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This article details the study protocol for a double-blind, randomized placebo-controlled trial to determine the effectiveness of permethrin-treated baby wraps to prevent Plasmodium falciparum malaria infection in children 6–24 months of age. Participating mother-infant dyads will be randomized to receive either a permethrin-treated or a sham-treated wrap, known locally as a “ lesu .” After a baseline home visit, during which time all participants will receive new long-lasting insecticidal nets, participants will attend scheduled clinic visits every two weeks for a period of 24 weeks. In the event of an acute febrile illness or other symptoms that may be consistent with malaria (e.g., poor feeding, headache, malaise), participants will be instructed to present to their respective study clinic for evaluation. The primary outcome of interest is the incidence of laboratory-confirmed, symptomatic malaria in participating children. Secondary outcomes of interest include: (1) change in children’s hemoglobin levels; (2) change in children’s growth parameters; (3) prevalence of asymptomatic parasitemia in children; (4) hospitalization for malaria in children; (5) change in the mother’s hemoglobin level; and (6) clinical malaria in the mother. Analyses will be conducted using a modified intent-to-treat approach, with woman-infant dyads who attend one or more clinic visits analyzed according to the arm to which they were randomly assigned. This is the first use of an insecticide-treated baby wrap for prevention of malaria in children. The study began recruitment in June 2022 and is ongoing. ClinicalTrials.gov Identifier: NCT05391230, Registered 25 May 2022.

Acute respiratory illness (ARI) is one of the most common reasons children receive antibiotic treatment. Measurement of C-reaction protein (CRP) has been shown to reduce unnecessary antibiotic use among children with ARI in a range of clinical settings. In many resource-constrained contexts, patients seek care outside the formal health sector, often from lay community health workers (CHW). This study's objective was to determine the impact of CRP measurement on antibiotic use among children presenting with febrile ARI to CHW in Uganda. We conducted a cross-sectional, stepped wedge cluster randomized trial in 15 villages in Bugoye subcounty comparing a clinical algorithm that included CRP measurement by CHW to guide antibiotic treatment (STAR Sick Child Job Aid [SCJA]; intervention condition) with the Integrated Community Care Management (iCCM) SCJA currently in use by CHW in the region (control condition). Villages were stratified into 3 strata by altitude, distance to the clinic, and size; in each stratum, the 5 villages were randomly assigned to one of 5 treatment sequences. Children aged 2 months to 5 years presenting to CHW with fever and cough were eligible. CHW conducted follow-up assessments 7 days after the initial visit. Our primary outcome was the proportion of children who were given or prescribed an antibiotic at the initial visit. Our secondary outcomes were (1) persistent fever on day 7; (2) development of prespecified danger signs; (3) unexpected visits to the CHW; (4) hospitalizations; (5) deaths; (6) lack of perceived improvement per the child's caregiver on day 7; and (7) clinical failure, a composite outcome of persistence of fever on day 7, development of danger signs, hospitalization, or death. The 65 participating CHW enrolled 1,280 children, 1,220 (95.3%) of whom had sufficient data. Approximately 48% (587/1,220) and 52% (633/1,220) were enrolled during control (iCCM SCJA) and intervention periods (STAR SCJA), respectively. The observed percentage of children who were given or prescribed antibiotics at the initial visit was 91.8% (539/587) in the control periods as compared to 70.8% (448/633) during the intervention periods (adjusted prevalence difference -24.6%, 95% CI: -36.1%, -13.1%). The odds of antibiotic prescription by the CHW were over 80% lower in the intervention as compared to the control periods (OR 0.18, 95% CI: 0.06, 0.49). The frequency of clinical failure (iCCM SCJA 3.9% (23/585) v. STAR SCJA 1.8% (11/630); OR 0.41, 95% CI: 0.09, 1.83) and lack of perceived improvement by the caregiver (iCCM SCJA 2.1% (12/584) v. STAR SCJA 3.5% (22/627); OR 1.49, 95% CI: 0.37, 6.52) was similar. There were no unexpected visits or deaths in either group within the follow-up period. Incorporating CRP measurement into iCCM algorithms for evaluation of children with febrile ARI by CHW in rural Uganda decreased antibiotic use. There is evidence that this decrease was not associated with worse clinical outcomes, although the number of adverse events was low. These findings support expanded access to simple, point-of-care diagnostics to improve antibiotic stewardship in rural, resource-constrained settings where individuals with limited medical training provide a substantial proportion of care. ClinicalTrials.gov NCT05294510. The study was reviewed and approved by the University of North Carolina Institutional Review Board (#18-2803), Mbarara University of Science and Technology Research Ethics Committee (14/03-19), and Uganda National Council on Science and Technology (HS 2631).

Background Malaria in pregnancy (MiP) remains a substantial public health problem, accounting for a large proportion of adverse outcomes for both mothers and developing child in endemic areas. Although interventions such as intermittent preventive treatment in pregnancy (IPTp) have been shown to be effective, uptake remains suboptimal. This study aimed to identify factors associated with MiP among pregnant women at their initial antenatal visit and to explore perceptions of MiP among both midwives and pregnant women in the community to identify barriers to the utilization of available prevention services. Methods Pregnant women attending their first antenatal clinic visit at one of four lower-level health facilities were screened for Plasmodium falciparum malaria using a rapid diagnostic test. Demographic characteristics and clinical measures were documented on case report forms to assess associations with the malaria test result. Quantitative findings informed focus group discussions with pregnant women and individual semi-structured interviews with midwives at each facility. Results From February 2021 to September 2022, 1,644 pregnant women underwent testing for malaria. A total of 225 (13.5%) had a positive rapid diagnostic test (RDT) result. Primigravid status and younger maternal age were associated with malaria positivity. In the qualitative arm, stakeholders identified the following risk factors and barriers regarding MiP: (i) delayed testing for pregnancy and MiP, (ii) fear or hesitancy of chemoprevention, (iii) financial constraints, (iv) transportation barriers, (v) antenatal clinic operations, (vi) low bed net use, (vii) knowledge gaps, (viii) and attitudes of spouses. Conclusion Young, primigravid women remain at the highest risk of MiP in rural western Uganda. Although consistent with findings from other regions, the impact of geographic barriers that may delay pregnancy testing and initiation of antenatal care merit further study. Approaches to decentralize services further into the community may be particularly beneficial.

Introduction Globally, the progress to attain the open defecation free (ODF) environment has remained very slow. This study examined context specific factors influencing household open defecation free status in Uganda. Methods A cross-sectional study was conducted in Kabale district in southwestern Uganda and 492 participants were randomly selected at household level. Data was obtained through conducting a face-to-face interview using the mobile data collection software KoBoCollect v2021.3.4 installed on tablet devices. Using the Firth’s penalized logistic regression, bivariate and multivariate analysis was conducted to determine if there existed significant associations between the outcome Household Open Defecation (HODF) status and independent variables. Variables with P  < 0.2 at bivariate analysis comprised the global model for the multivariate analysis. Results The average age of the participants was 49 (SD 23.4) years. Most (67.68%) of the study participants, were females while 144 (29.27%) of the participants had no formal education. The households that were open defecation free were as few as 15 (3%). At multivariable analysis, gender of the participants, remembering handwashing, latrine and household cleanliness factors were significantly association with HODF status. Male participants had more odds of having open defecation free households (aOR: 3.89; 95% CI: 1.26–12.06) compared to female participants. Households with clean compounds, with latrines not having their holes soiled with feces and where respondents always remembered to wash hands after visiting latrine had high odds of being open defecation free (aOR: 3.15; 95% CI: 1.03–9.66, aOR: 10.56; 95% CI: 1.87–59.63 and aOR: 3.96; 95% CI: 1.24–12.68, respectively). Conclusion The prevalence of HODF was very low and factors associated with it were; the gender of the participants, the latrine and household cleanliness and the behavioral factor of remembering handwashing. We propose behavioral change interventions that empower communities to adapt improved sanitation behavior, such as Community Led Total Sanitation and Hygiene (CLTSH) in order to increase households with the Open Defecation Free status.

Background In many resource-constrained settings, community health workers (CHW) often provide the initial care for children under five years of age. As part of integrated community case management (iCCM) programs, CHW frequently diagnose and treat acute respiratory illness (ARI), a leading cause of pediatric mortality and indication for antibiotic use globally. Yet knowledge and perceptions of antibiotic prescribing for ARI among CHW are not well-studied. The goal of this study was to assess knowledge, attitudes, and practices related to antibiotics among CHW implementing a stepped-wedge trial of an enhanced iCCM algorithm for children with ARI in rural Uganda to inform future antimicrobial stewardship strategies. Methods We conducted a nested mixed methods study with a convergent parallel design, administering surveys before and after the stepped wedge trial and individual semi-structured interviews at study end. We employed descriptive statistics, Wilcoxan rank sum tests, and thematic content analysis methods. Results A total of 63 of 67 (94.0%) CHW completed both baseline and follow-up surveys, and 15 CHW were interviewed. The median age of the full cohort was 40 (IQR: 35–47) years with 9.5 years of CHW experience (IQR: 4.0–14.0 years). Almost all CHW (95.2%) identified amoxicillin as an antibiotic at baseline, and most associated antibiotics with treating bacterial diseases (baseline: 82.5%, follow-up: 93.7%, p  = 0.05). Most perceived antibiotics as harmful to patients when prescribed unnecessarily. At follow-up, more CHW disagreed that antibiotics should be prescribed when in doubt. They welcomed additional education about antimicrobial resistance and diagnostic tools to advance antimicrobial stewardship (AMS). Conclusion CHW were overall familiar with antibiotics and their potential harms. They were eager to gain knowledge regarding AMS and AMR and share it with their communities. CHW represent an underutilized resource for AMS interventions and should be included in their design and implementation.

Introduction Achieving the Open defecation free (ODF) status remains a major challenge in Uganda, yet it contributes significantly to child health improvement. Literature on social, cultural and behavioral aspects that influence the ODF status in rural Uganda is limited. The study therefore, explored perceived factors influencing the ODF status in rural South Western Uganda. Methods An exploratory study employing qualitative techniques and based on deductive analysis between month December 2020 and January 2021 was conducted. Seven Focus Group Discussions (FGDs and three Key Informant Interviews (KIs) were conducted in Kabale District, southwestern Uganda. Focus Group Discussion participants were mothers and fathers having children of 2 years and below while KIIs included local community leaders and health extension workers. Data was analyzed using a categorization matrix derived from the Risks, Attitudes, Norms, Abilities, and Self-regulation (RANAS) model which is comprised of contextual and psychological factors. Text was further categorized into high and low statements for attainment of ODF status. Results The contextual factors influencing the Open Defecation Free status behavior included; farming activities far from home, financial constraints, rainy seasons, collapsible soft soils, and alcohol use. Psychological factors influencing ODF status included; perceived health risk for typhoid disease, low perceived severity for lack of ODF components, negative attitude of less value attached to ODF components, and a feeling of time wastage practicing ODF status behavior. The perception that the community has the ability to attain the ODF status was high. Although, the capability to maintain ODF was low when it comes to replacement of ODF component if stolen or destroyed. Conclusion Open Defecation Free status is influenced by contextual and psychological factors. Therefore, it’s crucial for sanitation promotors to always identify such context specific factors in order to design sanitation and hygiene promotion interventions to address the ODF free status related challenges.

Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18–59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI −2·60 to 5·28) for Bio-Manguinhos-Fiocruz, −0·90% (–4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (–2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (–3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage. The study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.

Background In Uganda, village health workers (VHWs) manage childhood illness under the integrated community case management (iCCM) strategy. Care is provided for malaria, pneumonia, and diarrhoea in a community setting. Currently, there is limited evidence on the cost-effectiveness of iCCM in comparison to health facility-based management for childhood illnesses. This study examined the cost-effectiveness of the management of childhood illness using the VHW-led iCCM against health facility-based services in rural south-western Uganda. Methods Data on the costs and effectiveness of VHW-led iCCM versus health facility-based services for the management of childhood illness was collected in one sub-county in rural southwestern Uganda. Costing was performed using the ingredients approach. Effectiveness was measured as the number of under-five children appropriately treated. The Incremental Cost-Effectiveness Ratio (ICER) was calculated from the provider perspective. Results Based on the decision model for this study, the cost for 100 children treated was US$628.27 under the VHW led iCCM and US$87.19 for the health facility based services, while the effectiveness was 77 and 71 children treated for VHW led iCCM and health facility-based services, respectively. An ICER of US$6.67 per under five-year child treated appropriately for malaria, pneumonia and diarrhoea was derived for the provider perspective. Conclusion The health facility based services are less costly when compared to the VHW led iCCM per child treated appropriately. The VHW led iCCM was however more effective with regard to the number of children treated appropriately for malaria, pneumonia and diarrhoea. Considering the public health expenditure per capita for Uganda as the willingness to pay threshold, VHW led iCCM is a cost-effective strategy. VHW led iCCM should, therefore, be enhanced and sustained as an option to complement the health facility-based services for treatment of childhood illness in rural contexts.

Background Malaria risk is not uniform across relatively small geographic areas, such as within a village. This heterogeneity in risk is associated with factors including demographic characteristics, individual behaviours, home construction, and environmental conditions, the importance of which varies by setting, making prediction difficult. This study attempted to compare the ability of statistical models to predict malaria risk at the household level using either (i) free easily-obtained remotely-sensed data or (ii) results from a resource-intensive household survey. Methods The results of a household malaria survey conducted in 3 villages in western Uganda were combined with remotely-sensed environmental data to develop predictive models of two outcomes of interest (1) a positive ultrasensitive rapid diagnostic test (uRDT) and (2) inpatient admission for malaria within the last year. Generalized additive models were fit to each result using factors from the remotely-sensed data, the household survey, or a combination of both. Using a cross-validation approach, each model’s ability to predict malaria risk for out-of-sample households (OOS) and villages (OOV) was evaluated. Results Models fit using only environmental variables provided a better fit and higher OOS predictive power for uRDT result (AIC = 362, AUC = 0.736) and inpatient admission (AIC = 623, AUC = 0.672) compared to models using household variables (uRDT AIC = 376, Admission AIC = 644, uRDT AUC = 0.667, Admission AUC = 0.653). Combining the datasets did not result in a better fit or higher OOS predictive power for uRDT results (AIC = 367, AUC = 0.671), but did for inpatient admission (AIC = 615, AUC = 0.683). Household factors performed best when predicting OOV uRDT results (AUC = 0.596) and inpatient admission (AUC = 0.553), but not much better than a random classifier. Conclusions These results suggest that residual malaria risk is driven more by the external environment than home construction within the study area, possibly due to transmission regularly occurring outside of the home. Additionally, they suggest that when predicting malaria risk the benefit may not outweigh the high costs of attaining detailed information on household predictors. Instead, using remotely-sensed data provides an equally effective, cost-efficient alternative.

Background Measles outbreaks are prevalent throughout sub-Saharan Africa despite the preventive measures like vaccination that target under five-year-old children and health systems strengthening efforts like prioritizing the supply chain for supplies. Measles immunization coverage for Kasese district and Bugoye HC III in 2018 was 72 and 69%, respectively. This coverage has been very low and always marked red in the Red categorization (below the national target/poor performing) on the national league table indicators. The aim of this study was to assess the scope of the 2018–2019 measles outbreak and the associated risk factors among children aged 0–60 months in Bugoye sub-county, Kasese district, western Uganda. Methods We conducted a retrospective unmatched case-control study among children aged 0–60 months with measles (cases) who had either a clinical presentation or a laboratory confirmation (IgM positivity) presenting at Bugoye Health Centre III (BHC) or in the surrounding communities between December 2018 and October 2019.. Caregivers of the controls (whose children did not have measles) were selected at the time of data collection in July 2020. A modified CDC case investigation form was used in data collection. Quantitative data was collected and analyzed using Microsoft excel and STATA version 13. The children’s immunization cards and health registers at BHC were reviewed to ascertain the immunization status of the children before the outbreak. Results An extended measles outbreak occurred in Bugoye, Uganda occured between December 2018 and October 2019. All 34 facility-based measles cases were documented to have had maculopapular rash, conjunctivitis, and cough. Also, the majority had fever (97%), coryza (94.1%), lymphadenopathy (76.5%), arthralgias (73.5%) and Koplik Spots (91.2%) as documented in the clinical registers. Similar symptoms were reported among 36 community-based cases. Getting infected even after immunized, low measles vaccination coverage were identified as the principal risk factors for this outbreak. Conclusion Measles is still a significant problem. This study showed that this outbreak was associated with under-vaccination. Implementing a second routine dose of measles-rubella vaccine would not only increase the number of children with at least one dose but also boost the immunity of those who had the first dose.