Leprosy Mailing List Blog: (LML) Lepr Rev (2015) 86, LETTER TO THE EDITOR, Reply to Role of Contact tracing and prevention Strategies in the interruption of leprosy transmission - Chemoprophylaxis: a call for more research

Leprosy Mailing List – March 27, 2015

Ref.: (LML) Lepr Rev (2015) 86, LETTER TO THE EDITOR,

Reply to Role of Contact tracing and prevention Strategies in the interruption of leprosy transmission - Chemoprophylaxis: a call for more research

From: Diana Lockwood, P Krishnamurthy, Vijay Pannikar, Gerson Penna

Dear Pieter,

We have the attached letter discussing the need for more evidence to support the policy of chemoprophylaxis coming out in Leprosy Review this month. Since there is an important IAL conference in Hyderabad we thought that it would be useful to have this letter available for people to read before the meeting. Paul Saunderson is happy for this letter to be published in LML ahead of publication in Leprosy Review.

Best wishes,

Diana Lockwood

Lepr Rev (2015) 86, LETTER TO THE EDITOR, Reply to Role of Contact tracing and prevention Strategies in the interruption of leprosy transmission - Chemoprophylaxis: a call for more research

We would like to thank Cairns Smith and Ann Aerts for writing such a comprehensive review on the challenges and research priorities of contact tracing and prevention strategies.¹ They have covered many facets of case detection in detail.

We would like to amplify the following points:

We agree that early case detection is critical. However contact screening is only part of this and many newly diagnosed cases are not related to known cases. Contact screening is actually often difficult to do in practice; it raises ethical problems because patients have to disclose their diagnosis. There can also be problems with students or migrant workers who do not want to disclose their diagnosis to their colleagues or house sharers and we have experienced this in locations including London. Thirdly, women may be disadvantaged when disclosing their diagnosis. In India many patients give false addresses or mobile numbers to avoid being traced.

Contact Screening involves examining many potential skin lesions in healthy people and so a range of other skin lesions will be detected as well as potential early leprosy cases. It is vital to involve dermatologists to draw on their expertise in evaluating a range of lesions. Contact screening also requires increased personnel who are able to recognise the early signs of leprosy. Early leprosy is often difficult to diagnose and patients may require periods of observation to monitor lesions. There may also be a need to support investment into histopathology services to look at biopsies of patients with early leprosy.

Stronger scientific evidence is needed for the effectiveness of chemoprophylaxis. The main study is the COLEP study in Bangladesh.² In this study 21711 contacts of newly diagnosed leprosy patients were randomised to receive single dose Rifampicin (SDR) or placebo. SDR did not give household contacts significant protection against developing leprosy, (OR 0.46 (0.15-1.38) p 0.1652) it only protected neighbours of neighbours OR 0.24 ( 0.11-0.52). SDR did not protect against the development of MB leprosy (0.52 0.22-1/19) p 0.1201, however it did protect against the development of PB (0.38 (0.16-0.87) p 0.0218 and single lesion leprosy (0.42 (0.20-0.89). Protection was only for two years. These findings are consistent with SDR treatment having a weak effect against a low mycobacterial load, hence the protection only against the development of PB leprosy.

These data indicate the usefulness of chemoprophylaxis but they also indicate the need for further scientific studies, high quality research studies in other settings are needed. This study suggests that a single dose gives only some protection against leprosy and it is vital that other studies are done to test other regimens. There are also ethical consequences because it is incorrect to tell household contacts of leprosy patients that they will be protected against leprosy by taking a single dose of Rifampicin.

A similar study on chemoprophylaxis was done in India with a similar design to COLEP and covered seven sites in South India and also two in Jharkhand and Bihar. It was difficult to recruit the required sample size (about 5000 subjects needed in each arm), and only 5000 were recruited. The population was reviewed three times in 6 years in follow-up surveys. The results were similar to COLEP with SDR giving about 50% efficacy and the effect lasting only 2 years. The Principal investigator was Dr. Vijaykumaran and it would be useful for this negative study to be published. A further under-powered study was done in Thailand which has not been published. Currently The Government of India Leprosy programme does not recommend the use of chemoprophylaxis.

Smith and Aerts note that pilot studies are being done on aspects of chemoprophylaxis but pilot studies are not comparable with scientific studies, they can generate useful data but can give misleading results. A good example of this was the report suggesting that Prednisolone treatment was a highly efficacious in preventing TIR, these data were taken from an observational study³ and the later formal randomised controlled trial did not show benefit for giving all MB patients prednisolone 20mg with their MDT.⁴

It is critical that key policies are supported by strong scientific evidence. Other aspects of leprosy treatment such as the treatment of nerve damage and ENL have suffered from there being too few high quality trials.⁵

It is also important to assess the cost effectiveness of giving chemoprophylaxis and data relating to all the costs of giving chemoprophylaxis should be analysed to inform policy decisions.

We also note the acronym post exposure prophylaxis (PEP) is a misnomer because it implies that a recently acquired infection is being treated whereas there is a long gap between infection and the development of disease. PEP is used when there is a recent possible infection such as rabies from a dog bite or exposure to HIV after a risky event.

We are very supportive of new initiatives in leprosy but it is critical that they are supported by the generation of high quality evidence to support the strategy. This would include studies such as testing the effect of multiple doses of chemoprophylaxis.

Diana NJ Lockwood, Professor of Tropical Medicine, London School of Hygiene & Tropical Medicine; Diana.Lockwood @lshtm.ac.uk

P Krishnamurthy, Director, The Damien Foundation Chennai, India; pkmurthy50@gmail.com

Dr Vijay Pannikar, Ex-director WHO Leprosy Unit; pannikarv@gmail.com

Prof Gerson Penna, Tropical Medicine Unit, University of Brasilia, Brazil; gpenna@gpenna.net

References

1. Smith WC, Aerts A. Role of contact tracing and prevention strategies in the interruption of leprosy transmission. Lepr Rev 2014; 85: 2―17.

2. Moet FJ, Pahan D, Oskam L, Richardus JH. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial. BMJ 2008; 336(7647): 761―764.

3. Croft RP, Nicholls P, Anderson AM, et al. Effect of prophylactic corticosteroids on the incidence of reactions in newly diagnosed multibacillary leprosy patients. Int J Lepr Other Mycobact Dis 1999; 67: 75―77.

4. Smith WC, Anderson AM, Withington SG, et al. Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD 1). BMJ 2004; 328(7454): 1459.

5. Van Veen NH, Nicholls PG, Smith WC, Richardus JH. Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev 2007(2): CD005491.

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Diana Lockwood
Professor of Tropical Medicine
London School of Hygiene & Tropical Medicine
Keppel St
London WC1E 7HT
diana.lockwood@lshtm.ac.uk
Tel: 020 7927 2457
Fax: 020 7637 4314