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Hindawi Publishing Corporation

Infectious Diseases in Obstetrics and Gynecology


Volume 2016, Article ID 5758387, 17 pages
http://dx.doi.org/10.1155/2016/5758387

Review Article
Extragenital Infections Caused by Chlamydia trachomatis and
Neisseria gonorrhoeae: A Review of the Literature

Philip A. Chan,1 Ashley Robinette,1 Madeline Montgomery,1 Alexi Almonte,1


Susan Cu-Uvin,1 John R. Lonks,1 Kimberle C. Chapin,2 Erna M. Kojic,1 and Erica J. Hardy1
1
Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School, Brown University, Providence,
RI 02903, USA
2
Department of Pathology, Rhode Island Hospital, Providence, RI 02903, USA

Correspondence should be addressed to Philip A. Chan; pchan@lifespan.org

Received 31 December 2015; Revised 12 April 2016; Accepted 20 April 2016

Academic Editor: Per Anders Mardh

Copyright 2016 Philip A. Chan et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major
public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent
studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections
in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by
anatomical site. Among women, prevalence was found to be 0.635.8% for rectal gonorrhea (median reported prevalence 1.9%),
029.6% for pharyngeal gonorrhea (median 2.1%), 2.077.3% for rectal chlamydia (median 8.7%), and 0.23.2% for pharyngeal
chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.224.0% for rectal gonorrhea (median 5.9%), 0.516.5%
for pharyngeal gonorrhea (median 4.6%), 2.123.0% for rectal chlamydia (median 8.9%), and 03.6% for pharyngeal chlamydia
(median 1.7%). Among MSW, the prevalence was found to be 05.7% for rectal gonorrhea (median 3.4%), 0.415.5% for pharyngeal
gonorrhea (median 2.2%), 011.8% for rectal chlamydia (median 7.7%), and 022.0% for pharyngeal chlamydia (median 1.6%).
Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral
intercourse. We discuss current clinical recommendations and future directions for research.

1. Introduction gender can likely be attributed to routine screening practices


among women [2]. The major primary care guidelines in the
Sexually transmitted diseases (STDs) continue to be a sig- US recommend annual chlamydia screening of all sexually
nificant cause of morbidity in the United States (US) with active young women (age 24 years and younger) as part of
an estimated $15.9 billion spent annually on healthcare costs annual routine reproductive healthcare services [3]. Similar
related to their diagnosis and treatment [1]. The two most to chlamydia, gonorrhea also disproportionately impacts
common reportable bacterial STDs in the US are gonorrhea younger populations. Gonorrhea is caused by the bacterium
and chlamydia [2]. Chlamydia is caused by the bacterium Neisseria gonorrhoeae with over 350,000 cases reported in
Chlamydia trachomatis and is the most commonly reported 2014, a 5.1% increase from the prior year and a 10.5% increase
STD. In 2014, over 1.4 million cases of chlamydia were since 2010 [2]. Unlike chlamydia, gonorrhea is now more
diagnosed in the US [2], a 2.8% increase from the prior prevalent among men than women. The number of gonorrhea
year and the greatest number of cases ever reported for an cases among men increased by 27.9% from 2010 to 2014,
STD. Of chlamydia cases in 2014, the majority were among whereas the number of cases among women decreased by
younger adults age 1524 and women (70%). Despite overall 4.1% during that time. The rising number of new chlamydia
higher prevalence of chlamydia infection among women and gonorrhea cases among men is likely due to increased
in the US, diagnoses among men increased by 6.8% from diagnoses among gay, bisexual, and other men who have sex
2013 to 2014. The difference in chlamydia diagnoses by with men (MSM) [4, 5].
2 Infectious Diseases in Obstetrics and Gynecology

Gonorrhea and chlamydia are often asymptomatic in men 3. Results and Discussion
as well as women. In men, only 14% infected with chlamydia
and 40% infected with gonorrhea may be symptomatic [6, 7]. 3.1. Current Screening Recommendations. The Centers for
In women, urogenital chlamydia initially infects the cervix, Disease Control and Prevention (CDC) currently recom-
causing symptoms of cervicitis which can then spread to mends that all sexually active women less than 25 years of
the upper reproductive tract and cause pelvic inflammatory age, as well as older women who have specific risk factors
disease (PID). Untreated urogenital infections can lead to (e.g., new or concurrent sex partners), be tested annually for
other serious complications such as chronic pain, ectopic urogenital chlamydia and gonorrhea infection [12]. Per the
pregnancy, and infertility [8]. The presence of gonorrhea or guidelines, the clinical significance of pharyngeal chlamydia
chlamydia at any site also increases the risk of acquiring infection is unclear and routine pharyngeal screening for
HIV in both men and women [9, 10]. Complications specific chlamydia is not recommended [1214]. The US Preventive
to men include epididymitis, prostatitis, and proctitis. Both Services Task Force (USPSTF), the preeminent primary care
men and women with symptomatic urogenital infection most guidelines in the US, recommends screening for chlamydia
commonly present with urethritis, characterized by dysuria and gonorrhea in all sexually active women of age 24 years
and urethral discharge. Reactive arthritis may also occur, and younger, and in older women who are at increased risk
often as part of a triad of other symptoms including urethritis for infection (e.g., due to another current STD, a previous
and conjunctivitis [11]. STD, new or concurrent sex partners, inconsistent condom
N. gonorrhoeae and C. trachomatis can also be detected use, drug use, commercial sex work, certain demographic
in the pharynx and rectum [2]. Gonorrhea and chlamydia characteristics, or high community prevalence of STDs).
infection in the rectum can cause rectal pain, bleeding, and The American Congress of Obstetricians and Gynecologists
discharge, as well as proctitis. In the pharynx, these infections (ACOG) recommends annual urogenital screening for gon-
can cause symptoms, such as pharyngitis and lymphadenitis, orrhea and chlamydia for sexually active women age 25 years
but are most often asymptomatic. Given that extragenital test- and younger, as well as for women over age 25 reporting risk
ing is not always part of routine STD screening, particularly factors for infection [15].
in the absence of symptoms, many extragenital infections The CDC does not recommend routine chlamydia or
are undiagnosed and untreated. These untreated extragenital gonorrhea screening in men [12], with the exception of
infections are a potential reservoir for ongoing transmission considering screening in high-prevalence clinical settings
and may also lead to increased risk of HIV acquisition. such as STD clinics or among high-prevalence populations
Extragenital testing for N. gonorrhoeae and C. trachomatis is such as MSM. The CDC recommends that MSM be screened
an emerging area that should be considered in both men and at least annually for chlamydia infection at sites of sexual
women. We review current screening recommendations and contact, including the rectum and urethra; for gonorrhea,
evidence to support extragenital testing for N. gonorrhoeae the guidelines recommend screening at the urethra, rectum,
and C. trachomatis and discuss areas where future research is and pharynx. Per these guidelines, screening should be based
needed. on risk behaviors. MSM who report insertive sex should be
screened for urogenital N. gonorrhoeae and C. trachomatis.
MSM who report receptive anal sex should be screen for
2. Materials and Methods rectal N. gonorrhoeae and C. trachomatis. MSM who report
receptive oral sex should be screened for pharyngeal N.
Current guidelines related to extragenital screening for N. gonorrhoeae only; screening for C. trachomatis pharyngeal
gonorrhoeae and C. trachomatis in men and women were infection is not recommended. The USPTF does not recom-
reviewed. A literature review was performed of all studies mend screening for chlamydia or gonorrhea in MSW due to
listed in PubMed evaluating extragenital gonorrhea and insufficient evidence to support this practice.
chlamydia infections through December 1, 2015. Studies The majority of international STD treatment guidelines
included those describing extragenital infections by N. gonor- provide recommendations for extragenital testing in MSM.
rhoeae, C. trachomatis, or both, conducted in the US as well as The International Union Against Sexually Transmitted Infec-
internationally. The goal of the review was to describe the cur- tions (IUSTI) recommends extragenital testing for both MSM
rent epidemiology and prevalence of extragenital infections and women at the rectum and pharynx if there is a reported
in the setting of the latest recommendations for screening. history of sexual exposure [16, 17]. Similarly, the British
We specifically examined extragenital infections in separate Association for Sexual Health and HIV (BASHH) recom-
subgroups of populations, including women, men who have mends that extragenital screening for chlamydia and gonor-
sex only with women (MSW), and MSM. Only studies in rhea infections be dependent on reported sexual behaviors
English were included. The search terms extragenital, rec- among men and women [18]. The guidelines also recommend
tal, pharyngeal, chlamydia, and gonorrhea were used in extragenital testing among specific groups of women, such
combination and individually. References were reviewed and as commercial sex workers [19, 20]. Other countries, such
subsequently excluded if the study did not include findings as South Africa, employ an algorithm-driven, syndromic
of extragenital N. gonorrhoeae or C. trachomatis infection. approach to STD testing and treatment [21].
Additionally, citations within these studies were reviewed The group of women who have sex with women (WSW)
and included if relevant. Full texts of relevant studies were encompasses a diverse set of individuals and sexual practices.
retrieved and reviewed. The CDC addresses this unique group, recommending that
Infectious Diseases in Obstetrics and Gynecology 3

screening for N. gonorrhoeae and C. trachomatis be based of asymptomatic extragenital infections and the inaccuracy
on a detailed history of sexual practices [12]. The CDC of testing based on self-reported behavior [19], the evidence
also specifically addresses transgender men and women and supports routine screening in high-risk settings such as STD
recommends STD risk assessment and testing be based on clinics. Universal screening for extragenital infection will
current anatomy and sexual behaviors in this group [12]. certainly increase case finding, which in turn will likely have
both clinical and public health benefits such as avoiding
3.2. Overview of Existing Literature. A total of 80 studies were reproductive health sequelae and limiting HIV transmission.
reviewed focusing on extragenital infection with N. gonor- However, extragenital screening protocols among sexually
rhoeae or C. trachomatis. Studies were published between 1981 active women are not currently widespread, and further
and 2015 and included sites in North America ( = 37), study is needed to evaluate the impact on sexual health
Europe ( = 29), Australia ( = 9), Asia ( = 4), and Africa outcomes. Additionally, given the paucity of extragenital
( = 2). Study settings included STD clinics ( = 38), other infection studies in other settings (e.g., primary care clinics),
outpatient clinics ( = 10), genitourinary clinics ( = 7), HIV prevalence in these settings is largely unknown and merits
clinics ( = 9), gay mens health centers ( = 3), community- further study.
based and outreach settings ( = 6), and other settings ( =
3); a minority of studies presented findings from multiple 3.4. Extragenital Infections in MSM. A total of 53 studies
sites ( = 6). Most studies evaluated a single population but evaluated the prevalence of extragenital infections
some did include multiple populations of women, MSW, and due to N. gonorrhoeae or C. trachomatis in MSM
MSM. The number of studies reporting specific populations [13, 19, 22, 2527, 36, 38, 44, 45, 4749, 5493] (Table 2).
included MSM ( = 54), women ( = 33), MSW ( = 9), and Extragenital infections among MSM have been studied more
mixed populations ( = 9). The following sections describe extensively compared to women. MSM experience high
extragenital N. gonorrhoeae and C. trachomatis infection in rates of both extragenital gonorrhea and chlamydia. The
these different populations. prevalence of extragenital infection among MSM in these
studies ranged from 0.224% for rectal gonorrhea (median
3.3. Extragenital Infections in Women. A total of 33 studies 5.9%), 0.516.5% for pharyngeal gonorrhea (median 4.6%),
reported prevalence of extragenital infection in women due 2.123% for rectal chlamydia (median 8.9%), and 03.6% for
to N. gonorrhoeae or C. trachomatis infection [19, 2252] pharyngeal chlamydia (median 1.7%); the differences are due
(Table 1). The range of prevalence of extragenital infections to different clinical settings and methods of diagnosis. Several
reported was 0.635.8% for rectal gonorrhea (median 1.9%), studies have evaluated the national prevalence of extragenital
029.6% for pharyngeal gonorrhea (median 2.1%), 2.077.3% infections among MSM in the US [12, 24, 29, 30, 35, 43, 59, 63
for rectal chlamydia (median 8.7%), and 0.23.2% for pha- 65, 6971, 73, 74, 7678, 80, 82, 83]. In a large cohort of 3,034
ryngeal chlamydia (median 1.7%). Most study sites were STD MSM who attended a STD clinic in Seattle, Washington in
clinics and other high-risk settings; few were primary care 2011, extragenital infections were common and included
settings, clinics focusing on womens care, or centers focusing pharyngeal gonorrhea (6.5%) and chlamydia (2.3%), and
on transgender patient care. rectal gonorrhea (9.7%) and chlamydia (11.9%) [57]. Fifty-
Most extragenital infections in women are asymptomatic, seven percent of cases were found in only extragenital sites
with estimates including 93% of pharyngeal gonorrhea [39], (nonurogenital).
53100% of rectal gonorrhea [39], 100% of pharyngeal Similarly, among 21,994 MSM screened as part of the
chlamydia [39], and 36100% of rectal chlamydia cases [29, CDC STD Surveillance Network, composed of 42 STD clinics
30, 39]. Furthermore, a significant number of women who across the US, the prevalence of infection was 7.9% for pha-
test positive for rectal gonorrhea or chlamydia do not report ryngeal gonorrhea, 2.9% for pharyngeal chlamydia, 10.2% for
anal sex [19, 29, 53]. Extragenital screening increases the yield rectal gonorrhea, and 14.1% for rectal chlamydia. Over 70% of
of detection of either gonorrhea or chlamydia at pharyngeal extragenital infections in this sample would have been missed
or rectal sites by approximately 650% or greater in women with urogenital screening alone. In summary, urogenital
compared to screening urogenital specimens alone [2325, testing alone misses a significant percentage of gonorrhea and
27, 2931, 39, 4446]. Overall, reported risk factors for rectal chlamydia infections among MSM; if MSM were screened
infection in women include younger age ( = 2 studies), sex for urogenital infections alone, 14% to 85% of rectal and
with an injection drug user ( = 1), exchanging sex for money oropharyngeal gonorrhea and chlamydia infections would
( = 2), anonymous partners ( = 1), a sex partner with have been missed [22, 57, 63, 64, 68, 79, 80].
gonorrhea or chlamydia ( = 1), and sex while under the The majority of extragenital infections among MSM are
influence of drugs or alcohol ( = 1) [23, 31, 48]. However, asymptomatic, with estimates ranging from 25% to 100%
other studies have not found any associations with these risk from reported studies [68, 76, 80, 89, 92, 94]. Men with
factors [29, 30]. extragenital gonorrhea may be more likely to be symptomatic
Based on prevalence data, universal screening for extra- than those with chlamydia [25, 62, 71, 95, 96]. For example,
genital infection due to N. gonorrhoeae or C. trachomatis in in one large study of MSM with extragenital infection,
settings which care for women who are at risk of these infec- only 5.1% of pharyngeal and 11.9% of rectal infections were
tions (e.g., those who are sexually active with concurrent or symptomatic with the most common pharyngeal symptoms
nonmutually monogamous partners, regardless of reported being pharyngitis (65%), localized lymphadenopathy (16%),
exposure sites) should be considered. Due to the frequency and inflammation of the oral cavity (10%). The most common
4

Table 1: Characteristics of studies reporting extragenital infections due to N. gonorrhoeae and C. trachomatis among women.
Gonorrhea Chlamydia
Author Study year Location Setting Time period Risk Sample
Urogenital Rectal Pharyngeal Urogenital Rectal Pharyngeal
Jones et al. [33] 1985 Indiana (US) STD clinic 1985 Women 686/1,223 28.00% 5.20% 3.20%
Ostergaard et
1997 Denmark STD clinic 1995-1996 Women 196 3.60% 3.10% 1.50%
al. [38]
Linhart et al. Sex worker
2008 Tel Aviv, Israel 2008 Women 300 5.00% 9.00% 6.30%
[35] outreach
van der Helm
2009 Netherlands STD clinic 2006-2007 Women 936 2.00% 9.00%
et al. [49]
Barry et al. [24] 2010 California (US) STD clinic 2007-2008 Women 1,308 1.80% 1.70% 5.40% 4.70%
STD clinic,
Giannini et al.
2010 Ohio (US) childrens 20032007 Women 1,949 5.69.3% 2.913.4% 2.56.8%
[28]
hospital
Hunte et al.
2010 Florida (US) STD clinic 2007 Women 97 8.20% 13.40% 16.50% 17.50%
[30]
Raychaudhuri Genitourinary
2010 United Kingdom 20052008 Women 120 27.50% 35.80%
and Birley [41] clinic
Sethupathi et Genitourinary
2010 United Kingdom 20062008 Women 152 11.90% 12.50%
al. [42] clinic
Peters et al.
2011 Netherlands STD clinic 2007-2008 Women 4,299 1.10% 1.70% 0.80% 10.00% 8.70% 1.90%
[39]
Javanbakht et
2012 California (US) STD clinic 20082010 Women 2,084 3.30% 3.00% 12.00% 14.60%
al. [31]
Koedijk et al.
2012 Netherlands STD clinic 20062010 Women 207,134 1.00% 1.20% 1.20% 10.40% 9.30% 2.70%
[22]
Mayer et al.
2012 US (4 cities) HIV clinic 20042006 Women (HIV+) 119 1.00% 1.00% 2.00% 3.00% 2.00% 2.00%
[36]
Diaz et al. [26] 2013 Spain STD clinic 20062010 Women 318 0.90% 3.10% 29.60%
Genitourinary
Shaw et al. [43] 2013 United Kingdom 2013 Women 2,808 0.50% 0.60% 0.30% 6.70% 7.10% 1.30%
clinic
van Liere et al.
2013 Netherlands STD clinic 2010-2011 Women 1,321 1.30% 0.90% 2.30% 5.40% 4.80% 1.40%
[45]
Dimech et al. Surveillance
2014 Australia 20082010 Women 415,069 6.710% 5.20% 1.70%
[102] system
Jenkins et al. Emergency
2014 Illinois (US) 2012-2013 Women 301 1.00% 0.70% 6.30% 0.70%
[32] room
Ladd et al. [34] 2014 US (multiple cities) Mail 20092011 Women 205 2.50% 11.10%
Peters et al. Primary care
2014 South Africa 2011-2012 Women 604 10.00% 2.50% 0.00% 16.00% 7.10% 0.20%
[40] clinic
van Liere et al.
2014 Netherlands STD clinic 2012-2013 Women 663 11.20% 8.40%
[46]
van Liere et al.
2014 Netherlands STD clinic 20102012 Women 1,321 1.30% 0.90% 2.30% 5.40% 4.80% 1.40%
[47]
Bazan et al.
2015 Ohio (US) STD clinic 2012-2013 Women 331 7.00% 6.00% 13.00% 13.00%
[23]
Infectious Diseases in Obstetrics and Gynecology
Table 1: Continued.
Gonorrhea Chlamydia
Author Study year Location Setting Time period Risk Sample
Urogenital Rectal Pharyngeal Urogenital Rectal Pharyngeal
Danby et al.
2016 Pennsylvania (US) STD clinic 2014-2015 Women 175 2.90% 2.30% 2.30% 10.30% 11.40% 1.70%
[25]
Dukers-
Muijrers et al. 2015 Netherlands STD clinic 20102013 Women 7,419 0.60% 0.70% 2.70% 10.20% 6.50% 1.40%
Infectious Diseases in Obstetrics and Gynecology

[19]
Garner et al. Sexual health
2015 United Kingdom 2010 Women 649 0.80% 1.10% 0.60% 13.30% 6.60% 2.50%
[27] clinic
Gratrix et al.
2015 Canada STD clinic 2012 Women 3055 9.40% 12.60%
[29]
Sexual health
Musil et al. [37] 2015 Australia 2013-2014 Women 56 77.00% 57.00%
clinic
Trebach et al.
2015 Maryland (US) STD clinic 20112013 Women 4,402 2.80% 3.00% 2.10% 10.00% 8.60% 2.60%
[44]
van Liere et al.
2015 Netherlands STD clinic 2011-2012 Women 11,113 0.90% 9.50%
[48]
van Liere et al.
2013 Netherlands STD clinic 2010-2011 Women (swingers) 461 1.08% 6.72%
[45]
Ding and
2014 United Kingdom STD clinic 2012-2013 Women 97 100% 77.3%
Challenor [50]
Cosentino et al.
2012 Pennsylvania (US) HIV clinic 2009-2010 Women 272 2.6% 7.7%
[51]
Bachmann et STD clinic,
2010 US 20032007 Women 99 20.30% 23.1054.30% 8.20% 27.40% 5.6019.20% 1.90%
al. [52] HIV clinic
Note. STD: sexually transmitted diseases; US: United States.
5
Table 2: Characteristics of studies reporting extragenital infections due to N. gonorrhoeae and C. trachomatis among men who have sex with men. 6
Gonorrhea Chlamydia
Author Study year Location Setting Time period Risk Sample
Urogenital Rectal Pharyngeal Urogenital Rectal Pharyngeal
McMillan et al.
1981 United Kingdom STD clinic 1981 MSM 150 6.70% 4.00% 1.30%
[73]
Rompalo et al.
1986 Washington (US) STD clinic 1983 MSM 1,429 8.00% 5.00%
[83]
Ostergaard et
1997 Denmark STD clinic 1995-1996 MSM 39 2.60% 2.60% 0.00%
al. [38]
Tabet et al. [87] 1998 Washington (US) Community 1995 MSM 578 0.00% 0.20% 0.70% 0.00%
Kim et al. [69] 2003 California (US) STD clinic 2000 MSM (HIV+) 564 7.10%
Manavi et al.
2004 United Kingdom Genitourinary clinic 19992002 MSM 443 7.20%
[72]
STD clinic, gay mens
Kent et al. [68] 2005 California (US) 2003 MSM 6,434 6.00% 6.90% 9.20% 5.20% 7.90% 1.40%
health center
Currie et al.
2006 Australia Sexual health clinic 20012003 MSM 314 6.8% (Did not specify site) 9.6% (did not specify site)
[60]
Hocking and
2006 Australia STD clinic 2002-2003 MSM 1,248 5.10% 6.20% 1.30%
Fairley [65]
Morris et al.
2006 California (US) Community 20012003 MSM 2,475 5.50%
[76]
Benn et al. [58] 2007 United Kingdom Genitourinary clinic 19992001 MSM 613 7.20% 7.30% 7.30% 4.30% 6.50% 1.20%
Alexander et al.
2008 United Kingdom Genitourinary clinic 20052007 MSM 272 14.90% 6.50% 13.60%
[54]
Gunn et al.
2008 California (US) STD clinic 19972003 MSM 7,333 10.80% 9.80% 4.00%
[64]
Lister et al. [71] 2008 Australia Sexual health clinic 2002-2003 MSM 366 5.00% 7.00%
Mimiaga et al. Gay mens health
2008 Massachusetts (US) 2007 MSM 114 1.00% 1.70% 0.00% 2.60% 6.10%
[74] center
Rieg et al. [82] 2008 California (US) HIV clinic 20042006 MSM (HIV+) 212 1.50% 4.30% 3.30% 1.50% 2.90% 1.40%
Templeton et
2008 Australia Community 2003 MSM 1,427 1.10%
al. [89]
Annan et al. HIV/genitourinary
2009 United Kingdom 2005-2006 MSM 3,076 4.10% 1.30% 5.40% 8.20%
[55] clinic
Baker et al. [56] 2009 Washington DC (US) Outpatient clinic 2006-2007 MSM 147 0.00% 1.40% 2.80% 0.00% 2.10% 0.70%
Dang et al. [61] 2009 Switzerland HIV clinic 2007-2008 MSM (HIV+) 147 10.90%
Klausner et al.
2009 US (5 cities) Outpatient clinic 2007-2008 MSM 3,410/14,189 5.40% 5.30% 8.90% 1.60%
[70]
Mimiaga et al. Gay mens health
2009 Massachusetts (US) 2003-2004 MSM 21,927 13.40% 8.80% 1.90% 5.70%
[75] center
Gay mens health
Ota et al. [77] 2009 Canada 20062008 MSM 248 11.70% 8.10% 7.70% 2.00%
center
van der Helm
2009 Netherlands STD clinic 2006-2007 MSM 1,458 7.00% 11.00%
[49]
Templeton et
2010 Australia Community 2003 MSM 1,427 0.60%
al. [90]
Marcus et al.
2011 California (US) STD clinic 2008-2009 MSM 3,398 0.40% 3.60% 5.00% 2.30% 7.80% 1.90%
[172]
Peters et al.
2011 Netherlands STD clinic 2007-2008 MSM 1,455 2.80% 6.00% 4.20% 4.00% 8.20% 1.50%
[39]
Soni and White
2011 United Kingdom HIV clinic 2009-2010 MSM (HIV+) 634 1.30% 4.20% 3.90% 2.60% 9.80% 1.70%
[86]
Vodstrcil et al.
2011 Australia Sexual health clinic 20022009 MSM 8,328/7,133 3.10% 1.80% 3.70% 5.40%
[93]
Infectious Diseases in Obstetrics and Gynecology

Koedijk et al.
2012 Netherlands STD clinic 20062010 MSM 69,506 3.40% 5.50% 3.90% 4.30% 10.10% 1.70%
[22]
Table 2: Continued.
Gonorrhea Chlamydia
Author Study year Location Setting Time period Risk Sample
Urogenital Rectal Pharyngeal Urogenital Rectal Pharyngeal
Mayer et al.
2012 US (4 cities) HIV clinic 20042006 MSM (HIV+) 365 0.00% 2.00% 3.00% 2.00% 7.00% 1.00%
[36]
HIV/STD clinic, gay
Park et al. [78] 2012 California (US) 2010 MSM 12,454 5.80% 1.70%
mens health center
Pinsky et al. University health
2012 New York (US) 20072010 MSM 200 0.50% 3.50% 3.00% 0.50%
[81] center
Diaz et al. [26] 2013 Spain STD clinic 20062010 MSM 1,320 58.30% 21.10% 5.20%
Jimenez et al.
2013 Spain HIV clinic 2011-2012 MSM (HIV+) 264 9.50%
[66]
Sexton et al. Primary care clinic,
2013 Washington DC (US) 20092011 MSM 374 8.00% 9.30% 12.70% 1.30%
[85] HIV/STD clinic
Turner et al.
2013 Ohio (US) STD clinic 2010-2011 MSM 125 24.00% 23.00%
[92]
Barbee et al.
2014 Washington (US) STD clinic 2011 MSM 3,034 5.50% 9.70% 6.50% 4.40% 11.90% 2.30%
[57]
Dudareva-
Vizule et al. 2014 Germany STD clinic 2009-2010 MSM 2,247 1.90% 4.60% 5.50% 3.40% 8.00% 1.50%
Infectious Diseases in Obstetrics and Gynecology

[62]
Gratrix et al.
2014 Canada STD clinic 2012 MSM 972 2.40% 5.90% 4.30% 14.10%
[63]
Keaveney et al.
2014 Ireland HIV clinic 2012 MSM (HIV+) 121 0.00% 4.10% 3.30% 1.70% 6.60% 0.80%
[67]
Patton et al.
2014 US (42 sites) STD clinic 2011-2012 MSM 21,994 11.10% 10.20% 7.90% 8.40% 14.10% 2.90%
[79]
Sanders et al.
2014 Kenya Medical clinic 2011 MSM 244 1.60% 5.70% 6.10% 8.10%
[84]
van Liere et al.
2014 Netherlands STD clinic 20102012 MSM 2,436 1.50% 3.70% 3.40% 3.30% 7.90% 1.10%
[47]
Chow et al.
2015 Australia Sexual health clinic 20072013 MSM 12,873 2.30% 2.90% 1.70% 3.00% 5.60%
[59]
Danby et al.
2016 Pennsylvania (US) STD clinic 2014-2015 MSM 224 5.40% 11.60% 16.50% 4.50% 17.40% 2.20%
[25]
Dukers-
Muijrers et al. 2015 Netherlands STD clinic 20102013 MSM 2,349 1.40% 4.00% 3.40% 3.20% 7.30% 0.70%
[19]
Garner et al.
2015 United Kingdom Sexual health clinic 2010 MSM 365 4.70% 9.00% 5.20% 5.30% 6.50% 2.20%
[27]
Taylor et al.
2015 Arizona (US) HIV clinic 20112013 MSM 1,591 19.60% 18.60%
[88]
Tongtoyai et al.
2015 Thailand Medical clinic 20062010 MSM 1,744 1.80% 6.10% 0.50% 4.50% 9.50% 3.60%
[91]
Trebach et al.
2015 Maryland (US) STD clinic 20112013 MSM 769 8.90% 17.90% 11.00% 1.50% 14.30% 2.50%
[44]
Van Liere et al.
2015 Netherlands STD clinic 2011-2012 MSM 9,549 4.20% 9.80%
[167]
van Liere et al.
2013 Netherlands STD clinic 2010-2011 MSM 926 3.46% 7.88%
[45]
Bachmann et STD clinic, HIV
2010 US 20032007 MSM 297 5.10% 7.90% 8.30% 2.00% 10.30% 1.70%
al. [52] clinic
Note. STD: sexually transmitted diseases; US: United States; MSM: men who have sex with men.
7
8 Infectious Diseases in Obstetrics and Gynecology

rectal symptoms were pruritus (36%) anal discharge (17%), N. gonorrhoeae in the pharynx and rectum may be linked to
burning (13%), inflammation (11%), pain (11%), and erythema substantial colonization of these extragenital sites by a wide
around the anus (6%) [62]. Symptom-based screening may range of other organisms, including other Neisseria species,
miss up to 60% of extragenital infections [30, 39, 45]. possibly leading to interference with N. gonorrhoeae isolation
Extragenital infections may also be increasing in preva- [111]. For suspected or documented treatment failure, N.
lence [59, 77, 95], as several studies have reported higher gonorrhoeae cultures should be obtained and antimicrobial
prevalence of extragenital infections among MSM in recent susceptibilities performed.
time periods. However, this could also reflect more thorough Extragenital specimens are collected via a swab of the
screening practices or improved testing methods [97, 98]. rectum or pharynx, by either a clinician or a self-collected
Extragenital infections among MSM are associated with swab. Self-collected swab as a means of collecting pharyngeal
concurrent partners, existing HIV infection ( = 2 studies), and rectal specimens is supported by the CDC guidelines
condomless anal sex ( = 3), and drug use during sex ( = 1) [12] and has been found to be an acceptable means of
[62, 65, 69, 89, 91]. Concurrent infections with other STDs are obtaining specimens among women [112, 113] and MSM
common [99]. The overwhelming evidence indicates a high [49, 54, 85, 114117], which may lead to an increase in extra-
prevalence of extragenital N. gonorrhoeae and C. trachomatis genital diagnoses [118] due to the noninvasive nature of the
infections among MSM, the asymptomatic nature of most of procedure. Self-collected swabs may also reduce the workload
these infections, and the prevalence of extragenital infection for clinic staff who obtain them and promote screening when
without concurrent urogenital infection, all of which support clinicians are not available for collection.
the need for routine screening at extragenital sites.
3.7. Treatment of Extragenital Infections. Current US guide-
3.5. Extragenital Infections in MSW. A total of nine studies lines regarding treatment of extragenital infections due to N.
evaluated the prevalence of extragenital infections due to N. gonorrhoeae and C. trachomatis are similar to those for the
gonorrhoeae or C. trachomatis in MSW [19, 26, 27, 33, 36, 38, treatment of urogenital infections [12]. Treatment guidelines
44, 45, 100] (Table 3). Overall, there are limited prevalence from the United Kingdom and Europe both recommend sim-
data of extragenital infections among MSW. The prevalence of ilar regimens for both urogenital and extragenital infections
extragenital infections among MSW in the studies reviewed [17, 18, 119]. Extragenital pharyngeal and rectal gonorrhea
ranged 05.7% for rectal gonorrhea (median 3.4%), 0.4 and chlamydia infections may spontaneously clear even in
15.5% for pharyngeal gonorrhea (median 2.2%), 011.8% for the absence of treatment among MSM and high-risk women
rectal chlamydia (median 7.7%), and 022.0% for pharyngeal [120, 121]. If extragenital sites are a reservoir for ongo-
chlamydia (median 1.6%). These data represent studies that ing transmission, then suboptimal treatment of extragenital
evaluated heterosexually identified men, some of whom may infections could lead to the spread of any existing resistant
have engaged in sex with other men [44], a distinction which organisms. Care should be taken with extragenital treatment
emphasizes the need to consistently focus on sexual behavior and retesting should be performed if persistent infection or
rather than identity. Other studies which did not evaluate treatment failure is suspected.
for or stratify by specific risk behaviors further support the The recommended treatment for urogenital chlamydia
prevalence studies in individual populations [32, 100107] infection is azithromycin 1000 milligrams orally in a single
(Table 3). dose or doxycycline 100 milligrams orally twice daily for
seven days. Due to the ease of administration, the ability
3.6. Diagnoses of Extragenital Infections. The gold standard for directly observed therapy in a single dose, and the high
for diagnosis of urogenital infection due to N. gonorrhoeae rates of adherence, azithromycin is the usual treatment option
and C. trachomatis is the nucleic acid amplification test in many clinics. Earlier reports demonstrated similar results
(NAAT). However, NAAT assays are not approved by the with both regimens for treatment of urogenital infection, with
US Food and Drug Administration (FDA) for detecting N. high (>96%) cure rates [122]. In contrast, recent analyses have
gonorrhoeae and C. trachomatis from pharyngeal or rectal suggested a potential small advantage of doxycycline com-
specimens [108]. Culture is still the only approved method pared to azithromycin for urogenital chlamydia infection;
for diagnosis at these sites. However, NAAT is the most the efficacy of doxycycline has been reported as being 100%
sensitive test for detecting C. trachomatis and N. gonorrhoeae compared to 97% for azithromycin [123, 124].
and is recommended for this purpose by the CDC [12]. Efficacy of chlamydia treatments may differ for extra-
NAAT has demonstrated higher sensitivity and specificity genital infections at rectal and pharyngeal sites [19]. Doxy-
compared to culture for detecting extragenital infections cycline may have slightly greater efficacy compared to
[52, 74, 109, 110]. At the present time, laboratories must azithromycin for both rectal [125132] and pharyngeal [133]
validate these tests in-house based on Clinical Laboratory chlamydia infection, as single-dose azithromycin may not
Improvement Amendments (CLIA) regulatory requirements lead to sustained drug concentrations capable of curing
before performing NAAT testing on rectal and pharyngeal extragenital infection [134]. For example, treatment failure
specimens; many large commercial laboratories have per- was significantly more common with azithromycin (10% of
formed this validation and offer this testing option. The main patients) compared to doxycycline (2%) in a small study
disadvantages of performing NAAT testing over culture is for treatment of pharyngeal chlamydia. In a meta-analysis
the inability to determine antimicrobial susceptibilities and of azithromycin and doxycycline for the treatment of rectal
bacterial viability. Potentially lower sensitivity of NAAT for chlamydia, azithromycin was 83% effective compared to
Table 3: Characteristics of studies reporting extragenital infections due to N. gonorrhoeae and C. trachomatis among men who have sex with women and populations with mixed behaviors.
Gonorrhea Chlamydia
Author Study year Location Setting Time period Risk Sample
Urogenital Rectal Pharyngeal Urogenital Rectal Pharyngeal
Jones et al. [33] 1985 Indiana (US) STD clinic 1985 MSW 706 21.00% 3.70%
Ostergaard et al. [38] 1997 Denmark STD clinic 1995-1996 MSW 169 0.60% 0.00% 0.00%
Mayer et al. [36] 2012 US (4 cities) HIV clinic 20042006 MSW (HIV+) 73 1.00% 0.00% 1.00% 0.00% 0.00% 1.00%
Infectious Diseases in Obstetrics and Gynecology

Wada et al. [173] 2012 Japan Urology clinic 2007-2008 MSW 42 47.60% 11.90% 26.20% 2.40%
Diaz et al. [26] 2013 Spain STD clinic 20062010 MSW 747 92.90% 0.00% 0.90%
Dukers-Muijrers et al. [19] 2015 Netherlands STD clinic 20102013 MSW 5,007 0.60% 0.40% 2.20% 11.70% 0.90% 0.20%
Garner et al. [27] 2015 United Kingdom Sexual health clinic 2010 MSW 553 0.90% 0.40% 12.40% 0.70%
Trebach et al. [44] 2015 Maryland (US) STD clinic 20112013 MSW 5,218 4.30% 5.70% 2.50% 2.30% 9.10% 1.60%
van Liere et al. [45] 2013 Netherlands STD clinic 20102012 MSW (swingers) 303 0.33% 1.32%
Ivens et al. [103] 2007 United Kingdom Genitourinary clinic 20032005 Mixed 1187 4.70% 8.50%
Tipple et al. [107] 2010 United Kingdom Sexual health clinic 2006-2007 Mixed 2,406 1.90%
Chan et al. [100] 2012 Rhode Island (US) Hospital system 2011-2012 Mixed 178/21,201 0.90% 5.30% 3.40% 5.70% 11.80% 1.70%
Primary care/adult
Rodriguez-Hart et al. [106] 2012 US 2010 Mixed 168 2.40% 2.40% 1.20% 18.50% 11.30% 22.00%
film
Dimech et al. [102] 2014 Australia Surveillance system 20082010 Men (mixed) 177,557 12.217.4% 5.20% 1.30%
Jenkins et al. [32] 2014 Illinois (US) Emergency room 2012-2013 Men (mixed) 192 4.70% 2.10% 4.70% 1.00%
Otorhinolaryngology
Oda et al. [104] 2014 Japan 2012 Mixed 225 2.20% 0.90%
clinic
Patterson et al. [105] 2014 US Military 2013-2014 Mixed (HIV+) 316 0.80% 4.30% 15.50% 1.00% 6.90% 6.50%
STD clinic,
den Heijer et al. [101] 2016 Netherlands gynecology, primary 20062010 Mixed 246/22,029 8.20% 10.10% 1.60%
care clinic
Note. STD: sexually transmitted diseases; US: United States; MSW: men who have sex with women.
9
10 Infectious Diseases in Obstetrics and Gynecology

>99% efficacy of doxycycline [125]. Treatment guidelines in 4. Conclusions


Europe [16] and Australia [135] recommend doxycycline as
the treatment of choice for rectal infections. However, care Several key questions exist regarding screening for and
should be taken when interpreting these smaller studies, and management of extragenital infections. Urogenital screening
the potential small benefits must be weighed against the ease for N. gonorrhoeae and C. trachomatis infection is generally
of administration, ability for directly observed therapy, and performed to reduce complications in women and to decrease
adherence for the single dose azithromycin therapy option. the risk of HIV infection in MSM [159162]. However, there is
No randomized controlled trials have evaluated treatment a lack of data on clinical outcomes associated with rectal and
regimens for extragenital chlamydia infection and further pharyngeal infections, including impact on overall morbidity.
studies are needed to determine optimal management of Two major questions are whether routine screening and treat-
these infections [136]. ment for extragenital gonorrhea and chlamydia infections
The current treatment recommendations for urogenital in women prevent sequelae observed in urogenital infection
N. gonorrhoeae infections involve a dual regimen of cef- (such as PID, ectopic pregnancy, and infertility), and whether
triaxone 250 milligrams intramuscularly as a single dose routine screening and treatment reduces the risk of HIV
in addition to azithromycin 1000 milligrams orally in a transmission in MSM. With regard to management, optimal
single dose [12]. Uncomplicated rectal infections with N. treatment regimens for rectal and pharyngeal extragenital
gonorrhoeae should be treated in the same manner. Given infections is unknown. Asymptomatic extragenital infections
that both ceftriaxone and azithromycin are administered as a may be a reservoir of ongoing transmission and antibiotic
single dose, these drugs should be administered together and resistant strains from these reservoir sites may go undetected
under direct observation. These recommendations are based and promote the spread of resistance.
on a number of treatment failures with ceftriaxone alone The contribution of extragenital infections to overall
and an increasing minimum inhibitory concentration (MIC) transmission of gonorrhea and chlamydia, including the
to oral cephalosporins which has been observed mostly transmission potential between different anatomic sites, is
outside of the US [137148]. The dual therapy also has the also unclear. In women, evidence suggests that rectal infec-
advantage of treating C. trachomatis infection, which fre- tions can be spread to urogenital sites [163]. It is also likely
quently accompanies N. gonorrhoeae infection. Doxycycline that pharyngeal infections can be spread to the male urethra
can be considered in place of azithromycin, but azithromycin [13, 14, 164] and rectum [165]. Contributing to potential
is strongly preferred given increased resistance to doxy- transmission risk may be bacterial load at different anatomic
cycline [144]. This regimen has a high (>98%) treatment sites [166, 167]. These data suggest that the prevalence and
efficacy for rectal infections [149, 150]. Pharyngeal infections associated morbidity of extragenital infections caused by N.
with N. gonorrhoeae are more difficult to treat and have gonorrhoeae and C. trachomatis, especially among women,
demonstrated ceftriaxone resistance and treatment failure may be reduced by thorough extragenital screening and
in a number of countries outside the US [138141, 143, 145, early treatment of extragenital infections, although this is
146, 151, 152]. In both pharyngeal and rectal gonorrhea, unproven. Screening and treatment for rectal infections,
persistence of the organism after treatment may be due to especially among populations at high risk of HIV (e.g.,
reinfection but can also reflect an elevated MIC to antibiotic MSM), may be a cost-effective intervention to prevent
regimens [153]. At this time, guidelines still recommend HIV [168]. Optimal screening strategies for extragenital
treating pharyngeal infection by N. gonorrhoeae with ceftri- infections are largely unknown. Further studies are needed
axone and azithromycin [12]. The addition of azithromycin in settings other than reproductive health and STD clin-
may improve treatment efficacy for pharyngeal infections ics, especially in primary care clinics and resource-limited
[154, 155]. settings.
In general, test of cure is not recommended except in Extragenital infections due to N. gonorrhoeae and C.
cases where there are persistent symptoms, therapy was not trachomatis are common, especially in settings which provide
completed, or reinfection is suspected. Retesting for both services to higher-risk men and women. In general, MSM
urogenital and extragenital infections less than three weeks demonstrate a higher prevalence of extragenital infection
after treatment is not recommended and can result in false compared to women and MSW [22, 2527, 44, 4749].
positive results due to the highly sensitive nature of NAAT Despite the accumulating data on the prevalence of these
and the possibility of detection of nonviable organisms [156, infections, screening at extragenital sites remains uncom-
157]. Furthermore, due to NAATs not being FDA-cleared mon [101, 102, 169]. STD and other sexual health clinics
at this time for the purpose of testing for cure, culture should consider implementing routine, universal extragenital
is the only retesting method that can be used to properly screening for N. gonorrhoeae and C. trachomatis infection
assess the efficacy of antibiotic treatments. The significance of among high-risk men and women. Importantly, guidelines
positive NAAT at extragenital sites during this time is unclear suggest screening based on reported risk behaviors; however,
and should be interpreted after a detailed clinical interview this may miss a significant amount of extragenital infection
including presence or absence of symptoms, potential risk [19, 22, 45, 47, 49, 52, 59, 62, 68, 7779, 90, 103, 107, 120, 133,
for reinfection, and adherence to treatment [158]. Men 170, 171]. In addition to targeting those with symptoms and
and women who are positive for N. gonorrhoeae and C. those reporting condomless anal or oral sex, screening should
trachomatis should generally be tested for reinfection three also include those without symptoms and those who do not
to six months after treatment [12, 16]. report condomless sex at a specific extragenital site, as the
Infectious Diseases in Obstetrics and Gynecology 11

nature of the infections are often asymptomatic, and high-risk [12] K. A. Workowski and G. A. Bolan, Sexually transmitted
behaviors are not consistently reported by patients. diseases treatment guidelines, 2015, MMWR Recommendations
and Reports, vol. 64, no. 3, pp. 1138, 2015.
[13] J. L. Marcus, R. P. Kohn, P. M. Barry, S. S. Philip, and K. T.
Competing Interests Bernstein, Chlamydia trachomatis and Neisseria gonorrhoeae
The authors report no conflict of interests. transmission from the female oropharynx to the male urethra,
Sexually Transmitted Diseases, vol. 38, no. 5, pp. 372373, 2011.
[14] K. T. Bernstein, S. C. Stephens, P. M. Barry et al., Chlamydia
Acknowledgments trachomatis and Neisseria gonorrhoeae transmission from the
oropharynx to the Urethra among men who have sex with men,
Philip A. Chan is supported by Grant K23AI096923 from Clinical Infectious Diseases, vol. 49, no. 12, pp. 17931797, 2009.
the National Institutes of Health. Additional support was
[15] American Congress of Obstetricians and Gynecologists, Gon-
provided by the Lifespan/Tufts/Brown Center for AIDS orrhea, chlamydia, and syphilis, Tech. Rep. FAQ071, American
Research, funded by the National Institute of Allergy and Congress of Obstetricians and Gynecologists, Washington, DC,
Infectious Diseases (P30AI042853). USA, 2016.
[16] E. Lanjouw, J. M. Ossewaarde, A. Stary, F. Boag, and W. I. van
References der Meijden, 2010 European guideline for the management of
Chlamydia trachomatis infections, International Journal of STD
[1] Office of Disease Prevention and Health Promotion, Sexually and AIDS, vol. 21, no. 11, pp. 729737, 2010.
transmitted diseases [Internet]. Healthy People 2020. 2014, [17] C. Bignell, M. Unemo, and European STI Guidelines Editorial
https://www.healthypeople.gov/2020/topics-objectives/topic/ Board, 2012 European guideline on the diagnosis and treat-
sexually-transmitted-diseases. ment of gonorrhoea in adults, International Journal of STD &
[2] Centers for Disease Control and Prevention, Sexually Transmit- AIDS, vol. 24, no. 2, pp. 8592, 2013.
ted Disease Surveillance 2014, U.S. Department of Health and [18] British Association for Sexual Health and HIV, Sexually Trans-
Human Services, Atlanta, Ga, USA, 2015. mitted Infections: UK National Screening and Testing Guidelines,
[3] D. Meyers, T. Wolff, K. Gregory et al., USPSTF recommenda- 2006.
tions for STI screening, American Family Physician, vol. 77, no.
[19] N. H. T. M. Dukers-Muijrers, J. Schachter, G. A. F. S. van Liere,
6, pp. 819824, 2008.
P. F. G. Wolffs, and C. J. P. A. Hoebe, What is needed to guide
[4] K. K. Fox, C. del Rio, K. K. Holmes et al., Gonorrhea in the HIV testing for anorectal and pharyngeal Chlamydia trachomatis
era: a reversal in trends among men who have sex with men, and Neisseria gonorrhoeae in women and men? Evidence and
American Journal of Public Health, vol. 91, no. 6, pp. 959964, opinion, BMC Infectious Diseases, vol. 15, no. 1, article 533, 2015.
2001.
[20] Australian Sexual Health Alliance, Australian STI Management
[5] C. A. Rietmeijer, J. L. Patnaik, F. N. Judson, and J. M. Douglas Jr.,
Guidelines for Use in Primary Care, Australian Government
Increases in gonorrhea and sexual risk behaviors among men
Department of Health, Darlinghurst, Australia, 2016.
who have sex with men: a 12-year trend analysis at the Denver
Metro Health Clinic, Sexually Transmitted Diseases, vol. 30, no. [21] D. A. Lewis and E. Marumo, Revision of the national guide-
7, pp. 562567, 2003. line for first-line comprehensive management and control of
sexually transmitted infections: whats new and why? Southern
[6] R. Detels, A. M. Green, J. D. Klausner et al., The incidence
African Journal of Infectious Diseases, vol. 24, no. 2, 2009,
and correlates of symptomatic and asymptomatic Chlamydia
http://sajei.co.za/index.php/SAJEI/article/view/161.
trachomatis and Neisseria gonorrhoeae infections in selected
populations in five countries, Sexually Transmitted Diseases, [22] F. D. H. Koedijk, J. E. A. M. van Bergen, N. H. T. M. Dukers-
vol. 38, no. 6, pp. 503509, 2011. Muijrers, A. P. van Leeuwen, C. J. P. A. Hoebe, and M. A. B.
[7] J. A. Cecil, M. R. Howell, J. J. Tawes et al., Features of Chlamydia van der Sande, The value of testing multiple anatomic sites
trachomatis and Neisseria gonorrhoeae infection in male army for gonorrhoea and chlamydia in sexually transmitted infection
recruits, The Journal of Infectious Diseases, vol. 184, no. 9, pp. centres in the Netherlands, 20062010, International Journal of
12161219, 2001. STD & AIDS, vol. 23, no. 9, pp. 626631, 2012.
[8] C. Mitchell and M. Prabhu, Pelvic inflammatory disease: [23] J. A. Bazan, P. Carr Reese, A. Esber et al., High prevalence of
current concepts in pathogenesis, diagnosis and treatment, rectal gonorrhea and chlamydia infection in women attending a
Infectious Disease Clinics of North America, vol. 27, no. 4, pp. sexually transmitted disease clinic, Journal of Womens Health,
793809, 2013. vol. 24, no. 3, pp. 182189, 2015.
[9] F. D. H. Koedijk, J. E. A. M. van Bergen, N. H. T. M. Dukers- [24] P. M. Barry, C. K. Kent, S. S. Philip, and J. D. Klausner, Results of
Muijrers, A. P. van Leeuwen, C. J. P. A. Hoebe, and M. A. B. a program to test women for rectal chlamydia and gonorrhea,
van der Sande, The value of testing multiple anatomic sites Obstetrics and Gynecology, vol. 115, no. 4, pp. 753759, 2010.
for gonorrhoea and chlamydia in sexually transmitted infection [25] C. S. Danby, L. A. Cosentino, L. K. Rabe et al., Patterns
centres in the Netherlands, 20062010, International Journal of of extragenital chlamydia and gonorrhea in women and men
STD and AIDS, vol. 23, no. 9, pp. 626631, 2012. who have sex with men reporting a history of receptive anal
[10] M. S. Cohen, Sexually transmitted diseases enhance HIV intercourse, Sexually Transmitted Diseases, vol. 43, no. 2, pp.
transmission: no longer a hypothesis, The Lancet, vol. 351, pp. 105109, 2016.
S5S7, 1998. [26] A. Diaz, C. Garriga, J. A. Varela et al., Gonorrhoea diagnoses in
[11] J. D. Carter and R. D. Inman, Chlamydia-induced reactive a network of STI clinics in Spain during the period 2006-2010:
arthritis: hidden in plain sight? Best Practice and Research: differences by sex and transmission route, BMC Public Health,
Clinical Rheumatology, vol. 25, no. 3, pp. 359374, 2011. vol. 13, article 1093, 2013.
12 Infectious Diseases in Obstetrics and Gynecology

[27] A. L. Garner, G. Schembri, T. Cullen, and V. Lee, Should we [41] M. Raychaudhuri and H. D. L. Birley, Audit of routine rectal
screen heterosexuals for extra-genital chlamydial and gonococ- swabs for gonorrhoea culture in women, International Journal
cal infections? International Journal of STD and AIDS, vol. 26, of STD and AIDS, vol. 21, no. 2, pp. 143144, 2010.
no. 7, pp. 462466, 2015. [42] M. Sethupathi, A. Blackwell, and H. Davies, Rectal Chlamydia
[28] C. M. Giannini, H. K. Kim, J. Mortensen, J. Mortensen, K. trachomatis infection in women. Is it overlooked? International
Marsolo, and J. Huppert, Culture of non-genital sites increases Journal of STD and AIDS, vol. 21, no. 2, pp. 9395, 2010.
the detection of gonorrhea in women, Journal of Pediatric and [43] S. G. Shaw, M. Hassan-Ibrahim, and S. Soni, Are we missing
Adolescent Gynecology, vol. 23, no. 4, pp. 246252, 2010. pharyngeal and rectal infections in women by not testing those
[29] J. Gratrix, A. E. Singh, J. Bergman et al., Evidence for increased who report oral and anal sex? Sexually Transmitted Infections,
chlamydia case finding after the introduction of rectal screening vol. 89, no. 5, p. 397, 2013.
among women attending 2 Canadian sexually transmitted [44] J. D. Trebach, C. P. Chaulk, K. R. Page, S. Tuddenham, and K.
infection clinics, Clinical Infectious Diseases, vol. 60, no. 3, pp. G. Ghanem, Neisseria gonorrhoeae and Chlamydia trachoma-
398404, 2015. tis among women reporting extragenital exposures, Sexually
[30] T. Hunte, M. Alcaide, and J. Castro, Rectal infections with Transmitted Diseases, vol. 42, no. 5, pp. 233239, 2015.
chlamydia and gonorrhoea in women attending a multiethnic [45] G. A. F. S. van Liere, C. J. P. A. Hoebe, A.-M. Niekamp, F. D. H.
sexually transmitted diseases urban clinic, International Jour- Koedijk, and N. H. T. M. Dukers-Muijrers, Standard symptom-
nal of STD and AIDS, vol. 21, no. 12, pp. 819822, 2010. and sexual historybased testing misses anorectal Chlamydia
[31] M. Javanbakht, P. Gorbach, A. Stirland, M. Chien, P. Kerndt, and trachomatis and Neisseria gonorrhoeae infections in swingers
S. Guerry, Prevalence and correlates of rectal chlamydia and and men who have sex with men, Sexually Transmitted Dis-
gonorrhea among female clients at sexually transmitted disease eases, vol. 40, no. 4, pp. 285289, 2013.
clinics, Sexually Transmitted Diseases, vol. 39, no. 12, pp. 917 [46] G. A. F. S. van Liere, C. J. P. A. Hoebe, P. F. G. Wolffs, and N.
922, 2012. H. T. M. Dukers-Muijrers, High co-occurrence of anorectal
[32] W. D. Jenkins, L. L. Nessa, and T. Clark, Cross-sectional study chlamydia with urogenital chlamydia in women visiting an STI
of pharyngeal and genital chlamydia and gonorrhoea infections clinic revealed by routine universal testing in an observational
in emergency department patients, Sexually Transmitted Infec- study: a recommendation towards a better anorectal chlamydia
tions, vol. 90, no. 3, pp. 246249, 2014. control in women, BMC Infectious Diseases, vol. 14, no. 1, article
[33] R. B. Jones, R. A. Rabinovitch, B. P. Katz et al., Chlamydia 274, 2014.
trachomatis in the pharynx and rectum of heterosexual patients [47] G. A. F. S. van Liere, C. J. P. A. Hoebe, and N. H. T. M. Dukers-
at risk for genital infection, Annals of Internal Medicine, vol. Muijrers, Evaluation of the anatomical site distribution of
102, no. 6, pp. 757762, 1985. chlamydia and gonorrhoea in men who have sex with men
[34] J. Ladd, Y.-H. Hsieh, M. Barnes, N. Quinn, M. Jett-Goheen, and in high-risk women by routine testing: cross-sectional
and C. A. Gaydos, Female users of internet-based screening study revealing missed opportunities for treatment strategies,
for rectal STIs: descriptive statistics and correlates of positivity, Sexually Transmitted Infections, vol. 90, no. 1, pp. 5860, 2014.
Sexually Transmitted Infections, vol. 90, no. 6, pp. 485490, 2014. [48] G. A. van Liere, M. S. van Rooijen, C. J. Hoebe et al., Prevalence
[35] Y. Linhart, T. Shohat, Z. Amitai et al., Sexually transmitted of and Factors Associated with Rectal-Only Chlamydia and
infections among brothel-based sex workers in Tel-Aviv area, Gonorrhoea in Women and in Men Who Have Sex with Men,
Israel: high prevalence of pharyngeal gonorrhoea, International PLOS ONE, vol. 10, no. 10, p. e0140297, 2015.
Journal of STD & AIDS, vol. 19, no. 10, pp. 656659, 2008. [49] J. J. van der Helm, C. J. P. A. Hoebe, M. S. van Rooijen et
[36] K. H. Mayer, T. Bush, K. Henry et al., Ongoing sexually al., High performance and acceptability of self-collected rectal
transmitted disease acquisition and risk-taking behavior among swabs for diagnosis of Chlamydia trachomatis and Neisseria
US HIV-infected patients in primary care: implications for gonorrhoeae in men who have sex with men and women,
prevention interventions, Sexually Transmitted Diseases, vol. Sexually Transmitted Diseases, vol. 36, no. 8, pp. 493497, 2009.
39, no. 1, pp. 17, 2012. [50] A. Ding and R. Challenor, Rectal chlamydia in heterosexual
[37] K. Musil, M. Currie, M. Sherley, and S. Martin, Rectal chlamy- women: more questions than answers, International Journal of
dia infection in women at high risk of chlamydia attending STD & AIDS, vol. 25, no. 8, pp. 587592, 2014.
Canberra Sexual Health Centre, International Journal of STD [51] L. A. Cosentino, T. Campbell, A. Jett et al., Use of nucleic
& AIDS, vol. 27, no. 7, pp. 526530, 2015. acid amplification testing for diagnosis of anorectal sexually
[38] L. Ostergaard, T. Agner, E. Krarup, U. B. Johansen, K. Weis- transmitted infections, Journal of Clinical Microbiology, vol. 50,
mann, and E. Gutschik, PCR for detection of Chlamydia no. 6, pp. 20052008, 2012.
trachomatis in endocervical, urethral, rectal, and pharyngeal [52] L. H. Bachmann, R. E. Johnson, H. Cheng et al., Nucleic acid
swab samples obtained from patients attending an STD clinic, amplification tests for diagnosis of Neisseria gonorrhoeae and
Genitourinary Medicine, vol. 73, no. 6, pp. 493497, 1997. Chlamydia trachomatis rectal infections, Journal of Clinical
[39] R. P. H. Peters, N. Nijsten, J. Mutsaers, C. L. Jansen, S. A. Microbiology, vol. 48, no. 5, pp. 18271832, 2010.
Morre, and A. P. van Leeuwen, Screening of oropharynx and [53] P. M. Barry, C. K. Kent, S. S. Philip, and J. D. Klausner, Results of
anorectum increases prevalence of Chlamydia trachomatis and a program to test women for rectal chlamydia and gonorrhea,
Neisseria gonorrhoeae infection in female STD clinic visitors, Obstetrics & Gynecology, vol. 115, no. 4, pp. 753759, 2010.
Sexually Transmitted Diseases, vol. 38, no. 9, pp. 783787, 2011. [54] S. Alexander, C. Ison, J. Parry et al., Self-taken pharyngeal
[40] R. P. H. Peters, J. H. Dubbink, L. van der Eem et al., Cross- and rectal swabs are appropriate for the detection of Chlamydia
sectional study of genital, rectal, and pharyngeal chlamydia trachomatis and Neisseria gonorrhoeae in asymptomatic men
and gonorrhea in women in rural South Africa, Sexually who have sex with men, Sexually Transmitted Infections, vol.
Transmitted Diseases, vol. 41, no. 9, pp. 564569, 2014. 84, no. 6, pp. 488492, 2008.
Infectious Diseases in Obstetrics and Gynecology 13

[55] N. T. Annan, A. K. Sullivan, A. Nori et al., Rectal chlamydia [68] C. K. Kent, J. K. Chaw, W. Wong et al., Prevalence of rectal,
a reservoir of undiagnosed infection in men who have sex with urethral, and pharyngeal chlamydia and gonorrhea detected in
men, Sexually Transmitted Infections, vol. 85, no. 3, pp. 176179, 2 clinical settings among men who have sex with men: San
2009. Francisco, California, 2003, Clinical Infectious Diseases, vol. 41,
[56] J. Baker, M. Plankey, Y. Josayma et al., The prevalence of rectal, no. 1, pp. 6774, 2005.
urethral, and pharyngeal Neisseria gonorrheae and Chlamydia [69] A. A. Kim, C. K. Kent, and J. D. Klausner, Risk factors for rectal
trachomatis among asymptomatic men who have sex with men gonococcal infection amidst resurgence in HIV transmission,
in a prospective Cohort in Washington, D.C., AIDS Patient Sexually Transmitted Diseases, vol. 30, no. 11, pp. 813817, 2003.
Care and STDs, vol. 23, no. 8, pp. 585588, 2009. [70] J. D. Klausner, K. T. Bernstein, M. Pandori et al., Clinic-
[57] L. A. Barbee, J. C. Dombrowski, R. Kerani, and M. R. Golden, based testing for rectal and pharyngeal Neisseria gonorrhoeae
Effect of nucleic acid amplification testing on detection of and Chlamydia trachomatis infections by community-based
extragenital gonorrhea and chlamydial infections in men who organizationsfive cities, United States, 2007, Morbidity and
have sex with men sexually transmitted disease clinic patients, Mortality Weekly Report, vol. 58, pp. 716719, 2009.
Sexually Transmitted Diseases, vol. 41, no. 3, pp. 168172, 2014. [71] N. A. Lister, N. J. Chaves, C. W. Pang, A. Smith, and C.
[58] P. D. Benn, G. Rooney, C. Carder et al., Chlamydia trachomatis K. Fairley, Clinical significance of questionnaire-elicited or
and Neisseria gonorrhoeae infection and the sexual behaviour of clinically reported anorectal symptoms for rectal Neisseria
men who have sex with men, Sexually Transmitted Infections, gonorrhoeae and Chlamydia trachomatis amongst men who
vol. 83, no. 2, pp. 106112, 2007. have sex with men, Sexual Health, vol. 5, no. 1, pp. 7782, 2008.
[59] E. P. F. Chow, J. Tomnay, G. Fehler et al., Substantial increases in [72] K. Manavi, A. McMillan, and H. Young, The prevalence of
chlamydia and gonorrhea positivity unexplained by changes in rectal chlamydial infection amongst men who have sex with
individual-level sexual behaviors among men who have sex with men attending the genitourinary medicine clinic in Edinburgh,
men in an Australian sexual health service from 2007 to 2013, International Journal of STD and AIDS, vol. 15, no. 3, pp. 162
Sexually Transmitted Diseases, vol. 42, no. 2, pp. 8187, 2015. 164, 2004.
[73] A. McMillan, R. G. Sommerville, and P. M. K. McKie, Chlamy-
[60] M. J. Currie, S. J. Martin, T. M. Soo, and F. J. Bowden, Screening
dial infection in homosexual men: frequency of isolation of
for chlamydia and gonorrhoea in men who have sex with men
Chlamydia trachomatis from the urethra, ano-rectum, and
in clinical and non-clinical settings, Sexual Health, vol. 3, no. 2,
pharynx, British Journal of Venereal Diseases, vol. 57, no. 1, pp.
pp. 123126, 2006.
4749, 1981.
[61] T. Dang, K. Jaton-Ogay, M. Flepp et al., High prevalence of [74] M. J. Mimiaga, K. H. Mayer, S. L. Reisner et al., Asymptomatic
anorectal chlamydial infection in HIV-infected men who have gonorrhea and chlamydial infections detected by nucleic acid
sex with men in Switzerland, Clinical Infectious Diseases, vol. amplification tests among Boston area men who have sex with
49, no. 10, pp. 15321535, 2009. men, Sexually Transmitted Diseases, vol. 35, no. 5, pp. 495498,
[62] S. Dudareva-Vizule, K. Haar, A. Sailer et al., Prevalence of 2008.
pharyngeal and rectal Chlamydia trachomatis and Neisseria [75] M. J. Mimiaga, D. J. Helms, S. L. Reisner et al., Gonococ-
gonorrhoeae infections among men who have sex with men in cal, chlamydia, and syphilis infection positivity among MSM
Germany, Sexually Transmitted Infections, vol. 90, no. 1, pp. 46 attending a large primary care clinic, Boston, 2003 to 2004,
51, 2014. Sexually Transmitted Diseases, vol. 36, no. 8, pp. 507511, 2009.
[63] J. Gratrix, A. E. Singh, J. Bergman et al., Prevalence and char- [76] S. R. Morris, J. D. Klausner, S. P. Buchbinder et al., Prevalence
acteristics of rectal chlamydia and gonorrhea cases among men and incidence of pharyngeal gonorrhea in a longitudinal sample
who have sex with men after the introduction of nucleic acid of men who have sex with men: the EXPLORE study, Clinical
amplification test screening at 2 Canadian sexually transmitted Infectious Diseases, vol. 43, no. 10, pp. 12841289, 2006.
infection clinics, Sexually Transmitted Diseases, vol. 41, no. 10, [77] K. V. Ota, D. N. Fisman, I. E. Tamari et al., Incidence and
pp. 589591, 2014. treatment outcomes of pharyngeal Neisseria gonorrhoeae and
[64] R. A. Gunn, C. J. OBrien, M. A. Lee, and R. A. Gilchick, Chlamydia trachomatis infections in men who have sex with
Gonorrhea screening among men who have sex with men: men: a 13-year retrospective cohort study, Clinical Infectious
value of multiple anatomic site testing, San Diego, California, Diseases, vol. 48, no. 9, pp. 12371243, 2009.
19972003, Sexually Transmitted Diseases, vol. 35, no. 10, pp. [78] J. Park, J. L. Marcus, M. Pandori, A. Snell, S. S. Philip, and K. T.
845848, 2008. Bernstein, Sentinel surveillance for pharyngeal chlamydia and
[65] J. Hocking and C. K. Fairley, Associations between condom gonorrhea among men who have sex with menSan Francisco,
use and rectal or urethral chlamydia infection in men, Sexually 2010, Sexually Transmitted Diseases, vol. 39, no. 6, pp. 482484,
Transmitted Diseases, vol. 33, no. 4, pp. 256258, 2006. 2012.
[66] E. Jimenez, M. G. Pedrazuela, M. M. Perez, S. F. de Mosteyrn, [79] M. E. Patton, S. Kidd, E. Llata et al., Extragenital gonorrhea and
J. J. Arrieta, and M. L. F. Guerrero, Prevalence of pharyngeal chlamydia testing and infection among men who have sex with
infection by Neisseria gonorrhoeae among human immunodefi- menSTD Surveillance Network, United States, 20102012,
ciency virus-positive men who have sex with men in downtown Clinical Infectious Diseases, vol. 85, no. 11, pp. 15641570, 2014.
Madrid, 2011, International Journal of STD & AIDS, vol. 24, no. [80] R. P. H. Peters, S. P. Verweij, N. Nijsten et al., Evaluation of
11, pp. 875878, 2013. sexual history-based screening of anatomic sites for chlamydia
[67] S. Keaveney, C. Sadlier, S. ODea, S. Delamere, and C. Bergin, trachomatis and neisseria gonorrhoeae infection in men having
High prevalence of asymptomatic sexually transmitted infec- sex with men in routine practice, BMC Infectious Diseases, vol.
tions in HIV-infected men who have sex with men: a stimulus 11, article 203, 2011.
to improve screening, International Journal of STD and AIDS, [81] L. Pinsky, D. B. Chiarilli, J. D. Klausner et al., Rates of asymp-
vol. 25, no. 10, pp. 758761, 2014. tomatic nonurethral gonorrhea and chlamydia in a population
14 Infectious Diseases in Obstetrics and Gynecology

of university men who have sex with men, Journal of American at an STD clinic in Melbourne, Sexual Health, vol. 1, no. 1, pp.
College Health, vol. 60, no. 6, pp. 481484, 2012. 4750, 2004.
[82] G. Rieg, R. J. Lewis, L. G. Miller, M. D. Witt, M. Guerrero, and E. [95] W. M. Geisler, W. L. H. Whittington, R. J. Suchland, and
S. Daar, Asymptomatic sexually transmitted infections in HIV- W. E. Stamm, Epidemiology of anorectal chlamydial and
infected men who have sex with men: prevalence, incidence, gonococcal infections among men having sex with men in
predictors, and screening strategies, AIDS Patient Care and Seattle: utilizing serovar and auxotype strain typing, Sexually
STDs, vol. 22, no. 12, pp. 947954, 2008. Transmitted Diseases, vol. 29, pp. 189195, 2002.
[83] A. M. Rompalo, C. B. Price, P. L. Roberts, and W. E. Stamm, [96] A. McMillan and H. Young, Clinical correlates of rectal
Potential value of rectal-screening cultures for Chlamydia gonococcal and chlamydial infections, International Journal of
trachomatis in homosexual men, Journal of Infectious Diseases, STD & AIDS, vol. 17, no. 6, pp. 387390, 2006.
vol. 153, no. 5, pp. 888892, 1986. [97] J. L. Marcus, K. T. Bernstein, S. C. Stephens et al., Sentinel
[84] E. J. Sanders, E. Wahome, H. S. Okuku et al., Evaluation of surveillance of rectal chlamydia and gonorrhea among males
WHO screening algorithm for the presumptive treatment of San Francisco, 20052008, Sexually Transmitted Diseases, vol.
asymptomatic rectal gonorrhoea and chlamydia infections in 37, no. 1, pp. 5961, 2010.
at-risk MSM in Kenya, Sexually Transmitted Infections, vol. 90, [98] N. Ryder, C. Bourne, and B. Donovan, Different trends for
no. 2, pp. 9499, 2014. different sexually transmissible infections despite increased
[85] M. E. Sexton, J. J. Baker, K. Nakagawa et al., How reliable is self- testing of men who have sex with men, International Journal
testing for gonorrhea and chlamydia among men who have sex of STD and AIDS, vol. 22, no. 6, pp. 335337, 2011.
with men? Journal of Family Practice, vol. 62, no. 2, pp. 7078, [99] A. McMillan, K. Manavi, and H. Young, Concurrent gonococ-
2013. cal and chlamydial infections among men attending a sexually
transmitted diseases clinic, International Journal of STD and
[86] S. Soni and J. A. White, Self-screening for Neisseria gonor-
AIDS, vol. 16, no. 5, pp. 357361, 2005.
rhoeae and chlamydia trachomatis in the human immunodefi-
ciency virus clinic-high yields and high acceptability, Sexually [100] P. A. Chan, M. Janvier, N. E. Alexander, E. M. Kojic, and K.
Transmitted Diseases, vol. 38, no. 12, pp. 11071109, 2011. Chapin, Recommendations for the diagnosis of Neisseria gon-
orrhoeae and Chlamydia trachomatis, including extra-genital
[87] S. R. Tabet, M. R. Krone, M. A. Paradise, L. Corey, W. E. Stamm,
sites, Medicine and Health, Rhode Island, vol. 95, no. 8, pp. 252
and C. L. Celum, Incidence of HIV and sexually transmitted
254, 2012.
diseases (STD) in a cohort of HIV-negative men who have sex
with men (MSM), AIDS, vol. 12, no. 15, pp. 20412048, 1998. [101] C. D. den Heijer, G. A. van Liere, C. J. Hoebe et al., Who tests
whom? A comprehensive overview of Chlamydia trachomatis
[88] M. M. Taylor, D. R. Newman, J. Gonzalez, J. Skinner, R. test practices in a Dutch region among different STI care
Khurana, and T. Mickey, HIV status and viral loads among providers for urogenital, anorectal and oropharyngeal sites in
men testing positive for rectal gonorrhoea and chlamydia, young people: a cross-sectional study, Sexually Transmitted
Maricopa County, Arizona, USA, 20112013, HIV Medicine, vol. Infections, vol. 92, no. 3, pp. 211217, 2016.
16, no. 4, pp. 249254, 2015.
[102] W. Dimech, M. S. C. Lim, C. Van Gemert et al., Analysis of
[89] D. J. Templeton, F. Jin, J. Imrie et al., Prevalence, incidence and laboratory testing results collected in an enhanced chlamydia
risk factors for pharyngeal chlamydia in the community based surveillance system in Australia, 20082010, BMC Infectious
Health in Men (HIM) cohort of homosexual men in Sydney, Diseases, vol. 14, article 325, 2014.
Australia, Sexually Transmitted Infections, vol. 84, no. 5, pp.
[103] D. Ivens, K. MacDonald, L. Bansi, and A. Nori, Screening for
361363, 2008.
rectal chlamydia infection in a genitourinary medicine clinic,
[90] D. J. Templeton, F. Jin, L. P. McNally et al., Prevalence, International Journal of STD and AIDS, vol. 18, no. 6, pp. 404
incidence and risk factors for pharyngeal gonorrhoea in a 406, 2007.
community-based HIV-negative cohort of homosexual men in [104] K. Oda, H. Yano, N. Okitsu et al., Detection of Chlamydia
Sydney, Australia, Sexually Transmitted Infections, vol. 86, no. trachomatis or Neisseria gonorrhoeae in otorhinolaryngology
2, pp. 9096, 2010. patients with pharyngeal symptoms, Sexually Transmitted
[91] J. Tongtoyai, C. S. Todd, W. Chonwattana et al., Prevalence and Infections, vol. 90, article 99, 2014.
correlates of Chlamydia trachomatis and Neisseria gonorrhoeae [105] S. B. Patterson, D. Rivera, T. S. Sunil, and J. F. Okulicz, Evalu-
by anatomic site among urban Thai men who have sex with ation of extragenital screening for gonorrhea and chlamydia in
men, Sexually Transmitted Diseases, vol. 42, no. 8, pp. 440449, HIV-infected active duty Air Force members, MSMR, vol. 21,
2015. no. 11, pp. 79, 2014.
[92] A. N. Turner, P. C. Reese, M. Ervin, J. A. Davis, K. S. Fields, and J. [106] C. Rodriguez-Hart, R. A. Chitale, R. Rigg, B. Y. Goldstein, P. R.
A. Bazan, HIV, rectal chlamydia, and rectal gonorrhea in men Kerndt, and P. Tavrow, Sexually transmitted infection testing
who have sex with men attending a sexually transmitted disease of adult film performers: is disease being missed? Sexually
clinic in a midwestern US city, Sexually Transmitted Diseases, transmitted diseases, vol. 39, no. 12, pp. 989994, 2012.
vol. 40, no. 6, pp. 433438, 2013. [107] C. Tipple, S. C. Hill, and A. Smith, Is screening for pharyngeal
[93] L. A. Vodstrcil, C. K. Fairley, G. Fehler et al., Trends in Chlamydia trachomatis warranted in high-risk groups? Inter-
chlamydia and gonorrhea positivity among heterosexual men national Journal of STD and AIDS, vol. 21, no. 11, pp. 770771,
and men who have sex with men attending a large urban sexual 2010.
health service in Australia, BMC Infectious Diseases, vol. 11, p. [108] R. K. Bolan and M. R. Beymer, One size does not fit all:
158, 2011. the public health ramifications of proposed food and drug
[94] N. A. Lister, A. Smith, T. Read, and C. K. Fairley, Testing administration premarket review for extragenital gonorrhea
men who have sex with men for Neisseria gonorrhoeae and and chlamydia testing, Sexually Transmitted Diseases, vol. 42,
Chlamydia trachomatis prior to the introduction of guidelines no. 7, pp. 403404, 2015.
Infectious Diseases in Obstetrics and Gynecology 15

[109] J. Schachter, J. Moncada, S. Liska, C. Shayevich, and J. D. [122] C.-Y. Lau and A. K. Qureshi, Azithromycin versus doxycycline
Klausner, Nucleic acid amplification tests in the diagnosis of for genital chlamydial infections: a meta-analysis of random-
chlamydial and gonococcal infections of the oropharynx and ized clinical trials, Sexually Transmitted Diseases, vol. 29, no. 9,
rectum in men who have sex with men, Sexually Transmitted pp. 497502, 2002.
Diseases, vol. 35, no. 7, pp. 637642, 2008. [123] F. Y. S. Kong, S. N. Tabrizi, M. Law et al., Azithromycin
[110] L. H. Bachmann, R. E. Johnson, H. Cheng, L. E. Markowitz, J. R. versus doxycycline for the treatment of genital chlamydia
Papp, and I. W. H. Edward, Nucleic acid amplification tests for infection: a meta-analysis of randomized controlled trials,
diagnosis of Neisseria gonorrhoeae oropharyngeal infections, Clinical Infectious Diseases, vol. 59, no. 2, pp. 193205, 2014.
Journal of Clinical Microbiology, vol. 47, no. 4, pp. 902907, 2009. [124] W. M. Geisler, A. Uniyal, J. Y. Lee et al., Azithromycin versus
[111] D. M. Whiley, J. W. Tapsall, and T. P. Sloots, Nucleic acid doxycycline for urogenital Chlamydia trachomatis infection,
amplification testing for Neisseria gonorrhoeae: an ongoing The New England Journal of Medicine, vol. 373, pp. 25122521,
challenge, Journal of Molecular Diagnostics, vol. 8, no. 1, pp. 3 2015.
15, 2006. [125] F. Y. S. Kong, S. N. Tabrizi, C. K. Fairley et al., The efficacy
of azithromycin and doxycycline for the treatment of rectal
[112] V. Schick, B. Van Der Pol, B. Dodge, A. Baldwin, and J. chlamydia infection: a systematic review and meta-analysis,
Dennis Fortenberry, A mixed methods approach to assess the Journal of Antimicrobial Chemotherapy, vol. 70, no. 5, Article ID
likelihood of testing for STI using self-collected samples among dku574, pp. 12901297, 2014.
behaviourally bisexual women, Sexually Transmitted Infections,
[126] J. S. Hocking, F. Y. S. Kong, P. Timms, W. M. Huston, and
vol. 91, no. 5, pp. 329333, 2015.
S. N. Tabrizi, Treatment of rectal chlamydia infection may
[113] A. M. Roth, J. G. Rosenberger, M. Reece, and B. Van Der Pol, be more complicated than we originally thought, Journal of
Expanding sexually transmitted infection screening among Antimicrobial Chemotherapy, vol. 70, no. 4, pp. 961964, 2014.
women and men engaging in transactional sex: the feasibility [127] S. J. Jordan and W. M. Geisler, Azithromycin for rectal chlamy-
of field-based self-collection, International Journal of STD and dia: is it time to leave azithromycin on the shelf?. . .Not yet,
AIDS, vol. 24, no. 4, pp. 323328, 2013. Sexually Transmitted Diseases, vol. 41, no. 2, pp. 8688, 2014.
[114] B. Dodge, B. Van Der Pol, J. G. Rosenberger et al., Field [128] N. M. Steedman and A. McMillan, Treatment of asymptomatic
collection of rectal samples for sexually transmitted infection rectal Chlamydia trachomatis: is single-dose azithromycin effec-
diagnostics among men who have sex with men, International tive? International Journal of STD & AIDS, vol. 20, no. 1, pp.
Journal of STD & AIDS, vol. 21, no. 4, pp. 260264, 2010. 1618, 2009.
[115] J. G. Rosenberger, B. Dodge, B. Van Der Pol, M. Reece, D. [129] E. Hathorn, C. Opie, and P. Goold, What is the appropriate
Herbenick, and J. D. Fortenberry, Reactions to self-sampling treatment for the management of rectal Chlamydia trachomatis
for ano-rectal sexually transmitted infections among men who in men and women? Sexually Transmitted Infections, vol. 88,
have sex with men: a qualitative study, Archives of Sexual no. 5, pp. 352354, 2012.
Behavior, vol. 40, no. 2, pp. 281288, 2011. [130] F. Drummond, N. Ryder, H. Wand et al., Is azithromycin
[116] B. Dodge, B. Van Der Pol, M. Reece et al., Rectal self-sampling adequate treatment for asymptomatic rectal chlamydia? Inter-
in non-clinical venues for detection of sexually transmissible national Journal of STD and AIDS, vol. 22, no. 8, pp. 478480,
infections among behaviourally bisexual men, Sexual Health, 2011.
vol. 9, no. 2, pp. 190191, 2012. [131] C. M. Khosropour, J. C. Dombrowski, L. A. Barbee, L. E.
Manhart, and M. R. Golden, Comparing azithromycin and
[117] A. H. Freeman, K. T. Bernstein, R. P. Kohn, S. Philip, L.
doxycycline for the treatment of rectal chlamydial infection: a
M. Rauch, and J. D. Klausner, Evaluation of self-collected
retrospective cohort study, Sexually Transmitted Diseases, vol.
versus clinician-collected swabs for the detection of Chlamydia
41, no. 2, pp. 7985, 2014.
trachomatis and Neisseria gonorrhoeae pharyngeal infection
among men who have sex with men, Sexually Transmitted [132] A. Elgalib, S. Alexander, C. Y. W. Tong, and J. A. White, Seven
Diseases, vol. 38, no. 11, pp. 10361039, 2011. days of doxycycline is an effective treatment for asymptomatic
rectal Chlamydia trachomatis infection, International Journal of
[118] F. Nyatsanza, A. Trivedy, and G. Brook, The effect of intro- STD and AIDS, vol. 22, no. 8, pp. 474477, 2011.
ducing routine self-taken extra-genital swabs in a genitourinary
[133] K. Manavi, F. Zafar, and H. Shahid, Oropharyngeal gonor-
medicine clinic cohort. A before and after study, International
rhoea: rate of co-infection with sexually transmitted infection,
Journal of STD & AIDS, 2015.
antibiotic susceptibility and treatment outcome, International
[119] E. Lanjouw, J. M. Ossewaarde, A. Stary, F. Boag, and W. I. van Journal of STD and AIDS, vol. 21, no. 2, pp. 138140, 2010.
der Meijden, 2010 European guideline for the management of [134] P. J. Horner, Azithromycin antimicrobial resistance and genital
Chlamydia trachomatis infections, International Journal of STD Chlamydia trachomatis infection: duration of therapy may be
& AIDS, vol. 21, no. 11, pp. 729737, 2010. the key to improving efficacy, Sexually Transmitted Infections,
[120] M. S. van Rooijen, M. F. S. van der Loeff, S. A. Morre, A. P. van vol. 88, no. 3, pp. 154156, 2012.
Dam, A. G. C. L. Speksnijder, and H. J. C. de Vries, Sponta- [135] D. J. Templeton, P. Read, R. Varma, and C. Bourne, Australian
neous pharyngeal Chlamydia trachomatis RNA clearance. A sexually transmissible infection and HIV testing guidelines for
cross-sectional study followed by a cohort study of untreated asymptomatic men who have sex with men 2014: a review of the
STI clinic patients in Amsterdam, the Netherlands, Sexually evidence, Sexual Health, vol. 11, no. 3, pp. 217229, 2014.
Transmitted Infections, vol. 91, no. 3, pp. 157164, 2015. [136] F. Y. S. Kong and J. S. Hocking, Treatment challenges for uro-
[121] S. K. Apewokin, W. M. Geisler, and L. H. Bachmann, Spon- genital and anorectal Chlamydia trachomatis, BMC Infectious
taneous resolution of extragenital chlamydial and gonococcal Diseases, vol. 15, no. 1, article 293, 2015.
infections prior to therapy, Sexually Transmitted Diseases, vol. [137] M. Y Chen, K. Stevens, R. Tideman et al., Failure of 500 mg
37, no. 5, pp. 343344, 2010. of ceftriaxone to eradicate pharyngeal gonorrhoea, Australia,
16 Infectious Diseases in Obstetrics and Gynecology

The Journal of Antimicrobial Chemotherapy, vol. 68, no. 6, pp. International Journal of STD & AIDS, vol. 16, no. 1, pp. 6870,
14451447, 2013. 2005.
[138] J. Tapsall, P. Read, C. Carmody et al., Two cases of failed [153] M. Bissessor, D. M. Whiley, C. K. Fairley et al., Persistence of
ceftriaxone treatment in pharyngeal gonorrhoea verified by Neisseria gonorrhoeae DNA following treatment for pharyngeal
molecular microbiological methods, Journal of Medical Micro- and rectal gonorrhea is influenced by antibiotic susceptibility
biology, vol. 58, no. 5, pp. 683687, 2009. and reinfection, Clinical Infectious Diseases, vol. 60, no. 4, pp.
[139] M. Ohnishi, T. Saika, S. Hoshina et al., Ceftriaxone-resistant 557563, 2015.
Neisseria gonorrhoeae, Japan, Emerging Infectious Diseases, vol. [154] L. Sathia, B. Ellis, S. Phillip, A. Winston, and A. Smith,
17, no. 1, pp. 148149, 2011. Pharyngeal gonorrhoeais dual therapy the way forward?
[140] M. Unemo, D. Golparian, M. Potocnik, and S. Jeverica, Treat- International Journal of STD and AIDS, vol. 18, no. 9, pp. 647
ment failure of pharyngeal gonorrhoea with internationally rec- 648, 2007.
ommended first-line ceftriaxone verified in Slovenia, Septem- [155] L. A. Barbee, R. P. Kerani, J. C. Dombrowski, O. O. Soge, and
ber 2011, Euro Surveillance: Bulletin Europeens sur les Maladies M. R. Golden, A retrospective comparative study of 2-drug
Transmissibles, vol. 17, no. 25, 2012. oral and intramuscular cephalosporin treatment regimens for
[141] M. Unemo, D. Golparian, and A. Hestner, Ceftriaxone treat- pharyngeal gonorrhea, Clinical Infectious Diseases, vol. 56, no.
ment failure of pharyngeal gonorrhoea verified by international 11, pp. 15391545, 2013.
recommendations, Sweden, July 2010, Eurosurveillance, vol. 16, [156] C. A. Renault, D. M. Israelski, V. Levy, B. K. Fujikawa, T. A.
no. 6, Article ID 19792, 2011. Kellogg, and J. D. Klausner, Time to clearance of Chlamydia
[142] Y. H. Grad, R. D. Kirkcaldy, D. Trees et al., Genomic epidemi- trachomatis ribosomal RNA in women treated for chlamydial
ology of Neisseria gonorrhoeae with reduced susceptibility to infection, Sexual Health, vol. 8, no. 1, pp. 6973, 2011.
cefixime in the USA: a retrospective observational study, The [157] Centers for Disease Control and Prevention, Recommenda-
Lancet Infectious Diseases, vol. 14, no. 3, pp. 220226, 2014. tions for the laboratory-based detection of Chlamydia tra-
[143] D. Golparian, A. Ohlsson, H. Janson et al., Four treatment chomatis and Neisseria gonorrhoeae2014, Morbidity and
failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or Mortality Weekly Report (MMWR), vol. 63, pp. 119, 2014.
cefotaxime (500 mg), Sweden, 2013 and 2014, Euro Surveillance: [158] M. R. Beymer, E. Llata, A. M. Stirland et al., Evaluation of
European communicable disease bulletin, vol. 19, no. 30, Article gonorrhea test of cure at 1 week in a Los Angeles community-
ID 20862, 2013. based clinic serving men who have sex with men, Sexually
[144] Centers for Disease Control and Prevention (CDC), Update to Transmitted Diseases, vol. 41, no. 10, pp. 595600, 2014.
CDCs sexually transmitted diseases treatment guidelines, 2010: [159] P. Pathela, S. L. Braunstein, S. Blank, and J. A. Schillinger,
oral cephalosporins no longer a recommended treatment for HIV incidence among men with and those without sexually
gonococcal infections, Morbidity and Mortality Weekly Report, transmitted rectal infections: estimates from matching against
vol. 61, no. 31, pp. 590594, 2012. an HIV case registry, Clinical Infectious Diseases, vol. 57, no. 8,
[145] P. J. Read, E. A. Limnios, A. McNulty, D. Whiley, and M. M. pp. 12031209, 2013.
Lahra, One confirmed and one suspected case of pharyngeal [160] K. T. Bernstein, J. L. Marcus, G. Nieri, S. S. Philip, and J.
gonorrhoea treatment failure following 500 mg ceftriaxone in D. Klausner, Rectal gonorrhea and chlamydia reinfection is
Sydney, Australia, Sexual Health, vol. 10, no. 5, pp. 460462, associated with increased risk of HIV seroconversion, Journal
2013. of Acquired Immune Deficiency Syndromes, vol. 53, no. 4, pp.
[146] J. Gratrix, J. Bergman, C. Egan, S. J. Drews, R. Read, and 537543, 2010.
A. E. Singh, Retrospective review of pharyngeal gonorrhea [161] K. J. P. Craib, D. R. Meddings, S. A. Strathdee et al., Rectal
treatment failures in Alberta, Canada, Sexually Transmitted gonorrhoea as an independent risk factor for HIV infection in
Diseases, vol. 40, no. 11, pp. 877879, 2013. a cohort of homosexual men, Genitourinary Medicine, vol. 71,
[147] A. Hustig, C. Bell, and R. Waddell, An audit of pharyngeal gon- no. 3, pp. 150154, 1995.
orrhoea treatment in a public sexual health clinic in Adelaide, [162] N. M. Zetola, K. T. Bernstein, E. Wong, B. Louie, and J. D. Klaus-
South Australia, International Journal of STD and AIDS, vol. 24, ner, Exploring the relationship between sexually transmitted
no. 5, pp. 399400, 2013. diseases and HIV acquisition by using different study designs,
[148] T. Matsumoto, T. Muratani, K. Takahashi et al., Multiple doses Journal of Acquired Immune Deficiency Syndromes, vol. 50, no.
of cefodizime are necessary for the treatment of Neisseria 5, pp. 546551, 2009.
gonorrhoeae pharyngeal infection, Journal of Infection and [163] A. P. Craig, F. Kong, L. Yeruva et al., Is it time to switch to
Chemotherapy, vol. 12, no. 3, pp. 145147, 2006. doxycycline from azithromycin for treating genital chlamydial
[149] J. S. Moran and W. C. Levine, Drugs of choice for the treatment infections in women? Modelling the impact of autoinoculation
of uncomplicated gonococcal infections, Clinical Infectious from the gastrointestinal tract to the genital tract, BMC
Diseases, vol. 20, supplement 1, pp. S47S65, 1995. Infectious Diseases, vol. 15, article 200, 2015.
[150] L. M. Newman, J. S. Moran, and K. A. Workowski, Update on [164] W. E. Lafferty, J. P. Hughes, and H. H. Handsfield, Sexually
the management of gonorrhea in adults in the United States, transmitted diseases in men who have sex with men: acquisition
Clinical Infectious Diseases, vol. 44, supplement 3, pp. S84S101, of gonorrhea and nongonococcal urethritis by fellatio and
2007. implications for STD/HIV prevention, Sexually Transmitted
[151] M. Y. Chen, K. Stevens, R. Tideman et al., Failure of 500 mg Diseases, vol. 24, no. 5, pp. 272278, 1997.
of ceftriaxone to eradicate pharyngeal gonorrhoea, Australia, [165] A. McMillan, H. Young, and A. Moyes, Rectal gonorrhoea in
The Journal of Antimicrobial Chemotherapy, vol. 68, no. 6, pp. homosexual men: source of infection, International Journal of
14451447, 2013. STD and AIDS, vol. 11, no. 5, pp. 284287, 2000.
[152] K. Manavi, H. Young, and A. McMillan, The outcome of [166] M. Bissessor, S. N. Tabrizi, C. K. Fairley et al., Differing
oropharyngeal gonorrhoea treatment with different regimens, Neisseria gonorrhoeae bacterial loads in the pharynx and
Infectious Diseases in Obstetrics and Gynecology 17

rectum in men who have sex with men: implications for


gonococcal detection, transmission, and control, Journal of
Clinical Microbiology, vol. 49, no. 12, pp. 43044306, 2011.
[167] G. A. F. S. Van Liere, J. A. M. C. Dirks, C. J. P. A. Hoebe, P. F.
Wolffs, and N. H. T. M. Dukers-Muijrers, Anorectal Chlamydia
trachomatis load is similar in men who have sex with men and
women reporting anal sex, PLoS ONE, vol. 10, no. 8, Article ID
e0134991, 2015.
[168] H. W. Chesson, K. T. Bernstein, T. L. Gift, J. L. Marcus, S. Pipkin,
and C. K. Kent, The cost-effectiveness of screening men who
have sex with men for rectal chlamydial and gonococcal infec-
tion to prevent HIV infection, Sexually Transmitted Diseases,
vol. 40, no. 5, pp. 366371, 2013.
[169] J. C. Dombrowski, Do women need screening for extragenital
gonococcal and chlamydial infections? Sexually Transmitted
Diseases, vol. 42, no. 5, pp. 240242, 2015.
[170] U. Marcus, J. Ort, M. Grenz, K. Eckstein, K. Wirtz, and A. Wille,
Risk factors for HIV and STI diagnosis in a community-based
HIV/STI testing and counselling site for men having sex with
men (MSM) in a large german city in 2011-2012, BMC Infectious
Diseases, vol. 15, article 14, 2015.
[171] E. R. Cachay, A. Sitapati, J. Caperna et al., Denial of risk
behavior does not exclude asymptomatic anorectal sexually
transmitted infection in HIV-infected men, PLoS ONE, vol. 4,
no. 12, Article ID e8504, 2009.
[172] J. L. Marcus, K. T. Bernstein, R. P. Kohn, S. Liska, and S. S. Philip,
Infections missed by urethral-only screening for chlamydia
or gonorrhea detection among men who have sex with men,
Sexually Transmitted Diseases, vol. 38, no. 10, pp. 922924, 2011.
[173] K. Wada, S. Uehara, R. Mitsuhata et al., Prevalence of pha-
ryngeal Chlamydia trachomatis and Neisseria gonorrhoeae
among heterosexual men in Japan, Journal of Infection and
Chemotherapy, vol. 18, no. 5, pp. 729733, 2012.
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