Efficacy of atovaquone-proguanil for treatment of acute multidrug-resistant Plasmodium falciparum malaria in Thailand.

A combination of atovaquone-proguanil (Malarone); GlaxoSmithKline, Research Triangle Park, NC) was previously shown to be highly effective in the treatment of uncomplicated Plasmodium falciparum malaria. However, there are only limited recent efficacy data, particularly from regions of multidrug resistance. In this study, we examined the efficacy of atovaquone-proguanil for the treatment of uncomplicated P. falciparum malaria on the Thailand-Myanmar border. Patients were given directly observed atovaquone-proguanil (1,000 mg/400 mg) once a day for three days and followed-up for four weeks in a non-transmission area. Of 140 eligible patients enrolled in this open-label study, 97.8% (95% confidence interval = 95.4-100%) responded to therapy and remained clear of parasitemia at follow-up. Mean parasite clearance time was 41.9 hours and mean fever clearance time was 37.1 hours. On the basis of genotyping, three cases of treatment failure were identified (1 RIII and 2 RI). These data indicate that atovaquone-proguanil remains highly efficacious for the treatment of multidrug-resistant P. falciparum malaria in Thailand.

In vitro antimalarial activity of azithromycin, artesunate, and quinine in combination and correlation with clinical outcome.

Azithromycin when used in combination with faster-acting antimalarials has proven efficacious in treating Plasmodium falciparum malaria in phase 2 clinical trials. The aim of this study was to establish optimal combination ratios for azithromycin in combination with either dihydroartemisinin or quinine, to determine the clinical correlates of in vitro drug sensitivity for these compounds, and to assess the cross-sensitivity patterns. Seventy-three fresh P. falciparum isolates originating from patients from the western border regions of Thailand were successfully tested for their drug susceptibility in a histidine-rich protein 2 (HRP2) assay. With overall mean fractional inhibitory concentrations of 0.84 (95% confidence interval [CI]=0.77 to 1.08) and 0.78 (95% CI=0.72 to 0.98), the interactions between azithromycin and dihydroartemisinin, as well as quinine, were classified as additive, with a tendency toward synergism. The strongest tendency toward synergy was seen with a combination ratio of 1:547 for the combination with dihydroartemisinin and 1:44 with quinine. The geometric mean 50% inhibitory concentration (IC50) of azithromycin was 2,570.3 (95% CI=2,175.58 to 3,036.58) ng/ml. The IC50s for mefloquine, quinine, and chloroquine were 11.42, 64.4, and 54.4 ng/ml, respectively, suggesting a relatively high level of background resistance in this patient population. Distinct correlations (R=0.53; P=0.001) between quinine in vitro results and parasite clearance may indicate a compromised sensitivity to this drug. The correlation with dihydroartemisinin data was weaker (R=0.34; P=0.038), and no such correlation was observed for azithromycin. Our in vitro data confirm that azithromycin in combination with artemisinin derivatives or quinine exerts additive to synergistic interactions, shows no cross-sensitivity with traditional antimalarials, and has substantial antimalarial activity on its own.

Anemia and survival in Thai hemodialysis patients: evidence from national registry data.

BACKGROUND: Anemia is a major contributor to morbidity and mortality in chronic dialysis patients. The K/DOQI guideline recommends the target hemoglobin of 11-12 g/dl (hematocrit of 33-36%). However the appropriate hematocrit level for Thai hemodialysis patients has been controversial. OBJECTIVE: To investigate the influence of anemia on mortality in Thai chronic hemodialysis patients who initiated their dialysis from 1999 through 2003. MATERIAL AND METHOD: The data from the Thailand Renal Replacement Therapy Registry who has conducted an annual report of chronic dialysis patients throughout Thailand since 1997 was used. Data of twice- and thrice-weekly hemodialysis patients who had recorded hematocrit from 1999 through 2003 were processed and confirmed before final analysis. Records of 3,211 hemodialysis patients from 301 centers were included. RESULT: The original kidney diseases were diabetes mellitus (31.5%) and hypertension (20.9%). Most patients received twice-weekly hemodialysis (86.3%). The mean hematocrit was 29.3 +/- 5.5%. Most patients (72.8%) had hematocrits of less than 33%. Kaplan-Meier analysis showed patients with hematocrit of ?33% or more had better survival than patients with hematocrits of less than 33% (p <0.01). Patients with hematocrits of less than 27, 27-29.9, 30-32.9 and 36% or more had mortality risks of 1.90 (95% CI: 1.31-2.76, p <0.01), 2.10 (95% CI: 1.42-3.09, p <0.01), 1.74 (95% CI: 1.18-2.56, p <0.01) and 1.174 (95% CI: 0.73-1.90, p = 0.51) respectively, compared to those with hematocrit of 33-35.9%. CONCLUSION: The best survival can be achieved in Thai patients with hematocrits of at least 33%.

Emergence and clearance of gametocytes in uncomplicated Plasmodium falciparum malaria.

We reviewed the records of 1,175 patients with uncomplicated Plasmodium falciparum malaria to determine the prevalence of gametocytemia. All patients were admitted and received artemisinin combination therapy. Blood films were checked daily until discharge. Circulating gametocytes were observed in 240 (20.2%) of patients and in most cases (222 of 240, 92.5%) gametocytemia was detected during the first 24 hours after admission. Gametocytes were first seen in 174 cases on admission, in 24 cases at 12 hours, and in 24 cases at 24 hours. The longest interval between admission and first appearance of gametocytes was 192 hours. The median gametocyte clearance time was 163 hours (range = 12-806) in the 219 patients in whom gametocytemia resolved. However, 21 patients (9.8%) still had gametocytemia on discharge. Gametocytemia generally is present within the first 24 hours after admission, and emerges in only 1.9% of patients later on during treatment with artemisinin.