Ivermectin, a medicine capable of killing the parasite embryos (the microfilariae) circulating in the organism of patients and temporarily interrupting the nematode’s reproduction, is the only treatment used for onchocerciasis control. Since 1995, the African Programme for Onchocerciasis Control (APOC) has been covering 19 of the continent’s 28 countries hit by the disease. Access to this treatment is possible for 70 million people and has significantly diminished the onchocerciasis-induced morbidity. However, the doubling of cases of infection in certain communities of Ghana between 2000 and 2005, in spite of annual treatments, created fear of the emergence of ivermectin-resistant strains. Such apprehension appears particularly justified in that a high degree of therapeutic cover is achieved during mass distribution campaigns and hence only a tiny part of the parasite population targeted remains unexposed to drug treatment pressure.
Since 1994, a team of IRD researchers, working jointly with Cameroon researchers and others from McGill University of Montreal, has been monitoring a cohort of Cameroon patients benefiting from repeated treatments with ivermectin. Regular parasite sampling from these subjects was performed over a 13-year period in order to determine the changes in the genetic structure of Onchocerca volvulus populations. Each occasion involved measurement of the genotype frequency of heterozygotes and homozygotes for the gene coding ß-tubulin, a protein involved in the organization of the parasite’s cells. The team focused on this particular gene because it acts as a marker of resistance to ivermectin in other nematode species parasitic on cattle. As a control, they monitored the changes in genotype frequency of two other genes, known for their high evolutionary stability over time. The proportion of homozygotes and heterozygotes for these two genes remained stable throughout the investigation, but the situation was completely different for the ß-tubulin gene.
Between 1994 and 1998, the percentage of parasites showing a genotype homozygous for this gene fell from 79 to 31% in subjects receiving quarterly treatment with ivermectin. At the same time, the proportion of heterozygous genotypes changed in the opposite sense, rising from 21 to 69%. These results could be the sign of adaptation of nematode worm populations to repeated treatments using this drug. The research team inferred that the parasites showing a genotype homozygous for ß-tubulin are more susceptible to it. As courses of treatment progressed, they would therefore gradually disappear, to the benefit of the more resistant heterozygous strains. Ivermectin’s effect on microfilariae, other than its direct one, is to prevent them from leaving the uterus of adult worms, for several months after treatment: this is its embryostatic effect. Post-treatment, there were more microfilariae in the uterus of homozygous female parasites than in those of heterozygous females. This could mean that, in the latter, the microfilariae succeed in leaving the uterus, as they usually do in the absence of treatment, and therefore that the embryostatic effect of ivermectin would be diminished. Contrary to the effect anticipated, the repeated exposure to treatments could in this way select those worms more able to keep up the production of new generations. Nevertheless, the drug’s direct action on the microfilariae appeared not to change, and hence, for the moment, there is no reason to call into question the current control strategy against the disease based on annual treatments with ivermectin.
Affirmation of the results requires further investigations¹, starting from new cohorts subjects infected by Onchocerca volvulus who have not yet been treated with ivermectin. This type of approach should bring more information on the risks of the parasite’s resistance to this drug. If such risks were confirmed, then the whole onchocerciasis control strategy would probably have to be revised. Nevertheless, for many years to come, ivermectin could well remain the sole drug applicable for mass treatment in measures to control river blindness.
Grégory Fléchet - DIC
1. A study coordinated by the IRD and financed by the French Agence nationale de la recherche (ANR), aiming to find more extensive information on possible resistance of the onchocerciasis parasite to ivermectin, is currently being conducted in Cameroon jointly with a team from INRA, research scientists from the universities of Yaoundé I and Buea (Cameroon), the Cameroon Ministry of Public Health, McGill University of Montreal (Canada) and Imperial College London (United Kingdom).
Grégory Fléchet | alfa
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences