Secondary Syphilis in Man Sex with Man Coinfection HIV

Dyah Ayu Savitri, Taufiq Hidayat

Department of Dermatovenereology, Brawijaya University
Dr. Saiful Anwar General Hospital, Malang
Abstract
Introduction : Syphilis and HIV are both transmitted sexually and so it is no surprise that a
substantial number of people are infected with both agents. Serology is the mainstay for
syphilis diagnosis and treatment monitoring.8
Case Report : A 27-year-old homosexual man presented with non-pruritic reddish rashes on
the palms and soles since 2 weeks before. Suddenly appeared as small multiple reddish
rashes in his palms and soles, reddish rashes then became wider and scaly. Patient had been
complained about genital ulcer 2 months ago, but slowly disappeared itself. He had been
diagnosed as HIV with CD4 value was 300 cells/L and advised not to take antiviral yet.
There were no severe weight loss, chronic diarrhea or persistent fever. On palmar and plantar
dermatological examination revealed well-defined erythematous patch irregular shaped cover
with whitish thick scales with diameter various 1-2 cm. On scrotum and penis, dermatological
diameter 1-2 cm. Lymphadenopathies were tender in axilla dextra and inguinal dekstra and
sinistra. VDRL was 1:64 and TPHA was reactive 1:320. CD4 revealed 341 cells/L.Skin biopsi
showed lichenoid reaction, mild acanthosis and hyperkeratosis on epidermis. Infiltrate of
lymphocyte and plasma cells in dermis. Darkfield microscoopy found presence of Treponema
pallidum spirochetes with an oblique manner. Benzathine benzylpenicilline 2,4 million IU
single dose intramuscular was administrated. Two weeks after injection VDRL showed 1:1280
and TPHA were reactive >1:64. Erythematous patches were decreased after two weeks follow
up.
Discussion : Generally, the VDRL titer should decline at least 4-fold within 36 months after
therapy for primary or secondary syphilis. No firm conclusion can be drawn regarding whether
HIV coinfection significantly alters the treatment response.
Keywords : Secondary syphilis, Man sex with man, HIV

INTRODUCTION
Syphilis, a sexually transmitted disease caused by the spirochete Treponema
pallidum, is a major worldwide, potentially life-long health problem with the potential
to manifest multiple patterns of skin and visceral disease. 1 If left untreated, syphilis
progresses through distinct initial symptomatic stages (primary and secondary
syphilis), an asymptomatic stage that can last for years (latent syphilis), and a late
symptomatic stage (late syphilis).1,2 In referring to the protean manifestations of
syphilis, Sir William Osler proclaimed the disease to be the great imitator and
indeed, secondary syphilis often demonstrates diverse clinical and histological
features.3 Syphilis may increase the risk of HIV transmission and acquisition by
causing genital ulcers.4
Syphilis and HIV are both transmitted sexually and so it is no surprise that a
substantial number of people are infected with both agents. HIV has several effects
on the presentation, diagnosis, disease progression, and therapy of syphilis. 4 In the
UK the incidence of syphilis fell dramatically through the 1980s to less than 1/100000
of the population. A rise in syphilis incidence has been seen since 1996 with most
cases occurring in young men. Over the same time period there has also been an
increase in new HIV diagnoses in the UK increasing the likelihood of HIV and syphilis
co-infection. In 2002 syphilis rates for men in England and Wales ranged from
0,5/100000 in rural areas to more than 2/100000 in metropolitan districts with
particularly high rates in Brighton, Manchester, and London.4,5
Co-infection of syphilis with HIV among Man Sex with Man (MSM) is expected
to have played an important role in this resurgence. The positive association
observed between syphilis and HIV among MSM can be explained by biological
plausibility and similar risk behaviors associated with both infections. 6 Serological
tests may be negative in early primary syphilis and here direct identification of the
organism by dark field microscopy or within tissue biopsies may confirm the clinical
diagnosis.2
Case reports have identified potential differences in serological testing for
syphilis between HIV-negative and HIV-positive patients although the clinical
importance of these differences remains unclear. These differences include an
increased rate of negative serological tests in both primary and secondary syphilis,
increased false-negative non-treponemal antibody tests due to the prozone effect,
high rate of failure to clear non-treponemal antibody after therapy (serofast) and
seroreversion to negative of specific treponemal antibody tests after therapy.2,7

Serology is the mainstay for syphilis diagnosis and treatment monitoring. 8

Hereby, report of a case secondary syphilis in man sex with man HIV patient treated
by benzathine benzylpeniciline showed by increasing significant rate of nontreponemal antibody test.

CASE REPORT
A 27-year-old homosexual man came to Dermatovenereology Department
Saiful Anwar Hospital presented with non-pruritic reddish rashes on the palms and
soles since 2 weeks before admission. Suddenly appeared as small multiple reddish
rashes in his palms and soles, reddish rashes then became wider and scaly. There
were no ulcer in genitalia and mouth. There was no fever. There was no hair loss.
Patient had been complained about genital ulcer 2 months ago, but slowly
disappeared itself. He also had complained about whitish discharge urethra, he took
Supratetra so the whitish discharge healed.
He had been diagnosed as HIV in Wlingi Regional Hospital with CD4 value
was 300 cells/L and advised not to take antiviral yet. There were no severe weight
loss, chronic diarrhea or persistent fever. There was no history of similar complains in
his family nor history of reddish rashes appeared after trauma to him and his family.
No history of bleeding in his rashes before. No history of pain group vesicles in
genital before. There were history of took Habbatus Sauda pills routinely after
diagnosed HIV.
Patient was unmarried man who has sex with man work as cosmetic sales.
History of multiple partners with last sexual activity was 2 months before year ago
intercourse through fellatio or anal sex never using condom. He denied of using
injection of any drugs, didnt have tattoo and never had any blood transfusion. On
palmar and plantar dermatological examination revealed well-defined erythematous
patch irregular shaped cover with whitish thick scales with diameter various 1-2 cm.
On

scrotum

and

penis,

dermatological

examination

showed

well-defined

erythematous plaque irregular shaped and flat surface with diameter 1-2 cm.
Physical examination revealed a compos mentis man with blood pressure
120/80mmHg, the pulse rate was 88 times per minute, the respiration rates was 20
times per minute and temperature axilla was 37 0C. There were no anemic
conjungtiva, no cyanotic, no alopecia and no papules or macules in oral mucosa.
Heart and lung were normal; liver and spleen were not palpable. There was no
edema in his extremities. Lymphadenopathies were tender in axilla dextra and
inguinal dekstra and sinistra.

B
Figure 1. Dermatological examination on palmar (A) and plantar (B) dekstra and sinista
showed well-defined erythematous patches irregularly shaped covered with whitish thick
scales diamater various in 1-3cm (showed in black arrow).

B
Figure 2. Well-defined erythematous plaque was revealed on scrotum and penis in diameter
1-2cm (showed in red arrow)(A). Orificium urethra externa were showed no edema, no
erythema nor discharge (B)

Figure 3. Dermatological examination on anal mucosa (A) and oral mucosa (B) showed no
papules or plaque.

Figure 4. There were no eyebrow loss (-), no lession in mouth and nose, split papules (-) (A)
and no alopecia (moth eaten) (B).

Figure 5. There were no erythematous papules or plaque in chest, abdomen (A) and back
(B).

Routine hematologic examination showed no abnormality. Differential count

showed neutrofilia 82,8% and lymphocyte 13,8%. Liver and renal function was within
normal limit. VDRL was 1:64 and TPHA was reactive 1:320. CD4 revealed 341
cells/L. Urinalysis was normal. Skin biopsi were taken in erythematous patch on
plantar pedis showed lichenoid reaction, mild acanthosis and hyperkeratosis on
epidermis. Infiltrate of lymphocyte and plasma cells in dermis. Darkfield microscoopy
found presence of Treponema pallidum spirochetes with an oblique manner (figure
7).

Figure 6. A. Histopathological examination revealed lichenoid reaction, mild acanthosis and

hyperkeratosis on epidermis. B. Infiltrate of lymphocyte (showed black arrow) and plasma
cells (showed green arrow) in dermis.

Figure 7. Darkfield microscopy revealed presence of Treponema pallidum spirochetes with an

oblique manner

From history taking, dermatological examination, serological test, skin biopsi

and darkfield microscopy, patient was assessed with secondary syphilis with HIV
infection stage 1. Benzathine benzylpenicilline 2,4 million IU single dose
intramuscular was administrated. Consulted to Internal Department, Anti Retro Viral
(ARV) and cotrimoxazole were given. Two weeks after injection erythematous
patches were decreases and VDRL and TPHA were checked. VDRL showed 1:1280
and TPHA were reactive >1:64. Complete blood count, liver function, and renal
function were within normal imit. Erythematous patches were decreased after two
weeks follow up.

Figure 8. Picture of palmar manus plantar pedis after two weeks therapy. Erythematous
patches have decreased.

DISCUSSION
Syphilis, a sexually transmitted disease caused by the spirochete Treponema
pallidum, is a major worldwide, potentially life-long health problem with the potential
to manifest multiple patterns of skin and visceral disease. 1 In 2002 syphilis rates for
men in England and Wales ranged from 0,5/100000 in rural areas to more than
2/100000 in metropolitan districts with particularly high rates in Brighton, Manchester,
and London.4,5 Co-infection of syphilis with HIV among Man Sex with Man (MSM) is
expected to have played an important role in this resurgence. The positive
association observed between syphilis and HIV among MSM can be explained by
biological plausibility and similar risk behaviors associated with both infections. 6
Hereby a case of secondary syphilis man who has sex with men co-infection HIV
patient. Diagnosis is generally made with history taking, dermatology and physical
examination, serology, histopathology and darkfield microscopy.
History taking was presented a 27-year-old homosexual man came to
Dermatovenereology Department Saiful Anwar Hospital presented with non-pruritic
reddish rashes on the palms and soles since 2 weeks before admission. Suddenly
appeared as small multiple reddish rashes in his palms and soles, reddish rashes
then became wider and scaly. Patient had been complained about genital ulcer 2
months ago, but slowly disappeared itself. He had been diagnosed as HIV in Wlingi
Regional Hospital with CD4 value was 300 cells/L and advised not to take antiviral
yet. Moreover, the infection was shown to predominate in those with a history of
blood transfusion. But, syphilis was not found to be associated with variables such as
level of CD4+ T-cell count, having multiple sexual partners, and current condom use
practice.19
The secondary stage of syphilis is a manifestation of widespread
hematogenous and lymphatic dissemination of the infection. The typical papular
eruption in the palms and soles, the well-known helpful diagnostic sign, is depicted
side by side with roseola syphilitica, moth-eaten alopecia, and leukoderma. 9 History
of untreated genital ulcer had been a proof of primary infection to support diagnosis
that could be disappeared even treatment was not administrated. Even history taking
and physical examination was not support diagnosis of either moth eaten alopecia or
leukoderma, the onset did. The macular rash had been appeared 8 weeks after
untreated genital ulcer had occured that disappeared by itself.
Typically syphilis occurs in three phasesnamely primary, secondary, and
tertiary disease. However, this is a gross oversimplification and the clinical

presentation of syphilis is extremely variable over many years (figure 10). 10 Several
differences have been reported in the manifestations of syphilis in HIV-positive
patients. In particular there seems to be a shift from presentation with primary to
secondary disease and more aggressive disease progression. Furthermore, HIV
itself or opportunistic infections may confuse clinical and diagnostic findings.4

Figure 9. Typical presentations of syphilis over time in the HIV-negative patient. 10

On palmar and plantar dermatological examination revealed well-defined

erythematous patch irregular shaped cover with whitish thick scales with diameter
various 1-2 cm. On scrotum and penis, dermatological examination showed welldefined erythematous plaque irregular shaped and flat surface with diameter 1-2 cm.
Skin lesions are a common manifestation of secondary syphilis (72%)42 and may be
the presenting feature. A number of different types of skin lesions are recognised
together with lymphadenopathy, malaise, arthralgia, and fever. The most common
type is of a diffuse maculopapular rash which typically appears about 6 weeks after
the primary lesions and signifies haematogenous spread of T pallidum.4,12
A generalised macular rash with palmar-plantar involvement may also occur
but other types may occur such as lichenoid, papular, papulosquamous, ulcerated,
and urticarial lesions with hair loss varying from alopecia to involvement of the
eyebrows and even total loss of body hair. Nodular and annular skin lesions over the
face, back, and limbs are reported as are large plaques on face, neck, and upper
extremities. Nodular skin lesions can be seen in secondary or tertiary syphilis and
clinical and histological stages may overlap.4,13
Lymphadenopathy was documented as being present in the head or neck in
20 patients (18.7%), in the axillary region in 12 patients (11.2%), in the inguinal
region in 16 patients (15.0%), in two out of three locations in 39 patients (36.4%), and
in all three locations in 20 patients (18.7%). Based on the lymph node biopsy,

malignancy was diagnosed in 46 patients (42.9%), infection in eight patients (7.5%),

and reactive changes in 53 patients (49.5%).11 There were enlargement of lymph
node in this patient with tender palpation in axilla dextra and inguinal dekstra and
sinistra.
Serological testing was revealed VDRL titer value 1:64 and TPHA titer
reactive in value 1:320. Case reports have identified potential differences in
serological testing for syphilis between HIV-negative and HIV-positive patients
although the clinical importance of these differences remains unclear. These
differences include an increased rate of negative serological tests in both primary
and secondary syphilis,15,16 increased false-negative non- treponemal antibody tests
due to the prozone effect,16,17 high rate of failure to clear non-treponemal antibody
after therapy (serofast),18 and seroreversion to negative of specific treponemal
antibody tests after therapy.19
Due to the varied appearances of syphilis manifestations, and because
several other diseases may cause similar appearances, biopsy is common and often
establishes the diagnosis. Histologically a wide range of changes is seen.
Treponomes are seen in both the epidermis and dermis. Plasma cells and
lymphocytes (which can be CD4+ lymphocyte, CD8+ lymphocyte, or histiocytic in
type) can be seen around blood vessels which may have marked endothelial swelling
and proliferation associated with increased levels of vascular endothelial derived
growth factor. No correlation is seen between types of skin lesion and VDRL titer.
Nodular lesions may show sarcoid-like granulomata with lymphocytes, histiocytes,
oeosinophils, plasma cells, and multinucleated giant cells.4,14 Skin biopsy was taken
from this patient skin rash to help diagnosis. The histopathological examination
revealed

to

roseola

syphilitica.

Lichenoid

reaction,

mild

acanthosis

and

hyperkeratosis on epidermis and infiltrate of lymphocyte and plasma cells in dermis

were figured (figured 6).
Because sustained in vitro cultivation of T. pallidum is not possible and animal
(i.e. rabbit) inoculation is time consuming and expensive, laboratory diagnosis of
syphilis is usually based on direct detection of T. pallidum and/or serology. Direct
detection of T. pallidum by dark-field microscopy has remained the gold standard for
diagnosis of syphilis in patients presenting with lesions of early, active syphilis (i.e.
primary and secondary stage). Dark-field microscopy has a sensitivity of 3981%
with a specificity of 82100%.21 A clinical diagnosis of syphilis is confirmed by using
darkfield microscopy to demonstrate Treponema pallidum in material from suspected
lesions or regional lymph nodes. A positive darkfield result is an almost certain
diagnosis of primary, secondary, or early congenital syphilis. For patients with early

primary syphilis or for patients with syphilitic lesions and advanced acquired
immunodeficiency syndrome (AIDS), the darkfield examination may identify the
etiologic agent of syphilis and help diagnose the disease even when antibodies to T.
pallidum cannot be detected.20 Darkfield microscopy taken from skin rash serum
patient was figured a athin,tightlywound, spiral organism but no movement.
T. pallidum is a thin, tightly wound, spiral organism capable of extreme
contortions from which it snaps back to its original form in a coiled spring-like
manner. It may spin rapidly without translation, move slowly forward and backward
without obvious change in direction of rotation or pitch of coils, or the organism may
more slowly thread its way corkscrew-fashion in viscous material. A spring-like rigidity
is constant and T. pallidum does not move rapidly from place to place with a
serpentine motion. Any coarsely wound spiral organism exhibiting great flexion and
rapid movement from place to place is not T. pallidum. The demonstration of
treponemes with characteristic morphology and motility for T. pallidum constitutes a
positive diagnosis of syphilis in primary, secondary, or early congenital stages,
whatever the outcome of serologic testing. False-positive darkfield tests may occur
with oral specimens; therefore, such positive specimens must be confirmed by direct
fluorescent antibody tests specific for identification of T. pallidum.20
HIV and syphilis affect similar patient groups and co-infection is common. All
patients presenting with syphilis should be offered HIV testing and all HIV-positive
patients should be regularly screened for syphilis. Syphilis agent may enhance the
transmission of the other, probably through increased incidence of genital ulcers.
Detection and treatment of syphilis can, therefore, help to reduce HIV transmission.
Syphilis may present with non-typical features in the HIV-positive patient, there is a
higher rate of symptomless primary syphilis and proportionately more HIV- positive
patients present with secondary disease. Secondary infection may be more
aggressive and there is an increased rate of early neurological and ophthalmic
involvement.
Penicillin remains the mainstay of therapy for all stages and sites of syphilis
and in all patient groups.4 Because there is no vaccine to prevent infection with T.
pallidum, antibiotic treatment is a key component of syphilis control programmes. The
U.S. Centers for Disease Control and Prevention (CDC) 2010 guidelines for
treatment of sexually transmitted diseases 22 and the UK 2008 guidelines for
management of syphilis23 recommend penicillin G, administered parenterally, as the
first-line drug for treatment of incubating syphilis and for all stages of syphilis. The
penicillin preparation (i.e. benzathine, aqueous procaine or aqueous crystalline),

dose, mode of delivery, and length of treatment are dependent upon the stage and
clinical manifestations of syphilis, as well as other management considerations (e.g.
pregnancy, HIV status, patients age). Use of the appropriate penicillin preparation is
critical since T. pallidum can reside in sequestered sites (e.g. central nervous system, aqueous humor, synovial fluid) where treponemicidal levels of penicillin are not
easily achievable. Because there are no proven alternatives to penicillin for treatment
of pregnant women with syphilis, those who are allergic to penicillin must be
desensitized and then treated with penicillin.22,23
Table 1. Antibiotic treatment of syphilis in HIV-negative adults 22,23

Treponemal STS cannot be used to assess the response of patients to

antibiotic treatment since patients with a positive test result usually continue to
remain positive for the remainder of their lives, regardless of treatment. Thus, nontreponemal STS are used as quantitative tests to monitor the effectiveness of
antibiotic treatment. The non-treponemal STS titer of serum usually declines after
effective antibiotic treatment of the patient and may become non-reactive with time.
Lack of a fourfold decline in serological titer within 3-6 months after therapy for early
syphilis (i.e. primary, secondary, or early latent) or 1224 months for late latent
syphilis may be due to treatment failure or possibly re-infection . Serological titers may
decline more slowly in HIV-infected patients. Fifteen to twenty per cent of syphilis
patients remain serofast (i.e. do not completely revert to a nonreactive test result)
after appropriate therapy regardless of HIV infection. The clinical significance of this
is unknown, but follow-up is recommended for such patients.24

In this case titer of VDRL higher after treatment was because of early
checked titer and need more follow up since it will decreased after 3-6 months after
therapy. One study provides evidence that a combination of the TPPA test and an
IgM ELISA is superior to the VDRL test for diagnosis of syphilis showed cumulative
serological response to treatment is shown in Table 2. For example, 3 months after
treatment, 85%100% of patients with primary syphilis had reached the endpoint (ie,
a 4-fold drop of the titer or reversion to nonreactive), as compared to 76%89% with
secondary syphilis and 44%79% with latent syphilis. 25 HIV coinfection did not
influence the overall time to serological response to treatment in the VDRL test.
Other studies, however, including one prospective trial, found a significant
association or a trend between HIV status and response to treatment (ie, HIV-positive
patients had a higher risk for serofailure or a longer time to serological response).
Overall, there seems to be a trend toward a slower response of nontreponemal tests
in HIV-coinfected patients. However, data in support of making a clear distinction
between HIV-positive and HIV-negative patients as recommended by the European
guidelines for management of syphilis are scarce. 25
Table 2. Serological Response to Treatment of Venereal Disease Research Laboratory and
Pathozyme Immunoglobulin M According to Clinical Stage of Syphilis and HIV Status. 25

For laboratory diagnosis of syphilis and for monitoring treatment response,

serological testing is the most important approach. IgM ELISA might be a supplement
for diagnosis and treatment monitoring.25 In patients co-infected with human
immunodeficiency virus (HIV), atypical serological courses have been reported. HIVpositive patients treated for syphilis may be at higher risk of serological failure.
Although the clinically defined treatment response does not seem to be influenced by
HIV co-infection, serologically defined treatment failure has been reported. This might

be a consequence of slower Venereal Disease Laboratory Research (VDRL) test

seroreversion in HIV-infected individuals. Despite recommendations for more
frequent serological follow-up, most patients did not have documentation of
serological response after standard treatment for syphilis. However, when reviewing
previous studies in this field, no firm conclusion can be drawn regarding whether HIV
coinfection significantly alters the treatment response. This issue still is important to
address, as today most HIV-infected individuals are treated with highly active
antiretroviral therapy and probably have a restored immune system. It is likely that
this changed the response to syphilis treatment in HIV patients.25

SUMMARY
Case reports of secondary syphilis in HIV patient are increasingly available
now, including one case report are presenting here, a 27-year old homosexual man
presented with history of non-pruritic reddish rashes on the palms and soles since 2
weeks before admission. Suddenly appeared as small multiple reddish rashes in his
palms and soles, reddish rashes then became wider and scaly. Patient had been
complained about genital ulcer 2 months ago, but slowly disappeared itself. The
diagnosis of secondary syphilis is not always easy as in the case of coinfecton with
HIV. Diagnosis was taken by clinical, serology, darkfield microscopy and
histopatological examination. Two weeks symptomatic therapy, VDRL was significant
higher before therapy. The clinical stage of syphilis had a significant impact on the
serological response; compared with primary stage syphilis, latent stage syphilis
showed a slower treatment response. Generally, the VDRL titer should decline at
least 4-fold within 36 months after therapy for primary or secondary syphilis, and
within 1224 months after therapy for latent syphilis. Patients with persistently low
VDRL titers after treatment may be considered to be a successfully treated. However,
when reviewing previous studies in this field, no firm conclusion can be drawn
regarding whether HIV coinfection significantly alters the treatment response. This
issue still is important to address, as today most HIV-infected individuals are treated
with highly active antiretroviral therapy and probably have a restored immune
system. It is likely that this changed the response to syphilis treatment in HIV
patients.

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