Onchocercal dermatitis: clinical impact.

The clinical features of onchocercal dermatitis include itching, papular and papulomacular rash, skin atrophy and depigmentation. The results of a multi-country study have shown that > 30% of the population in communities where onchocerciasis is endemic have onchocercal dermatitis. The most troubling symptom suffered by those affected was itching and this was closely related to reactive onchocercal dermatitis (acute papular, chronic papular and/or lichenified lesions). Reactive onchocercal dermatitis and troublesome itching were common in all age-groups and were an important cause of stigma in most endemic communities, those affected suffering from poor self-esteem. Concern about onchocercal depigmentation varied between study sites and subjects.

Human onchocerciasis in Nigeria: isotypic responses and antigen recognition in individuals with defined cutaneous pathology.

Antigen (Ag)-specific isotype responses to Onchocerca volvulus Ag (OvAg) were assessed by enzyme-linked immunosorbent assay and immunoblot in 123 residents of a mesoendemic area in northern Nigeria and 16 Nigerians from a nonendemic area. Individuals from an endemic area were divided into six groups on the basis of cutaneous onchocercal pathology: acute papular onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified onchodermatitis (LOD), atrophy (ATR), depigmentation (DPM) and normal skin, high microfilarial load (NSHMF). Immunoglobulin (Ig)G1-4 levels were all significantly associated with residence in an endemic area after controlling for age and sex (all P values = 0.0001). Both IgG1 and IgG3 were significantly associated with onchocercal clinical category after controlling for age, sex, and microfilarial load (P = 0.0031 and 0.0035, respectively). The IgG1 and IgG3 responses were both highest in LOD and lowest in NSHMF and ATR, respectively. A significant inverse association was found between IgG1 levels and microfilarial load after controlling for age, sex, and clinical category (P = 0.0061). On immunoblotting, 20 (44.4%) of 45 individual onchocerciasis sera contained IgG4 antibodies against a band of 29-31 kD, which was not recognized by pooled sera from individuals with other filarial infections. There was heterogeneity of antigen recognition within each of the onchocercal clinical groups, which together with the small numbers examined by immunoblotting, limits interpretation. Nevertheless, some differences in patterns of antigen recognition were found between the onchocercal groups. The LOD group demonstrated prominent immunoreactivity in IgG1 and IgG3 while a general paucity of low molecular weight reactivity was seen with NSHMF in IgG1-3 subclasses, but there was no specific banding pattern that differentiated NSHMF from those with pathology. Comparison of microfilariae-positive (mf+) and mf- individuals with onchocercal skin disease revealed significantly higher levels of all IgG subclasses and higher overall scores on semiquantitative assessment of immunoblots for IgG1, IgG2, and IgG4 for mf+ individuals. Differing isotypic responses may play a role in the pathogenesis of the clinical spectrum of cutaneous onchocerciasis.

Differences in eosinophil and neutrophil chemotactic responses in sowda and generalized form of onchocerciasis.

Extravasation of host's leukocytes from blood vessels into inflammatory tissues represents a prerequisite for a subsequent interaction with invaded parasites. The migratory responses of eosinophilic and neutrophilic granulocytes in the polar forms of the filarial infection onchocerciasis were investigated. The hyporeactive, generalized form, the chronic hyperreactive (sowda) form and persons without signs of onchocerciasis from a hypoendemic area for onchocerciasis were compared. Eosinophils from sowda patients responded more strongly to the inflammatory mediator platelet-activating factor (PAF) than those from generalized patients and persons without onchocerciasis. The most significant differences were found between the sowda group and a subgroup of the generalized form with 16-80 microfilariae/mg skin (P<0.05) while patients with low microfilarial density exhibited chemotactic responses similar to the sowda group. In contrast to the strong eosinophil response, neutrophils from sowda patients appeared unreactive to PAF and the tripeptide activator formyl-methionyl-leucyl-phenylalanine (fMLP), thereby differing from both other groups. Laboratory data confirmed a state of hyperreactivity in sowda patients similarly found in generalized patients with low microfilarial density and contrasting with those with a microfilarial density of 16-80 mf/mg. The results revealed an inverse chemotactic responsiveness of eosinophil and neutrophil granulocytes in sowda patients and strengthened the observation of a spectrum of host's responsiveness in onchocerciasis.

HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection.

Human infections with the tissue nematode Onchocerca volvulus result in a variety of clinical conditions that possibly include protective immunity. In a West African area hyperendemic for human onchocerciasis, 120 residents were classified according to clinical and laboratory findings as presenting with generalized onchocerciasis, localized onchocerciasis, or as being putatively immune. The three groups differed in the distribution of HLA-D variants as determined by DNA typing. The most pronounced differences were found among alleles of the DQ loci. The haplotype DQA1*0501-DQB1*0301 was significantly more frequent among putatively immune individuals than among patients with generalized or localized disease. Conversely, DQA1*0101-DQB1*0501 and, independently, the allele DQB1*0201 were more frequent in generalized disease than in localized disease or putative immunity. In these correlations, the frequencies of allelic variants were in localized disease intermediate to those of the two other groups. The only distinct association found with localized disease was that of the DP allele DPB1*0402. The findings indicate that HLA-D variants influence the course of O. volvulus infection and help to define a state that may reflect protective immunity.

A clinical classification and grading system of the cutaneous changes in onchocerciasis.

Although onchocerciasis is one of the most important diseases of the skin and eye in the tropical world, to date there has been no formal consensus regarding the description and terminology of skin lesions. Furthermore, the contribution of cutaneous pathology to the morbidity and socio-economic effects of the disease has been largely neglected. We present a clinical classification and grading system for recording the cutaneous changes of onchocerciasis, and propose that this system be used as a standard method of description to convey clinical information between workers in all endemic areas to assist local and comparative research.

Histochemical enzyme-staining patterns of onchocerca volvulus microfilariae and their occurrence in different onchocerciasis areas.

Histochemical differentiation of Onchocerca volvulus microfilariae from 164 patients in West African rain-forest (Liberia), Sudan-savanna (Upper Volta), Guatemala and the Yemen has been carried out using a staining method for the demonstration of acid phosphatase. Intrauterine microfilariae showed considerable changes in their enzyme activity during embryonic development which are probably associated with the maturation of the parasite before migration to the tissues. Five distinct types of staining patterns could be distinguished among microfilariae from the skin according to the localization of the enzyme in specific structures of the microfilaria. Two or more types of staining patterns were found in most persons in the different geographic regions. There were significant differences in the overall distribution of the various staining patterns in persons from the different areas. At the present state of our knowledge, little is known about the nature and significance of these differences in the staining patterns of microfilariae. The question of whether they can be ascribed to an ageing process, strain differences or other factors is discussed.