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Biomedical subjects

Stephane Proux

Publications and source records attributed to Stephane Proux.

6 recordsLinked to original sources

An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand.

BACKGROUND: Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A lower tablet burden should also facilitate adherence to treatment. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug-resistant falciparum malaria. METHODS: On the north-western border of Thailand 500 adults and children with uncomplicated falciparum malaria were randomized to receive either the new fixed combination or separate tablets. They were followed up weekly for 63 days. RESULTS: The day 63 polymerase chain reaction-adjusted cure rates were 91.9% (95% CI 88.2-95.6) in the fixed combination group and 89.2% (85.0-93.4) in the loose tablets group (P=0.3). There was a lower incidence of early vomiting in the group receiving the fixed combination. CONCLUSION: This new fixed combination of mefloquine and artesunate was efficacious, well tolerated and convenient to administer.

Adolescent↗

Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: the Tak Malaria Initiative.

BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS) have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000) living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI) intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5-34.4) and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0-39.9) during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0-63.9) reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was feasible and reduced the morbidity and mortality of multidrug-resistant P. falciparum.

Adult↗

Malaria.

Malaria is increasing worldwide due to the emergence and spread of drug resistant strains. This poses major health and economic problems for the population living in endemic areas and increases the risk of infections in travelers. The diagnosis of malaria relies on a biological proof of infection by microscopy or with a rapid test. The treatment must be initiated without delay preferably with an artemisinin containing regimen. Uncomplicated malaria can be treated with oral drugs while severe infections will be hospitalized and treated with injectables. Special attention will be given to the most susceptible groups: children and pregnant women.

Animals↗

A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria.

BACKGROUND: Dihydroartemisinin-piperaquine (DP) is a fixed-combination antimalarial drug increasingly deployed in Southeast Asia. The current regimen involves 4 doses given over 3 days. Simplification of the dose regimen should facilitate treatment adherence and thereby increase effectiveness. METHODS: In a randomized, controlled, 3-arm trial conducted along the northwestern border of Thailand, the standard 4-dose course of DP (DP4) was compared to an equivalent dose given as a once-daily regimen (DP3) and to the standard treatment of mefloquine-artesunate (MAS3). RESULTS: A total of 499 patients were included in the study. Times to fever and parasite clearance were similar in all groups. The PCR genotyping-adjusted cure rates at day 63 after treatment initiation were 95.7% (95% confidence interval [95% CI], 92.2%-98.9%) for MAS3, 100% for DP4, and 99.4% (95% CI, 98.1%-100%) for DP3. The DP4 and DP3 cure rates were significantly higher than that for MAS3 (P=.008 and P=.03, respectively). All regimens were well tolerated. There were 3 deaths (1 in the MAS3 group and 2 in the DP3 group), all of which were considered to be unrelated to treatment. Rates of other adverse events were comparable between the groups, except for diarrhea, which was more common in the DP4 group (P=.05 vs. the MAS3 group). CONCLUSIONS: A once-daily, 3-dose regimen of DP is a highly efficacious treatment for multidrug-resistant falciparum malaria. This simple, safe, and relatively inexpensive fixed combination could become the treatment of choice for falciparum malaria.

Adolescent↗

Central role of the spleen in malaria parasite clearance.

In acute malaria, red blood cells (RBCs) that have been parasitized, but no longer contain a malaria parasite, are found in the circulation (ring-infected erythrocyte surface antigen [RESA]-RBCs). These are thought to arise by splenic removal of dead or damaged intraerythrocytic parasites and return of the intact RBCs to the circulation. In a study of 5 patients with acute falciparum malaria who had previously undergone splenectomy, it was found that none of these 5 patients had any circulating RESA-RBCs, in contrast to the uniform finding of RESA-RBCs in all patients with acute malaria and intact spleens. Parasite clearance after artesunate treatment was markedly prolonged, although the parasites appeared to be dead and could not be cultured ex vivo. These observations confirm the central role of the spleen in the clearance of parasitized RBCs after antimalarial treatment with an artemisinin derivative. Current criteria for high-grade antimalarial drug resistance that are based on changes in parasitemia are not appropriate for asplenic patients.

Adult↗