Private sector antimalarial sales a decade after "test and treat": A cross-sectional study of drug shop clients in rural Uganda.

Background: The World Health Organization has promoted "test and treat" guidelines for malaria since 2010, recommending all suspected malaria cases be confirmed with a parasitological test, typically a rapid diagnostic test (RDT), prior to treatment with antimalarial medications. However, many fevers at private drug shops in Uganda continue to be treated presumptively as malaria without diagnostic testing. Methods: The purpose of this study was to document private sector malaria case management in rural Uganda through a cross-sectional survey of drug shop clients in Bugoye sub-county. Drug shop vendors (n = 46) recorded information about sales interactions with clients reporting fever or requesting antimalarials and collected capillary blood samples from clients who purchased medications without an RDT. We estimated the proportion of clients who purchased an RDT, adhered to the RDT result, and received antimalarials without having laboratory-confirmed malaria. Results: Most drug shops were unlicensed (96%) and sold RDTs (98%). Of 934 clients with suspected malaria who visited study drug shops during the data collection period, only 25% bought an RDT. Since some clients reported previous RDTs from the public sector, 40% of clients were aware of their malaria status at the drug shop. Among those with negative tests, 36% still purchased antimalarials. Sixty-five percent of clients who purchased an antimalarial without an RDT subsequently tested negative. Conclusions: Despite national guidelines, drug shop clients who purchase antimalarials from drug shops in Bugoye are often not tested to confirm a malaria diagnosis prior to treatment. Most clients treated presumptively with antimalarials did not have malaria. Interventions are needed to improve malaria case management and rational drug use in the private sector.

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.

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.

"Testing for malaria does not cure any pain" A qualitative study exploring low use of malaria rapid diagnostic tests at drug shops in rural Uganda.

The World Health Organization recommends all suspected malaria cases be confirmed with a parasitological test, typically a rapid diagnostic test (RDT), prior to treatment. Despite recommendations, many fevers presenting at private drug shops are treated presumptively as malaria without diagnostic testing. The purpose of this qualitative study was to describe community perceptions of RDTs and explore ways to improve malaria case management at drug shops in Bugoye, western Uganda. A total of 63 in-depth interviews were conducted between September and December 2021 with 24 drug shop clients, 19 drug shop vendors, 12 community health workers, and 8 health and community officials. Data was analyzed using thematic content analysis and narrative techniques. While drug shop clients valued RDTs, the cost of the test limited their use. Further, mistrust in negative results and fear about treatment options for conditions other than malaria led to nonadherence to negative RDTs. Improvement with antimalarials after a negative RDT, or no RDT at all, was seen as proof an individual had malaria, reinforcing the acceptability of liberal antimalarial use. Drug shop vendors were knowledgeable about malaria case management but financially conflicted between recommending best practices and losing business. While clients viewed drug shop vendors as trusted health professionals, health officials distrusted them as business owners focused on maximizing profits. Study results suggest public-private partnerships that recognize the essential role of drug shops, better incorporate them into the healthcare system, and leverage the high levels of community trust in vendors, could provide greater opportunities for oversight and training to improve private-sector malaria case management. Interventions that address financial barriers to RDT use, emphasize the financial benefits of malaria testing, increase vendor knowledge about illnesses confused with malaria, and improve the quality of vendor-client counseling could increase RDT uptake and improve adherence to RDT results.

Rapid Diagnostic Tests to Guide Case Management of and Improve Antibiotic Stewardship for Pediatric Acute Respiratory Illnesses in Resource-Constrained Settings: a Prospective Cohort Study in Southwestern Uganda.

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic's laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

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.

Measles outbreak in Western Uganda: a case-control study.

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.

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.

Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness.

BACKGROUND: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. METHODS: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. RESULTS: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). CONCLUSIONS: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.

Private sector drug shops frequently dispense parenteral anti-malarials in a rural region of Western Uganda.

BACKGROUND: Malaria is a leading cause of paediatric morbidity and mortality in Uganda. More than half of febrile children in rural areas initially seek care at private clinics and drug shops. These shops are generally unregulated and the quality of clinical care is variable, with the potential for misdiagnosis and the development of drug resistance. There is thus an urgent need to identify rural drug shops and coordinate their malaria treatment efforts with those of the public sector. The objective of the study was to identify all drug shops in the Bugoye sub-county of Western Uganda and assess their anti-malarial dispensing practices. METHODS: This study is a cross-sectional survey of drug shops in a rural sub-county of Western Uganda. In the first phase, shop locations, licensing and shopkeeper's qualifications, and supply and pricing of anti-malarials were characterized. In the second phase, the proportion of anti-malarials dispensed by private drug shops was compared to public health facilities. RESULTS: A total of 48 drug shops were identified. Only one drug shop (1 of 48, 2%) was licensed with the sub-county's records office. The drug shops stocked a variety of anti-malarials, including first-line therapies and less effective agents (e.g., sulfadoxine/pyrimethamine). Almost all drug shops (45 of 48, 94%) provided parenteral anti-malarials. Of the 3900 individuals who received anti-malarials during the study, 2080 (53.3%) purchased anti-malarials through the private sector compared to 1820 (46.7%) who obtained anti-malarials through the public sector. Drug shops were the primary source of parenteral anti-malarials. Inadequate dosing of anti-malarials was more common in drug shops. CONCLUSIONS: Drug shops are major sources of parenteral anti-malarials, which should be reserved for cases of severe malaria. Strengthening malaria case management and incorporating drug shops in future interventions is necessary to optimize malaria control efforts in the sub-county, and in similarly endemic regions.