WHO GUIDELINES FOR THE

Treatment of
Chlamydia trachomatis
WHO Library Cataloguing-in-Publication Data
WHO guidelines for the treatment of Chlamydia trachomatis.
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framework -- Web annex E: Systematic reviews -- Web annex F: Summary
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1.Chlamydia trachomatis. 2.Chlamydia Infections - drug therapy.
3.Sexually Transmitted Diseases. 4.Guideline. I.World Health Organization.
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World Health Organization 2016
All rights reserved. Publications of the World Health Organization are
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS i

CONTENTS

Acknowledgements iii

Abbreviations and acronyms iv

Executive summary 1

Overview of the guidelines for the prevention, treatment and management of STIs 6
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Approach to the revision of STI guidelines 8
References 9

WHO guidelines for the treatment of Chlamydia trachomatis 10

1. Introduction 10
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Laboratory diagnosis 11
1.2 Rationale for new recommendations 11
1.3 Objectives 11
1.4 Target audience 11
1.5 Structure of the guidelines 11

2. Methods 12
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2.2 Questions and outcomes 12
2.3 Reviews of the evidence 12
2.4 Making recommendations 13
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3. Dissemination, updating and implementation of the guidelines 15

3.1 Dissemination 15
3.2 Updating the STI guidelines and user feedback 15
3.3 Implementation of the WHO guidelines for the treatment of C. trachomatis 15
Adaptation, implementation and monitoring 15
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4. Recommendations for treatment of chlamydial infections 17

4.1 Uncomplicated genital chlamydia 17
Recommendation 1 17
4.2 Anorectal chlamydial infection 18
Recommendation 2 18
4.3 Chlamydial infection in pregnant women 19
Recommendation 3a 19
Recommendation 3b 19
Recommendation 3c 19
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ii WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

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Recommendation 7 21

References 22

Annex A: STI guideline development teams 23

Annex B: Detailed methods for guideline development 32

Questions and outcomes 32
Review of the evidence 35
Applying the GRADE approach to making the recommendations 38

Annex C: Lists of references for reviewed evidence 39

Recommendation 1 39
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Recommendation 3a, 3b, 3c 41
Recommendation 4 42
Recommendation 5 43
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Web annexes available at:

www.who.int/reproductivehealth/publications/rtis/chlamydia-treatment-guidelines/en/

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Web annex E: Systematic reviews for chlamydia guidelines
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS iii

ACKNOWLEDGEMENTS

The Department of Reproductive Health and Research Members: <DZ6D[$GX6DUNRGLH$QGUHZ$PDWR
DWWKH:RUOG+HDOWK2UJDQL]DWLRQ:+2ZRXOGOLNHWR
thank the members of the STI Guideline Development
Group for their consistent availability and commitment
to making these guidelines possible. The Department
is also grateful to the STI External Review Group for
peer reviewing these guidelines, and appreciates
the contribution of the WHO Steering Committee.
The names of the members of each group are listed
below, with full details provided in Annex A.
Special thanks to Dr Nancy Santesso, the guideline
methodologist who also led the systematic review
SURFHVVIRUKHUKDUGZRUNDQGUPFRPPLWPHQWRI
the guideline development process. We also thank
the members of the Systematic Review Team from
McMaster University.
We appreciate the overall support of the WHO
Guideline Review Committee Secretariat during the
guideline development process, with grateful thanks
to Dr Susan Norris.
We thank Theresa Ryle for the administrative
VXSSRUWDQG&RPPXQLFDWLRQVIRUDVVLVWDQFH
with the guideline design and layout. This guideline
document was edited by Ms Jane Patten, of Green Ink,
United Kingdom.
Dr Teodora Wi led the guideline development process
and Dr Nathalie Broutet co-led the process under
the supervision of Dr James Kiarie and leadership of
Dr Ian Askew. Lee Sharkey provided support during
the guideline development process.
FUNDING
The preparation and printing of the guidelines were
funded exclusively by the UNDP/UNFPA/UNICEF/
WHO/World Bank Special Programme of Research,
Gail Bolan, John Changalucha, Xiang-Sheng Chen,
Harrel Chesson, Craig Cohen, Francisco Garcia,
Suzanne Garland, Sarah Hawkes, Mary Higgins,
.LQJ+ROPHV-HUH\.ODXVQHU'DYLG/HZLV1LFROD/RZ
David Mabey, Angelica Espinosa Miranda, Nelly Mugo,
Saiqa Mullick, Francis Ndowa, Joel Palefsky,
.HLWK5DGFOLH8OXJEHN6DELURY-XGLWK6WHSKHQVRQ
Richard Steen, Magnus Unemo, Bea Vuylsteke,
Anna Wald, Thomas Wong and Kimberly A. Workowski
STI GDG working group for chlamydia:
Andrew Amato, Harrell Chesson, Craig Cohen,
Patricia Garcia, Nicola Low, David Mabey, Angelica
0LUDQGD)UDQFLV1GRZD.HLWK5DGFOLH-XGLWK
Stephenson, Magnus Unemo, Bea Vuylsteke and
Judith Wasserheit
STI External Review Group: Laith Abu-Raddad,
Adele Benaken-Schwartz, Mircea Betiu, Anupong
Chitwarakorn, Anjana Das, Carolyn Deal,
Margaret Gale-Rowe, William M. Geisler, Amina
El Kettani, Mizan Kiros, Ahmed Latif, Philippe
Mayaud, David McCartney, Ali M. Mir, Nuriye Ortayli,
Khantanouvieng Sayabounthavong and
Aman Kumar Singh
WHO Steering Committee:
:+2UHJLRQDORFHVMassimo Ghidinelli, Hamida
Khattabi, Lali Khotenashvili, Ornella Lincetto Ying-Ru Lo,
Frank Lule and Razia Pendse
WHO headquarters: Moazzam Ali, Avni Amin, Rachel
Baggaley, Venkatraman Chandra-Mouli, Jane Ferguson,
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Sami Gottlieb, Silvio Paolo Mariotti, Frances McConville,
Lori Newman, Annette Mwansa Nkowane, Anita Sands,
Igor Toskin and Marco Vitoria
WHO STI Secretariat: Ian Askew, Teodora Elvira Wi
Development and Research Training in Human OHDGGHYHORSPHQWRIWKHJXLGHOLQHV1DWKDOLH%URXWHW
5HSURGXFWLRQ+531RH[WHUQDOVRXUFHRIIXQGLQJ FROHDGGHYHORSPHQWRIWKHJXLGHOLQHV-DPHV.LDULH
was solicited or utilized. and Lee Sharkey
Systematic Review Team: 1DQF\6DQWHVVROHDG
CONTRIBUTORS TO WHO GUIDELINES FOR THE Housne Begum, Janna-Lina Kerth, Gian Paolo Morgano,
TREATMENT OF CHLAMYDIA TRACHOMATIS Kristie Poole, Nicole Schwab, Matthew Ventresca,
<XDQ=KDQJDQG$QGUHZ=LNLFPHPEHUV
STI Guideline Development Group (GDG):
Methodologist: Nancy Santesso.
Chairpersons: Judith Wasserheit, Holger Schnemann
and Patricia Garcia
iv WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

ABBREVIATIONS AND ACRONYMS

AIDS DFTXLUHGLPPXQHGHFLHQF\V\QGURPH

AMR antimicrobial resistance

DALY disability-adjusted life year

DFA GLUHFWXRUHVFHQWDQWLERG\

DOI declaration of interests

ELISA enzyme-linked immunosorbent assays

GDG Guideline Development Group

GRADE Grading of Recommendations Assessment, Development and Evaluation

GUD genital ulcer disease

HIV KXPDQLPPXQRGHFLHQF\YLUXV

HPV human papillomavirus

HRP UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research,

Development and Research Training in Human Reproduction

+69 herpes simplex virus type 2

LGV lymphogranuloma venereum

MSH Management Sciences for Health

MSM men who have sex with men

NAATs QXFOHLFDFLGDPSOLFDWLRQWHVWV1$$7V

PICO population, intervention, comparator, outcome

POCT point-of-care test

STI sexually transmitted infection

UNAIDS Joint United Nations Programme on HIV/AIDS

UNFPA United Nations Population Fund

UNICEF 8QLWHG1DWLRQV&KLOGUHQV)XQG

WHO World Health Organization

 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 1

WHO GUIDELINES FOR

THE TREATMENT OF
CHLAMYDIA TRACHOMATIS

EXECUTIVE SUMMARY

Sexually transmitted infections (STIs) are a

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and mortality. STIs have a direct impact on
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also have an impact on national and individual
economies. More than a million STIs are acquired
every day. In 2012, an estimated 357 million new
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V\SKLOLVDQGWULFKRPRQLDVLVRFFXUUHGDPRQJ
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cases of chlamydial infection.
2 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
Chlamydial infection, caused by Chlamydia trachomatis,
is the most common bacterial STI and results in
substantial morbidity and economic cost worldwide.
Occurring most commonly among young sexually active
adults, C. trachomatis causes cervicitis in women and
urethritis in men, as well as extra-genital infections,
including rectal and oropharyngeal infections.
Asymptomatic infections are common in both men
and women. Untreated chlamydial infection may
cause severe complications in the upper reproductive
tract, primarily in young women, including ectopic
pregnancy, salpingitis and infertility. Lymphogranuloma
OBJECTIVES
The objectives of these guidelines are:
to provide evidence-based guidance on treatment
of infection with C. trachomatisDQG
to support countries to update their national
guidelines for treatment of chlamydial infection.
METHODS
These guidelines were developed following the
PHWKRGVRXWOLQHGLQWKH:+2KDQGERRNIRU
YHQHUHXP/*9FDXVHGE\DPRUHLQYDVLYHVHURYDU guideline development. The Guideline Development
of C. trachomatis, is increasingly prevalent among *URXS*'*LQFOXGHGLQWHUQDWLRQDO67,H[SHUWV
PHQZKRKDYHVH[ZLWKPHQ060LQVRPHVHWWLQJV
Maternal infection is associated with serious adverse
outcomes in neonates, such as preterm birth, low birth
weight, conjunctivitis, nasopharyngeal infection and
pneumonia. C. trachomatis can be diagnosed by culture,
clinicians, researchers and programme managers.
The GDG prioritized questions and outcomes related
to treatment of chlamydial infections to include
in this update, and a methodologist and a team of
systematic reviewers from McMaster University, the
GLUHFWLPPXQRXRUHVFHQFHDVVD\V')$VDQGHQ]\PH WHO Collaborating Centre for Evidence-Informed
OLQNHGLPPXQRVRUEHQWDVVD\V(/,6$VEXWQXFOHLFDFLG Policy, independently conducted systematic reviews
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superior performance characteristics. chlamydial infections. The evidence was assessed
using the Grading of Recommendations Assessment,
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RATIONALE FOR THE GUIDELINES
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Since the publication of the World Health Organization managed according to WHO guidelines and declared
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epidemiology of STIs and advancements in prevention,
diagnosis and treatment necessitate changes in
STI management. These guidelines provide updated
treatment recommendations for common infections
caused by C. trachomatis based on the most recent
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JXLGHOLQHVIRUVSHFLF67,V2WKHUPRGXOHVZLOOIRFXV
before the recommendations were discussed and
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by the GDG.
RECOMMENDATIONS
The current guidelines provide nine treatment
recommendations for genital infections and LGV
caused by C. trachomatis. The recommendations
on treatments for Neisseria gonorrhoeaeJRQRUUKRHD summarized in Table 1 apply to adults, adolescents
KHUSHVVLPSOH[YLUXVW\SH+69JHQLWDOKHUSHV \HDUVRIDJHSHRSOHOLYLQJZLWK+,9DQG
and Treponema pallidum V\SKLOLV,QDGGLWLRQIXWXUH key populations, including sex workers, MSM and
work will provide guidance for syphilis screening and WUDQVJHQGHUSHUVRQV6SHFLFUHFRPPHQGDWLRQVKDYH
treatment of pregnant women, STI syndromic approach, also been developed for genital chlamydial infection in
clinical management, STI prevention, and treatments of pregnant women and for prophylaxis and treatment
other STIs. It is strongly recommended that countries of ophthalmia neonatorum caused by C. trachomatis.
take updated global guidance into account as they
establish standardized national protocols, adapting
this guidance to the local epidemiological situation
and antimicrobial susceptibility data.
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 3

Table 1. Summary of recommendations for treatment of chlamydial infections

Recommendations Strength of
recommendation and
quality of evidence
Uncomplicated genital chlamydia
Recommendation 1 Conditional
recommendation,
The WHO STI guideline suggests treatment with one of the following options:
moderate quality
azithromycin 1 g orally as a single dose evidence
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or one of these alternatives:
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HU\WKURP\FLQPJRUDOO\ four times a day for 7 days
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Remarks::KLOHJRRGSUDFWLFHEDVHGRQHYLGHQFHRIODUJHQHWEHQHWGLFWDWHVWKDW
patients should be treated for chlamydial infection, the choice of treatment may
depend on the convenience of dosage, the cost and quality of the medicines in
GLHUHQWVHWWLQJVDQGHTXLW\FRQVLGHUDWLRQV:KHQKLJKYDOXHLVSODFHGRQUHGXFLQJ
FRVWVGR[\F\FOLQHLQDVWDQGDUGGRVHPD\EHWKHEHVWFKRLFHZKHQKLJKYDOXH
is placed on convenience, azithromycin in a single dose may be the best choice.
A delayed-release doxycycline formulation may be an alternative to twice daily
dosing of doxycycline, but the high cost of the delayed-release formulation may
SURKLELWLWVXVH1RWHWKDWGR[\F\FOLQHWHWUDF\FOLQHDQGRR[DFLQDUHFRQWUDLQGLFDWHG
LQSUHJQDQWZRPHQVHHUHFRPPHQGDWLRQVbDF
Anorectal chlamydial infection
Recommendation 2 Conditional
recommendation,
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low quality evidence
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Remarks: This recommendation applies to people with known anorectal infection
and to people with suspected anorectal infections with genital co-infection.
Clinicians should ask men, women and key populations (e.g. men who have sex
ZLWKPHQWUDQVJHQGHUSHUVRQVDQGIHPDOHVH[ZRUNHUVDERXWDQDOVH[DQG
treat accordingly. Doxycycline should not be used in pregnant women because
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4 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

Genital chlamydial infection in pregnant women

Recommendation 3a Strong recommendation,
The WHO STI guideline recommends treatment with azithromycin over erythromycin. moderate quality
evidence
Recommendation 3b
The WHO STI guideline suggests treatment with azithromycin over amoxicillin. Conditional
recommendation,
low quality evidence
Recommendation 3c
The WHO STI guideline suggests treatment with amoxicillin over erythromycin. Conditional
recommendation,
Dosages:
low quality evidence
azithromycin 1 g orally as a single dose
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HU\WKURP\FLQPJRUDOO\ four times a day for 7 days.
Remarks: $]LWKURP\FLQLVWKHUVWFKRLFHRIWUHDWPHQWEXWPD\QRWEHDYDLODEOH
in some settings. Azithromycin is less expensive than erythromycin and since
it is provided as a single dose, may result in better adherence and therefore
better outcomes.
Lymphogranuloma venereum (LGV)
Recommendation 4 Conditional
recommendation, very
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low quality evidence
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Remarks: *RRGSUDFWLFHGLFWDWHVHHFWLYHWUHDWPHQWRI/*9LQSDUWLFXODUIRUPHQZKR
have sex with men and for people living with HIV. When doxycycline is contraindicated,
azithromycin should be provided. When neither treatment is available, erythromycin
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XVHGLQSUHJQDQWZRPHQEHFDXVHRIDGYHUVHHHFWVVHHUHFRPPHQGDWLRQVbDF
Ophthalmia neonatorum
Recommendation 5 Strong recommendation,
very low quality evidence
In neonates with chlamydial conjunctivitis, the WHO STI guideline recommends
WUHDWPHQWZLWKD]LWKURP\FLQbPJNJGD\RUDOO\RQHGRVHGDLO\IRUGD\VRYHU
HU\WKURP\FLQbPJNJGD\RUDOO\LQIRXUGLYLGHGGRVHVGDLO\IRUGD\V
Remarks: This is a strong recommendation given the potential for the risk of
pyloric stenosis with the use of erythromycin in neonates. In some settings,
azithromycin suspension is not available and therefore erythromycin may be used.
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 5

Recommendation 6 Strong recommendation,

low quality evidence
For all neonates, the WHO STI guideline recommends topical ocular prophylaxis
for the prevention of gonococcal and chlamydial ophthalmia neonatorum.

Recommendation 7 Conditional
recommendation, low
For ocular prophylaxis, the WHO STI guideline suggests one of the following options
quality evidence
for topical application to both eyes immediately after birth:
tetracycline hydrochloride 1% eye ointment
HU\WKURP\FLQH\HRLQWPHQW
povidone iodine 2.5% solution
silver nitrate 1% solution
chloramphenicol 1% eye ointment.
Remarks: 5HFRPPHQGDWLRQVDQGDSSO\WRWKHSUHYHQWLRQRIERWKFKODP\GLDODQG
gonococcal ophthalmia neonatorum. Cost and local resistance to erythromycin,
tetracycline and chloramphenicol in gonococcal infection may determine the choice
of medication. Caution should be taken to avoid touching eye tissue when applying
the topical treatment and to provide a water-based solution of povidone iodine.
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6 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

OVERVIEW OF THE GUIDELINES FOR THE PREVENTION,

TREATMENT AND MANAGEMENT OF STIs

STI EPIDEMIOLOGY AND BURDEN

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SXEOLFKHDOWKSUREOHPZRUOGZLGHDHFWLQJTXDOLW\
of life and causing serious morbidity and mortality.
STIs have a direct impact on reproductive and child
health through infertility, cancers and pregnancy
Both ulcerative and non-ulcerative STIs are associated
with a several-fold increased risk of transmitting or
acquiring HIV (7, 8). Infections causing genital ulcers
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in addition to curable ulcer-causing STIs (e.g. syphilis
complications, and they have an indirect impact through DQGFKDQFURLGKLJKO\SUHYDOHQW+69LQIHFWLRQV
their role in facilitating sexual transmission of human substantially increase that risk (9). Non-ulcerative
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an impact on national and individual economies. The
prevention and control of STIs is an integral component
of comprehensive sexual and reproductive health
services that are needed to attain the related targets
STIs, such as gonorrhoea, chlamydia and trichomoniasis,
have been shown to increase HIV transmission through
genital shedding of HIV (10). Treating STIs with the
right medicines at the right time is necessary to reduce
HIV transmission and improve sexual and reproductive
XQGHU6XVWDLQDEOH'HYHORSPHQW*RDO6'*1R health (11)(RUWVVKRXOGWKHUHIRUHEHWDNHQWR
(Ensure healthy lives and promote well-being for all at all strengthen STI diagnosis and treatment.
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WHY NEW GUIDELINES FOR THE PREVENTION,
to end the epidemics of AIDS and other communicable
GLVHDVHVWDUJHWWRUHGXFHSUHPDWXUHPRUWDOLW\ TREATMENT AND MANAGEMENT OF STIs?
from noncommunicable diseases and promote mental Since the publication of the World Health Organization
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and target 3.8 to achieve universal health coverage.
Worldwide, more than a million curable STIs are
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357 million new cases of curable STIs among adults aged
1549 years worldwide: 131 million cases of chlamydia,
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syphilis and 142 million cases of trichomoniasis (1).
The prevalence of some viral STIs is similarly high, with
an estimated 417 million people infected with herpes
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epidemiology of STIs and advancements in prevention,
diagnosis and treatment necessitate changes in STI
management. Indeed, 88% of countries have updated
their national STI guidelines or recommendations since
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recent evidence and expert opinion is therefore needed
to assist countries to incorporate new developments
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and treatment of STIs.
VLPSOH[YLUXVW\SH+69(2), and approximately There is an urgent need to update global treatment
291 million women harbouring human papillomavirus UHFRPPHQGDWLRQVWRHHFWLYHO\UHVSRQGWRWKH
+39DWDQ\SRLQWLQWLPH(3). The burden of STIs
varies by region and gender, and is greatest in
resource-poor countries.
When left undiagnosed and untreated, curable STIs
can result in serious complications and sequelae,
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ectopic pregnancy, miscarriage, fetal loss and
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of STIs, especially for Neisseria gonorrhoeae.
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global and local resistance patterns are essential to
reduce the risk of further development of AMR.
High-level gonococcal resistance to quinolones,
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is widespread and decreased susceptibility to the
PDWHUQDOV\SKLOLVLQIHFWLRQVUHVXOWHGLQDGYHUVH H[WHQGHGVSHFWUXPWKLUGJHQHUDWLRQFHSKDORVSRULQV
pregnancy outcomes, including stillbirths, neonatal DQRWKHUUVWOLQHWUHDWPHQWIRUJRQRUUKRHDLVRQ
deaths, preterm births and infected infants (4). the rise (13). Low-level resistance to Trichomonas
Curable STIs accounted for the loss of nearly 11 million vaginalis has also been reported for nitroimidazoles,
GLVDELOLW\DGMXVWHGOLIH\HDUV'$/<VLQ(5).
The psychological consequences of STIs include
stigma, shame and loss of self-worth. STIs have also
been associated with relationship disruption and
gender-based violence (6).
the only available treatment. Resistance to azithromycin
has been reported in some strains of Treponema
pallidum and treatment failures have been reported
for tetracyclines and macrolides in the treatment of
Chlamydia trachomatis (14, 15).
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 7

A WHO STI expert consultation recommended
XSGDWLQJWKH:+2JXLGHOLQHVIRUWKHUVWDQG
second-line treatments for C. trachomatis, increasing
WKHGRVDJHRIFHIWULD[RQHWRPJIRUWUHDWPHQW
of N. gonorrhoeae with continued monitoring of
antimicrobial susceptibility, and consideration of
1HZUDSLGSRLQWRIFDUHGLDJQRVWLFWHVWV32&7VDUH
changing STI management. Rapid syphilis diagnostic
tests are now widely available, making syphilis screening
more widely accessible and allowing for earlier initiation
RIWUHDWPHQWIRUWKRVHZKRWHVWSRVLWLYH(RUWVDUH
under way to develop POCTs for other STIs that will
ZKHWKHUD]LWKURP\FLQJVLQJOHGRVHVKRXOGEH
recommended in early syphilis (16).
The epidemiology of STIs is changing, with viral
pathogens becoming more prevalent than bacterial
HWLRORJLHVIRUVRPHFRQGLWLRQVWKLVPHDQVWKDWXSGDWHG
information is required to inform locally appropriate
prevention and treatment strategies. An increasing
proportion of genital ulcers are now due to viral
infections as previously common bacterial infections,
such as chancroid, approach elimination in many
countries (16, 17). As recommended during the STI
expert consultation, treatment guidelines for genital
augment syndromic management of symptomatic
cases and increase the ability to identify asymptomatic
infections (12). Updated guidelines are needed that
incorporate rapid tests into syndromic management
of STIs and provide algorithms for testing and
screening (16).
Although recent technological advances in diagnostics,
WKHUDSHXWLFVYDFFLQHVDQGEDUULHUPHWKRGVRHUEHWWHU
opportunities for the prevention and care of STIs, access
to these technologies is still limited, particularly in areas
where the burden of infection is highest. For optimal
HHFWLYHQHVVJOREDOJXLGHOLQHVIRUWKHPDQDJHPHQW
XOFHUGLVHDVH*8'VKRXOGEHXSGDWHGWRLQFOXGH+69 of STIs need to include approaches for settings with
treatment and a longer treatment duration for HSV-2 limited access to modern technologies, as well as for
should be explored. In addition, suppressive therapy settings in which these technologies are available.
for HSV-2 should be considered in areas with high HIV
It is strongly recommended that countries take
prevalence (16). The chronic, lifelong nature of viral
updated global guidance into account as they establish
infections also requires that renewed attention be paid
standardized national protocols, adapting this guidance
WRGHYHORSLQJHHFWLYHSUHYHQWLRQVWUDWHJLHVLQFOXGLQJ
to the local epidemiological situation and antimicrobial
expanding accessibility to available vaccines for HPV
susceptibility data. Standardization ensures that all
and development of new vaccines for HSV-2.
patients receive adequate treatment at every level
,QWKH:+2JXLGHOLQHVDV\QGURPLFDSSURDFK of health-care services, optimizes the training and
was recommended for the management of STIs. supervision of health-care providers and facilitates
The approach guides the diagnosis of STIs based on procurement of medicines. It is recommended that
LGHQWLFDWLRQRIFRQVLVWHQWJURXSVRIV\PSWRPVDQG QDWLRQDOJXLGHOLQHVIRUWKHHHFWLYHPDQDJHPHQWRI
easily recognized signs and indicates treatment for STIs be developed in close consultation with local STI,
the majority of organisms that may be responsible public health and laboratory experts.
for producing the syndrome. The syndromic
management algorithms need to be updated in
response to the changing situation. In addition to
changes to the GUD algorithm, other syndromes
need to be re-evaluated, particularly vaginal discharge.
The approach to syndromes for key populations
also needs to be updated. For example, addition of
a syndromic management algorithm for anorectal
LQIHFWLRQVLQPHQZKRKDYHVH[ZLWKPHQ060DQG
sex workers is urgently needed since a substantial
number of these infections go unrecognized and
untreated in the absence of guidelines (16).
8 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

APPROACH TO THE REVISION OF

STI GUIDELINES
7RHQVXUHHHFWLYHWUHDWPHQWIRUDOO67,V:+2SODQV
a phased approach to updating the STI guidelines to
address a range of infections and issues. Four phases
have been proposed by the WHO STI Secretariat and
agreed upon by the STI Guideline Development Group
*'*PHPEHUVVHH$QQH[$IRUPHPEHUVRIWKHVH
JURXSV7DEOHVXPPDUL]HVWKHSURSRVHGSKDVHV
and timeline.

Table 2: Phases for development of the STI guidelines

Phases Topics Timeframe

Phase 1 7UHDWPHQWRIVSHFLF67,VChlamydia trachomatis 1RYHPEHU$SULO
FKODP\GLDNeisseria gonorrhoeaeJRQRUUKRHD+69 
JHQLWDOKHUSHVDQGTreponema pallidum V\SKLOLV
Syphilis screening and treatment of pregnant women

STI syndromic approach

0D\'HFHPEHU
Clinical management package 
Phase 2 STI prevention: condoms, behaviour change 
communication, biomedical interventions and vaccines
Phase 3 7UHDWPHQWRIVSHFLF67,VDQGUHSURGXFWLYHWUDFW 
LQIHFWLRQV57,VQRWDGGUHVVHGLQ3KDVH7ULFKRPRQDV
YDJLQDOLVWULFKRPRQLDVLVEDFWHULDOYDJLQRVLV&DQGLGD
DOELFDQVFDQGLGLDVLV+HPRSKLOXVGXFUH\LFKDQFURLG
.OHEVLHOODJUDQXORPDWLVGRQRYDQRVLVKXPDQ
SDSLOORPDYLUXV+39JHQLWDOZDUWVFHUYLFDOFDQFHU
6DUFRSWHVVFDELHLVFDELHVDQG3KWKLUXVSXELVSXELFOLFH
Phase 4 STI laboratory diagnosis and screening 

Phase 1 will focus on treatment recommendations
IRUVSHFLF67,VDVZHOODVRWKHULPSRUWDQWDQGXUJHQW
STI issues. Recommendations for the treatment of
VSHFLFLQIHFWLRQVZLOOEHGHYHORSHGDQGSXEOLVKHG
as independent modules:
In addition, guidelines for the STI syndromic approach
and a clinical management package will be developed
later in Phase 1. Phase 2 will focus on guidelines for STI
prevention. The independent Phase 1 and 2 modules
will later be consolidated into one document and
published as comprehensive WHO guidelines on STI
Chlamydia trachomatisFKODP\GLD
case management. Phase 3 will address treatment of
Neisseria gonorrhoeaeJRQRUUKRHD additional infections, including Trichomonas vaginalis
+69JHQLWDOKHUSHV WULFKRPRQLDVLVEDFWHULDOYDJLQRVLV&DQGLGDDOELFDQV
Treponema pallidum V\SKLOLV FDQGLGLDVLV+HPRSKLOXVGXFUH\LFKDQFURLG.OHEVLHOOD
JUDQXORPDWLVGRQRYDQRVLV+39JHQLWDOZDUWVFHUYLFDO
Syphilis screening and treatment of pregnant women.
FDQFHU6DUFRSWHVVFDELHLVFDELHVDQG3KWKLUXVSXELV
SXELFOLFH3KDVHZLOOSURYLGHJXLGDQFHRQODERUDWRU\
diagnosis and screening of STIs.
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 9

REFERENCES

1. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N et al. Global estimates of the
SUHYDOHQFHDQGLQFLGHQFHRIIRXUFXUDEOHVH[XDOO\WUDQVPLWWHGLQIHFWLRQVLQEDVHGRQV\VWHPDWLF
UHYLHZDQGJOREDOUHSRUWLQJ3/R62QHHGRLMRXUQDOSRQH

2. Looker KJ, Magaret AS, Turner KME, Vickerman P, Gottlieb SL, Newman LM. Global estimates of
SUHYDOHQWDQGLQFLGHQWKHUSHVVLPSOH[YLUXVW\SHLQIHFWLRQVLQ3/R62QHH
GRLMRXUQDOSRQH

 'H6DQMRV6'LD]0&DVWHOOVDJX;&OLRUG*%UXQL/0XR]1%RVFK);:RUOGZLGHSUHYDOHQFH
and genotype distribution of cervical human papillomavirus DNA in women with normal cytology:
DPHWDDQDO\VLV/DQFHW,QIHFW'LV

4. Wijesooriya NS, Rochat RW, Kamb ML, Turlapati P, Broutet N, Newman L. Declines in maternal and
FRQJHQLWDOV\SKLOLVIURPWRSURJUHVVWRZDUGVHOLPLQDWLRQRIPRWKHUWRFKLOGWUDQVPLVVLRQ
RIV\SKLOLV/DQFHW*OREDO+HDOWKLQSUHVV

5. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C et al. Disability-adjusted life
\HDUV'$/<VIRUGLVHDVHVDQGLQMXULHVLQUHJLRQVDV\VWHPDWLFDQDO\VLVIRU
WKH*OREDO%XUGHQRI'LVHDVH6WXG\/DQFHWGRL6


 *RWWOLHE6//RZ11HZPDQ/0%RODQ*.DPE0%URXWHW17RZDUGJOREDOSUHYHQWLRQRIVH[XDOO\
WUDQVPLWWHGLQIHFWLRQV67,VWKHQHHGIRU67,YDFFLQHV9DFFLQHGRLM
YDFFLQH

 :
 DVVHUKHLW-1(SLGHPLRORJLFDOV\QHUJ\LQWHUUHODWLRQVKLSVEHWZHHQKXPDQLPPXQRGHFLHQF\YLUXV
LQIHFWLRQVDQGRWKHUVH[XDOO\WUDQVPLWWHGGLVHDVHV6H[7UDQVP'LV

8. Sexton J, Garnett G, Rttingen J-A. Metaanalysis and metaregression in interpreting study variability
in the impact of sexually transmitted diseases on susceptibility to HIV infection. Sex Transm Dis.


9. \Glynn JR, Biraro S, Weiss HA. Herpes simplex virus type 2: a key role in HIV incidence. AIDS.
GRL4$'EHHH

 - RKQVRQ/)/HZLV'$7KHHHFWRIJHQLWDOWUDFWLQIHFWLRQVRQ+,9VKHGGLQJLQWKHJHQLWDO
WUDFWDV\VWHPDWLFUHYLHZDQGPHWDDQDO\VLV6H[7UDQVP'LVGRL
2/4EHG

11. Cohen MS. Classical sexually transmitted diseases drive the spread of HIV-1: back to the future.
-,QIHFW'LVGRLLQIGLVMLV

12. Progress report of the implementation of the global strategy for prevention and control of sexually
WUDQVPLWWHGLQIHFWLRQV*HQHYD:RUOG+HDOWK2UJDQL]DWLRQKWWSDSSVZKRLQW
LULVELWVWUHDPBHQJSGIDFFHVVHG0D\

13. Ndowa FJ, Ison CA, Lusti-Narasimhan M. Gonococcal antimicrobial resistance: the implications for
SXEOLFKHDOWKFRQWURO6H[7UDQVP,QIHFW6XSSOLYGRLVH[WUDQV

14. Gottlieb SL, Low N, Newman LM, Bolan G, Kamb M, Broutet N. Toward global prevention of sexually
WUDQVPLWWHGLQIHFWLRQV67,VWKHQHHGIRU67,YDFFLQHV9DFFLQHGRLM
YDFFLQH

 0
 DEH\'(SLGHPLRORJ\RIVH[XDOO\WUDQVPLWWHGLQIHFWLRQVZRUOGZLGH0HGLFLQH
GRLMPSPHG

 5
 HSRUWRIWKHH[SHUWFRQVXOWDWLRQDQGUHYLHZRIWKHODWHVWHYLGHQFHWRXSGDWHJXLGHOLQHVIRUWKH
PDQDJHPHQWRIVH[XDOO\WUDQVPLWWHGLQIHFWLRQV*HQHYD:RUOG+HDOWK2UJDQL]DWLRQ:+2
5+5KWWSDSSVZKRLQWLULVELWVWUHDP:+2B5+5BBHQJSGI
DFFHVVHG0D\

 6WHHQ5(UDGLFDWLQJFKDQFURLG%XOO:RUOG+HDOWK2UJDQ

10 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

 CLINICAL PRESENTATION
Genital infections due to C. trachomatis are
DV\PSWRPDWLFLQDSSUR[LPDWHO\RIZRPHQDQG
RIPHQ (2). Symptoms of uncomplicated chlamydial
infection in women include abnormal vaginal discharge,
dysuria, and post-coital and intermenstrual bleeding.
Common clinical signs on speculum examination
include cervical friability and discharge. Symptomatic
INTRODUCTION men usually present with urethral discharge and
dysuria, sometimes accompanied by testicular pain.
If left untreated, most genital infections will resolve
spontaneously with no sequelae but they may result in
severe complications, mainly in young women. Infection
can ascend to the upper reproductive tract and can
FDXVHSHOYLFLQDPPDWRU\GLVHDVHHFWRSLFSUHJQDQF\
salpingitis and tubal factor infertility in women (3) and
epididymitis in men (4). The risk of complications may
increase with repeated infection.
Infections at non-genital sites are common. Rectal
infection may manifest as a rectal discharge, rectal
pain or blood in the stools, but is asymptomatic in
most cases. Oropharyngeal infections can manifest as
pharyngitis and mild sore throat, but symptoms are rare.
Chlamydial infection in pregnancy is associated with
1.1 EPIDEMIOLOGY, BURDEN AND CLINICAL preterm birth and low birth weight. Infants of mothers
CONSIDERATIONS with chlamydia can be infected at delivery, resulting in
Chlamydial infection, caused by Chlamydia trachomatis, neonatal conjunctivitis and/or nasopharyngeal infection
is the most common bacterial sexually transmitted (3). Symptoms of ophthalmia include ocular discharge
LQIHFWLRQ67,DQGUHVXOWVLQVXEVWDQWLDOPRUELGLW\ and swollen eyelids. In newborns, nasopharyngeal
and economic cost worldwide. The World Health infection can lead to pneumonitis.
2UJDQL]DWLRQ:+2HVWLPDWHVWKDWLQ
million new cases of chlamydia occurred among adults
and adolescents aged 1549 years worldwide, with a
JOREDOLQFLGHQFHUDWHRISHUIHPDOHVDQG
SHUPDOHV7KHHVWLPDWHGPLOOLRQSUHYDOHQW
cases of chlamydia result in an overall prevalence of
4.2% for females and 2.7% for males, with the highest
prevalence in the WHO Region of the Americas and the
:+2:HVWHUQ3DFLF5HJLRQ(1). In many countries, the
incidence of chlamydia is highest among adolescent
girls aged 1519 years, followed by young women aged
\HDUV7KHWKUHHELRYDUVRIC. trachomatis, each
consisting of several serovars or genotypes, cause
genital infections, lymphogranuloma venereum (LGV:
DJHQLWDOXOFHUGLVHDVH>*8'@WKDWDHFWVO\PSKRLG
LGV, caused by a more invasive serovar of
C. trachomatisDHFWVWKHVXEPXFRVDOFRQQHFWLYH
tissue and can spread to regional lymph nodes.
It commonly presents as a unilateral, tender
inguinal or femoral lymph node and a genital ulcer
or papule (5). Anorectal exposure may result in
proctitis, rectal discharge, pain, constipation or
tenesmus. Left untreated, LGV can lead to rectal
VWXODRUVWULFWXUH
WLVVXHDQGWUDFKRPDH\HLQIHFWLRQ
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 11

LABORATORY DIAGNOSIS 1.4 TARGET AUDIENCE

There have been major developments in the These guidelines are primarily intended for health-care
diagnosis of C. trachomatisLQWKHODVW\HDUV SURYLGHUVDWDOOOHYHOVSULPDU\VHFRQGDU\DQGWHUWLDU\
Although C. trachomatis can be diagnosed by of the health-care system involved in the treatment
FXOWXUHGLUHFWLPPXQRXRUHVFHQFHDVVD\V')$V and management of people with STIs in low-, middle-
and laboratory-based and point-of-care enzyme- and high-income countries. They are also intended for
OLQNHGLPPXQRVRUEHQWDVVD\V(/,6$VQXFOHLFDFLG individuals working in sexual and reproductive health
DPSOLFDWLRQWHVWV1$$7VDUHVWURQJO\UHFRPPHQGHG
due to their superior performance characteristics.
1$$7VDUHKLJKO\VHQVLWLYHDQGVSHFLFDQGFDQEH
used for a wide range of samples, including urine and
vulvovaginal, cervical and urethral swabs. Several
FRPPHUFLDO1$$7VXVLQJGLHUHQWWHFKQRORJLHVDUH
available. The increased sensitivity of NAATs compared
with other diagnostic tests, such as culture and antigen
programmes, such as HIV/AIDS, family planning,
maternal and child health and adolescent health, to
ensure appropriate STI diagnosis and management.
The guidelines are also useful for policy-makers,
PDQDJHUVSURJUDPPHRFHUVDQGRWKHUSURIHVVLRQDOV
in the health sector who are responsible for
implementing STI management interventions
at regional, national and subnational levels.
GHWHFWLRQPHWKRGV')$DQG(/,6$DOORZVWHVWLQJ
of non-invasive specimens, which can be collected
conveniently at the primary level of care. Commercially
available NAATs are not yet licensed for the diagnosis
of extra-genital samples but have shown to be reliable
for detection of chlamydial infection in rectal and
pharyngeal swabs. Several commercially available tests
for chlamydia are combined with tests for gonorrhoea.
Further information is available in the WHO publication
on laboratory diagnosis of STIs including HIV (6).
1.2 RATIONALE FOR NEW RECOMMENDATIONS
The guidelines for treatment of chlamydial infections
need to be updated to respond to the changes in
epidemiology and antimicrobial susceptibility for
chlamydia that have occurred since the previous WHO
Guidelines for the management of sexually transmitted
LQIHFWLRQVZHUHSXEOLVKHGLQ(7). LGV is increasingly
1.5 STRUCTURE OF THE GUIDELINES
These guidelines provide evidence-based
UHFRPPHQGDWLRQVIRUWKHWUHDWPHQWRIVSHFLF
clinical conditions caused by C. trachomatis.
These guidelines provide direction for countries as
WKH\GHYHORSQDWLRQDOWUHDWPHQWUHFRPPHQGDWLRQV
however, national guidelines should also take into
account the local pattern of AMR, as well as health
service capacity and resources.
Updated treatment recommendations based on
the most recent evidence are included for the
most important common conditions caused by
C. trachomatis. Recommendations were not updated
for rare conditions and other conditions for which
no new information has become available since the
:+267,JXLGHOLQHVZHUHLVVXHG
SUHYDOHQWDPRQJPHQZKRKDYHVH[ZLWKPHQ060LQ
Treatment recommendations for the following
some settings, and treatment failure has been reported
conditions caused by C. trachomatis are included
ZLWKWHWUDF\FOLQHDQGPDFUROLGHVLQDSSUR[LPDWHO\
in these guidelines:
of cases (8)0RUHRYHUWKH:+267,JXLGHOLQHVDUH
the only international guidelines that still recommend uncomplicated genital infections
treating chlamydial infections with amoxicillin or anorectal infections
tetracycline. As recommended by the WHO STI
uncomplicated genital infections in pregnant women
H[SHUWFRQVXOWDWLRQLQWKHUVWDQGVHFRQGOLQH
treatment recommendations for C. trachomatis needed LGV
to be reviewed and revised based on the most recent RSKWKDOPLDQHRQDWRUXPWUHDWPHQWDQGSURSK\OD[LV
available evidence.

1.3 OBJECTIVES
The objectives of these guidelines are:
to provide evidence-based guidance on treatment
of infection with C. trachomatisDQG
to support countries to update their national
guidelines for treatment of chlamydial infection.
12 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS


2.2 QUESTIONS AND OUTCOMES
,Q'HFHPEHUWKHUVW*'*PHHWLQJZDVKHOG
to identify and agree on the key PICO (population,
LQWHUYHQWLRQFRPSDUDWRURXWFRPHTXHVWLRQVWKDW
formed the basis for the systematic reviews and the
recommendations. Following this meeting, a survey
of GDG members was conducted to prioritize the
questions and outcomes according to clinical relevance
DQGLPSRUWDQFH6L[3,&2TXHVWLRQVZHUHLGHQWLHGIRU
the update on the treatment of genital and anorectal
METHODS chlamydial infections, treatment of LGV, and prevention
DQGWUHDWPHQWRIQHRQDWDORSKWKDOPLDVHH$QQH[%
These questions pertained to adults and other special
populations, namely adolescents, pregnant women,
people living with HIV, and populations at high risk
of acquiring and transmitting STIs, such as men
ZKRKDYHVH[ZLWKPHQ060DQGVH[ZRUNHUV
Only outcomes that were ranked as critical or important
to patients and decision-making were included: clinical
DQGPLFURELRORJLFDOFXUHDQGDGYHUVHHHFWVLQFOXGLQJ
7KHVHJXLGHOLQHVZHUHGHYHORSHGIROORZLQJWKH
methods outlined in the 2014 edition of the
:+2KDQGERRNIRUJXLGHOLQHGHYHORSPHQW(9)
(see Annex B for a detailed description).
2.1 GUIDELINE DEVELOPMENT GROUP (GDG)
To update the WHO guidelines for the prevention,
PDWHUQDODQGIHWDOHHFWVLQSUHJQDQWZRPHQ
2.3 REVIEWS OF THE EVIDENCE
The systematic reviews for each priority question
were conducted by McMaster University, the WHO
Collaborating Centre for Evidence-Informed Policy.
Evidence for desirable and undesirable outcomes,
patient values and preferences, resources, acceptability,
equity and feasibility were reviewed from published and
unpublished literature. Comprehensive searches for
previously conducted systematic reviews, randomized
controlled trials and non-randomized studies were
SHUIRUPHGIURP0DUFKWR2FWREHU$GGLWLRQDO
searches were conducted to identify studies on patient
values and preferences (e.g. qualitative research
treatment and management of STIs, a GDG was GHVLJQVDQGUHVRXUFHLPSOLFDWLRQVHJFRVWRI
established, comprising 33 international STI experts, LQWHUYHQWLRQVFRVWEHQHWDQGFRVWHHFWLYHQHVV
including clinicians, researchers and programme VWXGLHV7ZRPHPEHUVRIWKH6\VWHPDWLF5HYLHZ7HDP
PDQDJHUV$QQH[$$FRUHVXEJURXSWRIRFXVRQ screened studies, extracted and analysed the data,
the guidelines related to chlamydia was created and assessed the quality/certainty of the evidence
within the GDG, to provide more intensive feedback using the Grading of Recommendations Assessment,
WKURXJKRXWWKHSURFHVV$QQH[$7KH*'* 'HYHORSPHQWDQG(YDOXDWLRQ*5$'(DSSURDFK1
participated in meetings and teleconferences to
prioritize the questions to be addressed, discuss the
HYLGHQFHUHYLHZVDQGQDOL]HWKHUHFRPPHQGDWLRQV
7KH*'*UHYLHZHGDQGDSSURYHGWKHQDOYHUVLRQ
of the guidelines.

1 For more information, see: http://www.gradeworkinggroup.org/

 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
The quality/certainty of the evidence was assessed
at four levels:
+
 LJK:HDUHYHU\FRQGHQWWKDWWKHWUXHHHFWOLHV
FORVHWRWKDWRIWKHHVWLPDWHRIWKHHHFW
0
 RGHUDWH:HDUHPRGHUDWHO\FRQGHQWLQWKHHHFW
HVWLPDWHWKHWUXHHHFWLVOLNHO\WREHFORVHWRWKH
13
of the recommendations. Following the meeting, the
UHFRPPHQGDWLRQVZHUHQDOL]HGYLDWHOHFRQIHUHQFH
DQGQDODSSURYDOZDVREWDLQHGIURPDOO*'*PHPEHUV
electronically. These guidelines were subsequently
written up in full and then peer reviewed. The External
Review Group approved the methods and agreed with
the recommendations made by the GDG (members
HVWLPDWHRIWKHHHFWEXWWKHUHLVDSRVVLELOLW\WKDW
LWLVVXEVWDQWLDOO\GLHUHQW
/
 RZ2XUFRQGHQFHLQWKHHHFWHVWLPDWHLVOLPLWHG
WKHWUXHHHFWPD\EHVXEVWDQWLDOO\GLHUHQWIURPWKH
HVWLPDWHRIWKHHHFW
9
 HU\ORZ:HKDYHYHU\OLWWOHFRQGHQFHLQWKHHHFW
HVWLPDWHWKHWUXHHHFWLVOLNHO\WREHVXEVWDQWLDOO\
GLHUHQWIURPWKHHVWLPDWHRIHHFW
In addition, the direct costs of medicines were estimated
DUHOLVWHGLQ$QQH[$
According to the GRADE approach, the strength
of each recommendation was rated as either
strong or conditional. Strong recommendations are
presented using the wording The WHO STI guideline
recommends, while conditional recommendations
are worded as The WHO STI guideline suggests
throughout the guidelines. The implications of the
GLHULQJVWUHQJWKVRIUHFRPPHQGDWLRQVIRUSDWLHQWV
XVLQJWKH0DQDJHPHQW6FLHQFHVIRU+HDOWK06+ clinicians and policy-makers are explained in detail
International drug price indicator guide (10). References in Table 3.
for all the reviewed evidence are listed in Annex C.
All evidence was summarized in GRADE evidence
SUROHVDQGLQHYLGHQFHWRGHFLVLRQWDEOHVVHH:HE
DQQH[HV'DQG(

2.4 MAKING RECOMMENDATIONS

Recommendations were developed during a second
PHHWLQJRIWKH*'*LQ2FWREHUZKLFKZDV
facilitated by two co-chairs, one with expertise in
GRADE and the other with clinical STI expertise.
The methodologist presented the GRADE evidence
SUROHVDQGHYLGHQFHWRGHFLVLRQIUDPHZRUNVDWWKH
meeting. When formulating the recommendations,
the GDG considered and discussed the desirable and
XQGHVLUDEOHHHFWVRIWKHLQWHUYHQWLRQVWKHYDOXH
placed on the outcomes, the associated costs and use
of resources, the acceptability of the interventions to
DOOVWDNHKROGHUVLQFOXGLQJSHRSOHDHFWHGE\67,V
the impact on health equity and the feasibility of
implementation. Treatments were judged according
WRWKHDERYHFULWHULDDQGQDOGHFLVLRQVDQGJXLGHOLQH
recommendations were agreed. The discussion was
facilitated by the co-chairs with the goal of reaching
consensus across the GDG. Disagreements among the
GDG members were noted in the evidence-to-decision
framework for each judgement. In the case of failure to
reach consensus for a recommendation, the planned
procedure was for the GDG to take a vote and record
the results. However, no votes were taken because
the GDG reached consensus during discussion for all
14 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

Table 3. Implications of strong and conditional recommendations using the GRADE approach

Implications Strong recommendation Conditional recommendation

The WHO STI guideline recommends
For patients Most individuals in this situation would want
the recommended course of action, and only
a small proportion would not.
Formal decision aids are not likely to be needed
to help individuals make decisions consistent
with their values and preferences.
For clinicians Most individuals should receive the
recommended course of action.
Adherence to this recommendation according
to the guidelines could be used as a quality
criterion or performance indicator.
For policy- The recommendation can be adopted as policy
makers in most situations.
The WHO STI guideline suggests
The majority of individuals in this situation
would want the suggested course of action,
but many would not.
&OLQLFLDQVVKRXOGUHFRJQL]HWKDWGLHUHQW
choices will be appropriate for each individual
and that clinicians must help each individual
arrive at a management decision consistent
ZLWKWKHLQGLYLGXDOVYDOXHVDQGSUHIHUHQFHV
Decision aids may be useful to help individuals
make decisions consistent with their values
and preferences.
Policy-making will require substantial debate
and involvement of various stakeholders.

2.5 MANAGEMENT OF CONFLICTS OF INTEREST

0DQDJHPHQWRIFRQLFWVRILQWHUHVWZDVDNH\SULRULW\
throughout the process of guideline development. WHO
JXLGHOLQHVIRUGHFODUDWLRQRILQWHUHVWV'2,IRU:+2
experts were implemented (11). DOI statements were
obtained from all GDG members prior to assuming their
roles in the group. At the GDG meetings (December
DQG2FWREHUWKHPHPEHUVGLVFORVHG
their interests, if any, at the beginning of the meeting.
Their DOI statements are summarized in Web annex F.
After analysing each DOI, the STI team concluded
WKDWQRPHPEHUKDGQDQFLDORUFRPPHUFLDOLQWHUHVWV
UHODWHGWR67,WUHDWPHQW2WKHUQRWLHGLQWHUHVWVZHUH
PLQRUWKH\ZHUHHLWKHUQRWUHODWHGWR67,RUZHUHQRQ
commercial grants or interests. The STI team concluded
WKDWWKHUHZHUHQRVLJQLFDQWFRQLFWVRILQWHUHVWWKDW
would exclude any member from participating fully in the
guideline development process. Therefore, options for
conditional participation, partial or total exclusion of
any GDG member were not discussed.
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 15


$OOOHYHOVRI:+2KHDGTXDUWHUVUHJLRQDORFHVDQG
FRXQWU\RFHVZLOOZRUNZLWKUHJLRQDODQGQDWLRQDO
partners including the United Nations Population
)XQG81)3$WKH8QLWHG1DWLRQV&KLOGUHQV)XQG
81,&()WKH-RLQW8QLWHG3URJUDPPHRQ+,9$,'6
81$,'6QRQJRYHUQPHQWDORUJDQL]DWLRQV1*2VDQG
other agencies implementing sexual and reproductive

DISSEMINATION, health and STI services to ensure that the new

recommendations are integrated and implemented in
UPDATING AND sexual and reproductive health, family planning, and
maternal, neonatal, child and adolescent health services.
IMPLEMENTATION OF Reference to this document will be made within other
relevant WHO guidelines. These guidelines will also be
THE GUIDELINES disseminated at major conferences related to STIs and
HIV and the aforementioned programme areas.

3.2 UPDATING THE GUIDELINES AND USER

3.1 DISSEMINATION
These guidelines will be made available as a printed
publication, as a download on the website of the
WHO Department of Reproductive Health and
Research (where there will also be links to all supporting
FEEDBACK
A system of monitoring relevant new evidence and
XSGDWLQJWKHUHFRPPHQGDWLRQVDVQHZQGLQJV
become available will be established within a year
of implementing the guidelines. An electronic
follow-up survey of key end-users of the STI guidelines
will be conducted after the release of the guidelines.
The results of the survey will be used to identify
challenges and barriers to the uptake of the guidelines,
to evaluate their usefulness for improving service
delivery, and to identify topics or gaps in treatment
that need to be addressed in future editions.
3.3 IMPLEMENTATION OF THE WHO
GRFXPHQWDWLRQ2, and in the WHO Reproductive GUIDELINES FOR THE TREATMENT OF
+HDOWK/LEUDU\5+/3. The recommendations will also C. TRACHOMATIS
EHDYDLODEOHLQDJXLGHOLQHDSSOLFDWLRQDSSFUHDWHG
with the GRADEpro GDT software. The guidelines
will be announced in the next edition of the RHL
newsletter and in the Reproductive Health and
Research departmental newsletter, and other
relevant organizations will be requested to copy
the announcement in their respective newsletters.
:+2KHDGTXDUWHUVZLOOZRUNZLWK:+2VUHJLRQDO
RFHVDQGFRXQWU\RFHVWRHQVXUHWKDWFRXQWULHV
receive support in the adaptation, implementation
and monitoring of these guidelines using the WHO
Department of Reproductive Health and Research
JXLGDQFHRQ,QWURGXFLQJ:+2VUHSURGXFWLYHKHDOWK
guidelines and tools into national programmes (12).
2 These guidelines and all supporting documents will be available at:
www.who.int/reproductivehealth/publications/rtis/chlamydia-treatment-guidelines/en/
3 RHL is available at: http://apps.who.int/rhl/en/
ADAPTATION, IMPLEMENTATION AND MONITORING
These guidelines provide recommendations for
treatment of chlamydial infection based on the best
global evidence available at the time of compilation.
However, the epidemiology and AMR of STIs vary by
geographical location and are constantly changing,
sometimes rapidly. It is recommended that countries
conduct good quality studies to gather the information
needed to adapt these guidelines to the local STI
situation as they update their national guidelines.
In areas lacking local data as a basis for adaptation,
the recommendations in these guidelines can be
adopted as presented.
16 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
For further guidance on adaptation, implementation
and monitoring of national guidelines please refer to
,QWURGXFLQJ:+2VUHSURGXFWLYHKHDOWKJXLGHOLQHV
and tools into national programmes: principles and
processes of adaptation and implementation (12).
In adapting the guidelines for national use,
UHFRPPHQGHGWUHDWPHQWVVKRXOGKDYHDQHFDF\
of at least 95%. The criteria to be considered for
the selection of medicines are listed in Box 1.
Recommended medicines should meet as many of the
criteria as possible, taking into account local availability,
HFDF\URXWHDQGIUHTXHQF\RIDGPLQLVWUDWLRQ
BOX 1. CRITERIA FOR THE SELECTION OF
MEDICINES FOR THE TREATMENT OF STIS
In order to estimate the quantity of medicines needed,
it will be necessary to review the medicines that are
recommended for treatment, their unit prices, the
quantity required per treatment and the epidemiological
information on the prevalence of infection. One can
estimate medicine needs by multiplying the estimated
number of cases by the total quantity of medicine
VSHFLHGIRUWUHDWPHQWRIRQHFDVH7KHVHJXUHV
can be derived from health centres providing care but
WKH\PXVWEHYHULHGWRDYRLGZDVWHIXORYHURUGHULQJ
Budgeting for medicines is critical. If the national
ministry of health does not provide medicines for free
DQGWKHSDWLHQWFDQQRWDRUGWREX\WKHPHGLFLQHV
then there will essentially be no possibility of
curtailing the spread of infection and the occurrence
of complications. At the national level it is important
+LJKHFDF\DWOHDVWFXUHUDWH WKDWGHFLVLRQPDNHUVSROLWLFLDQVDQGVFDOFRQWUROOHUV
understand the need to subsidize STI medicines.
+LJKTXDOLW\SRWHQWDFWLYHLQJUHGLHQW
Low-cost STI medicines can be obtained through
Low cost international vendors of generic products, non-
Low toxicity levels SURWRUJDQL]DWLRQVZLWKSURFXUHPHQWVFKHPHVVXFK
Organism resistance unlikely to develop as UNICEF, UNFPA and UNHCR, and through joint
or likely to be delayed medicine procurement schemes. By way of such
schemes, national programmes can join other national
Single dose
programmes to jointly procure medicines, thus reducing
Oral administration the overall costs by sharing the overhead costs and
Not contraindicated for pregnant or taking advantage of discounts for purchasing in bulk.
lactating women Placing STI medicines on national lists of essential
medicines increases the likelihood of achieving a
Appropriate medicines should be included in the
supply of these medicines at low cost.
national essential medicines lists. When selecting
medicines, consideration should be given to the
competencies and experience of health-care
providers.

IDENTIFYING AND PROCURING STI DRUGS

It is important not only to identify medicines that will
EHUHFRPPHQGHGDVUVWOLQHWUHDWPHQWIRU67,VEXW
also the estimated quantities of the medicines that
will be required. Quantifying medication needs is
important in order to estimate costs, to reconcile
QDQFLDOUHTXLUHPHQWVZLWKDYDLODEOHEXGJHWDQGWR
make orders in advance so that the unit and freight
costs can be minimized.
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 17


Remarks: While good practice based on evidence
RIODUJHQHWEHQHWGLFWDWHVWKDWSDWLHQWVVKRXOGEH
treated for chlamydial infection, the choice of treatment
may depend on the convenience of dosage, the cost and
TXDOLW\RIWKHPHGLFLQHVLQGLHUHQWVHWWLQJVDQGHTXLW\
considerations. When high value is placed on reducing
costs, doxycycline in a standard dose may be the best

RECOMMENDATIONS FKRLFHZKHQKLJKYDOXHLVSODFHGRQFRQYHQLHQFH
azithromycin in a single dose may be the best choice.
FOR TREATMENT A delayed-release formulation of doxycycline may be
an alternative to twice daily dosing of doxycycline, but
OF CHLAMYDIAL the high cost of the delayed-release formulation may
prohibit its use. Note that doxycycline, tetracycline
INFECTIONS DQGRR[DFLQDUHFRQWUDLQGLFDWHGLQSUHJQDQWZRPHQ
VHHUHFRPPHQGDWLRQVDF
Research implications: The potential for resistance
to azithromycin, doxycycline and other treatment
options should be investigated. Future research could
compare these treatments and recommended dosages
in randomized controlled trials measuring important
outcomes such as clinical cure, microbiological cure,
FRPSOLFDWLRQVVLGHHHFWVLQFOXGLQJDOOHUJ\WR[LFLW\
JDVWURLQWHVWLQDOHHFWVFRPSOLDQFHTXDOLW\RIOLIH+,9
transmission and acquisition, and partner transmission
of chlamydia. Studies are also needed that evaluate
DPR[LFLOOLQPJWKUHHWLPHVDGD\IRUGD\V

7KHIROORZLQJQLQHUHFRPPHQGDWLRQVDSSO\ SUMMARY OF THE EVIDENCE

WRDGXOWVDGROHVFHQWV\HDUVRIDJH
Evidence from a Cochrane systematic review was used.
SHRSOHOLYLQJZLWK+,9DQGNH\SRSXODWLRQV This review included 25 randomized studies comparing
LQFOXGLQJVH[ZRUNHUVPHQZKRKDYHVH[ tetracycline, quinolones and macrolides. There are no
ZLWKPHQ060DQGWUDQVJHQGHUSHUVRQV
6SHFLFUHFRPPHQGDWLRQVKDYHDOVREHHQ
developed for ophthalmia neonatorum
caused by C. trachomatis.
4.1 UNCOMPLICATED GENITAL CHLAMYDIA
data available for amoxicillin. Overall, there is moderate
to low quality evidence for most comparisons of
treatments. Moderate quality evidence shows trivial
GLHUHQFHVEHWZHHQD]LWKURP\FLQJDQGGR[\F\FOLQH
PJRUDOO\WZLFHDGD\IRUGD\VLQWKHQXPEHUV
of people microbiologically cured and experiencing
DGYHUVHHYHQWV7KHUHZHUHIHZHUSHRSOHSHU
cured with azithromycin versus doxycycline, ranging
IURPIHZHUWRPRUHULVNUDWLR>55@
RECOMMENDATION 1 FRQGHQFHLQWHUYDO>&,@WR,QDGGLWLRQWKHUH
For people with uncomplicated genital chlamydia, ZHUHPRUHDGYHUVHHYHQWVSHUSHRSOHZLWK
the WHO STI guideline suggests one of the azithromycin versus doxycycline, ranging from 42 fewer
following options:
azithromycin 1 g orally as a single oral dose
GR[\F\FOLQHPJRUDOO\WZLFHDGD\IRUGD\V
or one of these alternatives:
WHWUDF\FOLQHPJRUDOO\IRXUWLPHVDGD\IRUGD\V
HU\WKURP\FLQPJRUDOO\IRXUWLPHVDGD\IRUGD\V
RR[DFLQPJRUDOO\WZLFHDGD\IRUGD\V
WRPRUH55&,WR6LPLODUUHVXOWV
are shown in a recently published randomized study.
Delayed-release doxycycline hyclate probably leads
WROLWWOHWRQRGLHUHQFHLQWKHSURSRUWLRQRISHRSOH
microbiologically cured but probably has fewer side-
HHFWVWKDQVWDQGDUGGRVHGR[\F\FOLQH2R[DFLQPD\
result in fewer cures but also slightly fewer adverse
events compared to doxycycline. When comparing
multiple high doses of azithromycin (1 g weekly for 3
ZHHNVWRDVLQJOHGRVHPRUHSHRSOHPD\EHFXUHGEXW
Conditional recommendation, moderate quality evidence
18 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

there are no data for adverse events related to Conditional recommendation, low quality evidence
very high doses. Higher doses of any tetracycline
Remarks: This recommendation applies to people
compared with lower doses may lead to more cures
with known anorectal infection and to people with
but will probably also lead to more adverse events.
suspected anorectal infections with genital co-
Tetracyclines compared with quinolones may lead
infection. Clinicians should ask men, women and key
to fewer cures but also slightly fewer adverse events.
populations (e.g. men who have sex with men [MSM],
Erythromycin compared with quinolones may lead
WUDQVJHQGHUSHUVRQVDQGIHPDOHVH[ZRUNHUVDERXW
to fewer cures and more adverse events.
anal sex and treat accordingly. Doxycycline should
There is no evidence relating to patient values and not be used in pregnant women because of adverse
preferences but the Guideline Development Group HHFWVVHHUHFRPPHQGDWLRQVDF
*'*DJUHHGWKDWWKHUHLVSUREDEO\QRYDULDELOLW\LQ
Research implications: The global incidence of
the values people place on the outcomes. Research
chlamydial anorectal infections should be determined.
related to other conditions indicates that adherence
0RUHUHVHDUFKLVQHFHVVDU\RQWKHHHFWVRIWUHDWPHQWV
may be improved with simpler medication regimens.
used for anorectal infections, particularly azithromycin,
The GDG therefore agreed that azithromycin may be
which is currently not on the WHO essential medicines
more acceptable to patients since it is a single dose
list for anorectal chlamydial infections (13)(HFWV
regimen (a majority of the GDG members considered
should be assessed in both men and women, and in
single-dose regimens to be preferable for patient
key populations (e.g. MSM, transgender persons and
FRPSOLDQFHRYHUPXOWLGRVHUHJLPHQV7KHUHLV
IHPDOHVH[ZRUNHUV
little to no evidence for equity issues and feasibility.
Resistance in other infections (e.g. gonorrhoea and
SUMMARY OF THE EVIDENCE
0\FRSODVPDJHQLWDOLXPWKDWRIWHQFRRFFXUZLWK
chlamydia may restrict the use of some medicines, There is low quality evidence from eight non-
VXFKDVRR[DFLQ)RUPDQ\RIWKHVHPHGLFLQHVFRVWV UDQGRPL]HGVWXGLHVYHGLUHFWFRPSDULVRQVDQGWKUHH
PD\GLHUEHWZHHQFRXQWULHVLQSODFHVZLWKKLJK VLQJOHDUPVWXGLHVWKDWHYDOXDWHGGR[\F\FOLQHDQG
LQFLGHQFHRIFKODP\GLDWKHFRVWGLHUHQFHVEHWZHHQ
azithromycin and doxycycline may be large due to
greater numbers of people requiring treatment.
In summary, there was moderate quality evidence
IRUWULYLDOGLHUHQFHVLQEHQHWVDQGKDUPVEHWZHHQ
D]LWKURP\FLQVHH:HEDQQH[HV'DQG(7KHUHDUH
no data for amoxicillin, erythromycin and quinolones.
(YLGHQFHVKRZHGWKDWWKHUHPD\EHIHZHU
PLFURELRORJLFDOFXUHVSHUSHRSOHZLWKD]LWKURP\FLQ
FRPSDUHGZLWKGR[\F\FOLQH55&,
WR(YLGHQFHIURPVWXGLHVRIJHQLWDOLQIHFWLRQV
azithromycin and doxycycline, and although the cost
VKRZVOLWWOHWRQRGLHUHQFHLQVLGHHHFWVZLWKWKHVH
of azithromycin is higher, the single dose may make
it more convenient to use than doxycycline. While the
GLHUHQFHVDUHDOVRWULYLDOZLWKWKHRWKHUPHGLFLQHV
the evidence is low quality and these are therefore
provided as alternatives, with the exception of delayed-
release doxycycline, which is currently expensive.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
WUHDWPHQWV55&,WR$OWKRXJK
there are fewer women than men in the studies, the
HYLGHQFHVXJJHVWHGOLWWOHGLHUHQFHLQHHFWVEHWZHHQ
men and women. There is no evidence relating to patient
values and preferences, but the GDG agreed that
there are no known reasons to suspect values would
YDU\IRUGLHUHQWSHRSOH7KHUHLVOLWWOHWRQRHYLGHQFH
for acceptability, but research in other conditions
indicates that adherence may be improved with simpler
IUDPHZRUNVSS
4.2 ANORECTAL CHLAMYDIAL INFECTION
RECOMMENDATION 2
In people with anorectal chlamydial infection, the
:+267,JXLGHOLQHVXJJHVWVXVLQJGR[\F\FOLQHPJ
orally twice daily for 7 days over azithromycin 1 g orally
single dose.
medication regimens. There is also little to no evidence
for equity issues and feasibility, but azithromycin is
more expensive and typically the cost is transferred
to consumers. The GDG agreed that equity may vary
between the medicines depending on the population:
in some populations, azithromycin may be more
acceptable since it is a single-dose treatment,
and some people may experience stigma related to
visibility of a multi-dose regimen with doxycycline.
Therefore, suggesting doxycycline over azithromycin
could create inequity for people sensitive to stigma
related to multi-dose regimens. Azithromycin is
currently not listed as an essential medicine for
anorectal chlamydial infection.
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
In summary, doxycycline may result in more cures,
but although it is less expensive than azithromycin,
azithromycin may be better accepted due to the
single-dose treatment.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
19
SUMMARY OF THE EVIDENCE
Overall, there is moderate to low quality evidence from
14 randomized controlled trials, two non-randomized
comparative studies and two large cohort studies
DVVHVVLQJWKHHHFWVRID]LWKURP\FLQHU\WKURP\FLQ
and amoxicillin in pregnant women with chlamydial
LQIHFWLRQV7KHGLHUHQFHVLQEHQHWVEHWZHHQWKHVH
IUDPHZRUNVSS GLHUHQWWUHDWPHQWVDUHVPDOODQGZLGHFRQGHQFH
intervals included the possibility of greater or lesser
EHQHWVZLWKD]LWKURP\FLQFRPSDUHGWRRWKHU
4.3 CHLAMYDIAL INFECTION IN PREGNANT medicines. Moderate quality evidence found that
WOMEN there are probably 94 more people microbiologically
FXUHGSHUZLWKD]LWKURP\FLQYHUVXVHU\WKURP\FLQ
RECOMMENDATION 3A 55&,WRDQGORZTXDOLW\
In pregnant women with genital chlamydial infection, evidence found that there may be 72 more people
the WHO STI guideline recommends using azithromycin FXUHGSHUZLWKD]LWKURP\FLQYHUVXVDPR[LFLOOLQ
over erythromycin. 55&,WR7KHUHDUHSUREDEO\
IHZHUSHRSOHPLFURELRORJLFDOO\FXUHGSHUZLWK
Strong recommendation, moderate quality evidence HU\WKURP\FLQYHUVXVDPR[LFLOOLQ55&,
WR7KHUHPD\EHVOLJKWO\IHZHUVLGHHHFWVZLWK
RECOMMENDATION 3B azithromycin compared with erythromycin or amoxicillin
In pregnant women with genital chlamydial infection, DSSUR[LPDWHO\IHZHUEXWWKHUHPD\EH
the WHO STI guideline suggests using azithromycin VXEVWDQWLDOO\PRUHVLGHHHFWVZLWKHU\WKURP\FLQ
over amoxicillin.
Conditional recommendation, low quality evidence
RECOMMENDATION 3C
In pregnant women with genital chlamydial infection,
the WHO STI guideline suggests using amoxicillin
over erythromycin.
Conditional recommendation, low quality evidence
Dosages:
azithromycin 1 g orally as a single dose
DPR[LFLOOLQPJRUDOO\WKUHHWLPHVDGD\IRUGD\V
HU\WKURP\FLQPJRUDOO\IRXUWLPHVDGD\IRU
days.
Remarks: $]LWKURP\FLQLVWKHUVWFKRLFHRI
treatment but may not be available in some settings.
Azithromycin is less expensive than erythromycin
and since it is provided as a single dose, may result in
YHUVXVDPR[LFLOOLQDSSUR[LPDWHO\PRUH
Much of the evidence was uncertain for fetal
outcomes as it came from indirect comparisons in
large cohort studies. There were few events, and
FRQGHQFHLQWHUYDOVDURXQGWKHVPDOOGLHUHQFHV
included the potential for fewer or more events
between comparisons.
In summary, the GDG agreed that azithromycin is
preferred over erythromycin because of greater
HHFWLYHQHVVDQGORZHUFRVWDQGSUHIHUUHGRYHU
DPR[LFLOOLQGXHWRJUHDWHUHHFWLYHQHVV$]LWKURP\FLQ
PD\DOVREHPRUHDFFHSWDEOHGXHWRVLQJOHGRVDJH
however, it may not be available in all settings due to
misconceptions that it is costly. Amoxicillin is preferred
over erythromycin as it is less costly and may result in
JUHDWHUEHQHWVDQGIHZHUVLGHHHFWV
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
better adherence and therefore better outcomes. IUDPHZRUNVSS

Research implications: Research in pregnant women

comparing these treatments and the recommended
dosages should be conducted. Although these
medicines are relatively safe in pregnancy, maternal and
fetal complications (e.g. adverse pregnancy outcomes,
IHWDOGHIHFWVZLWKWKHXVHRIWKHVHWUHDWPHQWVIRU67,V
and other infections should be monitored, collected
and analysed to inform updated recommendations in
the future. When conducting these studies, costs and
acceptability of the treatments could be measured.
20 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
4.4 LYMPHOGRANULOMA VENEREUM (LGV)
RECOMMENDATION 4
In adults and adolescents with LGV, the WHO STI
JXLGHOLQHVXJJHVWVXVLQJGR[\F\FOLQHPJRUDOO\
twice daily for 21 days over azithromycin 1 g orally,
weekly for 3 weeks.
Conditional recommendation, very low quality evidence
Remarks: Good practice dictates treatment of LGV,
agreed that these may be dependent on individuals and
countries. Data for medicine prices and procurement
indicate that doxycycline is cheaper than azithromycin
and erythromycin, although the latter medicines are
still inexpensive.
In summary, there is very low quality evidence for all
medicines for treatment of LGV. The evidence suggests
ODUJHEHQHWVZLWKGR[\F\FOLQHRYHUD]LWKURP\FLQDQG
WKHHHFWVRIHU\WKURP\FLQDUHXQNQRZQ,QDGGLWLRQ
doxycycline is the least expensive.
LQSDUWLFXODUIRUPHQZKRKDYHVH[ZLWKPHQ060
See Annex C for list of references of reviewed evidence,
and for people living with HIV. When doxycycline is
and Web annex D for details of the evidence reviewed,
contraindicated, azithromycin should be provided.
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
When neither treatment is available, erythromycin
IUDPHZRUNVSS
PJRUDOO\IRXUWLPHVDGD\IRUGD\VLVDQ
alternative. Doxycycline should not be used in
SUHJQDQWZRPHQEHFDXVHRIDGYHUVHHHFWV 4.5 OPHTHALMIA NEONATORUM
VHHUHFRPPHQGDWLRQVDF
Research implications: Additional research for each
of the treatments and the dosages recommended is
needed, in particular for erythromycin and azithromycin.
Randomized controlled trials should be conducted,
measuring critical and important outcomes, such
as clinical cure, microbiological cure, complications,
VLGHHHFWVLQFOXGLQJDOOHUJ\WR[LFLW\JDVWURLQWHVWLQDO
RECOMMENDATION 5
In neonates with chlamydial conjunctivitis, the WHO
STI guideline recommends using oral azithromycin
PJNJGD\RUDOO\RQHGRVHGDLO\IRUGD\VRYHU
HU\WKURP\FLQPJNJGD\RUDOO\LQIRXUGLYLGHG
doses daily for 14 days.
Strong recommendation, very low quality evidence
HHFWVTXDOLW\RIOLIH+,9WUDQVPLVVLRQDQGDFTXLVLWLRQ
compliance and LGV transmission to partners.
7KHHHFWVRIVKRUWHUFRXUVHVRIWUHDWPHQWVKRXOG
also be investigated.
SUMMARY OF THE EVIDENCE
There is very low quality evidence from 12 non-
randomized studies with no comparisons between
treatments. These studies assessed treatment
with azithromycin and doxycycline for 21 days, and
erythromycin for 14 days. Evidence for doxycycline
VKRZHGWKDWWKHUHPD\EHODUJHEHQHWVFOLQLFDODQG
Remarks: This is a strong recommendation given
the potential for the risk of pyloric stenosis with the
use of erythromycin in neonates. In some settings,
azithromycin suspension is not available and therefore
HU\WKURP\FLQPD\EHXVHG6LGHHHFWVVKRXOGEH
monitored with the use of either medication.
Research implications: Additional research should be
FRQGXFWHGWRGHWHUPLQHWKHHHFWVRIWKHVHPHGLFLQHV
WRWUHDWRSKWKDOPLDQHRQDWRUXP7KHHHFWVRIRWKHU
medications such as trimethoprim should also be
investigated. Pyloric stenosis should be monitored
PLFURELRORJLFDOFXUHUDWHVJUHDWHUWKDQDQG or research conducted to evaluate this risk with
WULYLDOVLGHHHFWVHJSHUVLVWHQWPXFRXVPHPEUDQH the medicines suggested.
DEQRUPDOLWLHVSHULUHFWDODEVFHVVDQGDOOHUJ\
7KHHHFWVRID]LWKURP\FLQDQGHU\WKURP\FLQZHUH SUMMARY OF THE EVIDENCE
uncertain, with only 14 people receiving azithromycin
There is low quality evidence for a cure rate of 98% with
and 31 people receiving erythromycin in the studies.
HU\WKURP\FLQPJNJGD\IRUGD\VDQGXQFHUWDLQ
6LGHHHFWVDUHOLNHO\WULYLDODQGVLPLODUWRWKHVLGH
HHFWVRQWKHFXUHUDWHIRUD]LWKURP\FLQJLYHQWKH
HHFWVRIWKHVHWUHDWPHQWVLQSHRSOHZLWKRWKHU
small numbers of neonates receiving azithromycin in
chlamydial infections. There is no evidence relating
WKHVWXG\VHH:HEDQQH[HV'DQG(7KHUHLVYHU\ORZ
to patient values and preferences, but the GDG
quality evidence for 7 more instances of pyloric stenosis
agreed that there are no known reasons to suspect
SHUZLWKHU\WKURP\FLQ7KH*'*UHJDUGHGWKH
YDOXHVZRXOGYDU\IRUGLHUHQWSHRSOH7KHUHLVOLWWOH
ULVNRIS\ORULFVWHQRVLVDVDVHULRXVDGYHUVHHHFW
to no evidence for acceptability, but research in other
of erythromycin use in children. There are no data
conditions indicates that adherence may be improved
evaluating pyloric stenosis due to use of azithromycin.
with simpler medication regimens. There is little
7KHUHDUHDOVRQRGDWDDVVHVVLQJWKHHHFWVRI
evidence for equity issues and feasibility, but the GDG
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
trimethoprim. There is no evidence for variation in
patient values and preferences, but compliance with
treatments ranged from 77% to 89%. The costs for
treatments are relatively low and similar, and most
treatments are currently being used.
In summary, azithromycin is preferred over
erythromycin because of the potential risk of serious
adverse events with erythromycin, and there are no
data for trimethoprim.
21
SUMMARY OF THE EVIDENCE
Overall, the quality of evidence is low to very low
IURPVWXGLHVUDQGRPL]HGVWXGLHVDQGRQH
non-randomized study with two comparison
JURXSV7KHUHDUHIHZDYDLODEOHGDWDIRUWKHHHFWV
RIFKORUDPSKHQLFRO/DUJHEHQHWVZHUHUHSRUWHG
for prophylaxis compared with no prophylaxis, in
particular in babies born to women with known infection
DSSUR[LPDWHO\UHGXFWLRQLQFRQMXQFWLYLWLVZLWK
SURSK\OD[LVXVLQJGLHUHQWPHGLFDWLRQV7KHEHQHWV
See Annex C for list of references of reviewed evidence,
ZLWKGLHUHQWPHGLFDWLRQVDUHVLPLODUKRZHYHUWKHORZ
and Web annex D for details of the evidence reviewed,
WRYHU\ORZTXDOLW\HYLGHQFHLQGLFDWHVWKDWWKHEHQHWV
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
of tetracycline hydrochloride, erythromycin or povidone
IUDPHZRUNVSS
5(&200(1'$7,21
For all neonates, the WHO STI guideline recommends
topical ocular prophylaxis for the prevention of
gonococcal and chlamydial ophthalmia neonatorum.
Strong recommendation, low quality evidence
RECOMMENDATION 7
For ocular prophylaxis, the WHO STI guideline suggests
one of the following options for topical application to
both eyes immediately after birth:
tetracycline hydrochloride 1% eye ointment
HU\WKURP\FLQH\HRLQWPHQW
iodine may be slightly greater than for silver nitrate.
Few data are available for the incidence of non-
infectious conjunctivitis after prophylaxis or no
prophylaxis. Low quality evidence shows a slight
UHGXFWLRQRUOLWWOHGLHUHQFHDQGLQGLFDWHVWKDW
EHWZHHQDQGSHULQIDQWVKDYHQRQLQIHFWLRXV
FRQMXQFWLYLWLVDIWHUDSSOLFDWLRQRIGLHUHQWSURSK\ODFWLF
medications. There is little evidence relating to patient
values and preferences, but the GDG agreed that
WKHUHZRXOGOLNHO\EHOLWWOHGLHUHQFHLQWKHKLJKYDOXH
placed on avoiding long-term consequences of both
gonococcal and chlamydial conjunctivitis. The GDG also
DJUHHGWKDWWKHUHZRXOGEHOLWWOHHHFWRQDFFHSWDELOLW\
equity and feasibility, as prophylaxis is currently used
in many countries. The GDG reported that alcohol-
based povidone iodine has erroneously been used
SRYLGRQHLRGLQHVROXWLRQZDWHUEDVHG
as prophylaxis resulting in serious harm to babies.
silver nitrate 1% solution Silver nitrate is the most expensive prophylaxis option.
chloramphenicol 1% eye ointment.
,QVXPPDU\WKHUHDUHODUJHEHQHWVIRUSURSK\OD[LVWR
Conditional recommendation, low quality evidence SUHYHQWRSKWKDOPLDQHRQDWRUXPDQGWKHVHEHQHWV
outweigh the risk of non-infectious conjunctivitis due
Remarks: 5HFRPPHQGDWLRQVDQGDSSO\WRWKH
to prophyalaxis with any of the topical medications.
prevention of both chlamydial and gonococcal
Some topical medications may provide greater
ophthalmia neonatorum. Cost and local resistance
protection (tetracycline hydrochloride, erythromycin
to erythromycin, tetracycline and chloramphenicol
in gonococcal infection may determine the choice of
medication. Caution should be taken to avoid touching
eye tissue when applying the topical treatment and
to provide a water-based solution of povidone iodine.
RUSRYLGRQHLRGLQHEXWDOODUHIHDVLEOHWRSURYLGH
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
LQFOXGLQJHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
Alcohol-based povidone iodine solution must not be IUDPHZRUNVSS
applied. The topical application should be administered
immediately after birth.
Research implications: The prevalence of gonococcal
ophthalmia should be determined given the high
prevalence of maternal gonorrhoea in some settings.
The state of resistance to the medications should be
explored and it should be established whether these
organisms would be killed by ocular prophylaxis despite
resistant strains being established in the organisms.
0RUHUHVHDUFKFRPSDULQJWKHEHQHWVDQGKDUPV
RIWKHGLHUHQWPHGLFDWLRQVLVQHHGHGLQSDUWLFXODU
comparisons with chloramphenicol.
22 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

REFERENCES

1. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N et al. Global estimates of the
SUHYDOHQFHDQGLQFLGHQFHRIIRXUFXUDEOHVH[XDOO\WUDQVPLWWHGLQIHFWLRQVLQEDVHGRQV\VWHPDWLF
UHYLHZDQGJOREDOUHSRUWLQJ3/R62QHHGRLMRXUQDOSRQH

2. Harryman L, Blee K, Horner P. Chlamydia trachomatis and non-gonococcal urethritis. Medicine.

GRLMPSPHG

3. Haggerty CL, Gottlieb SL, Taylor BD, Low N, Xu F, Ness RB. Risk of sequelae after Chlamydia
trachomatisJHQLWDOLQIHFWLRQLQZRPHQ-,QIHFW'LV6XSSO6GRL

4. Bbar C, de Barbeyrac B. Genital Chlamydia trachomatis infections. Clin Microbiol Infect.

GRLM[

 +HUULQJ$5LFKHQV-/\PSKRJUDQXORPDYHQHUHXP6H[7UDQVP,QIHFW6XSSOLY

GRLVWL

  DERUDWRU\GLDJQRVLVRIVH[XDOO\WUDQVPLWWHGLQIHFWLRQVLQFOXGLQJKXPDQLPPXQRGHFLHQF\
/
YLUXV*HQHYD:RUOG+HDOWK2UJDQL]DWLRQKWWSDSSVZKRLQWLULV
ELWVWUHDPBHQJSGIDFFHVVHG0D\

7. Guidelines for the management of sexually transmitted infections. Geneva: World Health
2UJDQL]DWLRQKWWSZZZZKRLQWKLYSXEVWLHQ67,*XLGHOLQHVSGIDFFHVVHG
0D\

8. Manhart LE, Gillespie CW, Lowens MS, Khosropour CM, Colombara DV, Golden MR et al. Standard
treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized
FRQWUROOHGWULDO&OLQ,QIHFW'LVGRLFLGFLV

 :+2KDQGERRNIRUJXLGHOLQHGHYHORSPHQWQGHGLWLRQ*HQHYD:RUOG+HDOWK2UJDQL]DWLRQ
KWWSZZZZKRLQWNPVKDQGERRNBQGBHGSGIDFFHVVHG0D\

 0
 DQDJHPHQW6FLHQFHVIRU+HDOWK06+DQG:RUOG+HDOWK2UJDQL]DWLRQ:+2,QWHUQDWLRQDOGUXJ
SULFHLQGLFDWRUJXLGHHGLWLRQXSGDWHGDQQXDOO\0HGIRUG0$06+KWWSDSSVZKRLQW
PHGLFLQHGRFVGRFXPHQWVVHQVHQSGIDFFHVVHG0D\

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 , QWURGXFLQJ:+2VUHSURGXFWLYHKHDOWKJXLGHOLQHVDQGWRROVLQWRQDWLRQDOSURJUDPPHVSULQFLSOHV
DQGSURFHVVHVRIDGDSWDWLRQDQGLPSOHPHQWDWLRQ*HQHYD:RUOG+HDOWK2UJDQL]DWLRQKWWS
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 +2HVVHQWLDOPHGLFLQHVOLVWWKHGLWLRQ*HQHYD:RUOG+HDOWK2UJDQL]DWLRQKWWSZZZ
ZKRLQWVHOHFWLRQBPHGLFLQHVFRPPLWWHHVH[SHUW(0/BB),1$/BDPHQGHGB$8*SGI
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 23

ANNEX A:
STI GUIDELINE DEVELOPMENT TEAMS

WHO STI STEERING COMMITTEE

WHO regional STI focal points Region

1. Massimo Ghidinelli 5HJLRQRIWKH$PHULFDV$05
:DVKLQJWRQ'&8QLWHG6WDWHVRI$PHULFD86$
2. Lali Khotenashvili (XURSHDQ5HJLRQ(85
Copenhagen Denmark
3. <LQJ5X/R :HVWHUQ3DFLF5HJLRQ:35
Manila Philippines
4. Frank Lule $IULFDQ5HJLRQ$)5
Brazzaville Congo
5. Razia Pendse 6RXWK(DVW$VLD5HJLRQ6($5
and New Delhi India
Ornella Lincetto WHO Country Representative, Bhutan
 Hamida Khattabi and Gabriela Reidner (DVWHUQ0HGLWHUUDQHDQ5HJLRQ(05
Cairo Egypt
WHO headquarters Department and Team
7. Moazzam Ali Department of Reproductive Health and Research
Human Reproduction Team
8. Avni Amin Department of Reproductive Health and Research
Adolescents and at-Risk Populations
9. Rachel Baggaley Department of HIV/AIDS
Key Populations and Innovative Prevention
 9HQNDWUDPDQ&KDQGUD0RXOL Department of Reproductive Health and Research
Adolescents and at-Risk Populations
11. Jane Ferguson Department of Maternal, Newborn, Child and Adolescent
+HDOWK5HVHDUFKDQG'HYHORSPHQW
12. Mario Festin Department of Reproductive Health and Research
Human Reproduction Team
13. 0DU\/\Q*DHOG Department of Reproductive Health and Research
Human Reproduction Team
14. Antonio Gerbase Department of HIV/ AIDS
Key populations and Innovative Prevention
15. Sami Gottlieb Department of Reproductive Health and Research
Human Reproduction Team
 Silvo Paolo Mariotti Department of Noncommunicable Disease and
Mental Health
Management of Noncommunicable Diseases, Disability,
Violence and Injury Prevention
Blindness Deafness Prevention, Disability and Rehabilitation
17. Frances McConville Department of Maternal, Newborn, Child and
Adolescent Health
24 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

18. Lori Newman Department of Reproductive Health and Research

Human Reproduction Team
19. Annette Mwansa Nkowane Department of Health Workforce
 Anita Sands Essential Medicines and Health Products,
3UHTXDOLFDWLRQ7HDP
21. Igor Toskin Department of Reproductive Health and Research
Human Reproduction Team
22. Marco Vitoria Department of HIV/AIDS
Treatment and Care
WHO STI Secretariat Department and Team
23. Ian Askew Department of Reproductive Health and Research
Human Reproduction Team
24. 1DWKDOLH%URXWHWFROHDGRIWKH Department of Reproductive Health and Research
development process) Human Reproduction Team
25. James Kiarie Department of Reproductive Health and Research
Human Reproduction Team
 Lee Sharkey Department of Reproductive Health and Research
Human Reproduction Team
27. Teodora Elvira Wi (lead of the Department of Reproductive Health and Research
development process) Human Reproduction Team

METHODOLOGIST
Nancy Santesso
Department of Clinical Epidemiology and Biostatistics
McMaster University
0DLQ6WUHHW:HVW
Hamilton, Ontario L8N 3Z5
Canada

SYSTEMATIC REVIEW TEAM:

MCMASTER UNIVERSITY
Team lead: Nancy Santesso
Team members: Housne Begum, Janna-Lina Kerth,
Gian Paolo Morgano, Kristie Poole, Nicole Schwab,
Matthew Ventresca, Yuan Zhang, Andrew Zikic
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 25

STI GUIDELINE DEVELOPMENT GROUP

Chairpersons: Judith Wasserheit, Holger Schnemann, Patricia Garcia

Name and address Region Sex

1. <DZ6D[$GX6DUNRGLH AFR M
School of Medical Sciences
.ZDPH1NUXPDK8QLYHUVLW\RI6FLHQFHDQG7HFKQRORJ\.1867
PO Box 1934, Bantama Kumasi
Ghana
2. Andrew Amato EUR M
European Centre for Disease Prevention and Control
Tomtebodavgen 11a
171 83 Stockholm
Sweden
3. Gail Bolan AMR F
Centers for Disease Control and Prevention
&OLIWRQ5G
$WODQWD*$
USA
4. John Changalucha AFR M
National Institute for Medical Research
Mwanza Medical Research Centre
32%R[
Mwanza
Tanzania
5. ;LDQJ6KHQJ&KHQ WPR M
National Center for STD Control
Chinese Academy of Medical Sciences and Peking Union Medical College
12 Jiangwangmiao Street
1DQMLQJ
China
 Harrel Chesson AMR M
Division of STI Prevention
Centers for Disease Control and Prevention
&OLIWRQ5G
$WODQWD*$
USA
7. Craig Cohen AMR M
University of California, San Francisco
%HDOH6WUHHW6XLWH
San Francisco, CA 94117
USA
8. Francisco Garcia AMR M
Pima County Health Department
6&RXQWU\&OXE5RDG
6XLWH
Tucson, AZ 85714
USA
26 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

9. 3DWULFLD*DUFLD&R&KDLU AMR F

School of Public Health and Administration
Universidad Peruana Cayetano Heredia
$YH+RQRULR'HOJDGR
31 AP, 4314 Lima
Peru
 Suzanne Garland WPR F
5R\DO:RPHQV+RVSLWDO/HYHO
%OGJ%LR,QVWLWXWH
Flemington Road, Parkville
Victoria
Australia
11. Sarah Hawkes EUR F
University College London
Institute for Global Health
London
United Kingdom
12. Mary Higgins EUR F
International Confederation of Midwives
/DDQYDQ0HHUGHUYRRUW
2517 AN The Hague
The Netherlands
13. King Holmes AMR M
Department of Global Health and Department of Medicine
University of Washington
Harborview Medical Center
325 9th Ave., Box 359931
6HDWWOH:$
USA
14. -HUH\.ODXVQHU AMR M
Division of Infectious Diseases and Program in Global Health
'DYLG*HHQ6FKRRORI0HGLFLQHDQG)LHOGLQJ6FKRRORI3XEOLF+HDOWK
University of California, Los Angeles
USA
15. David Lewis WPR M
Western Sydney Sexual Health Centre
Marie Bashir Institute for Infectious Diseases and Biosecurity
Sydney Medical School
Westmead, University of Sydney
Sydney
Australia
 Nicola Low EUR F
Epidemiology and Public Health
University of Bern
Institute of Social and Preventive Medicine
Finkenhubelweg 11
%HUQ
Switzerland
17. David Mabey EUR M
Communicable Diseases
/RQGRQ6FKRRORI+\JLHQHDQG7URSLFDO0HGLFLQH/6+70
Keppel Street
London WC1E 7HT
United Kingdom
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 27

18. Angelica Espinosa Miranda AMR F

Ncleo de Doenas Infecciosas
Universidade Federal do Espirito Santo
Av. Marechal Campos
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9LWULD(6&(3
Brazil
19. Nelly Mugo AFR F
Kenya Medical Research Institute
Mbagathi Rd.
32%R[1DLUREL
Kenya
 Saiqa Mullick AFR F
Implementation Science
University of the Witwatersrand
Hillbrow Health Precinct
Hillbrow, Johannesburg
South Africa
21. Francis Ndowa AFR M
7KDPHV5RDG
Vainona, Harare
Zimbabwe
22. Joel Palefsky AMR M
Division of Infectious Diseases
%R[
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University of California, San Francisco
San Francisco, CA 94143
USA
23. .HLWK5DGFOLH EUR M
European STI Guidelines Project
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Royal Society of Medicine
1 Wimpole Street
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United Kingdom
24. Ulugbek Sabirov EUR M
National STI Program
Republican Center for Dermato-Venereology
Tashkent
Uzbekistan
25. +ROJHU6FKQHPDQQ&R&KDLU AMR M
Department of Clinical Epidemiology and Biostatistics
McMaster University
0DLQ6WUHHW:HVW
Hamilton, Ontario L8N 3Z5
Canada
 Richard Steen EUR M
Localit Cassaluvo
Diano San Pietro
,PSHULD
Italy
28 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

27. Judith Stephenson EUR F

University College London
Gower Street
London
United Kingdom
28. Magnus Unemo EUR M
Department of Laboratory Medicine
Microbiology
rebro University Hospital
6(UHEUR
Sweden
29. Bea Vuylsteke EUR F
Institute of Tropical Medicine
Nationalestraat 155
$QWZHUS
Belgium
 Anna Wald AMR F
University of Washington
Virology Research Clinic
Harborview Medical Center
325 9th Ave, Box 359928
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31. -XGLWK:DVVHUKHLW&R&KDLU AMR F
Department of Global Health
Professor of Global Health and Medicine
Adjunct Professor of Epidemiology
University of Washington
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32. Thomas Wong AMR M
Division of Community Acquired Infections
Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 29

STI Guideline Development Group: Working group for chlamydia

1. Andrew Amato
2. Harrell Chesson
3. Craig Cohen
4. Patricia Garcia
5. Nicola Low
 David Mabey
7. Angelica Miranda
8. Francis Ndowa
9. .HLWK5DGFOLH
 Judith Stephenson
11. Magnus Unemo
12. Bea Vuylsteke
13. Judith Wasserheit

STI External Review Group: Working group for chlamydia

Name and address Region Sex

1. /DLWK$EX5DGGDG EMR M
Biostatistics, Epidemiology and Biomathematics Research Core
Infectious Disease Epidemiology Group
Department of Public Health
Weill Cornell Medical College
Cornell University
Qatar Foundation Education City
Qatar
2. $GHOH%HQDNHQ6FKZDUW] AMR F
Ministry of Health
STI, AIDS and Viral Hepatitis Department
SAF Sul Trecho 2, Ed. Premium
Torre I, Trreo, Sala 12
%UDVOLD')
Brazil
3. Mircea Betiu EUR M
1LFRODH7HVWHPLDQX6WDWH8QLYHUVLW\RI0HGLFLQHDQG3KDUPDF\
Republic of Moldova
4. Anupong Chitwarakorn SEAR M
Department of Diseases Control
Bureau of AIDS, TB and STIs
Ministry of Public Health
Nonthaburi
Thailand
30 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

5. Anjana Das SEAR F

)+,
New Delhi
India
 Carolyn Deal AMR F
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United States Department of Health and Human Services
National Institutes of Health
Washington, DC
USA
7. 0DUJDUHW*DOH5RZH AMR F
Professional Guidelines and Public Health Practice Division
Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada
Ottawa, Ontario
Canada
8. William M. Geisler AMR M
Medicine and Epidemiology
University of Alabama at Birmingham
Division of Infectious Diseases
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9. Amina El Kettani EMR F
'LUHFWLRQGHO(SLGPLRORJLH
Service des MST-sida
Ministry of Health
71 Avenue Ibn Sinaa, Agdal
Rabat
Morocco
 Ahmed Latif AFR M
Public Health Consultant
Zimbabwe
11. Mizan Kiros AFR M
Disease Prevention and Control Directorate
Federal Ministry of Health
Ethiopia
12. Philippe Mayaud EUR M
Clinical Research Department
)DFXOW\bRI,QIHFWLRXVDQG7URSLFDO'LVHDVHV
London School of Hygiene and Tropical Medicine
Keppel Street
London WC1E 7HT
United Kingdom
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 31

13. David McCartney EUR M

Research and Technical Support
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Population Council
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 Khantanouvieng Sayabounthavong WPR M
Ministry of Health
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32 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

ANNEX B:
DETAILED METHODS FOR GUIDELINE DEVELOPMENT

QUESTIONS AND OUTCOMES E 67,FRQGLWLRQVQRWLQFOXGHGLQWKH:+267,

guidelines that were selected by the GDG to be
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guidelines that were not updated but were selected
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diagnosis is not often made in the majority of
settings, or it is unlikely that there is new information
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United Kingdom national guidelines for the
management of sexually transmitted infections,
British Association for Sexual Health and HIV
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European sexually transmitted infections guidelines,
International Union of Sexually Transmitted
guidelines that are part of other national guidelines,
but were not selected by the GDG to be included
in the new WHO STI guidelines. These conditions
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of settings, or it is unlikely that new research or
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National guideline for the management and control decided on the initial list of population, intervention,
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National guidelines on prevention, management of the four STI topic areas (i.e. gonorrhoea, chlamydia,
and control of reproductive tract infections including
sexually transmitted infections, Ministry of Health
and Family Welfare, Government of India,
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administered among subgroups of the GDG members
with expertise relating to the relevant STIs. The goal
of the surveys was to rank the population, interventions
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importance. The surveys required the members of
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guidelines11 that were selected by the GDG to be
reviewed and updated in the new WHO STI guidelines.
These are important and common conditions.

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 0HOERXUQH6H[XDO+HDOWK&HQWUH7UHDWPHQW*XLGHOLQHVDYDLODEOHDWKWWSPVKFRUJDX+HDOWK3URIHVVLRQDO06+&7UHDWPHQW*XLGHOLQHVWDELG'HIDXOW
 /HZLV'$0DUXPD(5HYLVLRQRIWKHQDWLRQDOJXLGHOLQHIRUUVWOLQHFRPSUHKHQVLYHPDQDJHPHQWDQGFRQWURORIVH[XDOO\WUDQVPLWWHGLQIHFWLRQVZKDWVQHZ
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 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
)RXUGLHUHQWSULRULW\67,VXUYH\VZHUHFRQGXFWHG
DQGHDFKVXUYH\DWWDLQHGDUHVSRQVHUDWH
from the STI subgroup members. The survey results for
priority populations, interventions and outcomes were
analysed. Populations, interventions and outcomes with
DQDYHUDJHUDWLQJRIWRZHUHFRQVLGHUHGFULWLFDO
WKRVHZLWKDQDYHUDJHUDWLQJRIWRZHUHFRQVLGHUHG
LPSRUWDQWDQGWKRVHZLWKDQDYHUDJHUDWLQJRIWR
3 were considered not important and were thus not
covered in the guidelines. Some questions that scored
less than 7 were kept for consistency.
33
The number of comparisons in each question was also
UHGXFHGRQO\FULWLFDOLQWHUYHQWLRQVZHUHFRPSDUHG
with each other and with important interventions.
Thus, important interventions were not compared
to each other.
A revised list of questions was then compiled and all
members of the full STI GDG were requested to review
the priority questions. The priority questions were
then revised based on this feedback.
6L[TXHVWLRQVZHUHLGHQWLHGIRUWKHXSGDWHRIWKH
chlamydial infections guideline. Each question is
framed using the PICO format (population, intervention,
FRPSDUDWRUDQGRXWFRPH(DFKTXHVWLRQFRUUHVSRQGV
to a recommendation.

PRIORITY QUESTIONS AND OUTCOMES

FOR CHLAMYDIA TRACHOMATIS
1. Uncomplicated genital (cervix, urethra) chlamydial
infections in adults and adolescents

Population Intervention Comparator Outcome

Adults and Azithromycin 1 g orally Doxycycline extended release Critical: Clinical cure,
adolescents with x 1 dose (5PJGDLO\[GD\V microbiological cure, STI
uncomplicated 'R[\F\FOLQHPJ (U\WKURP\FLQPJRUDOO\ FRPSOLFDWLRQVVLGHHHFWV
genital (cervix, twice daily x 7 days four times daily x 7 days (including allergy, toxicity,
XUHWKUD Erythromycin ethylsuccinate JDVWURFRPSOLDQFH
chlamydial (6PJRUDOO\IRXUWLPHV
Important: Quality of life, HIV
infections daily x 7 days
transmission and acquisition,
(U\WKURP\FLQPJRUDOO\
partner transmission
WZLFHGDLO\[GD\V
$PR[LFLOOLQPJRUDOO\
thrice daily x 7 days
Quinolones

2. Uncomplicated anorectal chlamydial infections in adults and adolescents,

excluding lymphogranuloma venereum (LGV)

Population Intervention Comparator Outcome

Adults and Azithromycin 1 g orally 'R[\F\FOLQH(5PJGDLO\ Critical: Clinical cure,
adolescents with x 1 dose x 7 days microbiological cure, STI
uncomplicated 'R[\F\FOLQHPJ (U\WKURP\FLQPJRUDOO\ FRPSOLFDWLRQVVLGHHHFWV
anorectal twice daily x 7 days four times daily x 7 days (including allergy, toxicity,
chlamydial (U\WKURP\FLQ(6PJRUDOO\ JDVWURFRPSOLDQFH
infections four times daily x 7 days
Important: Quality of life, HIV
H[FOXGLQJ/*9 (U\WKURP\FLQPJRUDOO\
transmission and acquisition,
WZLFHGDLO\[GD\V
partner transmission
$PR[LFLOOLQPJRUDOO\WKULFH
daily x 7 days
Quinolones
34 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

3ac. Chlamydia in pregnancy

Population Intervention Comparator Outcome

Pregnant women Azithromycin 1 g orally $PR[LFLOOLQPJRUDOO\WKULFH Critical: Fetal outcomes (e.g.
with chlamydia x 1 dose daily x 7 days
(U\WKURP\FLQPJ (U\WKURP\FLQPJRUDOO\
orally, four times daily x twice daily x 14 days
7 days (U\WKURP\FLQPJRUDOO\
four times daily x 14 days
(U\WKURP\FLQ(6PJRUDOO\
four times daily x 7 days
WHUDWRJHQLFLW\WR[LFLW\IHWDO
loss, prematurity/low birth
weight, chorioamnionitis,
infant pneumonitis/neonatal
ophthamia, postpartum
endometritis, microbiological
FXUHVLGHHHFWVLQFOXGLQJ
(U\WKURP\FLQ(6PJRUDOO\ DOOHUJ\WR[LFLW\JDVWURFOLQLFDO
four times daily x 14 days FXUHV\PSWRPVFRPSOLDQFH
Important: HIV acquisition,
quality of life, transmission
to partner

4. Lymphogranuloma venereum (LGV) in all populations

Population Intervention Comparator Outcome

Adults and 'R[\F\FOLQHPJ 'R[\F\FOLQHPJWZLFHGDLO\ Critical: Clinical cure,
adolescents with twice daily x 21 days x 14 days microbiological cure
LGV Azithromycin 1 g orally (U\WKURP\FLQEDVHPJ
Important: STI complications,
once a week x 13 orally, four times daily x 21 days
VLGHHHFWVLQFOXGLQJDOOHUJ\
weeks
WR[LFLW\JDVWURTXDOLW\RI
life, HIV transmission and
acquisition, compliance, LGV
transmission to partner

5. Ophthalmia neonatorum treatment

Population Intervention and comparator Outcome

Neonates Erythromycin in 4 divided doses orally, daily x 14 days: Critical: Clinical cure,
with neonatal bPJNJGD\bPJNJGD\RUbPJNJGD\ microbiological cure,
conjunctivitis $]LWKURP\FLQPJNJGD\RUDOO\GDLO\[GD\V &RPSOLFDWLRQVVLGHHHFWV
7ULPHWKRSULPbPJVXOIDbPJRUDOO\WZLFHGDLO\ (including allergy, toxicity,
[bGD\V JDVWURDQWLPLFURELDO
resistance, compliance

6 and 7. Ophthalmia neonatorum prophylaxis

Population Intervention and comparator Outcome

Neonates at risk Ophthalmic ointment in each eye at the time of delivery: Critical: Absence of
for ophthalmia (U\WKURP\FLQ conjunctivitis, keratitis,
neonatorum Silver nitrate 1% complications, blindness,
Chloramphenicol corneal scarring, antimicrobial
Tetracycline 1% resistance
Povidone iodine 2.5%
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 35

REVIEWS OF THE EVIDENCE

SEARCH FOR EVIDENCE FOR EFFECTS Primary studies were searched for in the Cochrane
OF INTERVENTIONS &HQWUDO5HJLVWHURI&RQWUROOHG7ULDOV&(175$/
MEDLINE and Embase databases. Search end dates for
To avoid duplication of reviews that have been each PICO question varied between March and October
previously published, evidence was searched using VHHOLVWEHORZ7KHVWUDWHJLHVLQFOXGHGVHDUFKLQJ
DKLHUDUFKLFDODSSURDFK7KHWHDPUVWVHDUFKHGIRU for subject headings and text words that included
synthesized evidence then searched the primary FKODP\GLDDQGVSHFLFLQWHUYHQWLRQVHJPHGLFDWLRQ
studies for all the factors needed to complete the QDPHVDQGFODVVHV$GGLWLRQDOVWUDWHJLHVLQFOXGHG
evidence-to-decision framework for each question checking reference lists and consulting with the GDG
LHEHQHWVDQGKDUPVSDWLHQWYDOXHVDFFHSWDELOLW\ for any missed articles. We searched for RCTs for critical
IHDVLELOLW\HTXLW\DQGFRVWV and important outcomes, and non-randomized studies
The hierarchical approach consisted of identifying for critical outcomes when no evidence was available
pre-existing synthesized evidence, including from from RCTs.
previously published guidelines that included systematic Search end dates:
reviews of the literature. When synthesized evidence
DERXWEHQHWVDQGKDUPVIRUDQLQWHUYHQWLRQZDVQRW 8
 QFRPSOLFDWHGJHQLWDOFHUYL[XUHWKUDFKODP\GLDO
available or the synthesized evidence was not up to date, LQIHFWLRQVLQDGXOWVDQGDGROHVFHQWVXSWR0DUFK
a new systematic review of randomized controlled trials Uncomplicated anorectal chlamydial infections
5&7VDQGQRQUDQGRPL]HGVWXGLHVZDVFRQGXFWHG
The search strategies were developed by an information
specialist trained in systematic reviews. The strategies
included the use of keywords from the controlled
vocabulary of the database and text words based
on the PICO questions. There were no restrictions
based on language, publication status or study design.
RCTs were included for critical and important outcomes,
and non-randomized studies for critical outcomes
when no evidence was available from RCTs. Additional
strategies included contacting Cochrane review groups
and authors of study protocols.
The Cochrane Library suite of databases (Cochrane
Database of Systematic Reviews [CDSR], Database
RI$EVWUDFWVRI5HYLHZVRI(HFWV>'$5(@+HDOWK
Technology Assessment [HTA] database and the
H[FOXGLQJ/*9LQDGXOWVDQGDGROHVFHQWVXSWR
-XQH
&
 KODP\GLDLQSUHJQDQF\XSWR-XQHXSWR
'HFHPEHUIRUQRQUDQGRPL]HGFRPSDUDWLYH
studies
Lymphogranuloma venereum in all populations:
XSWR-XQH
2SKWKDOPLDQHRQDWRUXPWUHDWPHQWXSWR0D\
Ophthalmia neonatorum prevention: up to
2FWREHU
$PHULFDQ&ROOHJHRI3K\VLFLDQV>$&3@-RXUQDO&OXE
was searched for published systematic reviews and
SURWRFROVIURPWR
Search strategy:
1. chlamydia.mp.
2. trachomatis.mp.
3. ct infection*.tw.
4. or/1-3
36 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS
SCREENING STUDIES, DATA EXTRACTION
AND ANALYSIS
Two researchers independently screened titles and
DEVWUDFWVRIV\VWHPDWLFUHYLHZVLGHQWLHGWKURXJK
database searching to determine studies eligible for
inclusion in the analysis. Disagreements were resolved
by discussing study inclusion with a third member of
the research team. Data were extracted using a pilot-
tested form for patient characteristics (including the
PATIENT VALUES AND PREFERENCES,
ACCEPTABILITY, EQUITY AND FEASIBILITY
Studies on patient values and preferences, acceptability,
equity and feasibility were searched for and screened
using two methods. First, while screening studies for
WKHHHFWVRIWUHDWPHQWVDQGFRVWVWZRLQYHVWLJDWRUV
LGHQWLHGVWXGLHVRISRWHQWLDOUHOHYDQFHLQWKHVHDUHDV
Secondly, a separate search was conducted in MEDLINE,
(PEDVHDQG3V\F,1)2IURP-DQXDU\WR-XO\
VXEJURXSVLGHQWLHGE\WKH*'*GLDJQRVLVWUHDWPHQW 7H[WZRUGVDQGNH\ZRUGVIRUWKHGLHUHQW67,VZHUH
GRVHVFKHGXOHHWFVHWWLQJIROORZXSDQGRXWFRPHV
Two investigators independently abstracted data.
Risk of bias of each study was also assessed using risk
of bias tools appropriate for RCTs (http://handbook.
cochrane.org/chapter_8/8_assessing_risk_of_bias_
used in combination with words such as preference,
adherence, satisfaction, attitudes, health utilities
and value, equity and feasibility. The results
LQFOXGHGXQLTXHUHIHUHQFHV7ZRLQYHVWLJDWRUV
VFUHHQHGWKHVWXGLHVDQGVWXGLHVZHUHLGHQWLHG
LQBLQFOXGHGBVWXGLHVKWPDQGXVLQJWKH5LVN2I%LDV,Q for full text retrieval. Any study design was included
1RQUDQGRPL]HG6WXGLHVRI,QWHUYHQWLRQV52%,16, that addressed equity or feasibility. In addition,
SUHYLRXVO\FDOOHG$&52%$7WRROWRDVVHVVQRQ when adherence was measured in RCTs or non-
UDQGRPL]HGVWXGLHVZZZULVNRIELDVLQIR
7RPHDVXUHWKHWUHDWPHQWHHFWWKHGDWDZHUH
analysed using RevMan 5.2.12
For dichotomous outcomes, we calculated relative risks
ZLWKFRQGHQFHLQWHUYDOVHJULVNUDWLRVDQGRGGV
randomized studies, the data were collected,
V\QWKHVL]HGDQGSUHVHQWHGLQWKHHYLGHQFHSUROHV
for each PICO question.
The following study designs were included:
a. Patient utilities and health status values studies:
UDWLRVE\SRROLQJUHVXOWVIURP5&7VDQGSRROLQJUHVXOWV These studies examine how patients value alternative
IURPQRQUDQGRPL]HGVWXGLHVXVLQJWKHUDQGRPHHFWV health states and their experiences with treatment.
PRGHO0RGHUDWHWRKLJKKHWHURJHQHLW\,!ZDV The measurement techniques used can include:
H[SORUHG(HFWVZHUHFRQYHUWHGWRDEVROXWHHHFWV VWDQGDUGJDPEOHWLPHWUDGHRYLVXDODQDORJXH
XVLQJWKHFDOFXODWHGUHODWLYHHHFWDQGDUHSUHVHQWDWLYH scale, or mapping results based on generic surveys
EDVHOLQHULVNDJUHHGXSRQE\WKH*'*:KHQQRQ (XUR4ROYHGLPHQVLRQVKHDOWKTXHVWLRQQDLUH>(4
randomized studies with one group were included, a '@RUWKH,WHP6KRUW)RUP+HDOWK6XUYH\>6)@
SRROHGSURSRUWLRQRIDQHYHQWDQGFRQGHQFHLQWHUYDOV RUVSHFLFPHDVXUHPHQWHJ6W*HRUJH5HVSLUDWRU\
were calculated across the studies using the generic 4XHVWLRQQDLUHRIKHDOWKUHODWHGTXDOLW\RIOLIH
inverse variance. For continuous outcomes, a mean
E 6WXGLHVRISDWLHQWVGLUHFWFKRLFHVZKHQSUHVHQWHG
GLHUHQFHRUDVWDQGDUGL]HGPHDQGLHUHQFHZKHQ
with decision aids: These studies examine the
VWXGLHVXVHGGLHUHQWVFDOHVWRPHDVXUHDQRXWFRPH
choices patients make when presented with decision
was calculated. When possible, the forest plots of the
aids for management options (i.e. probabilistic
meta-analyses were made available to the GDG.
WUDGHRWHFKQLTXHV
When data could not be pooled across studies, narrative
c. Studies on non-utility measurement of health states:
synthesis methods were used (see http://methods.
7KHVHVWXGLHVTXDQWLWDWLYHO\H[DPLQHSDWLHQWV
FRFKUDQHRUJVLWHVPHWKRGVFRFKUDQHRUJOHV
views, attitudes, satisfaction or preferences through
0FNHQ]LHSGI5HVXOWVZHUHSUHVHQWHGLQWDEOHV
TXHVWLRQQDLUHVRUVFDOHVWKHVHDUHQHLWKHUXWLOLW\
HJPHGLDQHHFWVZLWKLQWHUTXDUWLOHUDQJHVRUZHUH
VWXGLHVQRUVWXGLHVRISDWLHQWVUHVSRQVHVWR
QDUUDWLYHO\GHVFULEHGE\GLUHFWLRQRIWKHHHFWRUE\
decision aids. Patients are asked about how
VWDWLVWLFDOVLJQLFDQFHDVUHSRUWHGLQWKHSULPDU\VWXG\
desirable or aversive a particular outcome is for
them. This category includes some studies that
use questionnaires or scales.
G 4XDOLWDWLYHVWXGLHV7KHVHVWXGLHVH[SORUHSDWLHQWV
views, attitudes, satisfactions or preferences related
WRGLHUHQWWUHDWPHQWRSWLRQVEDVHGRQTXDOLWDWLYH
research methods including focus group discussions,
interviews, etc.

 5HY0DQ&RPSXWHU3URJUDP&RSHQKDJHQ7KH1RUGLF&RFKUDQH&HQWHU

7KH&RFKUDQH&ROODERUDWLRQ
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 37

From the search, we included 17 studies reporting

LQIRUPDWLRQUHODWLQJWRGLHUHQW67,V,QPDQ\LQVWDQFHV
data for all infections informed the evidence for
FKODP\GLDVSHFLFDOO\

RESOURCES
We searched the published literature for evidence
on use of resources and obtained data on direct costs
of medicines.
%DVHGRQWKHOLVWRISRVVLEOHWUHDWPHQWVLGHQWLHGE\
the GDG, an estimate of the cost associated with each
alternative was calculated. This costing estimate refers
only to the actual market price of the medication and
does not include the costs of other resources that
could be involved, such as syringes, injection time or
needle disposal.
Data were presented in a table and included: treatment,
dose per day, treatment duration, days, medicine cost
per dose, medicine cost per full course of treatment,
DQGRISURFXUHPHQWFRVWVDVGHQHGLQWKH
06+,QWHUQDWLRQDOGUXJSULFHLQGLFDWRUJXLGH13$QDO
price for a full course of treatment for each medicine by
dosage was calculated as the number of doses per day,
multiplied by the number of days of the treatment, plus
25% of the procurement costs for the medicines used.
The unit price of the medicine was obtained from the
PHGLDQSULFHVSURYLGHGLQWKH06+,QWHUQDWLRQDO
drug price indicator guide and information available
on the Internet. In order to determine a precise and
reliable estimate, the price per unit (all expressed in
86GROODUVZDVSURYLGHGRQO\ZKHQWKHLQIRUPDWLRQ
available matched the dosage of interest (grams per
SLOORUXQLWVSHUYLDO1RFDOFXODWLRQVZHUHPDGH
based on assumptions about the cost per unit of
hypothetical packaging not listed in the directory.
The major medical databases were also searched
(MEDLINE, Embase and the Cochrane Library for
Economic Evaluation and Technology Assessment
UHSRUWVIURP-DQXDU\WR-XO\7KUHHVWXGLHV
DGGUHVVHGWKHFRVWHHFWLYHQHVVRIGLHUHQWWUHDWPHQW
strategies for chlamydia. In addition, while screening
VWXGLHVIRUWKHHHFWVRIWUHDWPHQWVWZRLQYHVWLJDWRUV
DOVRLGHQWLHGVWXGLHVRISRWHQWLDOUHOHYDQFHIRUFRVWV
and abstracted data regarding possible resources to be
considered during the decision-making process.

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0HGIRUG0$0DQDJHPHQW6FLHQFHIRU+HDOWKKWWSHUFPVKRUJ
GPSJXLGHSGI'UXJ3ULFH*XLGHBSGIDFFHVVHG-XQH
38 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS

APPLYING THE GRADE APPROACH TO

MAKING THE RECOMMENDATIONS

EVIDENCE PROFILES MAKING THE RECOMMENDATIONS

$QHYLGHQFHSUROHZDVPDGHIRUHDFK3,&2TXHVWLRQ ,Q2FWREHUWKH*'*PHWWRPDNHWKH
XVLQJWKH*5$'(SURVRIWZDUHZZZJUDGHSURRUJ recommendations. This meeting was facilitated by
(DFKSUROHLQFOXGHGWKHFULWLFDODQGLPSRUWDQW two co-chairs one with expertise in GRADE and the
RXWFRPHVWKHUHODWLYHDQGDEVROXWHHHFWVDQGWKH other with clinical expertise of chlamydia. During the
quality of evidence according to the GRADE domains PHHWLQJWKHHYLGHQFHSUROHVDQGHYLGHQFHWRGHFLVLRQ
VHHWKH*5$'(KDQGERRN14%ULH\WKH*5$'(
approach assesses the quality of evidence for treatment
interventions using well-established criteria for
the design, risk of bias, inconsistency, indirectness,
LPSUHFLVLRQHHFWVL]HGRVHUHVSRQVHFXUYHDQG
RWKHUFRQVLGHUDWLRQVWKDWPD\DHFWWKHTXDOLW\RI
the evidence. Two investigators used the GRADE
approach to assess the quality and level of
FHUWDLQW\RIWKHHYLGHQFH7KHHYLGHQFHSUROHVIRU
each recommendation are available in Web annex D.
(9,'(1&(72'(&,6,21)5$0(:25.6
Evidence-to-decision frameworks were also developed
frameworks were presented by the methodologists.
The GDG discussed each GRADE criterion and judged
ZKLFKLQWHUYHQWLRQZDVIDYRXUHG7KHQDQDOGHFLVLRQ
and guideline recommendation was developed.
The goal was to arrive at agreement across all members
of the GDG and this was facilitated by the chairpersons
through discussion. When there was disagreement for
a criterion, it was noted in the evidence-to-decision
framework for the relevant judgement. If there was
GLVDJUHHPHQWIRUDQ\RIWKHQDOUHFRPPHQGDWLRQV
the plan was for the GDG to vote and the numbers to
be recorded. Because there was no disagreement
IRUDQ\RIWKHQDOUHFRPPHQGDWLRQVKRZHYHUYRWHV
were not taken or reported in these guidelines.
XVLQJ*5$'(SURVRIWZDUHZZZJUDGHSURRUJ
The GDG made a strong or conditional recommendation
Evidence-to-decision frameworks present the desirable
for or against each intervention and described special
DQGXQGHVLUDEOHHHFWVRIWKHLQWHUYHQWLRQVWKHYDOXH
circumstances in the remarks. Research implications
of the outcomes, the costs and resource use, the
were also developed and presented, based on the gaps
acceptability of the interventions to all stakeholders,
LGHQWLHGLQWKHHYLGHQFH)ROORZLQJWKHPHHWLQJWKH
the impact on health equity, and the feasibility of
UHFRPPHQGDWLRQVZHUHQDOL]HGYLDWHOHFRQIHUHQFH
implementation (i.e. the GRADE criteria for making
DQGQDODSSURYDOZDVREWDLQHGIURPWKH*'*PHPEHUV
GHFLVLRQV7KHHYLGHQFHWRGHFLVLRQIUDPHZRUNV
electronically. All decisions and discussions from the
are based on a population perspective for these
GDG for each recommendation are available in the
recommendations. All GRADE criteria were
evidence-to-decision frameworks in Web annex D.
considered from this perspective.

 6FKQHPDQQ+%URHN-*X\DWW*2[PDQ$HGLWRUV*5$'(KDQGERRN
+DPLOWRQ2QWDULR0F0DVWHU8QLYHUVLW\DQG(YLGHQFH3ULPH,QF
(http://gdt.guidelinedevelopment.org/central_prod/_design/client/
KDQGERRNKDQGERRNKWPODFFHVVHG0D\
 WHO GUIDELINES FOR THE TREATMENT OF CHLAMYDIA TRACHOMATIS 39

ANNEX C:
LISTS OF REFERENCES FOR REVIEWED EVIDENCE

RECOMMENDATION 1 11. Ibsen HH, Mller BR, Halkier-Srensen L, From E. Treatment

RIQRQJRQRFRFFDOXUHWKULWLVFRPSDULVRQRIRR[DFLQDQG
Treatments for adults and adolescents with
uncomplicated genital (cervix, urethra)
chlamydial infections
HU\WKURP\FLQ6H[7UDQVP'LV
12. Kitchen VS, Donegan C, Ward H, Thomas B, Harris JR, Taylor-
5RELQVRQ'&RPSDULVRQRIRR[DFLQZLWKGR[\F\FOLQHLQWKH
treatment of non-gonococcal urethritis and cervical chlamydial
LQIHFWLRQ-$QWLPLFURE&KHPRWKHU6XSSO'
Systematic review
13. Lauharanta J, Saarinen K, Mustonen MT, Happonen HP.
1. Pez-Canro C, Martinez-Martinez F, Alzate JP, Lethaby A, Gaitn Single-dose oral azithromycin versus seven-day doxycycline
HG. Antibiotics for treating genital Chlamydia trachomatis in the treatment of non-gonococcal urethritis in males. J
LQIHFWLRQLQPHQDQGQRQSUHJQDQWZRPHQSURWRFRO $QWLPLFURE&KHPRWKHU6XSSO(
&RFKUDQH'DWDEDVH6\VW5HY&'
14. Lister PJ, Balechandran T, Ridgway GL, Robinson AJ.
Comparison of azithromycin and doxycycline in the treatment
Included studies
of non-gonococcal urethritis in men. J Antimicrob Chemother.
1. Bowie WR, Yu JS, Fawcett A, Jones HD. Tetracycline in 6XSSO(
nongonococcal urethritis. Comparison of 2 g and 1 g daily
15. Manhart LE, Gillespie CW, Lowens MS, Khosropour CM,
IRUVHYHQGD\V%U-9HQHU'LV
Colombara DV, Golden MR, et al. Standard treatment regimens
2. Campbell WF, Dodson MG. Clindamycin therapy for Chlamydia for nongonococcal urethritis have similar but declining
trachomatisLQZRPHQ$P-2EVWHW*\QHFRO cure rates: a randomized controlled trial. Clin Infect Dis.
3. Cramers M, Kaspersen P, From E, Mller BR. Pivampicillin
compared with erythromycin for treating women with
genital Chlamydia trachomatis infection. Genitourin

 0
 DUWLQ'+0URF]NRZVNL7)'DOX=$0F&DUW\--RQHV
RB, Hopkins SJ, et al. A controlled trial of a single dose of
0HG azithromycin for the treatment of chlamydial urethritis and
cervicitis. The Azithromycin for Chlamydial Infections Study
4. Csng PA, Gundersen T, Anestad G. Doxycycline in the *URXS1(QJO-0HG
treatment of chlamydial urethritis: a therapeutic study.
3KDUPDWKHUDSHXWLFD 17. McCormack WM, Dalu ZA, Martin DH, Hook EW 3rd, Laisi R,
.HOO3HWDO7URYDR[DFLQ&KODP\GLDO8UHWKULWLV&HUYLFLWLV
5. Fong IW, Linton W, Simbul M, Thorup R, McLaughlin B, Rahm V, 6WXG\*URXS'RXEOHEOLQGFRPSDULVRQRIWURYDR[DFLQDQG
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prophylactic agents used for the prevention of gonococcal
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3. Mabry-Hernandez IR, Koenig HC. Ocular prophylaxis for
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1. Ali Z, Khadije D, Elahe A, Mohammad M, Fateme Z, 1. Hedberg K, Ristinen TL, Soler JT, White KE, Hedberg CW,
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 3HGLDWU,QIHFW'LV-

5. Brussieux J, Boisivon A, Thron HP, Faidherbe C, Machado 2. Isenberg SJ, Apt L, Wood M. A controlled trial of povidone iodine
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9. Hammerschlag MR, Cummings C, Roblin PM, Williams TH,
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of chlamydial and gonococcal conjunctivitis. N Engl J Med.
resistance in Neisseria gonorrhoeae. The Gonococcal Isolate
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