The Leprosy Mission's Global Research 2022
The Leprosy Mission is the world's oldest and largest leprosy-focused organisation and a leading player in the fight to defeat leprosy.
Paving a path towards better knowledge, early diagnosis, improved care
The Leprosy Mission's Global Research
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International Leprosy Congress 2022
The Leprosy Mission's Research
International Leprosy Congress 2022
TLM's Research and Partnerships Are Paving a Way to Zero Leprosy
We are The Leprosy Mission
The Leprosy Mission is the world's oldest and largest leprosy-focused organisation and a leading player in the fight to defeat leprosy.
We have teams across 30 countries working in partnership with persons affected by leprosy, universities governments, local churches, and other stakeholders to achieve our vision of zero leprosy transmission by 2035.
Our work to defeat leprosy takes place in countries across Asia and Africa. Our research hubs are in Bangladesh, India, and Nepal, as well as an emerging research hub in Nigeria.
Dr Deanna Hagge,
Global Research Advisor
Our research has heritage
TLM has been involved in research for more than 70 years. Our contributions include the testing and development of MDT, the innovative surgical procedures pioneered by Dr Paul Brand, and improving the understanding and management of reactions and neuropathy.
We undertake research through our research laboratories, at our hospitals, and through field-based primary research. Our Bangladesh field operation is one of the largest leprosy field research operations in the world, which was the key to unlocking PEP (post-exposure prophylaxis).
1. Understanding Transmission
The transmission of leprosy remains poorly understood. If we are to end transmission of the disease, we must understand the mechanism of transmission better than we currently do.
Stanley Browne Laboratory (SBL) in India is an established leader in molecular studies focused on environmental reservoirs, transmission in households and communities, and nasal carriage.
The Mycobacterial Research Laboratories (MRL) in Nepal have been investigating transmission, including monitoring of leprosy drug resistance for over 40 years.
Meanwhile, our Leprosy Field Research in Bangladesh Program (LFRB) enables large transmission studies to consider factors among blood relatives, household members, and various degrees of contact, as well as the clinical aspects that need investigating in relation to transmission.
2. Developing Diagnostics
An early diagnosis of leprosy can reduce transmission and the risks that lead to permanent physical problems, such as reactions, nerve damage, and disability.
SBL in India is conducting immunological research and developing a PCR test for leprosy.
Both LFRB and MRL, in partnership with the University of Leiden Medical Center are developing and trialling a field-friendly finger-prick test for leprosy and reactions using biomarkers.
In Nepal, MRL and Anandaban Hospital are working with the University of Latvia to develop a spectral imaging tool that could potentially enable a smartphone to detect leprosy.
3. Reactions and Neuritis
Around 30-50 percent of leprosy patients develop one or more episodes of reaction. Leprosy reactions are the primary cause of nerve damage and disability development.
Our hospitals and laboratories are involved in clinical trials to innovate treatment, investigations of potential causes and biomarkers, and chart reviews utilising decades of medical records. In Nepal, MRL has been investigating associations between soil-transmitted helminth co-infections with leprosy and reactions (opening a can of worms).
Bangladesh, India, and Nepal are members of the Erythema Nodosum Leprosum International Study (ENLIST) Group which is a consortium that conducts global, multi-centric studies, such as profiling ENL across countries and developing an ENL Severity Scale.
4. Wound prevention and management
Around 20 percent of leprosy patients are at risk of developing ulcers. After their first ulcer, a patient is at high risk of developing future ulcers, which can lead to recurrent hospitalisations resulting in potential loss of income, employment, family, home and/or limbs (amputation). Approximately 50-90 percent of inpatients in our hospitals are ulcer cases who may require months or even more than a year to heal.
Among a number of projects on this topic, our team in Nepal is working on a new treatment for leprosy ulcers, known as LPRF. This new and innovative technique has so far shown a dramatic improvement in the recovery time for leprosy ulcers. Their research is also considering how ulcers can be prevented through interventions at the community level to address issues such as livelihoods that increase the risk of developing ulcers.
5. Inner wellbeing
Studies show that around 70 percent of people affected by leprosy experience anxiety and/or depression. However, mental health support for those affected by leprosy is extremely limited or absent for global cases. Research is needed to enable better screening, how to develop and optimise care options in limited resource contexts, identify risk factors, validate treatment options, and map pathways for any available integrated services.
Cover photo credit: Sabrina Dangol
We are supporting others who are leading the way in the following areas
1. Global Chemoprophylaxis Studies (PEP)
TLM and our partners are involved in a number of PEP trials across the world, including PEP++
2. Global monitoring of leprosy relapse and antimicrobial resistance
Our laboratories in India and Nepal are part of the global network of laboratories that monitor relapse and resistance.
3. Field trials or operational studies of global initiatives and innovations
TLM has a unique geographical footprint of hospitals, field programmes, and laboratories that allow us to support and trial new innovations, such as vaccines, in order to reduce leprosy transmission.
Priority 1: Understanding Transmission
Understanding transmission
Leprosy transmitted through soil and water
Our researchers in India have been looking at the extent to which leprosy bacteria can also be found within soil and water.
They have been looking at remote villages in India where there is a high level of leprosy transmission and only one water source per community, which can severely limit sanitation and hygiene for everyone dependent on it.
So far they have identified a link between leprosy DNA that they found in soil and water and new cases of leprosy that have been identified in 20 separate families.
Understanding transmission within households
Over the last 20 years, our team in Bangladesh has been collecting information about the contacts of people affected by leprosy through the COCOA (Contact Cohorts Analysis) study. The study reveals that fewer than 2% of people who have lived with a person affected by leprosy will contract this disease.
The study provided us with important details as homes with cases of PB leprosy see transmission at a rate of around 4 per 1000 household contacts per year. In households with cases of MB leprosy, this rate rises to around 13 per 1000 per year.
Using straintyping to identify the source of transmission
Our scientists in India have been tracking the spread of leprosy within an eight block radius of high leprosy transmission in Purulia, West Bengal.
They have taken samples from 112 people who have been diagnosed with leprosy and their close contacts so that they can be tested for genotypes – which is like strain typing - to connect cases carrying closely related versions of M.leprae.
What we learn from genotyping will help us to identify the source of transmission, which will direct the work of our field teams towards the most likely place to find further cases of leprosy.
There are 3 main categories of diagnostics for leprosy, each with their own strengths and challenges in application and field feasibility. The first that often comes to mind is for early detection of new leprosy – which could significantly impact global leprosy transmission, disability and discrimination.
However, diagnostics are also needed for early detection of reactions and/or neuropathy as well as treatment monitoring for those conditions and MDT. There is also need for differential diagnosis.
Immunodiagnostics
Our team in Bangladesh is currently working in partnership with Professor Annemieke Geluk on a finger-prick test that can diagnose leprosy within minutes (watch the webinar).
This is the first study that will simultaneously test for six different biomarkers in the blood.
The biomarkers that the team are testing show whether or not a person has asymptomatic leprosy; so, while they are testing for these biomarkers, they are also testing different forms of PEP (Post-Exposure Prophylaxis) treatment to see which is better at preventing a leprosy development in contacts.
Imaging
With funding from the NTD Innovation Prize, The Leprosy Mission Nepal are working on a project that would allow us to diagnose leprosy using a smartphone equipped with spectral imaging technology.
Humans can only see things in the visual light spectrum, which is around 400-600 nanometres. Spectral imaging allows us to see up to 900 nanometres. This will allow us to analyse skin for leprosy-specific lesions.
Spectral imaging is being used with skin cancers currently and could be used to help us diagnose leprosy in the field within minutes.
Molecular
The Leprosy Mission's Indian labs are working on a PCR test for leprosy.
Over a number of years, our team in India have been testing one gene marker of leprosy at a time to determine which of these genes have the most sensitivity to tests. In October 2021, the Stanley Browne Research Laboratories were in a position to combine three of the most sensitive gene markers into one multiplex PCR test.
This test is 90 percent successful at diagnosing cases of leprosy, including the really early cases of PB leprosy.
By 2024, it could be ready for a global rollout.
Priority 3: Reaction and neuritis
Erythema nodosum leprosum (ENL) is a severe and extremely painful complication of leprosy which can occur before, during or after completion of antibacterial treatment. Current treatments are not as effective as we would like and have severe side effects.
ENLIST - Methotrexate trial
This double-blinded randomised controlled study tests whether methotrexate is effective in ENL by comparing it with prednisolone (the corticosteroid most commonly used to treat ENL). At the end of the study the two groups of patients will be compared to see which have had the best response as measured against pre-determined outcomes. The participants in the study are drawn from Bangladesh, Brazil, Ethiopia, India, Indonesia, Nepal and the Philippines from centres who together form the ENL International STudy Group which is coordinated from the London School of Hygiene and Tropical Medicine. The Leprosy Mission centres in Bangladesh, India and Nepal are involved.
The study is funded by the Leprosy Research Initiative
Extra Clofazimine for MB cases at high risk of ENL
This Leprosy Research Initiative funded randomised controlled study tests the effectiveness of additional Clofazimine in reducing the incidence and severity of ENL in Bangladesh (The Leprosy Mission International - Bangladesh) and India (Bombay Leprosy Project).
The control group (with ENL reaction) will receive extra doses of Clofazimine for 6 to 12 months, while the intervention group (with ENL reaction) will be given placebo vitamin tablets. Both groups will also receive standard treatment with steroids, the same as given to people who are not in the trial.
Priority 4: Wound Management
Wound Prevention and Management
Between 50-90 percent of leprosy hospital beds are in continual use by patients with ulcers. Hospital stays for ulcer care can last weeks or months.
Thanks to a NIHR grant (almost £5million), The Leprosy Mission, University of Birmingham and GLRA are conducting a large study in India, Nepal and Nigeria “Transforming the Treatment and Prevention of Leprosy and Buruli ulcers in Low and Middle-Income Countries” with two main aims:
Improving clinical care of wounds
Supporting self-care for people in the community who are at risk of recurring ulcers.
Improving clinical care
Saline dressings are standard in the healing of wounds. Are there better, more sustainable ways to treat wounds - both in hospitals and in the community?
Anandaban Hospital, Nepal is trialling the use of Leukocyte Platelet Rich Fibrin (LRPF) to promote healing of wounds through the Trial of Autologous Blood products to promote ulcer healing in Leprosy (TABLE) study. The patient's own blood is centrifuged to separate and concentrate white blood cells and growth factors, which are then applied directly to the wound. Early results show wounds treated with LPRF heal completely within weeks, and, very importantly, without scarring, reducing the risk of recurrence.
The Leprosy Mission Nigeria is conducting a randomised controlled trial Honey Experiment on LeProsy Ulcer (HELP), comparing honey with standard saline dressings.
Supporting self-care
Leprosy Review Dec 2021 contains several papers from this part of the study.
One of the outcomes of the study will be the development of self-care guidelines. The Leprosy Mission Trust India are working alongside persons affected by leprosy to learn how these guidelines will work best within their lives and their communities. They will work with patients on co-developing a version of the guidelines that will be specific to the communities they are working with.
“The world class facilities of The Leprosy Mission and the number of people affected by leprosy which are served, provides a unique opportunity for researchers to collaborate in the global fight against leprosy.”
Professor Diana Lockwood, BSC, MD, FRCP, Professor of Tropical Medicine, LSHTM
Comparison of Removable Device and Total Contact Cast for Healing of Ulcer
This study, funded by the Leprosy Research Initiative aims to investigate whether removable off-oading devices are as effective as total contact cast to promote healing of non-complicated plantar ulcers. The Leprosy Mission Trust India explain the study in our February 2022 Research Magazine.
Priority 5: Mental Wellbeing
The consequences of leprosy are often disability and impairments. The physical health ramifications, as well as the stigma attached to the disease, have implications for a person’s mental health. Depression, among other mental health issues, is frequent among persons with leprosy.
A study on depression in West Bengal
Our team in India have conducted a study which assessed the burden of depression among individuals who are suffering with the consequences of leprosy and its association with demographic and clinical factors.
The study was conducted in the Premananda Memorial Leprosy Hospital in Kolkata, West Bengal. During the period of study, 99 consecutive patients aged 18 years and above attending the outpatient clinic were assessed for depression using Patient Health Questionnaire-9 (PHQ-9).
The burden of depression among these 99 leprosy patients attending Tertiary Care Hospital as screened with the PHQ9 was about 53.5 percent.
Reducing Leprosy Stigma among Healthcare Workers in Niger
The Leprosy Mission Niger, in partnership with the University of Niamey, and the Ministry of Health want to address stigma amongst healthcare workers in Niger.
This mixed-methods study, funded by the Leprosy Research Initiative has two phases.
First, using the WHO stigma framework, it aims to identify the local and contextual reasons behind stigma directed at patients by Health Care Workers, and the resulting impact on people affected by leprosy.
A second phase of the study aims to develop and test the feasibility, acceptability and effectiveness of a training programme to reduce stigmatising attitudes and behaviours among Health Care Workers. Results will provide a contextual, yet replicable model for a leprosy stigma-reduction programme.
Post-Exposure Prophylaxis
Post-Exposure Prophylaxis: Stopping leprosy in its tracks
TLM has one of the largest field research operations in the world of leprosy. The Leprosy Field Research in Bangladesh Program conducted the COLEP study - a randomised controlled trial of a large population (>20,000 contacts) which showed the effectiveness of a single dose of rifampicin (SDR-PEP) in preventing leprosy in contacts.
Ready4PEP
(Implementation research in Mozambique and Nigeria)
In this project we work with NLR and the national leprosy programmes to implement SDR-PEP in Mozambique and Nigeria. We aim to interrupt the spread and devastating effects of leprosy through well thought-out interventions targeting a range of stakeholders. The governments of both countries have shown enthusiasm and willingness to work together with the partners in this project to introduce SDR-PEP into their leprosy control programmes and improve care for persons affected.
PEP++ study
(Clinical trial in Bangladesh and Nepal and in a number of other non-TLM countries)
TLM and NLR have again joined hands to test an enhanced PEP regimen in Bangladesh and Nepal. The project’s multi-centre research programme uses a new, more robust preventive chemotherapy regimen. SDR-PEP reduces the risk of leprosy among contacts of new patients by 57%. We expect that three doses of the new PEP++ regimen, a combination of rifampicin/clarithromycin is expected to be 80-90% effective. The medication will be administered to a random sample of close contacts in multiple doses. These people are more likely to harbour a higher number of leprosy bacilli than the general population or may be infected without any visible symptoms yet. More than 800,000 will receive preventative treatment across the five countries involved (Bangladesh, Brazil, India, Indonesia, Nepal).
Our research is not possible without our partners
The Leprosy Mission is proud to be a funder of the Leprosy Research Initiative
