Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYRIMETHAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

The efficacies of artesunate-sulfadoxine-pyrimethamine and artemether-lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in an area of low transmission in central Sudan.

In an efficacy trial of artemisinin-based combination treatments (ACT) in central Sudan, cases of uncomplicated, Plasmodium falciparum malaria were given artesunate-sulfadoxine-pyrimethamine (ASP) or artemether-lumefantrine (AL) as first-line treatment. On enrolment, the 71 patients given ASP were similar to the 72 given AL, apart from having generally lower parasitaemias (geometric mean counts of 4893 nu. 10,215 asexual parasites/microl) and having a lower mean age (15 nu. 23 years). Each patient was treated on days 0, 1 and 2, and all 137 who completed follow-up without further, unscheduled treatment were found aparasitaemic and afebrile from day 2 until the last follow-up, on day 28. No moderate or severe adverse side-effects, clinical failures or parasitological failures were observed among these 137 patients. ACT therefore appear both efficacious and safe for the treatment of uncomplicated malaria in central Sudan.

Adolescent↗

Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan.

BACKGROUND: Early diagnosis and effective treatment with an appropriate drug form the main components of the World Health Organization's strategy to reduce malaria related mortality. The few available drugs might be safeguarded if combined with artesunate. The addition of artesunate to a standard antimalarial treatment substantially reduces treatment failure, recrudescence and gametocyte carriage. METHODS: During late 2004, the efficacy of artesunate (4 mg/kg. day, on days 0-2) plus sulfadoxine-pyrimethamine (25 mg/kg, on day 0) for the treatment of uncomplicated Plasmodium falciparum malaria was investigated in four sentinel areas in Sudan, with different malaria transmission (Damazin, Kassala, Kosti, and Malakal). RESULTS: Two hundreds and sixty-nine patients completed the 28-day follow-up. On day one, 60 (22.3%) patients were febrile and 15 (5.5%) patients were parasitaemic. On day three, all the patients were afebrile and aparasitaemic. While two patients (0.7%, Kassala) showed late Clinical and Parasitological Failures, the rest (99.3%) of the patients demonstrated Adequate Clinical and Parasitological Response. A gametocytaemia were detected during the follow-up in one patient (0.37%, Kassala). Adverse drug effects were detected in 32 (11.9%) patients. CONCLUSION: The study showed that AS plus SP is an effective, safe drug in the treatment of uncomplicated P. falciparum malaria in Sudan.

Adolescent↗

Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug.

INTRODUCTION: Research is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research evidence into drug policy action in Tanzania is often constrained by poor communication between researchers and policy decision-makers, individual perceptions or attitudes towards the drug and hesitation by some policy decision-makers to approve change when they anticipate possible undesirable repercussions should the policy change as proposed. Internationally, literature on the role of researchers on national antimalarial drug policy change is limited. OBJECTIVES: To describe the (a) role of researchers in producing evidence that influenced the Tanzanian government replace chloroquine (CQ) with sulfadoxine-pyrimethamine (SP) as the first-line drug and the challenges faced in convincing policy-makers, general practitioners, pharmaceutical industry and the general public on the need for change (b) challenges ahead before a new drug combination treatment policy is introduced in Tanzania. METHODS: In-depth interviews were held with national-level policy-makers, malaria control programme managers, pharmaceutical officers, general medical practitioners, medical research library and publications officers, university academicians, heads of medical research institutions and district and regional medical officers. Additional data were obtained through a review of malaria drug policy documents and participant observations were also done. RESULTS: In year 2001, the Tanzanian Government officially changed its malaria treatment policy guidelines whereby CQ--the first-line drug for a long time was replaced with SP. This policy decision was supported by research evidence indicating parasite resistance to CQ and clinical CQ treatment failure rates to have reached intolerable levels as compared to SP and amodiaquine (AQ). Research also indicated that since SP was also facing rising resistance trend, the need for a more effective drug was indispensable but for an interim 5-10 year period it was justifiable to recommend SP that was relatively more cost-effective than CQ and AQ. The government launched the policy change considering that studies (ethically approved by the Ministry of Health) on therapeutic efficacy and cost-effectiveness of artemisinin drug combination therapies were underway. Nevertheless, the process of communicating research results and recommendations to policy-making authorities involved critical debates between policy makers and researchers, among the researchers themselves and between the researchers and general practitioners, the speculative media reports on SP side-effects and reservations by the general public concerning the rationale for policy change, when to change, and to which drug of choice. CONCLUSION: Changing national drug policy will remain a sensitive issue that cannot be done overnight. However, to ensure that research findings are recognised and the recommendations emanating from such findings are effectively utilized, a systematic involvement of all the key stakeholders (including policy-makers, drug manufacturers, media, practitioners and the general public) at all stages of research is crucial. It also matters how and when research information is communicated to the stakeholders. Professional organizations such as the East African Network on Malaria Treatment have potential to bring together malaria researchers, policy-makers and other stakeholders in the research-to-drug policy change interface.

Animals↗

Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies.

BACKGROUND: Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up. METHODS: The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6-59 months presenting with raised temperature associated exclusively with P. falciparum (1,000-100,000 parasites per microl) were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO) definition as Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Clinical Failure (LCF) and Late Parasitological Failure (LPF) on day 14 and day 28. RESULTS: Overall 196 (85.2%) of 230 patients had ACPR on day 14 but only 116 (50.9%) on day 28 (57.7% after excluding new infections by parasite genotyping). Altogether 21 (9.1%) and 13 (5.7%) of the 230 patients assessed up to day 14 and 39 (17.1%) and 55 (24.1%) of the 228 followed up to day 28 had clinical and parasitological failure, respectively. CONCLUSION: These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.

Animals↗

Decreased availability of antimalarials in the private sector following the policy change from chloroquine to sulphadoxine-pyrimethamine in the Kilombero Valley, Tanzania.

BACKGROUND: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. METHODS: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. RESULTS: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment. CONCLUSION: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population.

Analgesics, Non-Narcotic↗

Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso.

BACKGROUND: A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age. METHODS: During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol, was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria. RESULTS: PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits. CONCLUSION: While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use.

Adolescent↗

Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.

BACKGROUND: Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. METHODS: The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. RESULTS: Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. CONCLUSION: In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries.

Animals↗

A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan.

BACKGROUND: Artemisinin-based combination therapy is increasingly being adopted as first-line antimalarial therapy. The choice of appropriate therapy depends on efficacy, cost, side effects, and simplicity of administration. METHODS: the efficacy of fixed co-formulated (f) artesunate-sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS: seventy-three patients (39 and 34 in the fixed and the loose regimen of AS+SMP respectively) completed the 28-days of follow-up. On day 3; all patients in both groups were a parasitaemic but one patient in the fixed group of AS+SMP f was still febrile. Polymerase chain reaction genotyping adjusted cure rates on day 28 were 92.3% and 97.1% (P > 0.05) for the fixed and loose combination of AS+SMP respectively. Three (4.1%) patients (one in the fixed and two patients in the loose group of AS+SMP) in the study suffered drug-related adverse effects. Gametocytaemia was not detected during follow-up in any of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice.

Adult↗

How sulfadoxine-pyrimethamine (SP) was perceived in some rural communities after phasing out chloroquine (CQ) as a first-line drug for uncomplicated malaria in Tanzania: lessons to learn towards moving from monotherapy to fixed combination therapy.

Malaria is a leading cause of death in Sub-Saharan Africa. Tanzania changed its malaria treatment policy from chloroquine (CQ) to Sulphadoxine-Pyrimethamine (SP) as first line drug in August 2001. We wanted to assess the perception and behaviour about SP after phasing out chloroquine which was very popular, cheap, available, and was preferred by many people for self-medication in homes as it was considered to have minimal side effects. Focus Group Discussions (FGDs) were carried out after one year of the anti-malarial drug treatment policy change in the country. The FGD themes were on malaria for under-five children and other age groups, anti-malarial drug use through self-medications, specific experiences people had about SP drug for both mothers/guardians, men in the communities and health workers. A total of twelve FGDs were performed with mothers/guardians, men and health workers in the selected public health care facilities in the district. In the FGDs people feared adverse reactions from SP; its slow ability of reducing fever and self-treatment in this case was less reported from the mothers/guardians groups. However, SP was reported by health workers to be administered using the direct observation approach under supervision in their health care facilities. This was done in order to increase compliance as there were worries that some mothers were throwing away the drug if they were instructed by health workers to go and administer SP to their sick children at home. Based on this information, it is obvious that fear and negative perceptions about SP drug was common in the study setting. As evidence of this, there was less reported home-stocking and self-medication in the discussions for this particular recommended new first-line anti-malarial. The public has demonstrated a lack of confidence in SP. Furthermore, some health workers expressed obvious fear and negative perceptions towards the drug despite the fact that some FGDs with health workers considered the drug to be good and effective against malaria. Such negative perception towards SP highlights the need to start earlier sensitization and educational campaigns to the rural communities for a new drug program to ensure its success. Messages should clearly state what should be expected from the new drug (Coartem), before its introduction. This is important especially as Tanzania is expected to move towards the expensive but efficacious and effective fixed-combination (Coartem) anti-malarial therapy early next year (2006).

Antimalarials↗

Effects of folic acid and pyrimethamine, a dihydrofolate reductase inhibitor, on intestinal absorption of folates in rats.

Oral co-administration of folic acid (pteroylglutamic acid, PteGlu) potentiates the decrease of plasma 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) concentration induced by pyrimethamine (PYR) in rats. To clarify the mechanisms of this potentiated decrease, we examined the effects of PteGlu and PYR on intestinal absorption of folates in rat jejunum loops, because plasma 5-CH3-H4PteGlu concentration is maintained by enterohepatic circulation of folates. The intestinal absorption of 5-[14C]CH3-H4PteGlu was inhibited by PteGlu, but not by PYR. The absorption of [3H]PteGlu was inhibited by reduced folates that exist in bile. These findings indicate that PteGlu competes with the bile reduced folates for the intestinal transport system. The bile secretion of reduced folates was also examined to observe the conversion of absorbed PteGlu to reduced folates in the liver in the presence of PYR. The bile secretion of reduced folates increased drastically after the administration of PteGlu alone, but not after the administration of PteGlu with PYR. These facts suggest that the absorbed PteGlu was not converted to reduced folates in the liver due to PYR. In conclusion, the potentiated decrease of plasma 5-CH3-H4PteGlu concentration must have resulted from a combination of the following two factors: the inhibition of reabsorption of bile reduced folates by PteGlu and the inhibition of PteGlu conversion to reduced folates in the liver by PYR.

Animals↗

Experimental induction of splayleg in piglets by pyrimethamine.

Dietary administration of 3.6 mg/kg (BW)/day of pyrimethamine (PYR) to the 10 pregnant Goettingen minipigs for the 1st quarter (during days 11 to 16) or the 2nd quarter (during days 17 to 22) of the organogenetic period elicited the congenital splayleg (CSL) in 20 out of 27 live newborns. Only a splayleg piglet out of 18 was found in the control group. The incidence of stillbirth was higher in the PYR groups than the control group, but no major external malformation was observed in the piglets of the PYR groups. Histological and biochemical examinations of the muscles from the hindleg, foreleg and truncus were carried out. The severity of myofibrillar hypoplasia depended on neither CSL symptoms nor PYR administration. Although a significant decrease of protein content of the muscles was observed in the piglets of the PYR groups, the mechanism underlying the pathogenesis of induced splayleg was obscure.

Animals↗

Sulfadiazine and pyrimethamine in the postnatal treatment of congenital toxoplasmosis: what are the options?

Pre- and neonatal screening for congenital toxoplasmosis rests upon the assumption that treatment is beneficial on either acute symptoms or in preventing later reactivation. Postpartum treatment of congenital toxoplasmosis with sulfadiazine and pyrimethamine has remained almost unchanged for 50 years. More recently, sulfadiazine has been substituted by sulfadoxine, which has a much longer half-life and provides a basis for a dose schedule with higher compliance. Newer drugs with potential effects against Toxoplasma gondii, such as azithromycin, atovaquone and clindamycin, require further evaluation in animal models and human studies. No randomized controlled trials have ever been conducted. The available studies are either observational studies of groups of referred patients or observational studies with historical controls accrued over many years, often decades. Pre- and neonatal screening for congenital toxoplasmosis is performed on more than two million pregnant women every year in Europe, North and South America at the estimated cost of more than 500 million annually. The benefit needs to be documented by a prospective, placebo-controlled randomized study, which needs to be organized and financed by the countries performing nationwide, universal screening programs.

Humans↗

[The evaluation of the efficacy of azithromycin and pyrimethamine used alone or in combination in the treatment of an experimental infection in mice by Toxoplasma gondii].

The efficacy of azithromycin and pyrimethamine in experimental infection of mice with Toxoplasma gondii was tested. Daily dosages of 200 mg/kg and 12.5 mg/kg, respectively, were given orally over a period of ten days. The medications were administered in combination or separately. The combined use of the drugs yielded better results, and a similar investigation using a cystogenic strain of the parasite will be conducted in a future study.

Animals↗

Effects of antifolates--co-trimoxazole and pyrimethamine-sulfadoxine--on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria.

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T), another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS--but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrollment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

Acute Disease↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 21). Comparison of the effects of 2- and 4-weeks pyrimethamine treatment in rats.

Pyrimethamine (PYR), clinically used as an antimalarial or antiparasitic agent, is known to exert testicular toxicity in rats on oral administration for 8 weeks. This study was performed to examine whether 2-weeks daily repeated doses of PYR might induce detectable toxicity on the male reproductive organs in rats. PYR was orally administered to Slc:SD male rats at doses of 12.5, 25 or 50 mg/kg for 2 weeks, or 6.25, 12.5 or 25 mg/kg for 4 weeks. No effects were seen in any group on physical examination and body weight measurement. Gross findings in autopsy exhibited no abnormalities in any of the animals. There were no meaningful changes in the weights of reproductive organs, or in the number and activity of sperm in the epididymides. Loss and degenerative changes of pachytene spermatocytes in stages I to III seminiferous tubules were observed in the rats given 50 mg/kg PYR for 2 weeks. From the results obtained, it is concluded that 2-weeks repeated dosing with PYR is sufficient to detect toxicity on male reproductive organs in rats using histopathological examination.

Administration, Oral↗

Quinine alone versus quinine plus a pyrimethamine-sulfadoxine combination in the treatment of Plasmodium faliciparum cerebral malaria.

Fifty-two patients with severe chloroquine resistant Plasmodium falciparum malaria were treated in a randomized double blind study with either quinine and a single dose of pyrimethamine-sulfadoxine (Fansidar) or quinine alone. Although no statistically significant differences were observed, the 25 patients who received both drugs responded faster and had a more favorable outcome (no deaths) when compared to the 27 who received quinine alone (2 deaths).

Clinical Trials as Topic↗