RESUMEN
BACKGROUND: Safe and effective antimalarials are required to protect pregnant women from the harmful effects of malaria. METHODS: Data were collected from two separate prospective cohorts to ascertain the safety of chloroquine-proguanil, sulfadoxine-pyrimethamine (SP), and mefloquine taken in the first trimester of pregnancy. RESULTS: In a traveler cohort of 236 pregnant women, spontaneous abortions were reported in 7.6% of 99 women taking chloroquine-proquanil, 0% of 19 taking sulfadoxine-pyrimethamine, and 9.1% of 118 women taking mefloquine. Anomalies were identified in 1.7%, 0% and 0% of the same cohort, respectively. Differences in rates of adverse outcomes between the three groups were not statistically significant. In a pharmaceutical database of 331 and 153 women exposed to mefloquine and SP, respectively, the overall rate of abnormal outcomes (spontaneous abortions plus fetal anomalies) was not significantly different (p=.29). Spontaneous abortions were significantly higher with mefloquine than SP (9.1% and 2.6%, respectively; p=.01), but the higher rate was comparable to background rates (7%-11%). Fetal anomalies in the mefloquine group (4.8%) were lower than the SP group (7.8%), but this was statistically not significant (p=.19), and was comparable with the background rate of 4.6% (p=.84). However, mefloquine exposure resulted in a significantly higher rate of therapeutically induced abortions, undertaken for perceived risk to the fetus, compared with SP (p<.0001). CONCLUSION: From the clinical data available, there is no indication that the risk of taking mefloquine in the first trimester of pregnancy is greater than that from any of the other antimalarials studied and the risk is considerably lower than that associated with falciparum malaria.
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Aborto Espontáneo/inducido químicamente , Antimaláricos/efectos adversos , Cloroquina/efectos adversos , Malaria/tratamiento farmacológico , Mefloquina/efectos adversos , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Proguanil/efectos adversos , Pirimetamina/efectos adversos , Seguridad , Sulfadoxina/efectos adversos , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Bases de Datos Factuales , Combinación de Medicamentos , Industria Farmacéutica , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
There is much confusion over which malaria chemoprophylaxis should be used in areas such as East Africa. We did two consecutive studies between 1985 and 1991 to assess the efficacy and side-effects of malaria chemoprophylaxis in short-term travellers to East Africa. All passengers returning from Kenya to Europe received an in-flight questionnaire and a second one three months later. Any report of documented malaria or of admission to hospital for possible side-effects was verified with the physician. 145 003 travellers completed questionnaires. Among the 139 164 who stayed in East Africa for less than one year, 296 cases of confirmed malaria were reported (275 due to P falciparum). In people who used no chemoprophylaxis, the incidence of falciparum malaria was 1.2% per month. Prophylactic effectiveness was 91% (95% Cl 85 to 94) for mefloquine, 82% (71 to 89) for pyrimethamine and sulfadoxine, 72% (56 to 82) for chloroquine plus proguanil, and 10 to 42% for chloroquine at various doses. Rates of side-effects, which were usually mild, were 18.8% for mefloquine users, 17.1% and 18.6% for chloroquine 300 mg and 600 mg base per week, respectively, 30.1% for chloroquine plus proguanil, and 11.7% for sulfadoxine and pyrimethamine. Mefloquine is significantly more effective than chloroquine plus proguanil for malaria prophylaxis in short-term tourists visiting East Africa and has a tolerance similar to that of chloroquine used alone.