| 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 19G1, 19G2, 19G3,
19G4and 19E profiles in two communities with high and low Wuchereria 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 (1gGl, 19G2, 19G3, 19G4 and
19E) using ELISA technique. Mean intensities of mf, CFA and filaria-specific
antibodies were all calculatedas 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 significantlyhigher 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-infectedparents.
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 19G1, 19G2, 19G4 and 19E were
significantly higher in Masaika than in Kingwede. The opposite pattern was seen
for 19G3.
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. 19G1 and 19G2
were more associated with mf status than with CFA status and 19G3 and 19G4 were
more associated with CFA status than with mf status, while 19E 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, IgG1
prevalence and intensity were significantly higher among mf negative individuals
than among mf positive individuals. The opposite pattern was seen in Kingwede
where both IgGI 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 IgGI, IgG4 and IgE were similar in
both communities. IgG1 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
uniformlylow 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
oppositewas 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 IgGI, 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 filariaspecific
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 |
