Objectives:To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Design:Randomized single-blinded clinical trial.Setting:Apac, Uganda, an area of very high malaria transmission intensity.Participants:Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Intervention:Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Outcome measures:Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Results: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.Conclusion: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.

BackgroundUganda 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.Methodology/Principal FindingsPatients 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.Conclusions/SignificanceDP 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.Trial RegistrationControlled-Trials.com ISRCTN75606663

AS/AQ treatment was followed by fewer recurrences than AL treatment, contrasting with older data. Each regimen selected for polymorphisms associated with decreased treatment response. Research should consider multiple or rotating regimens to maintain treatment efficacies.

Abstract. A single round of indoor residual spraying (IRS) using lambda-cyhalothrin was implemented in a district of Uganda with moderate transmission intensity in 2007. Individual patient data were collected from one health facility within the district 8 months before and 16 months after IRS. There was a consistent decrease in the proportion of patients diagnosed with clinical malaria after IRS for patients < 5 and > 5 years of age (52% versus 26%, P < 0.001 and 36% versus 23%, P < 0.001, respectively). There was a large decrease in the proportion of positive blood smears in the first 4 months after IRS for patients < 5 (47% versus 14%, P < 0.001) and > 5 (26% versus 9%, P < 0.001) years of age, but this effect waned over the subsequent 12 months. IRS was effective in reducing malaria morbidity, but this was not sustained beyond 1 year for the proportion of blood smears read as positive.Malaria is the leading cause of morbidity and mortality in Uganda, responsible for up to 40% of outpatient visits, 25% of hospital admissions, and 14% of hospital deaths (Uganda Ministry of Health, unpublished data). Malaria control efforts in Uganda include case management with artemisinin-based combination therapy (ACT), widespread coverage with longlasting insecticide treated nets (LLINs), and intermittent preventive therapy in pregnancy. To expand its malaria control activities, the Uganda National Malaria Control Strategic Plan 2005-2010 has included indoor residual spraying (IRS) as one of the major malaria control interventions. Uganda aims to establish and sustain a system of high-quality IRS services that cover at least 85% of all targeted structures in areas of unstable transmission while piloting and potentially scaling up IRS in stable malaria transmission areas.Kanungu District is a district in southwest Uganda where IRS was implemented with support from the President's Malaria Initiative ( www.pmi.gov ). This district experiences perennial malaria with moderate transmission intensity and an entomologic inoculation rate estimated to be six infectious bites per person year in 2002.1 During February and March 2007, ~45,000 households covering a population of 190,000 persons were sprayed with the synthetic pyrethroid lambda-cyhalothrin wettable powder formulation (ICON 10% WP; Syngenta, Sweden ). IRS was targeted to ~70% households that are situated in areas below an altitude of 1,200 m, resulting in coverage of ~90% of targeted households. This first round of spraying in Kanungu was to be followed by serial IRS in the targeted subcounties. Because of logistical constraints, the next round of IRS has been delayed but is scheduled to occur in mid-2009.Accurate evaluation of the impact of interventions is necessary to optimize malaria control efforts. In 2006, the Uganda Malaria Surveillance Project (UMSP) established a sentinel site surveillance system that routinely collects individual-level data on all patients presenting to the outpatient department of selected government health facilities representing areas of varyi...

BackgroundIntegrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda.Case descriptionThe Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the ‘case’ for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework.DiscussionWHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in consolidating inter-sectoral collaboration and coordination and providing the tactical direction for effective deployment of vector control interventions along the five key elements of the approach and to align them with contemporary epidemiology of VBD in the country.ConclusionsUganda has successfully established an evidence-based IVM approach and consolidated strategic planning and operational frameworks for VBD control. However, operating implementation arrangements as outlined in the national strategic guidelines for IVM and managing insecticide resistance, as well as improving vector surveillance, are imperative. In addition, strengthened information, education and communication/behaviour change and communication, collaboration and coordination will be crucial in scaling up and using vector control interventions.