Pfcrt 76T and pfmdr1 86Y allele frequency in Plasmodium falciparum isolates and use of self-medication in a rural area of Gabon.

BACKGROUND: Studies showed that chloroquine resistance may revert to sensitivity after its withdrawal mainly detected by a significant decrease of Plasmodium falciparum pfcrt 76T and pfmdr1 86Y alleles. Besides, self-medication is considered as a key factor of antimalarial drug resistance expansion. Thus, pfcrt 76T and pfmdr1 86Y allele frequency and its relationship with antimalarial drug self-medication was analyzed in P. falciparum isolates collected in Gabon. METHODS: Samples were collected from febrile children screened for P. falciparum infection in 2005 and 2008 at the regional hospital of Oyem. Self-use of antimalarial drugs before the day of consultation was recorded. Polymorphic codons 76 and 86 of pfcrt and pfmdr1 genes were analyzed by PCR-RFLP. RESULTS: The frequency of pfcrt 76T mutant allele was greater than 70.0% in 2005 and 2008. Wild type isolates were 1.7-fold more prevalent in 2008. The prevalence of pfmdr1 86Y mutant allele was comparable between 2005 and 2008 (p=0.1); the proportion of wild type allele reached 20.5% in 2008. The frequency of wild type allele pfcrt K76 or pfmdr1 N86 was higher among patients without anti-malarial drug self-medication compared to those who used it. CONCLUSIONS: An increase of the frequency of P. falciparum wild type allele pfcrt 76K and pfmdr1 86N was observed within a short period after chloroquine withdrawal. The proportion of mutant genotypes is still high, mainly among patients using self-medication with antimalarial drugs.

[Onchocerciasis in the area of Lastourville, Gabon. Clinical and entomological aspects]. / L'onchocercose dans la région de Lastourville, Gabon. Aspects cliniques et entomologiques.

The African Programme for Onchocerciasis Control (APOC) has implemented a series of surveys aimed at evaluating the long-term impact of its activities. The region of Lastourville (Gabon) is one of the selected sites for this study. A total of 886 persons was examined for skin lesions, and 459 out of them participated in detailed ocular examinations. Blackflies were collected during one year and dissected. Although the focus was found to be hypoendemic (prevalence of nodules: 7.7%), the frequency of onchodermatitis was relatively high. The lesions of the anterior segment of the eye were rare, but the prevalence of optic nerve disease, and of choroido-retinal lesions reached 5.2 and 2.7%, respectively. The annual transmission potential (2,171 infective larvae per man) was high, when compared with the results recorded in the human population. This may be due to the presence of Onchocerca spp. of animal origin in the blackflies. These results indicate that in the area of Lastourville, though regarded as the main focus of onchocerciasis in Gabon, the disease is relatively mild.

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine.

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 34.8 nM (mean IC50 5.0 nM) and the 95% confidence interval (CI95%) was 3.6-6.3 nM. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2 = 0.45, P < 0.001), artemether and chloroquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.31, P < 0.001), and artemether and halofantrine (r2 = 0.19, P < 0.01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.