History of Leprosy Antibiotic Treatment
Between 1943 and 1982, leprosy was treated with one antibiotic: dapsone monotherapy. Patients would take dapsone daily, as it was bacteriostatic (suppressing the growth of bacteria) and not bactericidal (killing bacteria), necessitating lifelong use. However, concerns about treatment duration, emerging drug resistance, and side effects prompted the development of a new approach.
Introduction of MDT and what it is
Since the 1980s, the World Health Organization (WHO) recommends a regimen consisting of three drugs: dapsone, rifampicin, and clofazimine, collectively known as multi-drug therapy (MDT). Treatment duration used to be 24 months for multibacillary (MB) leprosy, when MDT was introduced, but it was reduced because of its effectiveness. Treatment now spans six months for paucibacillary (PB) patients and 12 months for multibacillary (MB) patients. MDT kills mycobacterium (M.) leprae and cures patients. Treatment of leprosy is highly effective. The cure rate is >=98% and the relapse rate is very low, around 1% over 5-10 years. Over 20 million patients have been treated with MDT since it was introduced.
The PB treatment used to differ from the MB treatment in that no dapsone was included in the PB treatment. In their Guidelines on Diagnosis, Treatment and Prevention of leprosy, published in 2018, WHO advises the use of uniform MDT (UMDT): the same combination of three drugs for both PB and MB patients for 6 months and 12 months respectively, because there is evidence of better clinical outcomes with a 3-drug treatment for PB leprosy. Regarding UMDT: rifampicin is given once a month, clofazimine and dapsone are administered daily.
Problems of MDT
The antibiotics included in UMDT can cause the following side effects:
- Rifampicin may cause urine to be coloured slightly reddish for a few hours after its intake. This is harmless and self-limiting.
- Clofazimine causes brownish black discoloration and dryness of skin, which usually disappears within months after stopping treatment. However, stigma is associated with the skin discoloration. Therefore, health education, psychological support and monitoring of treatment adherence is required.
- Patients known to be allergic to any of the sulpha drugs, which is fortunately rare, should not be given dapsone, because it can lead to itchy skin rashes and a more serious condition, exfoliative dermatitis, a severe inflammation of the entire skin surface, which can be fatal. Dapsone is also known to cause hemolytic anemia, a disorder in which red blood cells are destroyed faster than they can be made. In case of adverse events, Dapsone should be stopped and specialised treatment should be provided.
The WHO provides MDT free of costs through an agreement with Novartis.
Antimicrobial resistance
Antimicrobial resistance (AMR) occurs when microorganisms, such as bacteria, evolve in a way that reduces or eliminates the effectiveness of drugs (antibiotics) designed to kill or inhibit them. This can happen through various mechanisms, causing genetic mutations, like errors in DNA replication. Incomplete treatment or monotherapy increases the pool and spread of drug-resistant M. leprae. When bacteria become resistant to a drug, they can continue to multiply and cause disease, making treatment less effective or ineffective altogether.
Leprosy drugs that have encountered Antimicrobial resistance
Because of the use of long-term monotherapy with dapsone, mycobacterium (M.) leprae strains became resistant to the drug, which is one of the main reasons for introducing multi-drug therapy (MDT). Since MDT was introduced some rifampicin resistance has also been detected. Clofazimine resistance cannot be detected and the spread of it is therefore unknown, but seems to be extremely low.
Alternative MDT
Several alternative drugs that are effective against M. leprae have been identified: fluoroquinolones, minocycline, and clarithromycin. Ofloxacin (a fluoroquinolone), minocycline, and clarithromycin are established second-line drugs. Minocycline may also cause hyperpigmentation of skin lesions, so it may not be an appropriate substitute for clofazimine if pigmentation is to be avoided. For leprosy resistant to rifampicin, it is recommended to use two second-line drugs (clarithromycin, minocycline, or a quinolone) along with clofazimine daily for 6 months, followed by clofazimine plus one of these drugs for another 18 months. If ofloxacin resistance is present, fluoroquinolones need to be avoided in treatment. Instead, it is recommended to opt for 6 months of clarithromycin, minocycline, and clofazimine, followed by clarithromycin or minocycline plus clofazimine for 18 months.
Limited to no current threat of Antimicrobial resistance in leprosy treatment
In 2008, the WHO Global Leprosy Program (GLP) initiated a Sentinel Surveillance Network to monitor the development of drug resistance, with a particular emphasis on rifampicin, the main component of MDT, because it has the strongest bactericidal effect (killing the bacteria). This network consists of clinicians, programme managers, and reference laboratories to test leprosy cases for antibiotic resistance. In line with WHO recommendations, testing for AMR should be undertaken for all relapse patients and a sample of new and other retreatment MB patients. Drug resistance surveillance in leprosy must be continued to ensure MDT remains effective for leprosy control. Fortunately, there currently is little drug resistance in M. leprae and very few reports of multi-drug resistance.
Please note that the information provided does not substitute the advice provided by a doctor. If you suspect that you may have leprosy and need treatment, please seek professional advice!