Efficacy and Tolerability of Artesunate Plus Sulfadoxine-Pyrimethamine and Sulfadoxine-Pyrimethamine Alone for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Peru

Abstract

To assist the Peruvian Ministry of Health in modifying the malaria treatment policy for their north Pacific coastal region, we conducted an in vivo efficacy trial of sulfadoxine-pyrimethamine (SP) and SP plus artesunate (SP-AS) for the treatment for uncomplicated Plasmodium falciparum infections. A total of 197 patients were randomized to therapy with either SP (25 mg/kg of the sulfadoxine component in a single dose on day 0) or a combination of SP plus AS (4 mg/kg on days 0, 1, and 2) and were followed for 28 days for symptoms and recurrence of parasitemia. No statistically significant differences between the two groups were observed on enrollment with respect to age, sex, history of malaria, or geometric mean parasite density. A total of 185 subjects completed the 28-day follow-up. Of the 91 subjects treated with SP alone, two had recurrences of parasitemia on day 7 and one on day 21. Of the 94 subjects treated with SP-AS, one had a recurrence of parasitemia on day 21. Fever and asexual parasite density decreased significantly more rapidly and the proportion of patients with gametocytemia on days 3-28 was significantly lower in subjects treated with combination therapy than in those who received SP alone. No severe adverse drug reactions were observed; however, self-limited rash and pruritus were significantly more common and an exacerbation of nausea, vomiting, and abdominal pain were observed significantly more frequently among patients who had received SP-AS. These results have contributed to a National Malaria Control Program decision to change to SP-AS combination therapy as the first-line treatment for uncomplicated P. falciparum malaria in northern coastal Peru in November 2001, making Peru the first country in the Americas to recommend this combination therapy.

South American Plasmodium falciparum after the Malaria Eradication Era: Clonal Population Expansion and Survival of the Fittest Hybrids

“…The parasite samples used in this study were obtained from sample collection protocols that were approved by the Ethical Review Committees of the Instituto Nacional de Salud (for northern Pacific Coast), US Naval Medical Research Center Institutional Review Board and the National Institutes of Health of Peru (for Peruvian Amazon); and Institutional Review Boards of the U.S. Army, the U.S. Navy, and the Universidad Cayetano Heredia (for central and northeastern Amazon) [20], [22], [24], [25], [26], [28] as well as the U.S. Centers for Disease Control and Prevention. Written informed consent was provided by study participants and/or their legal guardians.…”

“…We examined 220 Peruvian P. falciparum clinical isolates collected during 1999–2000 from the northern Pacific Coast (Bellavista, n = 2; La Arena, n = 11 and Zarumilla, n = 67), the western Peruvian Amazon (Pampa Hermosa, n = 10; Ullpayacu, n = 25) collected during drug efficacy trials [20], [22], [25], and from the central Peruvian Amazon (Padre Cocha, n = 65) and the eastern Peruvian Amazon (Caballococha, n = 40) collected during drug efficacy trials and surveillance studies [24], [26], [28].…”

“…Control efforts achieved near elimination of malaria from 1966 to 1989 [18]. This ended when Peru suffered multiple epidemics of malaria during the 1990s [19], reaching peak incidence in 1998 on the Pacific Coast and in the Amazon [1], [20]. Subsequent control reduced malaria throughout Peru, particularly on the Pacific Coast.…”

The history of 20th century malaria control in Peru

“…Such migration increased when plantations and associated businesses required workers during sowing and harvesting between March and August, which coincided with peak Anopheles densities due to increased breeding aided by seasonal rain and stagnant water accumulation. Andean workers had little access to preventative measures or treatment [2,3]. …”

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

“…Los derivados de la artemisinina, como el artesunato, son esquizonticidas y tienen actividad sobre los gametocitos de P. falciparum (40)(41)(42)(43)(44)(45), reducen de forma importante la viabilidad de esos gametocitos jóvenes, tienen poco o nulo efecto sobre los gametocitos maduros y no se sabe cómo afectan la potencialidad infecciosa de los gametocitos para los anofelinos; en resumen, tienen un gran efecto sobre los gametocitos (36,46). La mefloquina tampoco elimina los gametocitos maduros de P. falciparum, sino que evita el desarrollo posterior de esas células por su actividad contra sus precursores (46).…”