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PubMedDate not supplied

Treatment of malaria in north-eastern and south-eastern Nigeria: a population study of mefloquine, sulphadoxine, pyrimethamine combination (MSP) vs chloroquine (CQ).

In a population-based study involving 4019 patients in 20 peripheral health facilities in Nigeria, the outcome of presumptive malaria treatment with MSP was compared to that of CQ. The study was conducted between January 1995 and January 1996. Patients aged 6 months or more with a clinical diagnosis of malaria based on history of fever and axillary temperature > 37.5 degrees C were either treated with MSP (250 mg mefloquine, 500 mg sulphadoxine, and 25 mg pyrimethamine per tablet) or CQ (150 mg chloroquine base per tablet). The clinical cure rate was assessed by the disappearance of clinical signs and symptoms over a 7-day period. Tolerability was assessed by the incidence of adverse events (adverse drug reaction and intercurrent illness). The result shows that the clinical care rate of suspected malaria was 97.6% with MSP and 85.6% with CQ. The incidence of adverse event was 9.5% with MSP and 9.2% with CQ. The withdrawal rate was 2.0% with MSP and 5.0% with CQ; 3.5% of the patients in the CQ group withdrew due to adverse events compared to 0.47% with MSP. In conclusion it was observed that in addition to superior efficacy of MSP over CQ, fever clearance rate with MSP was comparable to that of CQ. The study also demonstrated that two tablets maximum dose of MSP is safe and effective in a large population of Nigeria malaria patients.

Adult↗
PubMed2001

Effectiveness of short-course quinine and single-dose sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria in Mpumalanga Province, South Africa.

INTRODUCTION: Quinine therapy for 7 days remains the mainstay for treating hospitalised malaria cases in South Africa. However, limited resources, including available beds and staff, often result in early discharge of non-severe cases, with quinine tablets for outpatient use. The effectiveness of shorter course quinine therapy coupled with a long-acting antimalarial drug has never been established in Africa, in particular in a population without malaria immunity. METHODS: A study was conducted to evaluate the effectiveness of a 3-day course of therapy with quinine sulphate (10 mg/kg 8-hourly) followed by a single dose of sulfadoxine-pyrimethamine (SP) according to weight category, before discharge, for 133 hospitalised patients with uncomplicated Plasmodium falciparum malaria at Shongwe Hospital, Mpumalanga province, between February and July 1998. Study endpoints included clinical recovery and parasitological cure, including polymerase chain reaction (PCR) 42 days after initiating treatment. RESULTS: One hundred and thirty of 131 patients (99%) successfully followed up for 42 days demonstrated clinical and parasitological cure. The remaining patient, who had evidence of a recrudescent infection on PCR, was 1 of 61 patients who were still parasitaemic on discharge from hospital. CONCLUSION: The abbreviated course of quinine therapy coupled with a single dose of SP for the treatment of non-severe hospitalised cases of P. falciparum malaria, in an area with demonstrated low levels of SP resistance, was highly effective. This approach has potential benefits, including reduced duration of hospitalisation, fewer quinine-associated adverse events and protection against the evolution of quinine resistance by limiting unsupervised quinine therapy in the community. It may, however, be prudent to document a negative blood film before discharge from hospital.

Adolescent↗
PubMed2001

Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga.

OBJECTIVES: To assess therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. SETTING: Tonga district with a population of 116,418 and subject to seasonal malaria, with an average annual incidence of 3,200 cases. SUBJECTS: One hundred and nineteen malaria patients presenting to a sentinel surveillance clinic and recruited according to World Health Organisation (WHO) criteria. METHODOLOGY: Patients satisfying WHO inclusion criteria were treated with a single oral dose of SP and the response of infection to treatment in each patient was routinely monitored clinically and parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42 post-treatment. One hundred and ten patients completed follow-up to day 42 or evidence of clinical or parasitological failure. RESULTS: The cure rate at day 42 was 93.6% (103/110). Two patients (1.8%, RII) were early treatment failures on day 3, while recrudescence (4.5%, RI) occurred in 5 patients on day 28 (N = 3) and on day 42 (N = 2). CONCLUSION: In Mpumalanga P. falciparum remains sensitive to SP, with no significant difference between the baseline cure rate (94.5%) and the cure rate in the present study (93.6%).

Adolescent↗
PubMed2002

Effect of sulfadiazine and pyrimethamine on selected physiologic and performance parameters in athletically conditioned thoroughbred horses during an incremental exercise stress test.

Following the regimen used to treat equine protozoal myeloencephalitis, sulfadiazine (20 mg/kg) and pyrimethamine (1mg/kg) were administered orally once daily to 12 physically conditioned Thoroughbred horses for 4 consecutive days. The horses were randomly assigned to two test groups in a crossover design, with each horse serving as its own control. A stepwise exercise stress test was conducted to exhaustion. No effect on athletic performance was observed, and only marginal effects were noted in some hematologic and serochemical measurements, including decreased total white blood cell counts, red blood cell distribution width, total hemoglobin, serum sodium, and serum chloride. Serum folic acid concentration decreased significantly following sulfadiazine/pyrimethamine treatment.

Animals↗
PubMed2003

Efficacy of chloroquine, sulfadoxine-pyrimethamine, and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria on the north coast of Peru.

As part of an effort to assess antimalarial drug resistance in Peru, we carried out 14-day in vivo efficacy trials of chloroquine (CQ; 25 mg/kg) and sulfadoxine-pyrimethamine (SP; 25 mg/kg of the sulfadoxine component) for the treatment of uncomplicated Plasmodium falciparum infections at three sites on the northern coast of Peru. Mefloquine (MQ; 15 mg/kg) also was evaluated at one site. The results from all three sites were similar. Of the 53 patients treated with CQ, 58.5% had RII/RIII responses. No RIII failures were observed among the 112 patients who received SP, but 4.5% and 1.8%, respectively, had RII and RI responses. All 33 patients treated with MQ showed a sensitive response. Early treatment failures were observed in 27.1% of the CQ patients but in no patients receiving SP or MQ. Late treatment failures were seen in 59.3% of the CQ patients and 6.4% of the SP patients but in none of those treated with MQ. Based on these findings and because of concern about the potential for development of resistance if SP were used alone, the National Malaria Control Program is planning a change in malaria treatment policy to SP-artesunate combination therapy for this region of the country.

Adolescent↗
PubMed1956

Suppression of malaria with pyrimethamine in Nigerian schoolchildren.

The authors describe a two-year investigation carried out on a group of Nigerian schoolchildren with the object of assessing the effect of suppressing malaria infection with pyrimethamine on the physical development of the African child. The results showed that the average gain in weight of the treated children over the period of the investigation was significantly greater than that of the untreated children. Despite the relatively high weekly dose of the drug no side-effects were observed, and no alarming manifestation of malaria was noted when administration of the drug was discontinued.

Antimalarials↗
PubMed1992

Chemoprophylaxis against malaria in Papua New Guinea: a trial of amodiaquine and a combination of dapsone and pyrimethamine.

A placebo-controlled chemoprophylaxis trial was carried out in 1980 in 318 semi-immune school children in the Madang area of Papua New Guinea, where there was a high prevalence of strains of Plasmodium falciparum resistant to 4-aminoquinolines. Since prophylaxis with amodiaquine at 5 mg/kg weekly had failed, amodiaquine at a dose of 10mg/kg weekly and Maloprim (half a tablet or one tablet depending on body weight, which gave ranges of dapsone of 1.7-3.3mg/kg and pyrimethamine 0.2-0.4 mg/kg) weekly were tried. Neither regimen was completely successful in preventing parasitaemia, though after 13 weeks of prophylaxis the slide positivity rate was 16% for the amodiaquine group and 2% for the Maloprim group, which was in each case significantly lower than the normal baseline rate in the controls of 42%. Amodiaquine was completely successful in suppressing Plasmodium vivax infections. Breakthrough parasitaemia occurred, with either P. falciparum or P. vivax, in 5% of subjects on Maloprim at some time during the 13-week period of prophylaxis. Significantly more children in both the amodiaquine and Maloprim groups than in the placebo group showed a reduction in spleen size. All groups showed an unexplained fall in haemoglobin level over the study period but the fall was significantly less in both the prophylaxis groups. There was no adverse effect on white cell counts by either drug regimen. Chemoprophylaxis as a component of an integrated malaria control program should not be overlooked, provided that compliance can be maintained. However, in this particular case the principal purpose of the study had been to evaluate the proposed chemoprophylactic regimens in school children before embarking on an intervention study in young children. As a result of this study it was decided not to go ahead with the chemoprophylactic intervention in young children but to adopt an approach based on early presumptive treatment.

Antimalarials↗
PubMed2003

Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria.

Surveillance of molecular markers for key mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) has been proposed as a means of predicting sulfadoxine/ pyrimethamine (SP) treatment outcomes in Africa. This study assessed the association between DHFR and DHPS mutations and standardized clinical outcomes in children treated with SP for uncomplicated malaria in Kampala, Uganda. Two mutations (DHFR Asn-108 and Ile-51) were too common to be useful predictors. Three other mutations (DHFR Arg-59, DHPS Gly-437, and DHPS Glu-540) were associated with clinical treatment failure after 14 days, although associations were not significant. When follow-up was extended to 28 days and genotyping was used to distinguish recrudescence from new infections, associations were significantly strengthened. The presence of both the DHFR Arg-59 and DHPS Glu-540 mutations had the strongest association with clinical treatment failure (odds ratio = 10.7, P = 0.009). These results support a previously proposed method of predicting clinical outcomes based on the prevalence of these two mutations.

Animals↗
PubMedDate not supplied

Assessment of therapeutic efficacy of chloroquine and sulphadoxine-pyrimethamine in uncomplicated falciparum malaria.

A standardised protocol has been developed by World Health Organization (CDS/RBM/2002) to assess the efficacy of common antimalarials in the treatment of clinically manifested infection with uncomplicated P. falciparum malaria for areas with low to moderate transmission. The therapeutic efficacy protocol is based on clinical and parasitological responses of the patients and it has the purpose of determining the practical efficacy of the drug regimen in study areas with the ultimate objective of ascertaining its continued usefulness or the necessity for replacing it in the routine treatment. Present study has been conducted at seven sites--Kathiatali and Simonabasti of District Nowgaon, Assam; Sonapur and Boko of District Kamrup, Assam; Keonjhar Town, Padampur and Basudebpur of District Keonjhar, Orissa. In order to reduce the patient recruitment time, health centre close to well-defined community was identified to conduct the activities at peak malaria season by selecting local pockets and organising mobile clinics. Microscopically confirmed cases of P. falciparum were enrolled according to the criteria for inclusion and exclusion. Treatment with recommended drug was given under supervision and a follow-up schedule at various intervals for 28 days was maintained. In chloroquine (CQ) study areas, wherever patients showed treatment failure, they were treated with second line drug--sulphadoxine-pyrimethamine (SP) combination and then followed-up as per study protocol. It was observed that 30% cases showed treatment failure to CQ in District Nowgaon, where revised drug policy has already been introduced. In Kamrup district, treatment failure with CQ was found to be less than 25%, which denotes the said regimen is still effective. Almost all the patients from Padampur and Basudebpur of District Keonjhar responded to CQ, treatment failure was noticed only in two patients (3%). The antifolate combination found to be fully effective as second line and also as first line wherever revised drug policy has been introduced.

Animals↗
PubMed2004

Comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for uncomplicated Plasmodium falciparum malaria and impact on gametocyte carriage rates in the East Nusatenggara province of Indonesia.

The efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was evaluated in 89 subjects greater than one year of age with uncomplicated P. falciparum malaria in the East Nusatenggara Province of Indonesia. Fever clearance time was longer in the SP group than in the CQ group. However, parasite clearance time was extended in subjects who received CQ compared with those who received SP. Major adverse events were not observed in either group, and no hospitalizations were required during the study. Treatment failure rates at day 28 were 69% for CQ and 8.5% for SP. In both treatment groups, gametocytemia developed during the follow-up period, but was more pronounced in the SP group, peaking at 94% on day 7. Regardless of treatment group, children < 10 years of age had significantly higher treatment failure rates than subjects >/=10 years of age (relative risk = 2.49), suggesting that acquired immunity influenced treatment outcomes in the presence of parasite drug resistance. Although a highly effective alternative to CQ for clearing infection, SP treatment also presented some potential drawbacks (e.g., increased and persistent gametocytemia). Replacement of CQ with SP as a first-line therapy, either alone or in combination with CQ, in those areas of Indonesia with high levels of CQ resistance should significantly improve treatment outcomes, particularly in vulnerable populations lacking clinical immunity. More efficacious and rapidly acting asexual stage treatments are generally associated with increased gametocyte clearance and combination therapy in areas where drug resistance is high or emerging may provide an additional means for reducing transmission.

Adolescent↗
PubMed2004

[In vivo evaluation of sulfadoxine-pyrimethamine efficacy during uncomplicated falciparum malaria in children of Yopougon (Abidjan, Côte d'Ivoire)].

The malaria, deadly parasite infection in its severe form, is widely spread in tropical zone where it rages in an endemic way. The emergence and the extension of Plasmodium resistance contributed to increase the morbidity and the mortality of this pathology in children under 5 years old. Facing the extend of this phenomenon, a monitoring of the expansion of the chemosensitivity proves to be necessary. The goal of the present study was to assess the sulfadoxine-pyrimethamine (S-P) efficacy according to the in vivo test WHO protocol of 14 days-follow-up. Children are treated to the S-P at the rate of 1/2 tablet per 10 kg of body weight in unique dose, then controls are done days 3, 7 and 14. At the end of this work, 179 on 475 subjects were effectively carriers of asexual parasites. So, the general plasmodic index and Plasmodium falciparum rate infection were respectively 37.7% and 100%. Among the 89 children followed until J14, those aged of 13 to 24 months represented 38% of the population of children suffering from Plasmodium malaria, against 7% of those aged between 49 and 59 months. In terms of therapeutic efficacy, 76.4% of adequate clinical and parasitological response (ACR) have been reached against 23.6% of therapeutic failure (TF).

Antimalarials↗
PubMed2004

Comparison of the parasitologic efficacy of amodiaquine and sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria in the Bungoma District of western Kenya.

The efficacy of amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) was assessed in 310 symptomatic children from western Kenya with uncomplicated Plasmodium falciparum malaria. A non-blinded, randomized, 14-day study was performed and parasitologic criteria were used. Of 310 patients included, 238 (77%) completed the study: 120 received AQ and 118 received SP. In those treated with AQ, there were sensitive (S) infections in 107 patients (89.2%, 95% confidence interval [CI] = 82.2, 94.1%), RI resistance in 10 (8.3%, 95% CI = 4.1, 14.8%), RII resistance in 1 (0.8%, 95% CI = 0, 4.6%), and RIII resistance in 2 (1.7%, 95% CI = 0.2, 5.9%). In those treated with SP, there were S infections in 74 patients (62.7%, 95% CI = 53.3, 71.4%), RI resistance in 21 (17.8%, 95% CI = 11.4, 25.9%), RII resistance in 11 (9.3%, 95% CI = 4.7, 16.1%), and RIII resistance in 12 (10.2%, 95% CI = 5.4, 17.1%). Resistance rates were consistently higher in the SP-treated patients (P < 0.001). Resistance to SP in this area has reached such levels that it should no longer be the first-line treatment. Alternative treatment, such as SP plus AQ combination treatment or artemisinin combination treatment, is urgently needed.

Amodiaquine↗
PubMed2004

Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance.

Prior to the 2001 malarial treatment policy change in Tanzania, we conducted trials to assess the efficacy of sulfadoxine-pyrimethamine (SP) and the usefulness of molecular markers in monitoring resistance. A total of 383 uncomplicated Plasmodium falciparum malaria patients (between 6 and 59 months old) were treated with SP and their responses were assessed. Mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes in admission day blood samples were analyzed. Results indicated that 85.6% of the patients showed an adequate clinical response, 9.7% an early treatment failure, and 4.7% a late treatment failure. The quintuple mutant genotype (pfdhfr 51 Ile, 59 Arg, and 108 Asn and pfdhps 437 Gly and 540 Glu) showed an association with treatment outcome (odds ratio = 2.1; 95% confidence interval = 0.94-4.48, P = 0.045). The prevalence of the triple pfdhfr mutant genotype (51 Ile, 59 Arg, and 108 Asn) at a site of high SP resistance (23.6%) was four times higher compared with that observed at sites of moderate SP resistance (6.8-14.4%) (P = 0.000001). The genotype failure index calculated by using this marker was invariable (1.96-2.1) at sites with moderate SP resistance, but varied (3.4) at a site of high SP resistance. In conclusion, our clinical and molecular findings suggest that SP may have a short useful therapeutic life in Tanzania; thus, its adoption as an interim first-line antimalarial drug. The findings also point to the potential of the triple pfdhfr mutant genotype as an early warning tool for increasing SP resistance. These data form the baseline SP efficacy and molecular markers profile in Tanzania prior to the policy change.

Animals↗
PubMed2004

Adherence to antimalarial combination therapy with sulfadoxine-pyrimethamine and artesunate in rural Tanzania.

Artemisinin-containing antimalarial combination therapies are recommended to confront drug-resistant Plasmodium falciparum malaria. Among the questions surrounding whether these complex multidose treatments will be practical is to what extent patients complete the recommended doses. Combination therapy through coadministration of sulfadoxine-pyrimethamine plus artesunate was introduced as a first-line treatment for uncomplicated malaria in one district in Tanzania. Interventions to optimize correct use were also implemented. We observed 453 patient encounters at one health facility and recorded key practices as health workers dispensed the combination. A total of 253 patients were followed-up at 24 or 48 hours. Complete adherence measured at 48 hours reached 75.0%, based on self-report and tablet counts. This is substantially better than reported elsewhere and compares favorably with intervention studies to optimize adherence to chloroquine. Counseling about what to do if a patient vomits appears to have been an independent risk factor for nonadherence.

Adolescent↗
PubMed2004

Principal role of dihydropteroate synthase mutations in mediating resistance to sulfadoxine-pyrimethamine in single-drug and combination therapy of uncomplicated malaria in Uganda.

Antimalarial resistance to sulfadoxine-pyrimethamine (SP) is mediated by mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. However, the relative importance of different mutations is incompletely understood and has not been studied with combination therapy. Samples from 812 patients treated for uncomplicated malaria in Kampala, Uganda were tested for the presence of mutations commonly found in Africa. The dhps Glu-540 mutation was the strongest independent predictor of treatment failure. The dhfr Arg-59 mutation was only predictive of treatment failure in the presence of the dhps Glu-540 mutation. Comparing combination regimens with SP monotherapy, the addition of chloroquine to SP did not improve efficacy, the addition of artesunate lowered the risk of treatment failure only for infections with both the dhfr Arg-59 and dhps Glu-540 mutations, and the addition of amodiaquine lowered this risk for all dhfr/dhps mutation patterns. The dhps Glu-540 mutation played a principal role and the dhfr Arg-59 mutation a secondary role in mediating resistance to SP alone and in combination.

Alleles↗
PubMed2005

Comparison of sulfadoxine-pyrimethamine with and without chloroquine for uncomplicated malaria in Nigeria.

While resistance to older antimalarials is increasingly common, newer antimalarials are still not widely available or affordable in much of Africa. Older antimalarials used in combination might be adequately effective in treating uncomplicated malaria. The objective of this study was to determine whether the combination of sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) is superior to SP alone in the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian patients. We recruited subjects with malaria, defined as the presence of fever and parasitemia > 2,000/microL, from the outpatient department of a Nigerian teaching hospital. We alternately assigned 280 subjects to receive SP with or without CQ. We assessed clinical and parasitologic responses on days 1, 2, 3, 7, and 14. A total of 114 in the SP + CQ group and 116 in the SP group completed the study. By day 3, 97 (75%) in the SP + CQ group and 52 (42%) in the SP group had cleared their parasitemia (P < 0.001); by day 14, 112 (98%) and 67 (58%), respectively, had cleared their parasitemia (P < 0.001). By day 3, 82 (63%) in the SP + CQ group and 20 (16%) in the SP group were symptom free (P < 0.001). When a modified World Health Organization clinical classification system was used, adequate clinical response occurred in 99 (87%) and 61 (53%) of those in the SP + CQ and SP groups, respectively. RI, RII, and RIII resistance to SP + CQ was 7.9%, 3.5%, and 1.8%, respectively, whereas resistance to SP was 23%, 17%, and 5%, respectively. Combined SP + CQ is superior to SP alone for treatment of uncomplicated malaria in Nigerian patients and may prolong the usefulness of these readily available and affordable drugs.

Adolescent↗
PubMed2005

Raising antibodies in chickens against primaquine, pyrimethamine, dapsone, tetracycline, and doxycycline.

Antibodies against primaquine, pyrimethamine, dapsone, tetracycline, and doxycycline were raised in chickens inoculated with each drug conjugated to a rabbit albumin carrier. Antibody titres against drug and carrier were highest during week 6 postinoculation. Affinity purified anti-primaquine antibodies did not recognise other drugs, but affinity purified anti-doxycycline and anti-tetracycline antibodies recognised both tetracycline and doxycycline in addition to primaquine. Primaquine was detected in urine from 6 to 12 hours after ingestion of therapeutic doses of the drug by anti-primaquine antibodies in a competitive ELISA. Affinity purified anti-primaquine antibodies detected primaquine in the cytoplasm and localised in organelles in monocytes that had been incubated with therapeutic concentrations of the drug.

Animals↗
PubMed2005

Therapeutic efficacy of sulfadoxine-pyrimethamine and amodiaquine among children with uncomplicated Plasmodium falciparum malaria in Zanzibar, Tanzania.

The efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was assessed at Kivunge and Micheweni in Zanzibar, Tanzania, in 2001. The main objective was to obtain baseline data after observations of high levels of chloroquine treatment failures. Children (6-59 months) were randomized to receive either drug. At Kivunge, SP and AQ were given to 64 and 63 cases, while for Micheweni, 61 and 70 cases were treated. Main findings were overall high rates (> 90%) of adequate clinical response (ACR) with AQ. A lower ACR was seen in the SP group at Kivunge (87.1%) compared with Micheweni (94.8%). Furthermore, in the ACR group, 16.7% AQ parasitological resistance (RI-RIII) was encountered at Kivunge. Most of the cases of SP parasitological resistance (14.5%; RI/RII) were seen at Micheweni. Notwithstanding this, the overall treatment failure was only 9.2% with SP and 5.5% with AQ. The Zanzibar Ministry of Health has since reviewed its antimalarial drug policy.

Amodiaquine↗