Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Abstract

Abstract. Following a 16-year clinical and parasitologic follow-up survey for Bancroftian filariasis in three endemic communities in northeastern Tanzania, serum antibody responses were analyzed in selected individuals in relation to the long-term observations on microfilaremia. Comparison of responses in three categories of adults (microfilaria [mf] positive at both surveys, mf positive at first but mf negative at the second survey, and mf negative at both surveys, respectively) indicated no significant differences between the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4, or IgE (measured by ELISA). However, specific IgG2 to the sheath of Wuchereria bancrofti mf (measured by an indirect fluorescence antibody test [IFAT]) was detected only in the third category. Comparison of responses in two categories of children born around the time of the first survey (to mf-positive and mf-negative mothers, respectively) showed a significantly higher mean level of filarial-specific IgG4 in the first than in the latter category, whereas the mean levels of filarial-specific IgG1, IgG2, IgG3, and IgE, and the prevalences of IgG2 IFAT positivity were similar. The overall prevalence of IgG2 IFAT positivity was considerably higher in the child study population (45.5%) than in the adult study population (16.7%). In both populations, however, a clear association between IgG2 IFAT positivity and a negative microfilarial status and negative specific circulating antigen status was seen. The study suggests that specific anti-sheath-antibodies are associated with an immunologic resistance mechanism that in the endemic community is expressed with highest prevalence in young individuals before development of patent microfilaremia.Despite the widespread occurrence of Wuchereria bancrofti infections in tropical areas, many aspects of the natural history of infection and disease in Bancroftian filariasis remain poorly understood. Basic knowledge on determinants related to host susceptibility, the longevity of infection and development of resistance, being of utmost importance for understanding the epidemiology of Bancroftian filariasis and for planning and implementation of control programs, is lacking. 1-3 A major reason for this is a scarcity of longitudinal studies.In an attempt to clarify some of these aspects, a 16-year follow-up study was carried out on Bancroftian filariasis in three endemic communities in northeastern Tanzania. All individuals were examined for microfilariae and clinical manifestations in 1975 4 and again in late 1991, 5 and as many as possible of the individuals examined in the first surveys were re-identified in the second surveys. Analyses of the parasitologic and clinical findings have already been presented. 5,6 Briefly, with respect to microfilaremia, the study showed that only few individuals had changed from a microfilaria (mf)-positive to -negative status over the 16-year period, despite the fact that the average life span of adult worms has been estimated to be much shorter. 1 In the 1991 survey...

Bancroftian filariasis infection, disease, and specific antibody response patterns in a high and a low endemicity community in East Africa.

“…Sera were examined for filarial-specific antibodies (IgG1, IgG2, IgG3, IgG4, and IgE) by an ELISA as previously described. 21,22 A Brugia pahangi adult worm homogenate was used as antigen. 21 Optimal dilutions of antigen, serum, and conjugate were determined by titration.…”

Natural History of Human Filariasis — The Elusive Road

“…The model thus accommodates disease development by inflammatory processes (proposed by immunological viewpoint) as well as by lymphatic dwelling parasites, (proposed by dynamic model) and it explains the presence of filarial infection in patients with chronic disease. It also accommodates the observations made by all the long-term follow-up studies mentioned above (Steel and Ottesen, 2001;Satapathy et al, 2001;Simonsen and Meyrowitsch, 1998;Dissanayake, 2001). Three sets of immuno-epidemiological observations made in endemic areas provide more direct evidence for the major component of the current linear model which proposes that inflammatory Th 1 responses will be observed in the host during the pre-patent phase of infection ie., before the onset of antigenemia/microfilaraemia.…”

“…In Cook Islands, loss of filarial infection in a cohort of Mf carriers (over a period of 17 years) failed to result in significant recovery of filarial specific T-cell proliferation or enhanced production of (Steel and Ottesen, 2001). In Tanzania (Simonsen and Meyrowitsch, 1998) and India (Satapathy et al, 2001), loss of Mf in parasite carriers after 18 or 13 years respectively failed to result in appearance of antibodies to Mf sheath. Absence of Mf and presence of such Mf sheath reactive antibodies is a consistent feature in vast majority of patients with chronic filarial disease (Ravindran et al, 2000).…”

“…Longitudinal follow-up of Mf carriers for 13-16 years has indicated persistence of adult worms as shown by the presence of CFA several years after loss of circulating microfilariae. (Satapathy et al, 2001;Simonsen and Meyrowitsch, 1998). The long life span of adult filarial worms is further indicated by several immunoepidemiological studies on the prevalence of CFA in age-stratified populations in endemic areas.…”

“…Longitudinal studies conducted on the same cohort of subjects, the results of which have been reported in recent years, do not offer credence to such a scenario expected of the "dynamic model". 1) infected subjects in the Cooke Islands continued to display immunological hyporesponsiveness to filarial antigens after loss of microfilaraemia as well as antigenaemia when examined after 17 years (Ravindran et al, 2000); 2) in two different studies, one after 13 years (Satapathy et al, 2001) and another after 18 years (Simonsen and Meyrowitsch, 1998) of follow-up, it was observed that absence of antibodies to microfilarial sheath (a hallmark of immunological hyporesponsiveness in microfilaraemic subjects) in Mf carriers persist several years after loss of peripheral microfilaremia; 3) chronic filariasis was found to develop in a significant proportion of endemic normals ( asymptomatic subjects without patent infection) after 18 years of follow-up-notably in the same area in Sri Lanka. Mf carriers, on the other hand, continued to be asymptomatic after 18 years even though a significant proportion of them were free of circulating Mf when examined 18 years later (Dissanayake, 2001) very similar observations have been made in two other areas in Orissa, where microfilarial carriers and endemic normals were followed-up for a period of 10-13 years, (Sahoo et al, 2001) and 4) the development of acute filarial episodes in several thousand American troops in South Samoa after an average exposure of 11 months indicated that a patent phase (which generally lasts several years) is not mandatory for development of filarial disease (Wartman, 1947).…”