Plasma levels of DDT/DDE and liver function in malaria control personnel 6 months after indoor residual spraying with DDT in northern Uganda, 2008

Objective. We investigated the relationship between plasma levels of dichlorodiphenyltrichloroethane (DDT) and liver function in malaria control personnel 6 months after one round of DDT indoor residual spraying (IRS). Method. This was a cross-sectional study in the districts of Apac and Oyam of Lango, northern Uganda. Volunteers were clinically examined, and 5 ml samples of venous blood were taken in heparinised tubes for a 6-month post-spray screening for DDT and plasma markers of liver function and internal organ disease. DDE/DDT was assayed using ELISA kits (Abraxis, USA); plasma enzyme activity concentrations of amylase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGT) were analysed using routine clinical chemistry-automated methods (Konelab, Vantaa, Finland). Results. All 96 plasma samples analysed for xenobiotics contained DDE/DDT in the empirical range of 24.00 - 128.00 parts per billion (ppb) with a mean (SD) of 77.00 (±26.00) ppb. All 119 plasma samples studied for the markers exhibited enzyme activity concentration values within the population reference ranges, with empirical means (SD) of amylase 71.86 (34.07), AST 23.83 (12.71), ALT 7.84 (10.01) and GGT 58.37 (62.68) µg/l. Conclusion. Six months after IRS with DDT, the spray team had an average concentration of plasma DDE/DDT of 77 ppb. This had no deleterious effect on liver function. We recommend continued use of DDT for IRS disease control in Uganda until better practical alternatives are available

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial

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

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda

BACKGROUND: Uganda 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 FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN75606663

Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda.

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

Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial.

ObjectivesTo compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.DesignRandomized single-blinded clinical trial.SettingApac, Uganda, an area of very high malaria transmission intensity.ParticipantsChildren aged 6 mo to 10 y with uncomplicated falciparum malaria.InterventionTreatment of malaria with AL or DP, each following standard 3-d dosing regimens.Outcome measuresRisks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.ResultsOf 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.ConclusionDP 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

Artesunate/Amodiaquine Versus Artemether/Lumefantrine for the Treatment of Uncomplicated Malaria in Uganda: A Randomized Trial.

BACKGROUND: In treating malaria in Uganda, artemether-lumefantrine (AL) has been associated with a lower risk of recurrent parasitemia, compared with artesunate-amodiaquine (AS/AQ), but changing treatment practices may have altered parasite susceptibility. METHODS: We enrolled 602 children aged 6-59 months with uncomplicated falciparum malaria from 3 health centers in 2013-2014 and randomly assigned them to receive treatment with AS/AQ or AL. Primary outcomes were risks of recurrent parasitemia within 28 days, with or without adjustment to distinguish recrudescence from new infection. Drug safety and tolerability and Plasmodium falciparum resistance-mediating polymorphisms were assessed. RESULTS: Of enrolled patients, 594 (98.7%) completed the 28-day study. Risks of recurrent parasitemia were lower with AS/AQ at all 3 sites (overall, 28.6% vs 44.6%; P < .001). Recrudescences were uncommon, and all occurred after AL treatment (0% vs 2.5%; P = .006). Recovery of the hemoglobin level was greater with AS/AQ (1.73 vs 1.39 g/dL; P = .04). Both regimens were well tolerated; serious adverse events were uncommon (1.7% in the AS/AQ group and 1.0% in the AL group). AS/AQ selected for mutant pfcrt/pfmdr1 polymorphisms and AL for wild-type pfcrt/pfmdr1 polymorphisms associated with altered drug susceptibility. CONCLUSIONS: 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

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial-0

<p><b>Copyright information:</b></p><p>Taken from "Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial"</p><p></p><p>PLoS Clinical Trials 2007;2(5):-.</p><p>Published online 18 May 2007</p><p>PMCID:PMC1876597.</p><p> © 2007 Kamya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p