Mycobacterium leprae

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Mycobacterium leprae
Microphotograph of Mycobacterium leprae taken from a skin lesion. Source: CDC
Microphotograph of Mycobacterium leprae taken from a skin lesion. Source: CDC
Scientific classification
Kingdom: Bacteria
Phylum: Actinobacteria
Order: Actinomycetales
Suborder: Corynebacterineae
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: M. leprae
Binomial name
Mycobacterium leprae
Hansen, 1874

Mycobacterium leprae, also known as Hansen’s bacillus, is the bacterium that causes leprosy (Hansen's disease).[1] It is an intracellular, pleomorphic, acid fast bacterium.[2] M. leprae is a Gram-positive, aerobic rod-shaped (bacillus) surrounded by the characteristic waxy coating unique to mycobacteria. In size and shape, it closely resembles Mycobacterium tuberculosis. Due to its thick waxy coating, M. leprae stains with a carbol fuscin rather than with the traditional Gram stain. The culture takes several weeks to mature.

Optical microscopy shows M. leprae in clumps, rounded masses, or in groups of bacilli side by side.

It was discovered in 1873 by the Norwegian physician Gerhard Armauer Hansen, who was searching for the bacteria in the skin nodules of patients with leprosy. It was the first bacterium to be identified as causing disease in man. [3][4]

The organism has never been successfully grown on an artificial cell culture media.[2] Instead it has been grown in mouse foot pads and more recently in nine-banded armadillos. This can be used as a diagnostic test for the presence of bacillus in body lesions of suspected leprosy patients. The bacterium can infect armadillos, so it is studied in them. The difficulty in culturing the organism appears to be due to the fact that the organism is an obligate intra-cellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes members of the Mycobacterium genus difficult to destroy is apparently also the reason for the extremely slow replication rate.

Virulence factors include a waxy exterior coating, formed by the production of mycolic acids unique to Mycobacterium.

M. leprae was sensitive to dapsone (diaminodiphenylsulfone, the first effective treatment which was discovered for leprosy in the 1940's), but resistance against this antibiotic has developed over time. Therapy with dapsone alone is now strongly contraindicated. Currently, a multidrug treatment (MDT) is recommended by the World Health Organization, including dapsone, rifampicin and clofazimine. In patients receiving the MDT, a high proportion of the bacilli die within a short amount of time without immediate relief of symptoms. This suggests that many symptoms of leprosy must be due in part to the presence of dead cells.

Mycobacterium leprae genome

Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory.[5] Comparing the genome sequence of Mycobacterium leprae with that of Mycobacterium tuberculosis provides clear explanations for these properties and reveal an extreme case of reductive evolution. Less than half of the genome contains functional genes. Gene deletion and decay appear to have eliminated many important metabolic activities, including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits. [6]

The genome sequence of a strain of M. leprae, originally isolated in Tamil Nadu and designated TN, has been completed recently. The sequence was obtained by a combined approach, employing automated DNA sequence analysis of selected cosmids and whole-genome 'shotgun' clones. After the finishing process, the genome sequence was found to contain 3,268,203 base pairs (bp), and to have an average G+C content of 57.8%, values much lower than the corresponding values for M. tuberculosis, which are 4, 441,529 bp and 65.6% G+C. There are 1500 genes which are common to both M. leprae and M. tuberculosis. The comparative analysis suggests that both mycobacteria derived from a common ancestor and, at one stage, had gene pools of similar size. Downsizing from a genome of 4.42 Mb, such as that of M. tuberculosis, to one of 3.27 Mb would account for the loss of some 1200 protein coding sequences. There is evidence that many of the genes that were present in the genome of M. leprae have truly been lost. [7]

Information from the completed genome can be useful to develop diagnostic skin tests, understanding the mechanism of nerve damage, drug resistance and to identify novel drug targets for rational design of new therapeutic regimens and drugs to treat leprosy and its complications.

Treatment

Antimicrobial regimen

  • 1. Multibacillary Leprosy (Skin smear positive) [8]
  • Preferred regimen: Dapsone 100 mg/day PO AND Rifampin 600 mg PO 4 times per week AND Clofazimine 50 mg/day PO supplemented by Clofazimine 300 mg PO loading dose monthly
  • Pediatric regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 450 mg PO <35 kg, 300 mg PO <20 kg, 150 mg PO <12 kg
  • Length of treatment: 12-24 months
  • 2. Paucibacillary Leprosy (Skin Smear negative)
  • Preferred regimen: Rifampin 600 mg PO once a month for 6 months AND Dapsone 100 mg/day PO for 6 months
  • 3. Erythema Nodosum Leprosum (ENL)
  • Continue anti-leprosy drugs throughout
  • 3.1 Mild
  • Preferred regimen: Rest affect limb, analgesics, follow-up q2wks, check for iridocyclitis; Chloroquine OR Aspirin may be useful
  • 3.2 Severe (numerous nodules + fever, ulcerating/pustular ENL, visceral involvement, nodules + neuritis, recurrent ENL)
  • Preferred regimen: Prednisolone 30-40 mg/day PO (not to exceed 1 mg/kg) for 1-2 weeks THEN taper over 12 weeks
  • Alternative regimen (1): (If unresponsive to corticosteroids or if risk of corticosteroids prevent administration) Start Clofazimine 100 mg PO TID for maximum of 12 weeks, taper the dose to 100 mg PO BID for 12 weeks THEN 100 mg qd for 12-24 weeks
  • Alternative regimen (2): (if not contraindicated) Thalidomide 200-400 mg/day PO, reduced to 50-100 mg/day after 1-2 weeks
  • 4. Reversal Reaction
  • Preferred regimen: Prednisolone start with 40 mg/day PO THEN taper by 10 mg twice a week for 12 weeks

Prophylaxis

  • 1.1 35 kg and over
  • Preferred regimen: Rifampin 600 mg PO single dose
  • 1.2 less than 35 kg
  • Preferred regimen: Rifampin 450 mg PO single dose
  • 2. Pediatric
  • 2.1 for children older than 9 yrs
  • Preferred regimen: Rifampin 450 mg PO single dose
  • 2.2 for children aged 5 to 9 yrs
  • Preferred regimen: Rifampin 300 mg PO single dose

External links

References

  1. Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, 451-3. ISBN 0838585299. 
  2. 2.0 2.1 McMurray DN (1996). Mycobacteria and Nocardia. in: Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch. ISBN 0-9631172-1-1. 
  3. Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)" (in Norwegian). Norsk Mag. Laegervidenskaben 4: pp. 1–88.
  4. Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr Nor Laegeforen 122 (7): 708-9. PMID 11998735.
  5. Truman RW, Krahenbuhl JL (2001). "Viable M. leprae as a research reagent". Int. J. Lepr. Other Mycobact. Dis. 69 (1): 1-12. PMID 11480310.
  6. Cole ST, Brosch R, Parkhill J, et al (1998). "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence". Nature 393 (6685): 537-44. doi:10.1038/31159. PMID 9634230.
  7. Cole ST, Eiglmeier K, Parkhill J, et al (2001). "Massive gene decay in the leprosy bacillus". Nature 409 (6823): 1007-11. doi:10.1038/35059006. PMID 11234002.
  8. Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580. 
  9. Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580. 


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