Randomized Controlled Trial of Artesunate Plus Tetracycline Versus Standard Treatment (Quinine Plus Tetracycline) for Uncomplicated Plasmodium falciparum Malaria in Brazil

Abstract

A triple 'blind randomized controlled trial was undertaken in a Brazilian Amazon region (Cuiabâ-MT), tn compare the effect;veness and side effects of oral artcsunate (7 days, total dose = 0.75 g) plus tetraeycline (7 days, total dose = 10.5 g) [AT) and oral quinine (3 days, total dose = 6 g) plus te(racydine (7 days, total dose = 10.5 g) [QT). Eligible patients had uncomph'c'ated P. falciparum malaria; age ~ 14 years; no previous malaria treatment related to ,the present attack; and, if women, indil,ation of absence of pregnancy. Clinical i\'lOEm and blood tests were pcrformt:d at baselinc (day 0) and thereafter at days 2, ·,l, 7, 14 and 28. EOE.:ctiveness was asscssed by cure rates (WHO criteria) and parasite dl!arance at day 2.176 patients were randomized, 88 to each group. 9\.\.1.6% of the AT group and 93.2% of the QT group completed the 7-day treatment. 81.8% of the AT group and 78.4% of the QT group completed follow-up visits to day 2g Groups had similar clinical characteristics at baseline. The incidence of side effects was much higher in the QT group (82%) th?n in the AT group (50%) [p<O.OOOl]. Cure rates were similar: 80% in the AT and 77% in the QT group (p=0.68). Parasiternia (by day 2) cleared faster in the AT group than in the QT group (98.5% versus 47.6%,These results indicate that AT is effective in the treatment of uncomplicated t~tlciparum malaria and may provide a useful alternative to other treatment regimens.•Un essai randomisé, contrôlé et à triple-insu a été entrepris dans une région de l'Amazône au Brésil (Cuiaha-MT) afin de comparer l'efficacité ct ks effets secondaires de l'artesunatl~ (7 jours, dose totale = 0,75 g) avec de la tétracycline (7 jours, dose totale = 10,5 g) [AT] et de la quinine orale (3 jours, dose totale = () g) avec de la tétracycline (7 jours, dose totale = 10,5 g) [QTI. Les patients chOIsis ont eu une malaria P.falciparum sans complications: âge > 14 ans, aucun tnlltement antipaludéen relié à la crise présente; en cas de femmes, aucune 'ossesse indiquée. Un examen clinique et des prises de sang ont été faits au départ (jour 0) puis aux jours 2, 4, 7, 14· et 28 suivants. L'efficacité a été évaluée par les fréquences de guénson Il is to my family that 1 dedicate this thesis.'É dificil expressar min.~a gradidao à pessoas que, embora distante, se lïzeram as mais presentes durante meu perfodo na McGi11.Meu agradecimento e carinho para minha mae e mclhor amiga. Barhara, quem me deu motivaçao e auto-confiança para ir em [rente nas mais malucas situaçoes cm que me coloco, e me ensinou dedicaçâo através ùe seu proprio cxemplo ùe vida.Também quero dividir esta conquista corn minhas irmàs e irmàos, Eliane, Elisa.Elisete, Luiz e Waldeck Junior. tia e segunda mae. Neuza, meu pai, Waldc(,;k, c meus av6s, Archanjo e Elisa (em mem6ria). Pessoas que sempre foram so sorriso e carinho.

No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate–Mefloquine in Northwestern Brazil

“…Between 2001 and 2007, uncomplicated falciparum malaria in Brazil was treated with quinine plus doxycycline (formerly tetracycline) for 7 days or a single MQ dose (15 mg/kg). 3 Clinical surveillance in the late 1990s revealed cure rates of 98.9% for MQ 4 and between 77.3% and 100% for quinine plus tetracycline 5,6 in northern Mato Grosso, central Brazil, despite emerging evidence for quinine 7 and MQ 8 resistance in vitro. The main P. falciparum transmission hotspot in the Amazon basin of Brazil is Juruá Valley, close to the border with Peru.…”

Plasmodium falciparumNa+/H+Exchanger 1 Transporter Is Involved in Reduced Susceptibility to Quinine

“…It is not clear whether these strains are associated with clinical failures. One strategy that health officials can pursue to reduce the prevalence of malaria is to combine QN with other antimalarial drugs such as tetracycline (8,18) or clindamycin (16).…”

Pharmacokinetics and Pharmacodynamics of Intravenous Artesunate in Severe Falciparum Malaria

“…The derivative with the widest potential application is artesunate (ARTS), a water-soluble prodrug that can be administered parenterally as well as by mouth and per rectum. A number of studies have demonstrated the efficacy of ARTS in uncomplicated (17,19,24,26,27,28), severe (20,21), and multidrugresistant (11,25,34) falciparum malaria. Since ARTS clears parasites more rapidly than quinine and may improve survival (1,16,22,24,38), intravenous (i.v.)…”