Differential recognition of microfilarial chitinase, a transmission-blocking vaccine candidate antigen, by sera from patients with Brugian and Bancroftian filariasis.

We examined the reactivity of human sera with recombinant microfilarial chitinase and with the antigenic determinant on the native parasite molecule identified by monoclonal antibody (MAb) MF1. In Brugian filariasis, the MF1 epitope is preferentially recognized by residents of endemic areas who remain amicrofilaremic and asymptomatic despite lifelong exposure to filarial worms. Reactivity with filarial chitinase and its MF1 epitope inversely correlates with microfilaremia levels in Bancroftian filariasis and is associated with a prolonged amicrofilaremic state following a single course of treatment with diethylcarbamazine. Chitinase does not appear to be a target of human antibodies that promote the adherence of cells to microfilariae, even though MAb MF1 itself promotes antibody-dependent, cell-mediated cytotoxic (ADCC) reactions that kill microfilariae in vitro. Such ADCC reactions are most often mediated by sera from amicrofilaremic patients with chronic elephantiasis that contain low or undetectable levels of IgG antibodies to chitinase. In contrast, antibodies to the MF1 epitope on this microfilarial stage-specific antigen are mostly present in amicrofilaremic donors without clinical lymphatic disease. These observations indicate that antibodies to the MF1 epitope of microfilarial chitinase reflect some degree of immune resistance to microfilaremia in a subgroup of patients with asymptomatic lymphatic filariasis. The amicrofilaremic state of individuals with chronic lymphatic disease appears to be mediated by reactivity to a different parasite antigen(s).

Lymphatic pathology in Wuchereria bancrofti microfilaraemic infections.

To determine the extent of lymphatic disease in persons infected with Wuchereria bancrofti who were microfilaraemic, we examined the superficial lymphatics of the legs by scintigraphy. In 4 endemic control subjects and in 10 of 14 clinically asymptomatic microfilaraemic individuals, lymphoscintigraphy revealed one major channel of lymphatic drainage in each leg. However, while trunk lymphatics were bilaterally symmetrical in the control, marked differences in the calibre of lymphatic vessels were observed in the microfilaraemic persons. Non-discrete lymphatics and a diffuse symmetrical distribution of collateral vessels in both legs were observed in all of 5 amicrofilaraemic patients with grade 2 lymphoedema. A similar diffuse drainage pattern was also seen in 3 previously microfilaraemic persons who had remained amicrofilaraemic and asymptomatic following treatment with diethylcarbamazine citrate (DEC). Thus, clearance of microfilaraemia by DEC therapy did not appear to reverse the type of lymphatic pathology observed in microfilaraemic subjects. The lymphoscintigraphy patterns did not correlate with serum levels of antibodies to 3 recombinant filarial antigens. Virtually all the asymptomatic microfilaraemic individuals infected with W. bancrofti examined had subclinical lymphatic disease detected by the non-invasive imaging technique of lymphoscintigraphy.

Evaluation of a recombinant parasite antigen for the diagnosis of lymphatic filariasis.

We evaluated the usefulness of a recombinant parasite antigen (recSXP1) for the serologic diagnosis of lymphatic filariasis. A large proportion of sera from microfilaremic donors living in five different endemic countries (356 of 446 [80%]) contained IgG antibodies to recSXP1, as do sera from approximately 33% of amicrofilaremic patients with acute filarial disease and/or indirect evidence of active filarial infection. Exposure to filarial worms per se does not appear sufficient to elicit an anti-SXP1 antibody response. Thus, this serologic test identifies a large proportion of persons with active lymphatic filariasis among residents of endemic areas.