dc.description.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
asymptomatic 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 but
increased 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. | en_US |