EFFECT OF INTENSIVE VERSUS STANDARD ANTHELMINTHIC TREATMENT ON INNATE IMMUNE RESPONSES IN HIGH HELMINTH BURDEN UGANDAN FISHING VILLAGES
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Background: Mass drug administration (MDA) was one of the strategies set by the World Health Organization (2012), to eliminate helminths, reduce helminth-associated morbidity and mortality. Following MDA implementation, a number of studies have assessed the effect of anthelminthic treatment on adaptive responses but limited work has been carried on the innate immune responses, yet the quality and magnitude of the adaptive immune responses to infections and vaccines may be shaped by the innate immune responses. Therefore, we aimed to investigate the effect of helminth infection, and of intensive versus standard anthelminthic treatment on the innate immune response in high-helminth-burden Ugandan fishing villages. Methods: Community members in selected households were randomized into: 1. standard (biannual single-dose albendazole and a yearly single-dose praziquantel) 2. intensive (quarterly triple-dose albendazole [daily, three days] and quarterly single-dose praziquantel) treatment arms. Forty-seven participants from the outcome survey done after three years of intervention were considered for this sub-study. Whole blood collected from these participants was cultured with a panel of innate stimuli (LPS, FSL-1, PAM, CPG, CL097, Mannan and Curdlan) for 24 hours. Cytokines and chemokines in culture supernatants were measured using the Luminex® assay. Associations between innate immune responses, treatment and helminth infections (adjusted for age and sex) were examined using multivariable linear regression. Patterns of cytokines and chemokines were examined using Principal Component Analysis (PCA). Results: The cytokines that were positively associated with intensive treatment were: IL-8 response to FSL-1 (p=0.0005) and CL097 (p=0.0001); VEGF response to PAM (p=0.0022), FSL1 (p=0.0005), CL097 (p=0.0004), LPS (p=0.0004), CPG (p=0.0169) and Mannan (p=0.0017). Intensive treatment was negatively associated with IL-10 response to PAM (p=0.0057), FSL-1 (p= 0.0023), CL097 (p=0.0023) and Curdlan (p= 0.0145). There was no association between having any individual worm infection and innate response. Additional evaluation of associations of cytokines/chemokines using PCA showed no differences for intensive and standard treatment, or for helminth infections. Conclusion: Intensive treatment was associated with an increased pro-inflammatory immune response, but a reduced regulatory innate immune response. Treatment and subsequent reduction of worm burden in infected individuals might enhance immunity to vaccines and other infectious pathogens.