Browsing by Author "Sserwanga, Asadu"
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Item Admission Risk Score to Predict Inpatient Pediatric Mortality at Four Public Hospitals in Uganda(PLoS ONE, 2015) Mpimbaza, Arthur; Sears, David; Sserwanga, Asadu; Kigozi, Ruth; Rubahika, Denis; Nadler, Adam; Yeka, Adoke; Dorsey, GrantMortality rates among hospitalized children in many government hospitals in sub-Saharan Africa are high. Pediatric emergency services in these hospitals are often sub-optimal. Timely recognition of critically ill children on arrival is key to improving service delivery. We present a simple risk score to predict inpatient mortality among hospitalized children. Between April 2010 and June 2011, the Uganda Malaria Surveillance Project (UMSP), in collaboration with the National Malaria Control Program (NMCP), set up an enhanced sentinel site malaria surveillance program for children hospitalized at four public hospitals in different districts: Tororo, Apac, Jinja and Mubende. Clinical data collected through March 2013, representing 50249 admissions were used to develop a mortality risk score (derivation data set). One year of data collected subsequently from the same hospitals, representing 20406 admissions, were used to prospectively validate the performance of the risk score (validation data set). Using a backward selection approach, 13 out of 25 clinical parameters recognizable on initial presentation, were selected for inclusion in a final logistic regression prediction model. The presence of individual parameters was awarded a score of either 1 or 2 based on regression coefficients. For each individual patient, a composite risk score was generated. The risk score was further categorized into three categories; low, medium, and high. Patient characteristics were comparable in both data sets. Measures of performance for the risk score included the receiver operating characteristics curves and the area under the curve (AUC), both demonstrating good and comparable ability to predict deathusing both the derivation (AUC =0.76) and validation dataset (AUC =0.74). Using the derivation and validation datasets, the mortality rates in each risk category were as follows: low risk (0.8% vs. 0.7%), moderate risk (3.5% vs. 3.2%), and high risk (16.5% vs. 12.6%), respectively. Our analysis resulted in development of a risk score that ably predicted mortality risk among hospitalized children. While validation studies are needed, this approach could be used to improve existing triage systems.Item Anti-malarial prescription practices among outpatients with laboratory-confirmed malaria in the setting of a health facility-based sentinel site surveillance system in Uganda(Malaria journal, 2013) Sears, David; Kigozi, Ruth; Mpimbaza, Arthur; Kakeeto, Stella; Sserwanga, Asadu; Staedke, Sarah G.; Chang, Michelle; Kapella, Bryan K.; Rubahika, Denis; Kamya, Moses R.; Dorsey, GrantMost 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.Item Anti‑malarial prescription practices among children admitted to six public hospitals in Uganda from 2011 to 2013(Malaria journal, 2015) Sserwanga, Asadu; Sears, David; Kapella, Bryan K.; Kigozi, Ruth; Rubahika, Denis; Staedke, Sarah G.; Kamya, Moses; Yoon, Steven S.; Chang, Michelle A.; Dorsey, Grant; Mpimbaza, ArthurIn 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.Item Assessing temporal associations between environmental factors and malaria morbidity at varying transmission settings in Uganda(Malaria journal, 2016) Kigozi, Ruth; Zinszer, Kate; Mpimbaza, Arthur; Sserwanga, Asadu; Kigozi, Simon P.; Kamya, MosesEnvironmental 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.Item Changing malaria fever test positivity among paediatric admissions to Tororo district hospital, Uganda 2012–2019(Malaria journal, 2020) Mpimbaza, Arthur; Sserwanga, Asadu; Rutazaana, Damian; Kapisi, James; Walemwa, Richard; Suiyanka, Laurissa; Kyalo, David; Kamya, Moses; Opigo, Jimmy; Snow, Robert W.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.Item A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda(Health security, 2018) Lamorde, Mohammed; Mpimbaza, Arthur; Walwema, Richard; Kamya, Moses; Kajumbula, Henry; Sserwanga, Asadu; Namuganga, Jane FrancesGlobal health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda. Fever may be the initial or sole symptom of many infectious diseases, including some with outbreak potential.1,2 Although clinical practice in many malaria-endemic areas has been to presumptively treat febrile patients for malaria, improved access to malaria diagnostics in recent years has revealed that a substantial proportion of acutely ill, febrile patients in sub-Saharan Africa do not have malaria.3-5 Yet, many countries lack resources and capacity for accurate diagnosis of most infectious conditions. Rapid response to diverse and emerging public health threats is severely challenged by lack of appropriate laboratory capacity and timely surveillance networks.6 These gaps foster antimicrobial and antimalarial resistance, limit evidence-based care and policy to improve population health, and hinder the ability to detect outbreaks early. Uganda, an inland East African country with a rapidly growing population estimated at 43 million people in 2017, has made progress in recent decades to improve life expectancy, reduce poverty and food insecurity, and expand access to immunizations and clean water.7 Yet, as with many African countries, Uganda faces diverse health challenges in a weak health infrastructure that limits the rapid detection and confirmation of infections with epidemic potential. In the past 2 decades, Uganda has experienced outbreaks of emerging and reemerging infectious diseases including Ebola, Marburg, Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, hepatitis E, cholera, typhoid fever, plague, and anthrax.8-16 Effective laboratory capacity and disease surveillance are critical to global health security and the basis for the 2005 International Health Regulations (IHR) signed by all World Health Organization (WHO) member states. IHR compliance has proven challenging for many low-income countries, including Uganda.17,18 The Global Health Security Agenda (GHSA), a multisectoral and multilateral partnership intended to support countries toward IHR compliance, launched officially in 2014 (www.ghsagenda.org). The government of Uganda and the US Centers for Disease Control and Prevention (CDC) jointly implemented a demonstration project a year earlier, in 2013. The pilot project improved specimen referral networks and information systems associated with outbreak response and created an emergency operations center; these activities set the stage for multiple GHSA activities in the country.19 Through GHSA-initiated partnerships, we introduced a cross-cutting surveillance approach to advance ability to detect unusual health events in Uganda. As conceived, this effort would provide comprehensive patient data and facilitate electronic systems infrastructure that could ultimately improve early detection of novel infections or outbreaks, define conditions causing human illness to inform appropriate and targeted laboratory capacity building efforts, and generate data for an antimicrobial resistance surveillance and intervention program in its infancy.Item 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(Malaria Journal, 2022) Ebong, Chris; Sserwanga, Asadu; Frances Namuganga, Jane; Kapisi, James; Mpimbaza, Arthur; Gonahasa, Samuel; Asua, Victor; Gudoi, Sam; Kigozi, Ruth; Tibenderana, James; Bwanika, John Bosco; Bosco, Agaba; Rubahika, Denis; Kyabayinze, Daniel; Opigo, Jimmy; Rutazana, Damian; Sebikaari, Gloria; Belay, Kassahun; Niang, Mame; Halsey, Eric S.; Moriarty, Leah F.; Lucchi, Naomi W.; Svigel Souza, Samaly S.; Nsobya, Sam L.; Kamya, Moses R.; Yeka, AdokeIn 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 trial was also registered with the Pan African Clinical Trial Registry (https:// pactr. samrc. ac. za/) with study Trial No. PACTR201811640750761.Item Evaluating Tuberculosis Case Detection via Real-Time Monitoring of Tuberculosis Diagnostic Services(American journal of respiratory and critical care medicine, 2011) Davis, J. Lucian; Katamba, Achilles; Vasquez, Josh; Crawford, Erin; Sserwanga, Asadu; Kakeeto, Stella; Kizito, Fred; Dorsey, Grant; Boon, Saskia den; Vittinghoff, Eric; Huang, Laurence; Adatu, Francis; Kamya, Moses R.; Hopewell, Philip C.; Cattamanch, AdithyaTuberculosis 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 casedetection 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 collecteddataonevery clinicalencounter,andmeasuredquality using indicatorsderivedfromthe International StandardsofTuberculosisCare. Measurements and Main Results: In 2009, there were 62,909 adult primary-care visits.During the first quarter of 2009, clinicians referred only21%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 5 0.005). The quarterly number of tuberculosis cases identified and prescribed treatment also increased four-fold, from 5 to 21. Conclusions: Pooradherence tointernationally acceptedstandards 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.Item The impact of stopping and starting indoor residual spraying on malaria burden in Uganda(Nature communications, 2021) Namuganga, Jane F.; Epstein, Adrienne; Nankabirwa, Joaniter I.; Mpimbaza, Arthur; Kiggundu, Moses; Sserwanga, Asadu; Kapisi, James; Arinaitwe, Emmanuel; Gonahasa, Samuel; Opigo, Jimmy; Ebong, Chris; Staedke, Sarah G.; Shililu, Josephat; Okia, Michael; Rutazaana, Damian; Maiteki-Sebuguzi, Catherine; Belay, Kassahun; Kamya, Moses R.; Dorsey, Grant; Rodriguez-Barraquer, IsabelThe 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.Item Malaria Burden through Routine Reporting: Relationship between Incidence and Test Positivity Rates(The American journal of tropical medicine and hygiene, 2019) Kigozi, Simon P.; Kigozi, Ruth N.; Sserwanga, Asadu; Nankabirwa, Joaniter I.; Staedke, Sarah G.; Kamya, Moses R.; Pullan, Rachel L.Test positivity rate (TPR)—confirmed cases per 100 suspected cases tested, and test-confirmed malaria case rate (IR)—cases per 1,000 population, are common indicators used routinely for malaria surveillance. However, few studies have explored relationships between these indicators over time and space. We studied the relationship between these indicators in children aged < 11 years presenting with suspected malaria to the outpatient departments of level IV health centers in Nagongera, Kihihi, and Walukuba in Uganda from October 2011 to June 2016. We evaluated trends in indicators over time and space, and explored associations using multivariable regression models. Overall, 65,710 participants visited the three clinics. Pairwise comparisons of TPR and IR by month showed similar trends, particularly for TPRs < 50% and during low-transmission seasons, but by village, the relationship was complex. Village mean annual TPRs remained constant, whereas IRs drastically declined with increasing distance from the health center. Villages that were furthest away from the health centers (fourth quartile for distance) had significantly lower IRs than nearby villages (first quartile), with an incidence rate ratio of 0.40 in Nagongera (95% CI: 0.23–0.63;P= 0.001), 0.55 in Kihihi (0.40–0.75;P< 0.001), and 0.25 in Walukuba (0.12–0.51; P < 0.001). Regression analysis results emphasized a nonlinear (cubic) relationship between TPR and IR, after accounting for month, village, season, and demographic factors. Results show that the two indicators are highly relevant for monitoring malaria burden. However, interpretation differs with TPR primarily indicating demand for malaria treatment resources and IR indicating malaria risk among health facility catchment populations.Item Malaria hospitalisation in East Africa: age, phenotype and transmission intensity(BMC medicine, 2022) Kamau, Alice; Paton, Robert S.; Akech, Samuel; Mpimbaza, Arthur; Khazenzi, Cynthia; Ogero, Morris; Mumo, Eda; Alegana, Victor A.; Agweyu, Ambrose; Mturi, Neema; Mohammed, Shebe; Bigogo, Godfrey; Audi, Allan; Kapisi, James; Sserwanga, Asadu; Namuganga, Jane F.; Kariuki, Simon; Otieno, Nancy A.; Nyawanda, Bryan O.; Olotu, Ally; Salim, Nahya; Athuman, Thabit; Abdulla, Salim; Mohamed, Amina F.; Mtove, George; Reyburn, Hugh; Gupta, Sunetra; Lourenço, José; Bejon, Philip; Snow, Robert W.Understanding the age patterns of disease is necessary to target interventions to maximise costeffective 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.Item Quality of Inpatient Pediatric Case Management for Four Leading Causes of Child Mortality at Six Government-Run Ugandan Hospitals(PLoS One, 2015) Sears, David; Mpimbaza, Arthur; Kigozi, Ruth; Sserwanga, Asadu; Chang, Michelle A.; Kapella, Bryan K.; Yoon, Steven; Kamya, Moses R.; Dorsey, Grant; Ruel, TheodoreA better understanding of case management practices is required to improve inpatient pediatric care in resource-limited settings. Here we utilize data from a unique health facilitybased surveillance system at six Ugandan hospitals to evaluate the quality of pediatric case management and the factors associated with appropriate care. Methods All children up to the age of 14 years admitted to six district or regional hospitals over 15 months were included in the study. Four case management categories were defined for analysis: suspected malaria, selected illnesses requiring antibiotics, suspected anemia, and diarrhea. The quality of case management for each category was determined by comparing recorded treatments with evidence-based best practices as defined in national guidelines. Associations between variables of interest and the receipt of appropriate case management were estimated using multivariable logistic regression. Results A total of 30,351 admissions were screened for inclusion in the analysis. Ninety-two percent of children met criteria for suspected malaria and 81% received appropriate case management. Thirty-two percent of children had selected illnesses requiring antibiotics and 89% received appropriate antibiotics. Thirty percent of children met criteria for suspected anemia and 38% received appropriate case management. Twelve percent of children had diarrhea and 18% received appropriate case management. Multivariable logistic regression revealed large differences in the quality of care between health facilities. There was also a strong association between a positive malaria diagnostic test result and the odds of receiving appropriate case management for comorbid non-malarial illnesses - children with a positive malaria test were more likely to receive appropriate care for anemia and less likely for illnesses requiring antibiotics and diarrhea. Conclusions Appropriate management of suspected anemia and diarrhea occurred infrequently. Pediatric quality improvement initiatives should target deficiencies in care unique to each health facility, and interventions should focus on the simultaneous management of multiple diagnoses.Item Rapid shifts in the age‑specific burden of malaria following successful control interventions in four regions of Uganda(Malaria journal, 2020) Kigozi, Simon P.; Kigozi, Ruth N.; Epstein, Adrienne; Mpimbaza, Arthur; Sserwanga, Asadu; Yeka, Adoke; Nankabirwa, Joaniter I.; Halliday, Katherine; Pullan, Rachel L.; Rutazaana, Damian; Sebuguzi, Catherine M.; Opigo, Jimmy; Kamya, Moses R.; Staedke, Sarah G.; Dorsey, Grant; Greenhouse, Bryan; Rodriguez‑Barraquer, IsabelMalaria 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.Item Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: an ecological analysis(Malaria journal, 2021) Okiring, Jaffer; Epstein, Adrienne; Namuganga, Jane F.; Kamya, Victor; Sserwanga, Asadu; Kapisi, James; Ebong, Chris; Kigozi, Simon P.; Mpimbaza, Arthur; Wanzira, Humphrey; Briggs, Jessica; Kamya, Moses R.; Nankabirwa, Joaniter I.; Dorsey, GrantMalaria 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.Item Resurgence of malaria after discontinuation of indoor residual spraying of insecticide in a previously high transmission intensity area of Uganda(The Lancet Global Health, 2016) Raouf, Saned; Mpimbaza, Arthur; Kigozi, Ruth; Sserwanga, Asadu; Rubahika, Denis; Katamba, Henry; Lindsay, Steve W.; Kapella, Bryan K.; Belay, Kassahun A.; Kamya, Moses R.; Staedke, Sarah G.; Dorsey, GrantIndoor 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.Item Salmonella Bacteremia in Hospitalized Ugandan Children with Febrile Illness(AMER SOC TROP MED & HYGIENE, 2017) Appiah, Grace D.; Mpimbaza, Arthur; Kigozi, Ruth; Sserwanga, Asadu; Kapisi, James; Kamya, Moses R.; Nanteza, Jane Frances; Kajumbula, Henry M.Salmonella is a known cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however its contribution to bacterial blood stream infections is poorly defined due to limited diagnostic capacity. To address this gap and to inform accurate patient diagnosis and treatment, improved AFI surveillance and expanded diagnostic testing is needed.Item Salmonella Bloodstream Infections in Hospitalized Children with Acute Febrile Illness—Uganda, 2016–2019(The American Journal of Tropical Medicine and Hygiene, 2021) Appiah, Grace D.; Mpimbaza, Arthur; Lamorde, Mohammed; Freeman, Molly; Kajumbula, Henry; Salah, Zainab; Kugeler, Kiersten; Mikoleit, Matthew; Bumpus White, Porscha; Kapisi, James; Borchert, Jeff; Sserwanga, Asadu; Van Dyne, Susan; Mead, Paul; Kim, Sunkyung; Lauer, Ana C.; Winstead, Alison; Manabe, Yukari C.; Flick, Robert J.; Mintz, EricInvasive 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.Item Short Report: Comparison of Routine Health Management Information System Versus Enhanced Inpatient Malaria Surveillance for Estimating the Burden of Malaria Among Children Admitted to Four Hospitals in Uganda(The American journal of tropical medicine and hygiene, 2015) Mpimbaza, Arthur; Miles, Melody; Sserwanga, Asadu; Kigozi, Ruth; Wanzira, Humphrey; Rubahika, Denis; Nasr, Sussann; Kapella, Bryan K.; Yoon, Steven S.; Chang, Michelle; Yeka, Adoke; Staedke, Sarah G.; Kamya, Moses R.; Dorsey, GrantThe primary source of malaria surveillance data in Uganda is the Health Management Information System (HMIS), which does not require laboratory confirmation of reported malaria cases. To improve data quality, an enhanced inpatient malaria surveillance system (EIMSS) was implemented with emphasis on malaria testing of all children admitted in select hospitals. Data were compared between the HMIS and the EIMSS at four hospitals over a period of 12 months. After the implementation of the EIMSS, over 96% of admitted children under 5 years of age underwent laboratory testing for malaria. The HMIS significantly overreported the proportion of children under 5 years of age admitted with malaria (average absolute difference = 19%, range = 8–27% across the four hospitals) compared with the EIMSS. To improve the quality of the HMIS data for malaria surveillance, the National Malaria Control Program should, in addition to increasing malaria testing rates, focus on linking laboratory test results to reported malaria cases.