The lack of influence of food and local alcoholic brew on the blood level of Mectizan(®) (ivermectin).

There is concern that extraneous factors, such as food and drink, may alter the pharmacodynamics of Mectizan(®) (ivermectin) in patients receiving this important anti-parasitic drug, and thus might put such individuals in danger of serious adverse events. The effects of a common local alcohol-containing beverage and a local food on plasma levels of ivermectin were studied in Sudanese volunteers after administration of the standard dose used in mass drug administration programs for onchocerciasis and filariasis. Plasma levels of ivermectin at various time points (0-48h) after administration of ivermectin were ascertained by HPLC assay in ten volunteers given 150µgkg(-1) ivermectin together with either a local sorghum-based food ('assida'), or a locally brewed alcoholic beverage ('arangi' made from sorghum grain) or in those who were fasting. Maximum mean (±SD) plasma levels of ivermectin (67±49ngml(-1)) were reached within 2h in fasting patients, and had dropped to 26±20ngml(-1) after 30h. The coadministration of local food or alcoholic beverage did not cause an increase in ivermectin plasma levels above those observed in people who were fasting. However, at 2h after ivermectin administration, patients given alcohol had significantly lower plasma ivermectin levels than fed patients or fasting patients. There were no significant differences among treatments for AUC0-30, Cmax, or tmax, and so the coadministration of local food or alcoholic beverage did not cause any change in pharmacokinetic parameters of ivermectin in the plasma in comparison with fasting. None of the measured levels of plasma ivermectin were greater than those reported in previous studies with this compound. These findings do not support the hypothesis that acute intake of alcohol is an important factor in the development of the serious adverse reactions that can occur during the treatment of loaisis patients with ivermectin (Mectizan(®)).

Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease: implications for the development of severe reactive onchodermatitis (ROD).

The pathologic manifestations of Onchocerca volvulus infection depend on the interplay between the host and the parasite. A genetic single nucleotide polymorphism in the Fc gamma RIIa gene, resulting in arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses and may influence the clinical variations seen in onchocerciasis. This study investigated the relationship between this polymorphism and disease outcome. Fc gamma RIIa genotyping was performed on clinically characterized onchocerciasis patients (N = 100) and healthy controls (N = 74). Fc gamma RIIa genotype R/R131 frequencies were significantly higher among patients with severe dermatopathology (P < 0.001). Increased risk of developing this form was mostly associated with one tribe (Masalit) (OR = 3.2, 95% CI 1-9.9, P = 0.042). The H131 allele was found to be significantly associated with a reduced risk of having the severe form of the disease (adjusted OR = 0.26, 95% CI = 0.13-0.46, P < 0.001). Our findings suggest that the polymorphism influences the clinical outcome of onchocerciasis.

Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history.

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.

Immunocompetence may be important in the effectiveness of Mectizan (ivermectin) in the treatment of human onchocerciasis.

Mectizan (Ivermectin) has been proved to be central to the control of onchoceriasis through self-sustainable community-based treatment. The possibility of parasitological unresponsiveness to this treatment or selection for drug resistance has emerged recently in many occasions. The reason for the reduced ability of Mectizan to maintain low levels of dermal microfilariae and early recurrent pruritus can only be speculated upon. Here, we report our own findings to address this particular issue.