Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso

BACKGROUND: A reduction in the therapeutic efficacy of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has recently been observed in Burkina Faso. As these two drugs are used in pregnancy, their efficacy in pregnant women was studied to directly assess the level of drug resistance in this specific population, rather than to extrapolate results of studies conducted in children < 5 years of age. METHODS: During the malaria transmission season of 2003 in Ouagadougou, the clinical efficacy of SP and CQ, using the WHO 28-day protocol, was assessed in primigravidae and secundigravidae presenting with uncomplicated malaria. RESULTS: PCR-corrected results by day 28 showed that among 62 women treated with SP, eight (12.9%) experienced late parasitological failure, but no clinical failures. Among 60 women treated with CQ, the overall failure rate was 46.7% including 1.7% early treatment failures, 5% late clinical failures and 40% late parasitological failures. SP induced a haemoglobin gain of 0.3 g/dL by day 14 and 0.9 g/dL by day 28. Treatment responses were independent of gravidity, gestational age and prior antenatal care visits. CONCLUSION: While CQ should no longer be used, the efficacy of SP is still compatible with use for intermittent preventive treatment (IPT) in pregnancy. However, given the possible spread of resistance, the drug should be restricted in its use

[Retrospective study of cases of neuromeningeal cryptococcosis at the University Hospital of Bobo Dioulasso since accessibility to antiretroviral in Burkina Faso].

International audienceAIMS OF THE STUDY: To study the prevalence of neuromeningeal cryptococcosis since the availability of antiretroviral drugs and to determine the epidemiological profiles, clinical and biological treatment of neuromeningeal cryptococcosis cases diagnosed in the service of parasitology and mycology of university hospital center of Bobo-Dioulasso from 2002 to 2010. PATIENTS, MATERIAL AND METHODS: We included all patients diagnosed with neuromeningeal cryptococcosis for which the presence of the fungi was observed on microscopic examination of cerebrospinal fluid after staining with Indian ink. Data were collected from the registers of the clinical service and from the laboratory of the university hospital center of Bobo Dioulasso. RESULTS: The prevalence of neuromeningeal cryptococcosis was 1.8% (61/5129). A decrease in the prevalence was observed from 2002 to 2010 (3.1%, to 0.2%). This decrease occurred even though the number of patients treated with antiretroviral drugs increase. Headaches were the predominant clinical signs (81.9%). The CD4 median count was 56/mm(3). All patients were successfully treated with fluconazole in relay to amphotericin B intravenous. Lethality rate is 27.8%. CONCLUSION: The overall prevalence of 1.8% of neuromeningeal cryptococcosis observed in this study was lower than that in previous studies in the same laboratory in 2001. The arrival of antiretroviral drugs could have contributed to the decline in the prevalence of neuromeningeal cryptococcosis in this study

Sulfadoxine-pyrimethamine efficacy and selection of Plasmodium falciparum DHFR mutations in Burkina Faso before its introduction as intermittent preventive treatment for pregnant women

Sulfadoxine-pyrimethamine efficacy was determined with a 28-day follow-up in 97 children between 6 months and 15 years of age. The polymerase chain reaction (PCR)-corrected treatment failure was 8.2% and the uncorrected was 21.6%. The presence of the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) mutations linked to sulfadoxine-pyrimethamine resistance before and after treatment was determined by PCR-restriction fragment length polymorphism (RFLP) and by a fluorogenic PCR assay. Before treatment, the prevalence of the triple DHFR mutations was higher among the patients having had a recurrent parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P = 0.1). The double mutation Ala-436/Gly-437 was observed in 67% of samples, whereas no Glu-540 mutation was found. After treatment, the triple DHFR mutation was found in 76.2% of patients with recurrent parasitemia, recrudescence, and new infection alike. Such high prevalence of mutant parasites indicates that sulfadoxine-pyrimethamine should not be used as monotherapy

Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 mutations in Plasmodium falciparum and in vitro/in vivo chloroquine resistance in Burkina Faso, West Africa

The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in Plasmodium falciparum was explored in samples from patients with uncomplicated malaria and tested in vitro and in vivo with chloroquine (CQ) in Burkina Faso. The two mutations were strongly related. The Pfcrt T76 mutation was found in 82% of the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the presence of the Pfcrt T76 mutation. This suggests that the occurrence of the Pfmdr-1 Y86 mutation is dependent on that of Pfcrt T76 mutation and could explain previous reports linking the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 geometric mean (GMIC50) values, while those carrying both Pfcrt T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single mutant Pfcrt T76 (MW) had the highest. Among pre-treatment samples there was a strong linkage disequilibrium with an excess of MM and WW and a deficit of single mutants (MW and WM), suggesting that parasite fitness is higher for the former and lower for the latter

Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso

The prevalence of chloroquine (CQ) treatment failure and the genotype failure index was determined in four sentinel sites in Burkina Faso. In three sites, the genotype failure index varied between 1.7 and 3, a result confirming the relationship between the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76 mutation and CQ resistance. In the remaining site, the genotype failure index was unusually low, 1.1, which was significantly different than that in the other sites (P < 0.00001). These findings are discussed. Often but not always, the prevalence of CQ resistance can be correctly estimated by the Pfcrt T76 genotype failure index