Malaria‐Filaria Coinfection in Mice Makes Malarial Disease More Severe unless Filarial Infection Achieves Patency

Graham, Andrea L.; Lamb, Tracey J.; Read, Andrew F.; Allen, Judith E.

doi:10.1086/426871

Cited by 139 publications

(146 citation statements)

References 70 publications

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“…Whenever possible, evidence was taken from the coinfection studies themselves. Helminths in genera Fasciola (43), Heligmosomoides (44), Nippostrongylus (45), Schistosoma (46), and Trichinella (47) were considered to alter RBC availability, whereas helminths in genera Echinostoma (48), Litomosoides (49), and Taenia (50) were not. In equivocal cases [e.g., Trichinella, which alters RBC availability by suppressing erythropoiesis rather than destroying mature RBCs (47)], statisti-cal analysis was used to confirm that conclusions were robust to categorical reassignment.…”

Section: Methodsmentioning

confidence: 99%

Ecological rules governing helminth–microparasite coinfection

Graham

2008

Proc. Natl. Acad. Sci. U.S.A.

344

396

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Coinfection of a host by multiple parasite species has important epidemiological and clinical implications. However, the direction and magnitude of effects vary considerably among systems, and, until now, there has been no general framework within which to explain this variation. Community ecology has great potential for application to such problems in biomedicine. Here, metaanalysis of data from 54 experiments on laboratory mice reveals that basic ecological rules govern the outcome of coinfection across a broad spectrum of parasite taxa. Specifically, resource-based (''bottomup'') and predator-based (''top-down'') control mechanisms combined to determine microparasite population size in helminthcoinfected hosts. Coinfection imposed bottom-up control (resulting in decreased microparasite density) when a helminth that causes anemia was paired with a microparasite species that requires host red blood cells. At the same time, coinfection impaired top-down control of microparasites by the immune system: the greater the helminth-induced suppression of the inflammatory cytokine interferon (IFN)-␥, the greater the increase in microparasite density. These results suggest that microparasite population growth will be most explosive when underlying helminths do not impose resource limitations but do strongly modulate IFN-␥ responses. Surprisingly simple rules and an ecological framework within which to analyze biomedical data thus emerge from analysis of this dataset. Through such an interdisciplinary lens, predicting the outcome of coinfection may become tractable.cytokine ͉ disease ecology ͉ metaanalysis ͉ predation ͉ resource limitation

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Section: Methodsmentioning

confidence: 99%

Ecological rules governing helminth–microparasite coinfection

Graham

2008

Proc. Natl. Acad. Sci. U.S.A.

344

396

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“…Independent studies in Thailand and Senegal demonstrated that individuals harboring helminth parasites have a higher risk of malaria attack than individuals who are worm-free (27,34). A recent study showed that mice coinfected with the filarial parasite Litomosoides sigmodontis and blood-stage Plasmodium chabaudi had more severe malaria disease than mice infected with malaria alone had (17). These observations indicate that a preexisting helminth infection strongly modulates the development of immune protection and immunopathology in the host following a primary malarial infection.…”

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confidence: 99%

Reduced Protective Efficacy of a Blood-Stage Malaria Vaccine by Concurrent Nematode Infection

Segura

Stevenson

2006

Infect Immun

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Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor ␤1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.Helminth infections, which are prevalent in many regions of the world, cause various morbidities in humans including reduced fitness, malnutrition, retarded growth, and anemia (7,8,25,41). In addition, studies with humans and animal models have demonstrated that helminth parasites modulate the immune responses to unrelated pathogens or antigens, which often results in impaired protective immunity to the pathogens (1,4,20,23). For example, patients infected with Ascaris lumbricoides exhibit lower interleukin-2 (IL-2) and gamma interferon (IFN-␥) cytokine responses to cholera vaccine than worm-free individuals exhibit (9). Blood mononuclear cells from patients with filarial infections are more susceptible to human immunodeficiency virus infection and replication than cells from control subjects are (16). In addition, immunization with Mycobacterium bovis BCG vaccine induces a lower level of protection against virulent Mycobacterium tuberculosis challenge in Schistosoma mansoni-infected mice than in S. mansoni-free mice (12).Helminth infections coexist with malaria in many parts of the world and have been shown to modulate the development of host protective immunity to natural malaria infection. Independent studies in Thailand and Senegal demonstrated that individuals harboring helminth parasites have a higher risk of malaria attack than individuals who are worm-free (27,34). A r...

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“…In this sense, theory predicts that multiple infections could be especially injurious for hosts, leading to anaemia, loss of body mass and reduced survival (Graham et al, 2005;Davidar & Morton, 2006). Such effects of malaria double infections have been poorly investigated and the reported results are inconclusive.…”

Section: Pathogenicity Of Avian Malaria Parasitesmentioning

confidence: 99%

Recent Advances in Studies on Avian Malaria Parasites

Marzal¹

2012

Malaria Parasites

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Malaria‐Filaria Coinfection in Mice Makes Malarial Disease More Severe unless Filarial Infection Achieves Patency

Cited by 139 publications

References 70 publications

Ecological rules governing helminth–microparasite coinfection

Ecological rules governing helminth–microparasite coinfection

Reduced Protective Efficacy of a Blood-Stage Malaria Vaccine by Concurrent Nematode Infection

Recent Advances in Studies on Avian Malaria Parasites

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