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Robert D Newman - One of the best experts on this subject based on the ideXlab platform.
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safety and toxicity of sulfadoxine Pyrimethamine implications for malaria prevention in pregnancy using intermittent preventive treatment
Drug Safety, 2007Co-Authors: Philip J Peters, Michael C Thigpen, Monica E Parise, Robert D NewmanAbstract:Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/Pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering ≥2 treatment doses of sulfadoxine/Pyrimethamine to pregnant women at predefined intervals after quickening (around 18–20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/Pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/Pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/Pyrimethamine use in IPTp programmes in Africa, with 2–4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/Pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/Pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/Pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/Pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/Pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/Pyrimethamine — when delivered as IPTp — has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.
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Safety and Toxicity of Sulfadoxine/Pyrimethamine
Drug Safety, 2007Co-Authors: Philip J Peters, Michael C Thigpen, Monica E Parise, Robert D NewmanAbstract:Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/Pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering ≥2 treatment doses of sulfadoxine/Pyrimethamine to pregnant women at predefined intervals after quickening (around 18–20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/Pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/Pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/Pyrimethamine use in IPTp programmes in Africa, with 2–4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/Pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/Pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/Pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/Pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/Pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/Pyrimethamine — when delivered as IPTp — has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.
Sarah G Staedke - One of the best experts on this subject based on the ideXlab platform.
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sulfadoxine Pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria a randomized multisite trial to guide national policy in uganda
American Journal of Tropical Medicine and Hygiene, 2005Co-Authors: Nathan Bakyaita, Sarah G Staedke, Moses R Kamya, Grant Dorsey, Adoke Yeka, Kristin Banek, Ambrose O Talisuna, Fred Kironde, Sam Nsobya, Albert KilianAbstract:The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine- Pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-Pyrimethamine and from 13% to 35% with amodiaquine plus sulfadox- ine-Pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-Pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-Pyrimethamine was significantly more efficacious; how- ever, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.
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amodiaquine sulfadoxine Pyrimethamine and combination therapy for treatment of uncomplicated falciparum malaria in kampala uganda a randomised trial
The Lancet, 2001Co-Authors: Sarah G Staedke, Moses R Kamya, Grant Dorsey, Anne Gasasira, Grace Ndeezi, Edwin D Charlebois, Philip J RosenthalAbstract:Summary Background Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/Pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/Pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/Pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/Pyrimethamine (25 mg/kg sulfadoxine, and 1·25 mg/kg Pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/Pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. Findings 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ Pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/Pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/Pyrimethamine was significantly more effective than sulfadoxine/Pyrimethamine alone in children aged younger than 5 years (clinical failure in 3·5% vs 13·9%, respectively, risk difference 10·4% [95% CI, 1·6–19·3] p=0·021; parasitological failure in 12·8% vs 26·4%, risk difference 13·6% [1·2–26·0] p=0·041). Interpretation Sulfadoxine/Pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/Pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/ Pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.
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.
Grant Dorsey - One of the best experts on this subject based on the ideXlab platform.
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sulfadoxine Pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria a randomized multisite trial to guide national policy in uganda
American Journal of Tropical Medicine and Hygiene, 2005Co-Authors: Nathan Bakyaita, Sarah G Staedke, Moses R Kamya, Grant Dorsey, Adoke Yeka, Kristin Banek, Ambrose O Talisuna, Fred Kironde, Sam Nsobya, Albert KilianAbstract:The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine- Pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-Pyrimethamine and from 13% to 35% with amodiaquine plus sulfadox- ine-Pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-Pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-Pyrimethamine was significantly more efficacious; how- ever, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.
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amodiaquine sulfadoxine Pyrimethamine and combination therapy for treatment of uncomplicated falciparum malaria in kampala uganda a randomised trial
The Lancet, 2001Co-Authors: Sarah G Staedke, Moses R Kamya, Grant Dorsey, Anne Gasasira, Grace Ndeezi, Edwin D Charlebois, Philip J RosenthalAbstract:Summary Background Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/Pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/Pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/Pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/Pyrimethamine (25 mg/kg sulfadoxine, and 1·25 mg/kg Pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/Pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. Findings 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ Pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/Pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/Pyrimethamine was significantly more effective than sulfadoxine/Pyrimethamine alone in children aged younger than 5 years (clinical failure in 3·5% vs 13·9%, respectively, risk difference 10·4% [95% CI, 1·6–19·3] p=0·021; parasitological failure in 12·8% vs 26·4%, risk difference 13·6% [1·2–26·0] p=0·041). Interpretation Sulfadoxine/Pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/Pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/ Pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.
Moses R Kamya - One of the best experts on this subject based on the ideXlab platform.
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sulfadoxine Pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria a randomized multisite trial to guide national policy in uganda
American Journal of Tropical Medicine and Hygiene, 2005Co-Authors: Nathan Bakyaita, Sarah G Staedke, Moses R Kamya, Grant Dorsey, Adoke Yeka, Kristin Banek, Ambrose O Talisuna, Fred Kironde, Sam Nsobya, Albert KilianAbstract:The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine- Pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-Pyrimethamine and from 13% to 35% with amodiaquine plus sulfadox- ine-Pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-Pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-Pyrimethamine was significantly more efficacious; how- ever, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.
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amodiaquine sulfadoxine Pyrimethamine and combination therapy for treatment of uncomplicated falciparum malaria in kampala uganda a randomised trial
The Lancet, 2001Co-Authors: Sarah G Staedke, Moses R Kamya, Grant Dorsey, Anne Gasasira, Grace Ndeezi, Edwin D Charlebois, Philip J RosenthalAbstract:Summary Background Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/Pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/Pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/Pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/Pyrimethamine (25 mg/kg sulfadoxine, and 1·25 mg/kg Pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/Pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. Findings 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ Pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/Pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/Pyrimethamine was significantly more effective than sulfadoxine/Pyrimethamine alone in children aged younger than 5 years (clinical failure in 3·5% vs 13·9%, respectively, risk difference 10·4% [95% CI, 1·6–19·3] p=0·021; parasitological failure in 12·8% vs 26·4%, risk difference 13·6% [1·2–26·0] p=0·041). Interpretation Sulfadoxine/Pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/Pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/ Pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.
