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At least 667 records · Page 37Linked to original sources
PubMed2005

Amodiaquine, sulfadoxine-pyrimethamine, and combination therapy for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso.

Increasing resistance to chloroquine necessitates the evaluation of other antimalarial therapies in Africa. We compared the efficacies of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and AQ + SP for the treatment of uncomplicated falciparum malaria in a randomized trial of patients 6 months of age or older in Bobo-Dioulasso, Burkina Faso. Of the 944 patients enrolled, 829 (88%; 53% under 5 years of age) were assigned 28-day efficacy outcomes. For all regimens, early treatment failures were uncommon (< 2%). Considering all treatment failures based on WHO criteria, AQ + SP was most efficacious (failures in 4.2%), followed by SP (9.1%) and AQ (17.9%; P < 0.02 for all pairwise comparisons). Considering only clinical failures, relative efficacies were similar (failures in 2.1% with AQ + SP, 6.5% with SP, and 13.2% with AQ; P < 0.02 for all pairwise comparisons). The risk of recrudescence was lower with AQ + SP (2.1%) compared with SP (6.1%, P = 0.02) and AQ (8.1%, P = 0.001). Risks of new infection were lower with AQ + SP (2.1%) and SP (2.4%) compared with AQ (9.1%, P < 0.001 for both comparisons). No serious adverse events were seen. AQ + SP appears to offer a highly effective, inexpensive, and available therapy for the treatment of uncomplicated malaria in Burkina Faso.

Adolescent↗
PubMedDate not supplied

Therapeutic efficacy of chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Papua New Guinea.

Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a possible change of the current first-line treatment of uncomplicated malaria with chloroquine alone (amodiaquine for children under five years) to chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the therapeutic efficacy of the new drug combination in Papua New Guinea, a study was carried out in 1998-1999 at five hospital outpatient departments. From the 513 patients enrolled for the study, 95 defaulted from follow-up. Of the remaining 418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients who did not have an ACR, 3 (0.7% of the total) developed severe signs in the first 24 hours and were treated in hospital; they were regarded as early treatment failures. The remaining 16 did not complete the study on the basis of various exclusion criteria but were not excluded from the analysis. From these results it was concluded that the combination was effective and a decision was taken in May 2000 to introduce the two-drug combination regimens as the standard first-line treatment of uncomplicated malaria, including falciparum malaria, in Papua New Guinea.

Adolescent↗
PubMed2006

Efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in East Timor.

The efficacy of sulfadoxine-pyrimethamine (SP) in East Timor is unknown. We treated 38 individuals with uncomplicated Plasmodium falciparum malaria with SP and monitored the outcome for 28 days. Recrudescent parasitemia, confirmed by genotyping, were detected in three individuals resulting in a late treatment failure rate of 7.9% (95% confidence interval = 1.7-21.4%). The results suggest that SP is still efficacious in treating uncomplicated P. falciparum malaria in East Timor. However, the useful life of SP in East Timor may be limited because 80% of the parasites in our samples were found to already carry double mutations in P. falciparum dihydrofolate reductase (S108N/C59R). The data from this study also highlights that the presence of gametocytes may significantly influence the estimate of SP efficacy determined by genotyping.

Adolescent↗
PubMed2006

Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi.

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.

Adolescent↗
PubMed2006

Roles of specific Plasmodium falciparum mutations in resistance to amodiaquine and sulfadoxine-pyrimethamine in Burkina Faso.

We evaluated associations between key polymorphisms in target genes and responses to treatment with sulfadoxine-pyrimethamine (SP) or amodiaquine (AQ) for uncomplicated Plasmodium falciparum malaria in Bobo-Dioulasso, Burkina Faso. Presence of the dihydrofolate reductase (dhfr) 108N or 59R mutations (but not dhfr 51I or dihydropteroate synthetase [dhps] 437G) and P. falciparum chloroquine resistance transporter (pfcrt) 76T or P. falciparum multidrug resistance 1 (pfmdr1) 86Y or 1246Y mutations (but not pfmdr1 184F) predicted recrudescence after treatment with SP and AQ, respectively. Treatment led to significant increases in the prevalence of the same mutations (except 1246Y) in new infections that presented after therapy. The dhfr 164L and dhps 540E mutations were not seen in any isolates. These results clarify the key roles of a small number of mutations in P. falciparum resistance to SP and AQ in west Africa.

Amodiaquine↗
PubMed2006

Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members.

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.

Animals↗
PubMed2006

[In vivo sensitivity of Plasmodium faciparum to chloroquine and sulfadoxine pyrimethamine in the Bobo Dioulasso region (1998-2001): risk factors associated with treatments failures to the two drugs].

The therapeutic efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was determined over a 4 year period (1998-2001) in Bobo Dioulasso, Burkina Faso, with an analysis of the risk factors associated to treatment failures to the 2 drugs. In total, 2008 children (6 months-15 years old) attending in 4 health centres (1 urban and 3 rural) were included in the study. Children were alternatively allocated to either CQ or SP The WHO 14-days in vivo field test was carried out. PCV was measured at day 0 and 14. CQ treatment failure was 24.4% (229/940), most of them being late failures. Between 1998 and 2001 a significant increase in CQ treatment failure (p < 0.001) was observed. SP showed a good efficacy with a total treatment failure of 4.4% (33/749). However; a significant increase of resistance to this drug (p=0.001) was also observed between 1998 and 2001. Among children with anaemia at day 0.85% (23/27) were no more anaemic by day 14 in the SP group, while in the CQ group the proportion was lower; 69% (27/39). However the difference between the two drugs was not significant (p > 0.1). Univariate analysis showed that the site, the age of children, the time of recruitment and the parasitaemia were significantly associated with CQ treatment failure. In the multivariate analysis these 4 variables remain significantly and independently associated with the risk of CQ treatment failure. After adjusting for the effect of the 3 other factors, the risk of treatment failure was reduced by half in rural area compared to urban area as well as in children of 5-15 years of age compared to those under 5. The risk of treatment failure was significantly increased in 2000-2001 (OR = 1.66, p < 0.05) as compared to the 2 previous years (1998-1999). It was also twice higher in children with parasitaemia > or = 16,000/microl than in those having a lower parasitaemia. For SP we have not observed such connexions with the univariate and multivariate analysis.

Adolescent↗
PubMed1991

Pyrimethamine-sulfadoxine (Fansidar) resistance in a non-immune Kenyan--a case report.

Drug resistance in an endemic zone is often difficult to prove. This case illustrating both chloroquine and pyrimethamine sulfadoxine resistance unfolded in an area without risk of reinfection. The long time lapse and hence danger, between exposure and clinical symptoms in those on chemoprophylaxis highlighted and emphasis is placed on adequate follow up to pick up resistance in long acting preparations.

Animals↗
PubMed1990

Pharmacokinetics of mefloquine in combination with sulfadoxine-pyrimethamine and primaquine in male Thai patients with falciparum malaria.

The pharmacokinetics of mefloquine (M) were studied in 59 male Thai patients with falciparum malaria. Mefloquine was administered alone (750 mg orally; group 1), or with primaquine (PQ, 45 mg; group 2), or in combination with sulfadoxine (1.5 g) + pyrimethamine (75 mg) (MSP; group 3), or as MSP + PQ (group 4). All patients in groups 1, 2 and 4 initially responded to treatment, but two patients from group 1 had RI recrudescent infections. One patient in group 3 failed to respond to treatment and was considered to have RII resistance, while a further patient from this group had RI recrudescence. The pharmacokinetic parameters for group 1 and group 3 were not significantly different. Co-administration of primaquine alone had no significant effect on the pharmacokinetics of mefloquine, but there was a statistically significant decrease in the terminal elimination half-life of mefloquine for group 4 relative to that for group 3.

Adolescent↗
PubMed1989

[Plasmodium falciparum drug resistance and sulfadoxine-pyrimethamine in Africa].

The sulfadoxine-pyrimethamine combination has not been recommended for the prophylaxis of malaria since 1985 following serious accidents in the USA. However, this drug is worth considering for treatment since it has the advantage over mefloquine of being cheaper, having fewer side effects and it avoids using mefloquine. A study of Plasmodium falciparum resistance to Fansidar should be carried out on cases imported to France to determine an adapted utilisation of this drug. This would be an appreciable advantage for tropical Africa.

Adult↗
PubMed1989

[Presumed toxoplasmic chorioretinitis: comparative study of treatment with pyrimethamine and sulfadiazine or clindamycin].

A prospective, randomized study was conducted in 29 patients with presumed toxoplasmic retinochoroiditis to compare the efficacy of oral pyrimethamine and sulfadiazine (P + S) with subconjunctival injections of clindamycin. There was no difference in the mean visual acuity in both groups after treatment; the mean healing time was similar in the two treatment groups, 1.80 months with clindamycin and 1.88 month with P + S. However subjective improvement was obtained earlier with clindamycin. After 14 months' follow up, recurrences of ocular toxoplasmosis developed in both groups, 21% with clindamycin and 36% with P + S, respectively (NS). Other than the discomfort due to topical treatment, clindamycin did not produce any side-effects, which did happened after oral P + S. Subconjunctival injections of clindamycin provide an interesting alternative in the choice of an antitoxoplasmic ocular therapy.

Acute Disease↗
PubMed1988

Comparison of the susceptibility of falciparum malaria to mefloquine-sulphadoxine-pyrimethamine and chloroquine in Nigeria.

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa, it is desirable to test alternative drugs for efficacy and safety. To this end we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef, Hoffman-La Roche, Switzerland) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was a rapidly acting blood schizontocide against the Nigerian strain of P. falciparum, and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fansimef in the trials conducted in Zambia, was not seen in any of the Nigerian patients.

Animals↗
PubMed1986

Chemotherapy and chemoprophylaxis of hepatic coccidiosis with sulphadimethoxine and pyrimethamine.

The activity of a mixture of sulphadimethoxine and pyrimethamine (10:3) as prophylactic medication and prophylactic and therapeutic medication was studied in rabbits experimentally infected with Eimeria stiedai. The haematocrit index (packed cell volume) and haemoglobin levels were studied for assessment of drug toxicity. The activity in serum of aspartate aminotransferase (AST) and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase were studied as indicators of hepatic lesions. Parasite development was followed on the basis of the presence of oocysts; other parameters were analysed in order to monitor the performance of infected animals. All the parameters studied showed that the chemoprophylactic medication provided efficient control of the infection and of the hepatic lesions. Serum AST activity was seen to be a good indicator of the effect of the drugs on the liver.

Alkaline Phosphatase↗
PubMed1985

Falciparum malaria treated with a fixed combination of mefloquine, sulfadoxine and pyrimethamine: a field study in adults in Burma.

In a field study conducted in Burma, 54 semi-immune adults suffering from falciparum malaria (mean parasite count, 15 328/mm(3) before treatment) were given a single dose of a fixed combination of 750 mg mefloquine base, 1500 mg sulfadoxine, and 75 mg pyrimethamine (3 tablets of Fansimef). All these patients were cleared of asexual parasites by day 7, giving a cure rate of 100%; the mean clearance time was 2.6 days. Reappearance of parasitaemia occurred in 10 patients on or before day 7 and persisted for one day in 8 of them and for two days in 2 patients. It eventually disappeared without further treatment. No recrudescence occurred during the follow-up time of four weeks despite the fact that there was active transmission of Plasmodium falciparum in the area throughout the whole of the study period. The drug was generally well tolerated, though mild to moderate giddiness was reported by 49 patients (90.7%) and severe giddiness by 3 patients (5.5%). Nausea occurred in 25 patients (46.3%) and vomiting in 17 (31.5%).

Adolescent↗
PubMed1988

Pathogenesis of limb and facial malformations induced by pyrimethamine in the rat.

The temporal sequence of morphological events resulting in limb and face malformations was studied in pyrimethamine (PY) treated female rats, 30 mg/kg of PY in a 10 ml/kg suspension of 0.9% NaCl were administered i.p. on days 12, 13 and 14 of gestation. Controls received only 0.9% NaCl solution. The females were killed at different stages of gestation (between 14 and 21 days). Early PY treated embryos showed mainly haematomas in the extremities and the mandibulo-maxillary areas. During the course of gestation, fewer haematomas and more malformations were observed. At term, malformations were observed in the same localisations where haematomas were previously seen.

Animals↗
PubMed1988

Observations on early and late post-sporozoite tissue stages in primate malaria. V. The effect of pyrimethamine and proguanil upon tissue hypnozoites and schizonts of Plasmodium cynomolgi bastianellii.

Two rhesus monkeys were each infected with 2.1 x 10(6) sporozoites of Plasmodium cynomolgi bastianellii; one was treated with 1.0 mg of pyrimethamine base per kg body weight for 5 d after sporozoite inoculation. A further 2 monkeys were each infected with 9.75 x 10(6) sporozoites of the same parasite; one was treated with 10 mg of proguanil per kg body weight for 4 out of 5 d after inoculation. The treated monkeys showed a delayed primary parasitaemia and relapses. In sections of liver biopsies taken 7.5 d after sporozoite inoculation, all monkeys showed numerous hypnozoites. However, there were no full grown schizonts and only rare retarded schizonts in the treated monkeys, in contrast to the untreated monkeys which had many mature or nearly mature schizonts. Later biopsies confirmed the continued presence of hypnozoites in all monkeys.

Animals↗
PubMed1987

A phase II/III double-blind, dose-finding clinical trial of a combination of mefloquine, sulfadoxine, and pyrimethamine (Fansimef) in falciparum malaria.

Fansimef is a combination of 250 mg mefloquine (base), 500 mg sulfadoxine, and 25 mg pyrimethamine per tablet. One hundred and fifty adult male Brazilian patients at Belém (Pará), who had peripheral blood smears positive for Plasmodium falciparum, with or without clinical symptoms of falciparum malaria, were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. Of those receiving one tablet (48 patients), 81% were cured and 19% exhibited RI recrudescences. All the patients receiving two or three tablets of Fansimef (49 patients in each group) were cured. The rates of initial clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects included nausea, vomiting, dizziness, diarrhoea and abdominal pain, but these were mild and transient and required no specific treatment. The incidence of vomiting and nausea was highest in patients given the three-tablet dose. The results of various haematological, biochemical and urine analyses were not adversely altered by the administration of Fansimef.

Administration, Oral↗
PubMed1987

Mefloquine, sulfadoxine, and pyrimethamine in the treatment of symptomatic falciparum malaria: a double-blind trial for determining the most effective dose.

A total of 89 adult male Thai patients who had acute, uncomplicated falciparum malaria were treated in a double-blind randomized trial with a single oral dose of two or three tablets, each consisting of 250 mg mefloquine, 500 mg sulfadoxine, and 25 mg pyrimethamine (MSP). The two-tablet regimen produced a cure rate (S response) of 93%, the three-tablet regimen a cure rate of 98%. The mean duration of parasitaemia for the two- and three-tablet groups was 50 and 29 hours, respectively, while the mean duration of fever was 43 and 40 hours, respectively. Differences between the groups were not statistically significant. Tolerance was good at both dose levels. The main side-effects were abdominal discomfort, nausea, vomiting, dizziness, and diarrhoea, but these were mild, transient, and required no specific treatment. The results of haematological and biochemical investigations and of urinalysis revealed no drug-related changes following administration of MSP. The electrocardiograms of some patients revealed sinus bradycardia or sinus arrythmia, but these conditions were transient, symptomless, and clinically not significant.

Administration, Oral↗