LLIN evaluation in Uganda project (LLINEUP2): association between housing construction and malaria burden in 32 districts.

BACKGROUND: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts. METHODS: Houses were classified as 'improved' (synthetic walls and roofs, eaves closed or absent) or 'less-improved' (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression. RESULTS: Between November 2021 and March 2022, 4.893 children aged 2-10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33-0.53, p < 0.0001) of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19-0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36-0.44, p < 0.0001) compared to communities with < 39% of houses improved. CONCLUSIONS: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control.

LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda.

BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results suggest that the disruptions in the 2020-2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.

House modifications as a malaria control tool: how does local context shape participants' experience and interpretation in Uganda?

BACKGROUND: Evidence that house design can provide protection from malaria is growing. Housing modifications such as screening windows, doors, and ceilings, and attaching insecticide-impregnated materials to the eaves (the gap between the top of the wall and bottom of the roof), can protect against malaria. To be effective at scale, however, these modifications must be adopted by household residents. There is evidence that housing modifications can be acceptable, but in-depth knowledge on the experiences and interpretation of modifications is lacking. This qualitative study was carried out to provide a holistic account of the relationship between experiences and interpretations of four types of piloted housing modifications and the local context in Jinja, Uganda. METHODS: Qualitative research was conducted between January to June 2021, before and during the installation of four types of housing modifications. The methods included nine weeks of participant observations in two study villages, nine focus group discussions with primary caregivers and heads of households (11-12 participants each), and nine key informant interviews with stakeholders and study team members. RESULTS: Most residents supported the modifications. Experiences and interpretation of the housing modifications were shaped by the different types of housing in the area and the processes through which residents finished their houses, local forms of land and property ownership, and cultural and spiritual beliefs about houses. CONCLUSIONS: To maximize the uptake and benefit of housing modifications against malaria, programme development needs to take local context into account. Forms of local land and house ownership, preferences, the social significance of housing types, and religious and spiritual ideas shape the responses to housing modifications in Jinja. These factors may be important in other setting. Trial registration Trial registration number is NCT04622241. The first draft was posted on November 9th 2020.

Late morning biting behaviour of Anopheles funestus is a risk factor for transmission in schools in Siaya, western Kenya.

BACKGROUND: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Anopheles funestus, previously documented in households in western Kenya, was replicated in schools. METHODS: From the 4th to the 6th of August 2023, human landing collections were conducted hourly in four schools in Alego Usonga sub-County, Siaya County. The collections were conducted in and outside five classrooms in each school and ran for 17 h, starting at 18:00 until 11:00 h the next morning. RESULTS: Anopheles funestus was the predominant species collected, forming 93.2% (N = 727) of the entire collection, with peak landing between 06:00 and 07:00 h and continuing until 11:00 h. More than half of the collected An. funestus were either fed or gravid, potentially indicative of multiple bloodmeals within each gonotrophic cycle, and had a sporozoite rate of 2.05%. CONCLUSION: School children spend up to 10 h of their daytime in schools, reporting between 06:00 and 07:00 h and staying in school until as late as 17:00 h, meaning that they receive potentially infectious mosquito bites during the morning hours in these settings. There is a need to consider vector control approaches targeting schools and other peridomestic spaces in the morning hours when An. funestus is active.

Pharmaceuticalised livelihoods: antibiotics and the rise of 'Quick Farming' in peri-urban Uganda.

The 'livestock revolution' has seen the lives and livelihoods of peri-urban peoples increasingly intertwine with pigs and poultry across Africa in response to a rising demand for meat protein. This 'revolution' heralds the potential to address both poverty and nutritional needs. However, the intensification of farming has sparked concern, including for antibiotic misuse and its consequences for antimicrobial resistance (AMR). These changes reflect a micro-biopolitical conundrum where the agendas of microbes, farmers, publics, authorities and transnational agencies are in tension. To understand this requires close attention to the practices, principles and potentials held between these actors. Ethnographic research took place in a peri-urban district, Wakiso, in Uganda between May 2018 and March 2021. This included a medicine survey at 115 small- and medium-scale pig and poultry farms, 18 weeks of participant observation at six farms, 34 in-depth interviews with farmers and others in the local livestock sector, four group discussions with 38 farmers and 7 veterinary officers, and analysis of archival, media and policy documents. Wide-scale adoption of quick farming was found, an entrepreneurial phenomenon that sees Ugandans raising 'exotic' livestock with imported methods and measures for production, including antibiotics for immediate therapy, prevention of infections and to promote production and protection of livelihoods. This assemblage - a promissory assemblage of the peri-urban - reinforced precarity against which antibiotics formed a potential layer of protection. The paper argues that to address antibiotic use as a driver of AMR is to address precarity as a driver of antibiotic use. Reduced reliance on antibiotics required a level of biosecurity and economies of scale in purchasing insurance that appeared affordable only by larger-scale commercial producers. This study illustrates the risks - to finances, development and health - of expanding an entrepreneurial model of protein production in populations vulnerable to climate, infection and market dynamics.

Asymptomatic School-Aged Children Are Important Drivers of Malaria Transmission in a High Endemicity Setting in Uganda.

Achieving malaria elimination requires a better understanding of the transmissibility of human infections in different transmission settings. This study aimed to characterize the human infectious reservoir in a high endemicity setting in eastern Uganda, using gametocyte quantification and mosquito feeding assays. In asymptomatic infections, gametocyte densities were positively associated with the proportion of infected mosquitoes (ß = 1.60; 95% CI, 1.32-1.92; P < .0001). Combining transmissibility and abundance in the population, symptomatic and asymptomatic infections were estimated to contribute to 5.3% and 94.7% of the infectious reservoir, respectively. School-aged children (5-15 years old) contributed to 50.4% of transmission events and were important drivers of malaria transmission.

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.

A quasi-experimental study estimating the impact of long-lasting insecticidal nets with and without piperonyl butoxide on pregnancy outcomes.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed. METHODS: Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators. RESULTS: ITSAs estimated the campaign was associated with a 26% [95% CI: 7-41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59-0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67-1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7-9 months after the campaign (IRR=0.60 [0.41-0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence. CONCLUSIONS: In this region of Uganda, where pyrethroid resistance is high, this study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.

Impact of different mosquito collection methods on indicators of Anopheles malaria vectors in Uganda.

BACKGROUND: Methods used to sample mosquitoes are important to consider when estimating entomologic metrics. Human landing catches (HLCs) are considered the gold standard for collecting malaria vectors. However, HLCs are labour intensive, can expose collectors to transmission risk, and are difficult to implement at scale. This study compared alternative methods to HLCs for collecting Anopheles mosquitoes in eastern Uganda. METHODS: Between June and November 2021, mosquitoes were collected from randomly selected households in three parishes in Tororo and Busia districts. Mosquitoes were collected indoors and outdoors using HLCs in 16 households every 4 weeks. Additional collections were done indoors with prokopack aspirators, and outdoors with pit traps, in these 16 households every 2 weeks. CDC light trap collections were done indoors in 80 households every 4 weeks. Female Anopheles mosquitoes were identified morphologically and Anopheles gambiae sensu lato were speciated using PCR. Plasmodium falciparum sporozoite testing was done with ELISA. RESULTS: Overall, 4,891 female Anopheles were collected, including 3,318 indoors and 1,573 outdoors. Compared to indoor HLCs, vector density (mosquitoes per unit collection) was lower using CDC light traps (4.24 vs 2.96, density ratio [DR] 0.70, 95% CIs 0.63-0.77, p < 0.001) and prokopacks (4.24 vs 1.82, DR 0.43, 95% CIs 0.37-0.49, p < 0.001). Sporozoite rates were similar between indoor methods, although precision was limited. Compared to outdoor HLCs, vector density was higher using pit trap collections (3.53 vs 6.43, DR 1.82, 95% CIs 1.61-2.05, p < 0.001), while the sporozoite rate was lower (0.018 vs 0.004, rate ratio [RR] 0.23, 95% CIs 0.07-0.75, p = 0.008). Prokopacks collected a higher proportion of Anopheles funestus (75.0%) than indoor HLCs (25.8%), while pit traps collected a higher proportion of Anopheles arabiensis (84.3%) than outdoor HLCs (36.9%). CONCLUSION: In this setting, the density and species of mosquitoes collected with alternative methods varied, reflecting the feeding and resting characteristics of the common vectors and the different collection approaches. These differences could impact on the accuracy of entomological indicators and estimates of malaria transmission, when using the alternative methods for sampling mosquitos, as compared to HLCs.

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.

LLIN Evaluation in Uganda Project (LLINEUP2)-Factors associated with coverage and use of long­lasting insecticidal nets following the 2020-21 national mass distribution campaign: a cross-sectional survey of 12 districts.

BACKGROUND: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution. METHODS: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities. RESULTS: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001). CONCLUSIONS: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted.

Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda.

BACKGROUND: Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. METHODS: This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. RESULTS: Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68-1.77, p < 0.001), with larger differences among those 15-39 years (IRR = 2.46, 95% CI 2.34-2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05-2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41-1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71-1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15-39 years (RR = 2.49, 95% CI 1.17-5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00-6.54, p = 0.049). CONCLUSIONS: Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.

Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors. METHODS: 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2-10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395. FINDINGS: LLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62-0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63-0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72-0·98; p=0·029). INTERPRETATION: In Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs. FUNDING: The Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation.

Marked reduction in antibiotic usage following intensive malaria control in a cohort of Ugandan children.

BACKGROUND: Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. METHODS: Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. RESULTS: Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4-5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01-0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27-0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. CONCLUSIONS: In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.

Factors associated with access and adherence to artemisinin-based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone.

BACKGROUND: Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five. METHODS: The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression. RESULTS: Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02-3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29-2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27-2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20-4.44; p = 0.025), and age (24-59 vs. 0-23 months; OR 1.45, 95% CI 1.07-1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34-0.89; p = 0.015). CONCLUSIONS: In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.

Plasmodium malariae infections as a cause of febrile disease in an area of high Plasmodium falciparum transmission intensity in Eastern Uganda.

BACKGROUND: Plasmodium falciparum is responsible for the vast majority of (severe) clinical malaria cases in most African settings. Other Plasmodium species often go undiagnosed but may still have clinical consequences. CASE PRESENTATION: Here, five cases of Plasmodium malariae infections from Eastern Uganda (aged 2-39 years) are presented. These infections were all initially mistaken for P. falciparum, but Plasmodium schizonts (up to 2080/µL) were identified by microscopy. Clinical signs included history of fever and mild anaemia. CONCLUSION: These findings highlight the importance of considering non-falciparum species as the cause of clinical malaria. In areas of intense P. falciparum transmission, where rapid diagnostic tests that detect only P. falciparum antigens are commonly used, non-falciparum malaria cases may be missed.

Opening the 'black box' of collaborative improvement: a qualitative evaluation of a pilot intervention to improve quality of malaria surveillance data in public health centres in Uganda.

BACKGROUND: Demand for high-quality surveillance data for malaria, and other diseases, is greater than ever before. In Uganda, the primary source of malaria surveillance data is the Health Management Information System (HMIS). However, HMIS data may be incomplete, inaccurate or delayed. Collaborative improvement (CI) is a quality improvement intervention developed in high-income countries, which has been advocated for low-resource settings. In Kayunga, Uganda, a pilot study of CI was conducted in five public health centres, documenting a positive effect on the quality of HMIS and malaria surveillance data. A qualitative evaluation was conducted concurrently to investigate the mechanisms of effect and unintended consequences of the intervention, aiming to inform future implementation of CI. METHODS: The study intervention targeted health workers, including brief in-service training, plus CI with 'plan-do-study-act' (PDSA) cycles emphasizing self-reflection and group action, periodic learning sessions, and coaching from a CI mentor. Health workers collected data on standard HMIS out-patient registers. The qualitative evaluation (July 2015 to September 2016) included ethnographic observations at each health centre (over 12-14 weeks), in-depth interviews with health workers and stakeholders (n = 20), and focus group discussions with health workers (n = 6). RESULTS: The results suggest that the intervention did facilitate improvement in data quality, but through unexpected mechanisms. The CI intervention was implemented as planned, but the PDSA cycles were driven largely by the CI mentor, not the health workers. In this context, characterized by a rigid hierarchy within the health system of limited culture of self-reflection and inadequate training and supervision, CI became an effective form of high-quality training with frequent supervisory visits. Health workers appeared motivated to improve data collection habits by their loyalty to the CI mentor and the potential for economic benefits, rather than a desire for self-improvement. CONCLUSIONS: CI is a promising method of quality improvement and could have a positive impact on malaria surveillance data. However, successful scale-up of CI in similar settings may require deployment of highly skilled mentors. Further research, focusing on the effectiveness of 'real world' mentors using robust study designs, will be required to determine whether CI can be translated effectively and sustainably to low-resource settings.

Challenges and opportunities for use of long-lasting insecticidal nets to prevent malaria during overnight travel in Uganda: a qualitative study.

BACKGROUND: Travel is a well-recognized risk factor for malaria. Within sub-Saharan Africa, travellers from areas of lower to higher transmission intensity are potentially at high risk of malaria. Long-lasting insecticidal nets (LLINs) are the primary tool for prevention of malaria, and their widespread use has contributed to substantial reductions in malaria burden. However, travellers often fail to use LLINs. To further explore the challenges and opportunities of using LLINs, travellers were interviewed in Uganda. METHODS: In August and September 2019, 20 participants attending outpatient clinics at Naguru General Hospital in Kampala with a history of travel out of Kampala within the previous 60 days were purposively selected. Data were collected through in-depth interviews and analysed thematically using NVivo 12. RESULTS: Of the 20 participants, 13 were male. Thirteen of the 20 participants tested positive for malaria by microscopy, and 5 reported using of LLINs during travel. The main reasons for travel were to attend social events (weddings, funerals, overnight prayers) and for work. travellers who attended social events reported using LLINs less commonly than those who travelled for work. Challenges to using LLINs during travel included: (1) limited access to LLINs; (2) challenges in planning ahead of travel; (3) lack of space or ability to hang LLINs while travelling; (4) impression that LLINs in lodging places were unhygienic; (5) cultural beliefs discouraging use of LLINs during social events; (6) participation in overnight ceremonies; and (7) doubts about efficacy of LLINs. Positive factors influencing use of LLINs during travel included knowledge regarding malaria prevention and good affordability and availability of LLINs. CONCLUSIONS: Despite good traveller knowledge regarding malaria control measures, use of LLINs was limited. Use of LLINs in the prevention of malaria among travellers from low to high transmission settings needs to be prioritized. This calls for increased behaviour change oriented communication to improve traveller preparedness and consideration of use of repellents in situations where LLINs may not be feasible. The Uganda Ministry of Health and Malaria Control Division should use educational messages to increase awareness about the risks of getting malaria during overnight travel through the media. Truck drivers should be sensitized through their companies to use the available space at the back of the trucks for hanging nets and consider using pop-up nets.

Malaria prevalence and long-lasting insecticidal net use in rural western Uganda: results of a cross-sectional survey conducted in an area of highly variable malaria transmission intensity.

BACKGROUND: Long-lasting insecticidal nets (LLINs) remain a cornerstone of malaria control, but strategies to sustain universal coverage and high rates of use are not well-defined. A more complete understanding of context-specific factors, including transmission intensity and access to health facilities, may inform sub-district distribution approaches and tailored messaging campaigns. METHODS: A cross-sectional survey of 2190 households was conducted in a single sub-county of western Uganda that experiences highly variable malaria transmission intensity. The survey was carried out approximately 3 years after the most recent mass distribution campaign. At each household, study staff documented reported LLIN use and source among children 2 to 10 years of age and performed a malaria rapid diagnostic test. Elevation and distance to the nearest health facility was estimated for each household. Associations between parasite prevalence and LLIN use were estimated from log binomial regression models with elevation and distance to clinic being the primary variables of interest. RESULTS: Overall, 6.8% (148 of 2170) of children age 2-10 years of age had a positive RDT result, yielding a weighted estimate of 5.8% (95% confidence interval [CI] 5.4-6.2%). There was substantial variability in the positivity rates among villages, with the highest elevation villages having lower prevalence than lowest-elevation villages (p < .001). Only 64.7% (95% CI 64.0-65.5%) of children were reported to have slept under a LLIN the previous night. Compared to those living < 1 km from a health centre, households at ≥ 2 km were less likely to report the child sleeping under a LLIN (RR 0.86, 95% CI 0.83-0.89, p < .001). Households located farther from a health centre received a higher proportion of LLINs from government distributions compared to households living closer to health centres. CONCLUSIONS: LLIN use and sourcing was correlated with household elevation and estimated distance to the nearest health facility. The findings suggest that current facility-based distribution strategies are limited in their reach. More frequent mass distribution campaigns and complementary approaches are likely required to maintain universal LLIN coverage and high rates of use among children in rural Uganda.

Effectiveness of in-service training plus the collaborative improvement strategy on the quality of routine malaria surveillance data: results of a pilot study in Kayunga District, Uganda.

BACKGROUND: Surveillance data are essential for malaria control, but quality is often poor. The aim of the study was to evaluate the effectiveness of the novel combination of training plus an innovative quality improvement method-collaborative improvement (CI)-on the quality of malaria surveillance data in Uganda. METHODS: The intervention (training plus CI, or TCI), including brief in-service training and CI, was delivered in 5 health facilities (HFs) in Kayunga District from November 2015 to August 2016. HF teams monitored data quality, conducted plan-do-study-act cycles to test changes, attended periodic learning sessions, and received CI coaching. An independent evaluation was conducted to assess data completeness, accuracy, and timeliness. Using an interrupted time series design without a separate control group, data were abstracted from 156,707 outpatient department (OPD) records, laboratory registers, and aggregated monthly reports (MR) for 4 time periods: baseline-12 months, TCI scale-up-5 months; CI implementation-9 months; post-intervention-4 months. Monthly OPD register completeness was measured as the proportion of patient records with a malaria diagnosis with: (1) all data fields completed, and (2) all clinically-relevant fields completed. Accuracy was the relative difference between: (1) number of monthly malaria patients reported in OPD register versus MR, and (2) proportion of positive malaria tests reported in the laboratory register versus MR. Data were analysed with segmented linear regression modelling. RESULTS: Data completeness increased substantially following TCI. Compared to baseline, all-field completeness increased by 60.1%-points (95% confidence interval [CI]: 46.9-73.2%) at mid-point, and clinically-relevant completeness increased by 61.6%-points (95% CI: 56.6-66.7%). A relative - 57.4%-point (95% confidence interval: - 105.5, - 9.3%) change, indicating an improvement in accuracy of malaria test positivity reporting, but no effect on data accuracy for monthly malaria patients, were observed. Cost per additional malaria patient, for whom complete clinically-relevant data were recorded in the OPD register, was $3.53 (95% confidence interval: $3.03, $4.15). CONCLUSIONS: TCI improved malaria surveillance completeness considerably, with limited impact on accuracy. Although these results are promising, the intervention's effectiveness should be evaluated in more HFs, with longer follow-up, ideally in a randomized trial, before recommending CI for wide-scale use.