Roles of single nucleotide polymorphisms in the promoter regions of tumour necrosis factor-α and interleukine-1o genes in Schistosoma haematobium infection susceptibility.
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Date
2020
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Abstract
Background: Schistosomiasis remains a public health threat in sub-Saharan Africa which
carries 85% of the global burden. With effective vaccines a distant future away, and no one allround
intervention, research is still required to ensure that only effective programmes are
introduced and implemented as well as evaluated and/or monitored. It is therefore key for
researchers, policy makers and implementers to understand the epidemiology, immunology,
immunopathology, immunogenetics, chemotherapy, management and control of Schistosoma
haematobium for optimal elimination strategies to be implemented. A research study was
therefore instituted to determine the prevalence, risk factors and host immunogenetic factors in
S. haematobium infections among pre- and school going children living in endemic regions of
Manicaland and Mashonaland central provinces in rural Zimbabwe. The relationship between
single nucleotide polymorphisms (SNPs) of the promoter regions of tumor necrosis factor alpha
(TNF-α or rs1800629) and interleukin- 10 (IL-10 or rs1800871) and susceptibility to
Schistosoma haematobium was investigated. In addition, the relationship between these SNPs
and cytokine levels, as well as the relationship between actual cytokine levels and susceptibility
to Schistosoma haematobium was assessed.
Methods: In this cross-sectional immune-epidemiological study Schistosoma haematobium
was diagnosed by the microscopic examination of urine specimens for the presence of parasite
eggs using the urine filtration technique. DNA for the genotyping was extracted from
approximately 300μl whole blood using the QiagenFlexiGene DNA extraction kit, following
the manufacturer’s protocol. IL-10 and TNF-α promoter region single nucleotide
polymorphisms were genotyped using amplification refractory mutation system-polymerase
chain reaction (ARMS-PCR).The allele frequencies and genotype distribution of S.
haematobium infected and uninfected participants were then analysed using the chi-square test.
All analyses were performed using SPSS (version 21) and p-values <0.05 were considered
statistically significant. The levels of the cytokines (IL-10 and TNF-α) were measured by
indirect enzyme linked immunosorbent assay (ELISA) using MABTECH, 3510-1H-6 kits,
according to the manufacturer’s instruction.
Results: The overall prevalence of S. haematobium among children in endemic rural and
farming communities of the two provinces of Zimbabwe assessed was 17.1% (158/924).
Gender specific prevalences were similar (17.5% in girls and 16.7% in boys; p = 0.735). Age
and location were significant risk factors for schistosomiasis in children living in endemic
regions surveyed. The older the child the higher the risk of getting infected by S. haematobium
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(10.5% in 0-5 year olds; 24.0% in 6-10 year olds and 30.7% in 11-15 year olds; p < 0.001).
IL-10 -1082 G/A, IL-10 -819 C/T and TNF-α -308 G/A single nucleotide polymorphisms were
not significantly associated with susceptibility to S. haematobium infection. TNF- α genotypes
AA, GA and GG were associated with high, moderate to high and low production of TNF-α
respectively. IL-10 TT, CT and CC genotypes were associated with low, moderate and high
IL-10 plasma levels respectively. Higher TNF-α and lower IL-10 serum levels were negatively
associated with schistosomiasis infection. Praziquantel treatment reduced prevalence among
the study participants as reinfections were only recorded in 6 of the 59 (10.2%) who were
infected at baseline of children.
Discussion and Conclusion: The determined schistosomiasis prevalence puts the regions of
Zimbabwe studied within the moderate range as described by the World Health Organisation
(10 – 49% prevalence), hence more concerted efforts are required to fight schistosomiasis.
Although cytokine genotypes were associated as expected with cytokine levels, genotypes did
not directly correlate with schistosomiasis infection while cytokine levels did. This indicates
that circulating TNF-α and IL-10 levels are a result of many factors apart from genotypes.
Taken together with previous work, this study suggests that high TNF-α and low IL-10 serum
levels confer protection against schistosomiasis infection. Since schistosomiasis prevalence
was similar between boys and girls and prevalence was high in all age groups (increasing with
age), all programmes aimed at eliminating schistosomiasis should include both genders and
children of all age groups. Specific locations could be targeted in resource limited settings as
location was a significant risk factor for infection. Praziquantel is effective, with few
reinfections observed, and therefore remains central in schistosomiasis management. To clearly
understand the role host genetic factors in infection and to inform effective control, elimination
and eradication programmes, more research on risk factors and host immunogenetics is
necessary
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.