Emergence of Plasmodium ovale malaria among the French Armed Forces in the Republic of Ivory Coast: 20 years of clinical and biological experience.

BACKGROUND: French military surveillance identified an increase in Plasmodium ovale attacks among soldiers in Ivory Coast. This emergence and the low sensitivity of biological tests raise the question of a possible role of P. ovale variant species. METHODS: Epidemiological data about P. ovale attacks from 1993 to 2012 were studied; the species diagnosis was based on a thin blood smear and/or a quick diagnostic test. Clinical and biological features in soldiers hospitalized in 2 French military hospitals were also reviewed. Malaria polymerase chain reaction followed by genotyping was performed when available. RESULTS: French military physicians declared 328 P. ovale attacks over the 20-year study. A peak of incidence occurred in 2005. Among patients with positive blood smears, the quick diagnostic test was positive in 33 of 101 tests performed. The hospital study showed that symptoms and biological changes were not specific, which made diagnosis challenging: fever, anemia, and thrombocytopenia were not present in 20%, 71%, and 23% of the 45 confirmed cases, respectively. It was possible to perform molecular investigations on 19 clinical isolates: 18 were classic haplotypes with additional polymorphism and 1 was variant. CONCLUSIONS: This emergence of P. ovale malaria enabled a good description to be made in nonimmune patients. The lack of sensitivity of both clinical features and quick diagnostic tests suggests an underestimation. Reasons for this outbreak are especially intense exposure to the vectors and the insufficient efficacy of doxycycline against P. ovale. The polymorphism of classic haplotypes of P. ovale rather than variant forms could be involved.

[Molecular markers of Plasmodium falciparum drug resistance]. / Marqueurs moléculaires des résistances de Plasmodium falciparum aux antipaludiques.

The main Plasmodium falciparum genes known to be associated with drug resistance are pfcrt, pfmdr1, pfdhfr pfdhps, pfcytb, pfmrp, pfnhe1, pfmdt, pfserca and pftetQ. Molecular markers for resistance to chloroquine, amodiaquine, mefloquine, sulfadoxine-pyrimethamine, cycloguanil and atovaquone have been validated and used to predict the parasitological and clinical efficacy of these drugs (i.e. based on in vivo tests). These molecular markers have numerous advantages. They allow evaluation of large series of samples in less time than in vivo tests. Collection, transport and storage of samples are much easier than for in vitro tests. These markers can be used for epidemiological monitoring of resistance for an entire country as well as for prediction of therapeutic outcome for a single individual. Development of high-throughput molecular biology techniques, availability of the nucleotidic sequences of P. falciparum genomes, and close collaboration between fundamental researcher workers, clinical practitioners, and officials in charge of the national malaria control programs are major assets in the research and development of molecular markers for P. falciparum resistance to antimalarial drugs.

[Distinguishing Plasmodium falciparum populations for clinical research]. / Distinguer les populations de Plasmodium falciparum en recherche clinique.

The genetic diversity of Plasmodium falciparum is generally high. Study of this diversity is useful to differentiate the strains present in an individual before and after malaria treatment or to check if several individuals have been infected by the same parasites. Interpretation of the in vivo test recommended by the WHO to evaluate antimalarial drug efficacy requires distinguishing recrudescence from new infection when recurrent parasitemia suggests the possibility of therapeutic failure and antimalaria resistance. For this purpose, molecular biology techniques such as nested-PCRs are becoming increasingly available and can now be used in most endemic areas. An effort has been made to standardize P. falciparum genotyping carried out to distinguish recrudescence from new infection. Standardization has focused not only on genotyping methods but also on interpretation criteria. Compliance with these recommendations should improve the quality of clinical research and allow comparison of data from different centers.

[Proteomic analysis and parasitosis: principles and applications]. / Analyses protéomiques et parasitoses: principes et applications.

O'Farrel described a method allowing two-dimensional (2D) protein separation more than 30 years ago. Since then the original technique has made enormous progress. This progress has been accompanied by advances in mass spectrometry technology as well as various genome-sequencing programs. Today 2D electrophoresis has become the workhorse of proteomics, allowing resolution of complex structures containing thousands of proteins and providing a global view of the state of a proteome. This article presents the different steps and limitations of proteomic analysis: preparation of biological material, 2D electrophoresis, protein detection systems, and available tools for protein identification. Alternative proteomic approaches to 2D electrophoresis are also presented. A few applications are described as examples to illustrate the utility of proteomic analysis for studying the mechanisms underlying virulence, resistance to antimalarial therapies and immune response against pathologic agents.

[Metallocenes and malaria: a new therapeutic approach]. / Métallocènes et paludisme: une nouvelle approche thérapeutique.

Rapid development of significant resistance to antimalarial drugs has been a major force driving research to identify and develop new compounds. The use of synthetic organometallic complexes seems to be promising for treatment of malaria infections. Recent progress in identification and development of new drugs promises to lead to a much greater range of antimalarial agents. Organometallic complexes and metalloporphyrins have shown in vitro activity against Plasmodium falciparum. Ferroquine (ferrocenyl chloroquine) is more active than chloroquine against strains and isolates of P. falciparum and shows efficacy against murine parasites.

Malaria epidemic and drug resistance, Djibouti.

Analysis of Plasmodium falciparum isolates collected before, during, and after a 1999 malaria epidemic in Djibouti shows that, despite a high prevalence of resistance to chloroquine, the epidemic cannot be attributed to a sudden increase in drug resistance of local parasite populations.