RESUMO
Chloroquine-resistant (CQR) vivax malaria has emerged as a threat to the malaria elimination agenda. The objective of this study was to assess if a combination of chloroquine (CQ) and prochlorperazine was able to reverse CQ resistance of the Plasmodium vivax AMRU-1 strain from Papua New Guinea in infected Aotus monkeys. For this purpose, in two independent experimental drug efficacy trials, a total of 18 Aotus monkeys infected with blood obtained from donor animals were randomly assigned to treatment and control groups and orally administered CQ at 10 mg/kg or prochlorperazine at 20 mg/kg, alone or in combination, for five consecutive days. Reversal of CQR was achieved in animals that received the drug combination, whereas neither drug alone produced cures. This same drug combination reverses CQR in P. falciparum and could be an alternative for treatment in humans with chloroquine-resistant P. vivax infections.
Assuntos
Antimaláricos/farmacologia , Cloroquina/farmacologia , Haplorrinos/microbiologia , Malária Vivax/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Animais , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Malária Falciparum/tratamento farmacológico , Malária Vivax/microbiologia , Masculino , Papua Nova Guiné , Plasmodium falciparum/efeitos dos fármacosRESUMO
A multidrug-resistant (MDR) clone of Plasmodium falciparum (C2A) from Thailand was adapted through serial passage to Aotus monkeys. During adaptation, the parasite showed resistance to a single 20 or 40 mg/kg oral dose of mefloquine (MQ). Infection was only cured when MQ was administered orally at 40 mg/kg once in combination with intravenous artesunic acid at 20 mg/kg for 3 days. Similarly, the parasite clone was found to be resistant to quinine, failing at 20 mg/kg orally for 5 days in combination with an experimental dihydrofolate reductase (DHFR) inhibitor (WR297608) at 10, 20, or 40 mg/kg orally for 3 days, and with atovaquone/proguanil at 25 mg/kg for 3 days. This new model will allow in vivo testing of new antimalarial compounds or their combinations against a currently circulating MDR P. falciparum strain.
Assuntos
Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/fisiologia , Adaptação Fisiológica , Animais , Aotidae , Resistência a Múltiplos Medicamentos , Feminino , Malária Falciparum/parasitologia , Masculino , Parasitemia , Tailândia , Fatores de TempoRESUMO
During 1983, a multinational military intervention took place on Grenada. After deployment, troops from several U.S. Army units noted signs and symptoms consistent with soil-transmitted helminthic infection. Of 684 soldiers screened five to seven weeks post-development, over 20 percent reported abdominal pain and/or diarrhea during or after the action. Eosinophilia of at least 10 percent was observed in 119 (22.5 percent) of 529 soldiers evaluated further; eosinophilia of 5-9 percent was documented in another 126 (23.8 percent) of the 529 soldiers. Stool examinations confirmed hookworm infection in 35 soldiers. One case of strongyloidiasis was also documented. Infection was attributed to ground exposure near homes with compromised sanitation. Units that joined the operation after the initial assault phase were at low risk of hookworm infection. (AU)