PhD defence N. (Nimer) Ortuño-Gutiérrez

Summary:

Leprosy or Hansen’s disease is a complex ancient infectious disease, caused by M.leprae and M.lepromatosis. The most believed frequent mode of transmission is airborne and therefore those in close contact with a new leprosy case are at the most risk of developing the disease although this depends on immunity heterogeneity. Despite leprosy has been the first infectious disease where the pathogen agent was identified, research and development have failed in the creation of reliable diagnostic tests for infection and disease. Therefore, the World Health Organization (WHO) recommends clinical cardinal signs and the ancient slit skin smear (SSS) for the diagnosis of the disease, and no diagnostic test for diagnosis of infection is currently recommended. Both clinical and laboratory skills and expertise are key for ensuring the reliability of diagnosis, which is dwindling due to the sustained decrease of leprosy prevalence worldwide. Nevertheless, the incidence has plateaued in the last decade around 200,000 new cases at the global scale and the highly effective treatment with multidrug therapy (MDT) has been insufficient to stop transmission. In 2018, the WHO has recommend single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for the contacts of new leprosy patients without signs of leprosy disease. The protection of PEP is around 60% and is based on the pivotal COLEP trial in Bangladesh. The Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP) study has documented the feasibility of PEP under programmatic conditions, and there is also evidence that PEP is cost-effective. Nevertheless, operational challenges for the most cost-effective approach to the provision of PEP for the high-risk population without causing harm to the persons eligible for SDR, and avoiding the increase of prevalence of rifampicin resistance, remain.

In this Ph.D., we developed and estimated the effectiveness of innovative active case detection strategies based on Geographic Information Systems-based (GIS-based) technologies for stopping transmission of M. leprae in high-priority countries i.e. Comoros, India, and Madagascar. Using GIS-based technologies, we studied highly prevalent clusters in Comoros and Madagascar. Clustering analysis was nested in a larger ongoing trial on post-exposure prophylaxis (PEP) for leprosy (the PEOPLE trial), where detailed mapping of entire village populations, including leprosy patients, was necessary for assessing different modalities for PEP. In India, we assessed the clustering of leprosy and mobility of leprosy patients, to identify highly prevalent clusters at the hamlet level. For this purpose, we developed a methodology to outline hamlets maps including their population to assess clustering for targeted active case detection strategies coupled with prevention activities.

The following research questions were answered:

• 1. What are the patterns of clustering of leprosy in Comoros and Madagascar?
• What is the pattern of clustering and mobility of leprosy patients in Bihar, India?
• How to build an approach for exploring clustering at the lower administrative levels in Bihar, India?