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  In this article
    Abstract
    Introduction
    Clinical issues
    Pathogenesis
    Diagnostic issues
    Isolation and id...
    Non- culture det...
    Chancroid and HI...
    References

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CONTINUING MEDICAL EDUCATION
Year : 2002  |  Volume : 68  |  Issue : 1  |  Page : 5-9

Chancroid: An update


Department of Dermatology, Venereology and Leprosy, BLDEA's SBMP Medical College, Bijapur - 586 103, Karnataka, India

Correspondence Address:
Department of Dermatology, Venereology and Leprosy, BLDEA's SBMP Medical College, Bijapur - 586 103, Karnataka, India

   Abstract 

Chancroid, an important sexually transmissible genital ulcer disease of the developing world, has gained new importance with the onset of HIV era. Though common, it poses diagnostic problem because of the difficulties in demonstrating Haemophilus ducreyi itself or indirect evidence of its presence. In the present discussion, various aspects of this challenging disease along with recent aspects of its pathogenesis, diagnosis and treatment have been focussed.

How to cite this article:
Inamadar AC, Palit A. Chancroid: An update. Indian J Dermatol Venereol Leprol 2002;68:5-9


How to cite this URL:
Inamadar AC, Palit A. Chancroid: An update. Indian J Dermatol Venereol Leprol [serial online] 2002 [cited 2019 Jun 16];68:5-9. Available from: http://www.ijdvl.com/text.asp?2002/68/1/5/12832



   Introduction Top


Chancroid is a sexually transmissible genital ulcerative disease, caused by Haemophilus ducreyi. It is most prevalent in the developing countries of Asia, Africa and Latin America, especially among the people of low socioeconomic strata. In these geographic areas, annual incidence of chancroid may exceed to that of syphilis.[1] Though uncommon, occasional outbreaks of the disease have been reported from the United States and Europe, among the communities with high risk behaviour.

Because of the fact of epidemiological synergy, in the current era of HIV infection and AIDS epidemic, prompt diagnosis and adequate treatment of chancroid as well as other genital ulcerative diseases have gained immense importance.


   Clinical issues Top


Incubation period of chancroid is short, between 3-7 days. Atypical chancroid lesion is characterised by the triad of undermined ulcer edge, purulent dirty gray base and moderate to severe pain. Multiple ulcers are seen in 50% of cases. All the three features are present in less than 50% of the sufferers. Untreated cases of chancroid have been reported to persist for months to years.[2] Painful, inflammatory inguinal lymphadenopathy, mostly unilateral, is seen in about 30-60% cases which may undergo suppuration.

Obviously symptomatic disease, directly related to the ulcer and inguinal lymphadenopathy is common in males. Depending on the site, females may present with atypical symptoms like dysuria, dyspareunia, pain on defaecation, bleeding per rectum or vaginal discharge. Incidence of chancroid seems to be apparently higher in males, which may be attributed to the facts like,[1]

  • Easily visible anatomy of male external genitalia.
  • Asymptomatic vaginal or cervical ulcers in females.
  • Less common occurrence of lymphadenitis and bubo formation in females.
  • Spontaneous healing of lesions resulting from autoinoculation in dry areas (inner thighs), which are common in females.


Variations to the classical clinical presentation of chancroid are seen[3] like, transient, popular, dwarf, follicular varieties and those forming giat, serpiginous and phagadenic ulcers.

Clinical presentation of chancroid may simulate other STD.s[1] like donovanosis or condylomata Iota (exuberant granulomatous lesion), herpes genitalis (superficial cluster of lesions) or gonorrhoea (endourethral lesion).

Mild constitutional features may be seen during acute illness but systemic spread of the organism never occurs. Extragenital lesions, though rare, result from autoinoculation. Breast, thighs, fingers, anal canal and oral cavity are the sites involved. Anal ulcers in women result from drainage or autoinoculation and not necessarily due to anal intercourse.[1]

Cicatrix formation and phimosis may be a late complication of chancroid requiring circumcision.


   Pathogenesis Top


The fact that H. ducreyi is a strict human pathogen, makes understanding of basic pathogenic mechanism of chancroid a challenging issue.

The potential virulence factors produced by H. ducreyi include[4],[5] fine tangled pill, lipooligosaccharide (Los), haemoglobin binding outer membrane protein (OMP), cell associated hemolysin, soluble cytolethal distending toxin (Hd -CDT) and cu-zu superoxide dismutase (Cu-Zw SOD). Exact mechanism of action of these factors is unknown. The pill help in adherence to the host cell. Hemolysin acts on RBCs, human foreskin fibroblasts and immune system cells relevant to chancroid lesion like, macrophages, T cells and B cells. The influx of these inflammatory cells is partly responsible for the tissue destruction characteristic of chancroid. Host immune system avoidance by H. ducreyi in chancroidal ulcers are provided by both hemolysin and Cu-Zn SOD.[7] CDT causes host cell cycle arrest at G-2 phase and hamper specific host response, contributing to the persistence of chancroid ulcer.[8],[9] OMP DSrA facilitates the ability of H. ducreyi to progress to pustular stage.[10]

The histopathology of infected site resembles a DTH response.[11] In in-vitro models of infection[12] H. ducreyi increases the reaction of pro-inflammatory cytokines IL-6 and IL-8.[12],[13] IL-8, a potent neutrophil chemoattractant, is responsible for local accumulation of neutrophils,[12],[13] hallmark of chancroid ulcer. Both IL-6 and IL-8 also produce keratinocyte proliferation in the tissue surrounding ulcer giving rise to acanthosis,[12] IL-6 also induces IL-2 receptor expression in T- cells, giving rise to TH1 type of CD4 T cells response. This is proved by the fact that there is increased urinary excretion of soluble IL-2 receptors in chancroid patients.[12]


   Diagnostic issues Top


According to CDC guidelines,[14] definitive diagnosis of chancroid requires identification of H. ducreyi on special culture media. Probable diagnosis for both clinical and surveillance purposes requires fulfilling the criteria,

a) Patient has one or more painful genital ulcers.
b) Syphilis and HSV infection excluded by appropriate laboratory tests.

Suggestive diagnosis can be made in presence of the pathognomonic features of chancroid, i.e., a combination of painful ulcers and tender regional lymphadenopathy.


   Isolation and identification of H. ducreyi Top


1. Culture methods:[15] Most widely used media for culture of H. ducreyi are enriched gonococcal agar and enriched Mueller - Hinton chocolate agar. Sensitivity of the culture method is <80%.


   Non- culture detection methods: Top


1. Direct microscopy:[15] Typical appearance of the organism is detected by Gram stained smears of clinical specimen. Sensitivity is < 50% even in culture positive cases. False positive diagnosis is also frequent.

2. DNA amplification techniques:[16]

PCR-to amplify H. ducreyi 16s RNA gene. It is less sensitive in clinical specimens due to presence of Taq polymerase inhibitors. Multiplex PCR -(M-PCR) - Simultaneous DNA amplification of H. ducreyi, T. pallidum and HSV 1 and 2 are possible. It is more sensitive than other standard diagnostic tests.

3. Antigen detection assays (Immunofluorescence)[5],[16]

  • Detection of monoclonal antibody (MAb) against 29 KDa outer membrane protein (OMP) of H. ducreyi. Positive in both culture+ve (>90%) and culture negative cases. It is a simple, rapid and sensitive method but may not be available in resource poor countries.
  • Indirect IF, using MAb against lipooligosaccharide (LOS) of H. ducreyi was assessed by Ahmed et al[1],[2],[3],[4],[5],[6] and was found to be superior to bacterial culture. It is a good method to be used in population with high chancroid prevalence.


4. Nucleic acid probe techniques:[15],[16]

DNA- DNA hybridisation techniques using labelled H. ducreyi derived probes.

Usefulness of this method in clinical specimens has not been assessed widely.

5. Serological methods:[15],[16]

  • Enzyme immuno assays (EIA): Using ultrasonicated whole cell antigen, purified LOS or OMP H. ducreyi as antigen.
  • DOT Immunoblot
  • Agglutination
  • Compliment fixation test


Cross reacting antibodies to other haemophilus species complicates the interpretation of serological testing.

6. Mass spectrometric method (MALDI/TOFMS)[16]

It identifies H. ducreyi in short time (10 minutes). It is also helpful to detect the strain differences of the organism.

7. Tissue biopsy[10]

Though not diagnostic, characteristic histopathological findings are seen, it may be helpful in diagnosing non healing or atypical ulcers.

To summarise, till date, culture using specialised media is the most practised method for diagnosis of infection with H. ducreyi. It has the added advantage that antimicrobial sensitivity of the organism can be tested at the same time.[16] PCR is a superior method than other available means of diagnosis. M- PCR is very useful in rapid diagnosis of difficult genital ulcer disease syndrome. However, in the study conducted by Risbud et al[17] in diagnosis of GUD, M -PCR was not found to be superior to the clinical diagnosis alone or in combination with basic laboratory tests. Serology has limited usefulness in routine diagnosis of H. ducreyi infection, but it is helpful in epidemiological studies as a screening method for past infection.[16]


   Chancroid and HIV synergy Top


Like other GUD, chancroidal ulcer is a major risk factor for heterosexual spread of HIV. Moreover, factors like lack of circumcision, prostitution, drug abuse (crack cocaine, alcohol) seem to be independent risk factors for transmission of both the diseases.[2],[3] Different retrospective seroprevalence surveys[18] have identified increased seroconversion rate in presence of H.ducreyi infection and it increases with number of previous ulcer episodes in a dose response relationship.[2]

The explanations for the enhanced HIV transmission in patients with chancroid ulcer may be due to the facts' like,

  • Genital ulcers act as both portals of entry and exit for (HIV can be detected on ulcer surface).


From the relatively few studies available[19] it is evident that, there are only minor research on such agents may cause an impact to cut down the incidence of multiple STDs in a patient as well as heterosexual transmission of HIV.

Molecular techniques can detect the presence of H. ducreyi DNA in clinical specimen. M-PCR[26] and nested single tube PCR techniques[27] have been shown to be more sensitive than standard methods. This can be extremely useful in designing locally appropriate syndromic management algorithm for genital ulcer.

Molecular techniques have also provided a better understanding to the pathogenesis of STDs. Such knowledge serves as an important basis for rational vaccine design and development.[23] Unless progress is made in developing models to study the pathogenesis of H. ducreyi infection, it is not likely that an effective vaccine against H. ducreyi will be developed in the near future. 

   References Top

1.Ballard R, Morse S. Chancroid. In: Atlas of Sexually Transmitted Diseases and AIDS. Eds. Morse SA, Moreland AA, Holmes KK. Mosby Wolfe Barcelona 1996;48-63.  Back to cited text no. 1    
2.Ronald AR, Albritton W. Chancroid and Haemophilus ducreyi. In: Sexually Transmitted Diseases. Eds. Holmes KK, Sparling A, March PA et al. Mc Grow Hill USA 1999;515-523.  Back to cited text no. 2    
3.Brown TJ, Yen - Moore A, Tyring SK. An overview of sexually transmitted diseases. Part I. J Am Acad Dermatol 1999;41:511-529.  Back to cited text no. 3    
4.Lewis DA, Tait JK, Lumbley SR, et al. Identification of the Znu-A encoded periplasmic zinc transport protein of Haemophilus ducreyi. Infect Immun 1999; 67: 5060 - 5060.   Back to cited text no. 4    
5.Ward KC, Lumbley SR, Latimer JL, et al. Haemophilus ducreyi, secretes a haemagglutinin like protein. Bacteria 1998;180: 6013-6022.  Back to cited text no. 5    
6.Wood GE, Dutro SM, Totten PA. Target cell range of Haemophilus ducreyi. hemolysin and its involvement in invasion of human epithelial cells. Infect Immun 1999;67: 3740-3749.  Back to cited text no. 6    
7.San Mateo LR, Hobbs MM, Kawula TH. Periplasmic copper-zinc superoxide dismutase protects Haemophilus ducreyi. from exogenous superoxide. Mol Microbial 1998;27:391-404.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Lewis DA, Stevens MK, Latimer JL, et al. Characterisation of Haemophilus ducreyi. cdt A, cdt B and cdt C mutants in in-vitro and in-vivo systems. Infect Immun 2001;69:5626-5634.  Back to cited text no. 8    
9.Bratti XC, Olarte EC, Lagergard T, et al. The cytolethal distending toxin from the chancroid becterium Haemophilus ducreyi. induces cell- cycle arrest in the G2 phase. J Clin Invest 1999; 103: 109-115.  Back to cited text no. 9    
10.Bong CT, Throm RE, Fortney KR, et al. Dsr A- deficient mutant of Haemophilus ducreyi. is impaired in its ability to infect human volunteers. Infect Immun 2001;69:1488-1491.  Back to cited text no. 10    
11.Gelfanova V Humphreys TL, Spinola SM. Characterisation of Haemophilus ducreyi. specific T cell lines from lesions of experimentally infected human subjects. Infect Immun 2001; 69:4224 -4231.  Back to cited text no. 11    
12.Hobbs MM, Paul TR, Wyrick PB, et al. Hoemophilus ducreyi. infection causes basal keratinocyte cytotoxicity and elicits a unique cytokine induction pattern in an in vitro human skin model. Infect Immun 1998; 66:2914 - 2921.  Back to cited text no. 12    
13.Zaretzky FR, Kawula TH. Examination of early interactions between Hoemophilus ducreyi. and host cells by using cocultured Ha CaT keratinocytes and foreskin fibroblasts. Infect Immun 1999; 67:5352-5360.  Back to cited text no. 13    
14.Centres for Disease Control and Prevention. 1998 guidelines for the treatment of sexually transmitted diseases. MMWR 1998;47(RR-1); 1-118.  Back to cited text no. 14    
15.Dyck EV. Meheus AZ, Piot P Chancroid. In: Laboratory Diagnosis of Sexually Transmitted Disease. World Health Organisation, Geneva 1999;57-66.  Back to cited text no. 15    
16.Lewis DA. Diagnostic tests for chancroid. Sex Transm Inf 2000; 76: 137- 141.  Back to cited text no. 16    
17.Risbud A, Chan Tack A, Gadkari D, et al. The etiology of genital ulcer disease by multiplex polymerise chain reaction and relationship to HIV infection among patients attending sexually transmitted disease clinics in Pune,Indian J. Sex Trans Dis 1999; 26: 55 -62.   Back to cited text no. 17    
18.Moss GB, Kreiss JK. The Interrelationship between Human Immunodeficiency Virus infection and other sexually transmitted diseases. Medical Clinics of North America 1990; 74: 1647 - 1659.   Back to cited text no. 18    
19.Czelusta A, Yen- Moore A, Straten MV, et al. An overview of sexually transmitted diseases. Part III. Sexually transmitted diseases in HIV infected patients. J Am Acad Dermatol 2000;43:409-432.   Back to cited text no. 19    
20.Donders GGG.Treatment of Sexually transmitted bacterial diseases in pregnant women. Drugs 2000;59: 477- 485.  Back to cited text no. 20    
21.D' Souza P, Pandhi RK, Khanna N, et al. A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin and cotrimoxazole. Sex Transm Dis 1998; 25:293- 295.  Back to cited text no. 21    
22.Schmid GP. Treatment of chancroid, 1997. Clin Infect Dis 1999;28 suppl 1:s 14 - 20.  Back to cited text no. 22    
23.Tyndal M, Malisa M, Plummer FA, et al. Ceftriaxone no longer predictably cures chancroid in Kenya. J Infect Dis 1993;167:469-471.  Back to cited text no. 23    
24.Tyndall M, Agoki E, Plummer FA, et al. Single doses azithromycin for the treatment of choncroid: a randomized comparison with erythromycin. Sex Transm Dis 1994;21:231-234.  Back to cited text no. 24    
25.Fortney K. Totten PA, Lehrer PI, et al. Haemophilus ducreyi is susceptible to Protegrin. Antimicrobial agents and Chemotherapy 1998; 42: 2690-2693.  Back to cited text no. 25    
26.Oral KA, Gates CA, Martin DH, et al. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum and HSV 1 & 2 from genital ulcers. J Clin Microbial 1996;34: 49- 54.  Back to cited text no. 26    
27.Hawker S, West B, Wilson S, et al. Asymptomatic carriage to Hoemophilus ducreyi confirmed by the polymerase chain reaction Genitourin Med 1995;71:224-227.  Back to cited text no. 27    

 

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