Quinine Treatment Selects the pfnhe-1 ms4760-1 Polymorphism in Malian Patients with Falciparum Malaria

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kolle and Faladie, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.Howard Hughes Medical Institute [55005502]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; European and Developing Countries Clinical Trials Partnership [EDCTP IP_07_31060_002]info:eu-repo/semantics/publishedVersio

Molekulare und zellulaere Mechanismen der Parasit-Wirt-Interaktion Schlussbericht

The research centered on two parasitic diseases, amoebiasis and onchocerciasis. Amebiasis is caused by Entamoeba histolytica that affects more than 50 Mio individuals worldwide. The causing agent on onchocerciasis is Onchocerca volvulus that affects 20 Mio people worldwide, 100 mio are at riks. Aim of the amoebiasis research projects was to identify factors responsible for invasion and destruction of host tissue and for interaction with host-derived defense cells. These factors could be identified and characterized on the molecular level. With recombinant proteins antigens were proven to be promising candidates for an effective vaccination against Entamoeba histolytica. By transfection studies genes shall now be identified that transforme apathogenic ameba into pathogenic ones. (orig.)Available from TIB Hannover: F98B1178 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman