Amodiaquine remains effective for treating uncomplicated malaria in West and Central Africa

Abstract

Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without <i>Plasmodium falciparum</i> infection in northeast Tanzania

“…The absolute number of neutrophils diminished slightly more in the AQ group compared with CQ groups, but variation was mild suggesting that the differences between the groups were not of clinical significance. Our findings are consistent with results from previous chemotherapeutic studies (Nevill et al, 1994;Olliaro et al, 1996;Brasseur et al, 1999;Mengesha & Makonne, 1999), which demonstrated that AQ given at therapeutic dosage exhibits no life-threatening toxicity. It appears that the reason of increasing risk of life-threatening agranulocytosis and hepatic toxicity during AQ prophylactic administration (Hatton et al, 1986;CDC, 1986;Phillips-Howard & West 1990) is a result of doseindependent hypersensitivity reactions (Hatton et al, 1986).…”

“…The most frequent adverse effect reported was gastrointestinal toxicity (nausea) among CQ recipients. A similar relatively high gastrointestinal toxicity has been observed in malaria patients treated with CQ in central and west Africa (Brasseur et al, 1999). Low gastrointestinal toxicity can be of particular importance for patients receiving chemotherapy, as many chemotherapeutic agents induce nausea and vomiting.…”

“…Amodiaquine when used for prophylaxis in non-immune travellers may induce toxic hepatic and potential lethal agranulocytosis (Hatton et al, 1986, Larrey et al, 1986, CDC, 1986. However, chemotherapeutic studies have uniformly indicated that AQ when given in doses required for treatment is efficacious both without serious haematological life threatening adverse effects (Mengesha & Makonne, 1999), and with no potential biological toxicity associated with liver or kidney functions (Brasseur et al, 1999).…”

“…Despite considerable ample body of literature on efficacy and safety in treating uncomplicated falciparum Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania malaria in African children (Nevill et al, 1994, Brasseur et al, 1999, Mengesha & Makonne, 1999, there is dearth of data on safety of AQ in healthy Tanzanian population. Since AQ will be administered to apparently healthy infants in attempt to protect them against malaria morbidity, a careful risk-benefit assessment is required to ensure that the toxicity of AQ does not outweigh the risk of acquiring malaria.…”

Susceptibilidad in vitro de aislamientos colombianos de Plasmodium falciparum a diferentes antipalúdicos

“…Estos hallazgos también concuerdan con los estudios que indican que la amodiaquina es efectiva aún en zonas donde la resistencia a la cloroquina es alta (33,34); sin embargo, contrastan con los estudios de eficacia terapéutica de la monoterapia con amodiaquina en Colombia, en donde se reporta una falla de 30% en Turbo y El Bagre (Antioquia) (7) y de 50% en Tumaco (Nariño) (35). Esta diferencia entre los resultados obtenidos en estudios in vivo e in vitro con la amodiaquina ya había sido informada en varios estudios.…”