Category: Bacteria

Mycoplasma genitalium: the next sexually transmitted superbug?

Antimicrobial resistance and treatment failures are the biggest challenges

The publication of national treatment guidelines does not usually generate headlines in national newspapers. However, the recent release of draft management guidelines for Mycoplasma genitalium infection was accompanied by high profile media coverage suggesting that it is the next sexually transmitted “superbug.” So what are the facts behind these headlines, and how concerned should we be?

First isolated in 1981, M genitalium is the smallest known self replicating bacterium. Most infections are probably asymptomatic and have no adverse health outcomes. Nonetheless, evidence that M genitalium is associated with serious genitourinary and reproductive health morbidity is accumulating.

In men, there is an unequivocal association with non-gonococcal urethritis, and it is detected in up to 40% of men with persistent and recurrent urethritis. In women, a recent meta-analysis found significant associations with a range of clinical syndromes and adverse reproductive health outcomes, including cervicitis, postcoital bleeding, pelvic inflammatory disease, preterm birth, and spontaneous abortion, and a weak association with infertility.

The population prevalence of M genitalium infection ranged from 1.3% to 3.9% and was higher in countries with a low development index. In Britain, a probability sample survey estimated a prevalence of around 1.3% in the sexually active British population aged 16-44 years.4 In common with many other sexually transmitted infections (STIs), M genitalium infection rates can be considerably higher in men who have sex with men, sex workers, and people attending STI clinics.

Antimicrobial resistance

The main concern is M genitalium’s increasing resistance to azithromycin and moxifloxacin, the recommended first and second line treatments in Europe, North America, and Australia, especially in the Asia-Pacific region. For example, single nucleotide polymorphisms in region V of the 23S rRNA gene, which confer macrolide resistance, were found in over 60% of M genitalium specimens from people attending STI clinics in Australia in 2015. Furthermore, selective pressure can lead to the emergence of macrolide resistance after exposure to suboptimal levels of drug.

Importantly, resistance markers are highly correlated with treatment failure, especially when the organism load is high.

Is antiretroviral treatment for HIV increasing the susceptibility to syphilis

Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (ARV) for HIV-1 infection.

Treatment with ARV reduces risk of infection (because of greatly reduced viral load) and near-normal life expectancy for those on treatment. The currently accepted hypothesis is that these factors result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 sexually transmitted infections, including gonorrhoea, chlamydia and syphilis.

However, syphilis incidence has increased more rapidly than other STDs. In a recent open access article in the journal Sexually Transmitted Infections, Reckart and colleagues hypothesise that ART itself  may alter the innate and acquired immune responses to Treponema pallidum, the bacterium causing infectious syphilis, and that this biological explanation plays an important role in the current syphilis epidemic.

In a leading article in the same journal, Susan Tuddenham and colleagues (only available to subscribers), find the hypothesis intriguing despite some flaws. They go on to suggest that further work is necessary to look at the mechanisms underlying the current syphilis epidemic.

In the same issue David Glidden et al point out that in the early double blind trials with pre-exposure prophylaxis (PrEP) no increase in syphilis was found between those taking PrEP and those taking placebo. These findings would suggest that short term exposure to ART has no effect on the acquired immune responses to Treponema pallidum.

Sexually transmitted infections: challenges ahead

A commissioned article in Lancet Infectious Diseases on July 9, 2017 highlights some of the major issues and challenges facing us in the growing global epidemic of sexually transmitted infections (STI). Authors Prof Mabhus Unemo et al summarise the key issues as follows:

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research.

In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control.

Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease.

The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials.

Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches.

STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control.

Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation.

Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

Read full article on Lancet Infectious Diseases

Cuts to sexual health services are putting patients at risk

Cuts to sexual health services in parts of England are placing the care of patients at risk, a new report has warned according to a report published in the BMJ.

The research by the healthcare think tank the King’s Fund concluded that budget cuts of more than 20% to genitourinary medicine (GUM) services in some parts of the country had led to service closures and staffing cuts that have harmed patient care. Experts said that the findings were particularly worrying given that numbers of diagnoses of sexually transmitted infections such as syphilis and gonorrhoea were rising.

Current pressures on services were also having a negative effect on staff morale and leading some staff to consider alternative careers, the report warned.

The researchers analysed data and interviewed frontline staff to examine the effect of funding pressure on patient care across four service areas: GUM, district nursing, elective hip replacements, and neonatal care.

Their findings indicated that sexual health and district nursing had been hardest hit which undermined the vision set out in NHS England’s Five Year Forward View to strengthen prevention and community based services.

The authors said that sexual health services such as GUM had become more prone to budgetary cuts since moving from the NHS to local government, because of local authorities’ legal obligation to balance their books.

Centenary of nationwide free access to sexual health clinics in England and Wales

STI began in 1925 as the British Journal of Venereal Disease, and you can read early editions on the sti.bmj.com website. The very first issue covers skin complaints often mistaken for syphilis, the use of bismuth and malaria inoculation to treat syphilis, and the establishment of a network of clinics following a Royal Commission.1 It also discusses diathermy in the treatment of gonorrhoea!

A hundred years ago, we had no effective treatment for gonorrhoea, and it is sobering to realise we may soon be in the same position. The GRASP surveillance system which tracks antimicrobial resistance in England and Wales shows indications that we are not far from ceftriaxone treatment failures in a report by Town et al.2 In an age of nucleic acid based diagnostics, we need alternatives to culture for detecting resistance. A fascinating report by Graham et al reports that whole genome sequencing can be achieved with urine specimens, including the detection of markers associated with resistance.3 On a related note, this month’s editorial by Nigel Garrett reflects on the perhaps brief life of syndromic management.4
Read full article

 

Project on chlamydia wins prize

Infection by Chlamydia trachomatis the commonest bacterial sexually transmitted infection in the UK and can result in long term complications such as pelvic inflammatory disease and infertility in women.gabriel schembri prize

Once treatment is given to the patient and their partner(s) a test of cure is recommended. However when this should be done is unclear. A similar question hangs over another common sexually transmitted bacterial infection, gonorrhoea.

Dr Gabriel Schembri and his colleagues in Manchester in collaboration with researchers in London have completed a study, part co-funded by STIRF (in conjunction with BASHH)  in an effort to answer these questions:

STIRF-015: Testing for chlamydia and gonorrhoea: persistence of a positive test result after successful treatment.

The study has now finished and was presented at the British Association for sexual Health and HIV (BASHH) meeting in Oxford (July 2016) and won the prize for the best oral presentation.TOC-BASHH presentation

The investigators showed that the site of infection may have an effect on time to clearance of infection, with pharyngeal gonorrhoea infections and vaginal chlamydia infections taking longer to clear than other sites.

 

The results of this study will help guide clinicians to the timing for tests of cure.

Risks for pelvic inflammatory disease in students

In the latest issue of the Sexually Transmitted Infections, Phillip Hay and colleagues in the UK report on a prospective study of female students attending 11 universities and 9 further education colleges in London.

At the start, the students were asked to fill a questionnaire and provide a self taken vaginal sample for infection screening. After 12 months, they were assessed for pelvic inflammatory disease (PID), a condition that can lead to infertility and other complications.

PID was found in 1.6% of the particpants. Unsurprisingly the strongest predictor of PID was the presence of Chlamydia trachomatis at the first visit (relative risk (RR) 5.7).

However, adjusting for this, the authors reported that significant predictors of PID were ≥2 sexual partners (RR 4.0) or a new sexual partner during follow-up (RR 2.8), and age <20 years (RR 3.3). Somewhat surprisingly recruitment from a further education college rather than a university also increased the relative risk of PID 2.6 fold, perhaps reflecting different health protection behaviors (eg condom use) between the two groups.

The study concluded that in addition to known risk factors such as multiple or new partners in the last 12 months and younger age, attending a further education college rather than a university were risk factors for PID.

They recommended that sexual health education and screening programs could be targeted at these high-risk groups.

The perils of chemsex

The term “Chemsex” is used in the United Kingdom to describe intentional sex under the influence of psychoactive drugs, mostly among men who have sex with men. The main drugs are mephedrone, γ-hydroxybutyrate (GHB), γ-butyrolactone (GBL), and crystallised methamphetamine. These drugs are often used in combination to facilitate sexual sessions lasting several hours or days with multiple sexual partners.

Mephedrone and crystal meth are physiological stimulants, increasing heart rate and blood pressure, as well as triggering euphoria and sexual arousal. GHB (and its precursor GBL) is a powerful psychological disinhibitor and also a mild anaesthetic.

Anecdotal reports and some small qualitative studies in the UK find that people engaging in chemsex report better sex, with these drugs reducing inhibitions and increasing pleasure.

Unfortunately use of chemsex can lead to mental health problems which can be permanent. Moreover Casual sex, particularly if under the influence of alcohol or drugs can lead to the acquisition of sexually transmitted infections and even such bugs as shigella, an infection causing severe bacillary dysentery and diarrhoea usually associated with travel to regions such as Indian subcontinent, North and East Africa and South America.

See trailer for Chemsex, a film ChemsexOfficial directed by William Fairman and Max Gogarty (a Peccadillo Pictures)  in the medical journal Lancet.