is unclear which elicit the most robust and durable transmission-blocking responses. From structure-function relationships of monoclonal antibodies in complex with both antigens, we report the development of a stabilized tandem antigen chimera (STAC), which presents the most potent epitopes from Pfs230 domain 1(Pfs230-D1) and Pfs48/45 domain 3(Pfs48/45-D3) in a single construct, while masking non-functional epitopes using an engineered pseudo-native domain disposition. Iterative structure-guided optimization improved antigen yields and stability, while nanoparticle-based multimerization enhanced the functional transmission-reducing activity elicited by the immunogen in female mice. Immunizations with STAC genetically conjugated to self-assembling protein nanoparticles elicited antibodies with potent transmission-reducing activity comparable or superior to the multimerized Pfs230-D1 and Pfs48/45-D3. These findings establish STAC as a promising next-generation TBV candidate to disrupt malaria transmission and accelerate elimination efforts. More broadly, our results support the engineering of highly ordered and stable multi-domain antigens in a single protein as a strategy for the cost-efficient development of multi-component vaccines.

ABSTRACTProtein and fat concentrations in donor human milk (DHM) can vary twofold to threefold and are influenced by the number of unique donors per pool. The aim of this study was to broadly characterize how the number of donors (2–10) randomly combined into a pool during milk bank processing influenced the variability of macronutrients, vitamins, minerals, and bioactive factors in DHM. The minimum number of donors required for 80% of the pools to meet pre‐defined targets for true protein, fat, and disialyllacto‐N‐tetraose (DSLNT) was also evaluated. Monte Carlo simulation was used to create models that accounted for donor lifetime donation volume and milk bank production constraints. Variability in nutrients was quantified as a Nutrient Inequality Index (NII) which was computed as the ratio of the 90th percentile to the 10th percentile for each simulation. Random multi‐donor pooling of 2–10 donors produced lower variability in DHM macronutrients than most vitamins and minerals. A priori targets of 0.9 g/dL of true protein, 3.5 g/dL of fat, and 210 µg/L of DSLNT could not be achieved with any random pooling scenario. The NII for lactose stabilized at less than 1.1 when there were 3+ donors per pool, while the NII for fat and true protein stabilized at less than 1.3 when there were 5+ donors per pool. The NII exceeded 1.5, even at 10 donors per pool, for several micronutrients including zinc, copper, sodium, iron, biotin, riboflavin, B6, B12, and pantothenic acid.

Combination vaccines combine several components in a single dose administration. They offer programmatic and public health advantages, particularly as vaccine schedules become increasingly crowded. They are often more expensive to develop and produce, which discourages manufacturer investment without clear market signals. Hence their benefits need to be captured with existing health economic evaluation reference cases used by decision-makers to guide vaccine investments. We propose that the value of combination vaccines can be captured through at least four domains: (1) reductions in tangible and intangible costs to caregivers, (2) operational efficiencies to the health system, (3) opportunity costs of vaccine schedule slots, and (4) more streamlined vaccine schedules. We demonstrate the practicality of our framework by comparing the value of introducing a hypothetical vaccine to a crowded schedule as a standalone formulation, a replacement for a vaccine already in the schedule, or a combination product. The framework could also be applied to estimate the value of reducing the number of separate administrations needed for a standalone vaccine. Applying it in real-world situations could be facilitated by further data collection, particularly on collating results on the value of existing vaccines in the schedule and estimating willingness-to-pay for fewer vaccine administrations.

Nearly 5 million children die each year of preventable causes, with pneumonia being a key contributor. The Integrated Management of Childhood Illnesses guidelines improve health care workers' diagnostic and management capabilities by relying mostly on clinical signs. Though there have been successes, challenges in the consistent application of IMCI and the accurate diagnosis of conditions like hypoxemia remain. Next generation pulse oximeters add functionality to stand alone pulse oximeters, like measurement of respiratory rate, temperature, and hemoglobin. While the TIMCI project sought to address gaps in the introduction of pulse oximetry in India, Kenya, Senegal, and Tanzania, research was also conducted to strengthen the market for multimodal pulse oximetry (PO) devices by filling evidence gaps around ideal product attributes and the validation of available and near to market photoplethysmography-derived clinical measurement tools (medical device and smartphone-based). A mixed-methods evaluation measured usability and diagnostic accuracy using multimodal PO devices among primary care providers in the four countries. Results showed good usability, minimal user errors, and high satisfaction and system usability scores across all devices. Additionally, across all age categories, device performance for hypoxemia, tachycardia, and fever exceeded 80% agreement; respiratory rate measurements exhibited greater variability in percent agreement between devices. A target product profile and an open-source data repository were developed to further advance device development and market alignment. This research provided data on the performance of various multimodal PO devices, considering different form factors and product attributes. Technological progress continues to expand opportunities for the collection of clinical measurements and data. Supporting providers with decision support and automated documentation tools ensures that the information generated is actionable and utilized, while an emphasis on integrated technologies is essential to maximize provider capabilities and improve the diagnosis and management of childhood illnesses in low- and middle-income countries.

ABSTRACT The recent technologies in IoT‐based smart healthcare services are gaining attention because of their quality of service and reliability. These remote health monitoring systems offer enhanced quality of comfort to individuals and also meet emergency situation management requirements. Automatic data recording, processing, and communication with a third party like a doctor, caretaker, or hospital wirelessly enables the system to supersede conventional healthcare techniques. This paper focuses on the major challenging issues faced in the implementation of wireless body area networks (WBANs) in a dynamic environment, and the performance evaluation of the currently used systems. As the data collected by the sensor nodes are highly critical, a machine learning algorithm, integrating a rule‐based screening and a bidirectional LSTM, is proposed to detect data manipulation by intruders. The performance of the network is then evaluated with the help of various parameters. The study results provide better insight into system performance and optimization of system parameters to achieve better reliability and throughput in the presence of false data.

RTS,S/AS01, an adjuvanted subunit malaria vaccine, induces protective but short-lived anti-Plasmodium falciparum circumsporozoite protein (CSP) antibody titers. To better understand the lack of sustained protection post-vaccination, we analyzed CSP-specific B cells over time in malaria-naive individuals following immunization with RTS,S/AS01 followed by controlled malaria infection. Longitudinal analyses revealed a shift in the repertoire and regional protein specificity of CSP-specific B cells over time. Early post-vaccine responses were dominated by class-switched memory B cells (MBCs) specific for the NANP-repeat region of CSP, epitopes associated with protective antibodies. However, the frequency of NANP-repeat-specific MBCs declines, while longer-term memory responses, including responses both before and after a malaria challenge, had increased frequencies of MBCs specific for the C-terminus of CSP. Despite class-switching and affinity maturation, C-term monoclonal antibodies derived from these MBCs failed to protect mice against a transgenic parasite challenge. Taken together, these findings suggest that RTS,S/AS01 induces a transient, protective NANP-repeat-specific B cell response that is subsequently replaced by B cells with non-protective reactivities, potentially explaining its limited long-term efficacy.

Artificial intelligence offers transformative potential for global health, yet regulatory disparities threaten equitable adoption. This brief examines whether the World Health Organization's Prequalification (PQ) framework should extend to AI. We highlight limitations of applying static product paradigms to dynamic systems, outline targeted reforms, and propose a reimagined PQ4AI that balances global technical assurance with local regulatory accountability to foster safe, effective, and equitable deployments.