title: Clinical implications of a gradual dormancy concept in malaria.
abstract: Malaria recurrences after an initially successful therapy and malarial fever occurring a long time after infection are well-known problems in malariology. Currently, two distinct types of malaria recurrences are defined: recrudescence and relapse. A recrudescence is thought to originate from circulating Plasmodium blood stages which do not cause fever before a certain level of a microscopically detectable parasitemia is reached. Contrary, a relapse is thought to originate from quiescent intracellular hepatic parasite stages called hypnozoites. Recrudescences would typically occur in infections due to Plasmodium falciparum. Plasmodium knowlesi, and Plasmodium malariae, whereas relapses would be caused exclusively by Plasmodium vivax and Plasmodium ovale. This schematic view is, however, insufficiently supported by experimental evidence. For instance, hypnozoites of P. ovale have never been experimentally documented. On the other hand, the nonfinding of P. malariae hypnozoites turned into the proof for the nonexistence of P. malariae hypnozoites. Clinical relapse-type recurrences have been observed in both P. ovale and P. malariae infections, and decade-long incubation times have also been reported in P. falciparum infections. We propose a gradual hypothesis in accordance with the continuity concept of biological evolution: both, relapse and recrudescence may be potentially caused by all Plasmodium spp. We hypothesize that the difference between the various Plasmodium spp. is quantitative rather than qualitative: there are Plasmodium spp. which frequently cause relapses such as P. vivax, particularly the P.v. Chesson strain, species which cause relapses less frequently, such as P. ovale and sometimes P. malariae, and species which may exceptionally cause relapses such as P. falciparum. All species may cause recrudescences. As clinical consequences, we propose that 8-aminquinolines may be considered in a relapse-type recrudescence regardless of the causal Plasmodium sp., whereas primaquine relapse prevention might not be routinely indicated in malaria due to P. ovale.
authors.affiliation: Tropical Medicine Unit, Department for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. Joachim.Richter@med.uni-duesseldorf.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Richter
authors.affiliation: Institute for the History of Medicine, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Franken
authors.affiliation: Tropical Medicine Unit, Department for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Holtfreter
authors.affiliation: Institute for Zoomorphology, Cell Biology and Parasitology, Faculty of Biology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walter
authors.affiliation: Institute for the History of Medicine, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Labisch
authors.affiliation: Institute for Zoomorphology, Cell Biology and Parasitology, Faculty of Biology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Mehlhorn
mesh_terms: D006801:Humans; D000634:Aminoquinolines / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary; D018512:Parasitemia; D010961:Plasmodium / Q000187:drug effects / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D016790:Plasmodium knowlesi / Q000187:drug effects / Q000502:physiology; D010965:Plasmodium malariae / Q000187:drug effects / Q000502:physiology; D041122:Plasmodium ovale / Q000187:drug effects / Q000502:physiology; D010966:Plasmodium vivax / Q000187:drug effects / Q000502:physiology; D011319:Primaquine / Q000627:therapeutic use; D012008:Recurrence; D013045:Species Specificity; D009033:Culicidae; D000818:Animals
chemical_list: C080436:8-aminoquinoline; D000634:Aminoquinolines; D000962:Antimalarials; D011319:Primaquine
keywords: Hypnozoites; Latency; Long incubation; Malaria; P. falciparum; P. knowlesi; P. malariae; P. ovale; P. vivax; Plasmodium; Recrudescence; Recurrence; Relapse