Sexually transmitted infections—Research
priorities for new challenges
Nicola Low 1*, Nathalie J. Broutet2
1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland, 2 Department of
Reproductive Health Research, World Health Organization, Geneva, Switzerland
The World Health Organization (WHO) estimates that more than 1 million new sexually
transmitted infections (STIs) are acquired each day . STIs are pernicious players in the
global burden of disease, their management stymied by the diversity of pathogens, social
stigma, and commonly mild or nonexistent symptoms. As quietly as they persist, STIs have
prominent sequelae—for example, roughly one-third of pregnant women infected with syphi-
lis experience adverse birth outcomes including stillbirth, human papillomavirus (HPV) infec-
tion leads to an estimated 266,000 cervical cancer deaths annually, and some bacterial STIs
cause pelvic inflammatory disease, female infertility, preterm delivery, and low birthweight.
The imperative for innovation at this time is one of the strategic directions of the WHO global
health sector strategy to address the burden of STIs .
This month, PLOS Medicine launches the research content from our Collection on Pre- vention, Diagnosis, and Treatment of STIs. The Collection will feature Research Articles
submitted in response to our call for papers this past summer, with related Perspectives
from international STI experts. Two pressing themes frame current research in this area.
First, the means of prevention for HIV and for other STIs are now decoupled, with gonor-
rhoea and syphilis amongst men who have sex with men on the rise as an unintended con-
sequence of antiretroviral therapy that renders HIV undetectable in blood, and of the
availability of pre-exposure prophylaxis (PrEP) . When condoms were the main preven-
tion technology for all sexually transmitted pathogens, prevention messages were unified
but uptake was patchy. PrEP, on the other hand, is now being adopted and adhered to
more readily by the people at highest risk of acquiring HIV infection, but does not prevent
any other STI. In anticipation of increases in risky sexual behaviours in the context of
PrEP, researchers and practitioners should actively promote primary STI prevention,
including promotion of barrier methods. Indeed, secondary prevention strategies, includ-
ing more frequent screening for STIs, are not a panacea because an increased rate of untar-
geted treatment can drive antimicrobial resistance (AMR) .
Second, modern STI management is being increasingly challenged by AMR, which has
already compromised the treatment of gonorrhoea  and is expanding geographically. Some
possible solutions to the threat of AMR are explored in the Collection. In their mathematical
modelling study, Xavier Didelot and colleagues project how cautious use of previously aban-
doned antimicrobials could mitigate the spread of resistance . A linked Perspective by Mag-
nus Unemo and Christian Althaus discusses the study in the context of current knowledge
about gonococcal resistance to cephalosporins . Additionally, risk assessment of the impact
on AMR should likely be required before the introduction of new preventive strategies or
guidelines. For example, new molecular diagnostic tests for Mycoplasma genitalium, which is under-recognised as a cause of urethritis and cervicitis, are considered likely to worsen already
PLOS Medicine | https://doi.org/10.1371/journal.pmed.1002481 December 27, 2017 1 / 3
Citation: Low N, Broutet NJ (2017) Sexually
transmitted infections—Research priorities for new
challenges. PLoS Med 14(12): e1002481. https://
Published: December 27, 2017
Copyright: © 2017 Low, Broutet. This is an open access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Funding: The authors received no funding for this
Competing interests: We have read the journal’s
policy and have the following conflicts: NL receives
a stipend as a Specialty Consulting Editor for PLOS
Medicine, and serves on the journal’s editorial
Abbreviations: AMR, antimicrobial resistance;
HCP, healthcare provider; HSP-2, herpes simplex
type 2; PrEP, pre-exposure prophylaxis; STI,
sexually transmitted infection; WHO, World Health
Provenance: Commissioned; not externally peer
alarming levels of resistance to macrolide and fluoroquinolone antimicrobials . Syndromic
treatment of symptomatic urethritis, the norm in both high- and low-income settings, has
actually limited the use of antimicrobials. Paradoxically, improved aetiological diagnosis will
result in increased treatment, and multidrug resistance, because asymptomatic infections will
also be detected and treated. New guidelines should recommend diagnostic test and treatment
strategies for urethritis and M. genitalium that minimise the risk of AMR. Challenges like these require real-world knowledge, and we believe that insights from social
science methodology are critical for illuminating possible solutions. We are delighted that this
Collection includes a qualitative study from Kipruto Chesang and colleagues, in which the
authors describe many of the challenges that healthcare providers (HCPs) worldwide face in
delivering STI care . The authors interviewed 87 HCPs working in HIV care centres across
Kenya. Their analysis shows strong HCP commitment to the provision of high-quality STI
care but underscores the impact of stigma and culturally embedded gender roles. This study
suggests that clinics often do not provide for the sexual and reproductive health needs of men
and boys, even though their active engagement is essential for the sexual health of both women
and men . Chesang and colleagues also describe the day-to-day health service barriers of
antimicrobial treatment failure, ascribed to resistance, insufficient training, and drug stock-
outs. In relation to the last point, Collection authors Stephen Nurse-Findlay and colleagues
explore the origins of a vexing worldwide shortage of benzathine penicillin for the treatment
of maternal syphilis, using country-level surveys and stakeholder interviews . They find
that local stock-outs are not just the result of demand-side under-procurement, but of supply-
side inflexibility and market exits for this cheap, off-patent drug.
In more auspicious developments, digital technologies and newer diagnostics with simple
requirements for specimen collection and transport are driving innovations in access to STI
care. In this area, Collection authors Emma Wilson and colleagues evaluated the benefits of
providing “e-STI testing and results” in a randomised controlled trial done in London, UK
. They used text messages to invite people to place an online order for self-sampling kits
for chlamydia, gonorrhoea, syphilis and HIV. The e-STI testing and results intervention
increased the proportion of people tested for STIs, and slightly increased the proportion diag-
nosed with any STI, compared with people sent a simple text message with information about
the location of STI clinics. The researchers used multiple active methods to reach and engage
their target group; therefore, to sustain the benefits of the e-STI testing intervention, these
health promotion activities would need to continue. Even in times of economic austerity, e-
STI testing should not be seen as a substitute for fully funded clinic-based services .
Meanwhile, highly efficacious vaccines against human papillomaviruses and hepatitis B virus
have demonstrated the benefits of innovation in vaccine development, and results in this Collec-
tion suggest that further innovation will not be wasted. Christine Johnston and colleagues’ find-
ings support the development of a vaccine against herpes simplex type 2 (HSV-2) as the next
most promising vaccine priority . In people with HSV-2 antibodies enrolled in epidemio-
logical studies in the Americas and sub-Saharan Africa, just 3.7% had prevalent infection with
more than one HSV-2 strain, indicating the effectiveness of naturally occurring protection.
Future progress in understanding the pathogenesis of STIs in women, who bear a large
proportion of the world population’s burden of STIs, will rely on the innovations of high-
throughput molecular sequencing methods that have revealed the complexity of the vaginal
microbiome. In a Perspective, Janneke van de Wijgert discusses what we now know about inter-
relationships between exogenous sexually transmitted bacterial pathogens, dysbiosis affecting
the lactobacillus-dominated microbiome, and pathobionts, commensal bacteria with patho-
genic potential . However, improved understanding of the nature and properties of vaginal
microbiomes will be required for the development of approaches for optimising vaginal health.
PLOS Medicine | https://doi.org/10.1371/journal.pmed.1002481 December 27, 2017 2 / 3https://doi.org/10.1371/journal.pmed.1002481
Successes in STI control require commitments to addressing the economic, social, cultural,
and behavioural determinants of STIs. In the face of a widening spectrum of infectious agents
that can be transmitted through sexual contact, as described in an Essay by Kyle Bernstein and
colleagues, interdisciplinary action will be important to the development of effective interventions
. High-quality research is one of the solutions that, together with strengthened capacity, pro-
motion of sexual rights and political commitment, can secure a future of effective STI prevention,
diagnosis, and treatment.
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