C-Reactive Protein And Interleukin-6 Are Elevated In Onchocerciasis Patients After Ivermectin Treatment

Abstract

Ivermectin treatment of onchocerciasis can induce adverse reactions. Mechanisms underlying these reactions are poorly understood but may include activation of neutrophils. This study investigated the acute-phase response in onchocerciasis patients during 2 days after ivermectin treatment. The acute-phase protein C-reactive protein (CRP) and cytokines that mediate the acute-phase response (tumor necrosis factor-alpha [TNF alpha] and interleukin-6 [IL-6]) were measured in 144 skin snip-positive onchocerciasis patients and 12 skin snip-negative controls who received one dose of ivermectin (150 micrograms/kg). No elevated TNF alpha levels were found, but IL-6 and CRP were elevated in 25.7% and 50.7% of the patients, respectively, after ivermectin treatment. Most patients (89.2%) with raised IL-6 also had raised CRP. Such increases were not observed in controls and in patients were correlated with adverse reactions and microfilarial densities. These findings suggest a possible role of the acute-phase response in microfilarial destruction following ivermectin treatment.

RANTES in onchocerciasis: changes with ivermectin treatment

“…A similar relationship has been described in DEC-treated patients [10,18] and suggests that microfilariae or their degradation products play a role in post-treatment reactions. Previous studies have demonstrated that levels of TNF- [18] and IL-6 [18,19] were elevated following microfilaricidal therapy in O. volvulus-infected subjects but remained unchanged in endemic controls without evidence of infection. No difference was seen in levels of any of the cytokines and chemokines assayed and infection status (data not shown), which is explained by the finding of O. volvulus DNA in skin biopsies taken from all subjects.…”

“…Neutrophils, which, like eosinophils, are able to kill O. volvulus microfilariae in vitro [15,16], may also be involved, and high circulating levels of elastase, a marker of neutrophil granule release, have been reported following ivermectin therapy [17]. Evidence has also emerged for a role of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-) and IL-6 in the pathogenesis of this reaction [18,19].…”

Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

“…Wolbachia DNA and even Wolbachia bacteria are detectable in the plasma of persons with onchocerciasis or lymphatic filariasis within 1 day of administration of diethylcarbamazine or ivermectin, drugs that rapidly kill microfilaria (21,22). These acute posttreatment reactions are accompanied by increases in plasma TNF-␣, IL-6, and LPS-binding protein (23,24), suggesting that Wolbachia released into the bloodstream by degenerating or dead microfilaria cause the acute adenolymphangitis and fever that occur after administering antifilarial drugs. Aside from these drug-related side effects, the contribution of Wolbachia to inflammation in infected individuals is unresolved, but several observations suggest they may also play a role in initiating or perpetuating local or systemic inflammatory reactions.…”

Elevated serum angiotensin-converting enzyme activity in onchocerciasis

“…Patients who developed side effects within 24 h were not included in this study. A blood sample for analysis of several parameters of disease activity [5,6] was obtained just before the administration of a single dose of 150 Ixg/kg ivermectin, and side effects occurring within 48 h were recorded. These side effects were graded: I (no reaction), II (mild), III (moderate), and IV (severe: fever, joint and bone pain, skin edema, and malaise requiring treatment).…”