Comparison of commercially available, rapid, point-of-care C-reactive protein assays among children with febrile illness in southwestern Uganda.

In Uganda, children with febrile illness are often treated with antibiotics even though most have self-limiting, likely viral, infections. C-reactive protein (CRP) measurement can help identify those who are more likely to have a bacterial infection and therefore need antibiotic treatment. Implementation of a CRP rapid diagnostic test (RDT) at the point-of-care in resource-constrained settings with minimal laboratory infrastructure could reduce unnecessary antibiotic use. In this study, we evaluated the performance of three semi-quantitative CRP RDTs (Actim, BTNX, Duo) against a reference CRP assay requiring an electrically powered analyzer (Afinion). While both tests demonstrated substantial agreement with Afinion, Actim had slightly higher agreement than BTNX. The sensitivity was higher for the BTNX test, whereas the Actim test had a higher specificity, at cut-offs of 40 mg/L and 80 mg/L. At a cut-off of 20 mg/L, Duo demonstrated substantial agreement with the Afinion test as well. Our results demonstrate the reliability of CRP RDTs when compared to a reference standard. CRP RDTs without the need for a laboratory-based analyzer are promising tools for optimizing antibiotic use in low-resource settings.

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.

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.

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.

It takes more than a machine: A pilot feasibility study of point-of-care HIV-1 viral load testing at a lower-level health center in rural western Uganda.

Barriers continue to limit access to viral load (VL) monitoring across sub-Saharan Africa adversely impacting control of the HIV epidemic. The objective of this study was to determine whether the systems and processes required to realize the potential of rapid molecular technology are available at a prototypical lower-level (i.e., level III) health center in rural Uganda. In this open-label pilot study, participants underwent parallel VL testing at both the central laboratory (i.e., standard of care) and on-site using the GeneXpert HIV-1 assay. The primary outcome was the number of VL tests completed each clinic day. Secondary outcomes included the number of days from sample collection to receipt of result at clinic and the number of days from sample collection to patient receipt of the result. From August 2020 to July 2021, we enrolled a total of 242 participants. The median number of daily tests performed on the Xpert platform was 4, (IQR = 2-7). Time from sample collection to result was 51 days (IQR = 45-62) for samples sent to the central laboratory and 0 days (IQR = 0-0.25) for the Xpert assay conducted at the health center. However, few participants elected to receive results by one of the expedited options, which contributed to similar time-to-patient between testing approaches (89 versus 84 days, p = 0.07). Implementation of a rapid, near point-of-care VL assay at a lower-level health center in rural Uganda appears feasible, but interventions to promote rapid clinical response and influence patient preferences about result receipt require further study. Trial registration: ClinicalTrials.gov Identifier: NCT04517825, Registered 18 August 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04517825.

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.

"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.