Cost of treating inpatient falciparum malaria on the Thai-Myanmar border.

BACKGROUND: Despite demonstrated benefits and World Health Organization (WHO) endorsement, parenteral artesunate is the recommended treatment for patients with severe Plasmodium falciparum malaria in only one fifth of endemic countries. One possible reason for this slow uptake is that a treatment course of parenteral artesunate is costlier than quinine and might, therefore, pose a substantial economic burden to health care systems. This analysis presents a detailed account of the resources used in treating falciparum malaria by either parenteral artesunate or quinine in a hospital on the Thai-Myanmar border. METHODS: The analysis used data from four studies, with random allocation of inpatients with falciparum malaria to treatment with parenteral artesunate or quinine, conducted in Mae Sot Hospital, Thailand from 1995 to 2001. Detailed resource use data were collected during admission and unit costs from the 2008 hospital price list were applied to these. Total admission costs were broken down into five categories: 1) medication; 2) intravenous fluids; 3) disposables; 4) laboratory tests; and 5) services. RESULTS: While the medication costs were higher for patients treated with artesunate, total admission costs were similar in those treated with quinine, US$ 243 (95% CI: 167.5-349.7) and in those treated with artesunate US$ 190 (95% CI: 131.0-263.2) (P=0.375). For cases classified as severe malaria (59%), the total cost of admission was US$ 298 (95% CI: 203.6-438.7) in the quinine group as compared with US$ 284 (95% CI: 181.3-407) in the artesunate group (P=0.869). CONCLUSION: This analysis finds no evidence for a difference in total admission costs for malaria inpatients treated with artesunate as compared with quinine. Assuming this is generalizable to other settings, the higher cost of a course of artesunate should not be considered a barrier for its implementation in the treatment of malaria.

Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria.

A randomized, open-label comparison of artesunate and quinine was conducted in 113 adults with clinically severe falciparum malaria in western Thailand. Mortality was 12% with artesunate and 22% with quinine treatment (relative risk, 0.53; 95% confidence interval, 0.23-1.26; P=.22). Multiple logistic regression analysis found admission plasma lactate level, Glasgow Coma Scale score, and total serum bilirubin level to be independent risk factors for death. Coma recovery and times to normalize plasma lactate levels were similar, but the parasite clearance time was much shorter among artesunate-treated patients (P=.019). Fewer patients became hypoglycemic during artesunate therapy (10%) than during quinine therapy (28%) (P=.03). Artesunate is at least as effective as quinine in the treatment of adults with severe malaria. Larger trials are required to determine whether mortality is reduced among patients treated with artesunate.

In vitro efficacy of antimalarial drugs against Plasmodium vivax on the western border of Thailand.

The susceptibility of 20 isolates of Plasmodium vivax on the Thailand-Myanmar border to seven antimalarial drugs was evaluated using the schizont maturation inhibition technique. The geometric mean 50% inhibition concentration (IC(50)) values were quinine = 308 ng/mL, amodiaquine =14 ng/mL, chloroquine =50 ng/mL, mefloquine = 127 ng/mL, sulfadoxine/pyrimethamine (80:1) = 800/10 ng/mL, pyrimethamine = 8 ng/mL, and artesunate = 0.5 ng/mL. Compared with P. falciparum in this area, P. vivax was more sensitive to chloroquine and artesunate, equally sensitive to quinine, and more resistant to mefloquine.

The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria.

OBJECTIVE: Intravenous artesunate is commonly used in the emergency treatment of patients with severe falciparum malaria in Asia. The choice of doses used has been empirical. To inform dosage recommendations we assessed the pharmacokinetics of intravenous artesunate after the first dose. METHODS: As part of a clinical trial of artesunate in adults with severe falciparum malaria in western Thailand, we assayed plasma concentrations of artesunate and the principal biologically active metabolite dihydroartemisinin (DHA) in 17 patients given an initial dose of 2.4 mg/kg body weight of intravenous artesunate. Drug levels were measured using high performance liquid chromatography with mass spectroscopy-electrospray ionisation detection. RESULTS: Median (range) observed DHA Cmax was 2128 (513-5789) nmol/L, elimination half-life was 0.34 (0.14-0.87) h, and the time to the last detectable DHA was 2 h. CONCLUSION: The large inter-individual variability (10 fold) in DHA Cmax and AUC in patients with potentially lethal, severe malaria, suggests that 2.4 mg/kg should be the minimum daily dose in severe malaria.

Pharmacokinetics of oral doxycycline during combination treatment of severe falciparum malaria.

The pharmacokinetics of oral doxycycline administered at 200 mg every 24 h were investigated in 17 patients recovering from severe Plasmodium falciparum malaria. The data suggest that the doses of doxycycline currently recommended (circa 3.5 mg/kg of body weight daily) may not be optimal.

Malaria and amphetamine 'horse tablets' in Thailand.

During recent clinical malaria research in Thailand we found a high frequency of amphetamine misuse and withdrawal amongst patients admitted to hospital with Plasmodium falciparum malaria. This comorbidity may cause diagnostic confusion, alter malaria pathophysiology and lead to drug interactions.

Platelet-induced autoagglutination of Plasmodium falciparum-infected red blood cells and disease severity in Thailand.

The relationship of the platelet-mediated autoagglutination of Plasmodium falciparum-infected red blood cells (IRBCs) to disease severity was investigated in 182 Thai patients with falciparum malaria; it was evident in 43% of uncomplicated malaria (n=63), 41% of severe malaria (n=104), and 100% of cerebral malaria (n=15; P=.001) isolates. The median (range) number of IRBCs in agglutinates per 1000 IRBCs was significantly higher in cerebral malaria (6 [3-42]) than in severe (0 [0-52]) and uncomplicated (0 [0-24]) malaria (P=.01). In multivariate analyses, high parasitemia and cerebral malaria were associated independently with parasite agglutination.

Comparison of oral artesunate and dihydroartemisinin antimalarial bioavailabilities in acute falciparum malaria.

Plasma antimalarial activity following oral artesunate or dihydroartemisinin (DHA) treatment was measured by a bioassay in 18 patients with uncomplicated falciparum malaria. The mean antimalarial activity in terms of the bioavailability of DHA relative to that of artesunate did not differ significantly from 1, suggesting that DHA can be formulated to be an acceptable oral alternative to artesunate.