L3 antigen-specific antibody isotype responses in human strongyloidiasis: correlations with larval output.

Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.

Humoral responses in human strongyloidiasis: correlations with infection chronicity.

Strongyloides stercoralis L3-specific antibody isotype responses amongst individuals with known long-standing (28-46 years) infection were compared with those of 'young' (6-29 years of age) and 'old' (30-80 years of age) infected individuals from an endemic Jamaican population. Characterization of age-dependent isotype patterns in the endemic community showed that immunoglobulin (Ig) G1 responses were significantly inversely correlated with age. Additionally, a trend towards lower IgE levels in the older age group was observed. Comparison with responses amongst known chronically infected individuals showed that IgG1 and IgE levels were similar to those of the 'old' endemic group, but were significantly lower than those of the 'young' group. In contrast, IgA levels were similar in both endemic groups, but were elevated in chronically infected individuals. IgG4 levels were similar in all groups studied. These findings suggest that age correlates with infection chronicity in communities endemic for S. stercoralis, and that individuals acquire infection early in their lives and remain infected into adulthood. Early and sustained upregulation of IgG4 may facilitate the establishment of infection and, in combination with developing IgE hyporesponsiveness, may promote chronic asymptomatic strongyloidiasis. Conversely, upregulated IgA may be involved in controlling chronic infection levels which are reflected in reduced IgG1 production.

Short report: long-term serum antibody isotype responses to Strongyloides stercoralis filariform antigens in eight patients treated with ivermectin.

The enzyme-linked immunosorbant assay was used to investigate long-term changes in serum immunoglobulin G1 (IgG1), IgG4, IgE, and IgA against Strongyloides stercoralis phosphate-buffered saline-soluble filariform larval antigens in eight Jamaican patients treated with ivermectin. Patients were followed for periods of between 170 and 542 days. Based on repeated formalin-ether concentration and agar plate culture, all patients were found to be uninfected up to 18 months following chemotherapy. Generally, all antibody isotype levels decreased following treatment, although there was considerable heterogeneity among patients. In a single patient with hyperinfection, the decrease in IgG4 was marginal and may represent a treatment failure. Reduction in serum antibody isotype responses to S. stercoralis following treatment may be used to assess the effectiveness of ivermectin in treating endemic strongyloidiasis.

Prospective evaluation of enzyme-linked immunosorbent assay and immunoblot methods for the diagnosis of endemic Strongyloides stercoralis infection.

Recently described enzyme-linked immunosorbent assay (ELISA) and immunoblot methods for the detection of serum IgG against Strongyloides stercoralis larval antigens were prospectively evaluated for the diagnosis of endemic strongyloidiasis. A modification of the ELISA involved preincubation of sera with Onchocerca gutturosa phosphate-buffered saline-soluble extract to remove cross-reactivity with other helminths. The sensitivity of the ELISA increased from 80% to 85% following preincubation. Similarly, there was an increase in specificity from 94% to 97%. The IgG recognition of 41-, 31-, and 28-kD filariform larval components showed sensitivities of 100%, 85%, and 65%, respectively. Both the ELISA following incubation of sera with O. gutturosa extract and serum IgG reactivity to a 41-kD larval component using immunoblotting are sensitive and specific techniques for diagnosing endemic strongyloidiasis.

Immunodiagnosis of Strongyloides stercoralis infection: a method for increasing the specificity of the indirect ELISA.

Indirect enzyme-linked immunosorbent assay (ELISA) allows sensitive detection of serum immunoglobulin (Ig) G against a soluble extract of Strongyloides stercoralis infective larvae. In this study, 40/40 (100%) human strongyloidiasis sera had high levels of anti-S. stercoralis IgG, but 30/40 (75%) filariasis sera, and 12/40 (30%) necatoriasis sera also had higher levels than control sera from UK residents. In attempts to increase the assay specificity by absorption of cross-reactive IgG, the effectiveness of pre-incubation of sera with extracts of different parasitic nematodes was investigated. One hour of incubation with 20 micrograms/ml aqueous extract of Onchocerca gutturosa absorbed cross-reactive IgG in most filariasis and necatoriasis sera, reducing the proportion with IgG levels above the positivity threshold by more than one-half. Preliminary results suggest that absorption with extracts of other filarial nematodes is equally effective, and that some of the cross-reactive IgG is directed against phosphorylcholine. Cross-reactive IgG in most necatoriasis sera was effectively absorbed with 20 micrograms/ml extract of Necator americanus. Cross-reactive IgG was not effectively absorbed with an extract of Ascaris lumbricoides. Absorption of cross-reactive IgG is an effective means of increasing the specificity of the indirect ELISA, for use in the immunodiagnosis and immuno-epidemiology of S. stercoralis infection.