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Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection.

ABSTRACT: Hyperbilirubinaemia (bilirubin >51.3 ?mol/L) alone is not indicative of severe malaria, and the immune response underlying hyperbilirubinaemia remains largely unexplored. Liver damage associated with hyperbilirubinaemia may alter the expression of hepcidin, which regulates systemic iron by degrading ferroportin. For this study, the association between hepcidin and the levels of cytokines and chemokines in the serum of individuals with mild and severe vivax malaria and subjects with malaria with isolated hyperbilirubinaemia was evaluated.Cytokines/chemokines and hepcidin were measured in individuals with mild (n = 72) and severe (n = 17) vivax malaria, as well as in the serum of subjects with vivax malaria with isolated hyperbilirubinaemia (n = 14) from the Brazilian Amazon between 2009 and 2013 by multiplex assay and ELISA, respectively. The polymorphism 744 G > T in the ferroportin gene was identified by restriction fragment-length polymorphism analysis and the restriction enzyme PvuII.The polymorphism at position 744 G > T in the ferroportin gene was typed and no differences in the distributions of genotypes or alleles were observed between the study groups. Subjects with severe malaria had higher levels of interleukin (IL)-2 and IL-13 than subjects with hyperbilirubinaemia. No differences in the expression of immune markers were observed between subjects with mild malaria and those with hyperbilirubinaemia. However, hepcidin levels were higher in individuals with severe malaria and hyperbilirubinaemia than those with mild malaria (p = 0.0002 and p = 0.0004, respectively) and cut-off values of hepcidin differentiated these groups from subjects with mild malaria. Hepcidin was positively associated with IL-6 and IL-10 levels and with parasitaemia in subjects with mild malaria and with IFN-? in subjects with severe malaria.Malaria in the presence of hyperbilirubinaemia produces a less robust inflammatory response compared to severe cases of malaria. Hepcidin levels are positively associated with immune markers in vivax malaria outcomes.

SUBMITTER: Mendonca VR

PROVIDER: S-EPMC4607001 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection.

Mendonça Vitor R R VR Souza Ligia C L LC Garcia Gabriela C GC Magalhães Belisa M L BM Gonçalves Marilda S MS Lacerda Marcus V G MV Barral-Netto Manoel M

Malaria journal 20151014

<h4>Background</h4>Hyperbilirubinaemia (bilirubin >51.3 μmol/L) alone is not indicative of severe malaria, and the immune response underlying hyperbilirubinaemia remains largely unexplored. Liver damage associated with hyperbilirubinaemia may alter the expression of hepcidin, which regulates systemic iron by degrading ferroportin. For this study, the association between hepcidin and the levels of cytokines and chemokines in the serum of individuals with mild and severe vivax malaria and subjects ...[more]

PMID: 26466783

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Project description:BackgroundPlasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.Methods/principal findingsWe searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%).ConclusionOverall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.

Project description:The identification of epidemiological pattern of infection with Plasmodium falciparum and Plasmodium vivax in malaria-endemic area, where multiple episodes are common, is important for intervention programmes.A longitudinal cohort study based on weekly house-to-house visits was conducted between July 2008 and June 2010 in 2040 children less than 10 years of age, living nearby the Gilgel-Gibe hydroelectric power dam reservoir in order to determine factors associated with increased P. vivax and P. falciparum incidence. Two types of multivariate frailty models were applied (using time-to-first malaria episode data and time-to-recurrent malaria episode data), allowing the estimation of adjusted hazard ratios (AHR) of potential risk factors (gender, age, proximity to the dam reservoir, and season) for species-specific malaria incidence.Of 2040 children in 96 weeks of follow up, 864 children experienced at least one malaria episode: 685 due to P. falciparum in 548 children, and 385 due to P. vivax in 316 children. Plasmodium vivax and P. falciparum malaria incidence rates were 8.2 (95 % CI: 7.3-9.1) and 14.6 (95 % CI: 13.4-15.6) per 1000 children per month, respectively. According to the time-to-recurrent event models, children aged ?7 years had a lower risk of presenting P. vivax episodes (AHR = 0.6; 95 % CI: 0.4-0.9), but a higher risk of P. falciparum episodes, when compared with children under ?3 years (AHR = 1.2; 95 % CI: 1.1-1.6). In addition, P. vivax (AHR = 2.7; 95 % CI: 2.2-3.5) and P. falciparum (AHR = 16.9; 95 % CI: 14.3-20.2) episodes were respectively 2.7 and 16.9 times more frequent in the dry season than in the long rainy season.The analysis of all malaria episodes (first and recurrent episodes) in the malaria cohort suggests different species-specific patterns of malaria disease in children, with mild seasonality in the incidence of P. vivax episodes mostly observed in younger age groups, and with marked seasonality in the incidence of P. falciparum episodes mainly seen in older children.

Project description:BACKGROUND:Malaria in Nigeria is principally due to Plasmodium falciparum and, to a lesser extent to Plasmodium malariae and Plasmodium ovale. Plasmodium vivax is thought to be absent in Nigeria in particular and sub-Saharan Africa in general, due to the near fixation of the Duffy negative gene in this population. Nevertheless, there are frequent reports of P. vivax infection in Duffy negative individuals in the sub-region, including reports from two countries sharing border with Nigeria to the west (Republic of Benin) and east (Cameroon). Additionally, there were two cases of microscopic vivax-like malaria from Nigerian indigenous population. Hence molecular surveillance of the circulating Plasmodium species in two states (Lagos and Edo) of southwestern Nigeria was carried out. METHODS:A cross-sectional survey between September 2016 and March 2017 was conducted. 436 febrile patients were included for the present work. Venous blood of these patients was subjected to RDT as well as microscopy. Further, parasite DNA was isolated from positive samples and PCR diagnostic was employed followed by direct sequencing of the 18S rRNA of Plasmodium species as well as sequencing of a portion of the promoter region of the Duffy antigen receptor for chemokines. Samples positive for P. vivax were re-amplified several times and finally using the High Fidelity Taq to rule out any bias introduced. RESULTS:Of the 256 (58.7%) amplifiable malaria parasite DNA, P. falciparum was, as expected, the major cause of infection, either alone 85.5% (219/256; 97 from Edo and 122 from Lagos), or mixed with P. malariae 6.3% (16/256) or with P. vivax 1.6% (4/256). Only one of the five P. vivax isolates was found to be a single infection. DNA sequencing and subsequent alignment of the 18S rRNA of P. vivax with the reference strains displayed very high similarities (100%). Remarkably, the T-33C was identified in all P. vivax samples, thus confirming that all vivax-infected patients in the current study are Duffy negative. CONCLUSION:The present study gave the first molecular evidence of P. vivax in Nigeria in Duffy negative individuals. Though restricted to two states; Edo in South-South and Lagos in South-west Nigeria, the real burden of this species in Nigeria and sub-Saharan Africa might have been underestimated, hence there is need to put in place a country-wide, as well as a sub-Saharan Africa-wide surveillance and appropriate control measures.

Dataset Information

Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection.

Publications

Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection.

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