A recently published investigation has identified a cluster of Guinean patients with dapsone-resistant Mycobacterium leprae, as well as a single case demonstrating rifampicin resistance.
These are the first cases of dapsone- and rifampicin-resistance reported in West Africa, according to Charlotte Avanzi, PharmD, PhD student at Ecole Polytechnique Fédérale de Lausanne, Switzerland, and colleagues.
“Despite a remarkable decline in the prevalence of leprosy following the global implementation of multidrug therapy (MDT) in the 1980s by [WHO], well over 200,000 new leprosy cases are still recorded annually worldwide,” the researchers wrote. “First-line drugs used for MDT against leprosy are dapsone, rifampicin and clofazimine, while second-line drugs include ofloxacin, minocycline and clarithromycin. Because of the lack of effective alternative antileprosy drugs, resistance to the first-line drugs could seriously affect leprosy control programs.”
There were 313 cases of leprosy reported in Guinea in 2014; however, no resistance data were available for any of these cases. To amend this, Avanzi and colleagues collected 24 skin biopsy samples from 2012 to 2015, and analyzed genes associated with resistance for any evidence of mutation. The researchers further examined a subset of these cases through whole-genome sequencing and an epidemiologic investigation.
All of the samples examined by Avanzi and colleagues were multibacillary and treated with WHO-recommended 12-month MDT. Among these, one sample from a patient living in the Boke region contained a mutation previously associated with high-level rifampicin resistance, while three patients living in the Kankan region had mutations indicating dapsone resistance. Although leprosy history data was unavailable for the patient in Boke, whole-genome phylogeny implied a relationship between the three Kankan strains. The researchers noted that while it was possible that all three acquired their infection from separate sources, it is more likely that some transmission occurred between these patients — two of whom were siblings.
Avanzi and colleagues wrote that the dapsone resistance shared by the Kankan cases is not considered a substantial threat to leprosy control; however the rifampicin-resistant strain “is a bigger concern due to the limited alternatives in leprosy treatment of rifampicin-resistant cases.”
The absolute number of samples tested by Avanzi and colleagues was low, but these “alarming results” remain clinically significant when considering the annual diagnosis rate of leprosy in Guinea, according to Milton Ozório Moraes, PhD, chief of the Leprosy Laboratory of the Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro. In a related editorial, he said efforts to limit the 200,000 annual infection estimated worldwide will depend on increased monitoring and study of M. leprae incidence and transmission mechanisms.
“New [treatment] strategies may block transmission and improve the quality of life of patients and household contacts,” he wrote. “Even so, it is important that these new strategies be aligned with careful surveillance for relapses and resistance in order that leprosy may be eliminated as a public health problem.” – by Dave Muoio
Disclosure: The researchers report no relevant financial disclosures.