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Chancroid

Category: Illness or disabilities

Type

Involuntary

Introduction and description

All the drawings on this page are by Egon Schiele

Chancroid, also known as soft chancre and ulcus molle, is generally a bacterial sexually transmitted infection characterized by painful sores on the genitalia.  But as we will see shortly, it has branched out and is taking new directions.  The etiological agent of chancroid was first described in 1889 by Auguste Ducrey following “repeated autoinoculation of purulent ulcer material from a series of patients”.  Chancroid is caused by a bacteria - Haemophilus ducreyi.

In the mid 1980s researchers were stating that “ In developing countries of tropical Africa and South-East Asia chancroid is the most important cause of genital ulcerations”.  By the early 1990s they were saying “H. ducreyi is the major cause of genital ulcer disease in Africa and Southeast Asia and is of increasing concern in the United States”.  It eventually became a worldwide disease affecting every country, considered endemic in tropical and subtropical areas of the world and more prevalent in Europe and North America. 

But who, these days, has heard of Chancroid? 

There appears to be a belief that Chancroid has declined in importance as a sexually transmitted infection in most countries where it was previously endemic. But the sheer difficulty of isolating the bacteria and the fact it has learned to co-exist with viruses, fungi and other sorts of bacteria, that also produce genital sores, means it may simply be being overlooked.  And we also have this:

The global prevalence of chancroid is unknown as most countries lack the required laboratory diagnostic capacity and surveillance systems to determine this. PMID:  24597521

 

The general belief [and it is a belief] is that it is a disease found in countries where unprotected and casual sex occurs, and is especially associated with commercial sex workers [of both sexes].

And this is partly true.

As such, men visiting countries where the sex trade is very prominent can easily contract it, come home, spread the disease and even if sores develop, be misdiagnosed with other more prevalent sexual diseases such as Herpes.  The bacteria can even live in the same ulcer as those in which the Herpes virus is found.   But this bacteria is a lot more complex than this implies.  Read on!

Symptoms

The defining symptom of chancroid are the genital ulcers, which in men are principally found on the penis, but other symptoms may also be present, meaning this bacteria can get round the body, via the lymph system and the blood supply.

Genital ulcers

The lesions are usually obvious in the male but may be undetected in women. The incubation period is 3-5 days and the typical lesion is a soft nonindurated ulcer with a dirty exudate at the base, which is painful and exquisitely tender to palpation. Bubo formation is common and about half suppurate. Diagnosis depends on differentiation from other genital ulcers. PMID: 6687703

And

We report a case of chancroid in a white heterosexual man in the United Kingdom. This patient was seen by four separate health services over a period of five weeks with excruciatingly painful penile ulcers. Despite several negative herpes simplex virus polymerase chain reaction tests and a self-diagnosis of chancroid, he was repeatedly offered multiple courses of aciclovir. This case highlights the need for awareness of alternative diagnoses in persistent cases of genital ulcer disease.  PMID: 24535694

 
 

poor man.

Eye diseases

Conjunctivitis can be caused by this bacteria – Reference: Conjunctivitis due to Haemophilus ducreyi infection - Gregory JE, Henderson RW, Smith R.  Br J Vener Dis. 1980 Dec;56(6):414. PMID: 6969619.

Lymphadenopathy

Lymphadenopathy is disease of the lymph nodes, in which they are abnormal in size, number, or consistency. Lymphadenopathy of an inflammatory type (the most common type) produces swollen or enlarged lymph nodes.

…a chancroid lesion starts out as papule that soon turns into an ulcer. Around 33% of all patients experience lymphadenopathy. If chancroid is not treated, the lymph nodes swell and exude pus. They eventually burst and drain chronically. PMID: 3532370

Urethritis

Urethritis is inflammation of the urethra. The most common symptom is painful or difficult urination. It is usually caused by infection with bacteria.

In this study 456 men with H. ducreyi-culture positive genital ulcers were investigated. Among these men, 16 (3.5%) had urethritis. H. ducreyi was isolated from the urethra of nine men (1.9%). Of 57 men who had chancroid but not urethritis, none had H. ducreyi isolated from the urethra. Of 106 patients presenting with only acute urethritis, H. ducreyi was found in one. We conclude that H. ducreyi is responsible for acute urethritis in men, but that it rarely, if ever, can be cultured from the urethra of men with chancroid who do not have symptomatic urethritis. PMID: 3258676

 

 

Anorectal disorders

H. ducreyi has been found colonising haemorrhoids, and causing ulcerous lesions in and around the anus that itch, bleed, spread and cause pain.   The preference of this bacteria for blood means that it tends to be attracted to bleeding haemorrhoids and the presence of blood in the anal passage.  The bacteria may work its way up the anal passage looking for food.  [Haematochezia  is the passage of fresh blood through the anus, usually in or with stools].  The research here provides no definitive answers, as if there is lower gastrointestinal bleeding, then the bacteria may be attracted to it.  On the other hand, it may also be the cause of this bleeding.   [Am Fam Physician. 1972 Aug;6(2):54-62. - Anorectal pain. Thiele GH. PMID: 5051600]

Note that we could find no connection to colon cancer, but as colon cancer can be caused by bacteria, there may be a risk.

Our results indicate that vancomycin-sensitive bacteria induced colon inflammation and DNA damage PMID: 27050089

And H. ducreyi is sensitive to vancomycin

Despite the development of various selective solid media in the last 20 years, cultural diagnosis of chancroid remains problematic. Many pitfalls may complicate this procedure, such as concomitant syphilis, syphilis, or herpes progenitalis simulating chancroid, strain differences in nutritional requirements, improper handling and delayed inoculation of clinical specimens, use of suboptimal growth conditions, and vancomycin hydrochloride-sensitive organisms. Highest cultural yield will be obtained by using enriched gonococcal agar base and enriched Müeller-Hinton agar in a biplate fashion. As most isolates are sensitive to vancomycin, incorporation of this antibiotic should be routine. However, screening for vancomycin-sensitive organisms is indicated when negative cultures are repeatedly obtained from clinically typical cases originating from the same community. Development of immunodiagnostic and DNA probe tests is underway.  PMID:  1845282

 

Paraphimosis

Paraphimosis is a rare complication.  It is when the foreskin of an uncircumcised penis becomes trapped behind the glans penis, and cannot be reduced (pulled back to its normal flaccid position covering the glans). If this condition persists for several hours or there is any sign of a lack of blood flow, paraphimosis is treated as a medical emergency, as it can result in gangrene:

After a visit to Hong Kong, a 27-year-old salesman developed penile ulceration which failed to respond to three weeks' penicillin therapy. He then presented to hospital with acute paraphimosis. A clinical diagnosis of chancroid was confirmed by isolation of Haemophilus ducreyi. …. Although chancroid is an uncommon venereal disease in Australia, its incidence is still high in many tropical countries. It should be considered as a possible cause of genital ulceration in patients who have travelled overseas. PMID: 887039

Skin disease

H. ducreyi has recently emerged as a cause of chronic skin ulceration in the Pacific region and Africa. Based on sequencing of whole genomes and defined genetic loci, it appears that the cutaneous H. ducreyi strains diverged from the class I genital strains relatively recently. ….

 

 

H. ducreyi should be considered as a major cause of chronic limb ulceration in both adults and children and appropriate molecular diagnostic assays are required to determine ulcer aetiology.

The high prevalence of H. ducreyi-related cutaneous ulceration in yaws-endemic countries has challenged the validity of observational surveys to monitor the effectiveness of the WHO's yaws eradication campaign. 

PMID:  26658654

HIV

Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin.  PMID:  25258485

We believe that this bacteria is responsible for far more disease and illness than we have listed here.  It thrives on blood and glucose, it can travel round the body with ease, feeding off selenium and iron, and in time we may find it is a truly major pathogen, a very significant adversary.

Cause

Chancroid is a bacterial infection caused by the fastidious Gram-negative streptobacillus Haemophilus ducreyi  -  either class I or class II; these two classes diverged from each other approximately 1.95 million years ago. There are several hundred strains of this bacteria, some isolated to specific parts of the world. 57 strains of Haemophilus ducreyi were isolated in Amsterdam alone during an eight year period from 1978 to 1985 [PMID: 3494720].

If ever there was a case for microbial intelligence, this little bacteria is it.  It has managed to arm itself, adapt to the food supply and has diversified, so that rather than just its normal genital habitat, it can now be found in all sorts of open sores and ulcers.

Fastidious feeders

A fastidious organism is any organism that has a complex nutritional requirement.  This may seem unimportant, but in order to treat a bacteria you have to be able to grow it to study it, and the growth of this organism in the clinical microbiology laboratory has been described as ‘challenging’, because of its in vitro fastidious nature.

One of the growth media in current use for Haemophilus ducreyi comprises Mueller Hinton agar, chocolatised horse blood, serum and IsoVitalex (BBL).  This latter contains glucose and a number of amino acids, as well as Vitamin B12

For a better understanding of growth factors, attempts were made to simplify this complex medium. The horse blood was replaced by haemin (200 micrograms/ml), the serum by albumin (0.2%), and IsoVitalex was substituted only by L-glutamine 0.01%. Most of the strains grew, but when selenium ions were added in a concentration of 3.25 x 10(-3) micrograms/ml, growth was stimulated and became more luxuriant than growth on conventional media.  PMID:  3500188

 

We need selenium, and it is possible that these bacteria in our system use our blood, our glucose and our selenium to proliferate.  They also need iron but they get this from haem in our blood

These results indicate that haem can supply the requisite iron for growth of H. ducreyi. PMID: 1647460

Heme or haem is a cofactor consisting of an Fe2+ (ferrous) ion contained in the centre of a large heterocyclic organic ring. Hemes are most commonly recognized as components of hemoglobin, the red pigment in blood.  Thus if we become anaemic, with far more white cells it is actually a good thing, as this starves the bacteria and provides more troops to fight the infection.

In vitro and in vivo

Another difficulty with this bacteria – a difficulty incidentally that has been found with many bacteria - is that growing a bacteria and testing it on a petri dish tells you very little about how it actually behaves in the body.  The bacteria adapts and changes according to its environment.  As such anyone who says that they have found a ‘cure’ for chancroid via tests on a petri dish, may be wrong.

Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.  PMID:  26930707

Antibiotic resistance

Some strains of Haemophilus ducreyi  are able to produce beta-lactamase.  Beta-lactamase production is mediated by plasmids very similar to the beta-lactamase specifying plasmid found in isolates of Neisseria gonorrhoeae.[PMID: 6287927]

 

Beta-lactamases (β-lactamases) are enzymes (EC 3.5.2.6) produced by bacteria (also known as penicillinase) that provide multi-resistance to β-lactam antibiotics such as penicillins, cephamycins, and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase.

Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-lactam. Through hydrolysis, the lactamase enzyme breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.  Beta-lactam antibiotics are typically used to treat a broad spectrum of Gram-positive and Gram-negative bacteria.

Haemophilus ducreyi  belongs to the much bigger family of Haemophilus bacteria and it would seem that the family are sharing information and plasmids.  They are there in H. influenza  and  in many strains of H. parainfluenzae.

New plasmids keep on being discovered - Plasmid pLS88, for example, from a clinical isolate of Haemophilus ducreyi with resistance to sulphonamides, streptomycin and for kanamycin has a ‘host range’ which includes Haemophilus influenzae, Actinobacillus pleuropneumoniae, and Escherichia coli.

Secondary invasion

At one time this bacteria concentrated on the genital region and was the main causative agent of the sores there.  It has now adapted in an extraordinary way, sharing sores and colonising any open wounds, happily living with viruses and other types of bacteria.  A kind of multi-cultural pathogen paradise.  Given the proximity of the anus to the genital region, there is clearly a risk for anyone with bleeding hemorrhoids.

The GU strain 35000HP, for example, does not infect intact skin; wounds are required to initiate infection.  It is worth adding that the cutaneous ulcers (CU) strains are genetically almost identical to the class I strain 35000HP and has no additional genetic content.

… from the time of Ducrey's original description of the organism in 1890 until about 1977, both clinical and laboratory experts in the United Kingdom believed that H. ducreyi infections were rare, generally acquired abroad, and almost impossible to confirm in the routine laboratory! In consequence it was a common view that it was not worth looking for H. ducreyi until all other possible causes of genital ulceration had been excluded. Moreover, the search for such an infection stopped as soon as any other cause for the patient's lesions had been found. This [approach] … led to our looking for H. ducreyi in specimens from an unselected series of patients with genital ulceration including a number with herpes genitalis infections. The surprise finding of H. ducreyi in circumstances suggesting that it was a secondary invader made us re-examine the whole question of H. ducreyi infections and chancroid and wonder if the same organism can act as a primary pathogen and as a secondary invader. PMID:  7153512

The phrase secondary invader has taken on a great deal more importance now it has been found that Haemophilus ducreyi is secreting itself in the ulcers of yaws victims.

Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue. The disease begins with a round, hard swelling of the skin, 2 to 5 centimeters in diameter. The center may break open and form an ulcer.  Yaws is spread by direct contact with the fluid from a lesion of an infected person. The contact is of a non-sexual nature.  Yaws was common in at least 14 tropical countries as of 2012.

Haemophilus ducreyi …. has recently been shown to be a significant cause of cutaneous lesions in tropical or subtropical regions where yaws is endemic. Here, we report the draft genome assemblies for 11 cutaneous strains of Haemophilus ducreyi, isolated from children in Vanuatu and Ghana. PMID: 27389258

So chancroid has ceased to be a sexually transmitted disease, it is a general disease that even little children can get, which causes excruciatingly painful sores, eye disease, lymph system disease, blood disease, intestinal disease and which can be spread via the ulcerous fluids caused by other pathogens.

I think we need to be worried about this pathogen and look at it a bit more closely.

Diagnosis

Specific tests have to be made for this bacteria simply because other pathogens – viruses and fungi – can produce symptoms very similar and even identical to those of chancroid.  For example:

The penile ulcerations of 100 consecutive men were tested for microorganisms. A polymicrobial flora was identified in the ulcers of 97 men. The microorganisms recovered from these ulcers included combinations of anaerobic and aerobic bacteria (including Mycoplasma), herpes simplex virus, yeasts, and filamentous fungi. Fifty-three study entrants had microorganisms, identified by culture or serologic tests, that were considered primary in ulcer pathogenesis. Herpes simplex virus was the most prevalent and Treponema pallidum was the next most prevalent pathogen identified. Of our patients, 5% had two recognized pathogens confirmed by laboratory tests, and only one of these was suspected at clinical examination. In addition, the study suggests that microorganisms other than Haemophilus ducreyi can produce ulcers with a morphology mimicking chancroid.  PMID:  203634

And another example

Of 97 patients with genital ulcers attending a special treatment clinic in Nairobi, Kenya, 60 harboured Haemophilus ducreyi, four herpes simplex virus, and five Neisseria gonorrhoeae. Eleven patients had serological evidence of syphilis; …... An enriched chocolate agar with vancomycin and serum was a useful medium for primary isolation of H ducreyi.  PMID:  6799142

The disease Granuloma inguinale (also known as donovanosis) , also a bacterial disease caused this time by Klebsiella granulomatis is also characterised by ulcerative genital lesions.  Furthermore, these other pathogens may occur in the same ulcers.

Twenty-two cases of chancroid were confirmed by the isolation of H ducreyi in 160 patients with genital ulceration examined over a one-year period. The cases were apparently unrelated, and in only five was there a history of recent sexual contact abroad. Concurrent infection with other sexually transmitted diseases was present in 18 (81.8%) patients, and in 14 (63.6%) both H ducreyi and herpes simplex virus were isolated from the same genital ulcers. Thus, these findings indicate that chancroid is underdiagnosed in England and that H ducreyi may frequently occur as a secondary invader of damaged genital skin and mucosa.  PMID:  6976815

This may also be helpful in classification and diagnosis:

The cell wall carbohydrates of 43 strains of Haemophilus ducreyi isolated in different parts of the world were subjected to lectin analysis using commercial panels containing 14 different plant lectins of known specificity. Preliminary evidence indicated both intrastrain and inter-strain variation in cell wall carbohydrate composition. In addition, it was possible to group strains from different geographical areas by lectin agglutination patterns. Lectin typing might thus become a useful marker system for epidemiological investigation of Haemophilus ducreyi infections.  PMID:  3143583

 Treatment

Once, the best treatment was prevention, the use of condoms, sticking to one faithful partner, but we now have the added problem of a bacteria that does not need sex to travel, it just needs ulcerous lesions filled with pus that have a tiny opening in which to creep into the wound. 

In this case the hygiene of anyone with an ulcerous lesion that is weeping becomes paramount.  In essence, it needs to be covered with sterile dressings to ensure the pus does not spread, and the dressings need to be frequently changed and incinerated.

One clear message is to try to make sure the ulcers from other pathogens are not punctured leaving an open wound.

The standard treatment is antibiotics – although as we have seen this bacteria is a survivor and quite capable of devising ways of destroying the antibiotics.  In Brazil they use thiamphenicol:

A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. ….For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. …. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002) and this drug should be avoided in these co-infected patients.  PMID:  20191200

 

Thiamphenicol is an antibiotic. It is the methyl-sulfonyl analogue of chloramphenicol and has a similar spectrum of activity, but is 2.5 to 5 times as potent.  What will it be doing to the person’s intestinal flora?

We will keep trying to find plant based medicines and posting them under the observations, many herbs and spices – cloves, thyme, and cinnamon have been traditionally used, thus possibly indicating a role for thymol, but this is speculative.

In the book by J D Keys,  -  Chinese Herbs [1976. Charles E. Tuttle Co., Tokyo.], Polygonum aviculare (Polygonaceae), is mentioned [Hemero Tea , Centinodia , T'Ieh Sien Ts'Ao , Miti-Yanagi , Nana Shwana , Knotweed]. 

A recent paper has also identified Terminalia paniculata as a possible base for an ointment, it is a tree native to southwest India (including the Western Ghats and Karnataka). Known in the timber trade as kindal, it has a variety of names in local languages

This may also be useful in future research:

Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.  PMID:  24520065

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References and further reading

  • J Infect Dis. 1978 Jan;137(1):50-6.  The microbiological flora of penile ulcerations.  Chapel T, Brown WJ, Jeffries C, Stewart JA.
  • Indian J Sex Transm Dis. 2015 Jan-Jun;36(1):30-4. doi: 10.4103/0253-7184.156697.  Pattern of sexually transmitted infections in a Muslim majority region of North India.  Hassan I1, Anwar P1, Rather S1, Sameem F1, Majid I1, Jabeen Y1, Mubashir S1, Nisa N1, Masood Q1.  1Department of Dermatology, Sexually Transmitted Diseases and Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India.
  • Int J STD AIDS. 2014 Sep;25(10):768-70. doi: 10.1177/0956462414522441. Epub 2014 Feb 17.  Chancroid - desperate patient makes own diagnosis.  Barnes P1, Chauhan M2.  1New Croft Centre for Sexual Health, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK pam.barnes@nuth.nhs.uk.
  • Nat Prod Res. 2015;29(16):1562-6. doi: 10.1080/14786419.2014.983919. Epub 2014 Nov 27. Antimicrobial activity of plant extracts against sexually transmitted pathogens.  Jadhav N1, Kulkarni S, Mane A, Kulkarni R, Palshetker A, Singh K, Joshi S, Risbud A, Kulkarni S.  1a Department of Virology , National AIDS Research Institute , Pune , India.  PMID: 25427632

 

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