Why do we need to know more about mixed Plasmodium species infections in humans?

doi:10.1016/j.pt.2004.07.004

Trends in Parasitology

Volume 20, Issue 9, September 2004, Pages 440-447

https://doi.org/10.1016/j.pt.2004.07.004 Get rights and content

Four Plasmodium species cause malaria in humans. Most malaria-endemic regions feature mixed infections involving two or more of these species. Factors contributing to heterogeneous parasite species and disease distribution include differences in genetic polymorphisms underlying parasite drug resistance and host susceptibility, mosquito vector ecology and transmission seasonality. It is suggested that unknown factors limit mixed Plasmodium species infections, and that mixed-species infections protect against severe Plasmodium falciparum malaria. Careful examination of methods used to detect these parasites and interpretation of individual- and population-based data are necessary to understand the influence of mixed Plasmodium species infections on malarial disease. This should ensure that deployment of future antimalarial vaccines and drugs will be conducted in a safe and timely manner.

Section snippets

Plasmodium species diagnosis

Blood-smear diagnosis is the most widely utilized approach for generating malaria infection data for epidemiological studies focused on mixed-species infections. In addition, PCR-based methodologies have introduced new strategies for malaria diagnosis worthy of consideration. Both techniques encounter qualitative and quantitative limitations.

The blood-smear produces quantitative information and the range of parasitemia detected generally corresponds with clinical malaria. However, blood-smear

Infection dynamics

Human infection studies such as those performed during the era of the neurosyphilis trials 31, 32, 33 are not repeatable [34]; however, these early patient studies contributed significantly to our ability to work with malaria parasites in research laboratories over the past 75 years, as well as to our understanding of the basic characteristics of human malaria infection [35]. To interpret mixed Plasmodium species infections, basic biological characteristics of infection by each species must be

Immunological crossreactivity

Although early studies investigating mixed Plasmodium species interactions suggested that it might be possible for antigenic similarities between species to allow an individual vaccine molecule derived from one species to offer protection from the other human malaria parasites [55], data to support this hypothesis have not been produced [56]. In fact, little if any cross-species immunity was observed during the malaria fever therapy trials, and individuals exposed to one Plasmodium species did

Impact of mixed-species infection on malarial disease

Several different studies have now reported that P. vivax infections help to reduce the severity of P. falciparum malaria 65, 66, 67, 68. The study conducted in Vanuatu [65] suggested that α⁺ thalassemia might predispose young children to the more ‘benign’ P. vivax infection, which proves beneficial later when children become most susceptible to severe P. falciparum malaria. In studies from Thailand, Luxemburger et al. [66] reported that severe P. falciparum malaria was reduced from 5.7% (293

Conclusion

We need to know more about mixed Plasmodium species infections because we know so little about the mechanisms regulating innate and acquired immunity against malaria in children under five years old, who bear the greatest risk of disease. As malaria affects humans at individual and population levels differently across environmentally varying regions [69], it is important to encourage continued survey of malaria through both prevalence and longitudinal studies, and to improve diagnostic

Acknowledgements

We thank the Wosera community for their willing participation in our ongoing malaria field studies; L. Rare, M. Baisor and B. Kiniboro for supervising and conducting our field studies; K. Lorry for malaria microscopy; and M. Bockarie for PNG field coordination. We thank J. Reeder, I. Mueller, J. Adams, C. King and S. Patel for helpful criticisms of this manuscript. This work was supported by grants from the National Institutes of Health (AI46919–01A2 and 1RO1AI52312–01).

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Trends in Parasitology

Why do we need to know more about mixed Plasmodium species infections in humans?

Section snippets

Plasmodium species diagnosis

Infection dynamics

Immunological crossreactivity

Impact of mixed-species infection on malarial disease

Conclusion

Acknowledgements

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Mol. Biochem. Parasitol.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

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Studies in the parasitology of malaria

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High prevalence of Plasmodium malariae and Plasmodium ovale in malaria patients along the Thai–Myanmar border, as revealed by acridine orange staining and PCR-based diagnoses

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Rare quadruple malaria infection in Irian Jaya Indonesia

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Random distribution of mixed species malaria infections in Papua New Guinea

Am. J. Trop. Med. Hyg.

A longitudinal study of human malaria in the West African Savanna in the absence of control measures: relationships between different Plasmodium species, in particular P. falciparum and P. malariae

Am. J. Trop. Med. Hyg.

The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity

Ann. Trop. Med. Parasitol.

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Parasitology

Mixed-species Plasmodium infections of humans

J. Parasitol.

Vernal vivax activity in persons simultaneously inoculated with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

Simultaneous inoculation with Plasmodium vivax and Plasmodium falciparum

Am. J. Trop. Med.

Epidemiological significance of repeated infections with homologous and heterologous strains and species of Plasmodium

Bull. World Health Organ.

Cross-species interactions between malaria parasites in humans

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Pathways and strategies for developing a malaria blood-stage vaccine

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Impact of microscopy error on estimates of protective efficacy in malaria-prevention trials

J. Infect. Dis.