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Prevalence of HIV infection, Syphilis, and Syphilis/HIV coinfection in blood donors from a blood bank of Porto Alegre, southern Brazil

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Introduction: Hemotherapy consists of therapeutic treatments performed through blood transfusion. Clinical and serological screening of donors is an essential strategy to avoid transmission of infectious agents in blood transfusion. Objectives: Toassess the seroprevalence of HIV infection, syphilis and syphilis/HIV coinfection in blood donors from a blood bank in Porto Alegre from 2014 to 2016. Methods: Retrospective analysis of all blood donors registered on a software for managing hemotherapy services (Hemodot) of the Blood Bank in the Marques Pereira Laboratory, Porto Alegre / RS, from 2014 to 2016. Results: Of the 28,173 users of the hemotherapy service during the study period, 198 (0.70%) were positive for syphilis, HIV infection, or syphilis/HIV co infection. The prevalence of positive results for syphilis was 0.3%, 0.57% and 0.70% in 2014, 2015 and 2016, respectively, and for HIV infection was 0.18%, 0.14%, and 0.16% for the same period. However, the prevalence of syphilis/HIV coinfection was not statistically significant. Conclusions: The prevalence of syphilis increased significantly from 2014 to 2016. Hovever, this did not occur with HIV infection or with coinfection. This finding may reflect the requirement of the nucleic acid technique (NAT) for HIV screening in blood banks, a procedure that has been increasing transfusion safety and reducing the window period. Further studies may shed new light on the combined use of serological tests and NAT assays in blood banks to diagnose HIV cases and syphilis/HIV coinfection. Key Words: Coinfection; transfusion safety; hemocenter; infectious disease; syphilis; HIV
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Original Article
http://seer.ufrgs.br/hcpa ISSN 2357-9730 275
Clin Biomed Res. 2017;37(4):275-280
http://dx.doi.org/10.4322/2357-9730.74414
Prevalence of HIv InfectIon, syPHIlIs, and syPHIlIs/HIv
coInfectIon In blood donors from a blood bank of Porto
alegre, soutHern brazIl
Leonardo Santos da Silva1, Deborah Veiga Santos2,
Cristine Blume Brietzke2, Laura Vicedo Jacociunas1
1 Biomedicine, Centro Universitário
Metodista (IPA). Porto Alegre, RS, Brazil.
2 Hemotherapy Service, Laboratório
Marques Pereira. Porto Alegre, RS,
Brazil.
Corresponding author:
Laura Vicedo Jacociunas
laura.jacociunas@ipa.metodista.br
Centro Universitário Metodista (IPA)
Rua Cel. Joaquim Pedro Salgado, 80.
90240-060, Porto Alegre, RS, Brazil.
ABSTRACT
Introduction: Hemotherapy consists of therapeutic treatments performed through
blood transfusion. Clinical and serological screening of donors is an essential strategy
to avoid transmission of infectious agents in blood transfusion. The objective of this
study is to assess the seroprevalence of HIV infection, syphilis and syphilis/HIV
coinfection in blood donors from a blood bank in Porto Alegre from 2014 to 2016.
Methods: Retrospective analysis of all blood donors registered on a software for
managing hemotherapy services (Hemodot) of the Blood Bank in the Marques Pereira
Laboratory, Porto Alegre / RS, from 2014 to 2016.
Results: Of the 28,173 users of the hemotherapy service during the study
period, 198 (0.70%) were positive for syphilis, HIV infection, or syphilis/HIV co
infection. The prevalence of positive results for syphilis was 0.3%, 0.57% and
0.70% in 2014, 2015 and 2016, respectively, and for HIV infection was 0.18%, 0.14%,
and 0.16% for the same period. However, the prevalence of syphilis/HIV coinfection
was not statistically signicant.
Conclusions: The prevalence of syphilis increased signicantly from 2014 to 2016.
Hovever, this did not occur with HIV infection or with coinfection. This nding may reect
the requirement of the nucleic acid technique (NAT) for HIV screening in blood banks,
a procedure that has been increasing transfusion safety and reducing the window
period. Further studies may shed new light on the combined use of serological tests
and NAT assays in blood banks to diagnose HIV cases and syphilis/HIV coinfection.
Keywords: Coinfection; transfusion safety; hemocenter; infectious disease; syphilis; HIV
Blood donation is a topic of global importance, especially with regard to
blood transfusion safety
1
. Hemotherapy is a therapeutic treatment consisting
of blood transfusion or transfusion of blood products and poses a high
epidemiological risk, since blood, as a living tissue, is able to transmit several
diseases2. Thus, quality parameters must be rigorously followed for blood
procurement and for the selection and protection of recipients and donors3.
In Brazil, hemotherapy procedures are currently governed by a technical
regulation of the Brazilian National Health Surveillance (Agência Nacional de
Vigilância Sanitária, ANVISA): Ordinance no. 158, dated February 4, 2016,
published in the Federal Ofcial Gazette of February 5, 2016 (no. 2, Section 1,
page 37)4. This ordinance aimed to establish procedures to prevent the
transmission of infection and improve the quality of the blood component to
be transfused. The process of blood donation is conducted under a rigorous
system divided into stages beginning with donor procurement and nishing
with transfusion of donor’s blood to the recipient The rst stage, known as
clinical screening, consists of taking the medical history of donor candidates
to analyze their clinical history and their health behavior. The second stage
is serological screening, which is the most common form of preventing the
transmission of several etiologic agents5,6. In this context, after donation,
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Silva et al.
blood undergoes laboratory screening, including
immunohematologic tests, serological tests, and acid
nucleic test (NAT)7,8
. These regulations ensure blood
donation safety. The article no. 130 of Ordinance
no. 158/16 sets out mandatory highly sensitive
laboratory serological tests to detect markers for
the following conditions: syphilis, Chagas disease,
hepatitis B, hepatitis C, human immunodeciency
virus (HIV), and human T-cell lymphotropic virus type
I and/or II (HTLV I/II)
4
. Additionally, NAT started to be
implemented according to the Brazilian legislation7.
In some blood banks in the city of São Paulo, it was
implemented to reduce HIV and hepatitis C virus
(HCV) transmission by blood transfusion and became
mandatory for the entire Brazilian blood transfusion
network, including public and private blood banks,
in February 2014 under Ordinance no. 2712 dated
November 12, 20138.
It is known that the disease most commonly
transmitted by blood transfusion are hepatitis C
and HIV. However, an important association has
been observed between syphilis and HIV in recent
years, especially with regard to their window periods.
Therefore, screening tests in blood bank should be
able to identify donors presenting with these diseases9.
Syphilis is a chronic infectious disease caused
by the spirocheteTreponema pallidum10. For an
effective diagnosis of syphilis, serological screening
with non-treponemal and/or treponemal tests are
recommended. Non-treponemal tests include
venereal disease research laboratory (VDRL)) and
rapid plasma reagin. Diagnosis is conrmed using
treponemal tests, such as uorescent treponemal
antibody-Abs (FTA-Abs), Treponema Pallidum
hemagglutination test, TPHA, and enzyme-linked
immunosorbent assay, ELISA )11,12. Treatment for
this condition is well-established, with penicillin as
the drug of choice. Recently, bacterial resistance to
this drug has made syphilis a public health problem
and the production of penicillin has become scarce.
Intramuscular benzathine penicillin is the drug of
choice in most cases, except for congenital syphilis
and neurosyphilis, when crystalline penicillin G sodium
is indicated13,14. However, even when treatment is
effective, results for treponemal tests remain positive, a
phenomenon known as serological scar15,16. From 2010
to June 2016, the Notiable Diseases Information
System (Sistema de Informação de Agravos de
Noticação, SINAN) notied a total of 227,663 cases
of syphilis acquired in Brazil, 62.1% coming from
the southeastern region of the country, 20.5% from
the southern region, 9.3% from the northeastern
region, 4.7% from the midwestern region, and 3.4%
from the northern region. Overall, 136,835 cases were
male and 90,755 were female. Moreover, patients
aged from 20 to 29 years accounted for 31.2% of
the cases. In 2015, 65,878 cases of syphilis were
notied, of which 39,638 (60.2%) were male and
26,220 (39.8%) were female17.
HIV, the causative agent of acquired immunodeciency
syndrome (AIDS), is a retrovirus classied into the
subfamily Lentiviridae and containing RNA genetic
material
18
. Brazil is one of the countries that provides
free universal antiretroviral (ARV) therapy19. The use of
this drug to treat HIV infection has reduced morbidity
and mortality rates, thus increasingly making AIDS
a chronic controllable disease worldwide20.
HIV infection is diagnosed using serological tests
through ELISA, enzyme linked uorescent assays,
immunouorescence assays, particle agglutination
assays chemiluminescence assays, and microparticle
enzyme immunoassays9. Blood banks are required
by the Brazilian Ministry of Health to perform tests
that detect antibodies against HIV, regardless of the
method or allow for the combined detection of antibody
against HIV + HIV p24 antigens and tests that aim to
detect HIV nucleic acid. To ensure transfusion, one
positive test is already considered and indication for
discarding blood bags4. The implementation of the
NAT in the testing routine for the laboratory detection
of the virus reduced the estimated window period
compared with serological tests for HIV detection
from 22 to 10 days21.
From 2007 to June 2016, SINAN notied 136,945 cases
of HIV infection in Brazil, 71,396 (52.1%) coming from
the southeastern region, 28,879 (21.1%) from the
southern region, 18,840 (13.8%) from northeastern
region, 9,152 (6.7%) from the midwestern region,
and 6,868 (6.3%) from the northern region.
Overall, 92,149 of patients were male and 44,766 were
female, and 52.3% were aged fro 20 to 34 years old.
In 2015, 32,321 cases of HIV infection were notied,
22,672 (70.2%) in male and 9,637 (29.8%) in female
22
.
Both syphilis and HIV are transmitted mainly by
unprotected sex. However, the presence of syphilis
increases the risk of contracting HIV from ulcerated
genital lesions, mucosal disruption, inammation,
and genital secretions. Therefore, all patients with
syphilis should undergo HIV testing, and all positive
HIV patients should be tested for syphilis on a regular
basis23-25.
Several studies reported that syphilis, such
as other acute infections, leads to increased viral
load and reduced CD4 cell count. This transient
increase in viral load results in increased risk for
HIV transmission among patients with the two
diseases and is a consequence of activation of
immunological response26-28. Studies suggest that
the window period for syphilis may predispose to
HIV infection, i.e., HIV transmission is facilitated in
patients with syphilis because both conditions share
http://seer.ufrgs.br/hcpa Clin Biomed Res 2017;37(4) 277
Blood donors and detection of HIV infection, syphilis, and syphilis/HIV coinfection
the same route of transmission. Additionally, the base
of primary chancre of syphilis have a high number
of T cells and macrophages, which are the primary
targets of HIV9,25,29.
The window period of syphilis is short, since tests
may yield positive results some days after the onset
of primary stage lesions30. Some tests, such as VDRL,
RPR, TPHA, and FTA-abs, become positive within
from 3 weeks to 3 months; Conversely, tests for
antibody against HIV become positive within 6 weeks
from 3 months, whereas Western blot and p24 antigen
tests, within 2 weeks
31
. Within this context, the
present study sought to evaluate the prevalence of
HIV infection, syphilis, and syphilis/HIV coinfection
in blood donors from a blood bank in Porto Alegre,
southern Brazil, from 2014 to 2016.
METHODS
A quantitative, descriptive, retrospective study
was carried out to analyze information from all blood
donors registered at the database of the blood bank
of Laboratório Marques Pereira at Porto Alegre,
southern Brazil, for the period from January 1st, 2014 to
December 31, 2016. This study was approved by the
Research Ethics Committee of Centro Universitário
Metodista IPA and registered at Platarforma Brasil
(protocol number 1.709.050).
The sample of the present study included data from
28,173 hemotherapy service users at the Laboratório
Marques Pereira. Data records were assessed using
a software for managing hemotherapy services
(Hemodot) to collect information on HIV I/II serology,
NAT assays, VDRL serology for syphilis to analyze
the frequency of these contagious diseases whether
alone or in combination among the study population.
To that end, data were inserted into the Statistical
Package for Social Sciences (SPSS) software and
analyzed considering a level of signicance of p<0,05.
Results were expressed as numbers and
percentages. In the blood bank under studies, donor
blood were assessed by chemiluminescent microparticle
immunoassays with specicity of 99.5% and sensitivity
of 100%, as recommended by the Brazilian Ministry
of Health. According to manufacturer’s instructions,
samples with serological values ≥ 1 are reactive
and < 1 are not. However, our service establishes a
margin of safety of 15% (grey zone), recommending
that results within this zone should be considered
indeterminate and donors should be asked to return
to the service to have blood drawn again.
RESULTS
The total number of donor candidates from 2014 to 2016
was 28,173 donors, distributed as follows: 8,695 in
2014, 10,009 in 2015, and 9,469 in 2016. Over the
3-year period, the number of blood bags positive for
syphilis, HIV infection, and syphilis/HIV coinfection
was 198 (0.70%). Data for positive serological and
NAT assays are presented in Table 1.
The prevalence of syphilis-positive blood bags
gradually increased over the years, while the
prevalence of HIV-positive cases did not change
signicantly. All reactive serological HIV tests were
conrmed by NAT assays, which were also positive
for HIV infection. The prevalence of syphilis in blood
donor is greater compared with that of HIV cases.
Conversely, the prevalence of syphilis/HIV coinfection
was not statistically signicant, as shown in Figure 1.
Table 1: Total of positive cases of syphilis, HIV, and syphilis/HIV coinfection per year.
Total (%) Men (%) Women (%)
2014
Positive results for syphilis 26 (0.3) 15 (0.17) 11 (0.13)
Positive results for HIV infection 16 (0.18) 13 (0.15) 3 (0.03)
Positive results for syphilis/HIV coinfection 0 (0.0) 0 (0.0) 0 (0.0)
Total of donors/year 8695 (100)
2015
Positive results for syphilis 57 (0.57) 33 (0.33) 24 (0.24)
Positive results for HIV infection 14 (0.14) 9 (0.09) 5 (0.05)
Positive results for syphilis/HIV coinfection 3 (0.03) 3 (0.03) 0 (0.0)
Total of donors/year 10009 (100)
2016
Positive results for syphilis 66 (0.70) 34 (0.36) 32 (0.34)
Positive results for HIV infection 15 (0.16) 4 (0.04) 11 (0.12)
Positive results for syphilis/HIV coinfection 1 (0.01) 1 (0.01) 0 (0.0)
Total of donors/year 9469 (100)
Source: designed by the author.
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Silva et al.
DISCUSSION
Currently, there is a clear concern from hemotherapy
services in ensuring blood transfusion safety both for
donors and recipients, which has been increasing
reducing the frequency of transmission of infectious
diseases by blood transfusion. This reduction may
be achieved through effective screening for these
diseases in blood banks, including donor procurement,
epidemiological and clinical analysis of donor health
status, and laboratory screening, in order to prevent
the risk of contamination and thus increase safety
Our ndings revealed the prevalence of positive
serology for syphilis increased on an yearly basis from
2014 to 2016. This fact may be explained by the high
prevalence of syphilis in the general population, by
the shortage of penicillin (the antibiotic of rst choice
for the treatment of syphilis), and by the fact that most
infections are diagnosed after solidarity initiatives such
as blood donation, and promotes the spread of both
infections. This nding corroborates surveillance data
showing that the prevalence of syphilis increased
42.7% in 201517. Conversely, positive HIV serology
remained stable over the 3-year period. These ndings
may be justied by the mandatory implementation of
NAT assays for HIV infection in blood banks, which
reduced the window period, because of the sensitivity
of the test, since it is required to have a sensitivity of
100%, with no acceptable false negatives4.
In a study conducted between December 2011
and May 2012 at the blood bank of the Edéa Regional
Hospital, Cameroon, the seroprevalence of HIV
was 4.1%, indicating a reduction in HIV cases in the
country over the last decade due to the implementation
of prevention programs32,33.
In the present study, the prevalence of HIV infection,
syphilis, and HIV/syphilis coinfection from 2014 to 2016
was higher in males. A study conducted by Rohr et al.
to assess the prole of unt donor candidates at the
hospital of Santo Ângelo, southern Brazil found that
the main cause for ineligibility in men was high risk
behavior and multiple sex partners. This may result
from greater sexual freedom, homosexual behavior,
extramarital affairs, and reduced use of condoms, all
of which make men more susceptible to contract a
sexually transmitted disease. Conversely, the main
cause for ineligibility in women was low hemoglobin
or hematocrit. This behavioral information obtained
from the study by Rohr et al. may explain the results
from the present study showing a higher prevalence
of syphilis in men.
With a prevalence of 0.014%, HIV/syphilis coinfection
was not very prevalent in the study population from
2014 to 2016, although the two diseases share the
same route of transmission. In contrast, a previous
study conducted at Hemocentro de Guarapuava,
southern Brazil found a much higher prevalence
of HIV/syphilis coinfection. From January 2009 to
December 2013, there were 28,851 blood donations,
of which 1,651 (5.6%) were positive for infectious
diseases. Of the 1,651 positive donations, 76 (4.7%)
were coinfected with syphilis/HIV
34
. In the present study,
which covered from 2014 to 2016, the non-statitiscally
signicant prevalence of syphilis/HIV coinfection
(0.014%) may be explained by the period of data
collection and by the peculiarites of the blood bank
under study, which also represents a limitation of
this study. It is important to note that a positive HIV
serology does not mandatorily mean positive syphilis
serology. One condition is known to predispose to
the other, but there is no dependence relationship
between them. The analysis of coinfection with
these diseases has an important role in assessing
the window period and may provide data for future
epidemiological studies to help treatment of positive
cases, since both conditions share the same route
of infection.
A study conducted in Campinas, southeastern
Brazil, assessed the prevalence of syphilis/HIV
coinfection in patients registered on an electronic
system for the notication of sexually transmitted
diseases (STD) (SINDST) at a STD/HIV referral
center from January 2004 to December 2012.
Overall, 3,106 cases of STD were notied. Of these,
860 presented with at least one episode of syphilis.
Of the patients with syphilis, 781 (90.8%) were male
and 79 (9.2%) were female. In turn, there were
377 (43.8%) cases of syphilis/HIV coinfecction, of
which 354 were male and 23 were female
35
. Another
study conducted from 1997 to December 2014 in Rio
de Janeiro, southern Brazil, with HIV seropositive
patients assessed the prevalence of syphilis/HIV
during HIV treatment. Of 793 HIV-positive patients,
417 met study requirements, of which 270 (64.7%)
Figure 1: Prevalence of positive serology for syphilis, HIV
infection, and syphilis/HIV infection in the blood bank of
Laboratório Marques Pereira from 2014 to 2016; *results
with a signicance level of p < 0.05. Source: designed by
the author.
http://seer.ufrgs.br/hcpa Clin Biomed Res 2017;37(4) 279
Blood donors and detection of HIV infection, syphilis, and syphilis/HIV coinfection
were male, 141 (33.8%) were female, and 6 (1.4%)
were transvestite/transexual. When only coinfected
patients were analyzed, 81 met study requirements,
of which 67 (82.7%) were male, 10 (12.3%) were
female, and 4 (4.4%) were transvestite/transexual
36
.
The prevalence of syphilis/HIV coinfection was 19.4%;
however, it is worth noting that the period covered
in the study was long and that there may have been
a change in the epidemiological prole of the study
over this period.
A cross-sectional study determined the prevalence
of syphilis and factors associated with syphilis infection
in patients with HIV/AIDS treated at Hospital Santa
Casa de Misericórdia de Vitória, southeastern Brazil,
from August 2010 to September 2011. Of 498 patients
selected, 438 (88%) HIV-positive patients HIV were
included in the study, of which 241 (55%) were male
and 197 (45%) were female. Of the 438 HIV-positive
patients, 23 (5.3%) were coinfected with syphilis, 20
(87%) men and 3 (13%) women37. Another study
conducted in Porto Alegre, southern Brazil, assessed
the prevalence of coinfection with syphilis in HIV
seropositive patients from 1991 to November 2008.
Of 2,262 patients infected with HIV, only 1,012 met
criteria for inclusion in the study. Of these, 580 (57%)
were male and 432 (43%) were female. The prevalence
of syphilis/HIV coinfection in this study was 20,5%
(208 cases, 166 men and 42 women)38. It is worth
emphasizing that there was a great variation in the
results found in the literature, resulting from differences
in study design, diagnostic tests, and study period.
Technological and scientific advances are
remarkably improving attempts to minimize the risks
posed by blood transfusion. Fourth-generation ELISA
assays have a sensitivity of nearly 100%. Recently,
the mandatory implementation of nucleic acid
amplication test for the screening of HIV and HCV in
blood banks has reduced the window period. It should
be noted that this study aimed to assess coinfection
in blood donors from a blood bank in Porto Alegre,
southern Brazil. However, there is scarce clinical
evidence on the topic in the literature. Thus, further
studies covering different study periods are needed
to investigate satisfactory results and to explain the
ndings obtained in the present study. Therefore,
this study sheds new light on the combined use of
serological tests and NAT assays in blood banks to
diagnose HIV cases and syphilis/HIV coinfection.
Conicts of interest
The authors declare no conicts of interest.
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Received: Jun 27, 2017
Accepted: Sep 18, 2017
... O processo transfusional no Brasil e no mundo é uma medida terapêutica amplamente utilizada 7,18 . Apesar do desenvolvimento de novas tecnologias para triagem sorológica no diagnóstico de doenças veiculadas pelo sangue e da adoção de medidas de segurança na triagem clínica com o intuito de eliminar os doadores com comportamento de risco, a transmissão do HIV ainda é um desafio nos serviços hemoterápicos devido ao risco de não detectar durante a janela imunológica 16,18,19 . ...
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Introdução: As transfusões sanguíneas começaram a ser realizadas no Brasil no século XX como forma de tratamento terapêutico. Com a descoberta do vírus HIV, a segurança do sangue doado passou a ser prioritária. Assim, candidatos à doação de sangue são submetidos a uma triagem clínica e sorológica, além do teste de ácido nucleico (NAT), obrigatório desde 2014 nos bancos de sangue. Métodos: Estudo retrospectivo através da análise de dados dos doadores de sangue de um Serviço de Hemoterapia em Porto Alegre/RS, nos anos de 2015 a 2017. Avaliando resultados sorológicos e da técnica NAT para HIV. Resultados: Das 28.625 amostras de usuários do serviço de hemoterapia, 41 (0,14%) foram reagentes para o HIV e 21 (0,07%) foram reagente para o teste NAT. Estes dados demonstram uma reatividade duas vezes maior nas amostras de bolsas testadas sorologicamente quando comparadas com a metodologia utilizada no NAT. Discussão: O avanço científico e tecnológico tem auxiliado no que se refere a redução dos riscos de transmissão de doenças infecto-contagiosa por transfusão sanguínea. O teste NAT teve um acréscimo significativo na pesquisa dos vírus para a segurança na liberação de hemocompoentes. O teste foi introduzido nas rotinas de banco de sangue no intuito de reduzir o período de janela imunológica quando comparado aos testes sorológicos, fato este não observado nos anos de coleta de dados no Serviço de Hemoterapia referido neste estudo. Palavras-chave: Sorologia; NAT; HIV; segurança transfusional; hemoterapia
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The past 15 years have seen a dramatic increase in syphilis diagnoses in several regions including China, North America, Western Europe and Australia. Worldwide, the disease remains prevalent, contributing to substantial adult morbidity and neonatal mortality. Testing and treatment strategies are largely informed by data from the early antibiotic era, but increasing use of molecular diagnostics and new screening strategies could improve the management of syphilis substantially. The review explores new testing strategies for syphilis, including the importance of screening test selection and advances in point-of-care diagnostics. It then examines molecular studies of Treponema pallidum, covering typing; macrolide resistance; association between genotype and phenotype and the use of PCR in testing and monitoring strategies. Clinicians should be aware of testing strategies employed by their laboratories to ensure optimal sensitivity and specificity. Locally available T. pallidum PCR assays may improve the diagnosis of early disease and inform antibiotic choice. Robust serologic follow-up is still required, but predictors of potential treatment failure, including PCR-measured bacterial load, have been identified. Re-treatment should be considered for patients in the serofast state. The publication of T. pallidum genomes would allow further and more detailed study of strains and disease pathogenesis.