Journal Article > ResearchFull Text
Ann Trop Med Parasitol. 2002 September 1; Volume 96 (Issue 6); DOI:10.1179/000349802125001654
Guthmann JP, Kasparian S, Phetsouvanh R, Nathan N, Garcia MG, et al.
Ann Trop Med Parasitol. 2002 September 1; Volume 96 (Issue 6); DOI:10.1179/000349802125001654
To assess the local efficacy of chloroquine for the treatment of acute, uncomplicated, Plasmodium falciparum malaria, children and adults from Sekong province (an area of Laos with a low intensity of transmission) were tested in a 28-day, in-vivo study. Complete data were collected from 88 of the 102 subjects enrolled between October 1999 and September 2000. After genotypic analysis to distinguish recrudescing infections from re-infections, 35 (39.7%, with a 95% confidence interval of 29.5%-50.7%) of these 88 patients were considered treatment failures. These results seriously question the use of chloroquine as the first-line treatment for P. falciparum malaria in the study area.
Journal Article > ResearchFull Text
Trop Med Int Health. 2004 June 1; Volume 9 (Issue 6); DOI:10.1111/j.1365-3156.2004.01249.x
van den Broek IVF, van der Wardt S, Talukder L, Chakma S, Brockman A, et al.
Trop Med Int Health. 2004 June 1; Volume 9 (Issue 6); DOI:10.1111/j.1365-3156.2004.01249.x
OBJECTIVE: To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. METHODS: A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). RESULTS: Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. CONCLUSIONS: The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh.
Journal Article > ResearchFull Text
Trop Med Int Health. 2004 April 1; Volume 9 (Issue 4); DOI:10.1111/j.1365-3156.2004.01217.x
Checchi F, Piola P, Kosack CS, Ardizzoni E, Klarkowski DB, et al.
Trop Med Int Health. 2004 April 1; Volume 9 (Issue 4); DOI:10.1111/j.1365-3156.2004.01217.x
We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.
Journal Article > ResearchFull Text
Trop Med Int Health. 2007 February 1; Volume 12 (Issue 2); DOI:10.1111/j.1365-3156.2006.01786.x
Janssens B, Van Herp M, Goubert L, Chan S, Uong S, et al.
Trop Med Int Health. 2007 February 1; Volume 12 (Issue 2); DOI:10.1111/j.1365-3156.2006.01786.x
OBJECTIVES: To compare the efficacy and tolerability of dihydroartemisinin-piperaquine (DHA-PQP) with that of a 3-day regimen of mefloquine and artesunate (MAS3) for the treatment of uncomplicated falciparum malaria in Cambodia. METHOD: Randomized open-label non-inferiority study over 64 days. RESULTS: Four hundred and sixty-four patients were included in the study. The polymerase chain reaction genotyping-adjusted cure rates on day 63 were 97.5% (95% confidence interval, CI, 93.8-99.3) for DHA-PQP and 97.5% (95% CI, 93.8-99.3) for MAS3, P = 1. There were no serious adverse events, but significantly more episodes of vomiting (P = 0.03), dizziness (P = 0.002), palpitations (P = 0.04), and sleep disorders (P = 0.03) reported in the MAS3 treatment group, consistent with the side-effect profile of mefloquine. CONCLUSIONS: DHA-PQP was as efficacious as MAS3, but much better tolerated, making it more appropriate for use in a routine programme setting. This highly efficacious, safe and more affordable fixed-dose combination could become the treatment of choice for Plasmodium falciparum malaria in Cambodia.