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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case–control study

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Eduard Rovira-Vallbona, Gemma Moncunill, Quique Bassat, Ruth Aguilar, Sonia Machevo, Laura Puyol, Llorenç Quintó, Clara Menéndez, Chetan E Chitnis, Pedro L Alonso, Carlota Dobaño, Alfredo Mayor
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-181) contains supplementary material, which is available to authorized users.
Eduard Rovira-Vallbona, Gemma Moncunill, Carlota Dobaño and Alfredo Mayor contributed equally to this work.

Competing interests

Authors declare that they have no competing interests.

Abstract

Background

The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM.

Methods

To identify immune responses associated with SM, a sex- and age-matched case–control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-α rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-γ, IL-4, IL-5, IL-10, IL-8, IL-6, IL-1β, TNF, TNF-β and TGF-β1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar’s and Signtest.

Results

Compared to UM, matched children with SM had reduced levels of IgG against DBLα (P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-β1 (P <0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047, respectively). Anti-DBLα IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P = 0.026).

Conclusions

The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting Pf EMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.
Zusatzmaterial
Additional file 1: Spearman’s rank correlation coefficients between IgG and IgM levels in the study population. * P < 0.05. (PDF 14 KB)
12936_2012_2197_MOESM1_ESM.pdf
Additional file 2: Matched comparisons of antibody levels and cytokine and chemokine concentrations in children with different severe malaria clinical presentations. (PDF 23 KB)
12936_2012_2197_MOESM2_ESM.pdf
Additional file 3: Spearman’s rank correlation coefficients between cytokine and chemokine concentrations in the study population. * P < 0.05. (PDF 12 KB)
12936_2012_2197_MOESM3_ESM.pdf
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
12936_2012_2197_MOESM6_ESM.pdf
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