Browsing by Author "Dorsey, Grant"
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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 Antiretroviral Agents and Prevention of Malaria in HIV-Infected Ugandan Children(The New England Journal of Medicine, 2012) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Ruel, Theodore; Clark, Tamara D.; Nsanzabana, Christian; Charlebois, Edwin; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J.; Havlir, Diane; Kamya, Moses RHuman immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV infected children would be lower among children receiving lopinavir–ritonavir– based antiretroviral therapy (ART) than among those receiving nonnucleosidereverse transcriptase inhibitor (NNRTI)–based ART.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 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 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 Artemisinin-Based Combination Therapies Are Efficacious and Safe for Treatment of Uncomplicated Malaria in HIV-Infected Ugandan Children(Clinical infectious diseases, 2014) Kakuru, Abel; Achan, Jane; Muhindo, Mary K.; Ikilezi, Gloria; Arinaitwe, Emmanuel; Mwangwa, Florence; Ruel, Theodore; Clark, Tamara D.; Charlebois, Edwin; Kamya, Moses R.; Tappero, Jordan W.; Dorsey, GrantArtemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)–infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor–based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes. There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated. Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.Item Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda(PloS one, 2014) Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochomi, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, AdithyaImproving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for children with cough $2 weeks’ duration presenting to community health centers in Uganda. Methods: Cross-sectional analysis of children (,15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results: From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough $ 2 weeks’ duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion: The quality of TB evaluation was poor for children with cough $2 weeks’ duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.Item Assessment of the accuracy of malaria microscopy in private health facilities in Entebbe Municipality, Uganda: a cross‑sectional study(Malaria Journal, 2021) Mutabazi, Tobius; Sendaula, Emmanuel; Kakeeto, Alex; Okimat, Paul; Orishaba, Philip; Katongole, Simon Peter; Mpimbaza, Arthur; Byakika‑Kibwika, Pauline; Karamagi, Charles; Nakayaga Kalyango, Joan; Kamya, Moses R.; Dorsey, Grant; Nankabirwa, Joaniter I.Although microscopy remains the gold standard for malaria diagnosis, little is known about its accuracy in the private health facilities in Uganda. This study evaluated the accuracy of malaria microscopy, and factors associated with inaccurate smear results at private health facilities in Entebbe Municipality, Uganda. Methods: Between April and May 2018, all patients referred for a malaria smear in 16 private health facilities in Entebbe municipality were screened, and 321 patients were enrolled. A questionnaire was administered to collect demographic and clinical information, facility-based smear results were recorded from the participant’s consultation notes, and a research slide was obtained for expert microscopy during exit interview. A health facility assessment was conducted, and information on experience in performing malaria microscopy was collected from all facility personnel reading smears and the data was linked to the participant’s clinic visit.Item Associations between environmental covariates and malaria incidence in high transmission settings of Uganda: A distributed non-linear lagged ecological analysis(Research Square, 2021) Okiring, Jaffer; Routledge, Isobel; Esptein, Adrienne; Namuganga, Jane F.; Kamya, Emmanuel V.; Odei Obeng-Amoako, Gloria; Maiteki-Sebuguzi, Catherine; Rutazaana, Damian; Kalyango, Joan N.; Kamya, Moses R.; Dorsey, Grant; Wesonga, Ronald; Kiwuwa, Steven M.; Nankabirwa, Joaniter I.Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in the incidence of symptomatic malaria. The study aim was to investigate the associations between environmental covariates and malaria incidence in high transmission settings of Uganda. Methods This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period (January 2019 - December 2020). Estimates of monthly malaria incidence (MI) were derived from MRCs’ catchment areas. Environmental data including monthy average measures of temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed non-linear lagged model was used to investigate the quantitative relationship between environmental covariates and malaria incidence. Results Overall, the median (range) monthly temperature was 30oC (26-47), rainfall 133.0 mm (3.0-247), NDVI 0.66 (0.24-0.80) and MI was 790 per 1000 person-years (73-3973). A non-linear relationship between environmental covariates and malaria incidence was observed. An average monthly temperature of 35oC was associated with significant increases in malaria incidence compared to the median observed temperature (30oC) at month lag 2 (IRR: 2.00, 95% CI: 1.42-2.83) and the cumulative increases in MI significantly at month lags 1-4, with the highest cumulative IRR of 8.16 (95% CI: 3.41-20.26) at lag month 4. An average monthly rainfall of 200mm was associated with significant increases in malaria incidence compared to the median observed rainfall (133mm) at lag month 0 (IRR: 1.24, 95% CI: 1.01-1.52) and the cumulative IRR increases of malaria at month lags 1-4, with the highest cumulative IRR of 1.99(95% CI: 1.22-2.27) at lag month 4. An average NVDI of 0.72 was associated with significant cumulative increases in IRR of malaria as compared to the median observed NDVI (0.66) at month lag 2-4, with the highest cumulative IRR of 1.57(95% CI: 1.09-2.25) at lag month 4. The rate of increase in cumulative IRR of malaria was highest within lag months 1-2 as compared to lag months 3-4 for all the environmental covariates. Conclusions In high-malaria transmission settings, high values of environmental covariates were associated with cumulative increases in the incidence of malaria, with peak associations occurring after variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.Item Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study(Malaria Journal, 2020) Kakande, Elijah; Greenhouse, Bryan; Bajunirwe, Francis; Drakeley, Chris; Nankabirwa, Joaniter I.; Walakira, Andrew; Nsobya, Samuel L.; Katureebe, Agaba; Rek, John; Arinaitwe, Emmanuel; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant; Rodriguez‑Barraquer, IsabelMultiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A—(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes.Item The effect of HIV on malaria in the context of the current standard of care for HIV-infected populations in Africa(Future virology, 2012) Kamya, Moses R.; Byakika-Kibwika, Pauline; Gasasira, Anne F.; Havlir, Diane; Rosenthal, Philip J.; Dorsey, Grant; Achan, JaneHIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim– sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistanceconferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in highmalaria- transmission areas. Artemether–lumefantrine and dihydroartemisinin– piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and posttreatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients.Item Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial(Bmj, 2009) Achan, Jane; Tibenderana, James K.; Kyabayinze, Daniel; Wabwire Mangen, Fred; Kamya, Moses R.; Dorsey, Grant; D’Alessandro, Umberto; Rosenthal, Philip J.; Talisuna, Ambrose O.Objective To compare the effectiveness of oral quininewith that of artemether-lumefantrine in treatinguncomplicated malaria in children.Design Randomised, open label effectiveness study.Setting Outpatient clinic of Uganda’s national referral hospital in Kampala.Participants 175 children aged 6 to 59 months withuncomplicated malaria.Interventions Participants were randomised to receiveoral quinine or artemether-lumefantrine administered bycare givers at home.Main outcome measures Primary outcomes wereparasitological cure rates after 28 days of follow-upunadjusted and adjusted by genotyping to distinguishrecrudescence from new infections. Secondary outcomeswere adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles.Results Using survival analysis the cure rate unadjustedby genotyping was 96% for the artemether-lumefantrinegroup compared with 64% for the quinine group (hazardratio10.7, 95% confidence interval 3.3 to 35.5, P=0.001).In the quinine group 69% (18/26) of parasitologicalfailures were due to recrudescence compared with none inthe artemether-lumefantrine group. The mean adherenceto artemether-lumefantrine was 94.5% compared with85.4% to quinine (P=0.0008). Having adherence levels of80% or more was associated with a decreased risk oftreatment failure (0.44, 0.19 to 1.02, P=0.06). Adverseevents did not differ between the two groups.ConclusionsThe effectiveness of a seven day course ofquinine for the treatment of uncomplicated malariainUgandanchildren was significantly lower than that ofartemether-lumefantrine. These findings question theadvisability of the recommendation for quinine therapyfor uncomplicated malaria in Africa.Trial registration ClinicalTrials.gov NCT00540202.Item Efficacy and Safety of Three Regimens for the Prevention of Malaria in Young HIV-Exposed Ugandan Children: A Randomized Controlled Trial(AIDS, 2014) Kamya, Moses R.; Kapisi, James; Bigira, Victor; Tamara, D. Clark; Kinara, Stephen; Mwangwa, Florence; Muhindo, Mary K.; Kakuru, Abel; Aweeka, Francesca T.; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey, GrantTrimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children. Tororo, Uganda, a rural area with intense, year-round, malaria transmission. 200 infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age). No chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily TS, or monthly dihydroartemisinin-piperaquine (DP) given from randomization to 24 months of age. The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrheal illness, or respiratory tract infection; prevalence of anemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped. During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% (95% CI, 53-80%, p<0.001) for DP, 49% (95% CI, 23-66%, p=0.001) for TS, and 9% for SP (95% CI, −35 to 38%, p=0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the DP arm. Monthly chemoprevention with DP was safe and associated with a significant reduction in malaria in young HIV-exposed children.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 Factors Associated with Malaria Parasitaemia, Malnutrition, and Anaemia among HIV-Exposed and Unexposed Ugandan Infants: A Cross-Sectional Survey(Malaria journal, 2012) Osterbauer, Beth; Kapisi, James; Bigira, Victor; Mwangwa, Florence; Kinara, Stephen; Kamya, Moses R.; Dorsey, GrantMalaria, malnutrition and anaemia are major causes of morbidity and mortality in African children. The interplay between these conditions is complex and limited data exist on factors associated with these conditions among infants born to HIV-uninfected and infected women. Two hundred HIV-exposed (HIV-uninfected infants born to HIV-infected mothers) and 400 HIV-unexposed infants were recruited from an area of high malaria transmission in rural Uganda. A cross-sectional survey was performed at enrolment to measure the prevalence of malaria parasitaemia, measures of malnutrition (z-scores <2 standard deviations below mean) and anaemia (haemoglobin <8 gm/dL). Multivariate logistic regression was used to measure associations between these conditions and risk factors of interest including household demographics, malaria prevention practices, breastfeeding practices, household structure and wealth index. The prevalence of malaria parasitaemia was 20%. Factors protective against parasitaemia included female gender (OR = 0.66, p = 0.047), mother’s age (OR = 0.81 per five-year increase, p = 0.01), reported bed net use (OR = 0.63, p = 0.03) and living in a well-constructed house (OR = 0.25, p = 0.01). Although HIV-unexposed infants had a higher risk of parasitaemia compared to HIV-exposed infants (24% vs 14%, p = 0.004), there was no significant association between HIV-exposure status and parasitaemia after controlling for the use of malaria preventative measures including bed net use and trimethoprim-sulphamethoxazole prophylaxis. The prevalence of stunting, underweight, and wasting were 10%, 7%, and 3%, respectively. HIV-exposed infants had a higher odds of stunting (OR = 2.23, p = 0.005), underweight (OR = 1.73, p = 0.09) and wasting (OR = 3.29, p = 0.02). The prevalence of anaemia was 12%. Risk factors for anaemia included older infant age (OR = 2.05 per one month increase, p = 0.003) and having malaria parasitaemia (OR = 5.74, p < 0.001). Compared to HIV-unexposed infants, HIV-exposed infants had a higher use of malaria preventative measures and lower odds of malaria parasitaemia. Having a better constructed house was also protective against malaria parasitaemia. HIV-exposure was the primary risk factor for measures of malnutrition. The primary risk factor for anaemia was malaria parasitaemia. These findings suggest the need to better target existing interventions for malaria, malnutrition and anaemia as well as the need to explore further the mechanisms behind the observed associations.Item High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda(Clinical infectious diseases, 2008) Gasasira, Anne F.; Kamya, Moses R.; Achan, Jane; Mebrahtu, Tsedal; Kalyango, Joan N.; Ruel, Theodore; Charlebois, Edwin; Staedke, Sarah G.; Kekitiinwa, Adeodata; Rosenthal, Philip J.; Havlir, Diane; Dorsey, GrantArtemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)–infected populations. Methods. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines. Results. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; Pp.08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; P ! .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, !750 cells/ mm3). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; Pp.001). Conclusions. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.Item How Are Insecticide-Treated Bednets Used in Ugandan Households? A Comprehensive Characterization of Bednet Adherence Using a Remote Monitor(The American Journal of Tropical Medicine and Hygiene, 2019) Krezanoski, Paul J.; Santorino, Data; Agaba, Alfred; Dorsey, Grant; Bangsberg, David R.; Carroll, Ryan W.Long-lasting insecticide-treated bednets are widely used and promoted for malaria control. Limitations in measurement methods have resulted in a poor understanding of how bednets are used in practice. We deployed a novel remote monitoring tool in Uganda to obtain, for the first time, a comprehensive characterization of bednet use in households at risk for malaria. Ten households each used one SmartNet adherence monitor over a commonly used sleeping area for 6 weeks. SmartNet continuously measures and records bednet use every 15 minutes. Bednet use was monitored for a total of 9,258 hours overall, with an average of 42 nights per household (SD: 3.5). Average duration of bednet use was 9 hours 49 minutes per night (SD: 1 hour 56 minutes), and adherence was 85–90% from 2100 to 0600. Bednets were not used at all on 4.5% (19/418) of observation nights. Overall, the average clock time that bednets were unfurled was 2034 (SD: 1 hour 25 minutes) and they were folded up at 0743 (SD: 43 minutes). The rate of interruptions per night observed in all households was 0.23 (86/369), with an average duration of 48 minutes (SD: 49 minutes). There was substantial heterogeneity between households, and some households had consistently poorer adherence relative to others. Variations in bednet use behaviors are a potentially important, and under-researched, component of long-lasting insecticide-treated bednet effectiveness. Remote bednet use monitors can provide novel insights into how bednets are used in practice, helping identify both households at risk of malaria due to poor adherence and also potentially novel targets for improving malaria prevention.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 Increased malaria parasitaemia among adults living with HIV who have discontinued cotrimoxazole prophylaxis in Kitgum district, Uganda(PLoS ONE, 2020) Orishaba, Philip; Kalyango, Joan N.; Byakika-Kibwika, Pauline; Arinaitwe, Emmanuel; Wandera, Bonnie; Katairo, Thomas; Muzeyi, Wani; Tendo Nansikombi, Hildah; Nakato, Alice; Mutabazi, Tobius; Kamya, Moses R.; Dorsey, Grant; Nankabirwa, Joaniter I.Although WHO recommends cotrimoxazole (CTX) discontinuation among HIV patients who have undergone immune recovery and are living in areas of low prevalence of malaria, some countries including Uganda recommend CTX discontinuation despite having a high malaria burden. We estimated the prevalence and factors associated with malaria parasitaemia among adults living with HIV attending hospital outpatient clinic before and after discontinuation of CTX prophylaxis.