Leprosy Mailing List – May 5, 2026
Ref.: (LML) Did capsule P have a dramatic impact?
From: Joel Almeida, Mumbai, India
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Dear Pieter and colleagues,
A randomised controlled trial revealed a relatively large drop in incident single lesion cases of HD. This was after using a certain capsule (P) once among contacts of index cases. The incidence rate fell from 14/10k person-years during years 1 and 2 of follow-up, to only 4.3/10k p-yrs during years 3 and 4. This was a 69% reduction in incidence rate between the initial and later years. During that time the incidence rate of PB HD with 2 to 5 lesions also declined, but by 60%. The incidence rate of MB HD also declined, but by 40%. These too were relatively large and rapid declines.
Could capsule P be the definitive solution to HD? First consider the comparator arm.
The comparator arm used a different capsule (X) once, and failed to show such a dramatic drop in incidence rate between the initial and later years. Instead, there was a numerical increase in incidence rate, of 12% in single lesion HD, 70% increase in PB with 2 to 5 lesions, and 60% increase in MB HD, between the initial 2 years and years 3 and 4.
Interestingly, the risk of incident HD was numerically higher in contacts of PB index cases vs contacts of MB index cases, but only in the capsule P arm. In the capsule X arm, the usual pattern of risk was observed: numerically higher risk in contacts of MB index cases vs contacts of PB index cases.
Before considering capsule P for the family members of your patients, know that the trial did not report the incidence rate of visible deformity at diagnosis. Therefore neither P nor X could be considered safe on the basis of the trial outcomes.
What were the capsules?
P was placebo. X was rifampicin. (Moet et al 2004 Lepr Rev, Moet et al 2008 Br Med J, Feenstra et al 2012 Lepr Rev).
Why did the P arm alone show a numerically higher risk of HD in contacts of PB index cases vs MB index cases? Most likely because of undiagnosed inapparent LL cases among the contacts of PB index cases, occurring disproportionately in the P arm.
Why was placebo so dramatically effective in years 3 and 4? Nine incident MB cases were diagnosed in the P arm by year 2, and were removed from the infectious pool by starting them on full MDT. By contrast, only four incident MB cases in the X arm were similarly removed by year 2. The 9 incident MB cases diagnosed in the P arm by year 2 are likely to have included one or more previously inapparent LL cases that were initially (and understandably) classed as healthy contacts of PB index cases.
Placebo is unlikely to have had a dramatic effect between the initial two years and the latter two years. The excess cases in the placebo arm during years 1 and 2 are likely to have been due to undiagnosed LL cases occurring disproportionately in the placebo arm, shedding astronomical numbers of viable bacilli (10^7 per day or even per nose blow, Davey and Rees 1974 Lepr Rev). Based on the whole set of observations, diagnosis of inapparent LL followed by prompt full MDT treatment appears highly effective. The overwhelming importance of undiagnosed LL cases together with the reported numerical excess risk of HD in the PB index clusters of the placebo arm, somewhat undermine the reliability of conclusions from this trial.
Inapparent LL cases seem overwhelmingly important in maintaining transmission.
With all sincerity,
Joel Almeida
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LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << edit...@gmail.com
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