Cytokine and Antibody Responses to Plasmodium falciparum in Naïve Individuals during a First Malaria Episode: Effect of Age and Malaria Exposure

Abstract

Age- and exposure-dependent immune responses during a malaria episode may be key to understanding the role of these factors in the acquisition of immunity to malaria. Plasma/serum samples collected from naïve Mozambican children (n = 48), European adults (naïve travelers, n = 22; expatriates with few prior malaria exposures, n = 15) and Mozambican adults with long-life malaria exposure (n = 99) during and after a malaria episode were analyzed for IgG against merozoite proteins by Luminex and against infected erythrocytes by flow cytometry. Cytokines and chemokines were analyzed in plasmas/sera by suspension array technology. No differences were detected between children and adults with a primary infection, with the exception of higher IgG levels against 3D7 MSP-142 (P = 0.030) and a P. falciparum isolate (P = 0.002), as well as higher IL-12 (P = 0.020) in children compared to other groups. Compared to malaria-exposed adults, children, travelers and expatriates had higher concentrations of IFN-γ (P≤0.0090), IL-2 (P≤0.0379) and IL-8 (P≤0.0233). Children also had higher IL-12 (P = 0.0001), IL-4 (P = 0.003), IL-1β (P = 0.024) and TNF (P = 0.006) levels compared to malaria-exposed adults. Although IL-12 was elevated in children, overall the data do not support a role of age in immune responses to a first malaria episode. A TH1/pro-inflammatory response was the hallmark of non-immune subjects.

Cytokine Profiling in Immigrants with Clinical Malaria after Extended Periods of Interrupted Exposure to Plasmodium falciparum

“…In this line, we had previously observed that this group of travelers had higher levels of IFN- γ compared to malaria-exposed individuals (after few or continuous exposure) [23]. Nevertheless, similar parasitemias were observed in immigrants and travelers suggesting that there are no differences in parasite-controlling immunity, but rather in the cellular responses controlling disease.…”

“…Sick volunteers enrolled in the study were African adults residing in Spain (immigrants, n=55) and adults from non-African origin without previous episodes of malaria (travelers, n=22) [23] who had been diagnosed with P. falciparum malaria after traveling to an African country.…”

“…Blood samples from acute malaria episodes (day 0) and at convalescence after malaria treatment (days 7 and 28) and blood samples from non-malaria patients were collected by venipuncture into one vacutainer without anticoagulant for serum cryopreservation at -80 ° C. Clinical and demographical data were recorded in standardized questionnaires. Data on cytokine levels in serum from travelers have been previously published [23], but are re-analysed here for comparison to the immigrant group.…”

“…For non-normally distributed continuous variables, medians and interquartile ranges (IRQ) were shown and their comparison between groups was done using the non-parametric Kruskal Wallis test or the Mann–Whitney U test. TNF-β was excluded from the statistical analysis since concentration in most samples was below the limit of detection (14/267 [5.24%]) as we have observed before in previous studies [8,23]. Correlations within groups were assessed by Spearman’s rank coefficient.…”

Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria

“…falciparum (n = 25) presenting clinical malaria at MDH were recruited between 2004 and 2005 [41]. European adults presenting a first episode of malaria after a travel to malaria endemic areas (n = 21), were recruited between 2005 and 2009 at HCB (Spain) [68]. Before treatment, peripheral blood was collected by venipuncture and 2 drops were spotted onto filter paper.…”