Leprosy Mailing List – July 26, 2019
Ref.: (LML) Drug costs and impact of post-MDT chemoprophylaxis for LL patients
From: Robert Gelber, San Francisco, USA
Dear Pieter,
First I want to express my gratitude to Joel Almeida for his scholarship, vision and tenacity in advocating for antimicrobial therapy after the completion of MB MDT. I never was convinced that finite therapy for MB leprosy could with conscience be recommended on the time-honored principal that therapeutic recommendations must first require convincing clinical trials of efficacy. In fact, the MB MDT regimen was recommended without any prior clinical trial. Currently there are several convincing studies and others of which I am aware but as yet unpublished demonstrating that after MB MDT clinical and bacteriologic leprosy recurred in a substantial number of patients, most commonly many years after treatment and in those with a high BI.
In the dapsone monotherapy era it was observed that MB patients often relapsed if dapsone was discontinued (1). Rather than WHO MDT between 1979 and 1995 I treated in San Francisco 125 previously untreated BL/LL patients with dapsone 100mg daily and rifampin 600mg daily for a minimum of 2 years followed by dapsone alone 100 mg daily indefinitely. In that cohort followed-up at least annually both clinically and bacteriologically an average of 9.7 years and an average of 4.1 years after smear negativity, none developed new skin lesions or became smear positive (2). Though a longer follow-up period would be optimal, such data is encouraging that prolonged chemoprophylaxis is effective in preventing relapse/reinfection.
In San Francisco at that time we regularly checked for dapsone sensitivity in the mouse model and found that in 101 patients all were prior to therapy dapsone sensitive (3). Also, in the 23 MB Cebu, Philippines patients who relapsed after 2 year MDT all were sensitive in mice to rifampin and clofazimine and only one dapsone resistant (4,5). Since in Cebu drug sensitivity was not assessed prior to MDT the single dapsone resistant relapsed patient might have been been dapsone resistant prior to MDT. These findings from the dapsone mono- therapy era, San Francisco and Cebu suggest monotherapy dapsone has reason to be effective as chemoprophylaxis after MDT.
The regimen I had used in San Francisco I had consistently recommended in the literature (1), and in several editions of the Merck Manual, several standard infectious and tropical disease textbooks and in the leprosy chapter in Harrison's Principals and Practice of Internal Medicine from 2001, edition 15 to the most recent one 2018 edition 20. Whether the chemoprophylactic regimen I recommended or the one of Dr Almeida of monthly moxifoxicin/minocycline/rifampin or yet another one should be evaluated and implemented.
In Cebu (4,5) it was noteworthy that following 2 year MB MDT new lesions and increasing BI was not confined to polar LL patients (11) but a similar number of BL patients (12). There recurrent leprosy did not occur in TT, BT or BB patients and in smear negative patients and in all but one patient with an average BI (4 to 6 sites) of 2.7 or more.
It thus appears that low tech skin smears and biopsies can both reliably predict those MB patients treated with MDT who are at risk for recurrence and would benefit from chemoprophylaxis and those where it would not be needed.
MDT promised reliable cure. Implementing chemoprophylaxis for those MB patients who are easily identified to be at risk for leprosy recurrence after MDT might well make that reliable cure a reality.
References:
1. The chemotherapy of leprosy: An interpretive history, Lepr. Rev., 2012, vol.83:221-240
2. Our experience with another multidrug therapy regimen for leprosy, Int. J Lepr, 1998, vol. 66:9a-10a.
3. Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates, Arch. Dermatol,1990, vol.126:1584-1586.
4. The relapse rate in MB leprosy patients treated with 2 years of WHO-MDT is not low, Int J.Lepr, 2012, vol.72:493-500.
5. Long-term relapse risk of multibacillary leprosy after completion of 2 years of Multiple drug therapy (WHO-MDT) in Cebu, Philippines. Am.J.Trop.Med Hyg.,2009,vol.81: 895-899.
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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