Relationship Between Schistosome Infections and Polymorphisms

The human schistosomiasis original name was bilharzia, named after Theodore Bilharz, who claimed first reported the disease in Cairo, Egypt 1851, is a parasitic disease in people caused by five different species of blood flukes of genus Schistosoma that belongs to class Trematoda. Schistosomiasis is an ancient disease whose eggs have been found in Egypt and Chinese mummies dating back thousands of years (53, 70). In 1847 a group of Japanese workers (70) described Katayama syndrome (acute schistosomiasis). Schistosoma mansoni, Schistosoma haematobium, or Schistosoma japonicum, are major causes of human schistosomiasis while Schistosoma intercalatum and Schistosoma mekongi can affect humans, however, are much less prevailing. S.mekongi, S. japonicum, S. intercalatum and S. mansoni reside in the mesenteric venules as adult worms, while S. heamatobium adults live in the venous plexus surrounding the urinary bladder (16). Over 200 million persons experience the effect of schistosomiasis globally. However, it majorly resides in tropical regions of Africa, other cases still in China, the Philippines, the Middle East, South America and Caribbean (16). Schistosoma mansoni is one of the prevalent infecting species of genes infecting more than 83 million human beings (20). Research proves that in between ten percent to five percent those infected with schistosomiasis develop the life-threatening symptoms of the disease, while tens of millions suffer understated morbidity.

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Polymorphism in biology is the process whereby two or more different morphs or forms occur. It also referred as phenotypes in the society of species. According to http://www.bbc.co.uk/nature/adaptations/Polymorphism_(biology) Polymorphism can be experienced in some ways. A true polymorphic species has individuals notably of different appearance living in the same locality. Army ants always have different sizes of workers yet live in the same net hence are considered to be a polymorphism. Polymorphism is seen as universal in nature; it is related to genetic variation, adoption, and biodiversity. It usually functions to preserve diversification of form in a population living in a varied environment. Most of the typical examples are mimetic forms of butterflies, sexual dimorphism which occurs in many organs and human blood types and hemoglobin.

Prevalence and intensity of schistosomiasis

Schistosomiasis is among one of the chronic and neglected tropical diseases affecting the poor rural people. Without proper medication, the disease can lead to anemia or retain the growth of a child, cognitive function, and physical activity. A study conducted to determine the prevalence, intensity and variation of Schistosoma mansoni infection among individuals subject in geographically apart localities. According to the methods and results respectively; a total of 1073 individuals (545 females and 528 males) were eligible for the study. Their ages were in between 5 60 years with mean age of 11 years in Area 1, 24 years in Area 2 and 22 years in Area 3. The study participants were distributed with small plastic sheets, and sizable stool specimens were later collected and examined using Kato-Kaz method (41.7mg template). From the study, the results showed that the prevalence of Schistosoma mansoni infection among the study participants in Area 1, Area 2 and Area 3 was 31.6%, 89.6%, and 59.9% respectively.

The belief that immunity is a major factor controlling the prevalence and intensity of schistosomiasis in man is a deep seated one. It is nonviable to most observers that subjects in endemic areas who are exposed to infested waters are not continually reinfected. Additionally, there is a continuous flow of anecdotal evidence for the infectivity of the parasite according to reports generated by individuals from nonendemic areas who became infected (in some cases, heavily) after being exposed for only a short duration of time. Despite the fact that the worms dont multiply in the human body, their ability to live for many years ranging from 20 years to 30 years suggests that the burden of the infection should steadily increase to a level in severe mortality and morbidity. In most endemic areas of the world, detection of the disease is relatively little and death due to schistosomal infection. When examining the curve of prevalence and intensity of infection to age, it reaches its peak in the teens and declines with advancing years.

The occurrence of immunity to schistosomiasis in man is not a patent phenomenon. Smithers stated that there is no sudden immunologic crisis leading to parasite elimination and a subsequent and immediate development of healthy immunity. Instead, resistance appears to develop gradually, taking several years to become pronounced: in early stages of infection, immunity may be only partial, but nevertheless of vital importance in limiting disease [2]. Attempts to study human resistance to reinfection has been few because of the chronic nature of illness, lack of effective, nontoxic drugs for its elimination and pathogenicity. Innumerable experiments in laboratory animals remain equivocal. Although several research hosts develop a high degree of resistance to reinfection, it is erratic, sometimes absent, often marginal, seldom absolute and usually takes long to develop [3]. All the above impressions and indirect and marginal evidence might suffice to validate the existence of immunity if there were no adequate alternatives to enlighten the fact that most individuals in endemic areas do not develop overwhelming schistosomal infections. A basic degree of protection against the development of massive worm burdens may, however, be related to the biological characteristics of the schistosomes and be afforded by many sociologic and even ecologic factors.

Genotype polymorphisms in IL-4, IL-5 and IL-13 genes

The cause of allergic asthma is by environmental and genetic factors that interact to determine disease susceptibility and severity. Most lines of evidence suggest that the interleukin (IL-4 and the IL-4 receptor alpha (IL-4Raphla) are engaged in the spread of atopic diseases. A study was conducted in a population to determine whether polymorphism sites in IL-4 and IL-4 Ralpha chain are associated with allergic asthma. Clinical data and DNA from allergic asthma patients were obtained; they were compared with those of a group of healthy control subjects. The subjects were genotyped for the IL-4R alpha chain Q576R and the IL-4 C-590T promoter polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Based on the results, it showed that the IL-4 C-590T was not related to allergic asthma in a population. Nonetheless, the IL-4R alpha chain 576R/R was notably increased in allergic asthma patients compared with control subjects (chi2 = 21.16; p<0.01), and the total plasma immunoglobulin E (lgE) level was raised in allergic asthma patients. The data implied that IL-4R alpha chain 576R/R genotypes confer susceptibility to allergic asthma.

IL-13 is a protein encoded by a gene that is a potent growth promoting cytokine. The cytokine is competent of supporting proliferation of a broad range of hematopoietic cell type. It is associated with a diversity of cell activities such as apoptosis, differentiation, and cell growth. The cytokine has also been shown to dominate neurotrophic activity, and it may be connected to neurologic disorders. Three previous genetic association studies carried out in China and Korea investigated between IL-13 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconstant. The focus was on the possibility and relationship between IL-13 rs40401 and smoking in young adult Japanese women. 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma were included. The control subjects were 700 women who had no asthma according to the ECRHS criteria who had not been allergic to a doctor or diagnosed with asthma or who had not met the criteria of International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis. A remarkable positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the odds ratio adjusted was 1.39 (95% Cl: 1.004-1.93). The study suggests that IL-13 rs40401 is associated with the risk of asthma in young adult Japanese women and reveals that composition of ever smoking and having the CC genotype of IL-13 SNP rs40401 is significantly linked to asthma.

According to another study that was conducted in Korea to determine if IL-5 and IL-5 receptor alpha polymorphisms are associated with atopic dermatitis (AD). 17 singlenucleotide polymorphisms (SNPs) were genotyped from five genes of the 1120 case-control samples (447 controls and 646 AD). Serum IL-5 concentrations in 87 individuals [36 ADe(AD extrinsic), 18 ADi(AD intrinsic) and 33 controls] were measured and results compared among the groups. From the results, haplotype T-A in the IL-5 gene and the rs25224111SNP were significantly associated with the Ade. The concentration of serum IL-5 was higher in the ADe than that in ADi patients without any correlation with the rs25224111SNP. In the IL-5RA gene, the rs334809SNP showed a weak association with AD, and the rs6771148SNP and the haplotype T-C-T of the three adjacent tagged SNPs had an effect on the blood eosinophil counts and the serum ECP levels in the AD patients. In conclusion, it was found that the rs25224111SNP and the haplotype T-A in the IL-5 gene and the serum IL-5 levels were strongly associated with the allergic type of AD, but with the nonallergic type of AD. The association of the rs6771148SNP and the haplotype T-C-T in the IL5RA gene with the blood eosinophil counts and the serum ECP levels indicates that the IL5RA gene has a role in controlling eosinophils in the peripheral blood

Relationship between Schistosome infections and polymorphisms

Genetic research of human susceptibility to Schistosoma (blood fluke) infections have previously identified a genetic locus was determining the intensity of infection with African species, Schistosoma mansori. The human genome in the region 5q31-33 which is known to contain the Th2 immune response cluster, including the genes encoding the IL-4, IL-5, IL-10 and IL-13 cytokines. These cytokines play a vital role in inflammatory immune response, and they have been previously incriminated in human susceptibility to infection with the Asian species, S. japonicum. A nested case control study conducted, 30 HipMap tagging single nucleotide polymorphism (SNP) were genotyped across the four genes in 133 individuals identified as putatively resistant and 159 individuals identified as putatively susceptible to reinfection with S. japonicum. A third group composed of 113 individuals was included to demonstrate symptomatic infection. The final results no significant association a global level between haplotype blocks or any of the individual SNPs. However, two tagging SNPs in IL-5 elaborated globally significant association with susceptibility to symptomatic infection. They were is strong relation imbalance with earth other and were found to belong to the same haplotype block that also provided valuable association after permutation testing. The location of haplotype was in the 3-untranslated region of IL-5, implying that variant in this region IL-5 may modulate the immune response in these individuals with symptomatic infection.

According to certain immunology journal, millions of people are exposed to schistosome infection that causes severe liver and kidney disease and a total death of 280,000 annually. The genetic locus IL-5, IL-4, and IL-13 control the Th2-mediated immunity that is critical to human d...