• Grant: LRI Regular Grant
• Budget round: 2019
• Research priorities: Transmission
• Country: Ethiopia, Mozambique, Tanzania
• Project no.: 707.19.58
• Budget: € 200,000
• Duration: October 2018 - September 2024
• Status: Completed

Project coordination
NLR, the Netherlands

Partners
Erasmus University Medical Center Rotterdam (Erasmus MC), the Netherlands
DAHW Deutsche Lepra- und Tuberkulosehilfe e. V., Germany
Ministry of Health, Community Development, Gender, Elderly and Children - Tanzania, United Republic of Tanzania
Catholic University of Health and Allied Sciences-Bugando (CUHAS), United Republic of Tanzania
Ministerio da Saúde – Mozambique, Mozambique
Universidade Lúrio, Mozambique
Federal Democratic Republic of Ethiopia Ministry of Health (FMOH), Ethiopia
Armauer Hansen Research Institute (AHRI), Ethiopia

Aim: The aim of the PEP4LEP study was to contribute to interrupting the transmission of M. leprae by identifying the most effective and feasible method of screening people at risk of developing leprosy and administering chemoprophylaxis in Ethiopia, Mozambique and Tanzania.

Full project title:
PEP4LEP: Chemoprophylaxis for leprosy: comparing the effectiveness and feasibility of a skin camp intervention to a health centre based intervention. An implementation trial in Mozambique, Ethiopia and Tanzania.

Final project summary:
A single dose of rifampicin (SDR) can reduce the risk of developing leprosy by nearly 60% when given to people who have been in contact with a person affected by the disease. Although the World Health Organization (WHO) recommends this form of post-exposure prophylaxis (PEP), there is limited evidence on the most effective and practical way to deliver it in routine health services.

The PEP4LEP project was established to compare two approaches to leprosy screening and SDR-PEP delivery in Mozambique, Ethiopia, and Tanzania. The first approach used community skin camps, while the second relied on household contact screening through health centres. To reduce stigma and increase the broader health benefits of screening, participants were not only examined for leprosy but also for other skin diseases. Eligible contacts received SDR-PEP following screening.

The study compared the two approaches by assessing case detection rates, delays in diagnosis, cost-effectiveness, and acceptability among health workers, participants, and other stakeholders. Both interventions also incorporated the NLR SkinApp, a mobile health tool developed to support health workers in conducting skin examinations in settings where access to dermatological expertise is limited.

The project included approximately 30,000 contacts of people affected by leprosy and generate evidence to inform future national and international guidelines on leprosy screening and prevention.

During the study period, data collection continued across all three countries, alongside ongoing data quality assurance activities. Additional work was conducted to support the cost-effectiveness and acceptability components of the study, including literature reviews, questionnaire development, adaptation and translation of study tools, and the transcription and translation of interviews. Two doctoral candidates successfully completed their dissertations based on the project, while a third planned to do so in 2025. Preliminary findings were presented at scientific meetings and conferences, and several peer-reviewed articles were published.

Project implementation was affected by global rifampicin shortages linked to the COVID-19 pandemic. However, once medication supplies became available again, all participating countries were able to resume recruitment and project activities.

A total of 177 index patients were enrolled in the community skin camp intervention and 3,375 index patients in the health centre-based intervention. In the community skin camp approach, 18,632 contacts were screened, resulting in the identification of 240 newly diagnosed leprosy patients. In addition, 9,080 participants (48.7%) were found to have one or more skin conditions. In the health centre-based screening approach, 1,269 contacts were examined, of whom 28 were diagnosed with leprosy, while 146 individuals (11.5%) were identified as having at least one skin condition.

The project findings have been shared nationally and internationally, and draft guidelines on leprosy screening and prevention have been developed. Study materials and publications have been made openly available to healthcare workers, researchers, and policymakers. A further outcome of the project was the integration of the NLR SkinApp into the WHO Skin NTD App, incorporating updates generated through the PEP4LEP study.

The project consortium also secured support to continue data collection beyond the original study period through a follow-on initiative, PEP4LEP 2.0, funded under the Global Health EDCTP3 programme. This continuation was established to enable the completion of research activities that had been affected by disruptions during the COVID-19 pandemic.

Overall, the PEP4LEP project has generated important evidence on different approaches to contact screening and SDR-PEP delivery while also strengthening the integration of skin disease screening into leprosy control activities. The findings are expected to contribute to future policy and programme development for leprosy prevention and early case detection.

Impact

Hambridge, T., Coffeng, L. E., De Vlas, S. J., & Richardus, J. H. (2023). Establishing a standard method for analysing case detection delay in leprosy using a Bayesian modelling approach. Infectious diseases of poverty, 12(01), 71-81.

Mwageni, N., van Wijk, R., Daba, F., Mamo, E., Debelo, K., Jansen, B., ... & Mshana, S. E. (2024). The NLR SkinApp: Testing a supporting mHealth tool for frontline health workers performing skin screening in Ethiopia and Tanzania. Tropical Medicine and Infectious Disease, 9(1), 18.

Mamo, E., van Wijk, R., Schoenmakers, A., Bobosha, K., Legesse, M., Hambridge, T., ... & Mieras, L. (2024). Case detection delay in leprosy: Testing tool reliability and measurement consistency in Ethiopia, Mozambique, and Tanzania. PLoS neglected tropical diseases, 18(7), e0012314.

Main funder

European & Developing Countries Clinical Trials Partnership

Supported by the European Union

• Grant: LRI Regular Grant
• Budget round: 2019
• Research priorities: Transmission
• Country: Comoros, Madagascar
• Project no.: 707.19.57
• Budget: € 200,000
• Duration: September 2018 - February 2023
• Status: Completed

Project coordination
Institute of Tropical Medicine (ITG), Belgium

Aim: This “cluster randomized” trial on effectiveness of different modalities of Single Double Dose of Rifampicin Post-Exposure Prophylaxis (SDDR-PEP) for leprosy in the Comoros (Anjouan and Mohéli) and Madagascar. 

Full project title:
PEOPLE: Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar

Final project summary:
Leprosy remains a public health challenge in several endemic countries, and new approaches are needed to reduce transmission and prevent new cases. One promising strategy is post-exposure prophylaxis (PEP), in which contacts of people affected by leprosy receive preventive treatment. The PEOPLE project evaluated different approaches to delivering PEP in highly endemic communities in the Comoros and Madagascar.

The study compared four approaches. One group received the standard approach without PEP, while three intervention groups received a single double dose of rifampicin (SDDR): household contacts only; all contacts living within a 100-metre radius of an identified case; or household contacts plus individuals living within a 100-metre radius who tested positive for anti-PGL-I antibodies. Annual door-to-door screening was conducted and eligible participants received preventive treatment.

Between 2019 and 2023, the study registered a total population of more than 110,000 people across participating villages in the Comoros and Madagascar. Nearly 87% of registered individuals were examined at least once during follow-up, and almost 20,000 people received preventive treatment. Despite disruptions caused by the COVID-19 pandemic, all planned screening rounds were completed.

The study showed that PEP provided protection against leprosy at both the individual and community levels. The findings also demonstrated a strong relationship between geographical proximity to a person affected by leprosy and the risk of developing the disease. The results suggest that the greatest impact on transmission may be achieved through systematic screening of household contacts and people living in close proximity to diagnosed patients, combined with the provision of preventive treatment.

Alongside the intervention trial, researchers explored community perceptions and acceptability of the programme in the Comoros and Madagascar. Overall, the intervention was well accepted, although some challenges were identified, including limited awareness of early leprosy symptoms and concerns related to blood sampling. The study also highlighted the importance of migration and social networks in understanding how leprosy spreads within and between communities.

A molecular component of the project investigated patterns of transmission and monitored antibiotic resistance. Using a newly validated sequencing method, researchers found no evidence of resistance to rifampicin, fluoroquinolones, or dapsone among the samples tested. Genetic analyses also provided new insights into the diversity and distribution of Mycobacterium leprae strains in the study areas.

The project generated a range of scientific outputs and contributed to strengthening local research and clinical capacity. Large field teams were trained in leprosy diagnosis and surveillance, while new tools and methods for epidemiological mapping, data collection, and molecular testing were introduced and strengthened.

Overall, the PEOPLE project provides important evidence on the use of post-exposure prophylaxis as a tool for leprosy prevention. The findings support the value of targeted contact screening and preventive treatment and contribute to ongoing efforts to reduce transmission and improve leprosy control in endemic settings.

Impact

Hasker, E., Assoumani, Y., Randrianantoandro, A., Ramboarina, S., Braet, S. M., Cauchoix, B., ... & de Jong, B. C. (2024). Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial. The Lancet global health, 12(6), e1017-e1026.

Main funder

European & Developing Countries Clinical Trials Partnership

Supported by the European Union

• Grant: LRI Regular Grant
• Research priorities: Transmission
• Country: Brazil
• Project no.: 704.16.31
• Budget: € 42,668 |
• Duration: April 2016 – June 2019
• Status: Completed
• Co-funding partners: Turing Foundation

Full project title:
Comparative sequencing analysis of genes associated with susceptibility to leprosy and its reactive states

Project coordination
Pontifícia Universidade Católica do Paraná (Brasil)

Partners
Federal University of Goiás (Brasil)

Aim: In this project, the research group applied next-generation sequencing technology to sequence six genes consistently associated with host susceptibility to leprosy and leprosy reactions. 

Final project summary
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an obligate, slow growth, intracellular pathogen with tropism for skin and peripheral nervous system. Development of leprosy is highly dependent of host genetic risk factors, as initially demonstrated by observational studies. With the advance of technology, molecular studies successfully identified various candidate genes involved in the control of leprosy phenotypes. However, none of these study designs is suited to pinpoint the true causative genetic variants underlying the observed association effects. This study aimed to identify rare and/or common changes in the DNA of 73 genes previously implicated in the molecular control of host susceptibility to leprosy.

The analysis of variants on the genetic material of the individuals included in the study led to the identification of 37 DNA changes distributed in 24 genes that may increase the chance of an individual developing leprosy after contact with the causative bacteria. Nine of these changes led to modifications in the structure of proteins, and two of these changes are predicted by computer systems to be damaging to the protein function. Six of these genes have more than one DNA change associated with leprosy and, for two out of these six genes, analysis considering combinations of the independent variants confirmed strong evidence for association with leprosy. In 4 of the 37 genes analysed, the combination of rare changes in the genome of the individuals caused an increased risk of development of leprosy. Finally, these genetic variants are being used to predict the risk of a leprosy patient to develop leprosy reactions, through a free-access computer-based, on-line artificial intelligence system that is operating with sensitivity and specificity higher than 85%.

Impact

- Oral presentation at the 20th International Leprosy Congress, 2019 in Manila, Philippines, with the title “Fine mapping of the transcribed sequences of genes associated with host susceptibility to leprosy"
- The study and part of the results have been presented in the “II Mostra de pesquisa PPGCS e Escola de Medicina” – a local event of our graduate program (2018).

• Grant: LRI Regular Grant
• Research priorities: Transmission
• Country: Philippines
• Project no.: 701.05.20
• Budget: € 476,348
• Duration: January 2011 - April 2018
• Status: Completed
• Co-funding partners: Turing Foundation

Project coordination
Leonard Wood Memorial Center for Leprosy Research (Philippines)

Partners
National Hansen's Disease Program (USA)

Aim: This project researched transmission patterns within the community to gain information on leprosy epidemiology and found continued new cases and a slight shift towards a more severe type in Cebu, the Phillipines. Moreover, full application of molecular epidemiological techniques for leprosy control activities can give valuable insights into the dynamics of leprosy transmission in a given population and help identify here-to-fore unrecognized transmission networks but will require technical refinement. 

Full project title:
Macroepidemiology & microepidemiology of leprosy in Cebu, Philippines

Final project summary:
The purpose of this project was to increase the knowledge about the spread of leprosy in Cebu, by linking epidemiological data with data of the specific M.leprae (geno)types. This information will help to understand the types of M.Leprae bacteria and the types of leprosy prevailing in the island. In addition, a better understanding on various factors affecting the spread of leprosy in the community will help to improve leprosy control strategies both locally and globally by redirecting attention to high risk populations (eg: children, family members, urban slum, etc.) who may need closer monitoring or intake of drugs that will protect them from developing leprosy.

Information was collected retrospectively of leprosy cases diagnosed in the period from 2000-2010, and prospectively of leprosy cases diagnosed in the period from 2011-2016. Apart from clinical and demographic data collected from the leprosy cases, different techniques were used to identify different M. leprae (geno)types. This type of data provides the opportunity to identify clusters of same-type of M.leprae, indicated transmission networks and furthermore to detect drug resistance.

The research group's findings suggest that despite the declining trend, the number of new leprosy cases detected each year and the average age of children developing the disease stays the same, suggesting that spread of leprosy in Cebu is still active and recent. In addition, there seems to be a slight shift of leprosy towards the more severe type suggesting that a huge reservoir of infection is still present in the area. The substantial number of cases detected in recent years also confirms the importance of continued funding support to sustain active case finding activities. The researchers furthermore concluded that full application of molecular epidemiological techniques for leprosy control activities will require technical refinement, but can give valuable insights into the dynamics of leprosy transmission in a given population and help identify here-to-fore unrecognized transmission networks.

 Impact

Scheelbeek, P. F., Balagon, M. V., Orcullo, F. M., Maghanoy, A. A., Abellana, J., & Saunderson, P. R. (2013). A retrospective study of the epidemiology of leprosy in Cebu: an eleven-year profile. PLoS neglected tropical diseases, 7(9), e2444.