Serendipity, a couple of STI’s, meningitis and MeNZB….

Late last year I had the privilege of being called in to join a team led by Helen Petousis-Harris to help with the design, data management and analysis of two similar studies designed to answer an odd question? Did the MeNZB vaccine have an effect on gonorrhoea infections?

The MeNZB vaccine was designed to protect New Zealand’s children and teenagers against an epidemic of Meningitis B. This disease occurs when a bacteria called Neisseria meningitidis (type B) invade, replicate and cause painful mayhem and destruction within and around the three layers of cells which form a lining (meninges) around your brain and spinal cord. Neisseria gonorrhoea is a related bacteria which causes a different disease – gonorrhoea or “the clap”. Neisseria gonorrhoea most commonly invade cells which make up the lining of sexual organs, penis, vagina, cervix etc, then also successfully invade cells of the immune system which gather to help fight off the invading bacteria. These two types of bacteria, N. meningitidis and N. gonorrhoea are related and sequencing of their DNA indicates they are about 80-90% similar.

Gonorrhoea, when diagnosed, is usually treated with antibiotics. However in recent years it has been notorious and newsworthy due to development of resistance to that antibiotics that we have available for treating it. If untreated then gonorrhoea can cause more serious disease such as pelvic inflammatory disease and infertility.

Gonorrhoea is considered a disease in need of a vaccine. Much effort and many years have been dedicated to finding a vaccine with limited success to date.

A group of researchers with an interest in Neisseria bacteria species noted that some data from Cuba, Norway and New Zealand suggested a possible effect of a vaccine for meningococcal B on gonorrhoea. These data were mainly coincidental declines in rates of gonorrhoea following meningococcal B vaccination campaigns.

In order to find out with more certainty if it was the vaccine for MeNZB that also helps protect people against gonorrhoea we conducted a case-control study. In this type of study we compare people who have the disease of interest with a group of people who are generally comparable to those who have the disease but do not have the disease. The control group must have the same risk of the disease as the group who developed the disease. For example, the control group needs to have people of the same ages, be living in the same area, have similar behaviour, similar gender composition, similar ethnic composition because all these thing influence whether or not you can develop a disease alongside other factors of influence such as a vaccine. You then find out what proportion of your cases has had the vaccine and compare that to the proportion of controls who have had the vaccine. If the vaccine really does help to prevent the disease then you expect a much lower proportion of people who are vaccinated to be cases compared to the proportion of controls who are vaccinated.

In order to control effectively for different risks due to sexual behaviour we needed controls that were likely to have had similar high risk behaviour. For this reason our controls were people who developed a different bacterial sexually transmitted disease, chlamydia.

Once we found our cases and controls and found out whether or not they had been vaccinated with MeNZB we did a type of statistical test called logistic regression. This is a test make sure that any difference we found between the proportion of controls vaccinated and the proportion of cases vaccinated is a real difference caused by the vaccine and not a difference that could arise easily by chance. We also used the statistical test to make sure that differences in proportion of genders, proportions of different ethnicities etc between the case and control groups did not explain the difference in proportion of vaccinated individuals.

We did find a difference in the proportion vaccinated amongst cases compared to controls that was unlikely to be due to chance. People who received three doses of the MeNZB vaccine and are at risk of developing gonorrhoea appear to be about 30% less likely to develop gonorrhoea.

This is very exciting. It gives us more clues as to what a successful vaccine against gonorrhoea needs. However it is the first study showing such an effect and more studies on the mechanisms and epidemiology are needed. Indeed we are also conducting a cohort study to see if our findings are consistent when using a different method. So stay tuned.