Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda.

BACKGROUND: Malaria epidemics result from extreme precipitation and flooding, which are increasing with global climate change. Local adaptation and mitigation strategies will be essential to prevent excess morbidity and mortality. METHODS: We investigated the spatial risk of malaria infection at multiple timepoints after severe flooding in rural western Uganda employing longitudinal household surveys measuring parasite prevalence and leveraging remotely sensed information to inform spatial models of malaria risk in the 3 months after flooding. RESULTS: We identified clusters of malaria risk emerging in areas (1) that showed the greatest changes in Normalized Difference Vegetation Index from pre- to postflood and (2) where residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage. CONCLUSIONS: The findings enhance our understanding not only of the spatial evolution of malaria risk after flooding, but also in the context of an effective intervention. The results provide a "proof of concept" for programs aiming to prevent malaria outbreaks after flooding using a combination of interventions. Further study of mitigation strategies-and particularly studies of implementation-is urgently needed.

High frequency of artemisinin partial resistance mutations in the Great Lakes region revealed through rapid pooled deep sequencing.

BACKGROUND: In Africa, the first Plasmodium falciparum artemisinin partial resistance mutation, was Kelch13 (K13) 561H - detected and validated at appreciable frequency in Rwanda in 2014. Surveillance to better define the extent of the emergence in Rwanda and neighboring countries is critical. METHODS: We used novel liquid blood drop preservation combined with pooled sequencing to provide cost-effective rapid assessment of resistance mutation frequencies at multiple collection sites across Rwanda and neighboring regions in Uganda, Tanzania, and the Democratic Republic of the Congo (DRC). Malaria-positive samples (n=5,465) from 39 health facilities collected between May 2022 and March 2023 were sequenced in 199 pools. RESULTS: In Rwanda, K13 561H and 675V were detected in 90% and 65% of sites with an average frequency of 19.0% (0-54.5%) and 5.0% (0-35.5%), respectively. In Tanzania, 561H had high frequency in multiple sites. 561H appeared at 1.6% in Uganda. 561H was absent from the DRC, although 675V was seen at low frequency. Concerningly candidate mutations were observed: 441L, 449A, and 469F co-occurred with validated mutations suggesting they are arising under the same pressures. Other markers for decreased susceptibility to artemether-lumefantrine are common: P. falciparum multidrug resistance protein 1 N86 at 98.0% (63.3-100%) and 184F at 47.0% (0-94.3%) and P. falciparum chloroquine resistance transporter 76T at 14.7% (0-58.6%). Additionally, sulfadoxine-pyrimethamine-associated mutations show high frequencies. CONCLUSION: K13 mutations are rapidly expanding in the region further endangering control efforts with the potential of engendering partner drug resistance.

Point-of-care C-reactive protein measurement by community health workers safely reduces antimicrobial use among children with respiratory illness in rural Uganda: A stepped wedge cluster randomized trial.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: 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).

Cost-effectiveness of village health worker-led integrated community case management (iCCM) versus health facility based management for childhood illnesses in rural southwestern Uganda.

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.

COVID-19 vaccine hesitancy: assessing the prevalence, predictors, and effectiveness of a community pharmacy based counseling intervention.

BACKGROUND: Coronavirus disease (COVID-19) vaccine hesitancy is a global challenge. In low- and middle-income countries (LMICs), the problem has persisted despite vaccine availability and decreasing infections. In Uganda, there is still limited information on the extent and predictors of vaccine hesitancy. This study sought to assess the prevalence and predictors of COVID-19 vaccine hesitancy, and the effectiveness of an intervention that involved community pharmacy counseling in combating COVID-19 vaccine hesitancy. METHODS: A total of 394 participants were enrolled in a 4-week prospective cohort interventional study. The study was conducted across eight community pharmacies in Mbarara City, between 9:00 AM and 5:00 PM daily. The study personnel ascertained the vaccination status of all clients seeking community pharmacy services. All unvaccinated clients were consecutively assessed for eligibility, and eligible clients were systematically enrolled after receiving the community pharmacy services for which they requested. The study intervention involved structured participant counseling (within the pharmacy premise), follow-up short message service (weekly), and telephone calls (bi-weekly). Only participants who did not accept to receive the COVID-19 vaccine despite counseling were followed up for four weeks, or until they accepted to receive a COVID-19 vaccine. The effectiveness of the community pharmacy counseling intervention was determined as an increase in COVID-19 vaccine acceptance, and desirable attitudinal change towards COVID-19 disease, vaccination exercise, and vaccines. Descriptive analysis was used to summarize data, and multivariate analysis was used to determine the predictors of COVID-19 vaccine hesitancy. A p-value < 0.05 was considered statistically significant. RESULTS: Out of 394 participants, 221 (56%) were hesitant to receive a COVID-19 vaccine. Participants expressed several reasons (mean 2±1) for COVID-19 vaccine hesitancy, mostly concerning vaccine safety (N=160, 47.3%). The overall COVID-19 vaccine acceptance rate increased by 25.4 percent points (43.9 - 69.3 percent points) after the study intervention. Age, religion, level of education, distance from the nearest public health facility, having a friend/family diagnosed with COVID-19, and personal suspicion of contracting COVID-19 were significant predictors of COVID-19 vaccine hesitancy. CONCLUSION: COVID-19 vaccine hesitancy is a big challenge in Uganda. A mix of sociodemographic and COVID-19 vaccine perceptions are the key predictors of COVID-19 vaccine hesitancy. Although COVID-19 vaccines were not available at the time of the study, this study found that structured counseling interventions can improve COVID-19 vaccine acceptance rates. Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other healthcare settings.

Assessment of pre-referral treatment for malaria, diarrhea, and pneumonia by rural community health workers in Southwestern Uganda: a cross-sectional study.

BACKGROUND: Pre-referral treatment aims to stabilize the child's condition before transferring them to a higher level of healthcare. This study explored pre-referral treatment for diarrhea, malaria and pneumonia in children U5. The study aims to assess pre-referral treatment practices among community health workers (CHWs) for children aged 2 to 59 months diagnosed with malaria, diarrhea, and pneumonia. METHODS: Conducted in 2023, this study employed a quantitative retrospective analysis of secondary data gathered from March 2014 to December 2018. Among the subjects, 171 patients received pre-referral treatment, serving as the foundation for categorical data analysis, presenting proportions and 95% confidence intervals across different categories. RESULTS: In this cohort, 90 (53%) of the 177 children U5 were male, and age distribution showed 39 (23%), 70 (41%), and 62 (36%) in the 2-11 months, 12-35 months, and 36-60 months categories, respectively. Rapid Diagnostic Test (RDT) malaria results indicated a negative outcome in 83(60%) and positive in 55 (40%) of cases. Symptomatically, 45 (26%) had diarrhea, 52 (30%) exhibited fast breathing, and 109 (63%) presented with fever. Furthermore, 59 (35%) displayed danger signs, while 104 (61%) sought medical attention within 24 h. CONCLUSION: The study analyzed a sample of 171 children under 5 years old to assess various characteristics and variables related to pre-referral treatment. The findings reveal notable proportions in gender distribution, age categories, RDT results, presence of diarrhea, fast breathing, fever, danger signs, and timely medical visits. The results highlight the need to strengthen pre-referral treatment interventions and enhance iCCM programs.

Hirschsprung disease: a cost analysis study of the direct, indirect costs and financial coping strategies for the surgical management in Western Uganda.

BACKGROUND: Surgical management of Hirschsprung disease (HD) in low- and middle-income countries is typically a staged procedure, necessitating multiple hospitalizations and clinic visits increasing family financial burden. Currently, there is limited information on the costs borne by caretakers of children with Hirschsprung disease seeking surgical intervention. This study seeks to measure the costs and economic burden of surgical treatment for Hirschsprung disease in western Uganda. METHODS: A cross-sectional study using cost analysis was conducted among caretakers of patients who completed surgical treatment of HD between January 2017 and December 2021 at two hospitals in western Uganda. The average direct and indirect costs incurred by caretakers presenting at a public and private hospital were computed. RESULTS: A total of 69 patients (M: F = 7:1) were enrolled in the study. The median age at diagnosis was 60.5 (IQR 3-151.25) days for children and two-staged pull-through procedure was the common surgery performed. The mean overall cost for treatment was US $960 (SD = $720), with the majority of costs coming from direct medical costs. Nearly half (48%) of participants resorted to distress financing to finance their child's surgical care. The overwhelming majority of patients (n = 64, 93%) incurred catastrophic expenditure from the total costs of surgery for HD, and 97% of participants fell below the international poverty line at the time treatment was completed. CONCLUSION: Despite the availability of 'free care' from government hospital and non-profit services, this study found that surgical management of Hirschsprung disease imposed substantial cost burden on families with Hirschsprung disease patients.

Outcomes of a honey and olive oil-based dressing material on wounds of women that have had a caesarean section in south-western Uganda.

Postpartum sepsis following caesarean sections among women in Uganda remains a risk. However, erratic supplies of standard dressing material make the risk a reality. Alternative wound dressing materials, therefore, remain a viable option. This study examined the outcome of a honey and olive oil-based dressing material on caesarean section wound healing. Using the Uganda Industrial Research Institute (UIRI), the study team created I-Dress, a wound dressing made of honey and olive oil. A case-series study was conducted on 25 women who received I-Dress following caesarean births at three health facilities in south-west Uganda. Vital signs (temperature, blood pressure, and heart rate) were measured, along with wound induration, dehiscence, and discharge. The primary outcome was the length of time it took for the wound to heal. The average age of the women who received I-Dress was 27.5 (±4.8) years. Following the application of I-Dress, all of the women (100%) had no wound induration or dehiscence, with only two (13%) experiencing wound discharge. The vast majority of the women (88%) had never had a Caesarean section before. The mean time required for wound healing was 2.2 (±0.7) days. The findings indicate that honey and olive oil-based dressings improve Caesarean section wound healing in terms of wound induration, dehiscence, and time to healing. These dressing materials can therefore supplement the standard dressing materials, especially in resource-constrained settings.

Comparing field-collected versus remotely-sensed variables to model malaria risk in the highlands of western Uganda.

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.

Promptness in seeking treatment from Village Health workers for children under five years with malaria, diarrhoea and pneumonia in rural southwestern Uganda.

BACKGROUND: Village Health Workers (VHWs) in Uganda provide treatment for the childhood illness of malaria, pneumonia, and diarrhoea through the integrated community case management (iCCM) strategy. Under the strategy children under five years receive treatment for these illnesses within 24 h of onset of illness. This study examined promptness in seeking treatment from VHWs by children under five years with malaria, pneumonia, and diarrhoea in rural southwestern Uganda. METHODS: In August 2022, a database containing information from the VHWs patient registers over a 5-year study period was reviewed (2014-2018). A total of 18,430 child records drawn from 8 villages of Bugoye sub-county, Kasese district were included in the study. Promptness was defined a caregiver seeking treatment for a child from a VHW within 24 h of onset of illness. RESULTS: Sixty-four percent (64%) of the children included in the study sought treatment promptly. Children with fever had the highest likelihood of seeking prompt treatment (aOR = 1.93, 95% CI 1.80-2.06, p < 0.001) as compared to those with diarrhoea (aOR = 1.43, 95% CI 1.32-1.52, p < 0.001) and pneumonia (aOR = 1.33, 95% CI 1.24-1.42, p < 0.001). CONCLUSION: The findings provide further evidence that VHWs play a critical role in the treatment of childhood illness in rural contexts. However, the proportion of children seeking prompt treatment remains below the target set at the inception of the iCCM strategy, in Uganda. There is a need to continually engage rural communities to promote modification of health-seeking behaviour, particularly for children with danger signs. Evidence to inform the design of services and behaviour change communication, can be provided through undertaking qualitative studies to understand the underlying reasons for decisions about care-seeking in rural settings. Co-design with communities in these settings may increase the acceptability of these services.

Prevalence of prediabetes and associated factors among community members in rural Isingiro district.

BACKGROUND: In rural Uganda a significant number of persons afflicted with pre-diabetes are unaware of the condition. This is likely to lead to diabetic complications resulting in catastrophic health expendirure.The burden of prediabetes in rural Isingiro has not previously been determined. This study examined the prevalence of prediabetes and the associated factors among rural community members. METHODS: We conducted a cross-sectional survey and enrolled 370 participants aged between 18 and 70 years in the Kabuyanda sub-county, rural Isingiro district in march 2021. Multistage sampling and systematic random sampling were conducted to select eligible households. Data was collected using a pretested WHO STEP-wise protocol questionnaire. The primary outcome was prediabetes (FBG = 6.1mmol/l to 6.9mmol/l), calculated as a proportion. Participants known to be diabetic or on medication were excluded. Chi-square tests and multivariate logistic regression model were performed for data analysis using STATA. RESULTS: The prevalence of prediabetes was 9.19% (95% CI 6.23-12.14). Independent factors significantly associated with pre-diabetes were; advancing age [AOR = 5.7, 95% CI:1.03-32.30], moderate-intensity work [AOR = 2.6,95% CI:1.23-5.63], high level of consumption of a healthy diet [AOR = 5.7, 95% CI:1.67-19.05] and body mass index [AOR = 3.7, 95% CI:1.41-9.20]. CONCLUSION: Prediabetes is prevalent among adult community members in rural Isingiro, southwestern Uganda. Age and lifestyle factors predict prediabetes in this rural population, suggesting a need for targeted health promotion interventions.

Dihydroartemisinin-Piperaquine Chemoprevention and Malaria Incidence After Severe Flooding: Evaluation of a Pragmatic Intervention in Rural Uganda.

BACKGROUND: Malaria epidemics are a well-described phenomenon after extreme precipitation and flooding. Yet, few studies have examined mitigation measures to prevent post-flood malaria epidemics. METHODS: We evaluated a malaria chemoprevention program implemented in response to severe flooding in western Uganda. Children aged ≤12 years from 1 village were eligible to receive 3 monthly rounds of dihydroartemisinin-piperaquine (DP). Two neighboring villages served as controls. Malaria cases were defined as individuals with a positive rapid diagnostic test result as recorded in health center registers. We performed a difference-in-differences analysis to estimate changes in the incidence and test positivity of malaria between intervention and control villages. RESULTS: A total of 554 children received at least 1 round of chemoprevention, with 75% participating in at least 2 rounds. Compared with control villages, we estimated a 53.4% reduction (adjusted rate ratio [aRR], 0.47; 95% confidence interval [CI]: .34-.62; P < .01) in malaria incidence and a 30% decrease in the test positivity rate (aRR, 0.70; 95% CI: .50-.97; P = .03) in the intervention village in the 6 months post-intervention. The impact was greatest among children who received the intervention, but decreased incidence was also observed in older children and adults (aRR, 0.57; 95% CI: .38-.84; P < .01). CONCLUSIONS: Three rounds of chemoprevention with DP delivered under pragmatic conditions reduced the incidence of malaria after severe flooding in western Uganda. These findings provide a proof-of-concept for the use of malaria chemoprevention to reduce excess disease burden associated with severe flooding.

Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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.

Contribution of community health workers to the treatment of common illnesses among under 5-year-olds in rural Uganda.

BACKGROUND: The control of malaria, pneumonia, and diarrhoea is important for the reduction in morbidity and mortality among children under 5 years. Uganda has adopted the Integrated Community Case Management strategy using Community Health Workers (CHWs) to address this challenge. The extent and trend of these three conditions managed by the CHWs are not well documented. This study was done to describe the epidemiology and trends of the three common illnesses treated by the CHWs in Bugoye Sub-County in rural Uganda. METHODS: A retrospective review of monthly morbidity data for children less than 5 years of age for the period April 2014-December 2018 for CHWs in rural Bugoye Sub-County in Kasese district, Uganda was done. The total number reviewed was 18,430 records. The data were analysed using STATA version 14. RESULTS: In total male were 50.2% of the sample, pneumonia was the highest cause of illness among the infants (< 1 year), while malaria was the highest among the children 1 year-59 months. Infection with a single illness was the commonest recorded cause of presentation but there were some children recorded with multiple illnesses. All the CHWs were managing the three common illnesses among children under 5 years. The trend of the three common illnesses was changing from malaria to pneumonia being the commonest. Children aged 12-24 months and 25-59 months were at 2.1 times (95% CI 1.7-2.4) and 5.2 times (95% CI 4.6-5.9), respectively, more likely to get malaria but less likely to get pneumonia and diarrhoea. CONCLUSION: Community Health Workers in rural Uganda are contributing significantly to the management of all the three commonest illnesses among under-5 years-old children. The trend of the commonest illness is changing from malaria to pneumonia. Children under 1 year are at a higher risk of getting pneumonia and diarrhoea and at a lower risk of getting malaria.

Permethrin-treated baby wraps for the prevention of malaria: results of a randomized controlled pilot study in rural Uganda.

BACKGROUND: Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed. METHODS: The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps-known locally as lesus-in children 6-18 months of age at a single site in rural western Uganda. Fifty mother-infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively. RESULTS: Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0-1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2). CONCLUSIONS: Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04102592, Registered 25 September 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT04102592.

Gaps in measles vaccination coverage in Kasese district, Western Uganda: results of a qualitative evaluation.

BACKGROUND: Despite the availability of a highly effective vaccine, measles remains a substantial public health problem in many countries including Uganda. In this study, conducted between June-August 2020 following a local outbreak, we sought to explore the factors that could affect measles vaccination coverage in rural western Uganda. METHODS: We conducted a descriptive study using qualitative data collection approaches in the Kasese district. The research team utilized purposive sampling to identify and select participants from the public health sector and district government. We conducted key informant interviews (KII) and one focus group discussion (FGD). Responses were recorded using portable electronic devices with the FGD and KII guide installed. Interviews were conducted at the health centre and district headquarters. Data was coded and analysed using ATLAS.ti version 8 software through deductive thematic analysis to identify key themes. RESULTS: Barriers to measles vaccination identified in this study were premised around six themes including: (i) availability of supplies and stock management, (ii) health worker attitudes and workload, (iii) financing of vaccination outreach activities, (iv) effectiveness of duty rosters (i.e., health workers' working schedules), (v) community beliefs, and (vi) accessibility of healthcare facilities. Respondents reported frequent vaccine supply disruptions, lack of resources to facilitate transportation of health workers to communities for outreach events, and health centre staffing that did not adequately support supplemental vaccination activities. Furthermore, community dependence on traditional medicine as a substitute for vaccines and long distances traveled by caregivers to reach a health facility were mentioned as barriers to vaccination uptake. CONCLUSIONS: Health system barriers limiting vaccination uptake were primarily logistical in nature and reflect inadequate resourcing of immunization efforts. At the same time, local beliefs favouring traditional medicine remain a persistent cultural barrier. These findings suggest an urgent need for more efficient supply management practices and resourcing of immunization outreaches in order to achieve the Uganda Ministry of Health's targets for childhood immunization and the prevention of disease outbreaks.

Improved maternal-fetal outcomes among emergency obstetric referrals following phone call communication at a teaching hospital in south western Uganda: a quasi-experimental study.

BACKGROUND: Emergency obstetric referrals develop adverse maternal-fetal outcomes partly due to delays in offering appropriate care at referral hospitals especially in resource limited settings. Referral hospitals do not get prior communication of incoming referrals leading to inadequate preparedness and delays of care. Phone based innovations may bridge such communication challenges. We investigated effect of a phone call communication prior to referral of mothers in labour as intervention to reduce preparation delays and improve maternal-fetal outcome at a referral hospital in a resource limited setting. METHODS: This was a quasi-experimental study with non-equivalent control group conducted at Mbarara Regional Referral Hospital (MRRH) in South Western Uganda from September 2020 to March 2021. Adverse maternal-fetal outcomes included: early neonatal death, fresh still birth, obstructed labour, ruptured uterus, maternal sepsis, low Apgar score, admission to neonatal ICU and hysterectomy. Exposure variable for intervention group was a phone call prior maternal referral from a lower health facility. We compared distribution of clinical characteristics and adverse maternal-fetal outcomes between intervention and control groups using Chi square or Fisher's exact test. We performed logistic regression to assess association between independent variables and adverse maternal-fetal outcomes. RESULTS: We enrolled 177 participants: 75 in intervention group and 102 in control group. Participants had similar demographic characteristics. Three quarters (75.0%) of participants in control group delayed on admission waiting bench of MRRH compared to (40.0%) in intervention group [p = < 0.001]. There were significantly more adverse maternal-fetal outcomes in control group than intervention group (obstructed labour [p = 0.026], low Apgar score [p = 0.013] and admission to neonatal high dependency unit [p = < 0.001]). The phone call intervention was protective against adverse maternal-fetal outcome [aOR = 0.22; 95%CI: 0.09-0.44, p = 0.001]. CONCLUSION: The phone call intervention resulted in reduced delay to patient admission at a tertiary referral hospital in a resource limited setting, and is protective against adverse maternal-fetal outcomes. Incorporating the phone call communication intervention in the routine practice of emergency obstetric referrals from lower health facilities to regional referral hospitals may reduce both maternal and fetal morbidities. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR20200686885039.

Contextual and psychological factors influencing open defecation free status: an exploratory qualitative study in rural South Western Uganda.

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.

Comparison of Capillary Versus Venous Blood for the Diagnosis of Plasmodium falciparum Malaria Using Rapid Diagnostic Tests.

We enrolled 250 febrile children in western Uganda to compare the results of malaria rapid diagnostic tests (RDTs) when using capillary vs venous blood. Participants were tested with 4 different RDT types. Polymerase chain reaction testing was performed as the reference standard. Sensitivity and specificity were broadly similar across RDT types and sampling method. Agreement between sample type was high, ranging from 0.95 to 0.99. When following the manufacturer's recommended interpretation, only 5 tests would have resulted in a different clinical diagnosis. These results demonstrate that malaria RDTs perform similarly when using capillary or venous blood in febrile children with Plasmodium falciparum malaria.

Cost-effectiveness analysis of integrated community case management delivery models utilizing drug sellers and community health workers for treatment of under-five febrile cases of malaria, pneumonia, diarrhoea in rural Uganda.

BACKGROUND: Malaria, pneumonia and diarrhoea continue to be the leading causes of death in children under the age of five years (U5) in Uganda. To combat these febrile illnesses, integrated community case management (iCCM) delivery models utilizing community health workers (CHWs) or drug sellers have been implemented. The purpose of this study is to compare the cost-effectiveness of delivering iCCM interventions via drug sellers versus CHWs in rural Uganda. METHODS: This study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs. The effect measure was the number of appropriately treated U5 children, and data on effectiveness came from a quasi-experimental study in Southwestern Uganda and the inSCALE cross-sectional household survey in eight districts of mid-Western Uganda. The iCCM interventions were costed using the micro-costing (ingredients) approach, with costs expressed in US dollars. Cost and effect data were linked together using a decision tree model and analysed using the Amua modelling software. RESULTS: The costs per 100 treated U5 children were US$591.20 and US$298.42 for the iCCM trained-drug seller and iCCM trained-CHW models, respectively, with 30 and 21 appropriately treated children in the iCCM trained-drug seller and iCCM trained-CHW models. When the drug seller arm (intervention) was compared to the CHW arm (control), an incremental effect of 9 per 100 appropriately treated U5 children was observed, as well as an incremental cost of US$292.78 per 100 appropriately treated children, resulting in an incremental cost-effectiveness ratio (ICER) of US$33.86 per appropriately treated U5 patient. CONCLUSION: Since both models were cost-effective compared to the do-nothing option, the iCCM trained-drug seller model could complement the iCCM trained-CHW intervention as a strategy to increase access to quality treatment.