Sent: 31 December 2020 18:04
To: Leprosy Mailing List <leprosymailinglist@googlegroups.com>
Subject: (LML) Previously treated but neglected persons multiply the risk of HD in a household
Leprosy Mailing List – December 31, 2020
Ref.: (LML) Previously treated but neglected persons multiply the risk of HD in a household
From: Joel Almeida, London and Mumbai
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Dear Pieter and colleagues,
Meticulous observational and analytical studies at the frontlines can unearth important clues. Unexpected clues tend to be the most valuable, because they can make the difference between harm and benefit.
Joel Almeida
= = = = =
Previously treated but neglected persons multiply the risk of HD in a household
Methods
The methods used were described by Vijayakumaran et al.(1) In summary, during the 11 years ending December 1994, all consecutively diagnosed skin-smear positive and previously untreated "index" patients living in a defined geographical area were started on 24 months of MDT. Every household contact of every such "index" patient was physically examined for HD. The physical examinations were repeated at annual intervals. New arrivals into each such household, who joined after the start of MDT in the "index" patient, likewise were examined. These new arrivals will be referred to below as "newcomers". Further, the presence or absence of "co-prevalent" persons was noted. These "co-prevalent" persons consisted of those previously started on anti-microbial treatment, including those who had already completed treatment prior to enrollment of the "index" patient.
The incidence rate of all types of HD in this defined area with a well-established control programme, estimated from sample surveys, was about 900 new patients/million population/year.
Results among "newcomer" children
The incidence rate of HD among "newcomer" children is shown in Figure 1.
Figure 1. (see attached file) Presence of a previously treated patient multiplied the risk of HD among "newcomer" children in a household, despite prior start of treatment in a newly diagnosed "index" patient.(1) Excess risk to "newcomer" children in household endured for as long as observation continued - up to 9 years
The presence of a previously treated patient in the household apparently increased the risk of HD among "newcomer" children to over 25 times that in the general population of the area, during the initial three years after the start of MDT in the "index" patient. When a previously treated patient was present in the household, treatment of the index patient alone did not suffice to reduce the risk to the "background" population level. Even seven to nine years after the start of 24 month MDT in the "index" patient, "newcomer" children showed a greatly elevated risk of HD if a previously treated (but since neglected) patient was present in the same household.
Discussion
Prolonged anti-microbial protection of previously treated but genomically anergic (2-5) persons in endemic areas is likely to reduce dramatically the risk of HD in their household contacts. It also would help protect the individuals from reactions,(6-9) which can be painful, distressing, and aggravate nerve damage. Reinfection in previously treated anergic patients remains a sustained threat in endemic areas.(10)
Preventive antimicrobials among contacts of such neglected previously treated but anergic patients would need to continue for over nine years, to cope with the sustained duration of risk. It seems wiser to rely on prolonged anti-microbial protection of the anergic patients.
Prolonged anti-microbial protection of patients with possible anergy (eg., LL patients) can be achieved by
a) prolonged MDT, after the usual duration. At least until smear negativity.
or
b) prolonged anti-microbials after the usual duration of MDT, with a combination of 3 bactericidal drugs. Some enlightened private practitioners and centres of excellence in endemic areas of India and Brazil already protect LL patients with combinations of bactericidal drugs after MDT.
This HD control area, served by the Schieffelin Centre in Karigiri (India) had earlier produced one of the world's great successes in rapidly reducing the incidence rate of LL HD (16%/year). As long as prolonged anti-microbial protection was ensured for persons with anergy, the exemplary success continued (as discussed here previously). Resurgence in LL HD occurred only after fixed-duration MDT replaced prolonged anti-microbial protection in even LL patients. Since the introduction of fixed duration MDT (in place of MDT till smear negativity) the world too has experienced stagnation in the number of new MB HD patients per year. This is evidenced in Weekly Epidemiological Records. MB types of HD rarely self-heal. Therefore sooner or later they come to the attention of health services and form a more reliable epidemiological indicator than most other indicators.
As the best young local talent is invited and encouraged to participate in HD work, we can expect increasingly astute investigations and openness to front-line clues. The evidence so far indicates that, in endemic areas, it is neither safe nor fair to exclude persons with anergy (mostly LL) from prolonged anti-microbial protection.
References
1. Vijayakumaran P, Jesudasan K, Mozhi NM, Samuel JD. Does MDT arrest transmission of leprosy to household contacts? Int J Lep 1998; Jun;66(2):125-30.
2. Chakravarti MR, Vogel F. A twin study on leprosy Georg Thieme Publishers, Stuttgart, Germany; 1973
3. Sartori PVU, Penna GO, Bührer-Sékula S et al. Human Genetic Susceptibility of Leprosy Recurrence. Scientific Reports 2020 volume 10, Article number: 1284
4. Gaschignard J, Grant AV, Thuc NV et al. Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases. PLoS Negl Trop Dis. 2016 May 24;10(5):e0004345. doi: 10.1371/journal.pntd.0004345
5. Wang N, Wang Z, Wang C et al. Prediction of leprosy in the Chinese population based on a weighted genetic risk score. PLoS Negl Trop Dis. 2018 Sep 19;12(9):e0006789. doi: 10.1371/journal.pntd.0006789.
6. Save MP, Dighe AR, Natrajan M & Shetty VP. Association of viable Mycobacterium leprae with Type 1 reaction in leprosy. Lepr Rev (2016) 87, 78–92
7. Arora P, Sardana K, Agarwal A, Lavania M. Resistance as a cause for chronic steroid dependent ENL - a novel paradigm with potential implications in management. Lepr Rev (2019) 90, 201– 205
8. Brito MDE F, Ximenes RA, Gallo ME, BÜhrer-SÉkula S. Association between leprosy reactions after treatment and bacterial load evaluated using anti PGL-I serology and bacilloscopy. Rev Soc Bras Med Trop. 2008;41 Suppl 2:67-72.
9. FajardoT1, Villahermosa L, Eleanor F et al Comparative Clinical Trial in Multibacillary Leprosy with Long-Term Relapse Rates of Four Different Multidrug Regimens. Am. J. Trop. Med. Hyg., 2010, 83(3), pp. 637–644
10. 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. reviewed and analysed further in 19a. Almeida J Recurrence rate among MB patients following RFT. LML 2 June 2019.
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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 << editorlml@gmail.com
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