The Leprosy Mission Research Magazine - July 2021
Welcome to TLM's Second Research Magazine.
TLM's Research Magazine
Issue 2: Summer 2021
Welcome to our second Research Magazine
Welcome to TLM's Second Research Magazine.
The first magazine was published in January 2021 and was well received across TLM's Global Fellowship.
This second edition aims to continue to provide you with the latest info on our ground-breaking research projects.
In the coming pages you can read about how TLM is looking at new diagnostic tests, ways to prevent ENL, new methods for improving the mental health of persons affected by leprosy, and how our research has revealed the extent to which leprosy spreads within households.
Jannine Ebenso
What do you first think of when you think of research?
- Lab techs using lab equipment
- Professors in universities
- Fieldworkers taking notes in the field
- Medical journals
- Funding applications
- Long words that you don't understand
Cover image copyright: Ricardo Franco
Could smartphones provide us with instant leprosy diagnosis?
After winning funding from ALM’s ‘NTD Innovation Prize’ in 2020 and further support from St Francis Leprosy Guild, our teams have been working on a new project that could allow us to use smartphones, equipped with spectral imaging technology, to diagnose leprosy instantly in the field.
Below, Tim Burton from the International Office talks to the project’s lead researcher, Dr Suwash Baral, a Consultant Dermatologist and Dermatopathologist at Anandaban Hospital in Nepal.
TB: Dr Suwash, why is this a project that TLM should be excited about?
SB: We currently have around 200,000 people diagnosed with leprosy each year. However, researchers estimate that there are ‘missing millions’ who go undiagnosed. Spectral imaging technology on smartphones will not help us to find every one of those missing millions, but it will certainly help us to close the gap.
At the moment, field workers and healthcare staff have to diagnose leprosy with skin smear tests. There are two main problems with this.
Firstly, the tests take a long time to run; they must be sent out to a lab, they must be looked at with a microscope, and then the results need to be sent back to the potential patient and relevant clinician. This process can take weeks. Leprosy may be a slow moving disease, but the sooner we can begin someone on MDT, the better. This prevents the development of preventable disabilities and it stops transmission.
The time lag between initial test and final result is also a problem for people who are not easy to locate. While a skin smear may be done in one place, that individual may have moved on by the time the result comes. If that happens, we have missed the chance to treat them; they may continue to be infectious and they will probably develop preventable disabilities.
Secondly, we have limited capacity with these tests. We are not able to take skin smears from every person who has a skin lesion. It takes too long and is too complicated. If a person has a skin lesion and the lesion still has feeling, most fieldworkers will not take a skin smear because it does not appear to be leprosy. This is an appropriate way to prioritise, given the tools we have available to us. However, with better tools we would be able to test every skin lesion we come across.
Of the ‘missing millions’, there could be many who have skin lesions that we cannot test. There could be many more who have been diagnosed with leprosy, but we cannot find them and cannot treat them. We should be excited about this project because it could help us to find and treat far more people in a much shorter period. It helps us to stop both transmission and disability.
Above: Dr Arie de Kruijff explains more
TB: What is spectral imaging and how is it going to help us diagnose leprosy faster?
SB: Spectral imaging allows us to see beyond the range of vision that is available to the human eye. We are able to see a skin lesion on the skin, but spectral imaging can see the lesion below the skin, as well.
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 makes all the difference.
Spectral imaging is currently being used in many places across the world to detect skin cancer, so we know that it can work to identify dermatological problems. We believe spectral imaging will be able to help us identify a leprosy lesion, as well. Prof Janis Spigulis and his team at the University of Latvia have lots of experience in this and have set up the hardware and software for us to trial it with leprosy.
As part of this project, we need to take spectral imaging scans of lesions from a minimum of 100 patients in Nepal. Some of these lesions will be leprosy and some will be doubtful. We will test these lesions under a microscope to confirm whether they are or are not leprosy lesions. We will then send the spectral imaging scans to the team at the University of Latvia. They will be looking at the scans to try to identify patterns that are unique to the lesions that have tested positive for leprosy.
We think there may also need to be some testing done in Africa, as skin cancer is less common in Africa and so spectral imaging has not been tested on darker skin.
Leprosy skin lesions are a lot bigger than skin cancer lesions, so we are going to have to be patient through this research and take many scans, covering each section of a lesion. Despite this, we are hopeful that the precedent set by skin cancer will be the same for leprosy. Once we have identified what is unique about a scan of a leprosy lesion, a fieldworker should be able to identify a leprosy lesion with just one scan of part of a lesion.
Above: The winning proposal video that was submitted to the NTD Prize
TB: How will this technology work on smartphones?
SB: At the moment, the spectral imaging scanner is a fairly large piece of kit. We will be carrying it with us to the field in Nepal in its own bag. However, once we have established that spectral imaging can be used to diagnose leprosy, the cost of mass-producing the scanner will be reduced and we will have a spectral image-scanning device that can be fitted over the top of a smartphone.
Clinicians are currently using smartphone scanners to diagnose skin cancer, so once more we have a helpful precedent to work with. We believe this field-friendly smartphone kit will be scalable and affordable, so that one day all fieldworkers can take one with them when they are doing case finding work. They could diagnose leprosy in the moment and prescribe the necessary MDT. The clinicians’ opinions of the lesion will still be important in the field, but we hope that this will be an invaluable tool for them.
TB: How long will it be before fieldworkers are bringing smartphone scanners with them?
SB: The pandemic has delayed our progress on this. We have not been able to conduct scanning in the field in Nepal due to government lockdown restrictions. It is hard to predict the trajectory of the pandemic, but we are hopeful that we may be able to start scanning in the next few months.
From then, we will take about a year to enrol the 100 patients that we are looking for, but we will be sending scans to the team in Latvia throughout this time.
We will aim to publish results sometime in 2022 and if we are successful, spectral imaging could be a regular part of leprosy work in 3-5 years’ time. If that happens, we think it will be a breakthrough; it will transform the process of leprosy diagnosis.
Cover image copyright: Ricardo Franco
Do you think supporters in your country would be interested in this project?
Riding the crest of the mental health wave
Mental health problems affect 1 in 4 people across the world. Over the course of the pandemic, that figure has certainly crept up and even those who have not experienced mental health problems may have been granted a small window into what it can feel like.
Thankfully, in many countries the conversation around mental health has been opening up over recent years. Alongside this, TLM, as well as our partners, are working increasingly towards holistic healthcare. But this work is only beginning and for now we are looking at the crest of this wave, waiting for it to crash and bring sweeping change for vulnerable people who are fighting personal battles with their mental health in communities across the world.
The first step to properly addressing what could prove to be a mental health crisis amongst persons affected by leprosy is to determine the scale of the problem. Our team in Nigeria are engaged in exactly that work. Their project, in partnership with the University of Jos and the Christian Blind Mission, could prove transformative.
How do we define the scale of the problem?
Dr Paul Tsaku is leading TLM Nigeria’s attempts to map the scale of the mental health crisis that is hurting persons affected by leprosy and other NTDs. His team have been doing this through the Mind-Skin Link project, using both qualitative and quantitative research.
Their quantitative data was gathered through a survey of 142 people affected by leprosy and Lymphatic Filariasis (LF). The survey data revealed that a significant number of those surveyed had at least one form of mental health problem. The team are still undergoing the process of analysing this data, which they hope will provide them with a much clearer indication of the sale of the problem.
The team’s qualitative data took the form of focus group discussions. They ran a series of groups of up to five people where participants were given the opportunity to talk about mental wellbeing and the associated stigma in their community. The groups have looked at how participants live their lives and the kinds of challenges they encounter and how these two factors relate to mental health problems.
The problem is too big for quick fixes
Although the research is still underway and final results are some way from being ready for publication, the team know that the problem is too serious to be fixed overnight.
The research is being conducted in Benue State in Nigeria and there is effectively no mental health support for the state’s NTD-affected population. Benue has only five psychiatrists for a population of 5 million people. On top of this, existing research indicates that 76 percent of people with NTDs suffer from psychosocial problems.
Benue has only five psychiatrists for a population of 5 million people.
Whilst realities will vary across Nigeria and in other countries around the world, we know that mental health problems are a huge unmet need amongst people affected by leprosy and other NTDs. These problems will not be fixed overnight; we will need to commit substantial resources to solving this crisis.
Thankfully, as well as helping us to grasp how significant our response needs to be in the long-term, Dr Tsaku’s research also gives us some helpful places to start.
Beginning to address the crisis
TLM Nigeria have been working with communities in Benue to develop resilience within their existing structures. Dr Tsaku told us “We wanted to put our research into practice right away, that’s why we’ve committed time to training and awareness-raising within communities. Our goal has been to integrate mental health within existing healthcare and NTD structures.”
Dr Tsaku and the team started with a theory of change workshop within the communities they have been working with. They invited health care professionals, mental health stakeholders, NTD stakeholders and persons affected by both leprosy and LF.
The workshop participants had the opportunity to speak up about the kind of mental health change they want to see within their community and together they drafted a theory of change map.
This initial workshop unlocked some of the significant barriers to mental health support within the community. Primarily, the workshop highlighted that there was a substantial gap in training for community healthcare workers, who were not equipped to handle mental health problems. The workshop participants agreed that these workers had to be equipped with the right skills and knowledge if the mental health problems within communities were to be addressed.
The team have responded to this right away by providing mental health training for the community and NTD healthcare workers in Benue State. This training was based on the WHO Mental Health Guidelines. They have more training planned on psychological first aid, which will guide these community health service providers on how to handle mental health emergencies within the community. The plan is to continue to supervise these healthcare workers so that we can learn from their experiences and improve their performance.
Another significant problem that the workshop highlighted was the stigma surrounding mental health problems. Stigma has been shown to be associated with reduced help-seeking and low adherence to treatment, further compounding the burden of mental health among people affected by NTDs. Following this, TLM Nigeria have been working with partners to increase community awareness of mental health so that the stigma can begin to disappear.
Although the mental health problems within leprosy and NTD communities might be a big one, we are seeing from Nigeria that integrating mental health support within the existing structures is possible and can have an impact.
We must grow from here
Dr Tsaku and his team are working on a manuscript for publication and may end up with several publications following this one project.
So far, the project has been presented to the WHO and at a webinar jointly organised by the London Centre for NTD Research, and The Royal Society of Tropical Medicine and Hygiene, and has been very well received by a global audience. The project hs set out to test the feasibility of WHO’s first guideline for mental health and NTDs integration tagged “towards a person-centred approach.”
As these projects progress and more projects start, we will begin to get a bigger and better picture of the problems we face and how we can address them.
Dr Tsaku has plans to expand this project to other states within Nigeria. It is crucial that such work continues, both in Nigeria and elsewhere in leprosy-affected countries. We are becoming more and more aware of the significance of this problem and our researchers are the key to unlocking the solutions that are so desperately needed.
I think TLM should...
- Put more resources into mental health research
- Put fewer resources into mental health research
- Continue with the existing resources
How we can limit ENL reactions with a simple course of medication
What are ENL reactions?
ENL reactions are extreme inflammatory episodes that occur in some leprosy patients with the highest bacterial loads. They can happen before, during, and after MDT treatment and they leave patients feeling extremely unwell, frequently requiring hospital treatment and sometimes leaving them with permanent disability.
Sadly, patients often experience multiple episodes of ENL over an extended period of time.
In TLM’s first Research Magazine, Dr Deanna Hagge spoke about the horrors of ENL reactions. She told us,
“When ENL develops, the whole body develops symptoms. Patients have a fever and incredibly inflamed skin lesions all over their body. They can experience severe pain in their skin, nerves, bones, muscles, eyes and/or testicles… At times I have heard men sobbing in pain because their skin is so inflamed that even taking a blood sample is agony.”
There is not much research available on this topic, but current estimates suggest that around half of patients who experience an ENL reaction will go on to experience at least one more.
These painful episodes can take months, if not years to subside
These painful episodes can take months, if not years to subside, which is very hard for a person as they recover in hospital or at home. They can create long-term disability (damage to eyes or nerves) and the current treatments can cause serious side effects, in rare occasions even leading to death. You can read more about that in our first Research Magazine.
Clofazimine could be the key to preventing multiple ENL reactions
If we can find a way to prevent more episodes of ENL, we will have achieved a serious victory. Research that is taking place in Bangladesh could be about to do just that.
Clofazimine is one of the medications used within Multi-Drug Therapy (the treatment for leprosy). As a part of MDT, Clofazimine at a low dose has an anti-bacterial effect, but it can also have an anti-inflammatory effect if given at higher doses. For decades, some clinicians have been using Clofazimine to reduce the seriousness of ENL reactions because it is known to reduce the inflammation.
Although there are many anti-inflammatory medications available, Clofazimine is the only one that has shown any indication of being effective against ENL Many other anti-inflammatory medications are also impractical because using them in combination with prednisolone, the most common treatment for ENL, leads to a serious risk of developing stomach ulcers.
However, there is too little research evidence currently available to support including this use of Clofazimine as a part of global guidelines and, because of this a lack of published evidence, many clinicians believe it would not work.
Our team in Bangladesh are using Leprosy Research Initiative (LRI) and Turing Foundation funding to work with the Bombay Leprosy Project on a research project that could provide the evidence base needed to make this standard practice across the world.
Six months of treatment could make all the difference
Our team is being led by Principal Investigator, Dr Vivek Pai of the Bombay Leprosy Project. Their current hypothesis is that giving a high dose of Clofazimine for six months to a person who is experiencing their first ENL reaction will lead to less chance of a second episode and, if there is a second episode, it will be less severe. This course of Clofazimine would be provided alongside the existing treatments for ENL.
This treatment would cut both suffering and the rates of disability amongst ENL patients
If their hypothesis proves correct, this treatment would cut both suffering and the rates of disability amongst ENL patients and have a significant impact on the livelihoods and household incomes of patients.
To test the hypothesis, the team will enrol 200 patients who have already experienced ENL across Bombay, Dhaka, and Chittagong for a randomised control trial. This means 100 patients will receive the increased Clofazimine dose and 100 patients will have standard care.
Unfortunately, it is not possible to conduct a double blind trial, where one group receives a placebo, because the increased Clofazimine dosage leads to a discolouration of a patient’s skin, which cannot be replicated by anything else.
The team will start patients with 100mg of Clofazimine three times a day and reduce that over the six-month treatment period. Within MDT treatment, the standard Clofazimine dose is 50mg once a day, so this will be a significant increase in dosage.
The team will monitor the patients through the trial to look for statistically significant differences between the groups in terms of quality of life, increased disability, the amount of steroids they require for treatment, and the time interval before the next episode of ENL, as well as the severity of that episode.
Results from the study will be available from 2025
The project was due to start at the beginning of 2020, but has been delayed by a combination of Covid-19 and supply issues with Clofazimine.
Once the team has a sufficient supply of Clofazimine and once the Covid-19 situation allows, they will be able to commence enrolling patients into the research immediately. The project will require two years for enrolment and two years to follow up the patients, which means results will be available from 2025.
From 2025, the team could have an evidence base that is significant enough to change global guidelines for treating ENL. If that were to happen, it would prevent thousands of avoidable episodes of ENL and transform the lives of the people and families that would have been so painfully affected.
Cover photo credit: Ricardo Franco
Research reveals level of leprosy transmission within households
New research by The Leprosy Mission’s team in Bangladesh, in partnership with the London School of Hygiene and Tropical Medicine, has revealed that people who share a home with a person affected by leprosy do have only a low risk of contracting the disease, even though their risk is higher than that for other members of their community.
The new research will change the way we trace new cases as we work to end the spread of the disease by 2035.
There is not a high chance of catching leprosy, even if it is present in your home
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 percent of people who have lived with a person affected by leprosy will contract this disease.
The research has involved analysis of households of historic cases of leprosy diagnoses in Northwest Bangladesh, combined with ongoing case finding to see what proportion of people who live in a household with a person affected by leprosy go on to be diagnosed with the disease themselves. The research indicates that it is less than 2 percent of household members, which is a reminder that there is no need to isolate people affected by leprosy.
This is further evidence that leprosy is only mildly infectious
A person affected by leprosy who undergoes the correct treatment for leprosy, Multi Drug Therapy (MDT), will stop being infectious within 72 hours of starting treatment and, even before treatment, only a minority of those affected by leprosy are infectious.
The findings will help us to target the disease better
The COCOA study also confirmed previous evidence, which shows that there is a higher rate of transmission in homes that have cases of MB leprosy. 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.
This knowledge is a valuable tool in our fight to end the transmission of leprosy. Before this study was conducted, many case workers would visit as many leprosy-affected homes as possible to check the household members for signs of leprosy, but they were often not clear on which homes to prioritise. Although priority has always been placed on MB patients, this new data confirms that these household contacts must be prioritised in our contact tracing efforts.
This data means that we must prioritise homes that have cases of MB leprosy, especially in the first year after the initial diagnosis, when new case detection within the household is at its highest rate.
Our practices in Bangladesh are beginning to change as MB houses receive regular follow up calls from our case workers. These regular follow up calls mean that we can diagnose and treat cases of leprosy at an earlier stage than before, which reduces the chances of transmission within a household or community.
As before, all households with cases of leprosy are taught about how to spot the early signs of leprosy, which include patches of skin that are differently coloured and often have no feeling.
These new practices are another excellent tool for The Leprosy Mission as we continue to work on slowing the rate of transmission of leprosy so that there will be no new cases by the year 2035.
Final research published by Dr Emily E. V. Quilter and Dr Diana Lockwood.
Cover image copyright: Ruth Towell
Did you learn anything from this magazine?
- Yes, a lot
- Yes, a bit
- Not a lot
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