Monitoring susceptibility to sulfadoxine-pyrimethamine among cases of uncomplicated, Plasmodium falciparum malaria in Saharevo, Madagascar.

Intermittent preventive treatment (IPT) of pregnant women with sulfadoxine-pyrimethamine (SP) is being considered as a routine practice in Madagascar, mainly to decrease the risks of malaria-associated severe anaemia in the women, and of low birthweight in their babies. There is, however, relatively little information available on the efficacy of SP when used, in Madagascar, to treat cases of Plasmodium falciparum malaria. In a preliminary study, carried out in 2003 in the village of Saharevo, 36 uncomplicated cases were each treated with a standard dose of SP and with paracetamol and then followed up for 28 days. No case of therapeutic failure occurred and all the asexual parasitaemias cleared by day 3. It therefore appears that SP is effective against P. falciparum in Saharevo (and probably in the whole, rural district of Moramanga in which the village lies). This is an encouraging observation to make before IPT is initiated throughout the country.

[Assessment of sulfadoxine-pyriméthamine (Fansidar, Paludar) efficacy in patients with uncomplicated malaria in Madagascar: preliminary study to propose a simplified study protocol]. / Surveillance de l'efficacité de sulfadoxine-pyriméthamine (Fansidar, Paludar) pour le traitement de l'accès palustre à Madagascar: proposition d'un protocole simplifié.

To alleviate the insufficient number of experienced medical teams invited to and accepting to monitor the effectiveness of drugs prescribed to patients with a diagnosis of uncomplicated malaria and to insure the surveillance of the susceptibility of P. falciparum to current antimalarials used in Madagascar, there is a need to draw a feasible study protocol carefully discussed with them. We carried out a preliminary study in two rural areas and assessed the efficacy of sulfadoxine-pyrimethamine (SP) for curing uncomplicated P. falciparum malaria, with a simplified protocol based on the principle of observational study. A single dose of SP was given on day 0 with paracetamol. The persons to whom the drugs were administered accepted two other interventions of one member of the medical teams on day 14 and day 28. Nineteen patients, 3-63 years old, fulfilled the follow-up. The efficacy of this combination was noted for the 19 persons. Our results show that P. falciparum strains are susceptible to SP. Since SP will be used in intermittent preventive treatment in pregnant women in Madagascar, one way to delay the occurrence of SP resistant parasites will be (a) to avoid massive use of SP for the non pregnant persons and (b) to monitor susceptibility of P. falciparum to SP as part of pilot studies using standard WHO protocol (which is not really easy for most of the peripheral health facilities--with the follow-up procedures with clinical examination and parasitological control at Days 0, 1, 2, 3, 7, 14, 21 and 28), and routinely with simplified protocol such as the analytical observational study illustrated in this present study. Limit and advantage of observational study are discussed.

[Drug resistance of Plasmodium falciparum in coastal regions of Madagascar]. / Chimiorésistance de Plasmodium falciparum sur les regions côtierès malgaches.

Chloroquine is still the drug of choice for first-line treatment of uncomplicated malaria in Madagascar. However development and spread of chloroquine-resistance could compromise this therapeutic strategy in the future. The purpose of this 1997 study was to compare the efficacy of combined treatment using sulfadoxine and pyrimethamine and single-agent treatment using chloroquine for management of uncomplicated malaria. Study data were collected at four sites in coastal areas of Madagascar where transmission of malaria is perennial. Prevalence of malaria ranged from 15 p. 100 to 22 p. 100 in school children and from 24 p. 100 to 72 p. 100 in outpatient consulting spontaneously at community health centers. All four Plasmodium species affecting man were identified. Plasmodium falciparum was involved in 83 p. 100 of cases. In vivo testing of the susceptibility of Plasmodium falciparum to chloroquine was performed in 149 patients according to the standard simplified 7-day protocol of the WHO. The 35 tests in school children demonstrated no evidence of resistance. However type R1 + R2 resistance was noted in 17 of the 114 tests performed on outpatients, i.e. 14.9 p. 100. In vitro testing demonstrated chloroquine resistance in four of the 90 specimens tested, i.e. 4.4 p. 100. With regard to combined sulfadoxine/pyrimethamine treatment, 45 of 46 in vivo tests in outpatients showed no evidence of resistance. Combination treatment was more effective than single-agent treatment (p = 0.02) and could offer an effective alternative for future use.

[Chemosensitivity of Plasmodium falciparum in Sainte Marie island, east coast of Madagascar: in vivo and in vitro studies]. / Sensibilité de Plasmodium falciparum dans l'île de Sainte Marie, côte Est de Madagascar: études in vivo et in vitro.

In order to document the evolution of the chemoresistance of Plasmodium falciparum to chloroquine in Madagascar, a study was carried out in Sainte-Marie island located at 6 km on the eastern border of the country. Symptomatic malaria patients who satisfied criteria for resistance testing, were recruited by a process of passive case detection at two clinics. These patients were enrolled in a sensitivity 14-day in vivo test for uncomplicated P. falciparum malaria attacks. All subjects received a supervised therapeutic regimen of chloroquine (25 mg base/kg over 3 days). Parasitemia and symptoms were monitored for 14 days. 62 (93.9%) out of the 66 enrolled patients completed the 14-day follow-up. A total of 50 of 62 patients (80.6%) presented an adequate clinical response. Early and late treatment failures were observed in 3 (4.8%) and 9 (14.5%) patients respectively. Failure therapeutic treatments treated with sulfadoxine-pyrimethamine were successful. Chloroquine remains effective in the treatment of malaria due to P. falciparum and therefore its choice as a first line drug remains justified. Likewise, guidelines for the use of sulfadoxine-pyrimethamine as second line drug are adequate. In vitro, 4 resistances out of 27 successful tests to chloroquine (14.8%) and 1 resistance out of 25 successful tests to mefloquine (4%) were recorded. No resistance to quinine nor to amodiaquine were noticed. Alternative antimalarial drugs such as quinine, amodiaquine or mefloquine can be used in patients for whom the treatment with chloroquine is not possible. Nevertheless, the level of therapeutic failures to chloroquine detected in this study highlights the need and importance of drug sensitivity test for the development of a rational national antimalarial drug policy.