Improving HIV Prevention and Sexual and Reproductive Health Care in High Risk Women in Rwanda Using Lessons Learnt From Previous Rinda Ubuzima Projects
Conditions: Sexually Transmitted Disease, Bacterial Vaginosis, Vaginal Candidiasis, Urinary Tract Infections
Sponsor: Janneke van de Wijgert

6 June 2016 
 
1 
 
 
 
 
 
 
 
STUDY PROTOCOL 
 
Rwanda WISH Study 
(Women’s Improvement of Sexual and reproductive Health) 
 
 
Sponsor 
University of Liverpool
Study site 
Rinda Ubuzima
KN 50th Avenue (formerly Rue Akagera 716), Kiyovu, Kigali, Rwanda 
P.O. Box 4560, Kigali, Rwanda 
Tel: +250-252-503431 
Fax: +250-252-503389 
Chief investigator
Professor Janneke van de Wijgert, PhD MPH MSc
Institute of Infection and Global Health, University of Liverpool 
Ronald Ross Building, 8 West Derby Street, Liverpool L69 7BE 
Tel office: +44-151-795-9613; Tel mobile: +44-755-719-5108 
Email: j.vandewijgert@liverpool.ac.uk 
Principal Investigator
Stephen Agaba, MD
Rinda Ubuzima (see contact details above) 
Tel mobile: +250-788 357 866 
Email: agabakarema@yahoo.co.uk 
Funder 
European and Developing Countries Clinical Trials Partnership (EDCTP)
Funding period
1 Jan 2016 – 31 Dec 2017
Data collection period
1 Jul 2016 – 30 Jun 2017
Protocol version, date
Version: 0.4; Date: 6 June 2016
Most recent approved 
version, date 
Not applicable
Previous approved 
versions, dates 
Not applicable
 
Protocol Approval: 
Chief Investigator
Principal Investigator
Janneke van de Wijgert
Stephen Agaba
 
 
 
Signature 
Signature
Date: 6 June 2016
Date: 6 June 2016

6 June 2016 
 
2 
STATEMENT OF PROTOCOL COMPLIANCE AND CONFIDENTIALITY  
 
By signing this statement, the Principal Investigator agrees to: 
 
• 
Conduct the present study in full accordance with the most recent approved version of the 
protocol, within applicable timelines, according to the relevant standard operating procedures 
(SOPs) and in full agreement with all applicable regulations and the international guidelines 
regarding the conduct of clinical research. 
• 
Permit study-related monitoring, audits, independent ethics committee review, and regulatory 
inspections, providing direct access to source data/documents during and after the course of 
the study. 
• 
Make the protocol and all relevant related study documentation available to all physicians, 
nurse/counsellors, laboratory staff and other personnel who participate in conducting this study. 
Ensure that the study team receives adequate training so that they are fully informed and 
qualified to conduct the study. 
• 
Maintain all study documentation in accordance with the International Conference on 
Harmonisation Good Clinical Practice and other relevant guidelines or until the Chief Investigator 
stipulates in writing that maintenance is no longer required. 
 
The Principal Investigator also acknowledges that this protocol contains confidential information. As 
such, the information may not be disclosed to anyone except persons involved in implementation of the 
study, relevant ethics committees and relevant drug regulatory authorities, unless specific permission is 
granted in writing by the Chief Investigator, or disclosure is required by relevant laws and regulations.  
The Principal Investigator: 
• 
Authorises the Chief Investigator and her team at the University of Liverpool, Liverpool, UK, to 
have full access to all data pertinent to this study and to receive and test study specimens as 
described in detail in this protocol. 
• 
Understands that copies of all computerised databases will be kept and fully accessible by the 
study team at the UoL, the study team at Rinda Ubuzima, as well as third parties who have been 
given permission by the Chief Investigator and the Principal Investigator. 
• 
Acknowledges that scientific publications and other planned uses of the study data and study 
specimens will be governed by a separate data and specimens sharing policy, and will adhere to 
the agreements set forth in that policy. 
 
Principal Investigator:
Stephen Agaba 
 
 
 
6 June 2016 
Signature 
Date
 
 
 

6 June 2016 
 
3 
TABLE OF CONTENTS 
 
Statement of protocol compliance and confidentiality .......................................................................... 2 
Table of contents .................................................................................................................................... 3 
List of acronyms ...................................................................................................................................... 4 
1. 
Protocol team roster ....................................................................................................................... 5 
2. 
Synopsis ........................................................................................................................................... 6 
3. 
Introduction .................................................................................................................................... 8 
3.1 
Background .............................................................................................................................. 8 
3.2 
Rationale ................................................................................................................................ 11 
4. 
Study design, objectives and endpoints ........................................................................................ 11 
4.1 
Study design .......................................................................................................................... 11 
4.3 
Sample size ............................................................................................................................ 14 
4.4 
Randomisation and blinding .................................................................................................. 14 
5. 
Study population ........................................................................................................................... 14 
5.1 
Target population .................................................................................................................. 14 
5.2 
Eligibility criteria .................................................................................................................... 14 
5.3 
Recruitment ........................................................................................................................... 15 
5.4 
Retention and withdrawals ................................................................................................... 15 
6. 
Study procedures - Clinical ............................................................................................................ 16 
6.1 
Schedule of assessments ....................................................................................................... 16 
6.2 
Procedures first WISH study visit (Main Visit) ....................................................................... 16 
6.3 
Procedures any additional WISH study visits (Additional Visits) ........................................... 17 
7. 
Study procedures – Qualitative research ...................................................................................... 17 
8. 
Study procedures - Laboratory...................................................................................................... 18 
8.1 
Diagnostic tests...................................................................................................................... 18 
8.2 
Research tests ........................................................................................................................ 18 
9. 
Data management and analysis .................................................................................................... 19 
10. Ethical issues and procedures ....................................................................................................... 20 
10.1 
Ethical review ........................................................................................................................ 20 
10.2 
Burdens and benefits ............................................................................................................. 20 
10.3 
Compensation and insurance ................................................................................................ 20 
10.4 
Confidentiality ....................................................................................................................... 20 
10.5 
Informed consent procedures ............................................................................................... 21 
11. Investigational products ................................................................................................................ 21 
12. Other ............................................................................................................................................. 21 
12.1 
Funding .................................................................................................................................. 21 
12.2 
Study management and oversight ........................................................................................ 22 
12.3 
Protocol amendments ........................................................................................................... 22 
12.4 
Good clinical practice ............................................................................................................ 22 
12.5 
Study termination .................................................................................................................. 22 
12.6 
Dissemination of results ........................................................................................................ 22 
12.7 
Archiving ................................................................................................................................ 22 
13. References ..................................................................................................................................... 23 
14. Appendices .................................................................................................................................... 26 
14.1 
Schedule of assessments ....................................................................................................... 26 
14.2 
WISH clinical algorithms ........................................................................................................ 26 
14.3 
WISH treatment guidelines by etiologic or syndromic diagnosis .......................................... 26 
 
 
 

6 June 2016 
 
4 
LIST OF ACRONYMS 
 
ART
Antiretroviral therapy
ASSURED 
Affordable, sensitive, specific, user-friendly, rapid and robust, 
equipment-free and deliverable to end users 
BV 
Bacterial vaginosis 
(e)CRF  
(electronic) Case report form 
CT 
Chlamydia trachomatis 
DALY
Disability adjusted life years
EDCTP 
European and Developing Countries Clinical Trials Partnership
GBP
Great Britain Pound
GCP 
Good Clinical Practice 
GCLP 
Good Clinical Laboratory Practice 
hCG
Human chorionic gonadotropin
HIV 
Human immunodeficiency virus 
HPV
Human papillomavirus
HSV-2
Herpes simplex virus type 2
ICF 
Informed consent form
ICH 
International Conference on Harmonization 
IDI 
In-depth interview 
IGH
Institute of Infection and Global Health, UoL, Liverpool, UK
ITM
Institute of Tropical Medicine, Antwerp, Belgium
LGV
Lymphogranuloma venereum
M&E
Monitoring and evaluation
NG 
Neisseria gonorrhoea 
NPV
Negative predictive value
PCR 
Polymerase chain reaction 
(e)PIR
(electronic) participant identification register
PIS
Participant information sheet
POC(T) 
Point of care (test)
PPV
Positive predictive value
RU 
Rinda Ubuzima 
SOP 
Standard operating procedure 
SRH
Sexual and reproductive health
STI 
Sexually transmitted infection 
TV 
Trichomonas vaginalis 
UoL
University of Liverpool, Liverpool, UK
UK
United Kingdom
USA
United States of America
UTI
Urinary tract infection
VCT
Voluntary counselling and testing
WHO
World Health Organisation
 
 

6 June 2016 
 
5 
1. PROTOCOL TEAM ROSTER 
 
Rinda Ubuzima (RU), Kigali, 
Rwanda 
Study role
E-mail address
Stephen Agaba, MD
Principal Investigator 
agabakarema@yahoo.co.uk
Gilles Ndayisaba, MD
Co-Investigator (clinical)
ndayisaba@gmail.com
Mireille Uwineza, BSc
Study coordinator
uwinezamireille@yahoo.fr
Marie Michelle Umulisa, MA
Coordinator recruitment, 
outreach, and social science 
mariemichelleu@yahoo.fr
Lambert Mwambarangwe, BSc
Laboratory coordinator
mwambara2@yahoo.fr
Vincent Karangwa
Administrative oversight at 
RU 
karavinc@yahoo.fr
University of Liverpool (UoL), 
Liverpool, UK 
Study role
Email address
Janneke van de Wijgert, MD PhD 
MPH 
Chief Investigator 
j.vandewijgert@liverpool.ac.uk
Marijn Verwijs, MD
Project Manager
marijnverwijs@gmail.com
Institute of Tropical Medicine 
(ITM), Antwerp, Belgium 
Study role
Email address
Vicky Jespers, MD PhD MEpi
Co-Investigator (clinical)
vjespers@itg.be
Tania Crucitti, PhD PharmD
Co-investigator (laboratory)
tcrucitti@itg.be
Thérèse Delvaux, MD PhD
Co-investigator (social 
science) 
tdelvaux@itg.be
 
 
 

6 June 2016 
 
6 
2. SYNOPSIS 
 
Purpose 
The current standard of care for urogenital infections in Rwanda is syndromic 
management. Many urogenital infections are asymptomatic and therefore 
completely missed, and the management of vaginal discharge syndrome is 
known to be suboptimal. The primary objective of this study is to evaluate 
whether it is feasible to improve urogenital infection care in high risk women 
in Kigali, Rwanda (see ‘study population’ below), using point of care (POC) 
diagnostic testing for HIV, Trichomonas vaginalis (TV), and bacterial vaginosis 
(BV) in all women; POC testing for Neisseria gonorrhoeae (NG), Chlamydia 
trachomatis (CT), and syphilis in pregnant women and women assessed to be 
at high risk for these infections using a risk scoring questionnaire; and 
management of vaginal candidiasis, urinary tract infection (UTI), genital 
ulcers/inguinal bubos, and lower abdominal pain in women reporting relevant 
symptoms. The secondary objectives of this study are 1) to evaluate the 
performance and 2) cost effectiveness of the POC tests for CT/NG, TV and BV; 
and 3) to obtain the opinions of stakeholders (clinicians, programme 
implementers and policymakers) about 3a) the potential improvement of 
urogenital infection care in Rwanda as well as 3b) the potential roll-out of 
novel vaginal microbicides and multipurpose prevention technologies for HIV 
and pregnancy prevention as soon as efficacious products become available 
(to prepare for future projects at Rinda Ubuzima (RU)).  
Study Design
1. This is a cross-sectional study. The improved urogenital infection care 
services will be advertised to women in Kigali, Rwanda, via RU’s existing 
networks, targeting women with urogenital complaints as well as women 
without urogenital complaints who have had high risk behaviour. The 
services will be available for free at RU’s research clinic for the duration of 
the project. All consenting women who attend RU’s research clinic during 
the study period will be offered:  
a. Voluntary counselling and testing (VCT) for HIV.  
b. Urine pregnancy test if indicated and contraception counselling.  
c. POC testing for UTI if UTI symptoms are present.  
d. POC testing for TV and BV regardless of symptoms, and management 
of vaginal candidiasis based on symptom-reporting. 
e. POC testing for syphilis and CT/NG if pregnant or considered at risk by 
risk scoring questionnaire.  
f. Syndromic management of genital ulcers/inguinal bubos and lower 
abdominal pain.  
g. Treatment and partner notification and treatment as appropriate, and 
referrals to antenatal, family planning, HIV and cervical cancer 
screening care. 
 
Information about sociodemographics, risk behaviour, sexual and 
reproductive health history and current urogenital symptoms will be 
collected during the clinic visit. Women can opt out of each service offered. 
Services will be delivered within one half day. However, women can choose 
to leave before all results are available, and be contacted by study staff 
when results are available, which is particularly relevant for women 
undergoing CT/NG POC testing (which takes about 90 minutes).  
2. Vaginal swabs for storage will be taken from all consenting women (women 
can choose between self- or clinician-sampling) for additional research 
testing at the end of the study to allow for performance evaluation of the 

6 June 2016 
 
7 
CT/NG, TV and BV POC tests.
3. Opinions of stakeholders will be gathered during workshops (one before 
and one after completion of the study) and in-depth interviews (IDIs). 
Study Site 
Rinda Ubuzima (RU) research clinic, Kigali, Rwanda
Study Products
None
POC Diagnostic 
Tests 
• HIV: POC tests and testing algorithm currently approved by the Rwanda 
Ministry of Health, locally available 
• Pregnancy: Validated urine human chorionic gonadotropin (hCG) test, 
locally available 
• UTI: Validated urinalysis test, locally available 
• BV: Ecocare Comfort Vaginal pH swab (Merete Medical, Luckenwalde, 
Germany), to be imported 
• TV: OSOM POCT (Sekisui Diagnostics, San Diego, CA, USA), to be imported 
• CT/NG: GeneXpert (Cepheid, Sunnyvale, CA, USA), to be imported 
• Syphilis: Alere Determine POCT (Alere International, Galway, Ireland), 
regionally available 
Study Population
Adult women living in the city of Kigali who are at high risk of HIV/urogenital 
infections (defined as having had more than one sexual partner in the last 12 
months OR having been treated for a sexually transmitted infection (STI) in the 
last 12 months) regardless of the presence of current urogenital symptoms. 
Women who are known to be HIV-positive and/or pregnant will not be 
excluded. 
Study Duration
One year
Study Endpoints
• Primary: Monitoring and Evaluation (M&E) indicators of the services 
offered (such as numbers of women counselled and risk scored, diagnostic 
tests conducted, infections diagnosed and treated, referrals made, etc.), 
and responses to a client satisfaction survey and staff survey about their 
experiences with the services. 
• 
Secondary: Sensitivity, specificity, positive predictive value (PPV), and 
negative predictive value (NPV) for 1) syndromic management, 2) risk 
scoring followed by POC testing (CT/NG), and 3) POC testing of everyone 
(CT/NG, TV and BV). 
• Secondary: Cost-effectiveness parameters (such as costs for each 
diagnostic algorithm, costs per correctly and incorrectly managed infection, 
and total cost per disability adjusted life year (DALY) averted) 
• 
Secondary: Consensus, majority and minority opinions of stakeholders 
from transcripts of workshops and IDIs. 
 
 
 
 

6 June 2016 
 
8 
3. 
INTRODUCTION 
 
3.1 
Background 
 
Rinda Ubuzima (RU) in Kigali, Rwanda, is a non-governmental organisation specialised in HIV 
prevention and sexual and reproductive health (SRH) research in women. RU has operated a 
research clinic and laboratory in Kigali since 2004, and has successfully implemented 9 large SRH 
studies (1-10). The main purpose of this study is to use the capacity that RU has built to evaluate 
whether it is feasible and affordable to improve SRH services, and particularly the diagnosis and 
treatment of urogenital infections, in high risk women. 
 
Urogenital infections in different female populations at risk in Rwanda 
In the context of the above-mentioned SRH studies, RU has worked with high risk women (most of 
whom were sex workers), female clients of public voluntary HIV counselling and testing (VCT) sites, 
HIV-positive women before and during antiretroviral therapy (ART) at public clinics, and women in 
the general population. The following table, containing data from these studies, shows that all 
urogenital infections are common in these populations.  
 
Prevalence (%) 
KHIS 
high risk 
women1 
KHIS 
female VCT 
clients2 
VBMS 
HIV-neg 
high risk1 
VBMS 
HIV-pos 
women3 
SEARCH 
HIV-pos3 
Pre-ART/on ART 
Year of the Study 
2006-2009 
2007-2009 
2010-2012 
2010-2012 
2007-2010 
HIV 
24 
13 
04
1004 
1004 
HSV-2 
60 
43 
47 
83 
86 / 92 
High risk HPV 
37 
ND 
ND 
ND 
38 / 53 
Syphilis 
7 
ND 
7 
20 
3 / 4 
Neisseria gonorrhoeae 
12 
ND 
7 
13 
14 / 7 
Chlamydia trachomatis 
5 
ND 
10 
0 
5 / 5 
Trichomonas vaginalis 
17 
ND 
10 
10 
ND 
Bacterial vaginosis  
(Nugent 7-10) 
40 
ND 
44 
 
36 
ND 
Intermediate microbiota 
(Nugent 4-6) 
15 
ND 
19 
21 
ND 
Vaginal candidiasis 
7 
ND 
10 
13 
ND 
Urinary tract infection 
ND 
ND 
23 
23 
ND 
Uses modern method of 
contraception excl. 
condoms 
19 
14 
70 
54 
40 
Never HIV tested before 
35 
25 
ND 
NA 
NA 
KHIS [1-4], VBMS [5-7] and SEARCH [8] are study acronyms; ND=not done; NA=not applicable. 
1. Female sex workers or other women with multiple partners. 
2. Clients of public VCT centres in Kigali city; not selected by risk behaviour. 
3. HIV positive women receiving care at a public HIV clinic in Kigali; not selected by risk behaviour.  
4. By study design; only HIV-negative or HIV-positive women included. 
 
The viral sexually transmitted infections (STIs) herpes simplex virus type 2 (HSV-2) and human 
papillomavirus (HPV) were the most common, followed by the various vaginal infections (bacterial 
vaginosis (BV) and intermediate microbiota, Trichomonas vaginalis (TV), and vaginal candidiasis) and 
urinary tract infections (UTIs). The bacterial STIs Neisseria gonorrhoeae (NG), Chlamydia trachomatis 
(CT), and syphilis were less common, but higher prevalence rates were measured in a currently 
ongoing study in high risk women at RU: 12% for NG and 20% for CT (unpublished data).  
 
 
 

6 June 2016 
 
9 
Sequelae of urogenital infections 
If left untreated, urogenital infections are associated with many devastating sequelae, particularly in 
women (11). NG, CT and BV are associated with infertility and pelvic inflammatory disease, and in 
pregnant women with miscarriage and preterm birth. Syphilis causes neurological symptoms, and in 
pregnant women congenital syphilis. UTIs can progress to kidney infection and sepsis. High risk HPV 
viruses are associated with the development of cervical, anal and head-and-neck cancers. 
Furthermore, it has become increasingly clear that the HIV and urogenital infection epidemics fuel 
one another (12, 13). Therefore, the admirable gains made in HIV prevention and care in Rwanda in 
the last decade (14), are threatened by the fact that urogenital infections have not yet been brought 
under control.  
 
With the increasing use of highly sensitive and specific molecular diagnostic tests for various 
urogenital infections in research studies, it has become clear that asymptomatic infections are also 
associated with the above-mentioned adverse outcomes, sometimes to the same extent as 
symptomatic infections (7, 15). Furthermore, a considerable body of research has now shown that 
the majority of urogenital infections in women are asymptomatic (11).  In addition to promptly 
identifying and treating symptomatic women, screening of asymptomatic women at high risk may 
therefore be necessary to reduce the prevalence of urogenital infections and their sequelae (11). 
 
Syndromic management 
The high burden of STIs worldwide, but particularly in sub-Saharan Africa, has long been recognised 
by the World Health Organisation (WHO). In an effort to control STIs in resource-poor settings with 
no or limited laboratory infrastructure, the syndromic management guidelines were launched in 
1978, and updated in 2003 (16) and 2008 (17). These guidelines categorise STIs by the symptoms 
they cause, and call for treatment of all pathogens that might cause that syndrome. The current 
WHO syndromic guidelines for women are as follows (16, 17): 
• 
Vaginal discharge syndrome without lower abdominal pain: Treat for BV and TV. If the discharge 
is curd-like and erythema and itching are present, also treat for vaginal candidiasis. If the NG 
and CT prevalence is high, or the individual’s risk for these infections is considered high, also 
treat for NG and CT. 
• 
Lower abdominal pain (with or without discharge): Requires abdominal and pelvic examination. 
If cervical motion or adnexal tenderness is present: treat for pelvic inflammatory disease. Refer 
to the hospital in case of a missed period, recent delivery/abortion/miscarriage, abdominal 
guarding or rebound tenderness, abnormal vaginal bleeding, or abdominal mass. 
• 
Genital ulcers: Treat for syphilis and HSV-2. Also treat for chancroid, lymphogranuloma 
venereum (LGV) and granuloma inguinale where these infections are prevalent. 
• 
Inguinal bubos without genital ulcers: Treat for LGV and chancroid. 
• 
Inguinal bubos with genital ulcers: Follow the genital ulcers guideline. 
The diagnosis and treatment of UTIs is not included in the WHO syndromic management guidelines, 
but in daily practice women who present with UTI-associated complaints are usually treated.  
 
The obvious advantage of the syndromic approach is that no laboratory testing is needed but the 
obvious disadvantage is that all asymptomatic infections are missed. As mentioned earlier, the 
majority of urogenital infections in women are asymptomatic. Furthermore, research has shown that 
the algorithm for vaginal discharge syndrome in women has low sensitivity and specificity (18, 19). 
Our own research at RU confirms this (data not yet published). In contrast, research has shown that 
syndromic management of genital ulcers/inguinal bubos is adequate for both men and women (17), 
and that UTIs can be adequately managed based on urinalysis in patients with self-reported UTI-
associated symptoms (20; although this is understudied in resource poor settings).  
 
 
 

6 June 2016 
 
10 
Point of care (POC) diagnostic tests 
One way to improve urogenital infection care in women is to introduce POC diagnostic testing (21). 
Validated POC tests for HIV (22), syphilis (23), UTIs and pregnancy have been available for many 
years and are well-integrated into public clinics, including in resource poor settings. Most POC tests 
for HIV and syphilis are immunochromatographic assays that detect pathogen antigens or antibodies 
in small amounts of blood (a finger prick is sufficient). UTI and pregnancy POC tests are dipsticks that 
are submerged in a urine sample. UTI dipsticks detect leukocytes (among other analytes), and 
pregnancy dipsticks detect the human chorionic gonadotropin (hCG) hormone.  
 
More recently, POC tests were developed for TV and CT/NG. The OSOM TV POC test (Sekisui 
Diagnostics, San Diego, CA, USA) is an immunochromatographic dipstick test that detects TV 
antigens in vaginal swab eluent; it was found to be 77% sensitive and 99% specific compared to TV 
polymerase chain reaction (PCR) in a study in Brazil and South Africa (24). This means that 24% of 
cases were misdiagnosed (23% false-negative and 1% false-positive). In Rwanda, TV is currently 
diagnosed by symptoms only, and a recent study in India found that 86% of patients with PCR-
proven TV were misdiagnosed on the basis of symptoms alone (25). The TV OSOM POCT is therefore 
a significant improvement over the current situation. 
 
The development of a POC enzyme immunoassay for NG and CT has proved difficult: all tests that 
were developed and evaluated thus far had poor sensitivity (26, 27). However, a POC real-time 
molecular test (detecting NG and CT DNA) is now available: the GeneXpert test (Cepheid, Sunnyvale, 
CA, USA) (28). While the GeneXpert test is highly sensitive and specific for NG and CT, it does not 
fulfil all ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free and 
deliverable to end users) criteria (27): for example, testing requires a machine and about 90 minutes 
per sample. Research on CT/NG POC tests that do fulfil the ASSURED criteria is ongoing. Meanwhile, 
the GeneXpert platform is a significant improvement over syndromic management (the above-
mentioned recent study in India found that 80% of women with PCR-proven CT and 50% of women 
with PCR-proven NG were misdiagnosed on the basis of symptoms alone; 25) and traditional PCR 
platforms, and is being rolled out in select specialised centres across Africa. 
 
BV is usually diagnosed empirically (based on self-reported symptoms) in public primary care clinics, 
by Amsel criteria in specialised clinics (29), and by Gram stain Nugent scoring in specialised referral 
clinics and research settings (30). The Amsel criteria and Nugent scoring require skilled 
microscopists, who are usually not available in resource-poor settings. In the last decade, entire 
bacterial communities in the vagina have been characterised in detail (referred to as ‘vaginal 
microbiota’) using novel molecular testing techniques. We now know that vaginal microbiota that 
are dominated by Lactobacillus species are healthy and that BV is a polybacterial dysbiosis: 
lactobacilli are no longer dominant and the bacterial diversity in the vagina increases (31). 
Intermediate microbiota might represent a transition to or from dysbiosis. RU studies showed that 
increasing bacterial diversity in the vagina is not associated with the presence of urogenital 
symptoms, but is associated with increasing prevalence of HIV, HSV-2, HPV, bacterial STIs, and UTIs 
(15). While more research is needed to investigate these relationships, we believe that the currently 
available evidence is sufficient to justify treatment of both symptomatic and asymptomatic BV. Our 
research has also shown that the vaginal pH (which can be easily measured by putting some vaginal 
fluid on litmus paper in the vaginal pH range) is strongly correlated with the types of bacteria that 
are present in the vagina. Lactobacilli are very strong lactic acid producers and cause the vagina to 
be acidic (low pH, typically 3.6-4.1) whereas the bacteria associated with BV produce no or less lactic 
acid and cause the vaginal pH to be higher (31). Based on data from our previous studies in similar 
populations, we have chosen to treat all women with a vaginal pH ≥ 5.0 regardless of symptoms for 
BV. This cut-off achieved a sensitivity of 71% and a specificity of 76% when a Nugent score of 7-10 
was used as the gold-standard for BV diagnosis in unpublished studies conducted at RU. In addition, 

6 June 2016 
 
11 
women with a lower vaginal pH will be treated when they have severe symptoms consistent with BV 
to minimise false-negative diagnoses. In comparison, a South African study in 2012 showed that the 
sensitivity of using symptoms alone to diagnose BV was only 10% (32). 
 
Integration of POC tests into urogenital infection care 
In this study, we will offer POC testing for HIV, TV and BV to all women, on a voluntary basis 
regardless of the presence of symptoms. As is clear from the table above, these infections are 
extremely common in high risk women in Kigali, which justifies testing of all women. Furthermore, 
validated, user-friendly and affordable POC tests for these infections are available, TV and BV are 
curable, and women testing HIV-positive will benefit from referral to clinics providing antiretroviral 
therapy. Vaginal candidiasis and UTIs are also common but these infections typically become 
symptomatic when the fungal/bacterial load increases, and are easily diagnosed based on 
symptoms. In this study, we will treat vaginal candidiasis based on symptoms alone, and we will test 
women with UTI symptoms by urinalysis dipstick test to determine whether UTI treatment is 
required. 
 
The curable STIs NG, CT and syphilis are less common, and the POC test for CT/NG is time-consuming 
and expensive. For these reasons, we will use a risk scoring questionnaire to determine which 
women are at sufficiently high risk to warrant POC testing. Risk scoring questionnaires were shown 
to be sensitive and specific in some studies (19, 33). To maximise the performance of the risk scoring 
questionnaire to be used in this study, we will use data collected at RU in previous studies to design 
the questionnaire. Pregnant women will be tested for NG, CT and syphilis regardless of their risk 
score because of the potential consequences of these curable STIs on the pregnancy and neonate. 
 
While HSV-2 and HPV are also very common, these infections cannot be cured and do not require 
lifelong therapy. Instead, we will offer acyclovir treatment for active HSV2 outbreaks (when genital 
vesicles are present) as part of syndromic management of genital ulcers. HPV testing and vaccination 
is currently not available in Rwanda for our study population of adult high risk women (34). 
However, we will refer women to cervical cancer screening programs available elsewhere in Kigali. 
 
3.2 
Rationale 
 
The primary objective of this study is to evaluate whether it is feasible to improve urogenital 
infection care in high risk women in Kigali, Rwanda, using POC diagnostic testing for HIV, TV, and BV 
in all women; POC testing for CT/NG, and syphilis in pregnant women and women assessed to be at 
high risk for these infections using a risk scoring questionnaire; and management of vaginal 
candidiasis, UTI, genital ulcers/inguinal bubos, and lower abdominal pain in women reporting 
relevant symptoms. The secondary objectives of this study are 1) to evaluate the performance and 
2) cost effectiveness of the POC tests for CT/NG, TV and BV; and 3) to obtain the opinions of 
stakeholders (clinicians, programme implementers and policymakers) about 3a) the potential 
improvement of urogenital infection care in Rwanda as well as 3b) the potential roll-out of novel 
vaginal microbicides and multipurpose prevention technologies for HIV and pregnancy prevention as 
soon as efficacious products become available (to prepare for future projects at RU). 
 
4. 
STUDY DESIGN, OBJECTIVES AND ENDPOINTS 
 
4.1 
Study design 
 
We will conduct a year-long cross-sectional study in RU’s research clinic, during which RU staff will 
routinely offer improved urogenital care services to all eligible high risk women who attend the 
clinic. The improved services will be advertised via RU’s existing network of community mobilisers 
and via word of mouth. The advertising will clearly state that the services are: 1) for women with 

6 June 2016 
 
12 
urogenital complaints as well as women without urogenital complaints who have had high risk 
behaviour; 2) at no cost to them; but are 3) only temporarily available for the duration of the 
project; and 4) only available once per participant (this includes one urogenital infection screening 
visit plus any additional follow-up that is required to manage diagnosed infections). 
 
During the informed consent process, each service will be explained, and women will be told that 
they can opt out of each service offered. Our aim is to conduct all services (including provision of 
treatment) within one half day (the Main Visit) to minimise loss to follow-up. However, women can 
choose to leave before all results are available, and be contacted by study staff when results are 
available (see section 5.4 for a description of how women will be contacted), which is particularly 
relevant for women undergoing CT/NG POC testing (which takes about 90 minutes). 
 
Services to be offered (see also section 6: study procedures and appendix 14.2: WISH clinical 
algorithms; all procedures will be implemented in accordance with existing RU SOPs): 
1. 
VCT for HIV. Women who are known HIV-positive but attend the clinic to be screened for 
urogenital infections can skip the HIV testing step. Women who do not know their HIV status, 
but do not want to be tested, can also skip the HIV testing step but will be strongly encouraged 
to get tested. The RU clinicians and on-site laboratory have much experience with HIV 
counselling and testing in accordance with the national testing algorithm that was approved by 
the Rwanda Ministry of Health. All women regardless of HIV status, and whether or not they 
choose to be tested, will be educated about HIV prevention options available in Kigali. 
2. 
Urine pregnancy test if indicated and contraception counselling. 
3. 
POC testing for UTI. Women will be asked about symptoms typically associated with UTIs; their 
urine will be tested by urinalysis strip if symptoms are reported; and treatment will be given as 
appropriate. 
4. 
POC testing for vaginal infections regardless of symptoms. All women regardless of symptoms 
will be offered vaginal pH measurement with litmus paper attached to a vaginal swab to 
diagnose BV, POC testing for TV, and treatment for BV and/or TV as appropriate. They will also 
be asked about symptoms typically associated with vaginal candidiasis, and treatment based on 
symptom-reporting. In addition, all women will be counselled about safer sex, cessation of 
harmful vaginal hygiene practices, and male penile hygiene, to minimise BV recurrence. 
5. 
POC testing for other curable STIs (syphilis, NG and CT) if pregnant or considered at risk by risk 
scoring questionnaire. The questionnaire will be developed in the beginning of the project using 
the behavioural factors that were most strongly associated with these curable STIs in previous 
RU studies. If considered at high risk by risk scoring questionnaire or pregnant, POC testing will 
be conducted, and treatment given as appropriate. 
6. 
Treatment of genital ulcers/inguinal bubos and lower abdominal pain according to the 
syndromic management guidelines.  
7. 
Partner notification and treatment, if applicable. 
8. 
Referrals to antenatal, HIV, family planning and other care, if applicable. 
 
In addition to offering these services, research activities will be carried out as follows: 
1. 
To monitor and evaluate the services offered, we will collect data on monitoring and evaluation 
(M&E) indicators. Data for most M&E indicators will be available as part of routine clinic 
procedures (such as numbers of women counselled and risk scored, diagnostic tests conducted, 
infections diagnosed and treated, referrals made, etc.) but others will require interviewing 
participants at the end of their visit (client satisfaction survey), interviewing staff at the end of 
the study (about their experiences providing the services), timing of procedures done by 
different staff members, and timing of client trajectories. 
2. 
To evaluate the performance of POC tests for NG, CT and TV compared to providing syndromic 
management alone, we will ask all women at the beginning of their visit (before any POC tests 

6 June 2016 
 
13 
have been done) whether they have urogenital complaints. We will ask them these questions 
exactly in the same manner as we would have done if we would only have offered syndromic 
management. In addition, we will ask all women to collect two vaginal swabs via self- or 
clinician-sampling (the woman’s own choice) for temporary storage and testing for research 
purposes after the client has left the clinic. Stored swabs from all women who did not undergo 
GeneXpert CT/NG POC testing during their Main Visit will be tested by GeneXpert soon after 
their Main Visit so that we have a GeneXpert result for all women. If funding permits, we will 
also test stored swabs from all women by molecular tests for TV, BV and UTI after completion of 
the study (within two years after termination of data collection). This will allow for sensitivity, 
specificity, PPV, NPV and cost effectiveness comparisons of syndromic management, POC 
testing after risk scoring, and POC testing of all women, and will improve our understanding of 
organisms associated with BV and UTI. If we identify any NG or CT infections by GeneXpert that 
had not been treated at the Main Visit, we will ask these women to return to the study clinic for 
repeat testing and treatment if applicable.  
3. 
To evaluate the cost effectiveness of introducing POC tests, we will collect data on cost-
effectiveness parameters (such as total costs for each diagnostic algorithm, costs per correctly 
and incorrectly managed infection, and total cost per DALY averted). 
4. 
We will conduct qualitative research with stakeholders (clinicians, programme implementers 
and policymakers) regarding the potential improvement of urogenital infection care in high risk 
women, and also the potential roll-out of novel vaginal microbicides and multipurpose 
prevention technologies for HIV and pregnancy prevention as soon as efficacious products 
become available (to prepare for future RU projects). The opinions of stakeholders will be 
solicited during two workshops (one to be held before the start of the study and one after 
completion of the study) as well as in about 10 individual IDIs. 
 
4.2 
Specific objectives and endpoints 
 
Primary objectives
Primary endpoints
1. Implement improved 
urogenital infection care 
services and monitor and 
evaluate these services 
• M&E indicators, such as: 
− Inputs: Procurement experiences, infrastructure/training 
requirements; 
− Activities/outputs: Numbers of clients counselled and risk 
scored, diagnostic tests conducted, infections diagnosed and 
treated, and referrals made; staff time required for each 
activity; time spent at the clinic for each client trajectory; 
− Outcomes/impacts: Improvements of access to and quality of 
services (from client satisfaction survey, staff interviews). 
Secondary objectives
Secondary endpoints
1. Compare performance of 
syndromic management, 
POC testing after risk 
scoring, and POC testing 
of everyone for the 
diagnosis of NG, CT, TV, 
and BV. 
• Sensitivity, specificity, PPV, and NPV for: 
− Syndromic vs POC testing of everyone (NG, CT, TV and BV) 
− Syndromic vs risk scoring followed by POC testing (NG, CT) 
− Risk scoring followed by POC testing vs POC testing of 
everyone (NG, CT) 
− If funding permits, also all of the above vs gold standard 
molecular testing of everyone (NG, CT, TV, BV, and UTI) 
2. Compare cost-
effectiveness of all of the 
above 
• Cost effectiveness parameters, such as: 
− Total costs for each diagnostic algorithm 
− Costs per correctly and incorrectly managed infection 
− Total cost per disability adjusted life year (DALY) averted 
Qualitative research objectives
Qualitative research endpoints
3a.Obtain stakeholder opinions about potential 
• Consensus, majority and minority 

6 June 2016 
 
14 
improvement of urogenital infection care in high risk 
women, as evaluated in the cross-sectional study. 
opinions of stakeholders from 
transcripts of workshops and IDIs. 
3b.Obtain stakeholder opinions about the potential roll-
out of novel vaginal microbicides and multipurpose 
prevention technologies for HIV and pregnancy 
prevention as soon as efficacious products become 
available (to prepare for future RU projects). 
• Consensus, majority and minority 
opinions of stakeholders from 
transcripts of workshops and IDIs. 
 
4.3 Sample size 
 
The primary objective is descriptive. Formal sample size calculations were therefore not performed. 
We estimated to be able to see 500-700 women in one year with the funding we received from 
EDCTP. However, our estimate may have been conservative, in which case the sample size may be 
increased to up to 1,000 women. Based on prevalence data from recent RU studies in the same high 
risk population, if we see 500 clients (assuming that they do not opt out of any services offered), we 
expect to diagnose 100 cases of HIV, 35 cases of syphilis, 60 cases of NG, 75 cases of CT, 75 cases of 
TV, 175 cases of BV, 50 cases of vaginal candidiasis, and 115 cases of UTI. 
 
Data for the qualitative research objectives will be gathered at two workshops with stakeholders: 
one to be held before initiation of the study and one after completion of the study. In addition, IDIs 
will be done with clinicians, programme implementers and policymakers. The number of IDIs to be 
held will be governed by data saturation: no new interviews will be done when they no longer 
generate new information. We expect to conduct approximately 10 IDIs. 
 
4.4 
Randomisation and blinding 
 
There will be no randomisation and blinding in this study. 
 
5. 
STUDY POPULATION 
 
5.1 
Target population 
 
Our target population is adult women living in the city of Kigali who are at high risk of HIV/STIs. In 
this study, high risk will be defined as having had more than one sexual partner in the last 12 months 
OR having been treated for an STI in the last 12 months. Women who are known to be HIV-positive 
and/or pregnant will not be excluded from participation. Women will be allowed to participate 
regardless of whether they currently have urogenital symptoms. 
 
5.2 
Eligibility criteria 
 
Inclusion criteria: 
− 
Female, at least 18 years old (no upper age limit) 
− 
At high risk of HIV/STIs, defined as having had more than one sexual partner in the last 12 
months OR having been treated for an STI in the last 12 months 
− 
Willing and able to provide written informed consent. According to the Rwandan ethics 
guidelines, unmarried women aged 18-20 also need the written informed consent of a parent or 
guardian.  
 
 
 

6 June 2016 
 
15 
Exclusion criteria: 
− 
Already participated in this study before (each woman can only participate once) 
− 
Participating in another health intervention study 
− 
For any other reason as judged by the Principal Investigator (these reasons will be recorded) 
 
5.3 
Recruitment 
 
RU will use its network of community mobilisers to advertise the services in the Kigali 
neighbourhoods where recruitment for previous RU studies with high risk women took place. The 
community mobilisers are high risk women themselves who have participated in RU projects in the 
past; RU has worked with them for several years. Advertisement may include handing out flyers and 
RU staff attending community meetings to explain the project to relevant communities. We also 
expect to reach women via word-of-mouth. Recruitment will not start until permission has been 
obtained from the local authorities in those neighbourhoods. Standard RU procedures will be used 
to ensure that confidentiality is not breached. For example, the project vehicles do not carry a logo 
and outreach staff do not wear uniforms. RU staff may check potential eligibility of individual women 
who are interested in participating using an anonymous checklist. At this stage, no individual data 
will be recorded. Women who are interested and eligible will be invited to attend the RU research 
clinic in Kiyovu, Kigali.  
 
5.4 
Retention and withdrawals 
 
All participants will be asked to provide contact information for herself and at least one other 
contact person. RU’s preferred way of contacting participants is by text message to a personal 
mobile phone, but this will only be done if the participant has given permission. If texting is not 
possible or not permitted by the participant, the participant will be asked permission for other ways 
of contacting her should this be necessary. RU staff will only leave neutral messages that cannot be 
linked to RU, the WISH study, or the various diagnostic tests that were conducted (see below). When 
phone calls are made, RU staff will identify themselves with their first name only, and will then verify 
that they have the right person on the phone by asking them for their full name, date of birth, and 
the name of the study. Medical information will only be shared by phone with the participant 
herself. When phoning a contact person, RU staff will only provide their first name and a contact 
phone number. Participants will be informed of these contacting procedures during their clinic visit. 
 
Our aim is to provide all study services within half a day (a morning or an afternoon). However, 
participants may elect to leave the clinic before all testing has been completed. This may be 
particularly relevant for women who are selected (by risk scoring tool) for CT/NG testing because the 
GeneXpert testing procedure takes about 90 minutes. In that case, participants will be contacted in 
the agreed-upon manner to let them know whether all results were negative (no need for a clinic 
visit) or whether they need to return to the clinic for further follow-up and/or treatment. We will 
use the following text messages: ‘This is [first name of RU staff member]; all clear’ when all results 
are negative, and ‘This is [first name of RU staff member]; please visit us as soon as possible’ when a 
clinic visit is needed. If a participant needs to return to the clinic but misses her visit, study staff will 
attempt to contact her again until the required follow-up has been conducted or three contact 
attempts have been made. The number of contact attempts will be recorded in the participant’s 
records. 
 
Participants may voluntarily withdraw from the study for any reason at any time. The Principal 
Investigator may also discontinue participants (for example, if this is deemed in the best interest of 
the participant). The reason(s) for withdrawal or discontinuation will be recorded in the participant’s 
records. 
 

6 June 2016 
 
16 
6. 
STUDY PROCEDURES - CLINICAL 
 
Curable urogenital infections (syphilis, NG, CT, TV, BV, vaginal candidiasis and UTI) will be treated at 
RU, and partner notification and treatment services will be offered if applicable, free of charge (see 
Appendix 14.3 for details). Participants will receive a full course of treatment in accordance with 
current Rwandan national treatment guidelines and, in the case of syphilis, NG, CT and TV, will be 
encouraged to bring regular sexual partners for treatment of the same infection. Treatment failure 
for all of these infections except for NG is rare if adherence is good, and standard of care for these 
infections does not include tests of cure (16, 17). Women will be advised that, if symptoms return, 
this is most likely due to reinfection by an infected sexual partner. They will be referred for 
treatment of this new infection to their local public clinic. Treatment failure for NG is expected to be 
more common due to rapid emergence of antibiotic resistance in this organism. Women who test 
positive for NG will therefore be actively followed-up by RU Physicians and will be offered a second-
line treatment if the first line treatment fails. 
 
Women will also receive reproductive health counselling and condoms free of charge. Any other 
medical conditions (including newly diagnosed HIV and pregnancy) and reproductive health needs 
(including contraception) will be actively referred to local clinics or referral hospitals. The RU study 
team is well connected with available services in Kigali.  
 
The order of procedures at study visits as described below may be modified somewhat to improve 
clinic flow but informed consent procedures will always be done before any other procedures, and 
face-to-face interviewing will be done before counselling in order not to bias the interview results. 
 
6.1 
Schedule of assessments 
 
See Appendix 14.1. 
 
6.2 
Procedures first WISH study visit (Main Visit) 
 
Upon arriving at the RU research clinic all potentially eligible participants will be assigned a 
participant identification number after which the informed consent process will be done according 
to existing RU SOPs (see section 10.5 for details). 
 
After written informed consent has been obtained, the following procedures will take place: 
1. 
Collect contact information (see section 5.4 for details); 
2. 
Complete eligibility checklist. Women who are menstruating at the time of this visit will be able 
to participate in most cases but may be asked to return after they have finished menstruating. 
3. 
Complete face-to-face interview (sociodemographic characteristics, sexual behaviour, medical 
and reproductive history, and current urogenital symptoms) including the risk scoring 
questionnaire; 
4. 
HIV/STI/BV risk reduction counselling; 
5. 
Determine which additional services will be offered and ask the participant whether she wants 
to opt out of any services: 
− HIV, BV and TV testing: offered to all women 
− Pregnancy testing: offered to all women if indicated 
− UTI testing: offered only if UTI symptoms are reported 
− Syphilis, NG and CT testing: offered only if selected by risk scoring questionnaire 
− Management of vaginal candidiasis, lower abdominal pain, genital ulcers/inguinal bubos, and 
genital warts if relevant symptoms are reported 
6. 
If applicable: Collect blood (one tube of about 10 ml; for HIV and syphilis testing), urine (for 

6 June 2016 
 
17 
pregnancy and urinalysis dipstick testing), and vaginal swabs (up to 5 swabs for BV, TV, and 
CT/NG testing, and temporary storage for research testing).  
− Women can choose to have the vaginal swabs collected by self-sampling instead of clinician-
sampling; vaginal swabs will be collected without the insertion of a speculum unless the 
clinician deems a speculum examination clinically necessary (see 10). Women who refuse 
collection of vaginal swabs altogether, and are selected for CT/NG testing, may have their 
urine tested instead (based on previous studies, we expect refusal of vaginal swab collection 
to be rare). 
− Women who refuse venepuncture will be offered HIV and syphilis testing by finger prick. 
However, they will be told that venepuncture will be necessary if the HIV or syphilis results 
come back positive for confirmatory testing.  
− Left-over blood, urine and two vaginal swabs will be temporarily stored for research testing 
(see 13 and sections 4.1 and 8.2). 
7. 
If applicable: HIV, pregnancy, urinalysis dipstick, vaginal pH, TV POC test, and/or syphilis POC 
test in the onsite RU laboratory; 
8. 
If applicable: GeneXpert CT/NG test in the onsite RU laboratory. Women who are selected for 
this test should be told that the test will take approximately 90 minutes. In the meantime, 
continue with 9. 
9. 
Provision of POCT results, and provision of treatment and referrals as needed (in accordance 
with the latest version of the RU SOP for Reproductive Tract Infection Management and the RU 
SOP for Referrals; see also Appendix 14.3). At this point, also provide treatment for 
symptomatic vaginal candidiasis, lower abdominal pain, genital ulcers/inguinal bubos, and 
genital warts as required. 
10. Pelvic examinations will only be conducted when deemed necessary by the study physician (e.g. 
in women reporting lower abdominal pain). 
11. If necessary: schedule a follow-up text message, phone call, or visit (e.g. for provision of 
GeneXpert CT/NG results if the participant does not want to wait). 
12. Participant leaves the RU clinic. 
13. Further research testing after the participant has left the clinic to assess POCT performance: 
− Vaginal swabs: GeneXpert CT/NG test on all women who were not selected for testing by risk 
scoring questionnaire (so that a GeneXpert CT/NG test result is available for everyone) 
− Urine: The GeneXpert CT/NG test may be done on urine instead of vaginal swabs when 
vaginal swabs are not available. 
If funding permits: 
− Vaginal swabs: Molecular testing for NG, CT, TV, and BV 
− Urine: Molecular testing for UTI. 
 
6.3 
Procedures any additional WISH study visits (Additional Visits) 
 
Study staff may ask participants to return to the RU clinic if they require additional provision of test 
results, partner notification, treatment and/or referral. Other unscheduled visits may take place at 
the request of participants. At unscheduled visits, only the procedures for which the visit was 
intended will take place, and all of these will be documented. 
 
7. 
STUDY PROCEDURES – QUALITATIVE RESEARCH 
 
Two workshops will be held with study staff and investigators, reproductive health care clinicians, 
programme implementers and policymakers in Kigali, Rwanda. One will be held before the start of 
the study (its main purpose is to discuss the study and to decide on M&E indicators to measure 
during the study) and one after completion of the study (to discuss the study results, implications for 
urogenital infection care in Rwanda, and the potential roll-out of novel vaginal microbicides and 

6 June 2016 
 
18 
multipurpose prevention technologies for HIV and pregnancy prevention as soon as efficacious 
products become available). The workshops will not be taped, but study staff will take detailed notes 
of the discussions. These notes will form one source of data to address the qualitative research 
objectives. For data management/analysis and confidentiality, see sections 9 and 10.4, respectively. 
 
In addition, a total of about 10 IDIs will be conducted with individual clinicians, programme 
implementers and policymakers to address the qualitative research objectives. The interviewees will 
be selected from among RU’s professional network in Kigali, and an attempt will be made to include 
professionals with different types of relevant expertise. They will be approached by the Principal 
Investigator. Selected interviewees will be asked to provide written informed consent for the IDI. 
The IDI procedures will take place in a private location chosen by the interviewee. The interviews will 
be taped. For data management/analysis and confidentiality, see sections 9 and 10.4, respectively. 
 
8. 
STUDY PROCEDURES - LABORATORY 
 
8.1 
Diagnostic tests 
 
The following diagnostic tests will be performed in the onsite RU laboratory using validated test kits 
and SOPs: 
− HIV by rapid test algorithm based on the most recent Rwandan HIV VCT guidelines, all tests 
locally available; 
− Urine hCG pregnancy test, locally available; 
− UTI by urinalysis dipstick test, locally available; 
− TV by OSOM POC test (Sekisui Diagnostics, San Diego, CA, USA), to be imported; 
− BV by EcoCare Vaginal pH Comfort Swab (Merete Medical, Luckenwalde, Germany), to be 
imported; 
− Syphilis by Alere Determine POC test (Alere International, Galway, Ireland), regionally available; 
− If syphilis treponemal POC test is positive, RPR (locally available) will be done to confirm current 
infection. 
− GeneXpert CT/NG test (Cepheid, Sunnyvale, CA, USA), to be imported. 
 
All RU staff handling specimens have been vaccinated against Hepatitis B. The RU SOPs for Universal 
Precautions, Accidental Exposure to Blood and Body Fluids, Disposal of Hazardous Waste and 
Medical Emergencies will be followed. 
 
8.2 
Research tests 
 
Research tests include: 
− Stored swabs from all women who did not undergo GeneXpert CT/NG POC testing at their Main 
Visit will be tested by GeneXpert before the end of the funding period (and as soon as possible 
after their Main Visit) so that we have a GeneXpert result for all women. These tests will be 
conducted in the onsite RU laboratory. 
− If funding permits, we will also test stored swabs from all women by molecular tests for TV, BV 
and UTI. These tests will be conducted at UoL within two years after termination of data 
collection in Rwanda.  
These research tests will allow for sensitivity, specificity, PPV, NPV and cost effectiveness 
comparisons of syndromic management, POC testing after risk scoring, and POC testing of all 
women, and will improve our understanding of organisms associated with BV and UTI. 
 
Specimens will be processed and temporarily stored (at -80°C, or -20°C if -80°C is not possible) at RU 
and either tested by GeneXpert in the onsite laboratory at RU or shipped in batches from RU to UoL 

6 June 2016 
 
19 
using RU SOPs (which are based on local and international shipping regulations) and Material 
Transfer Agreements. Specimens that are shipped to Liverpool will be labelled with ID numbers and 
specimen collection dates, but not with names or other personal identifiers. The electronic 
participant identification register (ePIR; see section 9), which is the only database that will link ID 
numbers with names and contact information, will remain at RU in Rwanda and the study team in 
Liverpool will not have access to it. After arrival at UoL, specimens will be stored until testing at -
80°C in the Ronald Ross building, Institute of Infection and Global Health (IIGH), under the 
custodianship of Prof. Janneke van de Wijgert. Sample storage and testing at UoL will be in 
accordance with the Human Tissue Authority Code of Practice 9 (see 
www.hta.gov.uk/guidance/codes_of_practice.cfm), UoL Code of Practice for the Control of 
Substances Hazardous to Health (COSHH), and IIGH SOPs. IIGH is used to handling specimens 
containing micro-organisms (dead or alive), including specimens containing HIV. The specimens 
collected and stored in this study will not contain viable HIV but may contain dead virus. Prior to 
commencement of any laboratory procedures, Prof. Janneke van de Wijgert will prepare the 
required risk assessments and will reach agreement on the specific procedures to be used with the 
Departmental Safety Advisor and University Safety Advisor. All UoL staff handling study specimens 
have been vaccinated against Hepatitis B. 
 
9. 
DATA MANAGEMENT AND ANALYSIS 
 
We will use two separate custom-built databases with automated quality control checks. The ePIR 
will contain names, identification numbers, contact information, and clinic visit attendance; the 
information will be entered directly into the database by a receptionist when the client first enters 
the clinic. The ePIR will be kept at RU on a stand-alone password-protected desktop computer with 
access limited to key project staff, and is backed up on a separate stand-alone password-protected 
hard drive (under the custodianship of Dr. Stephen Agaba) once per week. The second database will 
contain clinical data (such as sociodemographics, risk score, current genitourinary symptoms, 
services offered and accepted/declined, laboratory test results, and treatments/referrals given) by 
participant identification number and visit date, but will not contain any personal identifiers. The 
clinical data will be entered on paper-based medical records and laboratory forms when the 
participant is in the clinic, and will be entered into the database when all procedures for that 
participant have been completed. This database will be programmed by a professional database 
programmer (Robert Meester) using OpenClinica software, with password-protection at different 
access levels for different key staff, and with automated daily back-ups. This database and back-ups 
will be kept on a remote secure server (under the custodianship of Robert Meester). All paper-based 
forms will be kept at RU in lockable cabinets and/or rooms for confidentiality reasons. Documents 
containing names and/or signatures (such as consent forms) will be kept separately from all other 
documents containing identification numbers only.  
  
Note-takers will take notes in English during the workshops. The IDIs will be tape-recorded, 
transcribed verbatim, and translated into English (if the interview was not conducted in English). The 
workshop notes and English translations of IDI transcripts will be analysed using Nvivo software. The 
tapes will be destroyed after all data have been processed, information in documents that might 
identify interviewees will be anonymised, and reports will contain aggregate data only. The 
anonymised transcripts, Nvivo data, and workshop reports will be kept on a password-protected RU 
desktop computer with access limited to key project staff and regular back-up on a separate stand-
alone password-protected hard drive (under the custodianship of Dr. Stephen Agaba).  
 
Use of the data, and especially publication in the peer-reviewed literature, will be governed by a 
project-specific ‘data-sharing and publication policy’. For archiving procedures, see section 12.7. 
 

6 June 2016 
 
20 
10. 
ETHICAL ISSUES AND PROCEDURES 
 
10.1 Ethical review 
 
The protocol will be reviewed by the Chief Investigator, Principal Investigator, and co-investigators, 
and approved by the Chief Investigator and Principal Investigator. Prior to enrolment of the first 
participant, the protocol will be approved by the Rwanda National Health Research Committee (this 
is an administrative approval, not an ethics approval), and two ethics committees: the National 
Ethics Committee of Rwanda and the UoL Research Ethics Sub-committee for Physical Interventions. 
 
10.2 Burdens and benefits 
 
Physical burdens may include discomfort and bruising at the site of venepuncture and discomfort in 
the vagina during collection of vaginal swabs or pelvic examinations. Psychological burdens may 
include embarrassment during the face-to-face interview and sample collection procedures, and 
personal and/or interpersonal stress if HIV infection and/or an STI is diagnosed. Though unlikely, a 
breach of confidentiality is a potential risk. Furthermore, women may have to spend a significant 
amount of time at the study clinic (2-4 hours). 
 
Benefits for all participants include free HIV counselling and testing, free pregnancy testing, and free 
diagnosis and treatment of several common STIs, BV, vaginal candidiasis, and UTIs. In addition to 
treatment and referral for themselves, participants will be offered partner notification services if 
they are newly diagnosed with HIV or another STI. They will also receive male condoms free of 
charge. 
 
Workshop and IDI participants will not be exposed to any specific burdens or benefits, except for the 
time spent on these activities. They might contribute to improving urogenital health care in Rwanda. 
 
10.3 Compensation and insurance 
 
Participants will not receive any monetary compensation or reimbursements. They will be offered 
refreshments while waiting to be seen by a study clinician, or while attending the workshops or IDIs. 
 
UoL will obtain malpractice/no-fault liability insurance covering the entire conduct of the study. This 
insurance will cover the trial participants and study staff for any damage or injury that results from 
any study-related activities or procedures.  
 
10.4 Confidentiality 
 
Every attempt will be made to maintain the confidentiality of study participants. All women will be 
assigned a unique personal identification number for use on all study forms containing interview, 
clinical, and laboratory data. This identification number will be linked to women’s personal 
information in a central registry (the ePIR). Documents containing the names and/or signatures of 
participants (such as consent forms) will be kept separately from all other study documents 
containing identification numbers only. Each specimen will also be given a unique identification 
number to link them to other laboratory results and questionnaire data of the same person at the 
same visit. In IDIs, participants will be told they can use a name other than their given name for 
confidentiality. Transcripts from the IDIs will not contain participants’ given names. The workshop 
reports will contain a list of workshop attendees, but will not specify which opinions were voiced by 
which individuals. 
 

6 June 2016 
 
21 
All interviews, counselling procedures and clinical procedures will be conducted in private and study 
staff will be told not to share confidential information regarding study participants with anyone 
outside the study team without a participant’s consent. All completed study forms and documents 
will be kept in lockable rooms and/or cabinets at RU. Care will be taken to maintain confidentiality 
during follow-up. Study results will be presented as aggregated data, with no personal information. 
 
10.5 Informed consent procedures 
 
Written informed consent will be obtained from all study participants. The informed consent form 
(ICF) has to be co-signed by a parent or guardian when the participant is aged 18-20 and unmarried 
(by Rwandan law, women aged 18-20 who are legally married are no longer considered legal minors 
and can sign for themselves). Participants with insufficient literacy can provide a thumbprint but the 
informed consent process should be observed by an independent witness who co-signs the ICF. The 
witness cannot be a RU staff member, but can be another study participant. 
 
Two separate participant information sheets (PIS) and ICFs will be used: one for the cross-sectional 
study and one for the IDIs. In the cross-sectional study, the informed consent process may start with 
a video or group session in the waiting room, but will always be followed by an individual session 
attended by the participant and, if applicable, her parent/guardian and/or her witness. The consent 
procedures will be conducted in the language chosen by the participant and will be completed 
before study procedures take place. In all cases, two copies of the PIS and ICF documents will be 
provided to the participant (and her parent/guardian and/or witness if applicable); they will be 
asked to leave one fully signed copy at RU for the study files and to take one fully signed copy home 
for their own records. 
 
Participants will be asked to sign separately for long-term storage of specimens for future testing 
that is not currently specified in this study protocol. Any additional testing would be formally 
approved by the study sponsor and the ethics committees listed in section 10.1 via a protocol 
amendment prior to initiation of testing. If a participant does not consent to long-term storage, her 
specimens will be destroyed after the primary and secondary study objectives have been achieved. 
Similarly, participants will be asked to sign separately for their anonymised data to be used in future 
research studies by third parties in line with open data requirements. If a participant does not 
consent to this, her anonymised data will not be released to third parties. 
 
Participants can take the PIS and ICF home to think it over or discuss with others and come back on 
another day. After having signed the consent form, participants are free to withdraw at any time. 
This would entail notifying any RU staff member of the withdrawal. Data and samples that were 
already collected up to that point would be discarded. 
 
11. 
INVESTIGATIONAL PRODUCTS 
 
In this study, no investigational products will be used. 
 
12. 
OTHER 
 
12.1 Funding 
 
This study is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP). 
The main funding contract is between EDCTP and the UoL IGH (grant number EDCTP-CSA MI -2014-
592) and by subcontract between UoL IGH and RU and UoL IGH and ITM. 
 

6 June 2016 
 
22 
12.2 Study management and oversight 
 
The trial sponsor is UoL and this protocol and other study documentation was therefore reviewed 
and approved by the UoL Sponsorship Committee. Overall study management at UoL will be 
coordinated by the Chief Investigator Prof. van de Wijgert in the Institute of Infection and Global 
Health. She will make use of resources available through the UoL Research Support Office. 
 
Study implementation in Rwanda will be managed by the RU team, led by the Principal Investigator 
Dr. Stephen Agaba. He will work closely with the RU community outreach, clinical, laboratory, data 
management, and social science team leaders. All clinical and qualitative research procedures (with 
the possible exception of the IDI’s with stakeholders), as well as diagnostic laboratory testing, will 
take place at RU according to RU SOPs and using RU source documents.  
 
12.3 Protocol amendments 
 
This study will be conducted in full compliance with the most recent approved version of the study 
protocol. Protocol amendments will be reviewed and approved by the investigators and ethical 
review committees prior to implementing the amendment, except when necessary to protect the 
safety, rights and wellbeing of study participants. 
 
12.4 Good clinical practice 
 
This study will be implemented in accordance with the ICH-Good Clinical Practice (GCP) and Good 
Clinical Laboratory Practice (GCLP) guidelines. We will implement the following monitoring 
procedures: 
- 
The Chief Investigator will travel to Kigali to conduct the study training and study initiation visit. 
- 
During implementation of the demonstration project, daily internal quality control procedures 
will be implemented in accordance with the RU SOP for Data Management and Quality Control 
(which is based on ICH-GC(L)P). 
- 
A UoL project manager will conduct two monitoring visits during implementation of the 
demonstration project.   
- 
The Chief Investigator will travel to Kigali again to conduct the study close-out visit. 
 
12.5 Study termination 
 
If the study is prematurely terminated or suspended, the Chief Investigator will promptly inform the 
investigators/institutions involved in the study, the ethics committees listed in section 10.1, the 
Rwanda National Research Committee, and the Rwanda Ministry of Health of the termination or 
suspension and the reason(s) for the termination or suspension. The RU Principal Investigator is 
responsible for informing active study participants of study termination or suspension. 
 
12.6 Dissemination of results 
 
Findings from this project will be disseminated at a workshop in Kigali after the completion of the 
study as described in section 7. They will also be presented at national and international 
conferences, and published in peer-reviewed journals. Findings will be reported back to the study 
participants and their communities by RU staff with the help of the community mobilisers. 
 
12.7 Archiving 
 
Study records and data will be kept at RU according to the RU SOP for Archiving. RU will retain all 

6 June 2016 
 
23 
study records and data until all data analyses and report-writing have been completed, after which 
they will be destroyed. Study records and data may not be destroyed without prior written approval 
from the Chief Investigator.  
 
After database lock, all anonymised study data will also be kept on the UoL M-drive (under the 
custodianship of the Chief Investigator) until all data analyses and report-writing has been 
completed. After that, the anonymised study data will be archived in the UoL RDM DataStore 
(https://www.liverpool.ac.uk/csd/research-data-management/). 
 
All data generated in this project will be co-owned by RU and UoL. However, after database lock, the 
anonymised data will be shared with project partner ITM Antwerp and with the Ministry of Health in 
Rwanda. The anonymised data may also be made available to other interested parties using RDM 
DataStore facilities on a case-by-case basis. The ePIR will never be shared with third parties to 
protect participant confidentiality.  
 
13. REFERENCES 
 
1. 
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2013; 24(2):139-143. 
5. 
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vaginosis in different sub-populations of women in sub-Saharan Africa. PLoS One 2014; 
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Rees HV, Masenga G, Kiwelu I, Moyes J, Smythe SC. Safety, tolerability, and systemic absorption 
of dapivirine vaginal microbicide gel in healthy, HIV-negative women. AIDS 2009; 3:1531-1538. 
10. Schurmans C, De Baetselier I, Kestelyn E, Jespers V, Delvaux T, Agaba SK, van Loen H, Menten J, 
van de Wijgert J, Crucitti T, for the RingPlus study group. The RingPlus project: safety and 
acceptability of vaginal rings that protect women from unintended pregnancy. BMC Public 
Health 2015; http://dx.doi.org/10.1186/s12889-015-1680-y. 
11. Global Strategy for the Prevention and Control of Sexually Transmitted Infections: 2006-2015. 
Geneva, World Health Organisation, 2006. 
12. van de Wijgert J, Morrison C, Brown J, Kwok C, Van Der Pol B, Chipato T, Byamugisha J, Padian 
N, Salata R. Disentangling the contributions of reproductive tract infections on HIV acquisition in 
African women. Sex Transm Dis 2009; 36:357-364. 
13. Weiss HA, Buvé A, Robinson NJ, Van Dyck E, Kahindo M, Anagonou S, Musonda R, Zekeng L, 
Morison L, Caraël M, Laga M, Hayes RJ; Study Group on Heterogeneity of HIV Epidemics in 
African Cities. The epidemiology of HSV-2 infection and its association with HIV infection in four 
urban African populations. AIDS 2001; 15 Suppl 4:S97-108.  
14. Nsanzimana S, Remera E, Kanters S, Chan K, Forrest JI, Ford N, Condo J, Binagwaho A, Mills EJ. 
Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort 
study. Lancet Glob Health 2015; 3(3):e169-77. 
15. Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Ndayisaba GF, Jurriaans S, Schuren FH, van 
de Wijgert JH. Lactobacillus-dominated cervicovaginal microbiota associated with reduced 
HIV/STI prevalence and genital HIV viral load in African female sex workers. ISME J 2014; doi: 
10.1038/ismej.2014.26. 
16. Guidelines for the management of sexually transmitted infections. Geneva, World Health 
Organisation, 2003. 
17. Report of the expert consultation and review of the latest evidence to update guidelines for the 
management of sexually transmitted infections. Geneva, World Health Organisation, 2008. 
18. Otieno FO, Ndivo R, Oswago S, Ondiek J, Pals S, McLellan-Lemal E, Chen RT, Chege W, Gray KM. 
Evaluation of syndromic management of sexually transmitted infections within the Kisumu 
Incidence Cohort Study. Int J STD AIDS 2014; 25(12):851-859. 
19. Råssjö EB, Kambugu F, Tumwesigye MN, Tenywa T, Darj E. Prevalence of sexually transmitted 
infections among adolescents in Kampala, Uganda, and theoretical models for improving 
syndromic management. J Adolesc Health 2006; 38(3):213-221. 
20. Nys S, van Merode T, Bartelds AI, Stobberingh EE. Urinary tract infections in general practice 
patients: diagnostic tests versus bacteriological culture. J Antimicrob Chemother 2006; 
57(5):955-958. 
21. Huppert J, Hesse E, Gaydos CA. What’s the point? How point-of-care STI tests can impact 
infected patients. Point Care 2010; 9(1):36-46. 
22. Fonjungo PN, Boeras DI, Zeh C, Alexander H, Parekh BS, Nkengasong JN. Access and quality of 
HIV-related point-of-care diagnostic testing in global health programs. Clin Infect Dis 2016; 
62(3):369-374.   
23. Causer LM, Kaldor JM, Fairley CK, Donovan B, Karapanagiotidis T, Leslie DE, Robertson PW, 
McNulty AM, Anderson D, Wand H, Conway DP, Denham I, Ryan C, Guy RJ. A laboratory-based 
evaluation of four rapid point-of-care tests for syphilis. PLoS One 2014; 9(3):e91504. 
24. Jones HE, Lippman SA, Caiaffa-Filho HH, Young T, van de Wijgert JH. Performance of a rapid self-
test for detection of Trichomonas vaginalis in South Africa and Brazil. J Clin Microbiol 2013; 
51(3):1037-1039. 
25. Sonkar SC, Wasnik K, Kumar A, Mittal P, Saluja D. Comparative analysis of syndromic and PCR-
based diagnostic assay reveals misdiagnosis/ overtreatment for trichomoniasis based on 
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26. Natoli L, Maher L, Shephard M, Hengel B, Tangey A, Badman SG, Ward J, Guy RJ; TTANGO 
Investigators. Point-of-care testing for chlamydia and gonorrhoea: implications for clinical 
practice. PLoS One 2014; 9(6):e100518. 
27. Peeling RW, Holmes KK, Mabey D, Ronald A. Rapid tests for sexually transmitted infections 
(STIs): the way forward. Sex Transm Infect 2006; 82 Suppl 5:v1-6. 
28. Gaydos CA. Review of use of a new rapid real-time PCR, the Cepheid GeneXpert® (Xpert) CT/NG 
assay, for Chlamydia trachomatis and Neisseria gonorrhoeae: results for patients while in a 
clinical setting. Expert Rev Mol Diagn 2014; 14(2):135-137. 
29. Amsel R, Totten P, Spiegel C, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis - 
diagnostic-criteria and microbial and epidemiologic associations. Am J Med 1983; 74:14-22. 
30. Nugent R, Krohn M, Hillier S. Reliability of diagnosing bacterial vaginosis is improved by a 
standardized method of Gram stain interpretation. J Clin Microbiol 1991; 29:297-301. 
31. van de Wijgert JHHM, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H, Jespers V.  
The vaginal microbiota: what have we learned after a decade of molecular characterization? 
PLoS One 2014; 9(8):e105998. 
32. Mlisana K, Naicker N, Werner L, Roberts L, van Loggerenberg F, Baxter C, et al. Symptomatic 
vaginal discharge is a poor predictor of sexually transmitted infections and genital tract 
inflammation in high-risk women in South Africa. J Infect Dis 2012; 206(1): 6–14. 
33. Vuylsteke B, Laga M, Alary M, Gerniers MM, Lebughe JP, Nzila N, Behets F, Van Dyck E, Piot P. 
Clinical algorithms for the screening of women for gonococcal and chlamydial infection: 
evaluation of pregnant women and prostitutes in Zaire. Clin Infect Dis 1993; 17(1):82-88. 
34. Binagwaho A, Ngabo F, Wagner CM, Mugeni C, Gatera M, Nutt CT, Nsanzimana S. Integration of 
comprehensive women's health programmes into health systems: cervical cancer prevention, 
care and control in Rwanda. Bull World Health Organ 2013; 91(9):697-703. 
 

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26 
14. 
APPENDICES 
 
14.1 Schedule of assessments 
 
 
Procedures 
Main visit 
Additional 
visits 
IDI 
Informed consent 
X 
 
X 
Assign PIN and contact information 
X 
 
X 
Eligibility checklist 
X 
 
 
Face-to-face interview incl. risk scoring/symptoms, quantitative 
X 
 
 
Face-to-face interview, qualitative 
 
 
X 
Offer services and ask women if they want to opt out of any services 
X 
X1 
 
HIV/STI/BV risk reduction counselling 
X 
[X] 
 
If not opted out: Venepuncture (10 ml) or finger prick 
X 
 
 
- Rapid HIV testing2 
X 
 
 
- If pregnant or selected by risk scoring: Syphilis POCT 
X 
 
 
If not opted out and indicated: Urine collection 
X 
 
 
- If indicated: hCG urine pregnancy testing 
X 
 
 
- If UTI symptoms: Urinalysis dipstick testing 
X 
 
 
If not opted out: Collection of vaginal swabs without speculum  
 
(choose if self-sampling or clinician-sampling) 
X 
 
 
- Vaginal pH and TV POCT 
X 
 
 
- If selected by risk scoring: CT/NG POCT 
X 
 
 
Gynaecological exam3 
[X] 
[X] 
 
Provide POCT results 
X 
X 
 
Provide treatment based on POCT results and management of genital 
ulcers/inguinal bubos, vaginal candidiasis and lower abdominal pain if 
relevant symptoms reported 
[X] 
[X] 
 
Provide partner notification and treatment 
 
[X] 
 
Provide referrals 
[X] 
[X] 
 
Client satisfaction survey (on a subsample) 
X 
 
 
Laboratory procedures at end of study 
 
 
 
Vaginal swabs: 
 
 
 
- CT/NG POCT on stored samples from women who were not 
tested before 
X 
 
 
- If funding permits: NG, CT, TV, BV PCRs on all stored samples 
X 
 
 
Left-over urine: 
 
 
 
- If funding permits: molecular testing of stored samples to 
determine organisms associated with UTIs 
X 
 
 
BV=bacterial vaginosis; CT=Chlamydia trachomatis; FU=follow=up; hCG=human chorionic gonadotropin; IDI=in depth interview; 
NG=Neisseria gonorrhoeae; PIN=participant identification number; PCR=polymerase chain reaction; POCT=point-of-care test; STI=sexually 
transmitted infection; UTI=urinary tract infection; TV=Trichomonas vaginalis. [x] = only if indicated. 
1. Only procedures for which the visit was intended will be carried out. 
2. By the algorithm recommended in the most recent Rwandan HIV voluntary counselling and testing guidelines. 
3. Gynaecological exams will only be done when deemed necessary by the study physician (for example, in the case of genital ulcers or 
lower abdominal pain). 
 
 
14.2 
WISH clinical algorithms 
 
See attached as a separate document 
 
14.3 
WISH treatment guidelines by etiologic or syndromic diagnosis 
 
See attached as a separate document 

Appendix 14.2: WISH clinical algorithms
No or mild 
symptoms
Severe vaginal 
discharge, no lower 
abdominal pain
Lower abdominal 
pain  (+/- vaginal 
discharge)
Genital ulcers, 
buboes, warts
Pelvic/bimanual to 
confirm discharge
Pelvic/bimanual
Tenderness=PID
Inspection, pelvic 
to differentiate
• POCT pH TV
• POCT CT/NG & 
syph if score +
• POCT pH TV
• POCT CT/NG (& 
syph if score +)
• POCT pH TV
• POCT CT/NG if 
PID (& syph if 
score +)
• POCT pH TV
• POCT syph (& 
CT/NG if score+)
Treat any 
positive POCTs
Treat any positive 
POCTs or discharge 
indicative of vaginal 
candidiasis or 
severe discharge 
consistent with BV
Treat for PID
Add tx for NG if NG 
POCT +
Refer if severe
Treat 
syndromically
Also treat any 
positive POCTs.
CT= Chlamydia trachomatis; NG= Neisseria gonorrhoeae; pH=vaginal pH; PID=pelvic inflammatory disease; POCT=point of care test; 
syph=syphilis; TV= Trichomonas vaginalis.

APPENDIX 14.3: WISH TREATMENT GUIDELINES BY ETIOLOGIC OR SYNDROMIC DIAGNOSIS 
 
Diagnosis 
Treatment (follow latest Rwandan guidelines) 
Other Follow-Up 
Gonorrhea  
 
Positive GeneXpert NG test. 
Treat regardless of the presence of 
symptoms. 
 
1st choice: Ciprofloxacin 1g single oral dose 
 
2nd choice: Ceftriaxone 250 mg in one single IM dose 
- 
In female sex workers, also consider the possibility of rectal or pharyngeal 
NG (take throat and rectal swabs for testing if suspected). 
- 
Actively follow-up participants with laboratory-confirmed NG 
approximately 7 days after treatment to check for treatment failure (due to 
NG resistance). If symptoms are still reported, give the 2nd choice treatment. 
- 
Male partners should be treated in the same manner as the female index 
case. Couples should be treated around the same time and counseled to 
abstain from sex or use condoms during treatment to avoid re-infections. 
Chlamydia  
 
Positive GeneXpert CT test. 
Treat regardless of the presence of 
symptoms. 
1st choice: Doxycyclin 100 mg twice per day for 7 days 
 
2nd choice: Erythromycin 1g twice per day for 7 days 
- 
Most CT infections are asymptomatic so active follow-up after treatment is 
not useful. 
- 
Male partners should be treated in the same manner as the female index 
case. Couples should be treated around the same time and counseled to 
abstain from sex or use condoms during treatment to avoid re-infections. 
Trichomoniasis 
 
Positive TV OSOM test. 
Treat regardless of the presence of 
symptoms. 
 
1st choice: Metronidazole 2 g single oral dose 
OR Metronidazole 400 or 500 mg orally twice per day for 7 
days 
 
2nd choice: Tinidazole 2g single oral dose OR Tinidazole 500 
mg twice per day for 7 days 
- 
If BV is also present (see below), the 7 day treatment is preferred because it 
is more effective against BV. However, if poor adherence is suspected, use a 
single dose treatment. 
- 
Male partners should also be treated in the same manner as the female index 
case. Couples should be treated around the same time and counseled to 
abstain from sex or use condoms during treatment to avoid re-infections. 
Bacterial vaginosis 
 
Vaginal pH is 5.0 or higher.  
Treat regardless of the presence of 
symptoms. 
1st choice: Metronidazole 400 or 500 mg orally twice per day 
for 7 days OR Metronidazole 2g single oral dose. 
 
  
2nd choice: Tinidazole 2g orally once a day for 2 days or 1g per 
day for 5 days. 
Alternative: Clindamycin 300 mg orally twice per day for 7 
days 
 
- 
Metronidazole 2g single oral dose is a less effective treatment for BV than 
the 7-day treatment. Only give a single oral dose if you are worried that the 
patient will not be adherent for 7 days. 
- 
Women should be encouraged to wear clean underwear daily, not wash 
inside the vagina (and if this cannot be avoided, to use clean plain water 
only), and use hormonal contraception to prevent recurrence. 
- 
Male partners are not treated but women should be told that BV-associated 
bacteria can be passed between sexual partners. Their male partners should 
be encouraged to improve their penile hygiene and clean underneath the 
foreskin regularly. 
Vaginal candidiasis 
 
When symptoms typical for vaginal 
candidiasis are present: White, curd-like, 
odorless vaginal discharge with vaginal 
itching and/or burning. 
1st choice: Fluconazole 150 mg single oral dose 
 
2nd choice: Clotrimazole 200 mg pessaries every night for 3 
nights 
- 
Do not treat without lab confirmation; do not treat if asymptomatic) 
- 
Male partners are not notified but if a male partner has symptoms of 
balanoprosthitis, he can be given 1% Clotrimazole cream to be applied for 
14 days. 
- 
Patients should be counseled to abstain from sex or use condoms, until 
symptoms have cleared. 
 
 

Diagnosis 
Treatment 
Other Follow-Up 
Active primary syphilis 
 
When treponemal test (Determine) is positive and non-
treponemal test (RPR) has been positive for < 2 years. 
 
Treat regardless of the presence of symptoms (symptoms 
associated with primary syphilis: Painless, rubbery, mobile 
genital sores). 
1st choice: Benzathine benzyl penicillin 2.4 
million IU IM single dose. 
 
Alternatives: Erythromycin 1g orally 2x per 
day x 14 days OR Doxycyclin 100 mg orally 
twice per day x 14 days 
- 
Male partners should also be treated. If the woman has primary syphilis, her 
male partner(s) may have past, primary, secondary or neurosyphilis. For this 
reason, the male partner(s) should be seen by a RU Physician to determine 
which syphilis treatment is required. Syphilis testing of the male partner 
may be conducted. However, even if his tests show past instead of active 
infection, treatment for primary syphilis should be given because of recent 
exposure to the index case. 
- 
Couples should be treated around the same time and counseled to abstain 
from sex or use condoms during treatment to avoid re-infections. 
Active secondary syphilis or active syphilis of unknown 
duration 
 
When treponemal test (Determine) is positive and non-
treponemal test (RPR) has been positive for > 2 years or for 
unknown duration. 
 
Treat regardless of presence of symptoms (symptoms 
associated with secondary syphilis: generalised skin 
lesions, many others). 
1st choice: Benzathine benzyl penicillin 2.4 
million IU IM once a week x 3 weeks 
 
Alternatives: Erythromycin 500 mg orally 3x 
per day x 30 days OR Doxycyclin 100 mg 
orally twice per day x 30 days 
- 
Ask if the participant has ever been treated in the past. However, if the 
treponemal and non-treponemal tests are both still positive, treat anyway 
regardless of past treatments. 
- 
Male partners should also be treated. See active primary syphilis above. 
- 
Couples should be treated around the same time and counseled to abstain 
from sex or use condoms during treatment to avoid re-infections. 
Neurosyphilis 
 
When treponemal (Determine) and non-treponemal (RPR) 
tests are both positive and there is neuro-muscular 
involvement. 
Refer to a hospital as a matter of urgency for 
intravenous Benzathine benzyl penicillin 
treatment. 
- 
Male partners should also be treated. See active primary syphilis above. 
- 
Couples should be treated around the same time and counseled to abstain 
from sex or use condoms during treatment to avoid re-infections. 
Syndrome: Vaginal discharge without lower abdominal 
pain  
 
Conduct speculum and bimanual examination and treat 
only if cervical and/or vaginal discharge is seen and lower 
abdominal pain is ruled out. 
 
- If mucopurulent discharge from the cervix 
or cervicitis are present: Treat for NG, CT, 
and TV as described above; 
- If mucopurulent discharge from the cervix 
or cervicitis are NOT present: Treat for BV, 
vaginal candidiasis, and TV as described 
above. 
- 
Partner notification and treatment is not done but women will be advised to 
encourage their male partner(s) to get tested themselves. To avoid social 
harms, we will explain to women that their vaginal discharge may be 
physiological and that we did not confirm the presence of an STI. 
- 
Women should be advised to abstain from sex or use condoms during 
treatment just in case they do have a STI. 
Syndrome: Lower abdominal pain or deep dyspareunia 
with or without vaginal discharge (=PID) 
 
- RU Physician to conduct a speculum and bimanual 
examination; diagnose acute PID only in the case of 
cervical motion, uterine, or adnexal tenderness. 
- Conduct CT/NG testing. 
- Refer to the hospital in case of a missed period, recent 
delivery, abortion, or miscarriage, abdominal guarding or 
rebound tenderness, abnormal vaginal bleeding, or 
abdominal mass. Also refer to the hospital if the PID is 
severe (e.g. temp>38 ̊C).   
If PID confirmed by RU Physician: 
 
1st choice: Ciprofloxacin 500mg twice per day for 3 days 
AND Doxycycline 100 mg twice a day for 14 days AND 
Metronidazole 500mg twice a day for 14 days.  
Add Ceftriaxone 250 mg IM single dose if the participant is 
NG-positive. 
 
Alternatives: Ceftriaxone 250 mg IM in a single dose AND 
Erythromycin 1g twice per day for 14 days with meals AND 
Tinidazole 1g per day for 14 days. 
 
- 
Actively follow-up participants with laboratory-confirmed NG 
approximately 7 days after treatment completion to check if 
the PID symptoms have improved. If not, treatment with 
additional antibiotics should be considered to cover 
potentially 
- 
Male sexual partners will be tested for CT/NG, and will 
receive treatment according to those test results. If both tests 
are negative, they will not receive any treatment. 
- 
Couples should be treated around the same time and 
counseled to abstain from sex or use condoms during 
treatment to avoid re-infections. 

Diagnosis 
Treatment 
Other Follow-Up 
Syndrome: Genital vesicles with or without inguinal 
buboes with the notion of recurrence (= genital herpes) 
 
- RU Physician to inspect and palpate external 
genitalia/inguinal area and conduct speculum exam to 
differentiate between the various genital ulcer/bubo 
syndromes and genital warts. 
Note: herpetic vesicles are usually painful. 
If confirmed by RU Physician: 
 
1st (and only) choice: Acyclovir 400 mg orally 3 times per 
day x 7 days and 5 days in case of recurrence 
- 
In female sex workers, also consider the possibility of anal 
genital vesicles 
- 
The treatment will not cure genital herpes but will reduce 
HSV-2 shedding and onward transmission, and may reduce 
the duration of the outbreak. 
- 
Partner notification and treatment is not indicated but the 
women should be adviced to abstain from sex or use condoms 
during outbreaks to HSV-2 transmission to sexual partner(s). 
Syndrome: Genital ulcers not suggestive of genital 
herpes with or without inguinal buboes  
 
- RU Physician to inspect external genitalia/inguinal area 
and conduct speculum exam to differentiate between the 
various genital ulcer/bubo syndromes and genital warts. 
If confirmed by RU Physician: 
 
Treat for syphilis (as described above) and chancroid: 
Ciprofloxacin 500 mg orally twice per day for 3 days 
(Alternative: Ceftriaxone 250 mg in one single IM dose) 
- 
In female sex workers, also consider the possibility of anal 
genital ulcers 
- 
Male partners should receive the same treatments. 
- 
Couples should be treated around the same time and 
counseled to abstain from sex or use condoms during 
treatment to avoid re-infections. 
Syndrome: Inguinal buboes without ulcers 
 
- RU Physician to inspect and palpate external 
genitalia/inguinal area and conduct speculum exam to 
differentiate between the various genital ulcer/bubo 
syndromes and genital warts. 
If confirmed by RU Physician: 
 
Treat for chancroid (as described above) and LGV: 
Doxycycline 100mg twice per day for 21 days. 
- 
In female sex workers, also consider the possibility of anal 
LGV. Anal LGV may not cause inguinal buboes but may 
cause proctocolitis symptoms instead. 
- 
Male partners should receive the same treatments. Couples 
should be treated around the same time and counseled to 
abstain from sex or use condoms to avoid re-infections. 
Syndrome: Genital warts/condylomata 
 
- RU Physician to inspect and palpate external 
genitalia/inguinal area and conduct speculum exam to 
differentiate between the various genital ulcer/bubo 
syndromes and genital warts. 
- In the case of mild warts, provide treatment with 20% 
podophyllin solution. 
- In the case of severe warts/condylomata, refer for 
cryotherapy. 
 
- 
In female sex workers, also consider the possibility of anal 
genital warts 
- 
Treatment of male partners is not indicated. Women should be 
adviced to abstain from sex or use condoms during outbreaks 
to avoid HPV transmission to sexual partner(s). 
Urinary tract infection 
 
- Do urinalysis test only when UTI symptoms are present. 
- Treat when urinalysis test shows at least 1+ leukocytes 
or nitrites. Also consider treatment if there is blood in 
urine that cannot be explained by menstrual blood or 
spotting related to contraceptive use. 
 
- 1st choice: Ciprofloxacin 500 mg orally twice per day x 7 
day. Alternative: Ceftriaxone IM 125 twice per day x 5 
days. 
- 
No follow-up and no male partner treatment required. 
Cervical cytology (not done at RU) 
- Refer all high-risk women for cervical cancer screening if 
they have not undergone screening in the past five years. 
- 
No male partner referral required. 
CONTRAINDICATIONS:  
• 
Doxycyclin, tetracyclin, ciprofloxacin and cotrimoxazole should not be used during pregnancy and lactation; doxycyclin may reduce the effectiveness of hormonal contraception. 
Azithromycin and ceftriaxone may be used by pregnant women.  
• 
Metronidazole and fluconazole can be used only once during the first trimester of pregnancy; patients must not drink alcohol while taking metronidazole. 
• 
Benzathine benzyl penicillin is contraindicated in case of allergy or when using hormonal contraception. 
• 
Doxycyclin and erythromycin should be taken with meals.