Disease relevance of Pyrimethamine-sulfadoxine

• Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine [1].
• Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial [2].
• Trimethoprim-sulfamethoxazole has been recommended as part of the standard package of care for people with HIV and AIDS in Africa. A similar antifolate combination, sulfadoxine-pyrimethamine, is now the first-line antimalarial drug in several of the African countries with the highest rates of HIV infection [3].
• We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration [4].
• Pyrimethamine-sulfadoxine may be effective in preventing recurrent pneumonia caused by Pneumocystis carinii in patients with the acquired immunodeficiency syndrome, but life-threatening cutaneous reactions have also been reported in this setting [5].

High impact information on Pyrimethamine-sulfadoxine

• Resistance to sulfadoxine-pyrimethamine is now increasing, especially in southeast Africa. METHODS:We characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine [6].
• 2 of 36 Plasmodium falciparum infections were resistant (RII and RIII) in vivo to the combination of mefloquine (M) and sulfadoxine-pyrimethamine (SP) in Jayapura, Irian Jaya, Indonesia [7].
• Field studies were conducted in Kisumu, Kenya, to assess the susceptibility of local strains of Plasmodium falciparum to pyrimethamine alone (by a standard 7-day in-vivo test and a 48 h in-vitro field test) and to sulfadoxine-pyrimethamine (by a 7-day in-vivo test) [8].
• In this paper, we review the history of antimalarial drug resistance and the methods for monitoring it and assess the current magnitude and burden of parasite resistance to two commonly used drugs: chloroquine and sulfadoxine-pyrimethamine [9].
• Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications [10].

Chemical compound and disease context of Pyrimethamine-sulfadoxine

• A prospective trial in 80 patients randomly allocated to four antimalarial treatment regimens--mefloquine plus pyrimethamine-sulfadoxine ('Fansidar'); mefloquine plus qinghaosu; mefloquine, fansidar, and qinghaosu; and qinghaosu alone--was carried out on Hainan Island, China, in patients with chloroquine-resistant falciparum malaria [11].
• Resistance of Plasmodium falciparum malaria to sulfadoxine-pyrimethamine ('Fansidar') in a refugee camp in Thailand [12].
• In 1993, Malawi became the first African country to replace chloroquine with sulfadoxine-pyrimethamine nationwide in response to high rates of chloroquine-resistant falciparum malaria [13].
• The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria [14].
• Blood folate concentrations and in vivo sulfadoxine-pyrimethamine failure in Malawian children with uncomplicated Plasmodium falciparum malaria [15].

Biological context of Pyrimethamine-sulfadoxine

• Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps) [16].
• To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days [17].
• In this study, haplotyping and microsatellite analysis of malaria from 5 regions of the South American Amazon support the conclusion that the parasite mutations conferring mid- and high-level resistance to the antifolate combination sulfadoxine-pyrimethamine have a common origin [18].
• These results suggest that the HbAS phenotype should be included among factors that determine sulfadoxine-pyrimethamine treatment outcome [19].
• The resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) is an emerging public health threat [20].

Associations of Pyrimethamine-sulfadoxine with other chemical compounds

• Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria [21].
• Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene [17].
• Mutations associated with sulfadoxine-pyrimethamine and chlorproguanil resistance in Plasmodium falciparum isolates from Blantyre, Malawi [22].
• OBJECTIVES: To assess the relationship between the presence of DHFR and DHPS mutations in Plasmodium falciparum, parasite in vitro resistance, and in vivo efficacy of sulfadoxine-pyrimethamine (SP) treatment [23].
• A sensitive and selective reversed-phase high-performance liquid chromatographic assay has been developed to determine the concentration of pyrimethamine, sulfadoxine and N4-acetylsulfadoxine in serum and urine after oral administration of the antimalarial remedy Suldox [24].

Gene context of Pyrimethamine-sulfadoxine

• Mutations at DHFR 164 and DHPS 581 were common in Bolivia, where pyrimethamine-sulfadoxine resistance is widespread, but absent in African sites [25].
• Prevalence of mutations at DHFR codon 108 and a new mutation at DHPS 540 correlated with increased pyrimethamine-sulfadoxine resistance (P < .05) [25].
• Background. Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight [26].
• In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment [27].
• The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment [28].

Analytical, diagnostic and therapeutic context of Pyrimethamine-sulfadoxine

• Treatment failure was more common with sulfadoxine-pyrimethamine [2].
• Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain [16].
• We aimed to find out whether chlorproguanil-dapsone results in a higher retreatment rate for malaria than sulfadoxine-pyrimethamine [2].
• Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination [29].
• The role of the sickle cell hemoglobin type as a determinant of treatment outcome with sulfadoxine-pyrimethamine was retrospectively studied in young children with uncomplicated falciparum malaria who lived in an area with intense perennial malaria transmission [19].

References