While the multidrug antibiotic regimen of rifampin, dapsone, and clofazimine recommended by the World Health Organization (WHO) for the treatment of paucibacillary and multibacillary leprosy seemed to show better clinical improvement of lesions compared with combination rifampin, ofloxacin, and minocycline treatment and other treatment regimens, it showed almost no difference in cured and reduced relapse rate, according to a meta-analysis published in BMC Infectious Diseases.
Leprosy is an infection that affects the skin and peripheral nerves resulting in infection with Mycobacterium leprae. The prevalence of leprosy has significantly decreased and several previously endemic countries have eradicated the infection, but it continues to be global health concern. Of the roughly 214,000 incident cases of leprosy in 2014, the majority (81%) occurred in Brazil, India, or Indonesia.
According to the WHO, the use of the 3-drug regimen of rifampicin, dapsone, and clofazimine is recommended for all patients with leprosy, with treatment duration of 6 months for paucibacillary leprosy and 12 months for multibacillary leprosy. Since this recommended multidrug therapy has been in use for more than 30 years, researchers aimed to evaluate its effectiveness compared with other available regimens.
Two independent reviewers searched multiple electronic databases from 1982 to July 2018 without any language restriction and identified 25 studies for inclusion in the meta-analysis: 22 randomized controlled trials, 1 case-control study, and 2 nonrandomized trials. The studies collectively included 8214 patients (mean age, 35.2 years; range 6 to 75 years), with a follow-up period ranging between 3 months and 12 years. All the studies were conducted in the developing world, with 11 studies conducted in India. The most common treatment was a single monthly dose of rifampin, ofloxacin, and minocycline in 8 studies (6 for paucibacillary and 2 for multibacillary leprosy).
Due to the lack of standardization in definition of diagnostic criteria, outcome objectives, time to follow-up, and poor methodologic quality in the majority of studies no consensus was reached. While 4 studies comparing the recommended multidrug therapy with rifampin, ofloxacin, and minocycline in patients with paucibacillary leprosy showed clinical improvement of lesions with such therapy (standard mean difference, 1.33; 95% CI, −1.43 to −1.23), complete clinical cure in 5 studies comparing multidrug therapy with rifampin, ofloxacin, and minocycline did not show a statistically significant difference between them after 6 months of treatment (relative risk, 1.06; 95% CI, 0.88-1.27). There was no difference in treatment failure or relapse rate between the recommended multidrug therapy and rifampin, ofloxacin, and minocycline. This was also true when multidrug therapy was compared with other treatment schemes.
Of note, none of the studies included data on antibiotic resistance patterns of M leprae.
In addition to the high risk for bias, most studies did not report on adherence to treatment, and none reported antibiotic resistance pattern of M leprae.
While leprosy control faces many barriers including a lack of funding for research, “further studies evaluating adherence to the treatment, potential development of drug resistance, and short treatment regimens based on evidence are needed to reach the goal of leprosy elimination,” concluded the researchers.
Lazo-Porras M, Prutsky GJ, Barrionuevo P, et al. World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis. BMC Infect Dis. 2020;20(1):62.