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

Abstract

BackgroundIn 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.MethodologyThis 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 FindingsNearly 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/SignificanceSchistosomiasis 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.

Schistosoma mansoni PCR+-infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts

“…In a further new supplementary regression analysis we combined data from the first publication [18] with the new immune data measured here. Pvalues of less than 0·05 were considered statistically significant.…”

“…Next, epidemiological covariates [exposure, latrine, education, age (subgrouped), co-infection and gender], chemokine and SWA-Ig levels were included in a stepwise logistic regression with forward selection, as described previously [18], and results are shown in Table 2. This new data analysis revealed for the first time that SWAspecific IgG3 was significantly associated with infection per se , and additionally, SWA-specific IgG2 was associated with a Sm PCR + diagnostic state.…”

“…In this retrospective study, samples from Sudanese individuals were collected in Kassala and Khartoum State between March and October 2011, as described in Elfaki et al . [18]. In brief, study participants had to provide information about their health status, educational and living conditions and oral consent was noted by the examiner on these forms.…”

“…The present analysis builds on a previous study in which we profiled cytokine and egg-specific (SEA) antibody levels in individuals who were (i) schistosome-egg-positive in stool samples (egg + ), (ii) schistosome-egg-negative but S. mansoni polymerase chain reaction (PCR)-positive in sera (SmPCR + ) and (iii) individuals exposed to schistosomes but without a patent infection, and were thus both schistosome-egg-negative and S. mansoni PCR-negative (Sm uninfected) [18]. Here, we now expand on our first study by further analysing chemokine levels and schistosomeworm antigen (SWA) Ig levels in serum.…”

Interleukin 4 (IL-4) in Urinary Schistosomiasis as a Diagnostic Biomarker During Its Reinfection- A Review

“…The result showed that IgM and IgE are extremely high in serum of infected population compared to uninfected population. It synoptically means that without the help of or release of IL-4, there will be no protection to fighting parasitic reinfection, and 2016 result of [20] arrived at the same conclusion with Nmorsi. Hence, measurement of immunoglobulin concentration can be used as indicators of heavy and acute infection of S. haematobium in our endemic localities.…”