Trends in Parasitology
Worms can worsen malaria: towards a new means to roll back malaria?
Section snippets
Mixed infections
In contrast to laboratory models, humans infected with malaria are exposed to a large number of concomitant acute or persistent infections due to viruses (e.g. hepatitis B, influenza and HIV), bacteria (e.g. Shigella and Staphylococcus) and a variety of parasites (e.g. other protozoa, intestinal worms, schistosomes and filariae) 1, 2, 3. Each of these pathogens, particularly those causing chronic infection, can influence the host immune system. Because of the large number of pathogens
Insight into malarial immunity provides new hypotheses
Recent studies of the acquisition of immune protection against malaria that focused primarily on clinical investigations in humans 4, 5 provided information about the potential interaction between helminthic infections and malaria.
Immunity to malaria erythrocytic stages builds up progressively in children from endemic areas. The immune can control parasite loads and tolerate parasitemia without clinical manifestations of the disease by the age of 15–25 years [6]. The extremely slow development
An effect as significant as that of sickle-cell anemia
Further studies were initiated under epidemiological conditions in which no preliminary anthelmintic treatment by levamisole, which has immunomodulatory effects, was necessary.
One was conducted in the village of Dielmo (Sénégal), where all 220 inhabitants were actively followed on a daily basis to record malaria incidence [7]. All intestinal helminthic infections had been cured at the initiation of the field study, although a stool examination revealed that 13 of the 80 children in the village
Implications for rolling back malaria
These observations, all but one of which deal only with P. falciparum, have important fundamental and practical consequences. From a fundamental point of view, the influence of worms raises several immunological questions that are important for vaccine development. Initial epidemiological studies of worm–malaria interactions were prompted by the hypothesis that worms might trigger, through a T helper (Th)2 response, the production of non-cytophilic, clinically non-effective antibodies [8].
Vaccine trials risk flawed results
Currently, a large number of experimental antimalarial vaccines‡ is either undergoing or about to enter clinical trials. Worms seem to be an important confounding factor in assessing the efficacy of these trials, and one that deserves to be investigated systematically in future vaccine trials. Indeed, the effects of
Future perspectives
Many children are suffering and dying from malaria. If, as indicated by the studies discussed in this article, their status could be substantially improved by deworming and water sanitation, it would be important to document further this affordable means of control urgently. However, the single report that suggests an opposite effect [16], specifically that of protection against severe malaria, underscores the importance of conducting scientifically rigorous and carefully designed studies to
Acknowledgements
We thank the populations of Madagascar, Dielmo and Richard-Toll, and all members of the medical and technical teams who participated in these studies. We thank Jean Louis Pérignon, Georges Snounou, Christian Roussilhon and Zarifah Hussain-Reed for useful advice about the manuscript.
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