Monitoring the Effect of Prophylactic Interventions in Contacts of Leprosy Patients Including Field-application of a Novel Immunodiagnostic Test in Bangladesh

A stable leprosy new case detection rate in many endemic countries indicates that the transmission of M. leprae is continuing unabated and that the current control strategy of case finding and provision of multi drug therapy (MDT) is not sufficient. Immunoprophylaxis by vaccination or post-exposure prophylaxis (PEP) with antibiotics provide effective strategies for the prevention of leprosy. Prophylactic treatment with single dose rifampicin (SDR) has shown to be a successful method to prevent leprosy in contacts of newly diagnosed leprosy patients (1). Currently, the Leprosy Post-Exposure Prophylaxis (LPEP) program generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities within the national leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania [Steinmann P, et al]. Recently, the world health orginazation (WHO) has endorsed PEP for routine application in their new "Guidelines for the diagnosis, treatment and prevention of leprosy".

Genomic and transcriptomics analysis (e.g. population- and twin studies [5]), have determined that the host genetic background is an important risk factor for leprosy susceptibility. In addition, close contacts of leprosy patients have a higher risk of developing the disease (2, 3), which therefore represents the primary target group for interventions (4). To target individuals spreading leprosy bacilli for prophylactic treatment, M. leprae infection needs to be measurable objectively. Antibody levels correspond with bacterial load and risk of transmission. Also, individuals seropositive for anti-M. leprae phenolic glycolipid-I (PGL-I) antibodies, are at 5-8 fold higher risk of leprosy (5, 6). Moreover, in a leprosy endemic area in Bangladesh, we recently showed significant added value of cellular markers (cytokines, chemokines, acute phase proteins) to identify infection (7). Thus, for implementation in a PEP-approach, new tests that indicate who needs treatment should allow detection of both cellular-and humoral markers.

In previous studies applying UCP-LFA in 4 countries with variable leprosy endemicity (Bangladesh, Brazil, China and Ethiopia), we have shown that the combined assessment of serum levels of multiple biomarkers including anti-PGL-I Ab as well as cytokines, significantly improved the diagnostic potential for detection of M. leprae infected individuals. This demonstrates that UCP-LFAs for detection of multiple biomarkers can provide valuable tools for more accurate detection of M. leprae infection. Its low-complexity POC format and applicability for use of finger-stick blood allows large scale screening efforts in field settings. Moreover, the format of the UCP-LFA is being further developed in various other projects (focused on tuberculosis and leprosy diagnostic tests). This has recently resulted in a multi-biomarker test (MBT) format that allows simultaneous detection of up to 6 markers, which is currently further evaluated in the field for tuberculosis diagnostic purposes. Since the UCP-LFA format is flexible and can accommodate for detection of different markers, this latest development will also enable combined detection of humoral and cellular biomarkers which together represent a specific signature for M. leprae infection.