Leprosy Mailing List �C June 2, 2019
Ref.: (LML) Recurrence rate among MB patients following RFT
From: Joel Almeida, London and Mumbai
Dear Pieter,
What is the recurrence rate of disease among MDT-treated smear-positive multibacillary (MB) patients in each year following release from treatment (RFT)? Recurrence here is defined as the sum of endogenous relapse and exogenous re-infection.
A search of the scientific literature revealed only one paper (1) that included sufficiently detailed data for meaningful analysis of this question. Balagon and colleagues described their methods in Cebu, Philippines, as follows.
"From 1987 to 1994, we enrolled 500 subjects completing 2-year WHO multiple drug therapy (MDT) for multibacillary (MB) leprosy in a prospective relapse study. MB leprosy, on beginning MDT, was defined as skin lesions consistent with leprosy and at least one slit-skin smear BI of ≥ 2+ (≥ 1�C10 AFB/10 fields), among four to six sampled sites. Assessments included whole body clinical examinations and slit-skin smears, which, to the greatest extent possible, were done at yearly or every 2-year intervals or when new lesions were noted. Relapse was defined as new skin lesions and an increase in the bacterial index (BI) ≥ 2+ (≥ 100×) at any single slit-skin smear site..." (1).
The number of MB patients in the cohort during each year following RFT was reported. I have depicted this visually in Figure 1.
Figure 1. Number of MB patients in the cohort according to years since RFT.
Longer durations since RFT had fewer patients available for observation. A smaller number of patients tends to widen the confidence intervals around the observed recurrence rate.
I analysed the year-specific recurrence rate in the cohort during each year since RFT. For each year, the number of relapses was divided by the persons in the denominator for that year, and the upper 95% confidence limit calculated (Figure 2).
Figure 2. Year-specific recurrence rate of disease in each year since release from treatment among MB patients of any positive initial BI, following 24 monthly doses of MDT. Observed rate (lower line) with upper 95% confidence limit (upper line).
The upper line indicates the plausible maximum recurrence rate estimated by this sample. That is, there is only 5% chance that the true year-specific recurrence rate might be higher, in the universe of all such patients in all such areas of equivalent endemicity.
Figure 2 demonstrates that the year-specific recurrence rate is less than 0.5/100 persons/year during the first 5 years following RFT. Thereafter it remains under about 2/100 persons/year. The wide confidence interval beyond 18 years of observation might be narrowed in future if the study continues to observe the more recently recruited patients.
It seems safe to conclude that the year-specific recurrence rate among initially smear positive MB patients following 24 months of MDT is no higher than 3.5/100 persons/year in areas of similar endemicity, even beyond the sixth year following RFT.
Balagon et al also reported that a subset of 181 patients with high initial BI (4+ or greater) showed a cumulative recurrence rate materially higher than the averages shown above. Therefore, in patients with an initial BI of 4+ or more, the corresponding year-specific recurrence rate is likely to be materially higher than just the apparent 1 to 3.5/100 persons/year.
LLp patients are the most susceptible to recurrence, whether by endogenous relapse or re-infection. Therefore, the recurrence rate is likely to be highest of all among LLp patients. Over a period of 2 or more decades following RFT, LLp patients could well show a year-specific recurrence rate in excess of 5/100 persons/year. Therefore, in years 6 to 20 following RFT, as many as 75% of LLp patients could show recurrence following even 24 doses of MDT.
It seems important not only to treat LL patients for an adequate duration, but also to protect them with post-cure chemoprophylaxis (e.g., monthly Rifampicin + Moxifloxacin + Minocycline or similar). Such a regimen is likely to result in near-100% efficacy. Without post-cure chemoprophylaxis, LL patients probably suffer further nerve damage owing to the recurrent bacillary load. Further, they are forced unknowingly to serve as major enduring sources of bacilli, capable of shedding tens of millions of viable bacilli per day. No other known source, apart from armadillos, can compete with that sheer concentration of viable bacilli. Asia is not known to have armadillos.
Whatever else we do or fail to do, post-cure chemoprophylaxis seems necessary for LL patients in endemic areas. It is a clear precaution we ought to be taking in the best interests of patients. Further, Shandong interrupted transmission using prolonged anti-microbial protection for LL patients. We too could similarly interrupt transmission at source, by ensuring post-cure chemoprophylaxis for LL patients.
Joel Almeida
Reference
1. Balagon MF, Cellona RV, dela Cruz E et al. Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines. American Journal of Tropical Medicine and Hygiene, 2009; 81, 5: 895-9.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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