Symposium Report: Developing Strategies to Block the Transmission of Leprosy

Abstract

Remarkable progress has been made in the treatment and management of leprosy over the
last 60 years. Current control strategies rest on early detection of disease and appropriate
multidrug therapy (MDT) to cure the patient and halt transmission within the community.
These strategies are built on a solid understanding of therapeutics for mycobacterial diseases
but suffer from an incomplete understanding of transmission of Mycobacterium leprae and a
shortage of tools that can truly diagnose leprosy at an early stage. Accordingly, transmission
continues in many areas of the world.
To clarify the current state of our knowledge of M. leprae transmission and to establish
a research agenda to address gaps in our understanding of transmission, an international
symposium entitled “Developing Strategies to Block the Transmission of Leprosy” was
organized and sponsored by effect:hope (The Leprosy Mission Canada) and held on May
29–30, 2014. The meeting was hosted by the National School of Tropical Medicine, Baylor
College of Medicine in Houston, Texas.

Full text

Symposium Report: Developing Strategies to Block
the Transmission of Leprosy
DEBORAH MENSAH-AWERE*, MARTIN W.
BRATSCHI**,***, PETER STEINMANN**,***,
JESSICA K. FAIRLEY**** & THOMAS P. GILLIS*
*effect:hope, Markham, Canada
**Swiss Tropical and Public Health Institute, Basel, Switzerland
***University of Basel, Basel, Switzerland
****Emory School of Medicine, Atlanta, GA, USA
Accepted for publication 24 May 2015
Context
Remarkable progress has been made in the treatment and management of leprosy over the
last 60 years. Current control strategies rest on early detection of disease and appropriate
multidrug therapy (MDT) to cure the patient and halt transmission within the community.
These strategies are built on a solid understanding of therapeutics for mycobacterial diseases
but suffer from an incomplete understanding of transmission of Mycobacterium leprae and a
shortage of tools that can truly diagnose leprosy at an early stage. Accordingly, transmission
continues in many areas of the world.
To clarify the current state of our knowledge of M. leprae transmission and to establish
a research agenda to address gaps in our understanding of transmission, an international
symposium entitled “Developing Strategies to Block the Transmission of Leprosy” was
organized and sponsored by effect:hope (The Leprosy Mission Canada) and held on May
29–30, 2014. The meeting was hosted by the National School of Tropical Medicine, Baylor
College of Medicine in Houston, Texas.
GOALS AND OBJECTIVES OF SYMPOSIUM
The goal of the symposium was to establish a research agenda, aimed at bridging the gaps
in our understanding of M. leprae transmission, which will complement a global research
strategy focused on eliminating leprosy.
Correspondence to: Thomas P. Gillis, Effect:hope, Markham, Ontario, Canada (e-mail: tom.gillis48@gmail.com;
tgillis@effecthope.org)
Lepr Rev (2015) 86, 156–164
156 0305-7518/15/064053+09 $1.00 qLepra

The objectives were:
1. To identify the key gaps in our understanding of M. leprae transmission
2. To organise gaps into priority areas
3. To propose specific areas of investigation to address these priority areas
SYMPOSIUM CONTENT
Keynote speakers
“The NTDs: Prospects for Elimination.” Peter Hotez, National School of Tropical Medicine,
USA.
Peter Hotez presented an overview of the global burden of Neglected Tropical Diseases
(NTDs) and their impact on health and on exacerbating the effects of poverty. Dr. Hotez
discussed the current strategies in place for NTD control and elimination such as Mass Drug
Administration and the impact it has had on reducing NTD prevalence. He highlighted the
issues surrounding Disability-Adjusted Life Years (DALY) and how leprosy’s very low
DALY may not accurately reflect its sustained effect on people affected by leprosy. Dr. Hotez
suggested that the London Declaration
1
may be overly simplistic when considering leprosy
with regard to its road map and he supports focusing efforts on interrupting transmission for
eventual elimination of leprosy.
“Tracing Our Path to Today.” Paul Fine, London School of Hygiene and Tropical Medicine,
UK.
Paul Fine described the history of leprosy as a disease including its disappearance
from Northern Europe and the first attempts to estimate the global burden of the disease.
Prof. Fine also shared current data on leprosy prevalence citing India, Brazil and Indonesia
as the countries that account for 80% of new cases as of 2012. Prof. Fine discussed some
of the possible theories related to M. leprae transmission and the reasons for the decline in
leprosy prevalence globally. He also shared some of the issues related to semantics facing
those working in the leprosy field and the impact this has on addressing M. leprae
transmission.
“Systematic literature review on current knowledge regarding the transmission of leprosy
(Hansen’s disease).” Martin Bratschi, Swiss Tropical and Public Health Institute,
Switzerland.
Martin Bratschi presented the findings from the systematic review of the peer-reviewed
literature pertaining to M. leprae transmission which was carried out to assess the current state
of knowledge on this topic. Dr. Bratschi showed that the systematic literature review identified
a total of 79 relevant articles providing solid evidence for M. leprae transmission among
contacts and for zoonotic leprosy in the Southern States of the USA. He also reported that based
on the extant evidence, skin-to-skin contact, aerosols/droplets and shedding of bacteria into the
environment and subsequent infection, all remain possible options and there is no study which
has unequivocally demonstrated the mechanisms by which M. leprae bacteria are transmitted.
The full literature review entitled “Current knowledge on Mycobacterium leprae transmission:
a systematic literature review” is published concurrently with this article.
2
Blocking transmission of leprosy 157

“Modeling Leprosy: How mathematical models help us understand transmission and the
effect of interventions.” Jan Hendrik Richardus, Netherlands.
Jan Hendrik Richardus stated that the primary purposes of current leprosy models are to
predict the course of leprosy incidence and to analyse the impact of various intervention
strategies. He gave an overview of the Lechat, SIMLEP and SIMCOLEP mathematical
models used for leprosy. He also highlighted some of the results from current leprosy
modeling efforts including the cost-effectiveness of single-dose rifampin chemoprophylaxis
and the impact of early diagnosis and treatment.
ENDEMIC COUNTRIES PRESENTATIONS
Representatives from five countries discussed the current trends in M. leprae transmission
and control in their respective countries.
Brazil (Rosa Castillia Soares, Ministry of Health, Sao Paulo, Brazil)
India (Sunil Anand, TLMI India, Delhi, India)
Ethiopia (Abraham Aseffa, AHRI/ALERT, Addis Ababa, Ethiopia)
Bangladesh (Shaikh Hossain, ICDDR,B, Bangladesh)
Philippines (Marivic Balagon, LWM Center for TB & Leprosy Research, Cebu,
Philippines)
The general themes were:
1. Leprosy control programmes have become decentralised and integrated into general
health systems
2. Reduced numbers of cases were reported in the early 2000’s
3. A high proportion of MB cases remain in Ethiopia and the Philippines
4. All five countries noted stable transmission in children
5. The rate of grade 2 disabilities overall has shown no significant change
6. There is decreasing expertise in case finding
7. High endemic pockets remain in most countries and appear to be related to lack of access
to care, and poverty
BREAKOUT SESSIONS
Breakout sessions were held to discuss the following key topics related to M. leprae
transmission: reservoir, parasite and host. Each breakout session began with a panel of experts
speaking on key topics related to the session. Discussion groups were then formed around
specific sub-topics and a rapporteur for each group was selected. Dr. Edith Bahmanyar of the
Novartis Foundation then facilitated plenary discussions around the key findings presented by
each rapporteur. The goal of the sessions was to identify and define the gaps in knowledge and
needs within the key topic areas that would lead to an improved understanding of M. leprae
transmission and provide new tools and strategies to block M. leprae transmission.
RESERVOIR
Expert Panel: Active cases (Paul Saunderson), Occult human reservoir (Cairns Smith),
Animal reservoir (Richard Truman) and Environmental reservoir (Ravindra Turankar)
D. Mensah-Awere et al.158

Sub-topics: 1. Active cases/occult human reservoirs (Saunderson/Smith)
2. Animal/Environmental reservoirs (Truman/Turankar)
PARASITE
Expert Panel: M. leprae genome (Pushpendra Singh); M. lepromatosis (Xiang-Yang Han)
Sub-topics: 1. Pathogen characteristics (Singh/Han)
2. Genotyping (Singh/Han)
HOST
Expert Panel: Genetics (Erwin Schurr), Immunology (Tom Hawn), Vaccines (Steve Reed),
Diagnostics (Annemiek Geluk), Portal of exit/entry of M. leprae (Eric Brenner)
Sub-topics: 1. Genetics, Immunology (Shurr, Hawn)
2. Vaccines/Diagnostics (Reed, Geluk)
3. Portals of exit-entry of M. leprae (Brenner)
PARTNERS
Partners from an array of government and nongovernment research and research funding
organizations presented their current research priorities and funding commitments as well as
successful projects related to leprosy research and control. The partners represented were; National
Institute of Allergy and Infectious Disease (NIAID, USA), Pan-American Health Organization
(PAHO), The Leprosy Research Initiative (LRI) and Novartis Foundation (Switzerland).
GAPS IN OUR UNDERSTANDING OF M. leprae TRANSMISSION AND
IDENTIFIED NEEDS
Based on the breakout sessions and the literature review on M. leprae transmission (see
Keynote Speakers and 2) the following gaps in our understanding of M. leprae transmission
and needs to fill these gaps were identified.
1. Human-to-human transmission of M. leprae
Studies have clearly shown that close proximity to leprosy patients increases the risk of
contracting the disease. However, other members of endemic communities who are potentially
asymptomatically infected carriers may also contribute to the transmission of M. leprae.
Gap 1: Human Reservoirs
We do not understand the full extent of the human reservoir of M. leprae; specifically the
roles of undiagnosed patients, patient contacts and other members of endemic
communities in perpetuating M. leprae transmission are unknown.
Needs to fill gap 1:
a) Discovery of biomarkers for: all clinical cases of leprosy, subclinical infections
and asymptomatic carriers.
b) Develop platforms for field-friendly diagnostic tests.
Blocking transmission of leprosy 159

2. Route of entry/exit of M. leprae in humans
A series of case reports appear to show that injection of M. leprae at the site of skin trauma
(e.g. by tattoo or accident) can lead to localised as well as disseminated manifestations of
leprosy. For most leprosy cases, there is however no clear sign that entry of the pathogen
occurred through skin trauma, and the available evidence points more towards the
involvement of the upper respiratory tract.
3. Role of animals, the environment or insects in the transmission of M. leprae
In the Southern USA, leprosy has been shown to exist as a zoonosis, based on M. leprae strain
identification, indicating that there is transmission of M. leprae between armadillos and
humans. However, in other parts of the world, the role of animals as reservoirs or vectors in
M. leprae transmission remains unclear. It is also unknown how the recently described
existence of M. leprae in the environment contributes to the spread of the disease.
Gap 2: Entry and exit route
We do not understand the route of entry and exit of M. leprae in humans.
Needs to fill gap 2:
a) Assess the role of colonization and route of entry (e.g. nasal-oral mucosa, skin and
gastrointestinal tract) of M. leprae into the human host.
b) Investigate potential roles of co-infections on the entry/exit of M. leprae from the
human host (e.g. amoebiasis).
c) Study the stages of pathogenicity of M. leprae to understand the migration (port of
entry to the site of initial lesion to point of exit) of M. leprae inside the human host.
Gap 3a: Roles of animals or vectors
We do not understand the role animals (armadillos outside of the southern USA and other
animals) or vectors (e.g. insects or amoeba) play in the transmission of M. leprae.
Needs to fill gap 3a:
a) Investigate how the distribution of M. leprae infection in armadillos is spreading in the
Americas and how this affects the occurrence of human leprosy.
b) Investigate the genetic diversity of M. leprae in armadillos to better understand
zoonotic and cross-species transmission.
c) Systematically investigate the possible role of animals (e.g. by serological
surveillance) other than armadillos in M. leprae transmission in different endemic
areas worldwide.
d) Investigate the biological relationship between M. leprae and amoeba.
D. Mensah-Awere et al.160

4. Role of Poverty in Transmission
It has been demonstrated that the socio-economic status of an individual appears to affect the
risk of contracting leprosy. However, the driver of this correlation is not clear. Whilst there
was not a breakout session dedicated to the topic of poverty and M. leprae transmission,
it was a reoccurring theme discussed in several sessions of the symposium.
5. Role of Host-Parasite Interaction in Transmission
Despite recent advances in our understanding of M. leprae genetic diversity and the cellular
immune response of leprosy patients, there are considerable gaps in our understanding of the
interaction between M. leprae and the human host.
Gap 4: Role of poverty
We do not understand how poverty acts as a risk factor for M. leprae transmission.
Needs to fill gap 4:
a) Investigate the role of poverty-related factors, such as nutrition, hygiene and crowding
on M. leprae transmission.
Gap 3b: Role of environmental sources
We do not understand the source and relevance for transmission of M. leprae in the
environment (e.g. in soil or water).
Needs to fill gap 3b:
a) Systematically investigate the presence of M. leprae in the environment in different
endemic settings.
b) Use genotyping to characterize environmental M. leprae to determine how it relates to
genotypes found in human infections in the same area.
c) Demonstrate viability and role in transmission of environmental M. leprae.
Gap 5: Host-pathogen interaction
We do not sufficiently understand the impact of the interaction between M. leprae and the
human host on M. leprae transmission.
Needs to fill gap 5:
a) Investigate relationship between M. leprae genetic characteristics and virulence,
growth kinetics, drug resistance, tropism for nerves and the tendency to cause reactions.
b) Understand the role of host genetic risk factors in susceptibility and resistance to
M. leprae infection, clinical progression of leprosy and reactions.
c) Understand how the immune response affects the manifestation of the M. leprae
infection (including establishing of infection, progression of disease, nasal carriage and
reactions) and eventually transmission of M. leprae.
d) Increase understanding of similarities/differences between M. leprae and M. lepromatosis.
Blocking transmission of leprosy 161

6. Transmission Networks
Recent evidence has shown that depending on the endemic setting, there are various types of
M. leprae transmission networks.
7. Improving Epidemiology Data
Despite the elimination of leprosy in many countries, hot-spots of transmission with more
than 1 case per 10 000 inhabitants and active transmission remain.
Conclusion and way forward
The Developing Strategies to Block the Transmission of Leprosy symposium brought together
a broad spectrum of expertise in the field of infectious diseases (Table 1), in order to identify
the key gaps that exist in our knowledge of M. leprae transmission as well as associated needs
to close those gaps. Key overarching research principles that will help to improve our
Gap 6: Transmission networks
We do not understand the diversity and relevance of the various M. leprae transmission
networks.
Needs to fill gap 6:
a) Increase collection of genome sequenced M. leprae strains with isolates from various
origins (e.g. worldwide, PB patients) which are complemented with detailed
epidemiological data.
b) Investigate genetic diversity of M. leprae from different sources (patients, nasal
carriers, zoonotic and environmental) and various settings (e.g. high and low endemic)
to study the transmission ecology at the community level.
c) Develop molecular epidemiology tools which are customised to a region to allow for
fine typing from primary samples and investigation of transmission links.
Gap 7: Enhanced epidemiological data
We do not fully understand the geographic distribution of leprosy, especially at a
sub-national level.
Needs to fill gap 7:
a) Improve the quality of national epidemiological surveillance data including
sub-national geographic variation and prevalence data based on local population
densities.
b) Implement contact tracing and active case finding strategies to identify transmission
hot-spots.
c) Digitalize leprosy surveillance to improve data access and timely identification of
areas with high case numbers.
D. Mensah-Awere et al.162

understanding of M. leprae transmission were further identified from both the literature
review on M. leprae transmission and during discussions at the symposium. These research
principles are related to study design, the type of data to be collected in the course of studies
and the capacity to conduct research in endemic areas. Specifically, it was concluded, that
it is of great importance that long-term studies are performed and aspects of M. leprae
transmission are monitored over several years. Only such longitudinal studies will have the
potential to demonstrate how any novel tool, intervention or control measures can potentially
affect the transmission of M. leprae. Furthermore, the degree of detail and types of data
collected in different studies vary considerably and make comparison between findings from
different studies difficult. The leprosy research and control communities should strive to
define a minimal and standardised set of high quality clinical and demographic data that
should be collected about participants in all studies. Researchers should further consider
establishing a biobank of samples relevant for M. leprae transmission research. Finally, for
the long-term research efforts required to eventually block the transmission of M. leprae it is
of utmost importance to continue to support, expand and maintain research infrastructure and
capacity in leprosy endemic areas. Likewise, government entities involved in leprosy control
should continue to receive technical and other support so as to collect high quality
epidemiological data about trends in the number of leprosy cases detected and how
interventions are affecting the spread of the disease.
The key gaps and needs identified during this symposium and reported here are essential
in shaping a global research agenda designed to block transmission of M. leprae and move
toward eliminating the disease. These research priorities will form the foundation of the
Transmission Research Initiative (TRI) which will be launched in October 2015 by
effect:hope and partners, with a goal to support research aimed at closing gaps in our
understanding of M. leprae transmission.
Acknowledgements
We would like to thank all participants for their time and effort in helping to make this
symposium a success. We would also like to specifically extend our gratitude to National
School of Tropical Medicine, Baylor College of Medicine for hosting the symposium. The
symposium organizers Peter Hotez, Tom Gillis, Anna Wickenden, Kenneth Wong, Monica
Cazares, and Cynthia Johnson wish to thank all plenary speakers and the symposium
facilitator Edith Bahmanyar for their contributions. The symposium and participant costs
were funded by effect:hope (The Leprosy Mission Canada).
References
1
Uniting to combat neglected tropical diseases. London Declaration on Neglected Tropical Diseases. http://
unitingtocombatntds.org/sites/default/files/resource_file/london_declaration_on_nt ds.pdf.
2
Bratschi MW, Steinmann P, Wickenden A, Gillis TP. Current knowledge on M. leprae transmission: a systematic
literature review. Lepr Rev, 2015; 86: 142–155.
Blocking transmission of leprosy 163

Table 1. List of Participants affiliations
Participant Affiliation
Erwin Schurr McGill University, Montreal, Canada
Thomas Hawn University of Washington, Seattle, WA, USA
Steve Reed Infectious Disease Research Institute, Seattle, WA, USA
Annemiek Geluk Leiden University Medical Center, Leiden, The Netherlands
Pushpendrah Singh Ecole Polytechnique Federale de Laisanne (EPFL), Lausanne, Switzerland
Gerd Pluschke Swiss Tropical and Public Health Institute, Basel, Switzerland
W. Cairns Smith University of Aberdeen, Aberdeen, Scotland
Paul Fine London School of Hygiene and Tropical Medicine, London, UK
Peter Hotez National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA
Jan Hendrik Richardus Erasmus MC, University Medical Center, Rotterdam, The Netherlands
Eric Brenner University of South Carolina, Columbia, SC, USA
Masanori Matsuoka Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
Ravindra Turanka The Leprosy Mission India and Stanley Browne Laboratory, Delhi, India
Marivic Balagon Leonard Wood Memorial Center for TB and Leprosy Research, Cebu, The Philippines
Edith Bahmanyar Novartis Foundation, Basel, Switzerland
Rosa Castalia Soares Leprosy Program, Ministry of Health, Sao Paulo, Brazil
Sunil Anand The Leprosy Mission Trust India, Delhi, India
Ruth Butlin Nilphamari, Bangladesh
Abraham Aseffa Armauer Hansen Research Institute and ALERT, Addis Ababa, Ethiopia
Shaikh Shahed Hossain International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
Jessica Fairley Emory School of Medicine, Atlanta, GA, USA
Martin Bratschi Swiss Tropical and Public Health Institute, Basel, Switzerland
Anna Wickenden effect:hope (The Leprosy Mission Canada), Markham, Canada
Peter Derrick effect:hope (The Leprosy Mission Canada), Markham, Canada
Tom Gillis effect:hope (The Leprosy Mission Canada), Markham, Canada
Kenneth Wong effect:hope (The Leprosy Mission Canada), Markham, Canada
Paul Saunderson American Leprosy Mission, Greenville, SC, USA
Christa Kasang German Leprosy and TB Relief Association, Wurzburg, Germany
Wim van Brakel Netherlands Leprosy Relief, Amsterdam, The Netherlands
Tamara Prinsenberg Netherlands Leprosy Relief, Amsterdam, The Netherlands
Ken Gibson The Leprosy Mission Ireland, Dublin, Ireland
Xiang-Yang Han MD Anderson, Houston, TX, USA
Bide Landry WHO-AFRO, Brazzaville, Republic of Congo
David Scollard National Hansen’s Disease Programs, Baton Rouge, LA, USA
Rahul Sharma National Hansen’s Disease Programs, Baton Rouge, LA, USA
Richard Truman National Hansen’s Disease Programs, Baton Rouge, LA, USA
Christine Sizemore NIAID, National Institutes of Health, Bethesda, MD, USA
Terry Williams Houston Department of Health and Human Services, Houston TX, USA
Steven Mays Houston Department of Health and Human Services, Houston TX, USA
D. Mensah-Awere et al.164