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.

[Severe liver cytolysis could be a marker of the severity of hemorrhagic dengue: report of two cases]. / La sévérité de la cytolyse hépatique pourrait être un marqueur de gravité de la dengue hémorragique : à propos de deux cas.

We report two cases of severe dengue fever in persons returned from stays in endemic areas during the summer outbreak of 2010. Both presented a hemorrhagic syndrome associated with primary hemostasis disorders, neutropenia, and severe hepatic cytolysis without any hepatocellular insufficiency. Three days after hospitalization, the first patient's AST and ALT levels rose to 80 and 12 times the upper reference values respectively, and the second patient's to 12 and 7 times those values. The second also presented signs of hemodynamic shock. Our observations suggest that the combination of severe hepatic cytolysis and hemostatic disorders may be a predictive marker of the severity of dengue fever. The pathophysiologic mechanisms explaining this severity remain unknown.

[Evaluation of efficacy and tolerance of amodiaquine versus chloroquine in the treatment of uncomplicated malaria outbreak in children of Gabon]. / Evaluation de l'efficacité et de la tolérance de l'amodiaquine versus chloroquine dans le traitement de l'accès palustre simple chez l'enfant au Gabon.

We conducted a prospective study from September 1997 to January 1998 in Libreville (Gabon). Fifty-three (53) children with uncomplicated P. falciparum malaria were included and divided into two groups. The first group (27 patients) was treated with amodiaquine and the second (26 patients) with chloroquine. The efficacy and tolerance of amodiaquine 30 mg/kg base over 3 days (10 mg/kg daily) and chloroquine 25 mg/kg base over 3 days (10 mg/kg day 0, 10 mg/kg day 1, 5 mg/kg day 3) were estimated at days 7 and 14. Clinical examination and parasitaemia were assessed on days 0, 1, 2, 3, 7, 14. Haematological and biochemical parameters were determined on days 0 and 7. Amodiaquine was shown to be more effective than chloroquine in clinical response and ridding patients of parasites: adequate clinical response was significantly higher with amodiaquine than chloroquine [100% (27/27) versus 45% (9/20), p < 0.0005]. Rates for early treatment failure (ETF) and late treatment failure (LTF) were respectively 35% and 12% with chloroquine. The parasitological success rate was significantly higher with amodiaquine than chloroquine on days 7 [93% (25/27) versus 62% (13/21), p < 0.008] and 14 [100% (13/13) versus 44% (4/9), p < 0.01]. The RI resistance type was 7% in the amodiaquine group. The rate of in vivo chloroquino-resistance was 53%, essentially of RII and RIII type. Overall, the two drugs were well tolerated.

Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa.

Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.

Light microscopic changes in Plasmodium falciparum from Gabonese children treated with artemether.

The changes in Plasmodium falciparum in four Gabonese children suffering from severe malaria and treated with pure artemether were observed in thin blood smears fixed and stained with Giemsa and examined by light microscopy. Peripheral blood samples were taken every 8 hr up to 72 hr from three children and every 3 hr up to 9 hr from the other child. The morphologic changes involved all development stages (trophozoites, schizonts, and gametocytes); they were first seen 3 hr after the start of treatment and all parasites were abnormal after 24 hr. After two days of treatment, all infected erythrocytes disappeared except for a few with necrotic trophozoites. The morphologic changes were similar to the ultrastructural changes previously described in vivo and in vitro in experimental models. They confirm the rapid effect of artemisinin derivatives on parasite clearance and clinical recovery, particularly in cases of cerebral malaria.