Familial aggregation and heritability of Loa loa microfilaremia

Abstract

Background

For a given prevalence of Loa loa microfilaremia, the proportion of people with high densities varies significantly between communities. We hypothesized that this variation is related to the existence of familial clusters of hypermicrofilaremic individuals that would be the consequence of a genetic predisposition to present high L. loa microfilarial densities.

Methods

A familial study was performed in 10 villages in the Okola Health District of Cameroon. Intra-familial correlation coefficients and heritability estimates were assessed for both the presence of L. loa microfilaremia and individual microfilarial densities by controlling for age, sex, Mansonella perstans coinfection and household effects.

Results

Pedigrees were constructed for 1,126 individuals. A significant familial susceptibility to be microfilaremic for L. loa was found for first-degree relatives (ρ = 0.08, P < .05; heritability = 0.23). Regarding individual microfilarial densities, a significant familial aggregation was demonstrated (ρ = 0.36 for first- and 0.27 for second-degree relatives). For first-degree relatives, the highest coefficient was found between mothers and daughters (ρ = 0.57). Overall heritability estimate for L. loa microfilarial density was 0.24 (P = .003).

Conclusions

A significant genetic component governs L. loa microfilarial density. This supports the hypothesis that a genetic predisposition to be hypermicrofilaremic exists, leading to the presence of familial clusters of individuals at risk for post-ivermectin severe adverse events. This finding should be taken into account while developing sampling strategies (including a household-level sampling) to identify villages where community-directed treatment with ivermectin cannot be applied.