Mixed-Species Plasmodium Infections of Humans

Abstract

We analyzed point-prevalence data from 35 recent studies of human populations in which Plasmodium falciparum and one other Plasmodium species were the reported causes of malaria infections. For the P. falciparum-Plasmodium vivax pair, higher overall prevalence in a human population is associated with fewer mixed-species infections than expected on the basis of the product of individual species prevalences. This is not true for P. falciparum-Plasmodium malariae.Our current understanding of parasite communities rests on several decades of fruitful studies of helminths (Noble, 1960;Schad, 1963;Kennedy, 1975;Scott and Gibbs, 1986;Stock and Holmes, 1988;Esch et al., 1990;Fernandez and Esch, 1991; Booth and Bundy, 1992;Kennedy and Bush, 1992). Many of the ecological and evolutionary insights from these pioneering studies could be tested among parasitic protists as well, building from analyses of relatively static, simple patterns among a few congeners toward those of dynamic interactions among multiple genera. Among helminths, for instance, Dobson (1985Dobson ( , 1990 Dobson and Roberts, 1994) has emphasized that aggregated intraspecific distributions may diminish interspecific competition, and Font (1991, 1994;Lotz et al., 1995) have stressed that species rarity and recruitment may modulate patterns of interspecific association.Four species of Plasmodium cause human malaria, P. falciparum, P. malariae, P. ovale, and P. vivax. Sympatric combinations of these species occur in human populations and within infected individuals. Various phenomena associated with species co-occurrence have been studied as such for more than a century, e.g., Thayer and Hewetson (1895), since an era in which the very existence of more than one species was subject to debate. Biogeographic anomalies such as the absence of P. vivax and presence of P. ovale in West Africa and the spotty worldwide distribution of P. malariae have periodically attracted intense interest (see Molineaux, 1988), as have the frequencies of species co-occurrence within individuals and the possible correlates of mixed-species infections. This paper focusses on the latter 2 topics, particularly in those human populations in which recent reports suggest that only P. falciparum and 1 other Plasmodium species co-occur.In a massive survey of Plasmodium species prevalence in humans, Knowles and White (1930) recorded mixed-species infections at various frequencies at various sites on all 6 inhabited continents and noted that particular species combinations were often seasonal. They complained that mixed-species infections were often underreported, and demonstrated the phenomenon in a test of microscopists. Cohen's (1973) analysis of the epidemiological literature concluded that deficits in the reported prevalence of mixed-species infections were not wholly artifactual, but common, often statistically significant phenomena with a previously unsuspected biological basis in heterologous immunity. His hypothesis was later extended to encompass the seasonal species pa...

Age-structured red blood cell susceptibility and the dynamics of malaria infections

“…Because circulating RBCs are anucleate and cannot synthesize new surface molecules, receptors that decay cannot be replaced; reticulocyte susceptibility to P. vivax may be related to higher Duffy-antigen density, for instance (20). If RBC susceptibility to P. malariae is related to senescence markers, the accelerated senescence of uninfected RBCs reported with P. falciparum (21) should greatly affect mixed-species infections (22). The common portrayal of P. falciparum as a generalist is complicated by evidence of a seeming preference for young RBCs (23), but more detailed resolution is needed here as well: our model shows that the proportion of RBCs that is in young age classes increases as an infection proceeds.…”

Prospective risk of morbidity in relation to malaria infection in an area of high endemicity of multiple species of Plasmodium.

“…vivax/P. malariae species mix, 3,21 suggesting that there is suppression of heterologous parasites. A recent study from a site in PNG neighboring the Wosera with all four human malaria species found no associations.…”

“…2 A recent analysis of point-prevalence data from 35 studies of human populations found that for the P. falciparum-P. vivax pair, a higher overall prevalence is associated with fewer mixed-species infections than would be expected on the basis of individual species prevalences. 3 This may in part be due to immunologically cross-reactive epitopes between P. falciparum and P. vivax. 4 However, there was no negative correlation for the P. falciparum-P. malariae, 3 and longitudinal studies indicate that malarial parasites can also favourably affect the host environment for other species.…”

“…3 This may in part be due to immunologically cross-reactive epitopes between P. falciparum and P. vivax. 4 However, there was no negative correlation for the P. falciparum-P. malariae, 3 and longitudinal studies indicate that malarial parasites can also favourably affect the host environment for other species. 5,6 Summarizing the literature available in 1988, Richie 1 argued that suppression of one species by another could be a result of competition for nutrients or for host cells, or of an immune-mediated ceiling to parasite density.…”

Malaria infections are randomly distributed in diverse holoendemic areas of Papua New Guinea.

“…[1][2][3][4][5][6][7][8][9] Various epidemiologic studies involving species co-occurrence recorded fewer mixed infections than expected by chance, suggesting in-host competitive interactions whereby one species has eliminated, or reduced the density of, another species to an undetectable level. [6][7][8][9] These interactions may be mediated by innate host factors that regulate parasite density, 10 parasite metabolism, or factors contributing to the acquisition of heterologous (or cross-species) immunity. 11,12 If heterologous immunity reduces the prevalence of mixed species infections, as has been proposed, [11][12][13] a malaria vaccine may not need to be specific for each species of Plasmodium to be effective.…”