Relapses in Plasmodium Ovale and Efficacy of Artemether-lumefantrine for Mixed Species and Non-falciparum Malaria

Summary

Malaria is a protozoan infection transmitted by anopheline mosquitoes. The most severe forms are caused by Plasmodium (P) falciparum and to a much lesser extent by P. vivax. Although the interest in research on malaria has increased during the last years, yet little research is conducted on the "neglected" malaria species P. ovale and P. malariae. P. ovale being first described in 1922, it still remains unclear whether it displays dormant pre-erythrocytic liver stages, so called hypnozoites, or not. Primaquine, the only marketed drug with liver stage activity at present, can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient persons and methemoglobinemia. Because G6PD is widely spread in Central Africa, it is important to explore whether additional intake of liver-active medication is really needed and on this account further research to investigating new treatment options with liver stage activity should be conducted. While, due to widespread resistance, treatment recommendations for P. falciparum and mixed infections have switched from chloroquine to the safer applicable artemisinin-based combination therapies (ACTs), World Health Organization (WHO) guidelines still suggest chloroquine as first line treatment for P. malariae and P. ovale mono infections. Further studies assessing alternative treatment options are largely missing. Summing up the current situation for both topics shows the need for further research. Therefore this study aims to assess the evidence and characterize the frequency of relapses in P. ovale infections with respect to differences between its subspecies as well as the effectiveness of the ACT artemether-lumefantrine in P. malariae and P. ovale mono- and mixed infections.

Timeline

Start

2014-10

Primary completion

2016-10

Completion

2016-10

Publications

• Background Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, Kremsner PG. Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg. 2001 Nov;65(5):599-602. doi: 10.4269/ajtmh.2001.65.599.
• Background Richter J, Franken G, Mehlhorn H, Labisch A, Haussinger D. What is the evidence for the existence of Plasmodium ovale hypnozoites? Parasitol Res. 2010 Nov;107(6):1285-90. doi: 10.1007/s00436-010-2071-z. Epub 2010 Oct 5.
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• Background Greenwood BM, Bradley AK, Greenwood AM, Byass P, Jammeh K, Marsh K, Tulloch S, Oldfield FS, Hayes R. Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg. 1987;81(3):478-86. doi: 10.1016/0035-9203(87)90170-2.
• Background Perandin F, Manca N, Calderaro A, Piccolo G, Galati L, Ricci L, Medici MC, Arcangeletti MC, Snounou G, Dettori G, Chezzi C. Development of a real-time PCR assay for detection of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale for routine clinical diagnosis. J Clin Microbiol. 2004 Mar;42(3):1214-9. doi: 10.1128/JCM.42.3.1214-1219.2004.
• Groger M, Veletzky L, Lalremruata A, Cattaneo C, Mischlinger J, Zoleko-Manego R, Endamne L, Klicpera A, Kim J, Nguyen T, Flohr L, Remppis J, Matsiegui PB, Adegnika AA, Agnandji ST, Kremsner PG, Mordmuller B, Mombo-Ngoma G, Ramharter M. Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae, Plasmodium ovale, and Mixed Plasmodium Malaria in Gabon. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01758-17. doi: 10.1128/AAC.01758-17. Print 2018 Mar.

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