A comparative clinical trial of combinations of dihydroartemisinin plus azithromycin and dihydroartemisinin plus mefloquine for treatment of multidrug resistant falciparum malaria.

With the deteriorating situation of multidrug resistant falciparum malaria, a new drug or drugs in combinations are urgently needed. We conducted a study comparing a combination of dihydroartemisinin 240 mg and mefloquine 1,250 mg given over 3 days (Group 1) and a combination of dihydroartemisinin 240 mg and azithromycin 1,500 mg given over 3 days (Group 2), to determine safety, efficacy and tolerability. All of the patients stayed in a non-malaria endemic area during the study. By the third day after drug administration, most patients were free of parasites and none had serious adverse events. The cure rates at day 28 were 100% and 69.7% in Group 1 and Group 2, respectively (p<0.01). We conclude that a combination of dihydroartemisnin and azithromycin was safe and effective and may be another interesting regimen of the treatment of uncomplicated multidrug resistant Plasmodium falciparum malaria in Thailand.

Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand.

Primaquine (8-aminoquinoline), the only effective drug to prevent relapses of the persistent liver forms of Plasmodium vivax and Plasmodium ovale, can induce hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The severity varies considerably among affected individuals. Three hundred and sixty-four Plasmodium vivax cases (342 G6PD-normal and 22 G6PD-deficient) were given a 3-day course of chloroquine (total dose 1,500 mg) followed by primaquine 15 mg a day for 14 days and completed a 28-day follow-up. All G6PD-deficient patients were male; there were no relapses or serious adverse events during the study. Although a significant decrease in hematocrit levels and an increase in the percent reduction of hematocrit levels were observed on day 7 (34.9+/-5.0 vs 26.7+/-5.4; (-1.2)+/-14.4 vs (-24.5) +/-13.9 respectively) and on day 14 (35.7+/-4.3 vs 30.9+/-3.1; 1.6+/-17.8 vs (-11.0) +/-19.3 respectively) blood transfusion was not required. Daily doses of 15 mg of primaquine for 14 days following a full course of chloroquine when prescribed to Thai G6PD deficient patients where Mahidol variant is predominant, are relatively safe.

Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15.

Complicated malaria, caused by Plasmodium falciparum, is characterized by multiple organ dysfunction. The pathogenesis of complicated malaria involves complex host-parasite interactions that include polarized cytokine responses. Recently, correlates between Th1-like and Th2-like cytokines, especially interleukin-10 (IL), IL-12, and TNF-alpha, and specific types of organ dysfunction have been noted. Here, we measured IL-10, IL-12, and for the first time, IL-15, in 19 patients aged 16-55 years old with complicated malaria on days 0 (admission), 3, 7, and 14. For analysis, patients were grouped together or sub-categorized into hyperparasitemias or cerebral malaria (CM). For IL-10, a dramatic increase was noted on admission, followed by a reduction toward control values that closely paralleled parasite clearance. For IL-12, modest but persistent increases were noted over the entire 14 day period that did not correlate with parasitemia. In general, especially on days 0 and 3, hyperparasitemic patients had, in comparison with CM patients, higher IL-10 and IL-12 levels. In contrast, IL-15 was generally below detection in most samples. These results provide further insight into the pathogenesis of complicated malaria by strengthening the contention that cytokines such as IL-10 and IL-12 are involved in modulating the immune response to P. falciparum.

Serological evaluation of malaria patients in Thailand: antibody response against electrophoresed antigenic polypeptides of Plasmodium falciparum.

It was reported that a 47kDa antigenic polypeptide of Plasmodium falciparum had been strongly presented by the sera from 1) imported Japanese malaria patients with severe symptoms and 2) symptomatic and parasitemic inhabitants in endemic areas in the Sudan, Malaysia and the Philippines. In the present study, we observed the reactivity of the sera from falciparum malaria patients who had been hospitalized in the Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, and compared the antibody response against the 47kDa antigenic polypeptide according to the severity of the patients. It was observed that antibodies to this molecule were more commonly shared in sera from severer patients, although the IFAT titers against the whole P. falciparum parasite antigen were lower in the group, which suggested that this antibody against the 47kDa molecule was playing a specific role at a severe stage of the infection. Determination of the immunological features of the antigenic molecules of parasites by this type of sero-epidemiological study will provide a new assay system for evaluation of immune status of individuals in different severity and suggest a way of vaccine development.

The ICT Malaria Pf: a simple, rapid dipstick test for the diagnosis of Plasmodium falciparum malaria at the Thai-Myanmar border.

The ICT Malaria Pf test for the detection of Plasmodium falciparum infection was evaluated in the diagnosis of 305 patients with fever who were admitted to a hospital located on the Thai-Myanmar border. All patients were admitted for at least one week to exclude reinfection. The test was performed using admission blood samples collected into ethylenediaminetetraacetic acid. The sensitivity, specificity and accuracy of the test were 92.7%, 95.1% and 94.7% respectively, compared to standard microscopic diagnosis. The ICT Malaria Pf test is an accurate method for the diagnosis of P. falciparum infection. Its simplicity and rapidity make it particularly appropriate for use in remote areas where microscopic examination of blood films is unavailable.