Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

PLoS Negl Trop Dis. 2016 May 6;10(5):e0004629. doi: 10.1371/journal.pntd.0004629. eCollection 2016 May.

Abstract

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity.

Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis.

Principal findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis.

Conclusions/significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, Helminth / immunology*
  • Child
  • Child, Preschool
  • Female
  • Helminth Proteins / immunology*
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Ovum
  • Regression Analysis
  • Retrospective Studies
  • Sanitation
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni / epidemiology*
  • Schistosomiasis mansoni / immunology*
  • Sudan / epidemiology
  • Water Supply
  • Young Adult

Substances

  • Antigens, Helminth
  • Helminth Proteins
  • Immunoglobulin G
  • Interleukins
  • Immunoglobulin E

Grants and funding

TEME was supported by a fellowship awarded by the German Academic Exchange Committee (DAAD). The study was further supported by the BONFOR intramural funding program of the Medical Faculty of Bonn University and the European Commission (grant No. 242121, EPIAF). LEL and AH are recipients of further DFG funding within the "African-German Cooperation Projects in Infectiology" (HO 2009/10-1). AH is a member of the Excellence Cluster Immunosensation (DFG, EXC 1023) and of the German Centre for Infectious Research (DZIF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.