A Qualitative Assessment of a Training and Communication Intervention on Antibiotic Prescription Practices Among Health Workers and Outpatients at Public Health Facilities in Uganda.

BACKGROUND: Antibiotic prescribing practices are 1 of the contributing causes of antimicrobial resistance (AMR). The study explored the key drivers and barriers to adherence to prescribing instructions among healthcare workers and outpatient attendees with the aim of developing a training and communication intervention to improve adherence to prescription. METHODS: Prior to randomized trials at 3 health centers in Uganda (Aduku, Kihihi, and Nagongera), a pre-intervention qualitative assessment was conducted to explore behavioral drivers for adherence to prescriptions and the communication of adherence messages. Based on the findings, a training and communication package was developed for healthcare workers and patients at Day 0 of the trial. During the trial's Day 7 patient follow-up, in-depth interviews were conducted to further investigate adherence behaviors. RESULTS: Five main themes were identified that acted as drivers or barriers to prescription adherence. Key drivers included: drug availability at health facility, health worker knowledge, and communication to patients. Barriers included: care-seeker use of treatment resorts and an inability by care-seeker to buy drugs. CONCLUSIONS: The T&C appeared to influence both health workers' and patients' behavior and improve adherence to prescription.The adapted T&C should be considered a toolkit to improve antibiotic use across health facilities accompanied with appropriate guidelines to mitigate AMR.

Impact of the Introduction of a Package of Diagnostic Tools, Diagnostic Algorithm, and Training and Communication on Outpatient Acute Fever Case Management at 3 Diverse Sites in Uganda: Results of a Randomized Controlled Trial.

BACKGROUND: Increasing trends of antimicrobial resistance are observed around the world, driven in part by excessive use of antimicrobials. Limited access to diagnostics, particularly in low- and middle-income countries, contributes to diagnostic uncertainty, which may promote unnecessary antibiotic use. We investigated whether introducing a package of diagnostic tools, clinical algorithm, and training-and-communication messages could safely reduce antibiotic prescribing compared with current standard-of-care for febrile patients presenting to outpatient clinics in Uganda. METHODS: This was an open-label, multicenter, 2-arm randomized controlled trial conducted at 3 public health facilities (Aduku, Nagongera, and Kihihi health center IVs) comparing the proportions of antibiotic prescriptions and clinical outcomes for febrile outpatients aged ≥1 year. The intervention arm included a package of point-of-care tests, a diagnostic and treatment algorithm, and training-and-communication messages. Standard-of-care was provided to patients in the control arm. RESULTS: A total of 2400 patients were enrolled, with 49.5% in the intervention arm. Overall, there was no significant difference in antibiotic prescriptions between the study arms (relative risk [RR]: 1.03; 95% CI: .96-1.11). In the intervention arm, patients with positive malaria test results (313/500 [62.6%] vs 170/473 [35.9%]) had a higher RR of being prescribed antibiotics (1.74; 1.52-2.00), while those with negative malaria results (348/688 [50.6%] vs 376/508 [74.0%]) had a lower RR (.68; .63-.75). There was no significant difference in clinical outcomes. CONCLUSIONS: This study found that a diagnostic intervention for management of febrile outpatients did not achieve the desired impact on antibiotic prescribing at 3 diverse and representative health facility sites in Uganda.

Malaria hospitalisation in East Africa: age, phenotype and transmission intensity.

BACKGROUND: Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. METHODS: Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2-10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. RESULTS: 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2-10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2-10 < 5%), five low-moderate transmission (PfPR2-10 5-9%), 20 moderate transmission (PfPR2-10 10-29%) and 12 high transmission (PfPR2-10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69-85%) and rare among children aged 10-14 years (0.7-5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. CONCLUSIONS: Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2-23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.

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.

Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: an ecological analysis.

BACKGROUND: Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programmes often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings. METHODS: This study leveraged data from 5 malaria reference centres (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models. RESULTS: A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38. CONCLUSIONS: In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.

Impact of COVID-19 on routine malaria indicators in rural Uganda: an interrupted time series analysis.

BACKGROUND: In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. Interrupted time series analysis (ITSA) was performed to assess whether major changes in outpatient attendance, malaria burden, and case management occurred after the onset of the COVID-19 epidemic in rural Uganda. METHODS: Individual level data from all outpatient visits collected from April 2017 to March 2021 at 17 facilities were analysed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of patients with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Poisson regression with generalized estimating equations and fractional regression was used to model count and proportion outcomes, respectively. Pre-COVID trends (April 2017-March 2020) were used to predict the'expected' trend in the absence of COVID-19 introduction. Effects of COVID-19 were estimated over two six-month COVID-19 time periods (April 2020-September 2020 and October 2020-March 2021) by dividing observed values by expected values, and expressed as ratios. RESULTS: A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences between observed and expected total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria after COVID-19 onset. However, in the second six months of the COVID-19 time period, there was a smaller mean proportion of patients tested with RDTs compared to expected (relative prevalence ratio (RPR) = 0.87, CI (0.78-0.97)) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI (0.90-0.99)). CONCLUSIONS: In the first year after the COVID-19 pandemic arrived in Uganda, there were no major effects on malaria disease burden and indicators of case management at these 17 rural health facilities, except for a modest decrease in the proportion of RDTs used for malaria diagnosis and the mean proportion of malaria cases prescribed AL in the second half of the COVID-19 pandemic year. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda.

BACKGROUND: In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019. METHODS: This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days, respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR. RESULTS: There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2 to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples. In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm had one copy of the plasmepsin-2 gene. CONCLUSIONS: DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended. Trial registration The trail was also registered with the ISRCTN registry with study Trial No. PACTR201811640750761.

Changing malaria fever test positivity among paediatric admissions to Tororo district hospital, Uganda 2012-2019.

BACKGROUND: The World Health Organization (WHO) promotes long-lasting insecticidal nets (LLIN) and indoor residual house-spraying (IRS) for malaria control in endemic countries. However, long-term impact data of vector control interventions is rarely measured empirically. METHODS: Surveillance data was collected from paediatric admissions at Tororo district hospital for the period January 2012 to December 2019, during which LLIN and IRS campaigns were implemented in the district. Malaria test positivity rate (TPR) among febrile admissions aged 1 month to 14 years was aggregated at baseline and three intervention periods (first LLIN campaign; Bendiocarb IRS; and Actellic IRS + second LLIN campaign) and compared using before-and-after analysis. Interrupted time-series analysis (ITSA) was used to determine the effect of IRS (Bendiocarb + Actellic) with the second LLIN campaign on monthly TPR compared to the combined baseline and first LLIN campaign periods controlling for age, rainfall, type of malaria test performed. The mean and median ages were examined between intervention intervals and as trend since January 2012. RESULTS: Among 28,049 febrile admissions between January 2012 and December 2019, TPR decreased from 60% at baseline (January 2012-October 2013) to 31% during the final period of Actellic IRS and LLIN (June 2016-December 2019). Comparing intervention intervals to the baseline TPR (60.3%), TPR was higher during the first LLIN period (67.3%, difference 7.0%; 95% CI 5.2%, 8.8%, p < 0.001), and lower during the Bendiocarb IRS (43.5%, difference - 16.8%; 95% CI - 18.7%, - 14.9%) and Actellic IRS (31.3%, difference - 29.0%; 95% CI - 30.3%, - 27.6%, p < 0.001) periods. ITSA confirmed a significant decrease in the level and trend of TPR during the IRS (Bendicarb + Actellic) with the second LLIN period compared to the pre-IRS (baseline + first LLIN) period. The age of children with positive test results significantly increased with time from a mean of 24 months at baseline to 39 months during the final IRS and LLIN period. CONCLUSION: IRS can have a dramatic impact on hospital paediatric admissions harbouring malaria infection. The sustained expansion of effective vector control leads to an increase in the age of malaria positive febrile paediatric admissions. However, despite large reductions, malaria test-positive admissions continued to be concentrated in children aged under five years. Despite high coverage of IRS and LLIN, these vector control measures failed to interrupt transmission in Tororo district. Using simple, cost-effective hospital surveillance, it is possible to monitor the public health impacts of IRS in combination with LLIN.

Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda.

BACKGROUND: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. METHODS: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. RESULTS: Overall, 896,550 patient visits were included in the study; 211,632 aged < 5 years, 171,166 aged 5-15 years and 513,752 > 15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in < 5 years decreased from 31 to 16% and 35 to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58 to 30% and 64 to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases > 15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. CONCLUSIONS: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.

The age-specific incidence of hospitalized paediatric malaria in Uganda.

BACKGROUND: Understanding the relationship between malaria infection risk and disease outcomes represents a fundamental component of morbidity and mortality burden estimations. Contemporary data on severe malaria risks among populations of different parasite exposures are scarce. Using surveillance data, we compared rates of paediatric malaria hospitalisation in areas of varying parasite exposure levels. METHODS: Surveillance data at five public hospitals; Jinja, Mubende, Kabale, Tororo, and Apac were assembled among admissions aged 1 month to 14 years between 2017 and 2018. The address of each admission was used to define a local catchment population where national census data was used to define person-year-exposure to risk. Within each catchment, historical infection prevalence was assembled from previously published data and current infection prevalence defined using 33 population-based school surveys among 3400 children. Poisson regression was used to compute the overall and site-specific incidences with 95% confidence intervals. RESULTS: Both current and historical Plasmodium falciparum prevalence varied across the five sites. Current prevalence ranged from < 1% in Kabale to 54% in Apac. Overall, the malaria admission incidence rate (IR) was 7.3 per 1000 person years among children aged 1 month to 14 years of age (95% CI: 7.0, 7.7). The lowest rate was described at Kabale (IR = 0.3; 95 CI: 0.1, 0.6) and highest at Apac (IR = 20.3; 95 CI: 18.9, 21.8). There was a correlation between IR across the five sites and the current parasite prevalence in school children, though findings were not statistically significant. Across all sites, except Kabale, malaria admissions were concentrated among young children, 74% were under 5 years. The median age of malaria admissions at Kabale hospital was 40 months (IQR 20, 72), and at Apac hospital was 36 months (IQR 18, 69). Overall, severe anaemia (7.6%) was the most common presentation and unconsciousness (1.8%) the least common. CONCLUSION: Malaria hospitalisation rates remain high in Uganda particularly among young children. The incidence of hospitalized malaria in different locations in Uganda appears to be influenced by past parasite exposure, immune acquisition, and current risks of infection. Interruption of transmission through vector control could influence age-specific severe malaria risk.

Resurgence of Malaria Following Discontinuation of Indoor Residual Spraying of Insecticide in an Area of Uganda With Previously High-Transmission Intensity.

BACKGROUND: Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the primary tools for malaria prevention in Africa. It is not known whether reductions in malaria can be sustained after IRS is discontinued. Our aim in this study was to assess changes in malaria morbidity in an area of Uganda with historically high transmission where IRS was discontinued after a 4-year period followed by universal LLIN distribution. METHODS: Individual-level malaria surveillance data were collected from 1 outpatient department and 1 inpatient setting in Apac District, Uganda, from July 2009 through November 2015. Rounds of IRS were delivered approximately every 6 months from February 2010 through May 2014 followed by universal LLIN distribution in June 2014. Temporal changes in the malaria test positivity rate (TPR) were estimated during and after IRS using interrupted time series analyses, controlling for age, rainfall, and autocorrelation. RESULTS: Data include 65 421 outpatient visits and 13 955 pediatric inpatient admissions for which a diagnostic test for malaria was performed. In outpatients aged <5 years, baseline TPR was 60%-80% followed by a rapid and then sustained decrease to 15%-30%. During the 4-18 months following discontinuation of IRS, absolute TPR values increased by an average of 3.29% per month (95% confidence interval, 2.01%-4.57%), returning to baseline levels. Similar trends were seen in outpatients aged ≥5 years and pediatric admissions. CONCLUSIONS: Discontinuation of IRS in an area with historically high transmission intensity was associated with a rapid increase in malaria morbidity to pre-IRS levels.

Assessing temporal associations between environmental factors and malaria morbidity at varying transmission settings in Uganda.

BACKGROUND: Environmental factors play a major role in transmission of malaria given their relationship to both the development and survival of the mosquito and parasite. The associations between environmental factors and malaria can be used to inform the development of early warning systems for increases in malaria burden. The objective of this study was to assess temporal relationships between rainfall, temperature and vegetation with malaria morbidity across three different transmission settings in Uganda. METHODS: Temporal relationships between environmental factors (weekly total rainfall, mean day time temperature and enhanced vegetation index series) and malaria morbidity (weekly malaria case count data and test positivity rate series) over the period January 2010-May 2013 in three sites located in varying malaria transmission settings in Uganda was explored using cross-correlation with pre-whitening. Sites included Kamwezi (low transmission), Kasambya (moderate transmission) and Nagongera (high transmission). RESULTS: Nagongera received the most rain (30.6 mm) and experienced, on average, the highest daytime temperatures (29.8 °C) per week. In the study period, weekly TPR and number of malaria cases were highest at Kasambya and lowest at Kamwezi. The largest cross-correlation coefficients between environmental factors and malaria morbidity for each site was 0.27 for Kamwezi (rainfall and cases), 0.21 for Kasambya (vegetation and TPR), and -0.27 for Nagongera (daytime temperature and TPR). Temporal associations between environmental factors (rainfall, temperature and vegetation) with malaria morbidity (number of malaria cases and TPR) varied by transmission setting. Longer time lags were observed at Kamwezi and Kasambya compared to Nagongera in the relationship between rainfall and number of malaria cases. Comparable time lags were observed at Kasambya and Nagongera in the relationship between temperature and malaria morbidity. Temporal analysis of vegetation with malaria morbidity revealed longer lags at Kasambya compared to those observed at the other two sites. CONCLUSIONS: This study showed that temporal associations between environmental factors with malaria morbidity vary by transmission setting in Uganda. This suggests the need to incorporate local transmission differences when developing malaria early warning systems that have environmental predictors in Uganda. This will result in development of more accurate early warning systems, which are a prerequisite for effective malaria control in such a setting.

Anti-malarial prescription practices among children admitted to six public hospitals in Uganda from 2011 to 2013.

BACKGROUND: In 2011, Uganda's Ministry of Health switched policy from presumptive treatment of malaria to recommending parasitological diagnosis prior to treatment, resulting in an expansion of diagnostic services at all levels of public health facilities including hospitals. Despite this change, anti-malarial drugs are often prescribed even when test results are negative. Presented is data on anti-malarial prescription practices among hospitalized children who underwent diagnostic testing after adoption of new treatment guidelines. METHODS: Anti-malarial prescription practices were collected as part of an inpatient malaria surveillance program generating high quality data among children admitted for any reason at government hospitals in six districts. A standardized medical record form was used to collect detailed patient information including presenting symptoms and signs, laboratory test results, admission and final diagnoses, treatments administered, and final outcome upon discharge. RESULTS: Between July 2011 and December 2013, 58,095 children were admitted to the six hospitals (hospital range 3294-20,426).A total of 56,282 (96.9 %) patients were tested for malaria, of which 26,072 (46.3 %) tested positive (hospital range 5.9-57.3 %). Among those testing positive, only 84 (0.3 %) were first tested after admission and 295 of 30,389 (1.0 %) patients who tested negative at admission later tested positive. Of 30,210 children with only negative test results, 11,977 (39.6 %) were prescribed an anti-malarial (hospital range 14.5-53.6 %). The proportion of children with a negative test result who were prescribed an anti-malarial fluctuated over time and did not show a significant trend at any site with the exception of one hospital where a steady decline was observed. Among those with only negative test results, children 6-12 months of age (aOR 3.78; p < 0.001) and those greater than 12 months of age (aOR 4.89; p < 0.001) were more likely to be prescribed an anti-malarial compared to children less than 6 months of age. Children with findings suggestive of severe malaria were also more likely to be prescribed an anti-malarial after a negative test result (aOR 1.98; p < 0.001). CONCLUSIONS: Despite high testing rates for malaria at all sites, prescription of anti-malarials to patients with negative test results remained high, with the exception of one site where a steady decline occurred.

Long-lasting insecticide-treated bed net ownership and use among children under five years of age following a targeted distribution in central Uganda.

BACKGROUND: Universal coverage of long-lasting insecticide-treated bed nets (LLINs) for prevention of malaria was adopted by the Uganda National Malaria Control Programme in 2007. The first mass distribution of LLINs was implemented in 2010. Initially, a campaign targeted to households with pregnant women and children aged

Anti-malarial prescription practices among outpatients with laboratory-confirmed malaria in the setting of a health facility-based sentinel site surveillance system in Uganda.

BACKGROUND: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. METHODS: Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients ≥ 4 months of age and ≥ 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. RESULTS: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). CONCLUSIONS: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa.

Evaluating tuberculosis case detection via real-time monitoring of tuberculosis diagnostic services.

RATIONALE: Tuberculosis case-detection rates are below internationally established targets in high-burden countries. Real-time monitoring and evaluation of adherence to widely endorsed standards of tuberculosis care might facilitate improved case finding. OBJECTIVES: To monitor and evaluate the quality of tuberculosis case-detection and management services in a low-income country with a high incidence of tuberculosis. METHODS: We prospectively evaluated tuberculosis diagnostic services at five primary health-care facilities in Uganda for 1 year, after introducing a real-time, electronic performance-monitoring system. We collected data on every clinical encounter, and measured quality using indicators derived from the International Standards of Tuberculosis Care. MEASUREMENTS AND MAIN RESULTS: In 2009, there were 62,909 adult primary-care visits. During the first quarter of 2009, clinicians referred only 21% of patients with cough greater than or equal to 2 weeks for sputum smear microscopy and only 71% of patients with a positive sputum examination for tuberculosis treatment. These proportions increased to 53% and 84%, respectively, in the fourth quarter of 2009. The cumulative probability that a smear-positive patient with cough greater than or equal to 2 weeks would be appropriately evaluated and referred for treatment rose from 11% to 34% (P = 0.005). The quarterly number of tuberculosis cases identified and prescribed treatment also increased four-fold, from 5 to 21. CONCLUSIONS: Poor adherence to internationally accepted standards of tuberculosis care improved after introduction of real-time performance monitoring and was associated with increased tuberculosis case detection. Real-time monitoring and evaluation can strengthen health systems in low-income countries and facilitate operational research on the effectiveness and sustainability of interventions to improve tuberculosis case detection.

Impact of COVID-19 on routine malaria indicators in Uganda: An interrupted time series analysis.

Background In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. We performed an interrupted time series analysis (ITSA) to assess whether major changes in healthcare seeking behavior, malaria burden, and case management occurred after the onset of the COVID-19 epidemic. Methods Individual level data from all outpatient visits occurring from April 2017 through March 2021 at 17 facilities were analyzed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of visits with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Pre-COVID trends measured over a three-year period were extrapolated into the post-COVID period (April 2020- March 2021) using Poisson regression with generalized estimating equations or fractional regression. Effects of COVID-19 were estimated over the 12-month post-COVID period by dividing observed values by the predicted values and expressed as ratios. Results A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences in the observed versus predicted total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria. However, in the second six months of the post-COVID period, there was a smaller mean proportion of patients tested with RDTs compared to predicted (Relative Prevalence Ratio (RPR) = 0.87, CI [0.78, 0.97]) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI [0.90, 0.99]. Conclusions There was evidence for a modest decrease in the proportion of RDTs used for malaria diagnosis and the proportion of patients prescribed AL in the second half of the post-COVID year, while other malaria indicators remained stable. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

The impact of stopping and starting indoor residual spraying on malaria burden in Uganda.

The scale-up of malaria control efforts has led to marked reductions in malaria burden over the past twenty years, but progress has slowed. Implementation of indoor residual spraying (IRS) of insecticide, a proven vector control intervention, has been limited and difficult to sustain partly because questions remain on its added impact over widely accepted interventions such as bed nets. Using data from 14 enhanced surveillance health facilities in Uganda, a country with high bed net coverage yet high malaria burden, we estimate the impact of starting and stopping IRS on changes in malaria incidence. We show that stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months, but reinstating IRS was associated with an over 5-fold decrease within 8 months. In areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4. IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.

Salmonella Bloodstream Infections in Hospitalized Children with Acute Febrile Illness-Uganda, 2016-2019.

Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.