Leprosy pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
==Pathophysiology== | |||
The exact mechanism of transmission of leprosy is not known: prolonged close contact and transmission by nasal droplet have both been proposed, and, while the latter fits the pattern of disease, both remain unproved.<ref>{{cite journal |author=Reich CV |title=Leprosy: cause, transmission, and a new theory of pathogenesis |journal=Rev. Infect. Dis. |volume=9 |issue=3 |pages=590-4 |year=1987 |pmid=3299638 |doi=}}</ref> The only other animals besides humans to contract leprosy are the armadillo, chimpanzees, sooty mangabeys, and Crab-eating Macaque]].<ref>{{cite journal |author=Rojas-Espinosa O, Løvik M |title=Mycobacterium leprae and Mycobacterium lepraemurium infections in domestic and wild animals |journal=Rev. - Off. Int. Epizoot. |volume=20 |issue=1 |pages=219-51 |year=2001 |pmid=11288514 |doi=}}</ref> The bacterium can also be grown in the laboratory by injection into the footpads of mice.<ref>{{cite journal |author=Hastings RC, Gillis TP, Krahenbuhl JL, Franzblau SG |title=Leprosy |journal=Clin. Microbiol. Rev. |volume=1 |issue=3 |pages=330-48 |year=1988 |pmid=3058299 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=3058299}}</ref> There is evidence that not all people who are infected with ''M. leprae'' develop leprosy, and genetic factors have long been thought to play a role, due to the observation of clustering of leprosy around certain families, and the failure to understand why certain individuals develop lepromatous leprosy while others develop other types of leprosy.<ref>{{cite journal |author=Alcaïs A, Mira M, Casanova JL, Schurr E, Abel L |title=Genetic dissection of immunity in leprosy |journal=Curr. Opin. Immunol. |volume=17 |issue=1 |pages=44-8 |year=2005 |pmid=15653309 |doi=10.1016/j.coi.2004.11.006}}</ref> However, the role of genetic factors is not clear in determining this clinical expression. In addition, malnutrition and possible prior exposure to other environmental [[mycobacteria]] may play a role in development of the overt disease. | |||
The most widely-held belief is that the disease is transmitted by contact between infected persons and healthy persons.<ref>{{cite journal |author=Kaur H, Van Brakel W |title=Dehabilitation of leprosy-affected people--a study on leprosy-affected beggars |journal=Leprosy review |volume=73 |issue=4 |pages=346-55 |year=2002 |pmid=12549842 |doi=}}</ref> In general, closeness of contact is related to the dose of infection, which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one that is easily identified, although the actual incidence among contacts and the relative risk for them appear to vary considerably in different studies. In [[Incidence (epidemiology)|incidence studies]], infection rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu, Philippines<ref name=Doull_1942>{{cite journal | author = Doull JA, Guinto RA, Rodriguez RS, et al. | title = The incidence of leprosy in Cordova and Talisay, Cebu, Philippines | journal = International Journal of Leprosy | year = 1942 | volume = 10 | pages = 107–131 | url= }}</ref> to 55.8 per 1000 per year in a part of Southern India.<ref name=Noordeen_1978>{{cite journal |author=Noordeen S, Neelan P |title=Extended studies on chemoprophylaxis against leprosy |journal=Indian J Med Res |volume=67 |issue= |pages=515-27 |year=1978 |pmid=355134}}</ref> | |||
Two exit routes of ''M. leprae'' from the human body often described are the skin and the nasal mucosa, although their relative importance is not clear. It is true that lepromatous cases show large numbers of organisms deep down in the [[dermis]]. However, whether they reach the skin surface in sufficient numbers is doubtful. Although there are reports of [[Acid-fast|acid-fast bacilli]] being found in the desquamating [[epithelium]] of the skin, Weddell ''et al'' have reported that they could not find any acid-fast bacilli in the [[epidermis]], even after examining a very large number of specimens from patients and contacts.<ref name=Weddell_1963>{{cite journal |author=Weddell G, Palmer E |title=The pathogenesis of leprosy. An experimental approach |journal=Leprosy Review |volume=34 |issue= |pages=57-61 |year=1963 |pmid=13999438}}</ref> In a recent study, Job ''et al'' found fairly large numbers of ''M. leprae'' in the superficial [[keratin]] layer of the skin of lepromatous leprosy patients, suggesting that the organism could exit along with the [[Sebaceous gland|sebaceous]] secretions.<ref name=Job_1999>{{cite journal |author=Job C, Jayakumar J, Aschhoff M |title="Large numbers" of Mycobacterium leprae are discharged from the intact skin of lepromatous patients; a preliminary report |journal=Int J Lepr Other Mycobact Dis |volume=67 |issue=2 |pages=164-7 |year=1999 |pmid=10472371}}</ref> | |||
The importance of the [[nasal mucosa]] was recognized as early as 1898 by Schäffer, particularly that of the ulcerated mucosa. <ref name=Schaffer_1898>''Arch Dermato Syphilis'' 1898; 44:159–174</ref> The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000.<ref name=Shepard_1960>{{cite journal |author=Shepard C |title=Acid-fast bacilli in nasal excretions in leprosy, and results of inoculation of mice |journal=Am J Hyg |volume=71 |issue= |pages=147-57 |year=1960 |pmid=14445823}}</ref> Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose.<ref name=Pedley_1973>{{cite journal |author=Pedley J |title=The nasal mucus in leprosy |journal=Lepr Rev |volume=44 |issue=1 |pages=33-5 |year=1973 |pmid=4584261}}</ref> Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.<ref name=Davey_1974>{{cite journal |author=Davey T, Rees R |title=The nasal dicharge in leprosy: clinical and bacteriological aspects |journal=Lepr Rev |volume=45 |issue=2 |pages=121-34 |year=1974 |pmid=4608620}}</ref> | |||
The entry route of ''M. leprae'' into the human body is also not definitely known. The two seriously considered are the skin and the upper respiratory tract. While older research dealt with the skin route, recent research has increasingly favored the respiratory route. Rees and McDougall succeeded in the experimental transmission of leprosy through aerosols containing ''M. leprae'' in immune-suppressed mice, suggesting a similar possibility in humans.<ref name=Rees_1977>{{cite journal |author=Rees R, McDougall A |title=Airborne infection with Mycobacterium leprae in mice |journal=J Med Microbiol |volume=10 |issue=1 |pages=63-8 |year=1977 |pmid=320339}}</ref> Successful results have also been reported on experiments with [[nude mice]] when ''M. leprae'' were introduced into the nasal cavity by topical application. <ref name=Chehl_1985>{{cite journal |author=Chehl S, Job C, Hastings R |title=Transmission of leprosy in nude mice |journal=Am J Trop Med Hyg |volume=34 |issue=6 |pages=1161-6 |year=1985 |pmid=3914846}}</ref> In summary, entry through the respiratory route appears the most probable route, although other routes, particularly broken skin, cannot be ruled out. The CDC notes the following assertion about the transmission of the disease: "''Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that ''M. leprae'' is usually spread from person to person in respiratory droplets''."<ref name=CDC_2005>{{cite web | title = Hansen's Disease (Leprosy) | work = Technical Information | publisher = Centers for Disease Control and Prevention | date = 2005-10-12 | url = http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hansens_t.htm | accessdate = 2007-03-22}}</ref> | |||
In leprosy both the reference points for measuring the [[incubation period]] and the times of infection and onset of disease are difficult to define; the former because of the lack of adequate immunological tools and the latter because of the disease's slow onset. Even so, several investigators have attempted to measure the incubation period for leprosy. The minimum incubation period reported is as short as a few weeks and this is based on the very occasional occurrence of leprosy among young infants. <ref name=Montestruc_1954>{{cite journal |author=Montestruc E, Berdonneau R |title=2 New cases of leprosy in infants in Martinique. |journal=Bull Soc Pathol Exot Filiales |volume=47 |issue=6 | language = French | pages=781-3 |year=1954 |pmid=14378912}}</ref> The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between 3 to 5 years. | |||
==References== | ==References== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
The exact mechanism of transmission of leprosy is not known: prolonged close contact and transmission by nasal droplet have both been proposed, and, while the latter fits the pattern of disease, both remain unproved.[1] The only other animals besides humans to contract leprosy are the armadillo, chimpanzees, sooty mangabeys, and Crab-eating Macaque]].[2] The bacterium can also be grown in the laboratory by injection into the footpads of mice.[3] There is evidence that not all people who are infected with M. leprae develop leprosy, and genetic factors have long been thought to play a role, due to the observation of clustering of leprosy around certain families, and the failure to understand why certain individuals develop lepromatous leprosy while others develop other types of leprosy.[4] However, the role of genetic factors is not clear in determining this clinical expression. In addition, malnutrition and possible prior exposure to other environmental mycobacteria may play a role in development of the overt disease.
The most widely-held belief is that the disease is transmitted by contact between infected persons and healthy persons.[5] In general, closeness of contact is related to the dose of infection, which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one that is easily identified, although the actual incidence among contacts and the relative risk for them appear to vary considerably in different studies. In incidence studies, infection rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu, Philippines[6] to 55.8 per 1000 per year in a part of Southern India.[7]
Two exit routes of M. leprae from the human body often described are the skin and the nasal mucosa, although their relative importance is not clear. It is true that lepromatous cases show large numbers of organisms deep down in the dermis. However, whether they reach the skin surface in sufficient numbers is doubtful. Although there are reports of acid-fast bacilli being found in the desquamating epithelium of the skin, Weddell et al have reported that they could not find any acid-fast bacilli in the epidermis, even after examining a very large number of specimens from patients and contacts.[8] In a recent study, Job et al found fairly large numbers of M. leprae in the superficial keratin layer of the skin of lepromatous leprosy patients, suggesting that the organism could exit along with the sebaceous secretions.[9]
The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, particularly that of the ulcerated mucosa. [10] The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000.[11] Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose.[12] Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.[13]
The entry route of M. leprae into the human body is also not definitely known. The two seriously considered are the skin and the upper respiratory tract. While older research dealt with the skin route, recent research has increasingly favored the respiratory route. Rees and McDougall succeeded in the experimental transmission of leprosy through aerosols containing M. leprae in immune-suppressed mice, suggesting a similar possibility in humans.[14] Successful results have also been reported on experiments with nude mice when M. leprae were introduced into the nasal cavity by topical application. [15] In summary, entry through the respiratory route appears the most probable route, although other routes, particularly broken skin, cannot be ruled out. The CDC notes the following assertion about the transmission of the disease: "Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is usually spread from person to person in respiratory droplets."[16]
In leprosy both the reference points for measuring the incubation period and the times of infection and onset of disease are difficult to define; the former because of the lack of adequate immunological tools and the latter because of the disease's slow onset. Even so, several investigators have attempted to measure the incubation period for leprosy. The minimum incubation period reported is as short as a few weeks and this is based on the very occasional occurrence of leprosy among young infants. [17] The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between 3 to 5 years.
References
- ↑ Reich CV (1987). "Leprosy: cause, transmission, and a new theory of pathogenesis". Rev. Infect. Dis. 9 (3): 590–4. PMID 3299638.
- ↑ Rojas-Espinosa O, Løvik M (2001). "Mycobacterium leprae and Mycobacterium lepraemurium infections in domestic and wild animals". Rev. - Off. Int. Epizoot. 20 (1): 219–51. PMID 11288514.
- ↑ Hastings RC, Gillis TP, Krahenbuhl JL, Franzblau SG (1988). "Leprosy". Clin. Microbiol. Rev. 1 (3): 330–48. PMID 3058299.
- ↑ Alcaïs A, Mira M, Casanova JL, Schurr E, Abel L (2005). "Genetic dissection of immunity in leprosy". Curr. Opin. Immunol. 17 (1): 44–8. doi:10.1016/j.coi.2004.11.006. PMID 15653309.
- ↑ Kaur H, Van Brakel W (2002). "Dehabilitation of leprosy-affected people--a study on leprosy-affected beggars". Leprosy review. 73 (4): 346–55. PMID 12549842.
- ↑ Doull JA, Guinto RA, Rodriguez RS; et al. (1942). "The incidence of leprosy in Cordova and Talisay, Cebu, Philippines". International Journal of Leprosy. 10: 107–131.
- ↑ Noordeen S, Neelan P (1978). "Extended studies on chemoprophylaxis against leprosy". Indian J Med Res. 67: 515–27. PMID 355134.
- ↑ Weddell G, Palmer E (1963). "The pathogenesis of leprosy. An experimental approach". Leprosy Review. 34: 57–61. PMID 13999438.
- ↑ Job C, Jayakumar J, Aschhoff M (1999). ""Large numbers" of Mycobacterium leprae are discharged from the intact skin of lepromatous patients; a preliminary report". Int J Lepr Other Mycobact Dis. 67 (2): 164–7. PMID 10472371.
- ↑ Arch Dermato Syphilis 1898; 44:159–174
- ↑ Shepard C (1960). "Acid-fast bacilli in nasal excretions in leprosy, and results of inoculation of mice". Am J Hyg. 71: 147–57. PMID 14445823.
- ↑ Pedley J (1973). "The nasal mucus in leprosy". Lepr Rev. 44 (1): 33–5. PMID 4584261.
- ↑ Davey T, Rees R (1974). "The nasal dicharge in leprosy: clinical and bacteriological aspects". Lepr Rev. 45 (2): 121–34. PMID 4608620.
- ↑ Rees R, McDougall A (1977). "Airborne infection with Mycobacterium leprae in mice". J Med Microbiol. 10 (1): 63–8. PMID 320339.
- ↑ Chehl S, Job C, Hastings R (1985). "Transmission of leprosy in nude mice". Am J Trop Med Hyg. 34 (6): 1161–6. PMID 3914846.
- ↑ "Hansen's Disease (Leprosy)". Technical Information. Centers for Disease Control and Prevention. 2005-10-12. Retrieved 2007-03-22.
- ↑ Montestruc E, Berdonneau R (1954). "2 New cases of leprosy in infants in Martinique". Bull Soc Pathol Exot Filiales (in French). 47 (6): 781–3. PMID 14378912.