Project coordination
Erasmus MC, University Medical Center and Leiden University Medical Center
Partners
The Leprosy Mission International, Bangladesh (TLMIB)
Aim: Through detection of infected individuals and subsequent prophylactic treatment the researchers aim to be able to avoid leprosy ever becoming manifest in their lives.
Full project title:
Novel interventions and diagnostic tests for leprosy
Final project summary:
Previous research showed that a single dose of rifampicin (SDR)—an antibiotic also used in leprosy treatment—can reduce the risk of developing leprosy by more than 50% among people who have close contact with leprosy patients. SDR is a safe, simple, and inexpensive preventive intervention.
In a large study preceding the current research (the MALTALEP trial), the researchers studied whether BCG, a vaccine commonly used to prevent tuberculosis, in combination with SDR, could better protect contacts of leprosy patients against leprosy. In this study, the research team aimed to determine the effect of BCG, BCG combined with SDR, or SDR alone on the reduction of new cases, as well as on the reduction of infection in contacts of leprosy patients. Furthermore, the effect of the interventions on the level of M. leprae infection in contacts was assessed by using a low-complexity test (similar to a glucose dipstick or a pregnancy test) that can detect markers in blood associated with M. leprae infection. Through this project, it was aimed to: 1) evaluate the effect of BCG and SDR on the development of leprosy; and 2) evaluate the efficacy and feasibility of implementing the user-friendly test for the detection of infection.
In 2022, field teams completed the five-year follow-up of participants in the MALTALEP trial. Preliminary immunological analyses focused on several biomarkers. IP-10 and S100A12 are proteins associated with inflammation, while CRP and SAA are proteins involved in the body's acute response to infection. ApoA1 is a protein with anti-inflammatory properties.
Initial results showed that anti-PGL-I antibodies are a reliable indicator of bacterial burden. At the start of the study, leprosy patients had significantly higher levels of anti-PGL-I antibodies and IP-10 than their household contacts. CRP and SAA showed a similar pattern, with higher levels in patients. These differences remained evident six months later.
After six months of multidrug therapy (MDT), anti-PGL-I antibody levels had decreased in leprosy patients, while ApoA1 levels had increased significantly. Among household contacts, ApoA1 levels also increased during follow-up, whereas CRP levels decreased. Overall, these findings suggest that inflammatory markers decline over time in both patients and contacts, while the anti-inflammatory marker ApoA1 increases.
Further analysis using the complete dataset will determine whether these biomarker changes reflect a reduction in infection among contacts and whether outcomes differ between contacts who received a single dose versus a double dose of rifampicin.
Impact
Richardus, R., Alam, K., Kundu, K., Roy, J. C., Zafar, T., Chowdhury, A. S., ... & Richardus, J. H. (2019). Effectiveness of single-dose rifampicin after BCG vaccination to prevent leprosy in close contacts of patients with newly diagnosed leprosy: a cluster randomized controlled trial. International Journal of Infectious Diseases, 88, 65-72.
van Hooij, A., van den Eeden, S., Richardus, R., Fat, E. T. K., Wilson, L., Franken, K. L., ... & Geluk, A. (2019). Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field. EBioMedicine, 47, 301-308.
Tió-Coma, M., Avanzi, C., Verhard, E. M., Pierneef, L., Van Hooij, A., Benjak, A., ... & Geluk, A. (2020). Genomic characterization of Mycobacterium leprae to explore transmission patterns identifies new subtype in Bangladesh. Frontiers in microbiology, 11, 1220.
Van Hooij, A., Tió-Coma, M., Verhard, E. M., Khatun, M., Alam, K., Tjon Kon Fat, E., ... & Geluk, A. (2020). Household contacts of leprosy patients in endemic areas display a specific innate immunity profile. Frontiers in Immunology, 11, 1811.
Geluk, A. (2021). All mycobacteria are inventive, but some are more Daedalean than others. Immunological Reviews, 301(1), 5-9.