Studies on the Immune & Demiology of Bancroftian Filariasis in East Africa

Jaoko, Walter G Godfrey (2000) Studies on the Immune & Demiology of Bancroftian Filariasis in East Africa. PhD thesis, University of Nairobi.

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Abstract

This study assessed the effect of transmission intensity on the patterns of infection, disease and specific antibody response in bancroftian filariasis, by comparing observed patterns of infection, disease and specific IgGl, IgG2, IgG3, IgG4 and IgE profiles in two communities with high and low W. bancrofti endemicity. The communities were Masaika in Tanga Region, Tanzania, which was highly endemic for bancroftian filariasis, and Kingwede in Kwale District of Kenya, which had low endemicity. Detailed analyses of specific antibody responses were carried out in relation to infection and clinical status, age and gender. An additional smaller part of the study investigated if seasonal variation in transmission intensity influenced the stability of infection and specific antibody responses.The larger part of the study was cross-sectional and included all consenting individuals aged 12 months and over. From each individual, demographic information and medical history was obtained, followed by clinical examination and blood sampling. Finger-prick samples were examined for microfilarie (mf) by counting chamber method, and venous samples were analysed for circulating filarial antigen (CFA) by the Trop Bio commercial kit for detecting W. bancrofti circulating antigen in serum, and for filaria-specific antibodies (IgGl, IgG2, IgG3, IgG4 and IgE) using ELISA technique. Mean intensities of mf, CFA and filaria-specific antibodies were all calculated as geometric means.Overall mf and CFA prevalence and mean intensities were significantly higher in Masaika than in Kingwede. In Masaika but not in Kingwede, mf and CFA mean intensities were significantly higher in males than in females. This was mainly due to gender differences in the 15-39 year age group. In both communities, infection prevalence was higher, although not significantly, in children of infected parents than in children of non-infected parents. Chronic filarial disease manifestations (hydrocele and elephantiasis) among adults were more prevalent and presented earlier in Masaika than in Kingwede. The proportion of individuals reporting having experienced acute adenolymphangitis attacks during the one-year period preceding the survey was also significantly higher in Masaika than in Kingwede, and was higher in adults than in children, although this difference was statistically significant only in Masaika. Overall, prevalence and mean intensities of IgGl, IgG2, IgG4 and IgE were significantly higher in Masaika than in Kingwede. The opposite pattern was seen for IgG3. Antibody profiles were analysed in relation to clinical and infection status of the individuals in Masaika, but not in Kingwede where individuals with chronic disease were too few for such analysis. The profiles were similar in a symptomatic and chronic disease individuals. There was a highly significant association between antibody profiles of all the measured antibodies and infection status. IgGl and IgG2 were more associated with mf status than with CFA status, IgG3 and IgG4 were associated more with CFA status than with mf status, while IgE was associated with both mf and CFA status. These associations were not significantly influenced by clinical status. Due to few chronic filarial disease cases in Kingwede, inter-community antibody profile comparison was restricted to asymptomatic individuals. In Masaika, IgGl prevalence and intensity were significantly higher among mf negative individuals than among mf positive individuals. The opposite pattern was seen in Kingwede where both IgGl parameters were highest among the mf and CFA positive and lowest among the mf and CFA negative. In Masaika, IgG3 profiles were associated with both mf and CFA, while in Kingwede they were more associated with mf than CFA. Furthermore, although in Masaika IgG2 and IgE were significantly associated with mf status, in Kingwede, their profiles were uniform in all infection groups. Only IgG4 profiles were similar in the two communities, being highest among CFA positive individuals and lowest among CFA negative individuals. Age-specific antibody intensity patterns for IgGl, IgG4 and IgE were similar in both communities. IgGl and IgE decreased with age while IgG4 increased with age. IgG2 and IgG3 profiles differed between the communities. IgG2 intensity decreased with age in Masaika, but increased with age in Kingwede. IgG3 intensity remained uniformly low with age in Masaika butincreased with age in Kingwede. Despite clear gender differences in mf and CFA intensities in Masaika in the female reproductive age group, there were no clear gender differences in antibody intensities in this age group. IgG3 intensities were in general significantly higher among mf or CFA positive females than among their male counterparts. The opposite was seen for IgG4 intensities. Overall mean IgG4/IgE ratio was significantly higher in Masaika than in Kingwede. In Masaika, the ratios were higher among the chronic diseased than the asymptomatic individuals in each infection group. These findings contrast what is expected if this ratio indicates infection resistance level and if IgE mediates chronic filarial disease pathogenesis, as has been suggested. These results suggest that transmission intensity influences levels and patterns of infection, disease and specific antibodies, and the association between infection intensity and gender, and that antibody responses are more associated with infection status than disease status. The study further suggests that the measured specific antibodies are not the basis for the observed gender differences in infection intensities in the female reproductive age group. The last part of the study was longitudinal. A selected population of 37 CFA positive males aged 20 to 40 years participated. Blood samples from each individual were examined for mf, CFA and specific IgGl, IgG2, IgG3, IgG4 and IgE antibodies at the beginning of the study, and at 6 and 12 months later. The time points corresponded to high, low and high transmission seasons, respectively. Transmission intensity during the study year was assessed entomologically by catching, dissecting and examining mosquito vectors for infective larvae. W. bancrofti transmission was found to be seasonal, with highest intensities during the rainy season and lowest during the dry season in concert with mosquito vectors abundance. Despite the marked seasonal variation in transmission potential, no statistically significant variation was observed in the mf, CFA, measured filaria-specific antibody levels or IgG4/IgE ratios, suggesting that seasonal transmission may not result in seasonal fluctuations in the levels of infection, measured immune responses or resistance to infection.

Item Type:	Thesis (PhD)
Subjects:	R Medicine > R Medicine (General)
Divisions:	Africana
Depositing User:	Geoffrey Obatsa
Date Deposited:	24 Oct 2016 13:34
Last Modified:	24 Oct 2016 13:34
URI:	http://thesisbank.jhia.ac.ke/id/eprint/1048

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