杜克雷嗜血杆菌具有高度传染性。在一项试验模型中,仅接种 1 个集落形成单位的菌株便导致 50% 的志愿者形成丘疹。[22]Al-Tawfiq JA, Harezlak J, Katz BP, et al. Cumulative experience with Haemophilus ducreyi 35000 in the human model of experimental infection. Sex Transm Dis. 2000 Feb;27(2):111-4.http://www.ncbi.nlm.nih.gov/pubmed/10676978?tool=bestpractice.com 另一项研究发现同已经感染病原体的男性接触的妇女有70%会发病。[23]D'Costa LJ, Plummer FA, Bowmer I, et al. Prostitutes are a major reservoir of sexually transmitted diseases in Nairobi, Kenya. Sex Transm Dis. 1985 Apr-Jun;12(2):64-7.http://www.ncbi.nlm.nih.gov/pubmed/4002094?tool=bestpractice.com[24]Ronald AR, Plummer FA. Chancroid and granuloma inguinale. Clin Lab Med. 1989 Sep;9(3):535-43.http://www.ncbi.nlm.nih.gov/pubmed/2676322?tool=bestpractice.com 该病感染后的潜伏期为 4-7 天。杜克雷嗜血杆菌的传染性持续时间较短,并且需要频繁的更换性伴侣才能维持其在人群中的传染性。[10]Steen R. Eradicating chancroid. Bull World Health Organ. 2001;79(9):818-26.https://scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862001000900006&lng=en&nrm=iso&tlng=enhttp://www.ncbi.nlm.nih.gov/pubmed/11584729?tool=bestpractice.com[23]D'Costa LJ, Plummer FA, Bowmer I, et al. Prostitutes are a major reservoir of sexually transmitted diseases in Nairobi, Kenya. Sex Transm Dis. 1985 Apr-Jun;12(2):64-7.http://www.ncbi.nlm.nih.gov/pubmed/4002094?tool=bestpractice.com[25]Plummer FA, D'Costa LJ, Nsanze H, et al. Epidemiology of chancroid and Haemophilus ducreyi in Nairobi, Kenya. Lancet. 1983 Dec 3;2(8362):1293-5.http://www.ncbi.nlm.nih.gov/pubmed/6139629?tool=bestpractice.com 基于这个理由,性工作者在该病的流行环节中已经成为重要的宿主。
该病发病机制如下:
皮肤能够为防止感染提供一道很好的屏障,可经撕裂或磨损而破坏。杜克雷嗜血杆菌可从破损处进入,并最先攻击黏膜上皮。[26]Spinola SM, Bauer ME, Munson RS Jr. Immunopathogenesis of Haemophilus ducreyi infection (chancroid). Infect Immun. 2002 Apr;70(4):1667-76.http://iai.asm.org/content/70/4/1667.longhttp://www.ncbi.nlm.nih.gov/pubmed/11895928?tool=bestpractice.com[27]Bauer ME, Spinola SM. Localization of Haemophilus ducreyi at the pustular stage of disease in the human model of infection. Infect Immun. 2000 Apr;68(4):2309-14.http://iai.asm.org/content/68/4/2309.longhttp://www.ncbi.nlm.nih.gov/pubmed/10722634?tool=bestpractice.com
在病原体入口处,黏膜上皮被多形核白细胞及巨噬细胞浸润。 这导致白介素2(IL-2)及IL-6的分泌,促使单核细胞进入真皮层,包括CD4细胞。[15]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57.http://cmr.asm.org/content/2/2/137.longhttp://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com[26]Spinola SM, Bauer ME, Munson RS Jr. Immunopathogenesis of Haemophilus ducreyi infection (chancroid). Infect Immun. 2002 Apr;70(4):1667-76.http://iai.asm.org/content/70/4/1667.longhttp://www.ncbi.nlm.nih.gov/pubmed/11895928?tool=bestpractice.com
这种炎症反应表现为在红斑的基底面出现1个或以上的无痛性丘疹,在随后的数天时间里该炎症反应自发性缓解或进展成脓疱甚至溃烂。 女性身上的丘疹更容易自发性缓解,但男性身上丘疹往往发展成脓疱。[28]Bong CT, Harezlak J, Katz BP, et al. Men are more susceptible than women to pustule formation in the experimental model of Haemophilus ducreyi infection. Sex Transm Dis. 2002 Feb;29(2):114-8.http://www.ncbi.nlm.nih.gov/pubmed/11818898?tool=bestpractice.com[29]Spinola SM, Bong CT, Faber AL, et al. Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection. Infect Immun. 2003 Nov;71(11):6658-63.http://iai.asm.org/content/71/11/6658.longhttp://www.ncbi.nlm.nih.gov/pubmed/14573692?tool=bestpractice.com
如果不进行治疗,溃疡缓慢进展且持续数月,导致永久性瘢痕形成。[15]Morse SA. Chancroid and Haemophilus ducreyi. Clin Microbiol Rev. 1989 Apr;2(2):137-57.http://cmr.asm.org/content/2/2/137.longhttp://www.ncbi.nlm.nih.gov/pubmed/2650859?tool=bestpractice.com
杜克雷嗜血杆菌具有高传染性的原因尚不完全清楚。有许多可能的毒力因子介导最初的感染(菌毛和外膜蛋白),导致组织损伤(溶血素、热休克蛋白、脂多糖),使得逃脱并抵抗宿主的防御(脂多糖、抗 α-防御素和 β-防御素)。[1]Trees DL, Morse SA. Chancroid and Haemophilus ducreyi: an update. Clin Microbiol Rev. 1995 Jul;8(3):357-75.http://cmr.asm.org/content/8/3/357.longhttp://www.ncbi.nlm.nih.gov/pubmed/7553570?tool=bestpractice.com[26]Spinola SM, Bauer ME, Munson RS Jr. Immunopathogenesis of Haemophilus ducreyi infection (chancroid). Infect Immun. 2002 Apr;70(4):1667-76.http://iai.asm.org/content/70/4/1667.longhttp://www.ncbi.nlm.nih.gov/pubmed/11895928?tool=bestpractice.com[30]Throm RE, Spinola SM. Transcription of candidate virulence genes of Haemophilus ducreyi during infection of human volunteers. Infect Immun. 2001 Mar;69(3):1483-7.http://iai.asm.org/content/69/3/1483.longhttp://www.ncbi.nlm.nih.gov/pubmed/11179316?tool=bestpractice.com[31]Dutro SM, Wood GE, Totten PA. Prevalence of, antibody response to, and immunity induced by Haemophilus ducreyi hemolysin. Infect Immun. 1999 Jul;67(7):3317-28.http://iai.asm.org/content/67/7/3317.longhttp://www.ncbi.nlm.nih.gov/pubmed/10377108?tool=bestpractice.com[32]Purven M, Lagergård T. Haemophilus ducreyi, a cytotoxin-producing bacterium. Infect Immun. 1992 Mar;60(3):1156-62.http://iai.asm.org/content/60/3/1156.longhttp://www.ncbi.nlm.nih.gov/pubmed/1541531?tool=bestpractice.com[33]Mount KL, Townsend CA, Bauer ME. Haemophilus ducreyi is resistant to human antimicrobial peptides. Antimicrob Agents Chemother. 2007 Sep;51(9):3391-3.http://aac.asm.org/content/51/9/3391.longhttp://www.ncbi.nlm.nih.gov/pubmed/17620373?tool=bestpractice.com
包皮环切术能保护性抵抗细菌感染。 这可能是因为在包皮下的湿润区域有利于细菌繁殖。 同样,在包皮及系带内层表面上皮较少出现角质化且更易破损,尤其是在性交时, 为细菌提供更多的入侵途径。[17]Van Howe RS. Genital ulcerative disease and sexually transmitted urethritis and circumcision: a meta-analysis. Int J STD AIDS. 2007 Dec;18(12):799-809.http://www.ncbi.nlm.nih.gov/pubmed/18073009?tool=bestpractice.com[18]Weiss HA, Thomas SL, Munabi SK, et al. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systemic review and meta-analysis. Sex Transm Infect. 2006 Apr;82(2):101-10.http://sti.bmj.com/content/82/2/101.fullhttp://www.ncbi.nlm.nih.gov/pubmed/16581731?tool=bestpractice.com[19]Marrazzo JM, Handsfield HH. Chancroid: new developments in an old disease. In: Remington JS, Swartz MN, eds. Current clinical topics in infectious diseases. Malden MA: Blackwell Science; 1995:129-52.[13]Spinola, SM. Chancroid and Haemophilus ducreyi. In: Holmes KK, Sparling PF, Stamm WE, et al, eds. Sexually transmitted diseases. 4th ed. New York, NY: McGraw-Hill, 2008:689-700.