Research Article: Ivermectin Resistance in Onchocerca volvulus: Toward a Genetic Basis

Date Published: October 30, 2007

Publisher: Public Library of Science

Author(s): Sara Lustigman, James P. McCarter, Gavin Yamey

Abstract: None

Partial Text: Onchocerciasis (river blindness) is a human disease caused by the filarial worm
Onchocerca volvulus. Adult worms can live for over a decade in
skin nodules of affected humans, releasing millions of microfilariae that cause
debilitating itching and blindness [1]. An estimated 37
million people are infected [2], and there are 46,000 new cases of blindness
annually (

A new study by Catherine Bourguinat and colleagues published in PLoS
Neglected Tropical Diseases extends these previous reports and
concludes not only that IVM causes genetic selection on O. volvulus
worms, but that this selection is also associated with a lower reproductive rate of
the female parasites [27]. In this study of O. volvulus
treatment in a hyperendemic region of central Cameroon, parasite genotypes
(β-tubulin gene and two controls) and phenotypes
(female fertility) were characterized in worms collected from the same individuals
before and after four or 13 IVM treatments over three years. Parasites were
collected pre- and post-treatment from clinical trial patients in four IVM treatment
groups: 150 µg/kg of body weight annually or three-monthly, and 800
µg/kg annually or three-monthly.

A major strength of this study is that the O. volvulus parasites
were collected from the same individuals before and after IVM treatments. Therefore
the observed changes in genotype frequencies between IVM-naïve and treated
O. volvulus populations are not due to factors such as
geographical or sampling effects.

The finding that IVM treatment selected for β-tubulin
heterozygotes and that this selection was dependent on dosage raises important
concerns for the current river blindness control programs. These concerns are
heightened by the fact that this gene has been linked with IVM resistance in another
parasitic nematode [26], and by the recent evidence that IVM resistance
is occurring in O. volvulus[17]. Semiannual or more frequent treatments are ongoing
in some endemic areas and are under consideration in other areas. Such treatment
might increase the selection pressure. Therefore, Bourguinat and
colleagues’ study is a wake-up call for control programs to select their
treatment regimens carefully and to develop plans for detecting IVM resistance and
the associated genetic markers (control programs will require additional funding for
these plans). This study presents a possible structure of study design that will
incorporate the detection and validation of the genetic markers associated with IVM



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