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Schistosoma mansoni epidemiology is very uncertain in Gabon despite its wide distribution in Sub-Saharan African whereas knowledge of schistosomiasis endemicity setting has important implications for the national policy controls. To date only two cases of S. mansoni were diagnosed by the Department of Parasitology-Mycology (DPM), Libreville-Gabon between 1995 and 2009 and both came from Plaine Orety, an urban area of Libreville. As the result of this finding a survey that we report results here was conducted to determine the epidemiological status of S. mansoni in this site. Parasitological and malacological surveys were conducted prospectively from January to May 2012. Parasitological survey included people living in Plaine Orety (Libreville) area at least three months and aged from two years upwards. Stool examination was performed using Kato-Katz technique and malacological investigations were conducted in all the streams of this area for the same period to identify the intermediate snail host of S. mansoni. A total of 495 people were examined, of them 4 cases (0.81%) were identified positive to S. mansoni with no significant influence of sex or age group (p>0.05). Infected peoples said they never went out of the country but stayed in other regions of the country, i.e. Kango, Ovan, Lambarene, Port-Gentil, Bitam and Fougamou. No intermediate snail host of human schistosomes has been identified in the whole surveyed water sites of Plaine Orety. Freshwater snails identified are: Lymnea sp, Physa sp, Melanoides sp and Indoplanorbis exustus (intermediate snail host of cattle schistosomes in India). The finding of this study illustrate existing indigenous cases of S. mansoni in Libreville (Gabon) even if local active transmission area remains to be elucidate because of the absence of intermediate snail host Biomphalaria.

International audience; Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria. The aim of this clinical trial was to evaluate the efficacy, safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation. A total of 71 children aged 1-13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight: 10-20 kg, pediatric group (n = 41); 20-40 kg, tablet group (n = 30). All the children were treated once daily for three days: the pediatric group received the novel granule formulation, the tablet group received the co-blister tablets. The PCR-corrected cure rate on day 28 was evaluated. There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100% in per-protocol analysis. In intention-to-treat analysis the cure rates were 95% in the pediatric group and 97% in the tablet group. The most frequent adverse events were vomiting (17%), abdominal pain (11%) and headache (17%). This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children.

The distribution and range of 50% inhibitory concentrations (IC 50 s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC 50 geometric mean ranged from 6.2 μM to 11.1 μM according to the geographical origin, with a mean of 9.3 μM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC 50 mean of 4.9 μM (±2.1 μM [standard deviation]); component B, with an IC 50 mean of 7.7 μM (±1.2 μM); and component C, with an IC 50 mean of 17.9 μM (±1.4 μM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 μM.

Objectives Paediatric drug formulations of artemisinin combination therapies and pharmacokinetic data supporting their use in African children are urgently needed for the effective treatment of young children suffering from falciparum malaria in sub-Saharan Africa. Patients and methods In this study, the pharmacokinetic characteristics of a novel paediatric granule formulation of artesunate-mefloquine therapy were evaluated in comparison to the standard tablet formulation in the treatment of uncomplicated malaria in paediatric patients. Twenty-four patients were assigned to treatment according to body weight with either a fixed-dose paediatric granule co-formulation (10-20 kg body weight) or a free-dose co-blister tablet formulation of artesunate-mefloquine (>20-40 kg body weight). Results Median values for C(max) (861 and 930 ng/mL), T(max) (1.5 and 1.5 h) and AUC(0-)(t) (2,050 and 2,470 ng.h/mL) were comparable for dihydroartemisinin in the two groups. Exploratory analysis of mefloquine plasma levels revealed a trend towards higher concentrations in the younger age group during the absorption phase (2,550 and 1,815 ng/mL, 54 h after initiation of treatment, respectively). Median mefloquine concentrations at day 28 were 197 and 343 ng/mL, respectively. Conclusions The pharmacokinetic characteristics of the two paediatric dosage forms, i.e. the novel fixed-dose co-formulation and the standard co-blister of artesunate-mefloquine show comparable results in the two treatment groups. The novel fixed-dose paediatric formulation is an interesting option for outpatient treatment of uncomplicated malaria in African children.

Antimalarial drugs, when used as monotherapies, are rapidly losing their effectiveness. One promising new drug is the antimalarial 8-aminoquinoline tafenoquine (SB-252263 [formerly WR-238605]), a new synthetic primaquine analogue codeveloped by the U.S. Army and GlaxoSmithKline, which has been shown effective not only against the liver stages, gametocytes, and sporozoites of Plasmodium falciparum (4), but also against the blood stages of the parasite (13). Tafenoquine demonstrated significant protection against P. falciparum infection in Gabon, Ghana, and Kenya (6, 7, 12). Tafenoquine has been reported to be well tolerated, with only mild gastrointestinal effects (8). Isolates were collected in 1999 from malaria patients from Libreville (Gabon, Central Africa), Dielmo and Ndiop (Senegal, West Africa), and Djibouti (East Africa). The isotopic, microdrug susceptibility test used was described previously (10). The 50% inhibitory concentration (IC50) values for tafenoquine were in the range 0.9 to 9.7 μM in Djibouti, 0.6 to 33.1 μM in Gabon, and 0.5 to 20.7 μM in Senegal. The geometric mean IC50 was 2.68 μM in Djibouti, versus 4.62 μM in Gabon and 5.06 μM in Senegal (Table ​(Table1).1). Tafenoquine was found to possess marked blood schizonticidal activity in P. falciparum in areas with high percentages of multidrug-resistant parasite populations. There was no difference in the tafenoquine mean IC50 values between Dielmo-Ndiop and Libreville, even though the levels of reduced susceptibility for chloroquine, mefloquine, cycloguanil, and pyrimethamine were different. Conversely, tafenoquine was significantly more active in Djibouti than in Gabon or Senegal (P = 0.016). The results of these in vitro tests were comparable with those reported by other authors in culture-adaptated P. falciparum clones and strains (2, 11). TABLE 1. In vitro susceptibilities and prevalence of resistance or reduced susceptibility of wild isolates of Plasmodium falciparum from Djibouti, Gabon, and Senegal to the drugs shown Published in vitro data for the blood schizonticidal activity of primaquine in P. falciparum show a range of IC50 values between 0.3 μM and 14 μM (1, 2, 13). In this study, there was no difference in the tafenoquine mean IC50 values between the three areas (P = 0.111). Tafenoquine is more active in vitro than primaquine, wherever the area. Tafenoquine exerts a blood schizonticidal activity 4 to 100 times higher than that of primaquine in the Plasmodium berghei and Plasmodium yoelii mouse model (9). Tafenoquine had a half-life that is more than 50 times longer than that of primaquine (3, 5). The difference in kinetics results in more prolonged, high concentrations of tafenoquine in the blood. These properties permit weekly dosing for prophylaxis and short-term or single-dose therapy for radical cure. Only 3.5% of the variation of response to tafenoquine is explained by response variation to primaquine. The coefficients of determination, r2, ranging from 0.001 to 0.113, are too weak to consider that cross-resistance may exist between tafenoquine and standard antimalarial drugs. Since correlation analysis provides an insight into the mode of action and cross-susceptibilities between different drugs, these data may be seen as an indication of the relative independence of tafenoquine from the susceptibility of P. falciparum to standard antimalarial drugs. In conclusion, these data permit definition of the baseline of in vitro susceptibility to tafenoquine before its use and will allow the monitoring of its resistance or its reduced susceptibility when tafenoquine will be commonly used. Given its greater schizonticidal activity, tafenoquine is a promising candidate as a short treatment for P. falciparum and Plasmodium vivax malaria. However, the potential side effects of tafenoquine, such as the production of methemoglobin and the risk of hemolysis in glucose-6-phosphate dehydrogenase-deficient patients, have to be taken into consideration (14).

Background Substantial decline in malaria transmission, morbidity and mortality has been reported in several countries where new malaria control strategies have been implemented. In Gabon, the national malaria policy changed in 2003, according to the WHO recommendations. The trend in malaria morbidity was evaluated among febrile children before and after their implementation in Libreville, the capital city of Gabon. Methods From August 2000 to December 2008, febrile paediatric outpatients and inpatients, under 11 years of age, were screened for malaria by microscopic examination at the Malaria Clinical Research Unit (MCRU) located in the largest public hospital in Gabon. Climatic data were also collected. Results In total, 28,092 febrile children were examined; those under five years always represented more than 70%. The proportion of malaria-positive slides was 45% in 2000, and declined to 15% in 2008. The median age of children with a positive blood smear increased from 24(15-48) to 41(21-72) months over the study period (p < 0.01). Rainfall patterns had no impact on the decline observed throughout the study period. Conclusion The decrease of malaria prevalence among febrile children during the last nine years is observed following the introduction of new strategies of malaria cases management, and may announce epidemiological changes. Moreover, preventive measures must be extended to children older than five years.

Background In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines. Methods A random comparison of the efficacy of AQ (10 mg/kg/day × 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhps K540E mutation, as a molecular marker to predict SP-treatment failure. Results The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5–22.1) and 28.2% (20/71; 95% CI: 17.7–38.7), respectively This indicated that SP was significantly superior to AQ (P = 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The dhps K540E mutation was not found among the 76 parasite isolates tested. Conclusion The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.