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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. 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. 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. [ABSTRACT FROM AUTHOR]

Pompe disease (PD) is a neuromuscular disorder caused by acid α‐glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard‐of‐care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno‐associated virus (AAV) vectors based on liver‐ and muscle‐targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile‐onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver‐muscle tandem promoter (LiMP), and despite the extensive liver‐detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa−/− adult mice. In neonate Gaa−/−, complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle‐specific AAV capsid‐promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa−/− provides a potential therapeutic avenue for the infantile‐onset form of this devastating disease. [ABSTRACT FROM AUTHOR]

Background Malaria is a leading cause of morbidity and mortality in refugee children in high-transmission parts of Africa. Characterizing the clinical features of malaria in refugees can inform approaches to reduce its burden. Methods The study was conducted in a high-transmission region of northern Zambia hosting Congolese refugees. We analyzed surveillance data and hospital records of children with severe malaria from refugee and local sites using multivariable regression models and geospatial visualization. Results Malaria prevalence in the refugee settlement was similar to the highest burden areas in the district, consistent with the local ecology and leading to frequent rapid diagnostic test stockouts. We identified 2197 children hospitalized for severe malaria during the refugee crisis in 2017 and 2018. Refugee children referred from a refugee transit center (n = 63) experienced similar in-hospital mortality to local children and presented with less advanced infection. However, refugee children from a permanent refugee settlement (n = 110) had more than double the mortality of local children (P <.001), had lower referral rates, and presented more frequently with advanced infection and malnutrition. Distance from the hospital was an important mediator of the association between refugee status and mortality but did not account for all of the increased risk. Conclusions Malaria outcomes were more favorable in refugee children referred from a highly outfitted refugee transit center than those referred later from a permanent refugee settlement. Refugee children experienced higher in-hospital malaria mortality due in part to delayed presentation and higher rates of malnutrition. Interventions tailored to the refugee context are required to ensure capacity for rapid diagnosis and referral to reduce malaria mortality. [ABSTRACT FROM AUTHOR]

Background Severe malaria resulting from Plasmodium falciparum infection is the leading parasitic cause of death in children worldwide, and severe malarial anemia (SMA) is the most common clinical presentation. The evidence in support of current blood transfusion guidelines for patients with SMA is limited. Methods We conducted a retrospective cohort study of 911 hospitalized children with SMA in a holoendemic region of Zambia to examine the association of whole blood transfusion with in-hospital survival. Data were analyzed in adjusted logistic regression models using multiple imputation for missing data. Results The median age of patients was 24 months (interquartile range, 16–30) and overall case fatality was 16%. Blood transfusion was associated with 35% reduced odds of death in children with SMA (odds ratio, 0.65; 95% confidence interval,.52–.81; P =.0002) corresponding to a number-needed-to-treat (NNT) of 14 patients. Children with SMA complicated by thrombocytopenia were more likely to benefit from transfusion than those without thrombocytopenia (NNT = 5). Longer storage time of whole blood was negatively associated with survival and with the posttransfusion rise in the platelet count but was not associated with the posttransfusion change in hemoglobin concentration. Conclusions Whole blood given to pediatric patients with SMA was associated with improved survival, mainly among those with thrombocytopenia who received whole blood stored for <4 weeks. These findings point to a potential use for incorporating thrombocytopenia into clinical decision making and management of severe malaria, which can be further assessed in prospective studies, and underline the importance of maintaining reliable blood donation networks in areas of high malaria transmission. [ABSTRACT FROM AUTHOR]