Pathogenesis of Schistosomiasis and HIV Co-infecfion: Polymorpmsms in Il-23 Receptor in Schistosomiasis Patients undergoing Highly Active Antiretroviral Therapy (HAART)

Abstract

IllY and schistosomiasis co-infection is common around Lake Victoria region, raising the possibility of schistosomiasis-related immune reconstitution inflammatory syndrome (IRIS) in patients undergoing mv medication. Some patients develop schistosome-related IRIS while others do not, and the associated immunogenetic markers are not known. This longitudinal study aimed at identifying a possible role of Interleukin-23 receptor (IL-23R) gene polymorphism in the pathogenesis of schistosomiasis-associated IRIS. In addition, the study established the relationship between plasma viral load and CD4+ cell counts. Ninety adults, occupationally exposed to waterinfested with the infective stage of Schistosoma mansoni, working in L. Victoria in Uyoma Rarieda and undergoing Highly Active Antiretroviral Therapy (HAART), were sampled at baseline and followed up for six months to establish if they developed schistosome-related IRIS. Twenty six (26) persons who developed schistosomiasis-associated IRIS and forty five (45) who did not were included in data analysis, while those with incomplete follow-up data (n=19) were excluded. Genotyping for variants (rsI88444, rs7539625, rs7530511, rs11465754 and rs6682925) within the IL-23R was carried out on whole blood samples drawn from participants while KatoKatz was used to measure S.mansoni infestation from stool. Determinations of plasma viral load and CD4+ cell counts were done both at baseline (n=71) and post-treatment (n=71) to access response to HAART. The results showed an increase in CD4+ cell counts coupled with a decrease in mv viral load in patients undergoing HAART. However, across group comparison using Kruskal-Wallis test revealed comparable levels in mv viral load and CD4+ counts between the variants (P>O.05). A logistic regression analyses, while controlling for age and sex, revealed that homozygous GIG of IL-23R (rsI884444), relative to GIT genotype, was significantly associated with susceptibility to IRIS (OR, 0.25, 95% CI, 0.07-0.96, P=0.043). Pearson's Chi-Square analyses did not yield any significant association between IRIS cases and non-IRIS controls (P>0.05). This study showed that majority of schistosomiasis! mv co-infected patients responded well to HAART but their recovery was often complicated by the onset of IRIS, creating a need for health care providers to plan for its management. Homozygous GIG allele ofIL-23R (rsI884444) could be one of the possible predictors of schistosomiasis-associated IRIS. Further testing will be needed to determine the feasibility of using this gene variant by health care providers in screening patients for advance preparation in the management of the syndrome.