A population from the Wuchereria bancrofti-endemic island of Mauke was reevaluated retrospectively by use of the Og4C3 circulating antigen (CAg) enzyme-linked immunosorbent assay to assess active infection in relation to host responses by age and gender. Use of microfilaremia (Mf) alone misclassified 50% of infected people, although CAg and Mf levels were positively correlated. Levels of CAg peaked between those aged 31-60 years; men aged 60 years had a significantly higher CAg prevalence (90%) than women. Filaria-specific im-munoglobulin (Ig) G4 reached maximum levels in both genders at age 51-60 years. By analysis of variance, both age and gender significantly influenced CAg and IgG4, with men having higher levels of both in the total population. Individuals positive for CAg had significantly lower lymphocyte proliferation responses to parasite antigen than did CAg-negative people, regardless of clinical status. This study reemphasizes the importance of CAg measurements for accurately assessing filarial prevalence and clinical status and demonstrates the relationship between active infection and immune responsiveness.
A polymerase chain reaction (PCR) assay based on a highly repeated deoxyribonucleic acid (DNA) sequence found in Wuchereria bancrofti (the SspI repeat) has been developed to address the shortcomings of traditional diagnostic methods. In this field study in a W. bancrofti endemic region of French Polynesia, 373 human blood samples were collected and 100 microL of blood were screened by the SspI PCR assay and 1 microL by membrane filtration. The SspI PCR assay detected 99 of 113 blood samples in which microfilariae had been detected by filtration (sensitivity of 88%) with a specificity of 100%. All the samples missed by the SspI PCR assay had less than 8 microfilariae per mL of blood. To evaluate the efficacy of screening larger blood samples by PCR, both 100 microL and 500 microL samples from 50 patients with very low-level microfilaraemia were screened by the SspI PCR assay; the sensitivity increased from 60% to 84% when using the larger volume of blood. Finally, an enzyme-linked immunosorbent assay-based version of the SspI PCR assay was used to screen blood from 12 patients following treatment with diethylcarbamazine, ivermectin, or both. These results showed that the PCR assay closely paralleled the presence or absence of microfilariae in the blood and that no increase in the DNA level was seen immediately following drug treatment.
Circulating filarial antigen (CFA), determined with Og4C3 ELISA, is a marker of Wuchereria bancrofti adult worm infection. The reduction of CFA over 2 years was determined in 185 microfilaremic and 111 amicrofilaremic but CFA+ adults given an annual dose of either diethylcarbamazine (DEC) or ivermectin or the two combined. Reduction of CFA level was good with DEC but weak with ivermectin and followed the same pattern in amicrofilaremic and microfilaremic groups. Combinations and DEC alone had a similar impact on CFA level. CFA clearance was observed in amicrofilaremic but not in microfilaremic persons in all DEC-containing treatments. However, the highest clearance rate was observed in persons treated with DEC at 6 mg/kg combined with ivermectin. Continuous reduction of CFA level after repeated treatments shows that elimination of W. bancrofti infection, monitored by CFA clearance, might be achieved within a few years with annual treatments of DEC combined with ivermectin.
BackgroundEpidemics of meningococcal meningitis (MM) recurrently strike the African Meningitis Belt. This study aimed at investigating factors, still poorly understood, that influence annual incidence of MM serogroup A, the main etiologic agent over 2004–2010, at a fine spatial scale in Niger.Methodology/Principal FindingsTo take into account data dependencies over space and time and control for unobserved confounding factors, we developed an explanatory Bayesian hierarchical model over 2004–2010 at the health centre catchment area (HCCA) level. The multivariate model revealed that both climatic and non-climatic factors were important for explaining spatio-temporal variations in incidence: mean relative humidity during November–June over the study region (posterior mean Incidence Rate Ratio (IRR) = 0.656, 95% Credible Interval (CI) 0.405–0.949) and occurrence of early rains in March in a HCCA (IRR = 0.353, 95% CI 0.239–0.502) were protective factors; a higher risk was associated with the percentage of neighbouring HCCAs having at least one MM A case during the same year (IRR = 2.365, 95% CI 2.078–2.695), the presence of a road crossing the HCCA (IRR = 1.743, 95% CI 1.173–2.474) and the occurrence of cases before 31 December in a HCCA (IRR = 6.801, 95% CI 4.004–10.910). At the study region level, higher annual incidence correlated with greater geographic spread and, to a lesser extent, with higher intensity of localized outbreaks.ConclusionsBased on these findings, we hypothesize that spatio-temporal variability of MM A incidence between years and HCCAs result from variations in the intensity or duration of the dry season climatic effects on disease risk, and is further impacted by factors of spatial contacts, representing facilitated pathogen transmission. Additional unexplained factors may contribute to the observed incidence patterns and should be further investigated.
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