High, early IFN-gamma production by live parasite-stimulated peripheral blood mononuclear cells is a correlate of immunity to symptomatic malaria in Papua New Guinean children, and natural killer-like gammadelta T cells may contribute to protection.

The interaction between malnutrition and malaria is complex and there is evidence that malnutrition decreases the susceptibility to malaria. To investigate the relation between anthropometric measurements and subsequent malaria morbidity and to examine whether the effect observed was due to interaction with host immunity, we followed for 1 y a cohort of 136 children aged 10 to < 120 mo in Wosera, East Sepik Province, Papua New Guinea. At baseline, 21% were stunted, 10% were wasted, and 5% were both stunted and wasted. After adjustment for age and use of bed nets, height-for-age z score (HAZ) at baseline predicted the number of clinical episodes of falciparum malaria during the following year: incidence rate increased with increasing HAZ. Humoral responses to specific malarial antigens were lowest in the wasted children. The prevalence of lymphoproliferative responders was not significantly different between well-nourished and undernourished children. In contrast, the prevalence of cytokine producers was higher in the undernourished than in the well-nourished children. Our findings support the view that stunting but not wasting protects against falciparum malaria. The mechanism may be related to an improved ability of malnourished children to produce certain cytokines in response to stimulation by specific malarial antigens.

No abstract

The role of early to intermediate Plasmodium falciparum-induced cellular responses in the development of clinical immunity to malaria is not well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes. To investigate whether P. falciparum-induced cellular responses are able to function as predictive correlates of parasitological and clinical outcomes, we conducted a prospective cohort study of children (5 to 14 years of age) residing in a region of Papua New Guinea where malaria is endemic Live, intact P. falciparum-infected red blood cells were applied to isolated peripheral blood mononuclear cells obtained at baseline. Cellular cytokine production, including production of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and gamma interferon (IFN-␥), was measured, and the cellular source of key cytokines was investigated. Multicytokine models revealed that increasing P. falciparum-induced IL-6 production was associated with an increased incidence of P. falciparum clinical episodes (incidence rate ratio [ Individuals living in regions of moderate to high malaria endemicity slowly acquire clinical immunity to Plasmodium falciparum throughout their lives in an age-and exposuredependent manner (3,29). This immunity enables them to control parasite replication at densities below that which induces clinical symptoms (29,46). Both antibody-dependent and T-cell-dependent acquired immune responses have been shown to play an important role in the development of clinical immunity (13,29). The role of early to intermediate cellular responses, however, is less well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes (45,49,51).Early cellular immune responses are rapidly initiated during malaria infection and are thought to play an important role both in limiting initial parasite replication and in directly shaping subsequent adaptive immune responses (45,49,51). However, the overproduction or inappropriate regulation of both proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, gamma interferon (IFN-␥), and tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and anti-inflammatory cytokines, such as IL-10, IL-4, and transforming growth factor ␤ (TGF-␤), may also lead to localized and systemic inflammation and has been associated with symptomatic and severe malaria (7,45). The clinical outcome of an infection may thus depend on the appropriate induction and counterregulation of both pro-and anti-inflammatory cytokine secretion. Understanding how this network of P. falciparum-induced cellular responses is associated with immunity and risk of clinical disease in malaria exposed-children could provide important insights for the development of effective vaccines.Studies investigating the association between P. falciparumor antigen-induced secretion of cytokines from peripheral blood mononuclear cells (PBMCs) and prosp...

The prevalence and concentration of naturally acquired humoral response (IgG) to merozoite surface protein 2 (MSP2), RESA, SPf66 and crude schizont extract were measured in a population living in a malaria highly endemic area of Papua New Guinea. A prospective longitudinal study in 0.5-15 year old children was conducted for one year in order to examine the relationship between the humoral response to these antigens and subsequent susceptibility to clinical malaria using a series of clinical definitions. The prevalence and concentration of antibodies to all antigens increased with age. Such correlation with age was most marked for MSP2 recombinant proteins. When age and previous exposure were controlled for, only antibody levels to MSP2 recombinant proteins (3D7 and d3D7) and to RESA predicted a reduction in incidence rate of episodes of clinical malaria. Our results support the inclusion of the recombinant proteins of the 3D7 allelic family of merozoite surface antigen 2 and RESA into a subunit vaccine against malaria.