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Clin Vaccine Immunol. 2017 Jul 5;24(7). pii: e00057-17. doi: 10.1128/CVI.00057-17. Print 2017 Jul.

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

Author information

1
Pathology Department, College of Medicine, University of Malawi, Blantyre, Malawi tnyirenda@medcol.mw wmandala@mlw.mw.
2
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
3
Pathology Department, College of Medicine, University of Malawi, Blantyre, Malawi.
4
Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
5
Department of Paediatrics and Child Health, Queen Elizabeth Central Hospital, Blantyre, Malawi.
6
Division of Infection and Immunity, University College London, London, United Kingdom.
7
Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
8
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi tnyirenda@medcol.mw wmandala@mlw.mw.
9
Biomedical Sciences Department, College of Medicine, University of Malawi, Blantyre, Malawi.

Abstract

Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S Typhimurium were reduced in febrile P. falciparum-infected children (median, -0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In relation to SBA, C3 deposition on S Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10 [IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further.

KEYWORDS:

Salmonella; children; immunity; malaria; susceptibility

PMID:
28515136
PMCID:
PMC5498726
DOI:
10.1128/CVI.00057-17
[Indexed for MEDLINE]
Free PMC Article

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