Leprosy Mailing List – December 18, 2020
Ref.: (LML) Leprosy case finding should contain as many contacts as possible
From: Diana Lockwood, London, UK
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Dear Pieter,
We would like to thank Paul Saunderson et al for their post on LML (10.12.2020) about our paper in Plos neglected Tropical Diseases.(1) We have also replied to Saunderson's comments on the PLOS NTD website. Our paper reported a large cohort study with a 21-year follow up period and we found a single, dominant risk factor for leprosy development amongst household (HH) contacts – smear positivity. We are excited about this significant finding which helps to understand leprosy transmission risk factors. We are sorry that our colleagues are not more enthusiastic about this major piece of work on leprosy transmission that followed a large cohort of patients for 21 years.
We agree with Saunderson et al that ideally all contacts of all newly diagnosed leprosy cases should be examined. Our findings endorse the importance of conducting HH contact examinations for case detection and control. However, there is a cost associated with HH contact examinations. Economic and human resources for leprosy control are scarce and where leprosy control is integrated into general health services, comprehensive coverage of household contacts has not been possible.
We did not say that it was unnecessary to examine all contacts of all new cases as Saunderson et al suggested, but recommended that when leprosy resources are scarce, a prioritisation based on the probability of finding more new cases per household should be considered by leprosy control programmes, but only if slit-skin smears are available in the assessment of the index case . This is possible through our finding of a single, dominant risk factor for developing leprosy. This is similar to using the clinical prediction rule for nerve function impairment (2) to determine which patients need more attention for nerve function monitoring. In our other COCOA (Contact Cohort Analysis) paper that Saunderson et al cites, we concluded (3) "where resources are severely limited and observed prevalence rate is low.. managers could direct staff to give first priority to undertaking an initial HCE of MB/ smear positive index HHs. Then, as second priority, to undertake one more examination of MB HHs after 12 or 24 months, and only as third priority to do a single HH contact examination soon after diagnosis for each PB index case".
We agree that finding leprosy patients in settings beyond the household is important, but our study did not include neighbour or social contacts, which we carefully discussed, (1) so did not comment on these categories. "Extended contact surveys" will become more important as leprosy rates decline.
According to stepwise pr analysis (and as explained in the results below Table 4) the hazard ratio for HH contacts of index cases who are smear low positive is 1.57. The smear variable was grouped into 3 groups. Smear negative, smear low positive (bacterial index 1-3) and smear high positive (BI 4-6). The risk of their associated contacts developing leprosy increases by 1.57 times for each increase in smear grouping. HH contacts of smear high positive index cases are at 3.14 times increased risk of developing leprosy compared to contacts of smear negative patients.
Of 608 new cases detected throughout the follow-up, 405 (67%) were associated with index cases who were skin smear negative. So 33% of new cases detected amongst contacts were from HHs with smear positive index cases, comprising only 6.55% households examined. When looking at the absolute number of new cases one should consider the population they come from, especially when assessing relative risk. NW-Bangladesh has a high paucibacillary (PB) rate of leprosy cases compared to the rest of the country, maybe because of the active leprosy control unit work there by a specialist NGO for over 20 years.
Of the HH contacts of index cases with high positive smear leprosy (1480), 11.69% of them were diagnosed with leprosy throughout the follow up. This is compared to the HH contacts of smear negative index cases (32582), where 1.24% were diagnosed with leprosy (405). So the highest hazard ratio is being associated with high smear positive index case. Where smear services are lacking, multibacillary (MB) classification can be used as a proxy for identifying the HHs at higher risk of new case development.
We are pleased that Saunderson quickly changed his position on the value of slit-skin smears from initially stating in the PLOS NTD comment that it 'seems counter-productive to spend scarce resources on reviving skin smear services which have no added value for treatment decisions' (1) to acknowledging that 'the skin smear test is a useful test for other reasons'. (Saunderson et al post on LML (10.12.2020)). The presence of acid fast bacilli is a cardinal sign of leprosy so we need to be able to detect them in index cases. They are also needed to detect relapse of multi-bacillary leprosy. Slit-skin smears can predict the development of Erythema nodosum leprosum (ENL), BL/ LL patients with a BI of 4 or higher at greatest risk of ENL. (4)
This study highlights a single, dominant risk factor for leprosy development, skin smear positivity. Where skin smear services are available, and resources are scarce, the identification of this single risk factor enables the prioritisation of HH contact examination to those HHs at greatest risk. Performing slit-skin smears in this circumstance would be used for risk stratification and works in conjunction with contact examination. We are not pitching "two good interventions " against each other; slit-skin smears and HH contact examinations, both are needed. Conversely, our results could increase the effectiveness of leprosy control by using skin smears in conjunction with HH contact examinations. This is another piece of compelling evidence for the leprosy community as a whole to advocate, to revive and improve skin smear services.
Diana NJ Lockwood
Emeritus Professor of Tropical Medicine
London School of Hygiene and Tropical Medicine
Keppel Street
London WC1E 7HT
Emily Quilter
Department of Infectious and Tropical Diseases
London School of Hygiene and Tropical Medicine
Keppel Street
London WC1E 7HT
Steve L Walker
Associate professor
Department of Infectious and Tropical Diseases
London School of Hygiene and Tropical Medicine
Keppel Street
London WC1E 7HT
Peter Nicholls
Independent statistician
Ruth Butlin
The Leprosy Mission England and Wales
Peterborough
United Kingdom
References:
1. Quilter EEV, Butlin CR, Singh S, Alam K, Lockwood DNJ (2020) Patients with skin smear positive leprosy in Bangladesh are the main risk factor for leprosy development: 21-year follow-up in the household contact study (COCOA). PLoS Negl Trop Dis 14(10): e0008687. doi.org/10.1371/journal.pntd.0008687
2. R P Croft , P G Nicholls, E W Steyerberg, J H Richardus, W Cairns, S Smith. A clinical prediction rule for nerve-function impairment in leprosy patients. Lancet. 2000 May 6;355(9215):1603-6. doi.org/10.1016/s0140-6736(00)02216-9.
3. Butlin CR, Nicholls P, Bowers B, Quilter E, Singh S AK. Outcome of late healthy household contact examinations in leprosy-affected households in Bangladesh. Lepr Rev. 2019;90: 305–320
4. Pocaterra L, Jain S, Reddy R, et al. Clinical course of Erythema Nodosum Leprosum: an 11-year cohort study in Hyderabad, India. Am. J. Trop. Med. Hyg. 74(5), 2006, pp. 868–879
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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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