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Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rondoˆnia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region. [ABSTRACT FROM AUTHOR]

Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region.

Five patients with asexual and sexual parasites of Plasmodium vivax were treated orally with 600 mg chloroquine diphosphate (hour 0) followed with 300 mg at 8, 24 and 48 h later. Primaquine phosphate, 15 mg, was administered concurrently at h 0 and at 24 h intervals for 14 days. Anopheles darlingi were fed before the first dose (h -0.5) and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60 and 72 h later. Mosquitoes were examined for oocysts on day 8 and for sporozoites on day 15 after infection. Four of the five patients studied were still infective to mosquitoes from 1-5 h after the first dose of chloroquine plus primaquine. One of these and one other patient, who vomited 15 min after the first dose, became infective again at hours 10 and 12, respectively. Once produced, oocysts in mosquitoes fed on patients before, during and after chloroquine plus primaquine treatment appeared normal and produced sporozoite infected salivary glands. In view of these data, it is concluded that primaquine demonstrated rapid gametocytocidal activity and should be administered concurrently with chloroquine to reduce vivax malaria transmission.

Patients with asexual and sexual parasites of Plasmodium vivax were treated orally with 600 mg of chloroquine diphosphate at hour zero, followed by 300 mg at 8, 24 and 48 hr. Anopheles darlingi were fed before the first dose (-0.5 hr) and at 0.5, 1, 2, 4, 6, 8, 9, 10, 11, 12, 20, 24, 36, 48, 60, and 72 hr later. Mosquitoes were examined for oocysts on day 8 and sporozoites on day 15 after infection. The frequency of infected mosquitoes and the mean number of oocysts were lower in mosquitoes that fed on patients 2-4 hr after the initial dose of chloroquine than in mosquitoes fed before treatment and at 0.5 and 1 hr. This sporontocidal effect was temporary, since the frequency of infected mosquitoes and the mean number of oocysts increased in mosquitoes fed 4-8 hr after the first dose. Nearly all mosquitoes fed on patients after the third dose of chloroquine, at 24 hr, were negative for P. vivax oocysts. Oocysts in mosquitoes fed on patients before, during, and after chloroquine treatment appeared normal and produced sporozoites. We conclude that chloroquine affects either the gametocytes, fertilization, zygotes, and/or ookinetes of P. vivax, but not subsequent stages of development.

Seven anopheline species from Costa Marques, Rondonia, Brazil were compared with Anopheles darlingi for susceptibility to infection by Plasmodium vivax. Laboratory-reared F1 progeny of field-collected An. darlingi and the test anopheline species were fed at the same time on the same patients, all of whom had gametocytes in peripheral blood before treatment. Mosquitoes were dissected on day 8 after infection for oocysts and on days 14-16 after infection for sporozoites. The mean numbers of P. vivax oocysts and the percent of salivary gland infections for An. darlingi and An. deaneorum were similar and far exceeded those found in the other anopheline species tested. Anopheles albitarsis and An. mediopunctatus were less susceptible to infection by oocyst measurements than An. darlingi. However, for oocyst-infected An. albitarsis and An. mediopunctatus, the percent of mosquitoes with salivary gland infections and the numbers of sporozoites in the salivary glands were similar to An. darlingi. Anopheles triannulatus and An. oswaldoi were both susceptible to P. vivax infection, but the sporozoite infection rates and the numbers of sporozoites observed in the salivary glands were very low. Anopheles braziliensis and An. benarrochi both developed oocysts, but were never observed to have sporozoites in the salivary glands. These studies implicate some anopheline species as potential malaria vectors, but also show that species previously incriminated by ELISA techniques are not vectors of malaria parasites in Costa Marques, Rondonia, Brazil.

Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil. Laboratory reared F1 An. darlingi and anopheline test species were allowed to feed at the same time on falciparum malaria patients who had gametocytes in their blood, and who had not yet been treated with quinine. Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi. Anopheles albitarsis developed oocysts, but sporozoites did not invade the salivary glands. In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi.

Anopheles darlingi fed on eight falciparum malaria patients with gametocytes before and after treatment with quinine sulfate or quinine sulfate plus tetracycline became infected. Quinine and quinine plus tetracycline had no apparent sporontocidal or gametocytocidal effect on late stage immature and mature gametocytes. Plasmodium falciparum gametocytes are persistent and infected mosquitoes for up to 21 days after patients were treated with quinine plus tetracycline. Sporogonic development was similar for groups of mosquitoes fed before and after patients were treated with these schizontocides. The percentages of infected mosquitoes that developed salivary gland infections were also similar for groups of mosquitoes fed before and after treatment. Twenty-four hours after treatment with 45 mg of primaquine phosphate, falciparum malaria patients were not infective to An. darlingi.