Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine: An in silico pharmacological model

Objective: To explore the efficacy of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine and pyrimethamine (SP) against sensitive parasites. Methods: A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen, currently recommended three-dose regimen and 4, 6, 8-weekly regimens with specific focus on the impact of various non-adherence patterns in multiple transmission settings. Results: The effectiveness of the recommended three-dose regimen is high in all the transmission intensities, i.e. >99%, 98% and 92% in low, moderate and high transmission intensities respectively. The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women (>99%) regardless of transmission intensity. However, 8 weekly interval dose schedules were found to have 71% and 86% protective efficacies in high and moderate transmission areas, respectively. It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed. Conclusions: The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions. However, it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed. Adherence to the recommended IPTp-SP schedules is recommended.

Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine: An in silico pharmacological model

Objective: To explore the efficacy of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine and pyrimethamine (SP) against sensitive parasites. Methods: A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen, currently recommended three-dose regimen and 4, 6, 8-weekly regimens with specific focus on the impact of various non-adherence patterns in multiple transmission settings. Results: The effectiveness of the recommended three-dose regimen is high in all the transmission intensities, i.e. >99%, 98% and 92% in low, moderate and high transmission intensities respectively. The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women (>99%) regardless of transmission intensity. However, 8 weekly interval dose schedules were found to have 71% and 86% protective efficacies in high and moderate transmission areas, respectively. It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed. Conclusions: The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions. However, it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed. Adherence to the recommended IPTp-SP schedules is recommended.

Progress of researches on genes associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax / 中国血吸虫病防治杂志

Malaria is a parasitic disease which threatens human life and health seriously. Sulfadoxine-pyrimethamine (SP) has been recommended for intermittent preventive treatment of malaria in children and pregnant women, and also used as a compound component of artemisinin based therapy. The mechanisms of SP resistance in P. falciparum involve point mutations in the genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), and the drug pressure can also lead to the mutations in the two genes of P. vivax. To provide the information for the formulation of anti-malarial strategies, this article reviews the discovery, application, effect of SP, and the resistance mechanism and research progress of the related genes in P. vivax.

Progress of researches on genes associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax / 中国血吸虫病防治杂志

Malaria is a parasitic disease which threatens human life and health seriously. Sulfadoxine-pyrimethamine (SP) has been recommended for intermittent preventive treatment of malaria in children and pregnant women, and also used as a compound component of artemisinin based therapy. The mechanisms of SP resistance in P. falciparum involve point mutations in the genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), and the drug pressure can also lead to the mutations in the two genes of P. vivax. To provide the information for the formulation of anti-malarial strategies, this article reviews the discovery, application, effect of SP, and the resistance mechanism and research progress of the related genes in P. vivax.

Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal

Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required.

Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia / Mutant alleles associated to chloroquine and sulfadoxine-pyrimethanime resistance in Plasmodium falciparum of the Ecuador-Peru and Ecuador-Colombia borders

Se evaluó la frecuencia de mutaciones en los genes pfCRT y DHFR/DHPS del Plasmodium falciparum asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en 83 cepas provenientes de los distritos Esmeralda y Machala ubicados en las fronteras entre Ecuador-Perú y Ecuador-Colombia durante el año 2002. Se empleó la reacción en cadena de polimerasa (PCR) convencional y sus variantes. El gen pfCRT presentó más de 90% de muestras mutantes en Esmeralda y Machala. Para el gen DHFR, el 90% de las cepas fueron muestras mutantes en Esmeralda, tres fueron mutaciones dobles y una triple; en Machala se encontró 25% de formas mutantes simples y 75% de formas mixtas (formas silvestres/mutantes). En conclusión, la resistencia a cloroquina se ha fijado en las cepas portadoras de la mutación K76T pfCRT, mientras que la impronta genética a la resistencia a pirimetamina está en evolución, principalmente en el distrito de Esmeralda.

The frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda.

Assessment of efficacy and safety of artesunate plus sulfadoxine pyrimethamine combination for treatment of uncomplicated falciparum malaria.

Background: Resistance of Plasmodium falciparum to antimalarial drugs is common in India. World Health Organization (WHO) recommends artemisinin based combination therapy (ACT) to counter the development of resistance in P. falciparum. WHO recommends that ideally antimalarial drug treatment policy or guidelines should be reviewed regularly and updated at least once every 24 months. In consideration to the above recommendation, we planned to conduct the following study. The objective was to determine the efficacy and safety of artesunate + sulphadoxine pyrimethamine (AS + SP) in patients with uncomplicated P. falciparum malaria. Methods: The study included 60 patients of uncomplicated P. falciparum. Each patient received AS + SP as per WHO guidelines. Diagnosis was confirmed by peripheral blood film. All patients were followed up on days 1, 3, 14, and 28 for detailed clinical and parasitological examination. Results: Of a total 60 patients, 55 patients were followed up for 28 days. Remaining 5 patients were lost in follow up. As per protocol analysis, 91% (50) of patients had demonstrated adequate clinical and parasitological response. Remaining 9% (5) had treatment failure in which 5.5% (3) had late parasitological failure and 3.6% (2) had late clinical failure. In our study, mean parasite clearance time was 45.2 ± 4.2 hrs. Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance.

Mutaciones puntuales en los genes dhfr y dhps de Plasmodium falciparum de tres regiones endémicas para malaria en Colombia / Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum from three endemic malaria regions in Colombia

Introducción. La acumulación progresiva de mutaciones en los genes dhfr y dhps lleva al parásito Plasmodium falciparum a evadir la acción de la sulfadoxina-pirimetamina, situación que aumenta el nivel de resistencia del parásito a estos medicamentos y conlleva a la aparición de fallas del tratamiento. Objetivos. Determinar la frecuencia de mutaciones en los genes dhfr y dhps de P. falciparum asociadas con resistencia a sulfadoxina-pirimetamina, en muestras de pacientes de tres zonas endémicas de Colombia: La Carpa, Guaviare; Casuarito, Vichada; Tierralta y Puerto Libertador, Córdoba. Materiales y métodos. Se incluyeron 40 muestras de pacientes con malaria no complicada por P. falciparum. Los alelos 108, 59 y 164 del gen dhfr se analizaron mediante PCR específica de alelo y los alelos 51 del gen dhfr y 436, 437 y 540 del gen dhps por PCR y restricción enzimática. Resultados. En el gen dhfr encontramos en todas las muestras las mutaciones asparagina 108 e isoleucina 51. No se detectaron alelos mutantes en los codones 59 y 164 del gen dhfr, ni en el codón 436 del gen dhps. La mutación glicina 437 estuvo presente en 36 muestras y el alelo silvestre alanina en tres de Tierralta y una de La Carpa. La mutación ácido glutámico 540 sólo se halló en Casuarito. Conclusiones. En las poblaciones de P. falciparum analizadas prevalecen los alelos asparagina 108, isoleucina 51 y glicina 437, lo que indica un efecto acumulativo de mutaciones y la necesidad de vigilar la aparición de nuevos alelos mutantes que puedan conducir a la pérdida total de la eficacia de la sulfadoxina-pirimetamina.

Introduction. Plasmodium falciparum has the ability to counter the antiparasitic activity of sulphadoxine-pyrimethamine by progressively accumulating mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. These mutations gradually increase the resistance of the parasite to these drugs and lead to therapeutic failure. Objectives. To determine the frequency of mutations associated with resistance to sulphadoxine and pyrimethamine in the dhfr and dhps genes of P. falciparum in samples from patients in three endemic zones of Colombia -La Carpa, Guaviare; Casuarito, Vichada; and Tierralta and Puerto Libertador, Córdoba. Materials and methods. Forty samples were selected from patients with uncomplicated P. falciparum malaria. The frequency profiles of the 108, 59 and 164 alleles of dhfr were obtained by application of an allele-specific polymerase chain reaction, whereas the other alleles (alleles 51 of the dhfr gene and 436, 437 and 540 of dhps) were obtained by polymerase chain reaction and restriction fragment length polymorphism. Results. The 108N and 51I mutations in the dhfr gene were found in all of the 40 samples. No mutant alleles were found in the 59 and 164 codons of the dhfr gene, or in the 436 codon of the dhps gene. The 437G mutation was observed in 36 samples and the wild-type allele was present in 3 from Tierralta and one from La Carpa. The 540E mutation was only detected in two samples from Casuarito. Conclusions. The 108N, 51I and 437G mutations prevail in the populations of P. falciparum, indicating a cumulative effect of mutations and the need to continue surveillance for other changes which can lead to the total loss of the efficacy of sulphadoxine-pyrimethamine.

Seguridad hepatica y hematica de la sulfadoxina-pirimetamina en el tratamiento de malaria por Plasmodium falciparum no complicada / Liver and haematological safety of sulfadoxine-pyrimethamine treatment in non-complicated falciparum malaria

Introducción: Entre los farmacos ampliamente usados en la actualidad para el tratamiento de la malaria por Plasmodium falciparum se encuentra la sulfadoxina-pirimetamina, que es comúnmente administrada en combinación con otros medicamentos. Los eventos adversos informados se han asociado con altas dosis, uso como profilactico o en personas con hipersensibilidad a las sulfas. Objetivo: Evaluar la toxicidad hepßtica y hematica de la sulfadoxina-pirimetamina (SP) administrada en dosis y tiempos terapéuticos para la malaria por P. falciparum no complicada.Metodología: Como parte de un estudio con dise±o experimental, con determinación abierta del efecto, se hizo evaluación hematica y hepatica a 17 personas tratadas con SP. En Turbo (Antioquia, Colombia), los pacientes se captaron consecutivamente y se siguieron por 10 días. Resultados: Las variables hepßticas y hematicas estuvieron alteradas durante el cuadro malarico antes del tratamiento y se normalizaron al poco tiempo del inicio del mismo (1-5 días), que fue eficaz en 100% de los pacientes (medido el día 10). La normalidad de todas las variables en los días 5 y 10 (fase postratamiento) sugiere la ausencia de efectos tóxicos imputables al medicamento. Los efectos adversos fueron pocos y leves y desaparecieron en el control del día 10. Conclusiones: La SP no mostró eventos adversos, toxicidad hepatica ni hemßtica usada en la dosis y el tiempo definidos para el tratamiento de la malaria por P. falciparum sin complicaciones.

Introduction: Sulfadoxine-pyrimethamine is an antimalarial used currently in worldwide for non-complicated falciparum malaria. This drug is administrated in combination with other ones. Previously adverse events had been reported with high doses, used in malaria prophylaxis and patients with hypersensibility to sulfas. Objetive: To evaluate hepatic and haematic toxicity of treatment with sulfadoxine-pyrimethamine (SP) in non-complicated falciparum malaria. Methodology: This was a non-blinded experimental design. In Turbo (Antioquia, Colombia), 17 subjects treated with SP were evaluated for liver and hematic function. All individual were followed for 10 days. Results: Before treatment, liver and hematic function tests were slight altedered. Hematic and liver variables returned to physiological levels after treatment. Treatment had 100% efficacy. All tests were within normal levels throughout the following period (postreatment); this suggests absence of toxic effects associates with treatment. Adverse effects were few and slight, and disappeared on day-10.Conclusions: When is used in time and dose for treatment of non-complicated falciparum malaria, SP neither increased adverse events nor hepatic or hematic toxicity.

Efficacy of chloroquine, chloroquine plus sulphadoxine-pyrimethamine, and amodiaquine for treatment of vivax malaria in Bangka island, Indonesia: a randomized trial.

Plasmodium vivax malaria resistant to chloroquine is alarming in Indonesia and has been also reported in other countries. An alternative drug is needed. The study was a prospective evaluation and a comparative study of the therapeutic efficacy of chloroquine 25 mg base/kg bw for 3 days (CQ3, n=75), CQ3 plus sulfadoxine-pyrimethamine based on pyrimethamine dosage of 1.25 mg/kg bw single dose (SP1) [CQ3+SP1, n=84] and amodiaquine 25 mg base/kg bw for 3 days (AQ3, n=83) in symptomatic vivax malaria patients in children and adults. The new version of 2001 WHO test system was used in this study. PCR for genotyping was also done to validate and confirm the treatment outcomes. The therapeutic efficacy of CQ3, CQ3+SP1 and AQ3 on day 14 were very high (94.4%, 97.4% and 98.8%), and dropped on day 28 (81.7%, 87.2% and 96.2% by evaluable analysis; 78.9%. 82.0% and 92.5% after confirmation with PCR; and 74.7%, 78.0% and 90.2% by intention to treat analysis). Most of the ACPR cases (>96%) showed hematological recovery. Gametocyte carriages were documented on day 7 (2.9%, 1.3% and 1.2%), day 14 (4.3%, 1.3% and 1.2%) and day 28 (6.6%, 4.2% and none) in CQ3, CQ3+SP1 and AQ3 groups. Of these 3 regimens, AQ3 showed a better therapeutic efficacy than CQ3 and combined CQ3+SP1 by day 28. Introducing primaquine at the beginning of treatment day or giving a radical treatment in vivax malaria may improve the cure rate.

Resistência à sulfadoxina-pirimetamina em Maputo, Moçambique: presença de mutações nos genes dhfr e dhps do Plasmodium falciparum / Sulfadoxine-pyrimethamine resistance in Maputo, Mozambique: presence of mutations in the dhfr and dhps genes of Plasmodium falciparum

Foram analisadas a freqüência e distribuição de mutações nos genes dihidrofolato redutase e dihidropteroato sintetase do Plasmodium falciparum, usando a metodologia de reação em cadeia da polimerase e polimorfismos de hidrólise por enzimas de restrição, em amostras de sangue infectado proveniente de crianças moçambicanas, residentes em Maputo. A análise foi feita antes e 7 dias após o tratamento com sulfadoxina-pirimetamina (S/P). Os resultados mostraram a ocorrência de mutações pontuais nos genes estudados e a presença de combinações de três alelos em dhfr (51Ile, 59Arg e 108Asn) e do quintúplo mutante (dhfr 51Ile, 59Arg, 108Asn e dhps 437Gly, 540Glu), ambas situações associadas à falha terapêutica no sétimo dia após tratamento com S/P. Esses achados mostram a importância de se estudar a resistência à S/P em Moçambique, e como os marcadores moleculares de resistência aos antimaláricos podem fornecer dados importantes para a política nacional de controlo da malária.

The frequency and distribution of mutations in Plasmodium falciparum, dihydrofolate reductase and dihydropteroate synthase genes were analyzed, using the polymerase chain reaction and restriction fragment length polymorphism methodology, in infected blood samples from Mozambican children living in Maputo, before and seven days after treatment with sulfadoxine/pyrimethamine (S/P). The results showed the occurrence of point mutations in the genes studied and the presence of combinations of three alleles in dhfr (51Ile, 59Arg and 108Asn) and "quintuple" mutant (dhfr 51Ile, 59Arg, 108Asn and dhps 437Gly, 540Glu). Both of these situations were associated with seven-day therapeutic failure, following treatment with S/P. These findings show the importance of studying S/P resistance in Mozambique, and how molecular markers for antimalarial resistance can provide important data for national malaria control policy.

Malaria in Jayapura District, Papua Province, Indonesia and resistance to sulfadoxine-pyrimethamine.

Malaria poses a major public health problem in Papua. The rapid spread of drug-resistant parasites and deterioration of the malaria control program following the monetary crisis and civil strife in the late 90’es have worsened the malaria situation in many areas of Papua. To re-assess the current magnitude of malaria problem, a malariometric survey was conducted in three sub-districts of Jayapura District, as well as antimalarial drug sensitivity test using sulfadoxine-pyrimethamine (SP) at the outpatient clinics of Abepura General Hospital (RSU), Hamadi Primary Health Center and Panti Asuhan Katolik Clinics, Sentani, Jayapura District, Papua Province. Screening of 543 subjects in three sub-districts revealed 185 malaria positive subjects, either with P. falciparum, P. vivax or mixed of the two species. All of the malaria cases were asymptomatic. In the SP drug sensitivity test, of the 56 subjects involved, 32 were classified as early treatment failure and two subjects were classified as late treatment failure. The remaining 22 subjects were classified as adequate clinical and parasitological response (ACPR). These results indicated that the surveyed area has a high malaria prevalence and treatment failure to SP and therefore alert to the need of deploying new antimalarial regiment that suit the remote setting.

Efficacy of existing antimalarial drugs for uncomplicated malaria in Timika, Papua, Indonesia.

Chloroquine resistant malaria is a serious problem in Indonesia particularly in Papua. A trial of the existing antimalarial drugs was conducted in Timika, Papua. The objective of the study was to determine the efficacy of cloroquine (CQ) + sulfadoxine-pyrimethamine (SP). Patients with uncomplicated malaria due to Plasmodium falciparum, P. vivax, P. ovale or P. malariae were enrolled and treated with supervised CQ+SP (P. falciparum) or CQ (non-P. falciparum). Patients were followed for 28-42 days. Patients failing therapy were retreated with unsupervised quinine±doxycycline. 207 patients were enrolled in the study (88 P. falciparum, 40 P. vivax, 15 mixed infections, 50 P. malariae and 14 P. ovale). Early treatment failures occurred in 4 of 86 (5%) patients with falciparum malaria, 6 of 37 (16%) patients with vivax malaria and none of those with P. ovale or P. malariae infections. The failure rate by day 28 for P. vivax was 22 of 30 (73%) patients, with all recurrences occurring in the presence of plasma chloroquine concentration above the minimum effective concentration (MEC>15ng/ml). After correcting for reinfections the day 42 recrudescence rate for falciparum malaria was 48% [95%CI:31-65] and in 61% of cases this was in the presence of chloroquine levels above 30 ng/ml. Retreatment with unsupervised quinine±doxycycline resulted in further recurrence of malaria in 48% [95%CI:31-65] of P. falciparum infections and 70% [95%CI:37-100] of P. vivax infections. None of the patients with P. ovale or P. malariae had treatment failures within 28 days. There is a high prevalence of antimalarial drug resistance of P. falciparum and P. vivax to the existing antimalarial drugs. However chloroquine retains adequate efficacy against P. ovale and P. malariae in Papua.

El tratamiento amodiaquina-sulfadoxinapirimetamina tiene eficacia del 98 por ciento para la malaria falciparum no complicada (Antioquia, Colombia; 2003) / Treatment with amodiaquine-sulfadoxine-pyrimethamine is 98 per cent effective against uncomplicated falciparum malaria

Antecedentes: la combinación amodiaquina (AQ) con sulfadoxinapirimetamina (SP) es el tratamiento de primera elección para la malaria falciparum no complicada (MFNC) en el departamento de Antioquia desde 1985 y en Colombia desde 2000. Objetivo: medir la frecuencia de falla terapéutica de AQ-SP en pacientes con MFNC, residentes en Turbo (zona de Urabá) y en El Bagre (zona del Bajo Cauca), Antioquia. Metodología: este estudio hace parte de uno mayor, que tiene diseño experimental balanceado, con ocho grupos; muestra de tamaño 50 en cada municipio, diseñada con criterios estadísticos y epidemiológicos; tratamiento aplicado en orden de llegada de los pacientes y según los esquemas usuales; seguimiento por 21 días; evaluación no ciega del efecto con el protocolo 1998 de la Organización Mundial de la Salud OMS. Resultados: se evaluaron 90 pacientes con MFNC; la falla terapéutica fue 2.2 por ciento: un caso precoz y otro tardío. El tratamiento fue bien tolerado. La parasitemia asexual se eliminó totalmente en 90 por ciento en los tres días de tratamiento (otro 10 por ciento tenía 40-80 parásitos/?L, que no es falla) y en 100 por ciento antes de 7 días de haber iniciado el tratamiento. AQ-SP mostró total capacidad de eliminar la fiebre: 100 por ciento afebriles el día 3. En los pacientes con gametocitos la cantidad de estos creció entre los días 0 y 7 y decreció luego hasta el día 21, cuando 52 por ciento los presentaban (promedio: 63 gametocitos/?L), pero no se evaluaron la viabilidad ni la fertilidad de tales gametocitos.Conclusión: el tratamiento de la MFNC con AQ-SP es altamente eficaz y debe mantenerse como la primera opción terapéutica, reforzada su eficacia antimalárica por el bajo costo, la buena tolerancia y la escasez y levedad de los efectos adversos imputables al tratamiento. AUT

Abstract Background: The combination of amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) is the firstchoice treatment for uncomplicated falciparum malaria (UCFM) in Antioquia (northwestern Colombia) since 1985 and in the country at large, since 2000. Objective: To measure the frequency of therapeutic failure of AQ-SP in patients with UCFM, residents of Turbo (Urabá zone) and El Bagre (Bajo Cauca zone) of Antioquia in northwestern Colombia. Methodology: This study is part of a larger one which has balanced design, with eight groups; the sample size in each municipality was 50 patients and it was obtained with statistical and epidemiological criteria; treatment was administered in the order of admission of patients according to the usual schedule; follow-up was done during 21 days; not-blind evaluation of the effect with the 1998 WHO protocol. Results: Ninety patients with UCFM were evaluated; therapeutic failure frequency was 2%; that is 2 cases, one early and one late. Conclusion: Treatment of UCFM with AQ-SP is highly effective and should be maintained as the first therapeutic choice; its effectiveness is reinforced by its low cost and good tolerance; also by the fact that undesirable effects attributable to the treatment are few and mild

Timothy M.E. Davis, Janet Cox - Singh, Sean Hewitt. Treatment of uncomplicated falciparum malaria in Southern Vietnam: can chloroquine or sulfadoxine - pyrimethamine be introduced in combination with artesunate

The efficacy of chloroquine or sulfadoxine-pyrimethamine given combined with artesunate was assessed in Vietnamese patients with uncomplicated falciparum malaria from 2 Southern provinces, where there was in vitro evidence that the sensitivity of the parasite to conventional antimalarial therapies had returned in the absence of drug pressure, from October to December of 2000. In Dak Lak province, 57 patients (mean age 9.6 years) were randomized to artesunate-chloroquine (group 1) or artesunate-sulfadoxine/pyrimethamine (group 2). In Binh Phuoc province, 66 patients, who have just migrated in period of 1-7 years (mean age 24.2 years) were assessed with the 2 regimens. The results of 28 days in vivo response were over 96% and lower 52% of Dak Lak and Binh Phuoc respectively. PCR evidence of cure closely paralleled the in vivo results. The successful reintroduction of chloroquine and sulfadoxine-pyrimethamine as artemisinin partner drugs depends heavily on epidemiological and parasite factors