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Leprosy treatments developed

Leprosy is a disease with a long history, with evidence dating back to 4000 BC in ancient Egypt and numerous references in the Bible.ANCHOR However, it wasn’t until 1873 that Armauer Hansen determined the cause by observing the bacterium responsible, Mycobacterium leprae, under a microscope.ANCHOR In recognition of this, leprosy is also known as Hansen’s disease. In 1982 the World Health Organisation (WHO) recommended the use of a multi-drug therapy to treat leprosy, which has reduced cases worldwide by 97%.

Mouse footpads
Armadillos
References

Mouse footpads

As the M. leprae bacterium is not possible to grow in cultures, early research relied on the limited infection observed in the footpads of mice.ANCHOR This was an important system in screening drugs for treating leprosy. The anti-bacterial effect of clofazimine was discovered using the mouse footpad technique.ANCHOR The anti-tuberculosis drug rifamycin was discovered to be effective against M. leprae in mouse footpad.ANCHOR ANCHOR ANCHOR It also yielded further insights into the activity of dapsone, which had been in use since the 1940s.ANCHOR, ANCHOR Research done on these drugs in mice led to the development of rifampicin, clofazimine and dapsone multi-drug therapy, which was trialled in humans in Malta and recommended by the World Health Organisation in 1982.ANCHOR ANCHOR ANCHOR This combined therapy has been key in reducing the impact of leprosy worldwide and is still used today. The number of cases worldwide has fallen from 5.2 million in 1983 to 182,000 in 2011.ANCHOR

Armadillos

The lower body temperature of armadillos make them vulnerable to leprosy The nine-banded armadillo has become the principal source of M. leprae in vaccine research. The core body temperature of the armadillo is low enough to favour the growth of the leprosy-causing bacterium. In fact, leprosy is endemic among wild armadillos in the US and now form a reservoir of the disease from which humans can become infected.ANCHOR The use of armadillos in leprosy research dates back to the 1970s and has largely been focussed on the development of a vaccine. Using the armadillo, scientists were able to develop an experimental vaccine against leprosy, and have helped our understanding and the development of treatments for the disease.ANCHOR The vaccine development programme ran from the 1970s until the late 1990s when the BCG vaccine, which is given worldwide to prevent tuberculosis, was shown to be similarly effective against M. leprae. Although the vaccine programme eventually proved impractical, studying the purified bacteria led to a much greater understanding of leprosy, including sequencing of its genome. Armadillos also act as a source of bacilli, with bacteria derived from armadillos used in the lepromin skin test that tests for a M. leprae infection.ANCHOR


References

  1. Weymouth A (1938) Through the Leper Squint: A Study of Leprosy from Pre-Christian Times to the Present Day (London, Selwyn and Blount)
  2. Hansen GHA (1874) Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy) Norsk Mag. Laegervidenskaben 4:1–88
  3. Shepard CC (1960) The experimental disease that follows the injection of human leprosy bacilli into foot-pads of mice. J. Exp. Med. 112:445. http://jem.rupress.org/content/112/3/445.full.pdf
  4. Shepard CC, Chang YT (1964) Activity of antituberculosis drugs against Mycobacterium leprae. Int. J. Lepr. 32:260–271
  5. Rees RJW, Pearson JMH and Waters MFR (1970) Experimental and clinical studies on rifampicin in treatment of leprosy. Br. Med. J. 1:89
  6. Holmes IB and Hilson GRF (1972) The Effect Of Rifampicin And Dapsone On Experimental Mycobacterium Leprae Infections: Minimum Inhibitory Concentrations And Bactericidal Action J Med Microbiol 5:251-261 doi: 10.1099/00222615-5-2-251
  7. Hilson GRF, Banerjee DK and Holmes IB (1972) The activity of various anti-tuberculous drugs in suppressing experimental Mycobacterium leprae infection in mice. Int. J. Lepr.
  8. Shepard CC (1967) A kinetic method for the study of activity of drugs against Myco-bacterium leprae in mice. Int. J. Lepr. 35:429
  9. Shepard CC (1969) Further experience with the kinetic method for the study of drugs against Mycobacterium leprae in mice. Activities of DDS, DFD, ethionamide, capreo-mycin and PAM 1392. Int. J. Lepr. 37:389
  10. Freerksen E and Rosenfeld M (1977) Leprosy Eradication Project of Malta Chemotherapy 23:356–386 DOI: 10.1159/000222005
  11. World Health Organisation (1982) Chemotherapy of leprosy for control programmes http://whqlibdoc.who.int/trs/WHO_TRS_675.pdf
  12. Gelber RH (1998) Another View of the Therapy of Leprosy Antimicrob. Agents Chemother. 42(12):3334-3336
  13. WHO leprosy factsheet http://www.who.int/mediacentre/factsheets/fs101/en/index.html
  14. Truman RW et al (2011) Probable Zoonotic Leprosy in the Southern United States N Engl J Med 364:1626-1633 DOI: 10.1056/NEJMoa1010536
  15. http://www.nimr.mrc.ac.uk/documents/mill-hill-essays/Mill_Hill_Essays_2003.pdf
  16. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1471987/

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