Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection.
BACKGROUND
Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition.


METHODS
Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay.


RESULTS
Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups.


CONCLUSIONS
The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.
Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. vitorrosaramos@hotmail.com.|Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. vitorrosaramos@hotmail.com.
Vitor R R
VR
Mendonça
Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. bruno.andrade@bahia.fiocruz.br.
Bruno B
BB
Andrade
Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. ligiacorreialima@gmail.com.|Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. ligiacorreialima@gmail.com.
Ligia C L
LC
Souza
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. magalhaesbelisa@gmail.com.|Universidade do Estado do Amazonas, Manaus, Brazil. magalhaesbelisa@gmail.com.
Belisa M L
BM
Magalhães
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. mariapaula.mourao@gmail.com.|Universidade do Estado do Amazonas, Manaus, Brazil. mariapaula.mourao@gmail.com.
Maria P G
MP
Mourão
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. marcuslacerda.br@gmail.com.|Universidade do Estado do Amazonas, Manaus, Brazil. marcuslacerda.br@gmail.com.
Marcus V G
MV
Lacerda
Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. mbarral@bahia.fiocruz.br.|Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. mbarral@bahia.fiocruz.br.|Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia, São Paulo, Brazil. mbarral@bahia.fiocruz.br.
Manoel
M
Barral-Netto
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D060085:Coinfection / Q000453:epidemiology / Q000276:immunology*; D003715:Dengue / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000453:epidemiology / Q000276:immunology; D055815:Young Adult
D015415:Biomarkers