This confirmation of host sharing

This confirmation of host sharing characteristics has long been pending Coatney, 1971; Escalante et al., 1995 and might give a reason to re-appraise quartan malaria, a largely neglected disease thus far, with the qualities to become an emerging infection. In 1890, P. malariae was the first malaria species to get a scientific name (Collins and Jeffery, 2007). To date, the causative agent of quartan malaria has been largely understudied, mainly because—due to low levels of parasitaemia—in most epidemiological surveys only a few infections were detected (Mueller et al., 2007). Nonetheless, in studies with improved detection limits, P. malariae has been demonstrated in all malaria-endemic regions of the world Autino et al., 2012 and therefore—strictly speaking—might be the malaria parasite with the widest geographical distribution. Furthermore, quartan malaria hdac inhibitors might represent the best adapted malaria parasites. The adaption of these protozoans to its hosts results in a mainly chronic clinical outcome with many carriers suffering no symptoms. It is well-known that quartan parasites can persist in dormancy for decades in the host without causing symptoms (Collins and Jeffery, 2007). For example, two chimpanzees, Takaboh and Oumu, acquired quartan P. malariae-like parasites in the African rain forest when they were babies, and the parasites remained undiscovered until detection 30years after their first day of confinement in a Japanese zoo (Hayakawa et al., 2009). This is perplexing because “hypnozoites”—as in P. vivax and P. ovale—have never been discovered or have not been well investigated. What discriminates quartan malaria parasites from other Plasmodium spp. is their expansive reservoir of mammalian hosts. Besides the human host, there have been studies showing quartan malaria parasites in several dozens of monkey species. Merely in South America, quartan parasites were described in 35 monkey species (as P. brasilianum) (Fandeur et al., 2000). In Asia, monkeys are infected by the quartan Plasmodium inui (Coatney et al., 2003), and in the African rain forest, great apes are infected by quartan parasites (as Plasmodium rodhaini or P. malariae, and P. malariae-like) (Ramasamy, 2014). To our knowledge, this is by far the widest host reservoir compared with malaria of other periodicity. Clinically, quartan malaria is considered as relatively harmless, but sufficient data are lacking to substantiate this assessment. Many investigators assume that P. malariae is the causal factor—perhaps with co-factors—for renal pathologies (Ehrich and Eke, 2007). Generally, it can be assumed that the clinical outcome of P. malariae infections is misinterpreted (McKenzie et al., 2001). Due to the chronic nature of the infection, capturing the true burden of the disease would require large longitudinal studies to assess the impact of the infection on occupational and social life of an individual. Globally, the disease burden of quartan malaria is difficult to assess, because data on the incidence of P. malariae are faulty. The main reason is that P. malariae is principally underdiagnosed, because it thrives with a few hard-to-detect parasites, which are indistinguishable from P. vivax on the thick blood smear and which can also be misinterpreted as P. falciparum. Therefore, time-consuming reading of a thin smear or molecular methods would be necessary to identify this species. This explains why in the 1980s the Brazilian Health Ministry had “eradicated” P. malariae from Brazil by simply switching the official method of diagnosis from thin to thick blood smear (Oliveira-Ferreira et al., 2010). In areas with marked variation in seasonal climate, P. malariae may account for 50% of the malaria episodes during the low-transmission season (Greenwood et al., 1987). As P. malariae is commonly found in sympatry with other Plasmodium species of humans, better understanding of species-interaction is necessary. Especially the interactions with P. falciparum in mixed infections is a controversially discussed topic (Mueller et al., 2007). Recent seroepidemiological and biomolecular surveys indicated that the prevalence of P. malariae are underestimated Mueller et al., 2007; Autino et al., 2012 and high prevalences of P. malariae have been reported from Africa (Doderer-Lang et al., 2014), Asia (Bharti et al., 2013), and Latin America (Volney et al., 2002). These findings correspond well with results of our pilot study of the Upper Orinoco Metzger et al., 2008 which prompted us to undertake the current investigation.