Of Mice, Cattle, and Humans: The Immunology and Treatment of River Blindness

River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease

Detection of the acute phase of abdominal angiostrongyliasis with a parasite-specific IgG enzyme linked immunosorbent assay

Angiostrongylus costaricensis may cause intestinal lesions of varied severity when it accidentally infects man in Central and South America. First-stage larvae have never been detected in stools. Therefore, a parasite-specific IgG ELISA was evaluated for the determination of the acute phase of infection. The specificity and the sensitivity of the immunoassay was shown to be 76.2% and 91.1%, respectively. Eight serum samples taken from patients with histopathological diagnosis, at different time points (3 to 15 months) after surgical treatment, showed a sharp and early decline in antibody reactivity. The titration of anti-A. costaricensis antibodies has proved to be a useful method for the diagnosis of acute abdominal angiostrongyliasis

Detection of the acute phase of abdominal angiostrongyliasis with a parasite-specific IgG enzyme linked immunosorbent assay

Angiostrongylus costaricensis may cause intestinal lesions of varied severity when it accidentally infects man in Central and South America. First-stage larvae have never been detected in stools. Therefore, a parasite-specific IgG ELISA was evaluated for the determination of the acute phase of infection. The specificity and the sensitivity of the immunoassay was shown to be 76.2% and 91.1%, respectively. Eight serum samples taken from patients with histopathological diagnosis, at different time points (3 to 15 months) after surgical treatment, showed a sharp and early decline in antibody reactivity. The titration of anti-A. costaricensis antibodies has proved to be a useful method for the diagnosis of acute abdominal angiostrongyliasis

Microfilariae of the Filarial Nematode Litomosoides sigmodontis Exacerbate the Course of Lipopolysaccharide-Induced Sepsis in Mice▿

Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than sham-treated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilaria-releasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN-γ receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN-γ and TNF-α. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood

Sustainable Control of Onchocerciasis: Ocular Pathology in Onchocerciasis Patients Treated Annually with Ivermectin for 23 Years: A Cohort Study

<div><p>The evolution and persistence of ocular pathology was assessed in a cohort of <i>Onchocerca volvulus</i> infected patients treated annually with ivermectin for 23 years. Patients were resident in rural Central and Kara Region of Togo and ocular examinations included testing of visual acuity, slit lamp examination of the anterior eye segment and the eye fundus by ophthalmoscopy. Before ivermectin treatment, vivid <i>O.volvulus</i> microfilariae (MF) were observed in the right and left anterior eye chamber in 52% and 42% of patients (n = 82), and dead MF were seen in the right and left cornea in 24% and 15% of cases, respectively. At 23 years post initial treatment (PIT), none of the patients (n = 82) presented with MF in the anterior chamber and cornea. A complete resolution of punctate keratitis (PK) lesions without observable corneal scars was present at 23 years PIT (p<0.0001), and sclerosing keratitits (SK) lessened by half, but mainly in patients with lesions at early stage of evolution. Early-stage iridocyclitis diminished from 42%(rE) and 40%(lE) to 13% (rE+lE)(p<0.0001), but advanced iridocyclitis augmented (p<0.001) at 23 years PIT compared to before ivermectin. Advanced-stage papillitis and chorioretinitis did not regress, while early-stage papillitis present in 28%(rE) and 27%(lE) of patients at before ivermectin regressed to 17%(rE) and 18%(lE), and early-stage chorioretinitis present in 51%(rE+lE) of cases at before ivermectin was observed in 12%(rE) and 13%(lE) at 23 years PIT (p<0.0001). Thus, regular annual ivermectin treatment eliminated and prevented the migration of <i>O. volvulus</i> microfilariae into the anterior eye chamber and cornea; keratitis punctata lesions resolved completely and early-stage sclerosing keratitits and iridocyclitis regressed, whilst advanced lesions of the anterior and posterior eye segment remained progressive. In conclusion, annual ivermectin treatments may prevent the emergence of ocular pathology in those populations still exposed to <i>O.volvulus</i> infection.</p><p><i>Trial Registration</i>: <a href="http://www.pactr.org" target="_blank">www.pactr.org</a><a href="http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201303000464219" target="_blank">PACTR201303000464219</a>)</p></div

Ocular anomalies not caused by <i>Onchocerca volvulus</i> infection in patients (n = 82) examined before ivermectin treatment, and at 4 and 23 years post initial ivermectin treatment (PIT).

<p>Ocular anomalies not caused by <i>Onchocerca volvulus</i> infection in patients (n = 82) examined before ivermectin treatment, and at 4 and 23 years post initial ivermectin treatment (PIT).</p