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PubMed | Uganda Malaria Surveillance Project, Infectious Diseases Research Collaboration, University of Washington, Boston Childrens Hospital and 5 more.
Type: Journal Article | Journal: PLoS medicine | Year: 2016

Long-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.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 non-significant 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 pre-intervention 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 post-intervention; 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 post-intervention; 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.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.


Zinszer K.,McGill University | Charland K.,McGill University | Kigozi R.,Uganda Malaria Surveillance Project | Dorsey G.,University of California at San Francisco | And 2 more authors.
Bulletin of the World Health Organization | Year: 2014

Objective To illustrate the use of a new method for defining the catchment areas of health-care facilities based on their utilization. Methods The catchment areas of six health-care facilities in Uganda were determined using the cumulative case ratio: the ratio of the observed to expected utilization of a facility for a particular condition by patients from small administrative areas. The cumulative case ratio for malaria-related visits to these facilities was determined using data from the Uganda Malaria Surveillance Project. Catchment areas were also derived using various straight line and road network distances from the facility. Subsequently, the 1-year cumulative malaria case rate was calculated for each catchment area, as determined using the three methods. Findings The 1-year cumulative malaria case rate varied considerably with the method used to define the catchment areas. With the cumulative case ratio approach, the catchment area could include noncontiguous areas. With the distance approaches, the denominator increased substantially with distance, whereas the numerator increased only slightly. The largest cumulative case rate per 1000 population was for the Kamwezi facility: 234.9 (95% confidence interval, CI: 226.2-243.8) for a straight-line distance of 5 km, 193.1 (95% CI: 186.8-199.6) for the cumulative case ratio approach and 156.1 (95% CI: 150.9-161.4) for a road network distance of 5 km. Conclusion Use of the cumulative case ratio for malaria-related visits to determine health-care facility catchment areas was feasible. Moreover, this approach took into account patients' actual addresses, whereas using distance from the facility did not.


Zinszer K.,McGill University | Kigozi R.,Uganda Malaria Surveillance Project | Charland K.,McGill University | Dorsey G.,University of California at San Francisco | And 4 more authors.
Malaria Journal | Year: 2015

Background: Malaria thrives in poor tropical and subtropical countries where local resources are limited. Accurate disease forecasts can provide public and clinical health services with the information needed to implement targeted approaches for malaria control that make effective use of limited resources. The objective of this study was to determine the relevance of environmental and clinical predictors of malaria across different settings in Uganda. Methods: Forecasting models were based on health facility data collected by the Uganda Malaria Surveillance Project and satellite-derived rainfall, temperature, and vegetation estimates from 2006 to 2013. Facility-specific forecasting models of confirmed malaria were developed using multivariate autoregressive integrated moving average models and produced weekly forecast horizons over a 52-week forecasting period. Results: The model with the most accurate forecasts varied by site and by forecast horizon. Clinical predictors were retained in the models with the highest predictive power for all facility sites. The average error over the 52 forecasting horizons ranged from 26 to 128% whereas the cumulative burden forecast error ranged from 2 to 22%. Conclusions: Clinical data, such as drug treatment, could be used to improve the accuracy of malaria predictions in endemic settings when coupled with environmental predictors. Further exploration of malaria forecasting is necessary to improve its accuracy and value in practice, including examining other environmental and intervention predictors, including insecticide-treated nets. © 2015 Zinszer et al.


Kigozi R.,Uganda Malaria Surveillance Project | Baxi S.M.,University of California at San Francisco | Gasasira A.,Uganda Malaria Surveillance Project | Sserwanga A.,Uganda Malaria Surveillance Project | And 8 more authors.
PLoS ONE | Year: 2012

Background: Recently the use of indoor residual spraying of insecticide (IRS) has greatly increased in Africa; however, limited data exist on the quantitative impacts of IRS on health outcomes in highly malaria endemic areas. Methodology/Principal Findings: Routine data were collected on more than 90,000 patient visits at a single health facility over a 56 month period covering five rounds of IRS using three different insecticides. Temporal associations between the timing of IRS and the probability of a patient referred for microscopy having laboratory confirmed malaria were estimated controlling for seasonality and age. Considering patients less than five years of age there was a modest decrease in the odds of malaria following the 1st round of IRS using DDT (OR = 0.76, p<0.001) and the 2nd round using alpha-cypermethrin (OR = 0.83, p = 0.002). Following rounds 3-5 using bendiocarb there was a much greater decrease in the odds of malaria (ORs 0.34, 0.16, 0.17 respectively, p<0.001 for all comparisons). Overall, the impact of IRS was less pronounced among patients 5 years or older. Conclusions/Significance: IRS was associated with a reduction in malaria morbidity in an area of high transmission intensity in Uganda and the benefits appeared to be greatest after switching to a carbamate class of insecticide. © 2012 Kigozi et al.


Yeka A.,Uganda Malaria Surveillance Project | Harris J.C.,University of California at San Francisco
Current Opinion in Pediatrics | Year: 2010

Purpose of Review: In response to increased resistance to conventional drugs, the WHO is promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria. The objective of this report is to review the available evidence on the efficacy and effectiveness, acceptability, and deployment of ACT in resource-limited settings with a focus on sub-Saharan Africa. Recent Findings: ACTs are very effective in the treatment of uncomplicated Plasmodium falciparum malaria in children. ACTs are relatively safe and tolerable with no reported resistance in sub-Saharan Africa despite indications of delayed clearance of infections in south-east Asia. The major challenges to the widespread use of ACT include its high cost, availability, and inefficient delivery due to, among other things, weak healthcare systems. Summary: ACTs are an essential tool in the fight to control and eliminate malaria. They are currently the most effective drugs against P. falciparum malaria. They should be deployed through programs that address availability, cost, adherence, and quality assurance. Initiatives including home-based management of malaria, improving public sector procurement and supply chains, and reducing private sector pricing should make ACTs more accessible for sub-Saharan African children who bear the brunt of the burden of malarial disease. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Sears D.,San Francisco General Hospital | Kigozi R.,Uganda Malaria Surveillance Project | Mpimbaza A.,Uganda Malaria Surveillance Project | Mpimbaza A.,Makerere University | And 9 more authors.
Malaria Journal | Year: 2013

Background: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. Methods. Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients ≥ 4 months of age and ≥ 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. Results: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). Conclusions: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa. © 2013 Sears et al.; licensee BioMed Central Ltd.


Okiro E.A.,Kenya Medical Research Institute | Okiro E.A.,University of Oxford | Bitira D.,International HIV AIDS Alliance Uganda | Mbabazi G.,Uganda Malaria Surveillance Project | And 5 more authors.
BMC Medicine | Year: 2011

Background: Some areas of Africa are witnessing a malaria transition, in part due to escalated international donor support and intervention coverage. Areas where declining malaria rates have been observed are largely characterized by relatively low baseline transmission intensity and rapid scaling of interventions. Less well described are changing patterns of malaria burden in areas of high parasite transmission and slower increases in control and treatment access.Methods: Uganda is a country predominantly characterized by intense, perennial malaria transmission. Monthly pediatric admission data from five Ugandan hospitals and their catchments have been assembled retrospectively across 11 years from January 1999 to December 2009. Malaria admission rates adjusted for changes in population density within defined catchment areas were computed across three time periods that correspond to periods where intervention coverage data exist and different treatment and prevention policies were operational. Time series models were developed adjusting for variations in rainfall and hospital use to examine changes in malaria hospitalization over 132 months. The temporal changes in factors that might explain changes in disease incidence were qualitatively examined sequentially for each hospital setting and compared between hospital settings. Results: In four out of five sites there was a significant increase in malaria admission rates. Results from time series models indicate a significant month-to-month increase in the mean malaria admission rates at four hospitals (trend P < 0.001). At all hospitals malaria admissions had increased from 1999 by 47% to 350%. Observed changes in intervention coverage within the catchments of each hospital showed a change in insecticide-treated net coverage from <1% in 2000 to 33% by 2009 but accompanied by increases in access to nationally recommended drugs at only two of the five hospital areas studied.Conclusions: The declining malaria disease burden in some parts of Africa is not a universal phenomena across the continent. Despite moderate increases in the coverage of measures to reduce infection and disease without significant coincidental increasing access to effective medicines to treat disease may not lead to severe disease burden reductions in high transmission areas of Africa. More data is needed from a wider range of malaria settings to provide an honest tracking progress of the impact of scaled intervention coverage in Africa. © 2011 Okiro et al; licensee BioMed Central Ltd.


Nankabirwa J.,Uganda Malaria Surveillance Project | Cundill B.,London School of Hygiene and Tropical Medicine | Clarke S.,London School of Hygiene and Tropical Medicine | Kabatereine N.,Uganda Ministry of Health | And 8 more authors.
PLoS ONE | Year: 2010

Background: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisininpiperaquine (DP) among schoolchildren to inform IPT. Methods: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens. Results: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003). Conclusions: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa. © 2010 Nankabirwa et al.


Yeka A.,Uganda Malaria Surveillance Project | Tibenderana J.,Malaria Consortium | Achan J.,Uganda Malaria Surveillance Project | D'Alessandro U.,Institute of Tropical Medicine | And 2 more authors.
PLoS ONE | Year: 2013

Background: The treatment of falciparum malaria poses unique challenges in settings where malaria transmission intensity is high because recurrent infections are common. These could be new infections, recrudescences, or a combination of the two. Though several African countries continue to use quinine as the second line treatment for patients with recurrent infections, there is little information on its efficacy when used for rescue therapy. Moreover, such practice goes against the World Health Organisation (WHO) recommendation to use combination therapy for uncomplicated malaria. Methods: We conducted a nested, randomized, open label, three-arm clinical trial of rescue therapy in children 6-59 months old with recurrent malaria infection during 28 days post treatment with artemisinin combination treatment (ACT). Patients were randomly assigned to receive either quinine, artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHAPQ), and actively followed up for 28 days. Findings: Among 220 patients enrolled, 217 (98.6 %) were assigned an efficacy outcome and 218 (99.1 %) were assessed for safety. The risk of recurrent infection was significantly higher in patients treated with quinine (70 %, 74/110, HR = 3.9; 95 % CI: 2.4-6.7, p<0.0001) and AL (60%, 21/35, HR = 3.3; 95 % CI: 1.8-6.3, p<0.0002), compared to DHAPQ (25%, 18/72). Recrudescence tended to be lower in the DHAPQ (1%, 1/72) than in the quinine (7%, 8/110) or AL (6 %, 2/35) group, though it was not statistically significant. No serious adverse events were reported. Conclusion: Recurrent infections observed after the administration of an ACT can be successfully treated with an alternative ACT rather than with quinine. Trial Registration: Current Controlled Trials ISRCTN99046537. © 2013 Yeka et al.


Banek K.,Uganda Malaria Surveillance Project | Kilian A.,Malaria Consortium | Allan R.,MENTOR Initiative
Malaria Journal | Year: 2010

Background. By 2008, the WHO Pesticide Evaluation Scheme (WHOPES) recommended five long-lasting insecticidal nets (LLINs) for the prevention of malaria: Olyset®, PermaNet 2.0®, Netprotect®, Duranet® and Interceptor®. Field information is available for both Olyset® and PermaNet®, with limited data on the newer LLINs. To address this gap, a field evaluation was carried out to determine the acceptability and durability of Interceptor® LLINs. Methods. A one-year prospective field study was conducted in eight rural returnee villages in Liberia. Households were randomized to receive Interceptor® LLINs or conventionally treated nets (CTNs). Primary outcomes were levels of residual alpha-cypermethrin measured by HPLC and participant utilization/acceptability of the ITNs. Results. A total of 398 nets were analysed for residual alpha-cypermethrin. The median baseline concentrations of insecticide were 175.5 mg/m2 for the Interceptor® LLIN and 21.8 mg/m2 for the CTN. Chemical residue loss after a one year follow-up period was 22% and 93% respectively. Retention and utilization of nets remained high (94%) after one year, irrespective of type, while parasitaemia prevalence decreased from 29.7% at baseline to 13.6% during the follow up survey (p = < 0.001). Interview and survey data show perceived effectiveness of ITNs was just as important as other physical attributes in influencing net utilization. Conclusion. Interceptor® LLINs are effective and desirable in rural communities in Liberia. Consideration for end user preferences should be incorporated into product development of all LLINs in the future, in order to achieve optimum retention and utilization. © 2010 Banek et al.

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