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EDITORIAL

Sexually transmitted infections—Research

priorities for new challenges

Nicola Low1*, 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

* [email protected]

The World Health Organization (WHO) estimates that more than 1 million new sexually

transmitted infections (STIs) are acquired each day [1]. 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 [2].

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) [3]. 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) [4].

Second, modern STI management is being increasingly challenged by AMR, which has

already compromised the treatment of gonorrhoea [5] 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 [6]. A linked Perspective by Mag-

nus Unemo and Christian Althaus discusses the study in the context of current knowledge

about gonococcal resistance to cephalosporins [7]. 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

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OPENACCESS

Citation: Low N, Broutet NJ (2017) Sexually

transmitted infections—Research priorities for new

challenges. PLoS Med 14(12): e1002481. https://

doi.org/10.1371/journal.pmed.1002481

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

work.

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

board.

Abbreviations: AMR, antimicrobial resistance;

HCP, healthcare provider; HSP-2, herpes simplex

type 2; PrEP, pre-exposure prophylaxis; STI,

sexually transmitted infection; WHO, World Health

Organization.

Provenance: Commissioned; not externally peer

reviewed

alarming levels of resistance to macrolide and fluoroquinolone antimicrobials [8]. 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 [9]. 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 [10]. 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 [11]. 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

[12]. 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 [13].

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 [14]. 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 [15]. 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 / 3

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

[16]. 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.

References 1. World Health Organization. Sexually transmitted infections (STIs). Geneva: World Health Organiza-

tion; 2017 [cited 2017 Nov 23]. Available from: http://www.who.int/mediacentre/factsheets/fs110/en/.

2. World Health Organization. Global health sector strategy on sexually transmitted infections, 2016–

2021. Geneva: World Health Organization; 2016 [cited 2017 Nov 23]. Available from: http://www.who.

int/reproductivehealth/publications/rtis/ghss-stis/en/.

3. Mohammed H, Mitchell H, Sile B, Duffell S, Nardone A, Hughes G. Increase in sexually transmitted

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https://doi.org/10.3201/eid2201.151331 PMID: 26689861

4. Fingerhuth SM, Bonhoeffer S, Low N, Althaus CL. Antibiotic-resistant Neisseria gonorrhoeae spread

faster with more treatment, not more sexual partners. PLoS Pathog. 2016; 12(5):e1005611. https://doi.

org/10.1371/journal.ppat.1005611 PMID: 27196299

5. Wi T, Lahra MM, Ndowa F, Bala M, Dillon JR, Ramon-Pardo P, et al. Antimicrobial resistance in Neis-

seria gonorrhoeae: global surveillance and a call for international collaborative action. PLoS Med. 2017;

14(7):e1002344. https://doi.org/10.1371/journal.pmed.1002344 PMID: 28686231

6. Whittles LK, White PJ, Didelot X. Estimating the fitness cost and benefit of cefixime resistance in Neis-

seria gonorrhoeae to inform prescription policy: a modelling study. PLoS Med. 2017; 14(10):e1002416.

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7. Unemo M, Althaus CL. Fitness cost and benefit of antimicrobial resistance in Neisseria gonorrhoeae:

multidisciplinary approaches are needed. PLoS Med. 2017; 14(10):e1002423. https://doi.org/10.1371/

journal.pmed.1002423 PMID: 29088232

8. Jensen JS. Mycoplasma genitalium: yet another challenging STI. Lancet Infect Dis. 2017; 17(8):795–6.

https://doi.org/10.1016/S1473-3099(17)30364-X PMID: 28701270

9. Chesang K, Hornston S, Muhenje O, Saliku T, Mirjahangir J, Viitanen A, et al. Healthcare provider per-

spectives on managing sexually transmitted infections in HIV care settings in Kenya: a qualitative the-

matic analysis. PLoS Med. 2017; 14(12):e1002480. https://doi.org/10.1371/journal.pmed.1002480

10. Hawkes S. Sexual health: a post-2015 palimpsest in global health? Lancet Glob Health. 2014; 2(7):

e377–8. https://doi.org/10.1016/S2214-109X(14)70036-1 PMID: 25103379

11. Nurse-Findlay S, Taylor MM, Savage M, Mello MB, Saliyou S, Lavayen M, et al. Shortages of ben-

zathine penicillin for prevention of mother-to-child transmission of syphilis: an evaluation from multi-

country surveys and stakeholder interviews. PLoS Med. 2017; 14(12):e1002473. https://doi.org/10.

1371/journal.pmed.1002473

12. Wilson E, Free C, Morris TP, Syred J, Ahamed I, Menon-Johansson AS, et al. Internet-accessed sexu-

ally transmitted infection (e-STI) testing and results service: a randomised, single-blind, controlled trial.

PLoS Med. 2017; 14(12):e1002479. https://doi.org/10.1371/journal.pmed.1002479

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PMID: 29192020

14. Johnston C, Magaret A, Roychoudhury P, Greninger AL, Reeves D, Schiffer J, et al. Dual-strain genital

herpes simplex virus type 2 (HSV-2) infection in the US, Peru, and 8 countries in sub-Saharan Africa: a

nested cross-sectional viral genotyping study. PLoS Med. 2017; 14(12):e1002475. https://doi.org/10.

1371/journal.pmed.1002475

15. van de Wijgert JHHM. The vaginal microbiome and sexually transmitted infections are interlinked: con-

sequences for treatment and prevention. PLoS Med. 2017; 14(12):e1002478. https://doi.org/10.1371/

journal.pmed.1002478

16. Bernstein K, Bowen VB, Kim CR, Counotte MJ, Kirkcaldy RD, Kara E, et al. Re-emerging and newly rec-

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