Research in Bangladesh
Leading the way on transmission and reaction research
Our research activities in Bangladesh are coordinated by Dr Abu Sufian Chowdhury. Dr Sufian is a medical doctor with a heart to help people affected by leprosy and has taken a keen interest in research as a result of the activities of our Leprosy Field Research Programme.
Our research activities in Bangladesh are closely linked to our Rural Health Programme activities where we have access to large populations of people affected by leprosy and have records going back many decades. Studies on large numbers of people are an essential part of increasing our knowledge and understanding of leprosy. Whether we are researching how to interrupt transmission or how to reduce leprosy-related disability, our field research facilities are an essential part of many global research consortia – some of which are highlighted on this page.
There is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae. The Global Leprosy Strategy 2021-2030 has identified point-of-care diagnostic tests as a key research topic.
In partnership with Leiden University and Erasmus MC in the Netherlands, TLM Bangladesh are testing a field-friendly finger-prick test for leprosy. This test could diagnose individuals within five minutes, allowing us to treat them quickly, thereby increasing our chances of preventing both transmission and disability.
Anoukvan Hooij, Elisa M.Tjon Kon Fat, Danielle de Jong, Marufa Khatun, Santosh Soren, Abu Sufian Chowdhury, Johan Chandra Roy, Khorshed Alam, Jong-Pill Kim, Jan Hendrik Richardus Annemieke Geluk, Paul L.A.M.Corstjens. Prototype multi-biomarker test for point-of-care leprosy diagnostics. iScience: Volume 24, Issue 1, 22 January 2021, 102006 https://doi.org/10.1016/j.isci.2020.102006
Post-exposure prophylaxis (PEP)
The World Health Organization started recommending single-dose rifampicin for post-exposure prophylaxis (PEP) in contacts of leprosy patients in 2018. It is one of the key components of the Global Leprosy Strategy 2021-2030.
This recommendation is a result of, in no small part, the research conducted in North-West Bangladesh by our research team as part of the COLEP study group. In summary, they demonstrated that a single dose of rifampicin given to contacts of new patients with leprosy is 57% effective in preventing the development of clinical leprosy after two years
Moet FJ, Pahan D, Oskam L, Richardus JH for the COLEP study group. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomized controlled trial, BMJ 2008, 336, p761-4
Based on the experiences with BCG vaccination and SDR chemoprophylaxis in preventing leprosy among contacts of leprosy patients, a trial was initiated in Bangladesh to assess the efficacy of a combined strategy (acronym: MALTALEP study, named after the main sponsor of the research project)
The MALTALEP study demonstrated that “Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aimed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly.”
Richardus et al. The combined effect of chemoprophylaxis with single dose rifampicin and immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed leprosy cases: a cluster randomized controlled trial (MALTALEP study). BMC Infectious Diseases 2013 13:456 doi:10.1186/1471-2334-13-456
We know that:
- The number of newly detected leprosy cases worldwide has remained stable over the last ten years.
- Household contacts of leprosy cases are at increased risk of leprosy development.
- Household contact examinations and case detection are critical aspects of leprosy control.
Since it is known that members of the household of a person newly diagnosed with leprosy have a higher risk (than the general population) of becoming leprosy cases, it is normal practice to offer them physical examination on at least one occasion to confirm or exclude leprosy. It is not clear from available published evidence whether re-examinations at annual intervals are useful or for how long they should continue. It is also not known whether amongst all household members, who are not are equally at risk, some could be identified who would benefit from a more intensive or longer period of surveillance.
TLM Bangladesh’s Contact Cohort Analysis (COCOA) Study is the largest, most comprehensive study of development of leprosy in household contacts conducted recently. We followed up some of the study participants for up to 21 years. A large quantity of good quality data has been collected, some of which we are still analysing. However as a result of the study covering households of 11,221 leprosy cases diagnosed within past 20 years, the staff have detected an extra 82 new cases amongst the 50,260 contacts enrolled as subjects.
The data suggest that contacts may be at higher risk, and that contacts of cases who are multibacillary type or have positive skin smears or have more advanced disability at diagnosis are also at higher risk.
Why is this important? Prioritising households known to be at highest risk of leprosy development (contacts of multi-bacillary cases) would allow efficient allocation of resources.
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. https://doi.org/10.1371/journal.pntd.0008687
Reaction (an acute inflammatory response) is the main cause of disability in people affected by leprosy. The better we understand why it happens, what the risk factors are, how to assess it and how to treat it, the more we are able to prevent nerve damage and disability.
Erythema nodosum leprosum (ENL) is an unpleasant complication of leprosy which can lead to considerable suffering, impaired quality of life, and long term disability. It can occur before, during or after successful treatment of the infection.
ENL is characterised by severe pain and the development of new painful skin lesions, but other organ systems are often affected. It continues to affect people for many years leading to disability, significant loss of income and sometimes death. The standard treatment is prolonged courses of corticosteroids, thalidomide or other drugs that modulate the immune system. Thalidomide is the most effective treatment but is not widely available or affordable in many leprosy endemic settings. This results in many people taking high doses of corticosteroids for prolonged periods and being at risk of severe adverse effects.
TLM Bangladesh is involved in a number of ENL studies as part of the Erythema Nodosum Leprosum International STudy Group
ENLIST ENL Severity Scale
The ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy. Clinically it assists the monitoring and treatment of patients with ENL. It is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research.
Methotrexate Study (ENLIST MTX)
The most effective treatment for ENL is thalidomide but this is not available in many leprosy endemic countries or severely constrained by availability, cost, adverse effects and justified concerns about foetal damage. Therefore, Thalidomide, despite its effectiveness is rarely used as a first line agent.
Other effective and preferably cheaper drugs need to be identified to reduce the burden of this condition. There is some evidence that methotrexate may be useful in helping to control the debilitating symptoms of ENL and reduce the amount of corticosteroid treatment needed. Methotrexate has been available since the 1950s and is used throughout the world to treat common conditions such as psoriasis. It is also inexpensive. The ENLIST-MTX study tests whether methotrexate is effective in ENL by comparing it with prednisolone (the corticosteroid most commonly used to treat ENL).
Clofazimine has long been used to reduce severity and recurrence of ENL, however, there is limited published evidence for its effectiveness. This Leprosy Research Initiative funded study is testing the effectiveness of additional clofazimine in reducing the incidence and severity of ENL.
Why is this important? If we can reduce the frequency and severity of reactions, we can protect against nerve damage and the associated disabilities. The results of the study will help doctors decide best treatments for ENL patients in future.