Leprosy Mailing List – September 14, 2018
Ref.: (LML) Single-dose rifampicin chemoprophylaxis
From: Zhaudat Umerov, Moscow, Russia
Dr Joel de Almeida (LML, July 23, 2018) raised an important question about the reliability of evidence for the effectiveness of SDR chemoprophylaxis in leprosy. In many endemic countries of the world different variants of leprosy chemoprophylaxis have been tested for several decades. Despite careful preparation and multicentre randomized trials, the results did not meet expectations. Therapeutic drugs such as rifampicin, which has a powerful antibacterial effect, had only a slowing effect on the development of leprosy in contact persons.
This feature of leprosy chemoprophylaxis can probably explain the results of scientific research. According to scientific data, the unconvincing result of leprosy chemo-therapy is caused by the resistance of the pathogen to all anti-leprosy drugs in contact persons without developed disease.
Thus, S. Cole's research group (2001) was discovered this feature of ML (1). The deciphering of the genome ML showed the presence of large numbers translationally inert pseudogenes (50%) that prevent propagation of the pathogen. Consequently, this non- doubling form of ML may not respond to rifampicin or other anti-leprosy drugs since their target is blocking ML DNA replication. For example: rifampicin blocks transcription; dapsone target folic acid biosynthesis; fluoroquinolones, ofloxacin bind to the DNA gyrase and inhibit DNA replication.
The pathways spreading of this non-doubling invader into the body of contact persons are perfectly demonstrated the Smith's study 2. Researchers examined transmission of ML in three leprosy endemic villages on Maharashtra State in India. The results indicated that only 1.6% of 2552 nasal swabs were PCR positive and 68% of saliva samples were positive for ML-IgA. PCR positivity did not persist and most PCR positive results were in the wet season. It is evidence that ML persists in endemic communities as transient, mycobacterial carriage in the upper respiratory tract of clinically healthy individuals without immunological recognition and response. It can be assumed that SDR intervention of this population will not have an impact.
There is good reason to assume that the some of invaders can leave the host, others remain in non-activated tissue resident macrophages or dendritic cells of regional lymph nodes, include endothelial cells, without clinical manifestation till onset leprosy (from 1 year to 30 years according to epidemiological observation) or forever.
This natural resistance of contact persons to the development of leprosy is kept in check by the body's immune regulatory T-cells, B-cells controls, which under influence genetic factors coupled with exposure to environmental factors. Damage of this protective control leads to the beginning of ML doubling using the products of host's macrophages cell catabolism and the development of leprosy signs. Certainly, among the healthy contacts individuals will be persons with a developed subclinical leprosy, which will be cured by rifampicin. This may slow the emergence of new cases for 2 years but it will not protect other contacts from development disease.
As it seems, these research findings help to explain the failure of chemoprophylaxis of leprosy. The most promising area of prevention of leprosy is the development of medical therapy to strengthen the host's immune control system of contact individuals.
1. Cole ST, et al. Nature, 2001; 409: 1007- 1011.
2. Smith WCR, et al. Int. J. Lepr. & Other Mycobact. Dis, 2004; 72(3): 268-277.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << email@example.com