Editing Leprosy (section)

== Cause ==

=== ''M. leprae'' and ''M. lepromatosis'' ===
[[File:Mycobacterium leprae in Magnification of 2000X.jpg|thumb|upright=1.3|''M. leprae'', one of the causative agents of leprosy: As an [[acid-fast]] bacterium, ''M. leprae'' appears red when a [[Ziehl–Neelsen stain]] is used]]

''[[Mycobacterium leprae|Mycobacterioum leprae]]'' and ''[[Mycobacterium lepromatosis]]'' are the [[Mycobacterium|mycobacteria]] that cause leprosy.<ref name=Rei2019 /> ''M. lepromatosis'' is a relatively newly identified mycobacterium isolated from a fatal case of [[diffuse lepromatous leprosy]] in 2008.<ref name="New2008">{{cite web|url=https://www.sciencedaily.com/releases/2008/11/081124141047.htm|title=New Leprosy Bacterium: Scientists Use Genetic Fingerprint To Nail 'Killing Organism'|date=28 November 2008|work=ScienceDaily|archive-url=https://web.archive.org/web/20100313064458/https://www.sciencedaily.com/releases/2008/11/081124141047.htm|archive-date=13 March 2010|url-status=live|access-date=31 January 2010}}</ref><ref name="Sherris">{{cite book | veditors = Ryan KU, Ray CJ |title=Sherris Medical Microbiology |url=https://archive.org/details/sherrismedicalmi00ryan |url-access=limited |edition= 4th |pages=[https://archive.org/details/sherrismedicalmi00ryan/page/n468 451]–53 |publisher=McGraw Hill |year=2004 |isbn=978-0-8385-8529-0 |oclc=61405904}}</ref> ''M. lepromatosis'' is indistinguishable clinically from ''M. leprae''.<ref>{{Cite web|url=https://internationaltextbookofleprosy.org/chapter/genomic-insights-biology-and-evolution-leprosy-bacilli|title=Genomics Insights into the Biology and Evolution of Leprosy Bacilli|date=11 February 2016|website=International Textbook of Leprosy|access-date=11 February 2019|archive-date=12 February 2019|archive-url=https://web.archive.org/web/20190212070703/https://internationaltextbookofleprosy.org/chapter/genomic-insights-biology-and-evolution-leprosy-bacilli|url-status=live}}</ref> ''M. leprae'' is an [[Aerobic organism|aerobic]], rod-shaped, acid-fast [[Bacteria|bacterium]] with a waxy [[cell envelope]] characteristic of the genus ''[[Mycobacterium]]''.<ref name="Baron">{{cite book |author=McMurray DN |chapter=Mycobacteria and Nocardia |title=Baron's Medical Microbiology |editor1=Baron S |display-editors=etal |edition= 4th |publisher=Univ of Texas Medical Branch |year=1996 |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1833 |isbn=978-0-9631172-1-2 |oclc=33838234 |url-status=live |archive-url=https://web.archive.org/web/20090212202626/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1833 |archive-date=12 February 2009 }}</ref> ''M. leprae'' and ''M. lepromatosis'' are [[Intracellular parasite#Obligate|obligate intracellular pathogens]] and cannot grow or be [[Cell culture|cultured]] outside of host tissues.<ref name="New2008" /><ref name="Bhattacharya-2002">{{cite journal | vauthors = Bhattacharya S, Vijayalakshmi N, Parija SC | title = Uncultivable bacteria: implications and recent trends towards identification | journal = Indian Journal of Medical Microbiology | volume = 20 | issue = 4 | pages = 174–177 | date = October 2002 | pmid = 17657065 | doi = 10.1016/S0255-0857(21)03184-4 | doi-access = free }}</ref> However, they can be grown using research animals such as mice and [[armadillo]]s.<ref>{{Cite web|url=https://www.who.int/lep/in_vitro/en/|archive-url=https://web.archive.org/web/20200809141738/https://www.who.int/lep/in_vitro/en/|url-status=dead|archive-date=9 August 2020|title=WHO {{!}} Microbiology: culture in vitro|publisher=[[World Health Organization]] (WHO)|access-date=22 July 2019}}</ref><ref>{{Cite web|url=https://internationaltextbookofleprosy.org/chapter/armadillos|title=The Armadillo Model for Leprosy|date=11 February 2016|website=International Textbook of Leprosy|access-date=22 July 2019|archive-date=22 July 2019|archive-url=https://web.archive.org/web/20190722225203/https://internationaltextbookofleprosy.org/chapter/armadillos|url-status=live}}</ref>

Naturally occurring infections have been reported in nonhuman primates (including the African [[Common chimpanzee|chimpanzee]], the [[sooty mangabey]], and the [[cynomolgus]] macaque), armadillos,<ref>Loughry WJ, Truman RW, McDonough CM, Tilak MK, Garnier S, et al. (2009) "Is leprosy spreading among nine-banded armadillos in the southeastern United States?" ''J Wildl Dis'' 45: 144–52.</ref> and [[red squirrel]]s.<ref name="Meredith2004">{{cite journal | vauthors = Meredith A, Del Pozo J, Smith S, Milne E, Stevenson K, McLuckie J | title = Leprosy in red squirrels in Scotland | journal = The Veterinary Record | volume = 175 | issue = 11 | pages = 285–286 | date = September 2014 | pmid = 25234460 | doi = 10.1136/vr.g5680 | s2cid = 207046489 }}</ref> [[Multilocus sequence typing]] of the armadillo ''M. leprae'' strains suggests that they were of human origin for at most a few hundred years.<ref>Monot M, Honoré N, Garnier T, Araoz R, Coppee JY, et al. (2005). "On the origin of leprosy". ''Science'' 308: 1040–42.</ref> Thus, it is suspected that armadillos first acquired the organism incidentally from early European explorers of the Americas.<ref name="Han-2014" /> This incidental transmission was sustained in the armadillo population, and it may be transmitted back to humans, making leprosy a [[zoonotic disease]] (spread between humans and animals).<ref name="Han-2014">{{cite journal | vauthors = Han XY, Silva FJ | title = On the age of leprosy | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 2 | pages = e2544 | date = February 2014 | pmid = 24551248 | pmc = 3923669 | doi = 10.1371/journal.pntd.0002544 | doi-access = free }}</ref>

Red squirrels (''Sciurus vulgaris''), a threatened species in Great Britain, were found to carry leprosy in November 2016.<ref>[https://www.science.org/doi/10.1126/science.aah3783 "Red squirrels in the British Isles are infected with leprosy bacilli"] {{Webarchive|url=https://web.archive.org/web/20220612182108/https://www.science.org/doi/10.1126/science.aah3783|date=12 June 2022}}, Dr. Andrej Benjak, Prof Anna Meredith and others. ''Science'', 11 November 2016. [https://www.science.org/doi/10.1126/science.aah3783] . Retrieved 11 November 2016.</ref> It has been suggested that the trade in red squirrel fur, highly prized in the medieval period and intensively traded, may have been responsible for the leprosy epidemic in medieval Europe.<ref name="ScienceDaily" /> A pre-[[Norman England|Norman]] era skull excavated in [[Hoxne|Hoxne, Suffolk]], in 2017 was found to carry DNA from a strain of ''M. leprae'' which closely matched the strain carried by modern red squirrels on [[Brownsea Island]].<ref name="ScienceDaily">{{cite web|url=https://www.sciencedaily.com/releases/2017/10/171025103109.htm|title=Could squirrel fur trade have contributed to England's medieval leprosy outbreak?|website=ScienceDaily|access-date=21 November 2018|archive-date=22 November 2018|archive-url=https://web.archive.org/web/20181122005829/https://www.sciencedaily.com/releases/2017/10/171025103109.htm|url-status=live}}</ref><ref>{{cite journal | vauthors = Inskip S, Taylor GM, Anderson S, Stewart G | title = Leprosy in pre-Norman Suffolk, UK: biomolecular and geochemical analysis of the woman from Hoxne | journal = Journal of Medical Microbiology | volume = 66 | issue = 11 | pages = 1640–1649 | date = November 2017 | pmid = 28984227 | doi = 10.1099/jmm.0.000606 | s2cid = 33997231 | doi-access = free }}</ref>

=== Risk factors ===
The greatest risk factor for developing leprosy is contact with another person infected by leprosy.<ref name="WHO Fact Sheet" /> People who are exposed to a person who has leprosy are 5–8 times more likely to develop leprosy than members of the general population.<ref name="Schreuder2016">{{cite journal | vauthors = Schreuder PA, Noto S, Richardus JH | title = Epidemiologic trends of leprosy for the 21st century | journal = Clinics in Dermatology | volume = 34 | issue = 1 | pages = 24–31 | date = January 2016 | pmid = 26773620 | doi = 10.1016/j.clindermatol.2015.11.001 }}</ref> Leprosy occurs more commonly among those living in poverty.<ref name=Aka2012 /> Not all people who are infected with ''M. leprae'' develop symptoms.<ref name="Penna-2016">{{cite journal | vauthors = Penna ML, Penna GO, Iglesias PC, Natal S, Rodrigues LC | title = Anti-PGL-1 Positivity as a Risk Marker for the Development of Leprosy among Contacts of Leprosy Cases: Systematic Review and Meta-analysis | journal = PLOS Neglected Tropical Diseases | volume = 10 | issue = 5 | pages = e0004703 | date = May 2016 | pmid = 27192199 | pmc = 4871561 | doi = 10.1371/journal.pntd.0004703 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Alcaïs A, Mira M, Casanova JL, Schurr E, Abel L | title = Genetic dissection of immunity in leprosy | journal = Current Opinion in Immunology | volume = 17 | issue = 1 | pages = 44–48 | date = February 2005 | pmid = 15653309 | doi = 10.1016/j.coi.2004.11.006 }}</ref>

Conditions that reduce immune function, such as malnutrition, other illnesses, or genetic mutations, may increase the risk of developing leprosy.<ref name=Schreuder2016 /> Infection with [[HIV]] does not appear to increase the risk of developing leprosy.<ref>{{cite journal | vauthors = Lockwood DN, Lambert SM | title = Human immunodeficiency virus and leprosy: an update | journal = Dermatologic Clinics | volume = 29 | issue = 1 | pages = 125–128 | date = January 2011 | pmid = 21095536 | doi = 10.1016/j.det.2010.08.016 }}</ref> Certain genetic factors in the person exposed have been associated with developing lepromatous or tuberculoid leprosy.<ref>{{Cite web|url=https://www.internationaltextbookofleprosy.org/chapter/epidemiology-leprosy|title=Epidemiology of Leprosy|date=11 February 2016|website=International Textbook of Leprosy|access-date=30 July 2019|archive-date=23 July 2019|archive-url=https://web.archive.org/web/20190723224457/https://www.internationaltextbookofleprosy.org/chapter/epidemiology-leprosy|url-status=live}}</ref>

=== Transmission ===
Transmission of leprosy occurs during close contact with those who are infected.<ref name="WHO Fact Sheet" /> Transmission of leprosy is through the upper [[respiratory tract]].<ref name="WHO2018Tx" /><ref>{{cite journal | vauthors = Chavarro-Portillo B, Soto CY, Guerrero MI | title = Mycobacterium leprae's evolution and environmental adaptation | journal = Acta Tropica | volume = 197 | pages = 105041 | date = September 2019 | pmid = 31152726 | doi = 10.1016/j.actatropica.2019.105041 | s2cid = 173188912 }}</ref> Older research suggested the skin as the main route of transmission, but research has increasingly favored the respiratory route.<ref>{{cite journal | vauthors = Eichelmann K, González González SE, Salas-Alanis JC, Ocampo-Candiani J | title = Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment | journal = Actas Dermo-Sifiliograficas | volume = 104 | issue = 7 | pages = 554–563 | date = September 2013 | pmid = 23870850 | doi = 10.1016/j.adengl.2012.03.028 | s2cid = 3442319 | doi-access = free }}</ref> Transmission occurs through inhalation of bacilli present in upper airway secretion.<ref>{{cite journal | vauthors = Joel Carlos Lastória JC, Milanez Morgado de Abreu MA | title = Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - Part 1 | journal = An Bras Dermatol | volume = 89 | issue = 2 | pages = 205–218 | date = Mar–Apr 2014 | pmid = 24770495| doi = 10.1590/abd1806-4841.20142450 | pmc = 4008049 | s2cid = | doi-access = free }}</ref>

Leprosy is not sexually transmitted and is not spread through pregnancy to the unborn child.<ref name="WHO Fact Sheet" /><ref name="CDC2013T" /> The majority (95%) of people who are exposed to ''M. leprae'' do not develop leprosy; casual contact such as shaking hands and sitting next to someone with leprosy does not lead to transmission.<ref name="WHO Fact Sheet" /><ref name="CDC2013T3">{{cite web|url=https://www.cdc.gov/leprosy/transmission/|title=Hansen's Disease (Leprosy) Transmission|date=29 April 2013|website=cdc.gov|archive-url=https://web.archive.org/web/20150313120028/http://www.cdc.gov/leprosy/transmission/|archive-date=13 March 2015|access-date=28 February 2015|url-status=live}}</ref> People are considered non-infectious 72 hours after starting appropriate multi-drug therapy.<ref>{{cite journal | vauthors = Lockwood DN, Kumar B | title = Treatment of leprosy | journal = BMJ | volume = 328 | issue = 7454 | pages = 1447–1448 | date = June 2004 | pmid = 15205269 | pmc = 428501 | doi = 10.1136/bmj.328.7454.1447 }}</ref> Two exit routes of ''M. leprae'' from the human body that are often described are the skin and the nasal mucosa, although their relative importance is not clear. Lepromatous cases show large numbers of organisms deep in the [[dermis]], but whether they reach the skin surface in sufficient numbers is doubtful.<ref name="news-medical" /> Humans can acquire a leprosy infection from armadillos by handling them or consuming armadillo meat.<ref>{{Cite news |last=Harris |first=Gardiner |date=2011-04-27 |title=Armadillos Can Transmit Leprosy to Humans, Federal Researchers Confirm |url=https://www.nytimes.com/2011/04/28/health/28leprosy.html |access-date=2025-03-15 |work=The New York Times |language=en-US |issn=0362-4331}}</ref><ref>{{Cite news |last=Guiden |first=Mary |date=2018-06-29 |title=New evidence that wild armadillos spread leprosy to humans |url=https://cvmbs.source.colostate.edu/new-evidence-that-wild-armadillos-spread-leprosy-to-humans/ |archive-url=https://web.archive.org/web/20241128000723/https://cvmbs.source.colostate.edu/new-evidence-that-wild-armadillos-spread-leprosy-to-humans/ |archive-date=28 November 2024 |access-date=2025-03-15 |work=News from the College of Veterinary Medicine and Biomedical Sciences |language=en-US |url-status=live }}</ref>  The mechanism is not fully understood.<ref name="CDC2013T" /><ref name="Truman 2011">{{cite journal | vauthors = Truman RW, Singh P, Sharma R, Busso P, Rougemont J, Paniz-Mondolfi A, Kapopoulou A, Brisse S, Scollard DM, Gillis TP, Cole ST | title = Probable zoonotic leprosy in the southern United States | journal = The New England Journal of Medicine | volume = 364 | issue = 17 | pages = 1626–1633 | date = April 2011 | pmid = 21524213 | pmc = 3138484 | doi = 10.1056/NEJMoa1010536 }}</ref><ref name="CDC2013T2">{{cite web|url=https://www.cdc.gov/leprosy/transmission/|title=Hansen's Disease (Leprosy) Transmission|date=29 April 2013|website=cdc.gov|archive-url=https://web.archive.org/web/20150313120028/http://www.cdc.gov/leprosy/transmission/|archive-date=13 March 2015|url-status=live|access-date=28 February 2015}}</ref>

=== Genetics ===
{| class="wikitable" style="float: right; margin-left:15px; text-align:center"
|-
! Name
! [[Locus (genetics)|Locus]]
! [[OMIM]]
! Gene
|-
| LPRS1
| 10p13
| {{OMIM|609888||none}}
|
|-
| LPRS2
| 6q25
| {{OMIM|607572||none}}
| ''[[PARK2]], [[PACRG]]
|-'
<!--\
] -->
| LPRS3
| 4q32
| {{OMIM|246300||none}}
| ''[[TLR2]]''
|-
| LPRS4
| 6p21.3
| {{OMIM|610988||none}}
| ''[[Lymphotoxin alpha|LTA]]''
|-
| LPRS5
| 4p14
| {{OMIM|613223||none}}
| ''[[TLR1]]''
|-
| LPRS6
| 13q14.11
| {{OMIM|613407||none}}
|
|}
Not all people infected or exposed to ''M. leprae'' develop leprosy, and genetic factors are suspected to play a role in susceptibility to an infection.<ref name="Cambri-2018">{{cite journal | vauthors = Cambri G, Mira MT | title = Genetic Susceptibility to Leprosy-From Classic Immune-Related Candidate Genes to Hypothesis-Free, Whole Genome Approaches | journal = Frontiers in Immunology | volume = 9 | pages = 1674 | date = 20 July 2018 | pmid = 30079069 | pmc = 6062607 | doi = 10.3389/fimmu.2018.01674 | doi-access = free }}</ref> Cases of leprosy often cluster in families, and several genetic variants have been identified.<ref name="Cambri-2018" /> In many who are exposed, the immune system can eliminate the leprosy bacteria during the early infection stage before severe symptoms develop.<ref>{{cite book| vauthors = Cook GC |title=Manson's tropical diseases|date=2009|publisher=Saunders|location=[Edinburgh]|isbn=978-1-4160-4470-3|page=1056|edition= 22nd|url=https://books.google.com/books?id=CF2INI0O6l0C&pg=PA1056|url-status=live|archive-url=https://web.archive.org/web/20170904030040/https://books.google.com/books?id=CF2INI0O6l0C&pg=PA1056|archive-date=4 September 2017}}</ref> A genetic defect in [[cell-mediated immunity]] may cause a person to be susceptible to develop leprosy symptoms after exposure to the bacteria.<ref name="Buschman-2004" /> The region of [[DNA]] responsible for this variability is also involved in [[Parkinson's disease]], giving rise to current speculation that the two disorders may be linked at the biochemical level.<ref name="Buschman-2004">{{cite journal |last1=Buschman |first1=Ellen |last2=Skamene |first2=Emil |title=Linkage of leprosy susceptibility to Parkinson's disease genes |journal=International Journal of Leprosy and Other Mycobacterial Diseases |volume=72 |issue=2 |pages=169–170 |date=June 2004 |doi=10.1489/1544-581X(2004)072<0169:LOLSTP>2.0.CO;2 |doi-broken-date=1 November 2024 |url=http://ijl.ilsl.br/detalhe_artigo.php?id=OTg%3D |pmid=15301585 |s2cid=43103579 }}</ref>