Plasmodium malariae is widely distributed across the tropics, causing symptomatic
malaria in humans with a 72-hour
fever periodicity, and may present after latency periods lasting up to many decades. Delayed occurrence of symptoms is observed in humans using
chemoprophylaxis, or patients having received
therapies targeting P. falciparum intraerythrocytic asexual stages, but few investigators have addressed the
biological basis of the ability of P. malariae to persist in the human host. To investigate these interesting features of P. malariae epidemiology, we assembled, here, an extensive case series of P. malariae
malaria patients presenting in non-endemic China, Sweden, and the UK who returned from travel in endemic countries, mainly in Africa. Out of 378 evaluable P. malariae cases, 100 (26.2%) reported using at least partial
chemoprophylaxis, resembling the pattern seen with the relapsing parasites P. ovale spp. and P. vivax. In contrast, for only 7.5% of imported UK cases of non-relapsing P. falciparum was any
chemoprophylaxis use reported. Genotyping of parasites from six patients reporting use of
atovaquone-proguanil chemoprophylaxis did not reveal mutations at
codon 268 of the cytb locus of the P. malariae mitochondrial genome. While travellers with P. malariae
malaria are significantly more likely to report prophylaxis use during endemic country travel than are those with P. falciparum
infections,
atovaquone-proguanil prophylaxis breakthrough was not associated with pmcytb mutations. These preliminary studies, together with consistent observations of the remarkable longevity of P. malariae, lead us to propose re-examination of the dogma that this species is not a relapsing parasite. Further studies are needed to investigate our favoured hypothesis, namely that P. malariae can initiate a latent hypnozoite developmental programme in the human hepatocyte: if validated this will explain the consistent observations of remarkable longevity of parasitism, even in the presence of
antimalarial prophylaxis or treatment.