The role of cytokines in Plasmodium vivax malaria

Abstract

The cytokine tumor necrosis factor and other as yet unidentified factor(s) which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s) are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TNF levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheless serum TNF levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.

CD4+CD25+Foxp3+Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

“…Cytokine levels correlated with changes in hemoglobin levels and lymphocyte and platelet counts, but not with the expansion of the CTLA-4 ϩ subset of Treg cells observed during acute infections, and decreased substantially in vivax malaria patients after chemotherapy with chloroquine. We and others (12) failed to confirm previous observations of extremely high levels of circulating proinflammatory cytokines in vivax malaria patients, close to those usually found in P. falciparum-infected cerebral malaria patients (32). In fact, the balance between pro-and anti-inflammatory responses tended to differ between P. vivax and P. falciparum infections, in opposite directions, with the highest IL-10/TNF-␣ ratio observed in vivax malaria patients.…”

Plasmodium vivax Blood-Stage Dynamics

“…We found no evidence of the 5-day intervals between gametocyte "showers" remarked on by Boyd, Stratman-Thomas, and Muench (1936). Fevers did not affect the presence or density of gametocytes or the success of feeds, in contrast to the report of Eyles et al (1948), who found infectivity lower in asymptomatic than in symptomatic phases of P. vivax infection, and that of Mendis and Carter (1992), who reported a decline in infectivity at the febrile "crisis" stages of infections.…”

“…We found no evidence of the 5-day intervals between gametocyte "showers" remarked on by Boyd, Stratman-Thomas, and Muench (1936). Fevers did not affect the presence or density of gametocytes or the success of feeds, in contrast to the report of Eyles et al (1948), who found infectivity lower in asymptomatic than in symptomatic phases of P. vivax infection, and that of Mendis and Carter (1992), who reported a decline in infectivity at the febrile "crisis" stages of infections.Our results indicate that an absence of detected gametocytes of either sex does not hinder P. vivax transmission to Anopheles and that the presence of abundant gametocytes of either sex does not guarantee it; this is in line with most previous reports (Boyd and Stratman-Thomas, 1932;Boyd et al, 1935;Boyd, 1942a;Watson, 1945). However, our results also support the hypothesis that "the best estimate of the potential infectivity of a patient can be made on the basis of the male gametocyte count" (Eyles et al, 1948).…”

The anaemia of Plasmodium vivax malaria

“…The non-specific immune response for a given parasitaemia is greater for P. vivax than P. falciparum and may partially explain the greater proportional removal of non-parasitized cells and lower fever threshold in vivax malaria [114-116]. This is a relatively weak speculation however since in severe falciparum malarial anaemia, cytokine levels are generally lower than in cerebral or uncomplicated attacks [96,97] and cytokine concentrations have not been found to correlate with the degree of anaemia in P. vivax infections [105].…”