Search

The response pattern of specific antibodies to the microfilarial sheath (sheath-Ab) of the mosquito-borne filarial parasite Wuchereria bancrofti was investigated in individuals from two East African communities with different levels of endemicity. Individuals from both communities presented a strong inverse relationship between positivity for sheath-Ab and being positive for microfilariae (mf) and circulating filarial antigens (CFA). The prevalence of sheath-Ab positivity was highest in young individuals, but peaked at a younger age in the high (1-14 years) than the low (15-19 years) endemicity community. IgG1, IgG2, IgG3 and IgE intensities to a crude adult filarial worm antigen were higher, and IgG4 intensities were lower, in sheath-Ab positive than in sheath-Ab negative individuals, probably reflecting the infection status of individuals. From the study it appears that individuals become sheath-Ab positive before mf and/or CFA can be detected in the peripheral blood, and only after later disappearance of sheath-Ab from the circulation can CFA and mf be diagnosed. In light of the findings, possible roles of the distinct sheath-Ab in the host-parasite relationship are discussed, and a hypothesis is proposed which suggests that sheath-Ab play an important role in the regulation of host microfilaraemia.

We compared the age profiles of infection and specific antibody intensities in two communities with different transmission levels in East Africa to examine the contribution of humoral responses to human immunity to the vector-borne helminth Wuchereria bancrofti. The worm intensities were higher and exhibited a nonlinear age pattern in a high-transmission community, Masaika, in contrast to the low but linearly increasing age infection profile observed for a low-transmission community, Kingwede. The mean levels of specific immunoglobulin G1 (IgG1), IgG2, IgG4, and IgE were also higher in Masaika, but intriguingly, the IgG3 response was higher in Kingwede. The age-antibody patterns differed in the two communities but in a manner apparently contrary to a role in acquired immunity when the data were assessed using simple correlation methods. By contrast, multivariate analyses showed that the antibody response to infection may be classified into three types and that two of these types, a IgG3-type response and a response measuring a trade-off in host production of IgG4 and IgG3 versus production of IgG1, IgG2, and IgE, had a negative effect on Wuchereria circulating antigen levels in a manner that supported a role for these responses in the generation of acquired immunity to infection. Mathematical modeling supported the conclusions drawn from empirical data analyses that variations in both transmission and worm intensity can explain community differences in the age profiles and impacts of these antibody response types. This study showed that parasite-specific antibody responses may be associated with the generation of acquired immunity to human filarial infection but in a form which is dependent on worm transmission intensity and interactions between immune components.

A hospital based open-label clinical trial of 19 apparently healthy adult males with microfilaraemia was conducted to assess safety, tolerability and efficacy of doxycycline on Wuchereria bancrofti. Study individuals were assigned 8 weeks treatment with doxycycline 200 mg daily. The results of different selected tests showed that, the haematological, hepatic, renal and clinical parameters pre-and post-drug administrations were within the normal range for all treated individuals. Clinical adverse events were mild, transient, tolerable and reported in 7/19 (36.8%) of the study cohort. The mf clearance rate was 100% at 12 months post treatment for the 13 individuals who completed the follow up. These findings indicate that, although the drug was administered for a long period, there was no evidence of toxicity to the myocardium, hepatocytes, renal, bone marrow and blood cells, suggesting that an 8-week course of 200 mg/day doxycycline is a safe and tolerable regime for the treatment of Wuchereria bancrofti infections.

Bancroftian filariasis infection, disease and specific antibody response patterns in a high and a low endemicity community in East Africa were analyzed and compared to assess the relationship between these parameters and community transmission intensity. Overall prevalences of microfilaremia and circulating filarial antigenemia were 24.9% and 52.2% in the high and 2.7% and 16.5% in the low endemicity community, respectively. A positive history of acute attacks of adenolymphangitis was given by 12.2% and 7.1% of the populations, 4.0% and 0.9% of the adult (> or = 20 years old) individuals presented with limb lymphedema, and 25.3% and 5.3% of the adult males had hydrocele, in the high and the low endemicity community, respectively. Both infection and disease appeared earlier and reached much higher levels in the high than in the low endemicity community. The observed overall and age-specific infection and disease patterns in the two communities were in agreement with the view that these are primarily shaped by transmission intensity. No statistically significant relationships between infection status of fathers and mothers and that of their children were observed in any of the communities for either microfilaremia or for circulating filarial antigenemia. The overall levels (prevalence and geometric mean intensity) of filarial-specific IgG1, IgG2, IgG4, and IgE were significantly higher in the high endemicity community than in the low endemicity dommunity. Surprisingly, the opposite pattern was found for IgG3. Community transmission intensity thus appears to be an important determinant of observed inter-community variation in infection, disease, and host response patterns in Bancroftian filariasis.