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Pascal Ringwald - One of the best experts on this subject based on the ideXlab platform.
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efficacy of Sulfadoxine pyrimethamine amodiaquine and Sulfadoxine pyrimethamine amodiaquine combination for the treatment of uncomplicated falciparum malaria in the urban and suburban areas of brazzaville congo
Acta Tropica, 2007Co-Authors: Mathieu Ndounga, Rachida Tahar, Pembe Issamou Mayengue, Prisca Nadine Casimiro, Davy Matondo W Maya, Valentine Miakassissampassi, David A Malonga, Freddy Nsondentandou, Godefroy Mallanda, Pascal RingwaldAbstract:Abstract Congo-Brazzaville has recently adopted artesunate-amodiaquine as the first-line antimalarial drug to replace chloroquine. Before the implementation of this new strategy, we conducted several clinical studies to assess the therapeutic efficacy of former, classical first-line antimalarial drugs in the city of Brazzaville, in which reside about 30% of the Congolese population. From 2003 to 2005, non-randomised trials were conducted to evaluate the efficacy of Sulfadoxine-pyrimethamine (SP) ( n = 97 patients), amodiaquine (AQ) ( n = 62 patients), and the combination of Sulfadoxine-pyrimethamine–amodiaquine ( n = 54 patients) in children aged between 6 months and 5 years with uncomplicated malaria using the 2003 WHO guidelines during the 28-day follow-up period. After excluding new infections by PCR, the proportion of treatment failure on day 28 was 30.2% (95% confidence interval, 19.2–43.0%) for Sulfadoxine-pyrimethamine, 34.8% (95% confidence interval, 21.4–50.2%) for amodiaquine, and 14.2% (95% confidence interval, 5.9–27.2%) for Sulfadoxine-pyrimethamine + amodiaquine combination. Treatment with Sulfadoxine-pyrimethamine was associated with an increase of gametocyte charge. These results suggest that neither Sulfadoxine-pyrimethamine nor amodiaquine is efficacious as monotherapy and that their combination may not remain effective in the coming years. Based on our results, the implementation of artemisinin-based combination therapy appears to be urgent in the country.
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therapeutic efficacy of Sulfadoxine pyrimethamine amodiaquine and the Sulfadoxine pyrimethamine amodiaquine combination against uncomplicated plasmodium falciparum malaria in young children in cameroon
Bulletin of The World Health Organization, 2002Co-Authors: Leonardo K Basco, Vincent Foumane Ngane, Mathieu Ndounga, Pascal Ringwald, Albert Sameekobo, Theresia N Metoh, Georges SoulaAbstract:OBJECTIVE: To evaluate the therapeutic efficacy of Sulfadoxine-pyrimethamine, amodiaquine, and the Sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon. METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) Sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of Sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the Sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs. FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects. CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.
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sequence variations in the genes encoding dihydropteroate synthase and dihydrofolate reductase and clinical response to Sulfadoxine pyrimethamine in patients with acute uncomplicated falciparum malaria
The Journal of Infectious Diseases, 2000Co-Authors: Rachida Tahar, Leonardo K Basco, A Keundjian, Pascal RingwaldAbstract:Mutations in dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) are associated with in vitro resistance to Sulfadoxine and pyrimethamine, respectively. The response of 75 patients to Sulfadoxine-pyrimethamine was determined, and the genes of the corresponding Plasmodium falciparum isolates were sequenced. Of 12 different unmixed allelic combinations, the triple dhfr mutation Asn-108/Arg-59/Ile-51 was observed in all patients responding with early treatment failure. Some, but not all, patients with an adequate clinical response also harbored isolates with the triple dhfr mutation. Higher initial parasitemia and fever distinguished these 2 patient groups. The dhps genotype apparently had no influence on the clinical outcome. The other dhfr alleles with 1 or 2 mutations and the wild-type allele were found in patients with an adequate clinical response. The triple dhfr mutation is one of the genetic determinants associated with in vivo resistance to Sulfadoxine-pyrimethamine.
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molecular epidemiology of malaria in yaounde cameroon ii baseline frequency of point mutations in the dihydropteroate synthase gene of plasmodium falciparum
American Journal of Tropical Medicine and Hygiene, 1998Co-Authors: Leonardo K Basco, Pascal RingwaldAbstract:Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to treat chloroquine-resistant Plasmodium falciparum malaria. The molecular target of Sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde, Cameroon, and compared with the sequence of reference clones and Cambodian strains of P. falciparum. Of the 32 Cameroonian isolates, 31 displayed one of the Sulfadoxine-sensitive mutation patterns: Ala-436/Ala-437/Ala-581/Ala-613 (n = 20), Ser-436/Gly-437/Ala-581/Ala-613 (n = 6), Ser-436/Ala-437/Ala-581/Ala-613 (n = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a Sulfadoxine-resistant profile characterized by a double mutation: Phe-436/Ala-437/Ala-581/Ser-613. Although the majority of the isolates had a Sulfadoxine-sensitive genetic profile, further studies are needed to correlate the mutation patterns and in vitro and in vivo Sulfadoxine sensitivity.
Leonardo K Basco - One of the best experts on this subject based on the ideXlab platform.
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therapeutic efficacy of Sulfadoxine pyrimethamine amodiaquine and the Sulfadoxine pyrimethamine amodiaquine combination against uncomplicated plasmodium falciparum malaria in young children in cameroon
Bulletin of The World Health Organization, 2002Co-Authors: Leonardo K Basco, Vincent Foumane Ngane, Mathieu Ndounga, Pascal Ringwald, Albert Sameekobo, Theresia N Metoh, Georges SoulaAbstract:OBJECTIVE: To evaluate the therapeutic efficacy of Sulfadoxine-pyrimethamine, amodiaquine, and the Sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon. METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) Sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of Sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the Sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs. FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects. CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.
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sequence variations in the genes encoding dihydropteroate synthase and dihydrofolate reductase and clinical response to Sulfadoxine pyrimethamine in patients with acute uncomplicated falciparum malaria
The Journal of Infectious Diseases, 2000Co-Authors: Rachida Tahar, Leonardo K Basco, A Keundjian, Pascal RingwaldAbstract:Mutations in dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) are associated with in vitro resistance to Sulfadoxine and pyrimethamine, respectively. The response of 75 patients to Sulfadoxine-pyrimethamine was determined, and the genes of the corresponding Plasmodium falciparum isolates were sequenced. Of 12 different unmixed allelic combinations, the triple dhfr mutation Asn-108/Arg-59/Ile-51 was observed in all patients responding with early treatment failure. Some, but not all, patients with an adequate clinical response also harbored isolates with the triple dhfr mutation. Higher initial parasitemia and fever distinguished these 2 patient groups. The dhps genotype apparently had no influence on the clinical outcome. The other dhfr alleles with 1 or 2 mutations and the wild-type allele were found in patients with an adequate clinical response. The triple dhfr mutation is one of the genetic determinants associated with in vivo resistance to Sulfadoxine-pyrimethamine.
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molecular epidemiology of malaria in yaounde cameroon ii baseline frequency of point mutations in the dihydropteroate synthase gene of plasmodium falciparum
American Journal of Tropical Medicine and Hygiene, 1998Co-Authors: Leonardo K Basco, Pascal RingwaldAbstract:Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to treat chloroquine-resistant Plasmodium falciparum malaria. The molecular target of Sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde, Cameroon, and compared with the sequence of reference clones and Cambodian strains of P. falciparum. Of the 32 Cameroonian isolates, 31 displayed one of the Sulfadoxine-sensitive mutation patterns: Ala-436/Ala-437/Ala-581/Ala-613 (n = 20), Ser-436/Gly-437/Ala-581/Ala-613 (n = 6), Ser-436/Ala-437/Ala-581/Ala-613 (n = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a Sulfadoxine-resistant profile characterized by a double mutation: Phe-436/Ala-437/Ala-581/Ser-613. Although the majority of the isolates had a Sulfadoxine-sensitive genetic profile, further studies are needed to correlate the mutation patterns and in vitro and in vivo Sulfadoxine sensitivity.
Kalifa Diarra - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of primaquine and methylene blue for prevention of plasmodium falciparum transmission in mali a phase 2 single blind randomised controlled trial
Lancet Infectious Diseases, 2018Co-Authors: Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John S Bradley, Koualy Sanogo, Daouda T Kone, Kalifa DiarraAbstract:Summary Background Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. Methods This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali). We enrolled male participants aged 5–50 years with asymptomatic P falciparum malaria. G6PD-normal participants with gametocytes detected by blood smear were randomised 1:1:1:1 in block sizes of eight, using a sealed-envelope design, to receive either Sulfadoxine-pyrimethamine and amodiaquine, Sulfadoxine-pyrimethamine and amodiaquine plus a single dose of 0·25 mg/kg primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days. Laboratory staff, investigators, and insectary technicians were masked to the treatment group and gametocyte density of study participants. The study pharmacist and treating physician were not masked. Participants could request unmasking. The primary efficacy endpoint, analysed in all infected patients with at least one infectivity measure before and after treatment, was median within-person percentage change in mosquito infectivity 2 and 7 days after treatment, assessed by membrane feeding. This study is registered with ClinicalTrials.gov, number NCT02831023. Findings Between June 27, 2016, and Nov 1, 2016, 80 participants were enrolled and assigned to the Sulfadoxine-pyrimethamine and amodiaquine (n=20), Sulfadoxine-pyrimethamine and amodiaquine plus primaquine (n=20), dihydroartemisinin-piperaquine (n=20), or dihydroartemisinin-piperaquine plus methylene blue (n=20) groups. Among participants infectious at baseline (54 [68%] of 80), those in the Sulfadoxine-pyrimethamine and amodiaquine plus primaquine group (n=19) had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with Sulfadoxine-pyrimethamine and amodiaquine alone (n=12; −10·2%, IQR −143·9 to 56·6; p Interpretation Adding a single dose of 0·25 mg/kg primaquine to Sulfadoxine-pyrimethamine and amodiaquine or 3 days of 15 mg/kg per day methylene blue to dihydroartemisinin-piperaquine was highly efficacious for preventing P falciparum transmission. Both primaquine and methylene blue were well tolerated. Funding Bill & Melinda Gates Foundation, European Research Council.
Malcolm E Molyneux - One of the best experts on this subject based on the ideXlab platform.
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decreasing burden of malaria in pregnancy in malawian women and its relationship to use of intermittent preventive therapy or bed nets
PLOS ONE, 2010Co-Authors: Gaoqian Feng, Malcolm E Molyneux, Julie A Simpson, Ebbie Chaluluka, Stephen J RogersonAbstract:BACKGROUND: The World Health Organization recommends insecticidal bednets and intermittent preventive treatment to reduce malaria in pregnancy. Longitudinal data of malaria prevalence and pregnancy outcomes are valuable in gauging the impact of these antimalarial interventions. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 8131 women delivering in a single Malawian hospital over 9 years. We recorded demographic data antenatal prescription of intermittent preventive therapy during pregnancy with Sulfadoxine-pyrimethamine and bed net use and examined finger-prick blood for malaria parasites and hemoglobin concentration. In 4712 women we examined placental blood for malaria parasites and recorded the infants birth weight. Peripheral and placental parasitemia prevalence declined from 23.5% to 5.0% and from 25.2% to 6.8% respectively. Smaller declines in prevalence of low birth weight and anemia were observed. Coverage of intermittent preventive treatment and bednets increased. Number of Sulfadoxine-pyrimethamine doses received correlated inversely with placental parasitemia (Odds Ratio (95% CI): 0.79 (0.68 0.91)) maternal anemia (0.81 (0.73 0.90)) and low birth weight from 1997-2001 (0.63 (0.53 0.75)) but not from 2002-2006. Bednet use protected from peripheral parasitemia (0.47 (0.37 0.60)) and placental parasitemia (0.41 (0.31 0.54)) and low birth weight (0.75 (0.59 0.95)) but not anemia throughout the study. Compared to women without nets who did not receive 2-dose Sulfadoxine-pyrimethamine women using nets and receiving 2-dose Sulfadoxine-pyrimethamine were less likely to have parasitemia or low birth weight babies. Women receiving 2-dose Sulfadoxine-pyrimethamine alone had little evidence of protection whereas bednets alone gave intermediate protection. CONCLUSIONS/SIGNIFICANCE: Increased bednet coverage explains changes in parasitemia and birth weight among pregnant women better than Sulfadoxine-pyrimethamine use. High bed net coverage and Sulfadoxine-pyrimethamine resistance may be contributing to its apparent loss of effectiveness.
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sustained clinical efficacy of Sulfadoxine pyrimethamine for uncomplicated falciparum malaria in malawi after 10 years as first line treatment five year prospective study
BMJ, 2004Co-Authors: Christopher V Plowe, Fraction K Dzinjalamala, James G Kublin, Deborah S Kamwendo, Rabia A G Mukadam, Phillips Chimpeni, Malcolm E Molyneux, Terrie E TaylorAbstract:Abstract Objective To measure the efficacy of Sulfadoxine-pyrimethamine treatment of falciparum malaria in Malawi from 1998 to 2002, after a change from chloroquine to Sulfadoxine-pyrimethamine as first line treatment in that country in 1993. Design Prospective open label drug efficacy study. Setting Health centre in large peri-urban township adjacent to Blantyre, Malawi. Participants People presenting to a health centre with uncomplicated Plasmodium falciparum malaria. Main outcome measures Therapeutic efficacy and parasitological resistance to standard Sulfadoxine-pyrimethamine treatment at 14 days and 28 days of follow up. Results Therapeutic efficacy remained stable, with adequate clinical response rates of 80% or higher throughout the five years of the study. Analysis of follow up to 28 days showed modest but significant trends towards diminishing clinical and parasitological efficacy over time within the study period. Conclusion Contrary to expectations, Sulfadoxine-pyrimethamine has retained good efficacy after 10 years as the first line antimalarial drug in Malawi. African countries with very low chloroquine efficacy, high Sulfadoxine-pyrimethamine efficacy, and no other immediately available alternatives may benefit from interim use of Sulfadoxine-pyrimethamine while awaiting implementation of combination antimalarial treatments.
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Chlorproguanil-dapsone versus Sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial
Lancet (London England), 2002Co-Authors: J. Sulo, William M. Watkins, Christopher V Plowe, Terrie E Taylor, James G Kublin, Phillips Chimpeni, Malcolm E Molyneux, J. Hatcher, Kevin Marsh, Peter WinstanleyAbstract:Summary Background Chlorproguanil-dapsone exerts lower resistance pressure on Plasmodium falciparum than does Sulfadoxine-pyrimethamine, but is rapidly eliminated. We aimed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than Sulfadoxine-pyrimethamine. Methods In a randomised trial of paediatric outpatients with uncomplicated falciparum malaria, patients received either chlorproguanil-dapsone or Sulfadoxine-pyrimethamine and were followed up for up to 1 year. Sites were in Kenya (n=410) and Malawi (n=500). We used perprotocol analysis to assess the primary outcome of annual malaria incidence. Findings Drop-outs were 117 of 410 (28·5%) in Kenya, and 342 of 500 (68·4%) in Malawi. Follow-up was for a median of 338 days (IQR 128–360) and 342 days (152–359) in Kilifi (chlorproguanil-dapsone and Sulfadoxine-pyrimethamine, respectively), and for 120 days (33–281) and 84 days (26–224) in Blantyre. Mean annual malaria incidence was 2·5 versus 2·1 in Kenya (relative risk 1·16, 95% Cl 0·98–1·37), and 2·2 versus 2·8 in Malawi (0·77, 0·63–0·94). 4·3% versus 12·8%, and 5·4% versus 20·1%, of patients were withdrawn for treatment failure in Kenya and Malawi, respectively. In Kenya haemoglobin concentration of 50 g/L or less caused exit in 6·9% of chlorproguanil-dapsone patients and 1·5% of Sulfadoxine-pyrimethamine patients, but most anaemia occurred before re-treatment. In Malawi only one patient exited because of anaemia. Interpretation Despite the rapid elimination of chlorproguanil-dapsone, children treated with this drug did not have a higher incidence of malaria episodes than those treated with Sulfadoxine-pyrimethamine. Treatment failure was more common with Sulfadoxine-pyrimethamine. Cause of anaemia in Kenya was probably not adverse reaction to chlorproguanil-dapsone, but this observation requires further study.
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molecular markers for failure of Sulfadoxine pyrimethamine and chlorproguanil dapsone treatment of plasmodium falciparum malaria
The Journal of Infectious Diseases, 2002Co-Authors: James G Kublin, Fraction K Dzinjalamala, Deborah S Kamwendo, Rabia A G Mukadam, Joseph F Cortese, Stephen J Rogerson, Elissa M Malkin, Lisa M Martino, Andres G Lescano, Malcolm E MolyneuxAbstract:Molecular assays for monitoring Sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes. This study analyzed pretreatment dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genotypes and treatment outcomes in a double-blind, placebo-controlled trial of Sulfadoxine-pyrimethamine and chlorproguanildapsone treatment for uncomplicated P. falciparum malaria. Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors. Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with Sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant. If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.
Alassane Dicko - One of the best experts on this subject based on the ideXlab platform.
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effect of adding azithromycin to seasonal malaria chemoprevention
The New England Journal of Medicine, 2019Co-Authors: Daniel Chandramohan, Issaka Zongo, Alassane Dicko, Issaka Sagara, Matthew Cairns, Irene Kuepfer, Modibo Diarra, Amadou Barry, A Tapily, Frederic NikiemaAbstract:Abstract Background Mass administration of azithromycin for trachoma control led to a sustained reduction in all-cause mortality among Ethiopian children. Whether the addition of azithromycin to the monthly Sulfadoxine–pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention could reduce mortality and morbidity among African children was unclear. Methods We randomly assigned children 3 to 59 months of age, according to household, to receive either azithromycin or placebo, together with Sulfadoxine–pyrimethamine plus amodiaquine, during the annual malaria-transmission season in Burkina Faso and Mali. The drug combinations were administered in four 3-day cycles, at monthly intervals, for three successive seasons. The primary end point was death or hospital admission for at least 24 hours that was not due to trauma or elective surgery. Data were recorded by means of active and passive surveillance. Results In July 2014, a total of 19,578 children were randomly assigned to receive seasonal mal...
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efficacy and safety of primaquine and methylene blue for prevention of plasmodium falciparum transmission in mali a phase 2 single blind randomised controlled trial
Lancet Infectious Diseases, 2018Co-Authors: Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John S Bradley, Koualy Sanogo, Daouda T Kone, Kalifa DiarraAbstract:Summary Background Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. Methods This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali). We enrolled male participants aged 5–50 years with asymptomatic P falciparum malaria. G6PD-normal participants with gametocytes detected by blood smear were randomised 1:1:1:1 in block sizes of eight, using a sealed-envelope design, to receive either Sulfadoxine-pyrimethamine and amodiaquine, Sulfadoxine-pyrimethamine and amodiaquine plus a single dose of 0·25 mg/kg primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days. Laboratory staff, investigators, and insectary technicians were masked to the treatment group and gametocyte density of study participants. The study pharmacist and treating physician were not masked. Participants could request unmasking. The primary efficacy endpoint, analysed in all infected patients with at least one infectivity measure before and after treatment, was median within-person percentage change in mosquito infectivity 2 and 7 days after treatment, assessed by membrane feeding. This study is registered with ClinicalTrials.gov, number NCT02831023. Findings Between June 27, 2016, and Nov 1, 2016, 80 participants were enrolled and assigned to the Sulfadoxine-pyrimethamine and amodiaquine (n=20), Sulfadoxine-pyrimethamine and amodiaquine plus primaquine (n=20), dihydroartemisinin-piperaquine (n=20), or dihydroartemisinin-piperaquine plus methylene blue (n=20) groups. Among participants infectious at baseline (54 [68%] of 80), those in the Sulfadoxine-pyrimethamine and amodiaquine plus primaquine group (n=19) had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with Sulfadoxine-pyrimethamine and amodiaquine alone (n=12; −10·2%, IQR −143·9 to 56·6; p Interpretation Adding a single dose of 0·25 mg/kg primaquine to Sulfadoxine-pyrimethamine and amodiaquine or 3 days of 15 mg/kg per day methylene blue to dihydroartemisinin-piperaquine was highly efficacious for preventing P falciparum transmission. Both primaquine and methylene blue were well tolerated. Funding Bill & Melinda Gates Foundation, European Research Council.
