Redesigning multi-drug therapy: Hasty or judicious?

Dear Editor,

We read with interest the study by Singh I et al (2023),¹ “Efficacy of fixed duration multidrug therapy for the treatment of multibacillary leprosy: A prospective observational study from Northern India”, which strongly suggests redesigning the treatment regimen for highly bacillated cases given positivity of viable lepra bacilli evidenced by histopathology and two-step real-time polymerase chain reaction in-spite of completing currently recommended WHO MDT regimen. The study also showed active granuloma with foamy macrophages having a substantial load of acid-fast bacilli (AFB) in haematoxylin and eosin (H&E) stained image at the time of recruitment as well as at the time of release from treatment primarily having slit skin smear positivity of ≥4+.

Redesigning alternate regimens for highly bacillated cases despite having a highly potent and effective standard MDT regimen raises concerns since, the efficacy of WHO-MDT has been repeatedly tested from time to time which proves worthy. It is also imperative to know whether antimicrobial resistance (AMR) testing was done for all the viable bacilli-positive cases after therapy and whether second-line treatment was considered. As per WHO, the relapse rate is very low (0.1% per year for PB and 0.66% per year for MB) on average. Additionally, the lower frequency of side effects has made it highly acceptable to patients.²

A previous study by Hamlet C and Nair P (2023) showed that 18.1% of patients required substitution of standard multi-drug therapy (MDT) with alternate drugs or required alternative treatment regimens; however, about two-thirds of patients who received modified treatment were for adverse drug reactions.³

About 10 cases in the study were non-responders to standard MBMDT. The authors also suggested that the lack of response could be due to drug default by patients, persistent bacilli, or drug resistance.

Even after the standard MDT regimen is completed, live bacilli warrant surveillance for antimicrobial resistance (AMR). According to the declaration by the National Strategic Plan and Roadmap for Leprosy 2023–2027, nationwide robust surveillance for anti-microbial resistance (AMR) must be set up, and all relapse cases should be adequately treated as per the NLEP guidelines. The Guidelines Development Group (GDG) by WHO recommends that leprosy patients with rifampicin resistance have to be treated using at least two of the following second-line drugs, i.e. clarithromycin, minocycline or a quinolone (Ofloxacin, levofloxacin or moxifloxacin) plus clofazimine daily for 6 months, followed by clofazimine plus one of the second-line drugs daily for an additional 18 months. For rifampicin plus ofloxacin resistance, quinolones should be avoided, and the recommended treatment is clarithromycin, minocycline and clofazimine for 6 months, followed by clarithromycin or minocycline plus clofazimine for an additional 18 months.⁴

A study by Girdhar B. K. et al. (2000) favours treatment duration of patients with high bacillary load may be continued till smear negativity.⁵

A study by Williams D. L. et al. (2012) suggests alternative drugs in resistant cases and favours standard WHO MDT regimens to reduce the development of drug resistance.⁶

In the above studies and following standard guidelines, it is evident that viable smear-positive cases must be meticulously tested for antimicrobial resistance (AMR) to identify drug resistance and must be treated as per the standard protocol. So, we conclude that before consequential redesigning of the presently available multidrug treatment (MDT) regimen, strict attention may be given to testing antimicrobial resistance in all cases showing viable bacilli after completion of standard MDT.

Critical analysis of the manuscript

It is noted that the reporting of acid-fast bacilli in the H&E image is inaccurate. No AFB were appreciable in Fig. 1 as AFB visualisation mostly requires a special staining procedure (Ziehl Neelsen staining & Wade Fite staining). Hence, the assertion of showing isolated acid-fast bacilli in the H&E stain is not correct.