Diagnosis and Management of Chancroid in Nigeria

Background

There is a broad group of venereal disease that is referred to as the “Tropical Venereal Disease”. They are so-called because they are most frequently seen in the tropical and sub-tropical areas of the world. Among them are conditions like chancroid, lymphogranuloma venereum (LGV or climatic bubo) and granuloma inguinale (chronic venereal sores). Chancroid is variously called “soft sore” or “soft chancre” because it bleeds easily and “ulcus moile“.¹ It is an acute infection and auto-innoculable disease. The extent of chancroid genital ulceration in Nigeria is greater in the Northern partly due to permissive sexual practices especially for men.

Aetiology

The aetiological agent of chancroid is Haemophilus ducreyi, also commonly called “Streptobacillus of Ducreyi” because it was first isolated by Ducreyi in 1889. In specimens from the ulcerated surface of lesions organisms appear as small gram-negative cocco-bacillary forms, arranged in pairs, in groups or in chains lying parallel to each other - the so called “school of fish” or “Fingerprint” arrangement. They may appear either intra- or extracellularly.²

The organism is non-motile, non-sporing and non acid-fast. It requires X-factor (haematin) but not V-factor (NAD) for growth. Both these factors are present in blood.

Clinical Features

Chancroid is wide spread in distribution. It is less common in the developed than in developing countries. It is more common in men that women. The disproportionately low incidences in woman are due to difficulties in diagnosis in this sex. Although, it has been described as a disease of the “socially unemployed and economically unfortunate by King and Nico.¹ The condition is transmitted usually by sexual intercourse, accidental infection is rare, the female mainly act as reservoirs.³

The incubation period is short, varying from two to ten days, but may be up to 14 days. The first lesion may even be noticed within 24 hours if there was an excoriation of the genital skin at the time of sexual intercourse, but may rarely be delayed for about 4 weeks. A small red, painful papule appears on the genitalia, which rapidly breaks down to form an ulcer. Several genital ulcers then develop, auto-innoculability being a special feature. These ulcers are painful with ragged edges, sometimes undermined, usually unindurated and bleed easily.

Bubo formation is also a salient feature of chancroid. The nodes are painful, soft from the beginning, become matted together to form a unilocular suppurating mass, and often referred to as bubo. The overlying skin is hot; the mass becomes fluctuant and may break down to discharge pus if left unaspirated and if the patient is not properly treated. In the latter case a large ulcer may be formed in the groin. Other complications of chancroid include haemorrhage from erosive lesions, urethral structure, phimosis and paraphimosis, fusospiro chaetosis and gangrene.

Clinical Diagnosis

Chancroid should not be confused with syphilis, which usually produces painless, indurated genital ulcers uncomplicated by bubo formation. Serological tests for should be performed in all cases of genital ulceration to exclude syphilis. Chancroid may sometimes be confused with secondarily infected herpes simplex⁴ and granuloma inguinale.⁵ The clinical differential between chancroid and lymphogranuloma inguinale is shown in Table 1. Other conditions, which must be excluded, include infected traumatic wounds, balanitis, specific drug eruptions and myiasis.

Table 1.

Clinial differential of chancroid and Granuloma Inguinale.

Clinical Feature	Chancroid	Granuloma Inguinale
Incubation Period	1 week	2 wks – 6 months
Ulcer characteristics:
Induration	Soft, without induration	Indurated
Border	Ragged, Undermined erythematous	Elevated, rolled cord like rim
Center	Purulent	Beefy red granulation
Pain	Painful	Painless, painful if Secondarily infected
Odour	Malodorous	unremarkable

Other differentials of chancroid include of course pediculosis pubis and scabies. Typical lesions of scabies are found between the fingers and toes and Sarcoptes scabei can be easily identified under the microscope.

The following two cases reports illustrate a typical salient features of chancroid in Nigeria.

Case No 1

A 20 years old Nigerian man whose presenting symptoms were painful swelling of the right groin, which occurred two weeks after sexual exposure with a school girl. Physical examination of the patient showed a very tender ulcer (1 cm diameter) with undermined edges on the penis (figure 1a). The lesion was not indurated. There was an enlarged suppurating inguinal lymph node on the right groin. The gram-stained appearance of the smear from the ulcer showed numerous pus cells with several gram-negative coccobacilli. Serological test for syphilis was negative. Although appropriate media for isolating Haemophilus ducreyi were not available in the laboratory, we attempted on chocolate agar. There was no recovery of H. ducreyi after 5 days incubation at 37°C in a candle extinction jar. The characteristic “school of fish” arrangement of H. ducreyi was however demonstrated from the patient's serum inoculated with material from the lesion and incubated at 37°C for 48 hours. The patient responded favourably to antibiotic treatment of Erythromycin 500mg orally four times a day for 7 days.

Fig. 1A.

Case No 2

A 45 years old married middle classman reported with a five-day history of painful penis. He had sexual exposure with his casual girl friend a week before reporting at the clinic for the treatment of sexually transmitted disease. He noticed a small swelling on the glans penis a day after the sexual contact. The swelling broke down and within 5 days he had developed large painful ulcers. On examination large multiple, erosive, non-indurated bleeding ulcers with ragged edges were seen on the glans penis and the Coronal sulcus (figure 1b). There were also some discrete enlarged nodes in the left inguinal region. The gram-stained smears of the ulcers showed gram-negative coccobacillary forms. Serological test for syphilis was negative. He was successfully treated with sulphadiazine 1g 6 hourly for 14 days. The ulcers healed without leaving any scars. Examination of the sexual partner did not reveal any clinical infection but she was given treatment of ceftriaxone 250mg im. in a single dose.

Fig. 1B.

Laboratory Diagnosis

Culture: Culture of scraping from the ulcer base or of pus aspirate from the bubo. Culture media include chocolate agar enriched with vancomycin hydrochloride.

Modification of these techniques includes the use of more than one medium to increase sensitivity.⁶ It is necessary to note that due to the need for X-factor (haematin) by ^{H. ducreyi}, the media is to be enriched with blood that has been carefully heated to release the growth factor haematin from haemoglobin. The inoculated plate should then be incubated in an atmosphere of 3–5% CO₂ with high humidity in the region of 100%. This can be provided by candle jar containing moist plates. The plates should then be incubated at lower temperatures of 33–35°C. After 24–48 hours incubation, suspect H. ducreyi colonies which appear waxy when scraped up with a loop and subculture until characterized by the procedures shown in Table 2 and sensitivity testing performed on isolates on Mueller- Hinton agar. It is desirable for cultures to be saved for further studies. This can be done by freezing at −70°C in defibrinated rabbit blood or lyophilized in serum-inositol for long-term storage.

Table 2.

Procedure for identification of Haemophilus ducreyi

Test performed		Typical H. ducreyi reactions
Gram staining		Gram negative rods
Prophyrin		Negative
Nitrate reductase		Positive
Oxidase		Weakly positive
Catalase		Negative
Alkaline phosphatase		Positive
Carbohydrate -
Fermentation:	Glucose	Negative
	Xylose	Negative
	Mannitol	Negative
	Sucrose	Negative
	Maltose	Negative
	Arabinose	Negative

Nucleic Acid (DNA) Detection

Detection of nucleic acid DNA by amplification techniques such as polymerase chain reaction (PCR) using nested techniques.^7,8

Expert opinion has estimated that in endemic areas, a positive H. ducreyi culture is achievable in 60–80 percent of patients considered to have chancroid on clinical grounds.

Microscopy is only 50% sensitive compared to culture and prone to multiple errors, given the poly-microbial flora of many ulcers. PCR is the most sensitive technique, and has been demonstrated to be 95% sensitive compared to culture: Conversely, culture may be only 75% sensitive relative to PCR. Yet PCR may be negative in a number of cultures-proven chancroid cases owing to the presence to Taq polymerase inhibitors in the DNA preparations extracted from genital ulcer specimens. ⁹ A multiple PCR assay has also been developed for the simultaneous amplification of DNA targets from HSV type 1 and 2, H. ducreyi, and Treponena pallidum, 10 unfortunately, it is not commercially available, except for research purposes.

Serology

Serologic diagnosis of Chancroid has been useful in a number of epidemiological studies, using enzyme -linked immunoassays (EIAs) using either lysed whole cell, lipo-oligosaccharide (LOS) or outer membrane proteins (OMPs) as antigen source.^11,12 However, for the individual patient, the method lacks sensitivity, specificity and cannot distinguish between remote and recent infection.

Treatment

Successful treatment of Chancroid should cure infection, resolve clinical symptoms and prevent transmission to sexual partners. The main treatment of chancroid is with the administration of antibiotics. Evidence of their clinical usefulness has been obtained in randomized controlled trials for most, however grading of recommendation will also take account of ease of administration, side effect and compliance. ¹³ The recommended regimens in Nigeria are as follows.

• Azithromycin 1g orally in a single dose, or

• Ceftriaxone 250g intramuscularly in a single dose, or

• Ciprofloxacin 5oomg orally in a single dose, or

• Ciprofloxacin 500mg orally two times a day for 3 days, or

• Erythromycin base 500mg orally four times a day for 7 days.

The safety of azithromycin for pregnant and lactating women has not been established Ciprofloxacin is contra-indicated for pregnant and lactating women, children and adolescents less than 18 years of age. The erythromycin or ceftriaxone regimens should be applied. No adverse effects of chancroid on pregnancy outcome or on the foetus have been reported.

Patients co-infected with HIV should be closely monitored. There have been reported cases that healing may be slower and in some cases resulted in treatment failures among HIV -infected people.

Control

There is no immunization against chancriod. It is however beneficial to some extent if genitalia are thoroughly washed with soap and water immediately after sexual intercourse. Health education and in particular personal cleanliness is of prime importance in controlling the infection. Early diagnosis and effective therapy of cases of chancroid would limit spread in a community. It is advisable that patients avoid sexual intercourse until all lesions are healed. Patients should be given detailed explanation of their condition with particular emphasis on the long-term implications for the health of themselves and their partner. Giving them clear and accurate written information (if deemed appropriate) should reinforce this.

Finally understanding the exact nature of the diseases is very important. Screening could do this for other possible causes of genital ulcerative disease particularly the diagnosis of T. pallidum and genital herpes but also, the diagnosis of lymphogranuloma venereum (LGV). In addition screening for serological syphilis and possibly for UIV should be offered. The use of Latex condoms for sexually active persons will alleviate the risk of contracting chancroid and other sexually transmitted diseases (STDs).