Leprosy Mailing List – November 12, 2023
Ref.: (LML) Frequency of HD transmission or infection or disease
From: Joel Almeida, Mumbai, India
Dear Pieter & colleagues,
What is the frequency of HD (leprosy) transmission or infection or disease in endemic areas? These reports might be of interest..
Transmission indicated by Lymphocyte changes (1)
This is one of the earliest reports and still an intriguing one. While only 1 out of 12 personnel at an HD research centre not directly working with HD patients showed relevant lymphocyte transformation suggesting exposure to HD bacilli, 15 out of 17 workers (88%) at an HD outpatient clinic there did so. This does not necessarily indicate disease nor presence or replication of bacilli in the subjects, nor even carriage of bacilli. It suggests merely exposure to HD bacilli consistent with transmission of bacilli. None of any expatriate study subjects showed such indications of exposure/transmission until they had lived in an endemic area for over 2 months. However, after living in an endemic area for over a year, more than 50% of those in contact with HD patients showed such evidence of exposure/transmission. This is consistent with subsequent serology findings elsewhere among contacts using antigens specific to M. leprae. Therefore, it appears that transmission of bacilli sufficient to induce distinctive host responses has been affecting tens of millions of people in endemic areas. These tens of millions are missing from our statistics, and have escaped any stigma or deformity because they are apparently inhospitable hosts for the bacilli. With increasingly sensitive tests more and more of these tens of millions can potentially be depicted as a problem, with the accompanying risk of stigma (but with near-zero risk of progressive disease, deformity or onward transmission).
Transmission indicated by physical signs
The less frequently and more inexpertly a population is surveyed in endemic areas, the fewer self-healing cases are detected and the less frequent does transmission appear to be. Even in Karigiri (India), where contacts of HD patients were periodically monitored by reasonably competent paramedical workers/supervisors backed by highly experienced physicians, the detected incidence rate among contacts was inversely related to the frequency of monitoring. (2) It appears that self-healing patients escape inclusion in statistics of HD while evading diagnosis, deformity and stigma. The true incidence rate of HD for academic purposes, including ALL who develop any physical signs of infection regardless of self-healing, is probably several times higher than reported in statistics. Most of those remaining undetected in reasonably well-run programmes are self-healing cases. Sufficiently sensitive tests can unmask such self-healing persons. Even simply examining the population more frequently and expertly can help unmask self-healing cases. For example, in Tamil Nadu (India) the Leprosy Elimination Campaigns greatly boosted case detection by discovering patients with a single lesion who formed as much as 80% or more of all newly detected cases.(3) Single lesion cases are more likely than other cases to self-heal without sequelae. Hopefully most of the self-healing cases so discovered escaped the worst impacts of stigma. Without LEC campaigns nobody would have known they had HD. On the other hand, the LEC campaigns very likely helped discover progressive cases who otherwise would have developed irreversible nerve damage and deformity before diagnosis. In Agra (4) expert teams doing house to house surveys found 16,400/million persons to have previously undetected signs of HD. This was remarkably more than the 900/million such persons discovered by Leprosy Elimination Campaigns done only a couple of years earlier.
Indian national sample survey
Sample surveys are generally not influenced by financial incentives to either under-report or over-report cases, nor to mis-assess or misreport the degree of deformity at diagnosis. The national sample survey carried out in India in or around 2011 seems particularly useful.(5) It was undertaken in response to a petition to members of the Upper House (Rajya Sabha) of the Indian Parliament initiated by an association of persons affected by HD. This is a good example of effective action by persons who experience(d) HD. At the behest of the parliamentarians, expert teams reliably examined a stratified random sample of the entire Indian population for previously undetected signs of HD. No more than 3660 persons per million population were newly detected to have accumulated signs of HD. No more than around 380,000 Indians in total were estimated by this sample survey to have previously undetected signs of HD. Around 70% of these were in rural populations. Implied claims that millions of Indians have hidden signs of HD are inconsistent with this reasonably reliable sample survey. The Supreme Court of India ordered that such sample surveys be repeated at intervals, which is a useful aid in getting such reliable surveys done. Without such surveys, financial incentives can (unintentionally) distort reported statistics especially when it comes to the frequency of visible deformity or the proportion of child cases among newly detected patients. In the absence of repeated school surveys, most self-healing cases among children escape detection and the child proportion among new cases falls regardless of the underlying epidemiology.
Reliable estimation of trends and magnitude
The total number of HD cases detected per year can be varied at will. To reduce detection, simply reduce efforts to detect. To increase the number detected, use more sensitive methods and deploy them more frequently. To boost the child proportion, do frequent school surveys. To reduce the child proportion, stop school surveys. It is possible in this way to show that the magnitude of the HD problem is ten to twenty times lesser or greater than previously imagined. It all depends on what one wishes to show.
Whatever else we do, we can count on the newly detected MB cases to reveal the underlying epidemiological situation because they rarely self-heal. To know the trend of HD in an endemic area and the magnitude of the problem, newly detected MB offer a reliable indicator albeit with some time lag. A multi-year moving average of the newly detected MB cases helps to smooth out artefacts in case-finding (e.g. due to COVID).
Can we impact transmission?
None of this affects the fundamental problem in stopping transmission: the failure to protect genetically anergic LL (lepromatous) patients against (re)infection in endemic areas. In otherwise well-run programmes, this is the fundamental flaw that can maintain transmission indefinitely. By contrast, it is easy to reduce the incidence rate of MB (multibacillary) HD by up to 20%/year, as shown by projects in endemic areas that inadvertently or otherwise protected LL patients against reinfection (6-8). 40%/year decline in HD is available from periodic mass multi-drug admin in hot spots together with expert skin camps to detect missed LL patients and give them prolonged antimicrobial protection. (9,10)
Given all this, are we in favour of condoning single drug use for contacts of largely non-infectious patients, that too without competently ruling out LL HD in the contacts? Brazil has rejected SDR-PEP/LPEP. This seems wise because SDR-PEP/LPEP was both ineffective (as shown in Tocantins and other Brazilian states, and in well-implemented projects in Bima / Sampang / Sumenep - Indonesia and elsewhere) plus harmful through the inevitable selection of drug-resistant mutants in missed LL patients as well possibly increasing the risk of MB HD in patients with prior exposure to mycobacteria. (11)
We know how to do reliable sample surveys. We know how to achieve 16 to 20% annual decline in the incidence rate of MB HD, or even 40%/year in hot spots. Success is within reach if we protect LL patients against reinfection in endemic areas. As more and more endemic areas protect LL patients, we can look forward to an accelerating decline in new MB HD cases. As we exploit available interventions to the fullest, we can keep improving interventions in the light of new knowledge and technology.
The future is bright, as the heavy clouds of anti-microbial neglect are lifted from the backs of LL patients in endemic areas and they again can walk tall as every human being deserves to.
Joel Almeida
References
1. Godal T, Negassi K. Subclinical infection in leprosy. BMJ 1973; 3: 557-559
2 Jesudasan K, Bradley D, Smith PG, Christian M. The effect of intervals between surveys on the estimation of incidence rates of leprosy. Lepr Rev (1984) 55, 353-359
3. WHO 1997 Action Program for Elimination of Leprosy.. Status Report
4. Kumar A, Girdhar A, Girdhar BK. Prevalence of leprosy in Agra District (UP) from 2001 to 2003. Int J Lepr 2005. 73(2): 115-121
5. Katoch K, Aggarwal A, Yadav VS, Pandey A. National sample survey to assess the new case disease burden of leprosy in India. Indian Journal of Medical Research, 2017; 146(5): 585-605.
6. Norman G, Bhushanam JDRS, Samuel P. Trends in leprosy over 50 years in Gudiyatham Taluk, Vellore, Tamil Nadu. Ind J Lepr 2006. 78(2): 167-185. reviewed and analysed further in: 1a. Almeida J. Karigiri, India: How transmission rapidly was reduced in a low-income population. LML 29 Oct 2020
7. Tonglet R, Pattyn SR, Nsansi BN et al. The reduction of the leprosy endemicity in northeastern Zaire 1975/1989 J.Eur J Epidemiol. 1990 Dec;6(4):404-6 reviewed in: 2a. Almeida J. Reducing transmission in poor hyperendemic areas - evidence from Uele (DRC). LML 29 Nov 2019
8. Li HY, Weng XM, Li T et al. Long-Term Effect of Leprosy Control in Two Prefectures of China, 1955-1993. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):213-221. reviewed & analysed further in: 3a. Almeida J. What really happened in Shandong? LML 16 Nov 2019
9. WORKSHOP ON THE PREVENTION OF LEPROSY, POHNPEI, FEDERATED STATES OF MICRONESIA. 25-27 MAY 1999 sponsored by the Sasakawa Memorial Health Foundation Tokyo, Japan and the Western Pacific Regional Office of the World Health Organization. Int J Lepr, 67 (4) (SUPPLEMENT)
10. Diletto C, Blanc L, Levy L. Leprosy chemoprophylaxis in Micronesia. Lepr Rev. 2000;71(Suppl):S21–3.
11. Richardus R, Alam K, Kundu K et al. Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: A cluster randomized controlled trial. International Journal of Infectious Diseases 88 (2019) 65–72
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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