THE SUBJECT NOBODY LIKES TO TALK ABOUT: GONORRHOEA

Let’s face it, nobody likes to discuss the topic of sexually transmitted infections (STIs), but there’s something about this disease that seems to make it particularly taboo.

Gonorrhoea.

I mean, could they have found a more unattractive word?! It’s also hard to pronounce, it’s longwinded, and it’s nearly impossible to spell.

Yet here we are, making gonorrhoea our latest subject of choice for the GlycoBuzz blog.  You may ask why?

Well, it just so happens that we have good reason to shed light on the subject. This disease infects an estimated 87 million people worldwide each year!

Our expert in this area of research is Professor Kate Seib, also sometimes humorously referred to as ‘gonorrhoea girl’, a nickname she doesn’t actively promote…for obvious reasons!

Jokes aside, Kate is a Research Leader and the Associate Director of Research at the Institute for Glycomics. She has spent the greater part of her career tackling this disease, looking for an effective vaccine to prevent and new, more effective antibiotics to treat gonorrhoea infection.

In this blog article, Kate demonstrates just how important her research is in the fight against gonorrhoea.

Read on!

What is gonorrhoea and what pathogen causes it?

Gonorrhoea is a sexually transmitted infection caused by the bacteria Neisseria gonorrhoeae (N. gonorrhoeae). It is an ancient disease of humans, and symptoms resembling gonorrhoea have been described in ancient Chinese and Middle Eastern records dating as far back as 3500 BC, and in the Old Testament of the Bible.

Other names for gonorrhoea include gonococcal disease and the clap.

What is the global impact of gonorrhoea?

The World Health Organisation (WHO) estimates that more than 1 million STIs occur every day, and there are an estimated 87 million cases of gonorrhoea infections occurring each year.

However, current figures likely underestimate the burden of gonorrhoea due to limitations in diagnosis and reporting in several parts of the world, along with the fact that the infection with N. gonorrhoeae often has no symptoms and is not diagnosed.

What are the implications of the disease for men versus women?

The outcomes of N. gonorrhoeae infection range from asymptomatic infection to severe disease.

N. gonorrhoeae can infect all mucosal surfaces of the body, including the genital tract, rectum, pharynx and eyes.

Symptomatic infection typically presents as urethritis in males and cervicitis in females. However, asymptomatic infections occur in up to 80% of infected females and in up to 40% of infected males, which, if not diagnosed and treated may lead to serious sequelae that include urogenital tract abscesses, pelvic inflammatory disease, adverse pregnancy outcomes, infertility and neonatal complications. Infection with N. gonorrhoeae also increases the risk of acquiring and transmitting HIV.

Why are antibiotics proving to be ineffective against the disease?

The ongoing emergence of antibiotic resistant strains of N. gonorrhoeae is a major challenge to the management of gonorrhoea.

N. gonorrhoeae has developed resistance to all classes of antibiotics used to treat it since the 1940s, and new antibiotics have had to be introduced into treatment schedules every 5-10 years. In 2018, ‘Super gonorrhoea’, resistant to all routine antibiotics was reported in the UK and Australia, and has since been seen in other parts of the world.

What is your team currently focusing on in terms of gonorrhoea research?

Our work focuses on understanding how N. gonorrhoeae causes infection, so that we can identify and target those parts of the bacteria that are essential for its survival in humans. We are aiming to identify key targets for the development of new antibiotics to treat infections, and for a vaccine to prevent infection.

Is there a vaccine against gonorrhoea currently available on the market?

There is currently no gonorrhoea vaccine. Four gonococcal vaccine candidates have been tested

in human clinical trials pre-2000, but they did not provide any protection against N. gonorrhoeae infection. This is most likely due to the vaccine targets used and the fact that many antigens are variable between N. gonorrhoeae strains.

We understand that you will soon be starting a world-first trial to test whether a meningococcal B vaccine may protect against gonorrhoea. Can you tell us a bit about that?

An observational study from New Zealand suggested that a vaccine against the closely related bacteria Neisseria meningitidis, the outer membrane vesicle (OMV) meningococcal B vaccine MeNZB, had a moderate level of effectiveness against infection with N. gonorrhoeae.

My research team has since shown that a newer meningococcal B vaccine, 4CMenB (marketed as Bexsero) that contains the MeNZB OMV component plus three recombinant protein antigens, is able to induce cross reactive antibodies to N. gonorrhoeae. We are now conducting a randomised controlled trial (RCT) to determine the effectiveness of 4CMenB in preventing infection with N. gonorrhoeae.

This is a double-blind, randomised placebo-controlled trial of a two-dose schedule of 4CMenB to prevent N. gonorrhoeae infection in 730 gay and bisexual men (GBM), either taking pre-exposure prophylaxis (PrEP) against HIV, or HIV positive. These populations have high gonococcal incidence and are recommended under Australian guidelines to attend clinics every 3-6 months for comprehensive sexual health screening.

(See this link for more information)

Where and when will this trial be run?

The trial is funded by the National Health and Medical Research Council and participants are currently being recruited at four large sexual health clinics in Australia: the Melbourne Sexual Health Centre (MSHC), Sydney Sexual Health Centre (SSHC), Western Sydney Sexual Health Centre (WSSHC), and Gold Coast Sexual Health Centre (GCSHC).  

What are the benefits of repurposing an existing vaccine versus developing a completely new vaccine?

There are several benefits of testing a vaccine that has already been licensed, for example the vaccine has already been shown to be safe and able to induce an immune response in humans. 

The safety and efficacy of the 4CMenB vaccine has been established in individuals from 2 months to 50 years of age, and is used in >37 countries worldwide, so there is a lot of data already available about how it works.

Being able to use an already licensed vaccine may therefore be a relatively rapid and cost-effective approach compared to developing a completely new vaccine.

If proven effective, what impact could this vaccine have on global health?

Given the high level of asymptomatic gonorrhoea infections that occur, as well as increasing rates of antibiotic resistance, a vaccine to prevent gonorrhoea is desperately needed.

If proven effective, this vaccine couldrevolutionise approaches to gonorrhoea prevention globally and would greatly improve sexual health.

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