A Randomized Trial of Artesunate Mefloquine versus Artemether Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Senegalese Children

An open randomized clinical trial study was carried out to compare efficacy and tolerability of artesunate mefloquine 25 mg/kg body weight (Artequin paediatric) versus artemether lumefantrine (Coartem) in the treatment of uncomplicated Plasmodium falciparum malaria in children. In each arm, 160 patients were assigned to receive either AS + MQ or AL with 28 days follow-up. The adequate clinical and parasitological response at Day 28 for per protocol analysis was after polymerase chain reaction correction, 100% for AS + MQ and 96.8% for AL. In the intention-to-treat analysis, the respective cure rates were 96.2% for AS + MQ and 93.7% for AL. No serious adverse events (AEs) were reported. The most frequent AE was vomiting, 30% in AS + MQ arm and 36% in AL arm. No biological significant abnormal values related to the study drug have been reported. The new pediatric artesunate mefloquine formulated in granule fixed dose combination is well adapted to children in Africa.     

Prediction of Plasmodium falciparum placental infection according to the time of infection during pregnancy

Malarial infection during pregnancy leads to placental infection, a known risk factor for low birth weight. Whether the stage of pregnancy at infection has a differential influence on these effects is not clearly known, but may be of importance for prevention strategies, including intermittent preventive treatment of pregnant women. Malaria infection during early (before 20 weeks), middle (20-28 weeks), or late (after 28 weeks) pregnancy was evaluated by logistic regression and receiver operating characteristics analysis in relation to placental infection in pregnant Senegalese women. Plasmodium falciparum infections during late pregnancy are strongly related to placental infection, as well as those that occur in middle pregnancy. Knowledge of parasitological events over the entire duration of pregnancy permits a highly accurate prediction of placental infection. Not only malaria infections during late pregnancy increase the likelihood of placental infection. The current policy of intermittent preventive treatment of pregnant women, which implies an initial antimalarial cure after 20 weeks of pregnancy, will not avoid early infections. An earlier initiation of malaria prevention might improve its efficacy.     

HIV-1 superinfections in a cohort of commercial sex workers in Burkina Faso as assessed by an autologous heteroduplex mobility procedure

OBJECTIVE: To describe and evaluate a simple procedure to identify HIV-1 co- or super-infections based on a heteroduplex mobility assay (HMA). METHODS: To identify heteroduplexes corresponding to divergent viral populations in a the same individual, HMA was applied to single DNA samples from each subject in a prospective cohort of commercial sex workers (CSW) in Bobo-Dioulasso, Burkina Faso. After denaturation and renaturation of env DNA amplicons, hybridized DNA was separated by electrophoresis through polyacrylamide gel. HIV-1 co-infections were suspected by slow migration of heteroduplex, at a level comparable to that of mixed reference strains. Following electrophoresis, DNA in bands representing heteroduplex was extracted and cloned in a plasmid vector; identification of phylogenetically distinct clones was confirmed by sequencing divergent clones identified through a second HMA step of a pair of two mixed clones. RESULTS: Among 147 HIV-1 infected CSW, four had an autologous HMA profile comparable to low mobility of hybridized DNA from mixed reference strains representing most frequent HIV-1 clades and circulating recombinant forms (CRF) prevalent in Burkina Faso. In two of them, two phylogenetically distinct HIV-1 populations were coexisting. The first woman presented with a CRF02-AG and CRF06-cpx co-infection, and the second with a CRF02-AG and a divergent virus co-infection not significantly related to any other known subtypes. In both women, retrospective analyses of stored samples by the same HMA procedure showed acquisition of a second virus concomitent with an increasing plasma HIV RNA. CONCLUSIONS: Autologous HMA procedure followed by acrylamide extraction of heteroduplexes allowed identifying HIV-1 co- and super-infections in a large cohort study. HIV-1 super-infection is not an uncommon phenomenon.     

Disseminated Paracoccidioidomycosis

When the U.S. Agency for International Development (USAID) began to support national programs integrating their neglected tropical disease (NTD) program activities, the expected impact on individual disease-specific programs was unclear, particularly with respect to program financing and coverage. To assess this impact, data were collected by NTD program managers and their non-governmental organization (NGO) partners in Burkina Faso, Mali, and Uganda from 2 years prior and 2 years after their individual programs received funding for an integrated NTD program. Findings show that these countries experienced some increases in overall funding available for integrated NTD programs, an expansion of geographical coverage and of the number of persons treated, and the addition of treatments targeted at new diseases. What is not clear is whether these achievements can be sustained if there are decreases in external support in the future. Seeking increased government commitment or sustained external donor support should be a top priority.     

Gall stone disease in African patients with sickle cell anaemia: a preliminary report from Yaounde, Cameroon.

Cholecystosonography was undertaken in 90 patients with sickle cell disease aged 15 years and over. Gall stones were found in 26 (28.9%) patients. There was no sex difference, but the incidence increased with age from 13.2% at under 20 years to 75% at 30 years and over. The mean serum cholesterol and total and unconjugated bilirubin concentrations were not significantly different between patients with and without gall stones. As most (80.8%) stones were radiolucent they were probably of pigment type, containing little or no calcium, and further investigation into how they are produced is needed. Sickle cell patients with acute abdominal crisis should have gall bladder disease excluded before a diagnosis of vascular crisis is made.     

Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT

Argemone mexicana (AM), a validated herbal medicine for uncomplicated malaria, seems to prevent severe malaria without completely clearing parasites in most patients. This study, in a high transmission area of South Mali, explores whether residual parasitaemia at day 28 was associated with subsequent malaria episodes and/or anaemia.Three hundred and one patients were randomly assigned to AM or artesunate/amodiaquine as first line treatment, of whom 294 were followed up beyond the standard 28 days, to 84 days. From day 29 to day 84, there were no significant differences between treatment groups in new clinical episodes of uncomplicated malaria (0.33 vs 0.31 episodes/patient), severe malaria (<6% per month of patients aged ≤5 years) or moderate anaemia (hematocrit <24%: 1.1% in both groups at day 84). Total parasite clearance at day 28 was not correlated with incidence of uncomplicated or severe malaria or of moderate anaemia over the subsequent two months.Total parasite clearance at day 28 was not clinically important in the context of high transmission. If this finding can be confirmed, some antimalarials which are clinically effective but do not completely clear parasites could nevertheless be appropriate in high transmission areas. Such a policy could be tested as a way to delay resistance to artemisinin combination therapies.     

Estimated coefficient of variation values for sample size planning in bioequivalence studies

OBJECTIVE: The aim of the present communication is to provide information regarding the intrasubject coefficent of variation obtained from 30 bioequivalence studies covering 16 drugs which can be used for estimation of sample size. Additionally, an attempt was also made to estimate the test power of each of the studies conducted. METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991]. RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991].     

Reemergence of Rift Valley Fever,Mauritania, 2010

A Rift Valley fever (RVF) outbreak in humans and animals occurred in Mauritania in 2010. Thirty cases of RVF in humans and 3 deaths were identified. RVFV isolates were recovered from humans, camels, sheep, goats, and Culex antennatus mosquitoes. Phylogenetic analysis of isolates indicated a virus origin from western Africa.     

Economic benefits of keeping vaccines at ambient temperature during mass vaccination: the case of meningitis?A vaccine in Chad

Objective

To evaluate the potential economic benefits of keeping a meningitis A vaccine at or near ambient temperature for up to 4 days during a mass vaccination campaign.

Methods

During a 10-day mass vaccination campaign against meningitis A in three regions of Chad in 2011, the costs associated with storage and transport of the vaccine in a traditional cold chain system were evaluated. A mathematical model was used to estimate the savings that could have been achieved if the vaccine had been stored at or near ambient temperature – in a “controlled temperature” chain – at the peripheral levels of the supply chain system.

Findings

The cost of the cold chain and associated logistics used in the campaign in Chad was 0.24 United States dollars (US$) per person vaccinated. In the modelled scenario for a controlled temperature chain, however, these costs dropped by 50% and were estimated to be only US$ 0.12 per person vaccinated.

Conclusion

The implementation of a “controlled temperature” chain at the most peripheral levels of the supply chain system – assuming no associated loss of vaccine potency, efficacy or safety – could result in major economic benefits and allow vaccine coverage to be extended in low-resource settings.