SPECIAL FOCUS y Non-viral sexually transmitted infections Review
Epidemiology, clinical
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David A Lewis
Centre for HIV and STIs, National
Institute for Communicable Diseases,
National Health Laboratory Service,
1 Modderfontein Road, Sandringham
2131, Johannesburg, South Africa
For personal use only.
and
Department of Internal Medicine,
Faculty of Health Sciences, University
of the Witwatersrand, Johannesburg,
South Africa
and
Division of Medical Microbiology,
University of Cape Town, Cape Town,
South Africa
Tel.: +27 115 550 468
davidl@nicd.ac.za
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features, diagnosis and
treatment of Haemophilus
ducreyi a disappearing
pathogen?
Expert Rev. Anti Infect. Ther. 12(6), 687696 (2014)
Chancroid, caused by Haemophilus ducreyi, has declined in importance as a sexually transmitted
pathogen in most countries where it was previously endemic. The global prevalence of
chancroid is unknown as most countries lack the required laboratory diagnostic capacity and
surveillance systems to determine this. H. ducreyi has recently emerged as a cause of chronic
skin ulceration in some South Pacific islands. Although no antimicrobial susceptibility data for
H. ducreyi have been published for two decades, it is still assumed that the infection will
respond successfully to treatment with recommended cephalosporin, macrolide or
fluoroquinolone-based regimens. HIV-1-infected patients require careful follow-up due to
reports of treatment failure with single dose regimens. Buboes may need additional treatment
with either aspiration or excision and drainage.
KEYWORDS: azithromycin ceftriaxone chancroid ciprofloxacin erythromycin genital ulcer Haemophilus
ducreyi HIV-1
Chancroid, also known as soft chancre (ulcus
molle), is caused by the fastidious Gram- Epidemiology
negative bacillus Haemophilus ducreyi [1]. The Chancroid is more prevalent among individu-
organism is usually spread through sexual als from lower socioeconomic groups as well
intercourse and it is believed that microabra- as among female commercial sex workers
sions are required to be present before infec- (CSWs) and their male partners [9]. Impor-
tion can be established in the genital tantly, men have a much higher incidence of
epithelium and underlying tissue [2,3]. Chan- chancroid than women, while uncircumcised
croid usually presents as multiple painful males are more susceptible than circumcised
superficial genital ulcers and may be associated men [10,11]. A link has also been described
with suppurated regional lymphadenopathy [4]. between chancroid in men and sexual exposure
Chancroid used to be one of the most preva- to crack cocaine-using CSWs [12].
lent sexually transmitted infections (STIs), par- Although two studies have reported asymp-
ticularly so in several resource-poor countries tomatic carriage rates of 24% in female CSWs,
of Africa, Asia, Latin America and the Carib- it is generally believed that asymptomatic car-
bean [5]. Several prospective and cross-sectional riage of H. ducreyi plays little or no role in dis-
casecontrolled studies, undertaken in coun- ease transmission [2,13,14]. The cross-sectional
tries where chancroid used to be a common design of these two studies, one culture-based
cause of genital ulcer disease (GUD) and and the other based on the use of nucleic acid
where analyses were appropriately adjusted for amplification tests (NAATs), made it impossible
differences in sexual behavior, have highlighted to determine if asymptomatic carriage of
the importance of GUD as a risk factor for H. ducreyi does indeed exist or contribute signif-
the transmission of HIV-1 [68]. icantly to chancroid transmission. Specifically,
10.1586/14787210.2014.892414
2014 Informa UK Ltd ISSN 1478-7210 687
 Review Lewis
these studies were unable to differentiate persistent asymptomatic
infection from transient carriage following sexual inoculation or
either the incubation or recovery phases of true H. ducreyi
infection.
Chancroid enhances HIV-1 transmission
Men and women with genital ulceration have been shown to be
substantially more likely to be co-infected with HIV-1 infection,
with odds and risk ratios being higher than for non-ulcerative
STIs [6,15]. A re-analysis of data from longitudinal studies of
female CSWs and men in Nairobi showed that GUD can pro-
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duce high co-factor effects per sexual exposure for male-to-female
(10- to 50-fold) and for female-to-male (50- to 300-fold) trans-
mission of HIV-1 [16]. These estimates suggest that GUD may
have been responsible for a high proportion of heterosexually
acquired HIV-1 infections in sub-Saharan Africa during the time
when chancroid was highly prevalent. Strong correlations have
also been reported between HIV-1 seropositivity and serological
evidence of previous chancroid [17,18]. Further supportive evi-
dence for the epidemiological synergy between chancroid and
HIV-1 infection comes, first, from the observations that
HIV-1 infection rates are the highest in the world in those Afri-
can countries where chancroid was previously common and, sec-
ond, from reports that those Asian countries with early
For personal use only.
generalized HIV-1 epidemics had co-existent endemic levels of
chancroid [5].
Decline in chancroid
Over the past 1020 years, there has been a substantial decline
in the prevalence of chancroid in several countries in Southeast
Asia and Africa [5]. At the same time, several authors have
reported a rise in the relative prevalence of genital herpes sim-
plex virus type 2 (HSV-2), and to a lesser extent, HSV
type 1 (HSV-1) infections, which now account for the vast
majority of GUD cases in these countries [1921].
In Thailand, a 95% reduction was reported in the incidence
of chancroid between 1987 and 1994 [22,23]. Within Africa,
chancroid virtually disappeared in Kenyas capital city by the
end of the 1990s and has been followed by a marked reduction
in the HIV-1 prevalence among Nairobis sex workers [24,25]. In
Uganda, H. ducreyi was detected in only 1% of genital ulcer
swabs obtained from the Rakai Community cohort between
2002 and 2006 [26]. Within Southern Africa, several molecular-
based GUD etiological studies have demonstrated similar
reductions. In South Africa, several surveys undertaken since
2007 have repeatedly demonstrated that chancroid now
accounts for <1% of genital ulcers [LEWIS D, UNPUBLISHED DATA].
Likewise, no H. ducreyi infections were detected among almost
200 GUD cases recruited in two cities in Namibia in
2007 [27]. As chancroid prevalence has plummeted in resource-
poor countries, diagnoses have also fallen in Europe, as exem-
plified by the results of a prospective study of 278 GUD cases
enrolled between 1995 and 2005 at a STI clinic in France [28].
In this study, only eight bacteriologically confirmed cases of
chancroid were detected up until 2001, in contrast to no cases
688
in period 20022005. Likewise, a total of only 24 cases of
chancroid were detected in the USA in 2010, which represents
a 99.4% decline in the number of reported cases since
1990 [29].
For chancroid, the reproductive rate (Ro) is critically depen-
dent on the average number of exposed sexual contacts per
unit time [11]. Accordingly, any intervention that reduces the
number of sexual exposures will have a profound effect on Ro
and the number of new chancroid cases will rapidly decline
once Ro falls below unity. Such interventions include better
health-seeking behavior, improved access to services, improved
quality of sexual health services through the introduction of
STI syndromic management, high levels of treatment, a reduc-
tion in high-risk sexual behavior and increased condom use as
well as better sexual healthcare for sex workers and their
partners [23,30,31].
As a result of the painful nature of the genital ulcers, as well
as the belief that persistent asymptomatic carriage of H. ducreyi
is of limited or of no importance in transmission, chancroid
may continue to exist only among those individuals who
belong to sexual networks characterized by high turnover
of sexual partners in resource-poor communities with limited
access to healthcare services. As an example, surveillance
studies undertaken in other Southern African Development
Community countries since 2004 suggest that chancroid still
remains an important cause of GUD in some parts of Lesotho
[LEWIS D, UNPUBLISHED DATA], Madagascar [LEWIS D, UNPUBLISHED DATA] and
Malawi [32].
There are some key challenges in interpreting data on the
prevalence of chancroid. First, genital herpes cases are easily
misdiagnosed as chancroid on clinical examination and so
reports based on clinical diagnosis alone can be erroneous [3335].
Second, laboratory culture is technically difficult as well as
insensitive, while NAATs are rarely available outside of national
reference laboratory of specialized STI research settings; this
makes it difficult to confirm clinical diagnoses. Determination
of the true global burden of chancroid is made even more diffi-
cult given that those countries that use the syndromic approach
for STI management report, at best, only total numbers of
GUD presentations and genital ulcer etiological surveys are
rarely, if ever, carried out. These include those resource-poor
countries where chancroid is most likely to occur.
Clinical features
After initiation of infection at sites of microabrasions, H.
ducreyi infection may first manifest as tender erythematous pap-
ules within 47 days. These papules may subsequently progress
to a pustular stage and then an ulcerative stage (FIGURE 1) [4].
Human studies of experimental H. ducreyi infection have dem-
onstrated that a delivery dose of approximately 30 colony form-
ing units (CFU) of the pathogen results in a papule formation
rate of 95% and a pustule formation rate of 69% [36]. Charac-
teristically, the ulcers of chancroid are multiple, painful, puru-
lent and deep with ragged undermined edges and evidence of
bleeding points in the base [4].
Expert Rev. Anti Infect. Ther. 12(6), (2014)
 Epidemiology, clinical features, diagnosis & treatment of H. ducreyi
Chancroid typically appears on the prepuce (FIGURE 1) and
penile frenulum in men and severe infection may result in phi-
mosis and phagedenic ulceration [3,4]. Perianal chancroid,
although rare, may occur in men-who-have-sex-with-men. In
women, chancroid typically presents as vulval ulceration,
although internal cervical ulcers may also occur [3,4].
The phenomenon of auto-inoculation is well-described for
H. ducreyi and may result in extra-genital lesions on inner
thighs and breasts. More recently, through use of a 16S rRNA
PCR assay and subsequent sequencing of the PCR-generated
amplicons, H. ducreyi has been identified as the causative agent
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for chronic skin ulceration in lower limbs of children visiting
Samoa and an adult female resident in Vanuatu [37,38]. This
pathogen has also caused lesions in fingers of laboratory work-
ers following accidental inoculation of H. ducreyi bacteria [39].
Co-existent with the ulcers, painful lymphadenopathy and
bubo formation has been reported in up to 50% of chancroid
cases (FIGURE 2) [3]. These pathological lesions are most often seen
in men in keeping with the gender-related epidemiology of
chancroid described above.
Laboratory diagnosis of H. ducreyi infection
Specimen collection & transport
Material from the ulcer base is the preferred sample for detection
For personal use only.
of H. ducreyi [40]. In purulent ulcers, it is recommended that the
superficial inflammatory exudate is first removed using a swab or
by flushing the ulcer with sterile physiological saline. As the path-
ogen only survives on swabs for 24 h, it is recommended that
inoculation of selective enriched H. ducreyi culture media is per-
formed at the time of specimen collection [41,42]. Alternatively,
but less ideal, swabs with ulcer-derived material may be placed in
Amies transport medium and sent immediately to the local labo-
ratory for culture [40]. An in-house thioglycolate hemin-based
transport media has been described, which retained viability of
H. ducreyi for up to 4 days, but this transport medium is not
commercially available [43]. If diagnosis is to be undertaken using
molecular assays, the ulcer swab should be placed in an empty
sterile tube and sent as a dry swab to the laboratory [40]. Bubo
pus is an alternative diagnostic sample and may be the only
option in the absence of associated GUD. However, culture of
bubo pus is quite often negative and published experience with
molecular diagnostic assays is extremely limited.
Bacteriological diagnostic techniques
H. ducreyi is a Gram-negative bacillus and organisms tend to
clump together, a phenomenon that gives rise to the character-
istic schools of fish, fingerprints or railroad track morpholo- anaerobic environment [1]. It is important to note that the opti-
gies described in the literature [2]. However, as these
morphological features lack both sensitivity and specificity,
microscopy should not be used as a means to diagnose
chancroid [1,42].
For many years, culture was the gold standard method for
diagnosing H. ducreyi infection. Molecular methods (see below)
have now replaced culture as the diagnostic method of choice
and it has been reported that culture is at best only 75%
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Review
Figure 1. Penile ulceration due to Haemophilus ducreyi
infection.
Reproduced with permission from [4].
sensitive in comparison with molecular assays [33,44]. However,
given that most of these DNA/RNA-based assays are in-house
and few are commercially available, most diagnostic microbiol-
ogy laboratories would still employ culture-based techniques if
they are required to identify H. ducreyi from clinical specimens.
The pathogen has fastidious growth requirements and optimal
recovery is obtained through the use of freshly made media
and attention to the incubation conditions.
Ideally, a minimum of two different media should be
employed to improve the sensitivity of culture as a diagnostic
method [45,46]. Several media have been described and recom-
mended media options have been reviewed in detail else-
where [3]. The most widely used media require either
Gonococcal agar or Mueller-Hinton agar as the base to which
TM
is added, first, a nutritional supplement (e.g., IsoVitaleX
enrichment) and, second, either 1% hemoglobin with 5% fetal
calf serum or 5% chocolatized blood [3]. Overgrowth of com-
mensal Gram-positive bacteria on the ulcer swab is prevented
through use of vancomycin (3 mg/ml); however, some clinical
H. ducreyi strains are inhibited by vancomycin at this concen-
tration and additional non-selective plates may require inocula-
tion to ensure recovery of the pathogen [47]. In an attempt to
reduce the cost of culture media for H. ducreyi, an activated
charcoal-containing medium has been used in some resource-
poor settings with success [48].
Once inoculated, agar plates should be incubated at 3335C
in a humidified incubator, ideally in a microaerophilic or strict
mal temperature for H. ducreyi is 33C and that viability is
compromised if the incubator temperature exceeds 35C [40].
Identification of presumptive H. ducreyi colonies typically
relies upon colony morphology, the fact that colonies can be
pushed across the plate intact due to bacterial adherence
(clumping), as well as Gram staining of single colonies [40].
Presumptive identification can be assisted with demonstration of
a positive oxidase reaction and a negative catalase reaction [49].
689
 Review Lewis
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Figure 2. Right-sided inguinal bubo and penile ulcer in a
man with chancroid.
Reproduced with permission from [4].
Full biochemical identification is hampered by the fact that
H. ducreyi cannot grow on the media used in commercially
available biochemical test strips and demonstration of
X-factor dependence relies on a negative porphyrin test [40].
Additional biochemical tests that may be helpful include
For personal use only.
demonstration of alkaline phosphatase production and nitrate
reduction [1].
Molecular-based detection
Several molecular diagnostic approaches have been evaluated
and employed in research and reference laboratories.
32
P-labeled DNA probes reliably detect 104 CFU of H. ducreyi
in both pure and mixed cultures, but this technology lacks the
sensitivity associated with NAATs [50]. Several PCR assays have
been described that amplify DNA sequences from a number of
targets on the H. ducreyi genome, including the 16S rRNA
gene, the rrs (16S rRNA)/rrl (23S rRNA) intergenic spacer
region, an anonymous fragment of cloned H. ducreyi DNA,
the gene encoding a 27 kDa H. ducreyi-specific protein and the
groEL gene and the recD gene [44,5158]. Although PCR assays
for H. ducreyi may perform well using bacterial colonies as the
source of DNA template, the sensitivity of these assays can be
reduced by the presence of Taq polymerase inhibitors in the
GUD swab specimen, particularly if a sodium phosphate-
containing transport medium is used [59]. In such situations,
the assay sensitivity may be improved through the use of deter-
gents in preparing nucleic acid from clinical specimens and the
inclusion of a dialysis step prior to amplification [59].
Given the rarity of H. ducreyi as an etiological cause of
GUD, the most useful PCR assays are those which are available
in a multiplex format. The first multiplex PCR (M-PCR) to
detect multiple GUD pathogens (HSV-1/2, Treponema pal-
lidum and H. ducreyi) was developed by Roche in the 1990s,
although it was never made available on a commercial basis [44].
This assay has been used to study the etiology of GUD in a
number of geographic locations, including the USA, India,
690
Lesotho, Madagascar, South Africa and Thailand [20,33,44,6063].
A novel in-house GUD M-PCR assay, with the added advan-
tage of an internal control, was developed by Mackay and col-
leagues to additionally detect Klebsiella (Calymmatobacterium)
granulomatis, the causative agent of donovanosis [51]. Recently,
commercially produced Seeplex M-PCR panels (Seegene,
Seoul, South Korea) have become available, which include the
STD4 ACE Detection test (H. ducreyi, T. pallidum, HSV-1/
2 and Candida albicans) and the STI Master Panel 5 test (H.
ducreyi, T. pallidum, Chlamydia trachomatis L1-L3, Streptococcus
agalactiae and cytomegalovirus). However, the performance
characteristics of the Seeplex M-PCR panels for H. ducreyi
diagnosis have yet to be independently evaluated in countries
where chancroid is still endemic.
Other non-culture-based methods of detection
Given the technical challenges of H. ducreyi culture and the
general unavailability of molecular diagnostic assays, there is a
need to develop other non-culture modalities to assist with the
diagnosis of chancroid cases. Matrix assisted laser desorption/
ionisation/TOF-mass spectrometry can enable rapid identifica-
tion of bacteria (within 10 min) and this technique has been
evaluated as a diagnostic and typing tool using H. ducreyi colo-
nies [64]. A large number of monoclonal antibodies (mAb)
against H. ducreyi have been generated in research laboratories
and some of these have been harnessed for potential diagnostic
use [65,66]. An anti-lipo-oligosaccharide mAb was used with suc-
cess in an immunolimulus system, which enabled detection of
as few as 103 CFU of cultured H. ducreyi per ml of buffer as
well as detection of this pathogen in experimental rabbit
lesional material [65]. Patterson et al. developed a rapid
immunochromatographic-based diagnostic test for chancroid
using mAb directed against the H. ducreyi hemoglobin recep-
tor [66]. However, although the test only took 15 min to per-
form, it required at least 2  106 CFU of H. ducreyi to
generate a positive reaction and would therefore be an insensi-
tive tool to detect this pathogen in genital ulcer swabs.
Serological detection
The humoral immune response to H. ducreyi infection only
starts to develop as the disease progresses through the ulcerative
stage [42,67]. This is supported by the observed lack of IgG anti-
body responses to either H. ducreyi lipo-oligosaccharide or
ultrasonicated whole cell antigen in subjects experimentally
infected with the pathogen up to the pustular stage [67]. Due to
their low sensitivity compared with PCR, serological techniques
have no place in the diagnosis of chancroid among GUD
patients [57]. However, they may be useful as a tool to perform
sero-epidemiological studies within communities [17,68,69].
Antimicrobial susceptibility testing
As one would expect from the fastidious nature of H. ducreyi
and its tendency to clump, antimicrobial susceptibility testing
presents a technical challenge and there is no standardized pro-
cedure for this activity. Minimum inhibitory concentrations of
Expert Rev. Anti Infect. Ther. 12(6), (2014)
 Epidemiology, clinical features, diagnosis & treatment of H. ducreyi
antimicrobial agents may be determined by conventional agar
dilution or through use of Etest methodology, although this
is rarely performed in practice [70,71].
Although historically susceptible to a wide range of antimi-
crobial agents, H. ducreyi has acquired a variety of resistance
mechanisms over time. Plasmid-mediated resistance has been
described for tetracycline, chloramphenicol, sulfonamides, peni-
cillin and aminoglycosides [2,7276]. Different antimicrobial
resistance-encoding plasmids may exist in the same bacterial
cell and some plasmids contain genes that encode resistance to
more than one antimicrobial agent. In addition, chromosomally
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mediated antimicrobial resistance has been described for tri-
methoprim, penicillin and fluoroquinolones among plasmid-
free H. ducreyi isolates [2,77,78]. The upward drift in the in vitro
minimum inhibitory concentrations for ciprofloxacin and
erythromycin in the 1990s emphasizes the importance of moni-
toring, wherever possible, H. ducreyi clinical isolates for antimi-
crobial susceptibility as part of ongoing chancroid eradication
strategies [78].
Treatment
Due to the substantial decline in chancroid, as well as the tech-
nical difficulty of performing antimicrobial susceptibility testing
for H. ducreyi, there have been no published antimicrobial
For personal use only.
resistance data for this pathogen for approximately two decades.
Despite this, chancroid may still be treated effectively with
macrolides (azithromycin, erythromycin) cephalosporins (ceftri-
axone) and fluoroquinolones (ciprofloxacin) (TABLE 1) [79].
Although the combination of amoxicillin with clavulanic acid
may be effective in some countries, it is no longer recom-
mended in the USA due to concerns over chromosomally
mediated b-lactam resistance [78]. As advocated by WHO, geni-
tal ulceration is normally treated syndromically in most
resource-poor countries where chancroid is still, or has recently
been, endemic. Typically, GUD treatment flow charts contain
additional treatment to cover syphilis and, in many countries,
also genital herpes and lymphogranuloma venereum [80].
Treatment failures to single dose oral fleroxacin, intramuscu-
lar ceftriaxone and oral azithromycin therapies for proven chan-
croid cases have been reported among HIV-1 co-infected
patients [8183]. These treatment failures appear to be due to
causes other than antimicrobial resistance and it is believed that
single-dose therapies are not always sufficient to cure chancroid
in the context of HIV-1-associated immunosuppression [81].
Accordingly, HIV-1 seropositive patients may require repeated
or longer courses of treatment than those normally prescribed
for HIV-1 seronegative patients. All patients, particularly those
infected with HIV, should be carefully followed-up by the
attending clinician to ensure that clinical cure is achieved with
currently recommended antimicrobial therapies [79].
Both chancroid and lymphogranuloma venereum may result
in inguinal bubo formation and this complication requires at
least 2 weeks antimicrobial therapy. Large suppurated buboes
may require aspiration or incision and drainage in order to
avoid spontaneous rupture [84,85]. In a US-based study,
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Review
Ernst et al. reported that patients with buboes who received
incision and drainage required no further intervention, whereas
approximately half of those who received aspiration required
further attempts at aspiration [84]. There has been some debate
as to which of these two options should be recommended in
resource-poor settings and, currently, WHO only recommends
aspiration for the management of suppurated buboes [79,86]. In
comparison with bubo aspiration, incision and drainage may
take longer to heal, which may lead to secondary infection, par-
ticularly in immunosuppressed HIV-1-infected patients.
Conclusion
Chancroid is a disease in terminal decline and is now likely
close to extinction in many of those countries where it was pre-
viously endemic. The successful and widespread implementa-
tion of GUD syndromic management incorporating effective
drugs to treat chancroid, the behavioral changes observed
within communities following the escalation of the HIV epi-
demic and a rise in socioeconomic circumstances in some
countries have undoubtedly played a role in the demise of H.
ducreyi infection. However, the inaccuracy of clinical diagnosis,
the absence of laboratory specimens as a result of the STI syn-
dromic approach, the difficulty to detect H. ducreyi in most
laboratories and the lack of molecular-based etiological surveil-
lance for GUDs in many countries means that we have little or
no recent prevalence data for chancroid. Now is surely the time
to call for public health investment in setting up a task team to
document where we have got to in terms of chancroid elimina-
tion through targeted surveillance activities. Such an exercise
would highlight those countries where efforts should be focused
over the next decade in order to achieve the reality of chan-
croid eradication on a global scale.
Expert commentary & five-year view
The substantial decline in chancroid ulcers and buboes within
many countries of Africa and Southeast Asia over the past two
decades has been remarkable. This decline, which followed the
implementation of the syndromic approach for STI manage-
ment and control, has been cited by proponents of this
approach as strong supporting evidence for the impact of STI
syndromic management in resource-poor settings. Syndromic
management for STIs, a tool established to improve the man-
agement of symptomatic STIs and which can be delivered by
nurses in a variety of urban and rural settings, has certainly
improved the quality of sexual health service provision in many
countries. The approach works best for those STIs that are
mostly or exclusively symptomatic as well as those that are
severe enough to motivate a patient to seek early STI care. It is
therefore entirely predictable that syndromic management
would exert its strongest effect on an STI such as chancroid,
which is characterized by multiple, deep and painful genital
ulcerations and for which asymptomatic carriage is not thought
to play a major role in transmission.
However, it is important to note that there are several other
additional factors that may also have made significant
691
 Review Lewis

Table 1. Summary of recommended regimens for the treatment of chancroid in various international
guidelines.
Guideline (year) WHO (2003) [86] CDC (2010) [87] European (2011) [88] BASHH (2013, draft) [89]

Recommended Ciprofloxacin, Azithromycin, Ceftriaxone, Azithromycin,

regimens 500 mg orally, 1 g orally, 250 mg intramuscularly, 1 g orally,
12 h for 3 days as a single dose as a single dose as a single dose
OR OR OR OR
Erythromycin base, Ceftriaxone, Azithromycin, Ceftriaxone,
500 mg orally, 250 mg intramuscularly, 1 g orally, 250 mg intramuscularly,
6 h for 7 days as a single dose as a single dose as a single dose
OR OR OR
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Azithromycin, Ciprofloxacin, Ciprofloxacin,

1 g orally, 500 mg orally, 500 mg orally,
as a single dose 12 h for 3 days as a single dose
OR OR
Erythromycin base, Ciprofloxacin,
500 mg orally, 500 mg orally,
8 h for 7 days 12 h for 3 days
OR
Erythromycin base,
500 mg orally,
6 h for 7 days
Alternative Ceftriaxone, None stated Ciprofloxacin, None stated
regimens 250 mg 500 mg orally,
intramuscularly, 12 h for 3 days
For personal use only.

as a single dose OR
Erythromycin base,
500 mg orally,
6 or 8 h for 7 days
Specific Follow patients up Monitor patients closely as more No specific The erythromycin regimen is
recommendations weekly until likely to experience treatment recommendations recommended for HIV-infected
for treating clear evidence of failure with any of stated patients rather than any of
HIV-infected improvement the above regimens the single-dose therapies
individuals Azithromycin and ceftriaxone
regimens to be used only when
follow-up can be assured
BASHH: British Association for Sexual Health and HIV.

contributions to the reported decline in chancroid during the
same time period. The rise of the HIV-1 epidemic in chan-
croid endemic areas of the world, from the late 1980s onward,
was accompanied by changes in sexual behavior within commu-
nities and key populations as a result of the perceived fears for
personal health and implementation of a number of general
and targeted HIV-1 prevention programs. Public health
responses to the HIV-1 epidemic included efforts to change
sexual behavior in terms of promoting abstinence, faithfulness
and/or condom use within the general population. Very rele-
vant to chancroid, an STI strongly associated with exposure to
or practice of commercial sex work, sexual health and
HIV-1 prevention programs targeted at CSWs are thought to
have been very important in curtailing the transmission of H.
ducreyi [23]. Such programs are characterized by use of peer
educators, provision of CSW-focused sexual health services in
the workplace or through mobile outreach services, marketing
and distribution of male and female condoms, appropriate
management of STI syndromes, provision of periodic
presumptive therapy and ongoing sexual health education.
Finally, the magnitude of the effect of the roll-out of medical
male circumcision programs within sub-Saharan Africa is
unknown, but this mass HIV-1 prevention strategy has also
likely played, and will continue to play a role in the demise
of chancroid.
While it is clear that chancroid has declined as a cause of
sexually acquired GUD in many countries, the recent reports
of chronic lower limb ulceration in individuals from the South
Pacific islands is of particular interest [37,38]. These ulcers, which
may be clinically misdiagnosed as yaws without appropriate
investigation using sensitive and specific diagnostic assays, are a
relatively newly described presentation for H. ducreyi, and are
most likely transmitted non-sexually between individuals. Fur-
ther ulcerative lesions may occur on the limb though the pro-
cess of auto-inoculation. Further clinical and epidemiological
research is required to improve our understanding of this der-
matological manifestation of H. ducreyi infection using appro-
priate diagnostic tools. It is unclear, at the present time, as to

692 Expert Rev. Anti Infect. Ther. 12(6), (2014)

 Epidemiology, clinical features, diagnosis & treatment of H. ducreyi Review

DATA]. Whether such a strategy would lead to the resurgence of

whether or not this pathogen can cause similar cutaneous
lesions in individuals residing in other regions of the world.
The importance of GUD, and particularly chancroid, as a co-
factor in HIV-1 transmission, particularly in terms of
HIV-1 acquisition, and the epidemiological synergy that exists
between the two should not be underestimated at the individual
level. Accordingly, it is important to ensure that appropriate
treatment is given for all suspected chancroid cases. While we do
not have recent antimicrobial susceptibility data to guide current
treatment guidelines, the lack of reported treatment failures over
the past two decades suggests that treatment with the recom-
Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by CDL-UC San Diego on 12/31/14
chancroid in the future remains to be seen.
In terms of future diagnostics, commercialization of cheap
GUD-targeted M-PCR assays, which should include primers
for H. ducreyi infection, will be essential if we are going to be
able to accurately determine the global prevalence of H. ducreyi
infection and identify which countries require extra support to
eliminate chancroid as a cause of GUD. As chancroid has
become less prevalent in those countries with high-quality diag-
nostic capability, now is perhaps the time to undertake a global
mapping exercise to determine exactly where and at what prev-

mended cephalosporins, macrolides and fluoroquinolones should
still be effective. It is, however, important for clinicians to be
aware that HIV-1 immunosuppressed patients may not respond
to single dose oral or intramuscular treatments and that all
HIV-1-infected patients treated for suspected chancroid should
be followed-up at 1 week to assess the degree of ulcer healing.
Chancroid has become so rare in some countries that there
is now discussion regarding removing antimicrobial therapy for
H. ducreyi from first-line GUD treatment algorithms and
reserving it instead for second-line therapy. For example, in
South Africa, now that chancroid accounts for less than 1% of
GUD cases, it has been recently debated as to whether first-line
GUD therapy should be dispensed for only genital herpes and
For personal use only.
alence chancroid exists in those countries which lack data. It is
possible that chancroid could be the first bacterial STI to be
eradicated. This would be a huge achievement, given that it
would have been achieved by improving the quality of sexual
healthcare, sexual behavior change and use of appropriate anti-
microbial agents in the absence of an effective vaccine.
Financial & competing interests disclosure
The author has a PEPFAR grant from the US Centers for Disease Control
and Prevention (CDC) to support STI surveillance activities in South
Africa, although this is not relevant to the current review. The author has no
other relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the subject matter

syphilis, with single-dose azithromycin being reserved for or materials discussed in the manuscript apart from those disclosed.
second-line treatment of non-healing ulcers [LEWIS D, UNPUBLISHED No writing assistance was utilized in the production of this manuscript.

Key issues
A number of studies and surveillance reports have reported marked declines in the prevalence of chancroid in many countries where it
was previously endemic.
There have been some recent reports of Haemophilus ducreyi causing chronic skin ulceration in patients visiting or from the South
Pacific islands.
The current prevalence of chancroid is unknown for most countries as they lack the required laboratory diagnostic capacity and
surveillance systems to report on this.
The optimal diagnostic method involves H. ducreyi-specific nucleic acid amplification, but few molecular assays are commercially available.
H. ducreyi culture is technically challenging and requires freshly made specialized vancomycin-containing media and strict incubation conditions.
It is still assumed that chancroid will usually respond successfully to treatment with recommended cephalosporin, macrolide or
fluoroquinolone-based regimens, despite the absence of recent antimicrobial susceptibility data for H. ducreyi.
HIV-1-infected patients require careful follow-up due to reports of treatment failure with single-dose regimens.
Fluctuant buboes may require aspiration or excision and drainage.

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