Quebec scientists explore issues around using the meningitis vaccine to reduce gonorrhea risk

• Bacteria that cause some forms of meningitis are related to those that cause gonorrhea
• Scientists in Quebec reviewed data on the possibility of using a meningitis vaccine to prevent gonorrhea
• An immunization program for gonorrhea may one day be possible if clinical trial results are promising

The germs that cause gonorrhea (Neisseria gonorrhoeae) are most commonly spread during condomless anal, oral and vaginal intercourse. These germs can also be passed from mother to child during the birthing process.

Gonorrhea causes inflammation in delicate wet tissues, and such inflammation can act as a portal, or gateway, for other sexually transmitted infections (STIs), including HIV. 

Gonorrhea does not always cause symptoms. However, it can cause discharge from the urethra and a burning sensation while urinating. Some women can develop pain in the lower abdomen and vaginal bleeding between periods or after sex. What’s more, gonorrhea can contribute to pelvic inflammatory disease, infertility and other complications. If left untreated, the germs that cause gonorrhea can affect the testicles and prostate. 

These symptoms, inflammation and risks for other infections underpin the need for sexually active people to go for regular checkups and screening for STIs such as gonorrhea. 

Antibiotic treatment

Since 1945, a range of treatment options—antibiotics—were developed for gonorrhea. However, over time, the germs that cause this infection have gradually developed the ability to resist many antibiotic treatments. 

A scientific advisory panel to the Public Health Agency of Canada (PHAC) has released interim guidance for the treatment of gonorrhea. 

In adults (and in young people 10 years of age and up), the advisory panel recommends the following treatment “for all uncomplicated infections (urethral, endocervical, vaginal, rectal and pharyngeal)”:

• the antibiotic ceftriaxone 500 mg given as an intramuscular injection in a single dose

In many countries, ceftriaxone has become the leading treatment for gonorrhea.

PHAC provides information about gonorrhea treatment here.

Gonorrhea in Canada

According to a team of scientists in Quebec, “the burden of gonorrhea [in Canada] has been increasing over the past decade, with a reported rate almost tripling from 2010 to 2019.” They added that “males account for 56% of all cases diagnosed and the most commonly affected age group consists of those 15 to 39 years old, accounting for 82% of total cases.”

Enter a meningitis vaccine for reducing gonorrhea risk

Due to rising rates of gonorrhea and dwindling effective treatment options, more researchers are exploring a vaccine that was originally developed to treat meningitis caused by bacteria related to those that cause gonorrhea. 

The vaccine is called 4CMenB (sold as Bexsero) and it is meant to prevent complications caused by Neisseria meningitis. This vaccine is safe and highly effective in reducing the risk of meningitis caused by these bacteria.

As mentioned earlier, gonorrhea is caused by different but related bacteria — Neisseria gonorrhoeae. There is currently no vaccine specifically designed to prevent gonorrhea. 

Tricky bacteria

It is difficult to make a vaccine against gonorrhea-causing bacteria, as these bacteria can suppress the immune response against it. This ability to suppress the immune response against gonorrhea means that the immune systems of people who are infected with gonorrhea do not usually acquire protection from infection with gonorrhea-causing bacteria in the future.

However, there is increasing interest in 4CMenB, because although this vaccine was designed and approved to prevent meningitis-causing bacteria, some studies suggest that it can also moderately reduce the risk of infection by gonorrhea-causing bacteria. This vaccine has proteins that are similar to those found in both Neisseria meningitis and Neisseria gonorrhoeae (the bacteria that cause gonorrhea). 

Laboratory experiments with cells suggest that the 4CMenB vaccine causes the immune system to produce antibodies that also attack gonorrhea-causing bacteria. Studies of blood samples from people vaccinated with 4CMenB have found that antibodies are important in reducing the risk of gonorrhea. This vaccine also appears to stimulate some cells of the immune system, such as T-cells, to strengthen the immune response. 

A team of researchers from universities in Montreal and Laval as well as the Institut national de santé publique du Québec reviewed published evidence and ongoing clinical trials of the 4CMenB vaccine to reduce gonorrhea risk.

Partial protection

The researchers noted that in 2009 there was a mass vaccination campaign in Quebec (in the Saguenay-Lac-Saint-Jean region) to help reduce the risk of meningococcal disease using 4CMenB. This campaign reached 86% of people aged six months to 20 years. Most people in this campaign received two doses of the vaccine. 

According to the researchers, after vaccination, public health authorities in this region observed an “unexpected decrease in the number of gonococcal infections among persons below the age of 20.” A decrease in infections in adults over the age of 20 was not seen (they were not a part of the mass vaccination campaign). Despite the decrease in diagnoses of gonorrhea in people under the age of 20, cases of chlamydia infection continued to rise among all age groups. These findings suggest that the 4CMenB vaccine provides cross-protection against gonorrhea.

The Quebec researchers reviewed similar studies in Australia, New York City, Philadelphia, Oregon, Southern California and Italy. All of these studies suggest that the 4CMenB vaccine can reduce the risk of gonorrhea by 35% to nearly 60% for up to three years. The study in Italy also found a reduction of gonorrhea risk in people with HIV.

These studies were observational in design and cannot produce high-quality levels of evidence. However, observational studies can be an important starting point to develop more robust clinical trial designs.

The Quebec researchers also reviewed and commented on randomized clinical trials for reducing gonorrhea risk after vaccination with 4CMenB (which, if well designed, can in theory produce higher-quality evidence) that have either been completed or are underway. 

One trial in France, called Doxyvac, did not find a significant degree of protection conferred by vaccination. However, this study had a relatively small number of participants and was likely not able to detect protection induced by the vaccine. What’s more, it ended prematurely. 

There are other trials underway in several countries and these should provide clear answers about 4CMenB vaccination’s protective effect against gonorrhea. 

Public health implementation

In the UK, there have been multiple cases of treatment-resistant gonorrhea reported in the past decade. Given high rates of gonorrhea in that country, public health authorities have recommended that the 4CMenB vaccine be offered at sexual health clinics that can help to identify people at heightened risk for gonorrhea. Researchers in the UK plan to collect data as this program is rolled out. Analysis of this data can help policy makers understand the effectiveness of the 4CMenB vaccine in reducing gonorrhea risk, the duration of protection and the potential impact on the development of antibiotic resistance by gonorrhea-causing bacteria.

The New York State Department of Health also recommends offering the 4CMenB vaccine to people at high risk of gonorrhea.

The Quebec researchers call for “careful evaluation of the integration of 4CMenB into publicly funded provincial/territorial immunization programs for high-risk groups, including the scientific evidence, expected health benefits, budgetary impact, cost-effectiveness, feasibility and acceptability of different vaccine strategies.” 

The researchers caution that “it is always difficult to extrapolate the country-specific results of economic evaluations, and it would thus be interesting to develop a Canadian model or to adapt an existing model to the Canadian context. A first step would be an estimation of the size of high-risk groups and corresponding [gonorrhea] infection rates in Canada, as well as practical ways to reach these high-risk groups without stigmatization.”

The researchers also note that in the coming years results from well-designed trials will be available and that these results can “hopefully support the relevance of a Canadian immunization initiative for the prevention of [gonorrhea].”

—Sean R. Hosein

Resources

Gonorrhea guide: Key information and resources – Public Health Agency of Canada

Sexually transmitted and blood-borne infections: Guides for health professionals – Public Health Agency of Canada

Gonorrhea – CATIE 

New antibiotic (gepotidacin) looks promising for gonorrhea – CATIE News

TreatmentUpdate 245 – CATIE

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