Unveiling the population dynamics of the filarial worm Loa loa using population genetics
Loiasis is a parasitic disease caused by Loa loa, a nematode (round worm) belonging to the family of Onchocercidae. L. loa is transmitted from human to human via bites of horseflies (Chrysops spp.).
In humans, adult worms live under the skin or within inter-muscular fascia layers and migrate episodically under the eye conjunctiva. After mating with a male, female worms produce millions of larvae (microfilariae, mf), which invade the circulatory system.
L. loa is exclusively found in Africa, from Benin to South Sudan and from Chad to Angola and about 20 million people are infected.
Given the vectors’ biology, the highest loiasis endemicity levels are recorded in rainforest areas: loiasis is typically a rural parasitosis.
It attracted relatively little interest until the launching, in 1995, of the African Programme for Onchocerciasis Control (APOC), based on mass drug administration (i.e. without individual diagnosis) of ivermectin. APOC activities were impeded in the loiasis-endemic areas because subjects with high L. loa microfilarial density (MFD) can develop a potentially fatal encephalopathy after ivermectin treatment.
To tackle this issue, many studies on the epidemiology, population dynamics and treatments of loiasis have been conducted, notably by the main applicant’s team.
Long regarded as a benign disease per se, we are building a case to have loiasis registered in the World Health Organization’s list of Neglected Tropical Diseases (NTDs). We have already demonstrated that high-grade infection with L. loa is associated with a significant excess mortality.
With the present application, we want to focus on the parasite, more precisely on its genetics. We will use molecular markers to investigate genetic diversity, mating system and gene flow of L. loa.
Position of the project as it relates to the state of the art
L. loa transmission dynamics has mainly been documented during the period 1950-1970. Specific studies addressing the biological basic parameters (life expectancy of adult stages and of mf, mating behavior, fecundity, etc.) are very few.
In 2018, we published a review summarizing available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argued for the mobilisation of resources to develop mathematical transmission models to guide deployment of interventions against L. loa.
So far, it has been assumed that L. loa is a homogeneous species. However, when we studied the phenotype of response of L. loa to ivermectin in a meta-analysis, we found that some parasites could be less sensitive to ivermectin. In addition, it appears that contrasting epidemiological patterns exist: in most areas, the prevalence of L. loa microfilaremia is clearly positively correlated with the mean MFD in the communities. However, in eastern Nigeria, high prevalence of microfilaremia can be associated with low MFDs.
Whether it is due to differences in genetic profiles of the parasite, or of the hosts, or to other factors, is not known. The two attempts made so far to assemble L. loa genomes have been driven by different purposes. Wolbachia bacteria are widespread endosymbiotic bacteria in nematode parasites, but it is absent in L. loa.
Desjardin et al. focussed on a possible integration of Wolbachia genes into the L. loa genome, to explain how L. loa worms could survive without Wolbachia. In the second attempt to sequence the genome of L. loa, the approach was essentially academic, and it was the opportunity to assess an improved method for sequencing.
In this project, analyses on the L. loa genome will be done with the perspective to define public health interventions. We assume that a better understanding of the population dynamics of the parasite will help define the best strategies to eliminate the disease.
This ANR-funded project is a collaborative research project including two teams from the French Institut de Recherche pour le Développement, TransVIHMI and DIADE, and the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT) – based in Yaoundé, Cameroon.