Browsing by Author "Yeka, Adoke"
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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 Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda(PloS one, 2008) Yeka, Adoke; Dorsey, Grant; Kamya, Moses R.; Talisuna, Ambrose; Lugemwa, Myers; Rwakimari, John Bosco; Staedke, Sarah G.; Rosenthal, Philip J.; Mangen, Fred Wabwire; Bukirwa, HasifaUganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0–28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI −0.2–7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.Item Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial(PLoS clinical trials, 2007) Kamya, Moses R.; Yeka, Adoke; Bukirwa, Hasifa; Lugemwa, Myers; Rwakimari, John B.; Staedke, Sarah G.; Talisuna, Ambrose O.; Mangen, Fred WabwireTo compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Randomized single-blinded clinical trial.Apac, Uganda, an area of very high malaria transmission intensity.Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%–26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%–19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%–12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%–16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.Item Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda(PLoS clinical trials, 2006) Bukirwa, Hasifa; Yeka, Adoke; Kamya, Moses R.; Talisuna, Ambrose; Banek, Kristin; Bakyaita, Nathan; Rwakimari, John Bosco; Rosenthal, Philip J.; Mangen, Fred Wabwire; Dorsey, Grant; Staedke, Sarah G.To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda.Randomized single-blind controlled trial.Tororo, Uganda, an area of high-level malaria transmission.Children aged one to ten years with confirmed uncomplicated P. falciparum malaria.Amodiaquine + artesunate or artemether–lumefantrine.Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether–lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether–lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%–24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether–lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%–25.2%). Amodiaquine + artesunate and artemether–lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens.Amodiaquine + artesunate and artemether–lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether–lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.Item Bacteremia among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test(The American journal of tropical medicine and hygiene, 2015) Kibuuka, Afizi; Byakika-Kibwika, Pauline; Achan, Jane; Yeka, Adoke; Nalyazi, Joan N.; Mpimbaza, Arthur; Rosenthal, Philip J.; Kamya, Moses R.Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27–5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40–9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09–4.47) were independent predictors of bacteremia. At a hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results.Item Effects and factors associated with indoor residual spraying with Actellic 300 CS on malaria morbidity in Lira District, Northern Uganda(Malaria Journal, 2019) Tugume, Abdulaziz; Muneza, Fiston; Oporia, Frederick; Kiconco, Arthur; Kihembo, Christine; Nakanwagi Kisakye, Angela; Nsubuga, Peter; Sekimpi, Deogratias; Yeka, AdokeIndoor residual spraying (IRS) with Actellic 300 CS was conducted in Lira District between July and August 2016. No formal assessment has been conducted to estimate the effect of spraying with Actellic 300 CS on malaria morbidity in the Ugandan settings. This study assessed malaria morbidity trends before and after IRS with Actellic 300 CS in Lira District in Northern Uganda. Methods: The study employed a mixed methods design. Malaria morbidity records from four health facilities were reviewed, focusing on 6 months before and after the IRS intervention. The outcome of interest was malaria morbidity defined as; proportion of outpatient attendance due to total malaria, proportion of outpatient attendance due to confirmed malaria and proportion of malaria case numbers confirmed by microscopy or rapid diagnostic test. Since malaria morbidity was based on count data, an ordinary Poisson regression model was used to obtain percentage point change (pp) in monthly malaria cases before and after IRS. A household survey was also conducted in 159 households to determine IRS coverage and factors associated with spraying. A modified Poisson regression model was fitted to determine factors associated with household spray status. Results: The proportion of outpatient attendance due to malaria dropped from 18.7% before spraying to 15.1% after IRS. The proportion of outpatient attendance due to confirmed malaria also dropped from 5.1% before spraying to 4.0% after the IRS intervention. There was a decreasing trend in malaria test positivity rate (TPR) for every unit increase in month after spraying. The decreasing trend in TPR was more prominent 5–6 months after the IRS intervention (Adj. pp = − 0.60, P-value = 0.015; Adj. pp = − 1.19, P-value < 0.001). The IRS coverage was estimated at 89.3%. Households of respondents who were formally employed or owned any form of business were more likely to be unsprayed; (APR = 5.81, CI 2.72–12.68); (APR = 3.84, CI 1.20–12.31), respectivelyItem 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 Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda(Research Square, 2022) Echodu, Dorothy C.; Yeka, Adoke; Eganyu, Thomas; Odude, Wycliff; Bukenya, Fred; Nankabirwa, JoaniterDeclines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC). Methods: The 32-month prospective controlled community trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) in Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty: MDA+IRS, IRS, and SOC (insecticide treated bednets and case management). IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round. Results: Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months, post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z=9.6, p= 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5’s (95% CI: [10.5%, 16.8%], Z=4.02, p= 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z=4.7, p= 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%,83.0%, p¡.0001] in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p<.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of MDA+IRS, which may have understated the impact of MDA, and lack of MDA-only arm, considered to violate equipoise. Conclusions: Despite being assessed at long timepoints 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Future cohort studies of impact on incidence recommended.Item Implementing population‑based mass drug administration for malaria: experience from a high transmission setting in North Eastern Uganda(Malaria Journal, 2019) Mulebeke, Ronald; Wanzira, Humphrey; Bukenya, Fred; Eganyu, Thomas; Collborn, Kathryn; Elliot, Richard; Geertruyden, Jean‑Pierre Van; Echodu, Dorothy; Yeka, AdokeMass drug administration (MDA) is a suggested mean to accelerate efforts towards elimination and attainment of malaria-free status. There is limited evidence of suitable methods of implementing MDA programme to achieve a high coverage and compliance in low-income countries. The objective of this paper is to assess the impact of this MDA delivery strategy while using coverage measured as effective population in the community and population available. Methods: Population-based MDA was implemented as a part of a larger program in a high transmission setting in Uganda. Four rounds of interventions were implemented over a period of 2 years at an interval of 6 to 8 months. A housing and population census was conducted to establish the eligible population. A team of 19 personnel conducted MDA at established village meeting points as distribution sites at every village. The first dose of dihydroartemisinin– piperaquine (DHA-PQ) was administered via a fixed site distribution strategy by directly observed treatment on site, the remaining doses were taken at home and a door-to-door follow up strategy was implemented by community health workers to monitor adherence to the second and third doses. Results: Based on number of individuals who turned up at the distribution site, for each round of MDA, effective coverage was 80.1%, 81.2%, 80.0% and 80% for the 1st, 2nd, 3rd and 4th rounds respectively. However, coverage based on available population at the time of implementing MDA was 80.1%, 83.2%, 82.4% and 82.9% for rounds 1, 2, 3 and 4, respectively. Intense community mobilization using community structures and mass media facilitated community participation and adherence to MDA. Conclusion: A hybrid of fixed site distribution and door-to-door follow up strategy of MDA delivery achieved a high coverage and compliance and seemed feasible. This model can be considered in resource-limited settings.Item Measures of Malaria Burden after Long- Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study(PLoS medicine, 2016) Katureebe, Agaba; Zinszer, Kate; Arinaitwe, Emmanuel; Rek, John; Kakande, Elijah; Charland, Katia; Kigozi, Ruth; Kilama, Maxwell; Nankabirwa, Joaniter; Yeka, Adoke; Mawejje, Henry; Mpimbaza, Arthur; Katamba, Henry; Donnelly, Martin J.; Rosenthal, Philip J.; Drakeley, Chris; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Greenhouse, Bryan; Kamya, Moses R.; Dorsey, GrantLong-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites. Methods and Findings Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period, universal LLIN distribution was associated with no change in the incidence of malaria (0.39 episodes PPY pre-intervention versus 0.20 post-intervention; adjusted rate ratio [aRR] = 1.02, 95% CI 0.36±2.91, p = 0.97) and nonsignificant reductions in the TPR (26.5% pre-intervention versus 26.2% post-intervention; aRR = 0.70, 95% CI 0.46±1.06, p = 0.09) and HBR (1.07 mosquitoes per house-night preintervention versus 0.71 post-intervention; aRR = 0.41, 95% CI 0.14±1.18, p = 0.10). In Kihihi, over the 21-mo post-intervention period, universal LLIN distribution was associated with a reduction in the incidence of malaria (1.77 pre-intervention versus 1.89 post-intervention; aRR = 0.65, 95% CI 0.43±0.98, p = 0.04) but no significant change in the TPR (49.3% pre-intervention versus 45.9% post-intervention; aRR = 0.83, 95% 0.58±1.18, p = 0.30) or HBR (4.06 pre-intervention versus 2.44 post-intervention; aRR = 0.71, 95% CI 0.30±1.64, p = 0.40). In Nagongera, over the 12-mo post-intervention period, universal LLIN distribution was associated with a reduction in the TPR (45.3% pre-intervention versus 36.5% post-intervention; aRR = 0.82, 95% CI 0.76±0.88, p < 0.001) but no significant change in the incidence of malaria (2.82 pre-intervention versus 3.28 post-intervention; aRR = 1.10, 95% 0.76±1.59, p = 0.60) or HBR (41.04 pre-intervention versus 20.15 postintervention; aRR = 0.87, 95% CI 0.31±2.47, p = 0.80). The addition of three rounds of IRS at ~6-mo intervals in Nagongera was followed by clear decreases in all outcomes: incidence of malaria (3.25 pre-intervention versus 0.63 post-intervention; aRR = 0.13, 95% CI 0.07±0.27, p < 0.001), TPR (37.8% pre-intervention versus 15.0% post-intervention; aRR = 0.54, 95% CI 0.49±0.60, p < 0.001), and HBR (18.71 pre-intervention versus 3.23 postintervention; aRR = 0.29, 95% CI 0.17±0.50, p < 0.001). High levels of pyrethroid resistance were documented at all three study sites. Limitations of the study included the observational study design, the lack of contemporaneous control groups, and that the interventions were implemented under programmatic conditions. Conclusions Universal distribution of LLINs at three sites with varying transmission intensity was associated with modest declines in the burden of malaria for some indicators, but the addition of IRS at the highest transmission site was associated with a marked decline in the burden of malaria for all indicators. In highly endemic areas of Africa with widespread pyrethroid resistance, IRS using alternative insecticide formulations may be needed to achieve substantial gains in malaria control.Item Prevalence and risk factors of latent Tuberculosis among adolescents in rural Eastern Uganda(African Health Sciences, 2015) Mumpe-Mwanja, Daniel; Verver, Suzanne; Yeka, Adoke; Etwom, Alfred; Waako, James; Ssengooba, Willy; Matovu, Joseph K. B.; Wanyenze, Rhoda K.; Musoke, Phillipa; Mayanja-Kizza, HarrietLatent Tuberculosis treatment is a key tuberculosis control intervention. Adolescents are a high risk group that is not routinely treated in low income countries. Knowledge of latent Tuberculosis (TB) burden among adolescents may influence policy. Objectives: We determined the prevalence and risk factors of latent TB infection among adolescents in rural Uganda. Methods: We analyzed baseline data from a study that assessed the prevalence and incidence of Tuberculosis disease among adolescents. We extracted socio-demographics, medical assessment information, and tuberculin skin test results and estimated prevalence ratios (PR) of latent TB infection risk factors by binomial regression. Results: The prevalence of latent TB was 16.1%, 95% CI (15.1 – 17.2). Significant risk factors were: a BCG scar, APR 1.29 (95% CI 1.12 – 1.48); male gender, APR 1.37 (95% CI 1.21 – 1.56); age 17 -18 years, APR 1.46 (95% CI 1.24 – 1.71) and 15-16 years, APR 1.25 (95% CI 1.07 – 1.46) compared to 12-14 years; being out of school, APR 1.31 (95% CI 1.05 – 1.62); and a known history of household TB contact in last 2 years, APR 1.91 (95% CI 1.55 – 2.35) Conclusion: Targeted routine latent TB treatment among adolescents out of school may be crucial for TB disease control in low income countries.Item Quinine, an old anti-malarial drug in a Modern world: role in the treatment of Malaria(Malaria journal, 2011) Achan, Jane; Talisuna, Ambrose O.; Erhart, Annette; Yeka, Adoke; Tibenderana, James K.; Baliraine, Frederick N.; Rosenthal, Philip J.; D’Alessandro, Umberto;Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented.However, itscontinued use is challenged by its poor tolerability, poor compliance with complex dosing regimens,and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine,considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In lightof recent research findings intravenous artesunate should be thefirst-line drug for severe malaria, with quinine asan alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored,but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the managementof malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives becomeavailable. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option thanquinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapidwithdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions toACT stock-outs, maintain quinine in case ofACT stock-outs, and evaluate strategies for improving quininetreatment outcomes by combining it with antibiotics. In HIV andTB infected populations, concerns about potentialinteractions between quinine and antiretroviral and antituberculosis drugs exist, andthese will need furtherresearch and pharmacovigilance.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 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.Item Systematic review of the status of pfhrp2 and pfhrp3 gene deletion, approaches and methods used for its estimation and reporting in Plasmodium falciparum populations in Africa: review of published studies 2010–2019(Malaria journal, 2019) Agaba, Bosco B.; Yeka, Adoke; Nsobya, Sam; Arinaitwe, Emmanuel; Nankabirwa, Joaniter; Opigo, Jimmy; Mbaka, Paul; Seung Lim, Chae; Kalyango, Joan N.; Karamagi, Charles; Kamya, Moses R.Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa, where Plasmodium falciparum is predominant. However, their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp3). Use of standard and recommended methods is key for accurate investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion. Methods: A systematic review was conducted to assess the status, methods and approaches that have been used for investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion in Africa. An online search was done using PubMed and MEDLINE Google Scholar for all articles published in English on pfhrp2/3 gene deletion in Africa. Relevant articles that met the inclusion criteria were summarized and assessed based on the protocol recommended by the World Health Organization for confirmation and reporting of pfhrp2/3 gene deletion. Results: The search identified a total of 18 articles out of which 14 (77.7%) fulfilled the criteria for inclusion and were retained for review. The articles were distributed across 12 countries where the pfhrp2 and pfhrp3 gene deletion studies were conducted and reported. The level of pfhrp2/3 gene deletion across selected studies in Africa ranged from the highest 62% to the lowest 0.4%. There was wide variation in methods and approaches including study designs, size and sampling and whether both pfhrp2 and pfhrp3 double deletions or pfhrp2 single deletion were investigated, with a wide variation in laboratory methods. Conclusion: Based on the review, there is evidence of the presence of pfhrp2/3 gene-deleted P. falciparum parasites in Africa. The approaches and methods used for investigation, confirmation and reporting of pfhrp2/3 deleted parasites have varied between studies and across countries. Countries that are considering plans to investigate, confirm and report pfhrp2/3 deletion should use recommended standard and harmonized methods to prevent unnecessary recommendations for costly switch of RDTs in Africa.