Combatting a serious cause of meningitis in the UK and Africa

Meningococcal disease is one of the major causes of meningitis and septicaemia worldwide. At least 10% of those who develop the disease will die, and many more will be left with serious disabilities. It affects several hundred people a year in the UK, and in the sub-Saharan African Meningitis Belt (stretching from Senegal in the West to Kenya in the East) it has caused epidemics that kill or disable tens of thousands of people, making it one of the most feared diseases on the continent. Children are particularly vulnerable; however, the bacterium that causes the disease, Neisseria meningitidis, is often carried at the back of the throat without causing any symptoms. It is still not fully understood why carriage is harmless in most people but develops into serious disease in others.

Meningococcal disease epidemiology is complicated by the fact that the Neisseria meningitidis bacterium has 13 types or serogroups, of which 6 (serogroups A, B, C, W, X and Y) cause almost all cases of invasive disease. In addition, there is further diversity within these serogroups. This includes differences in components on the surface of the bacteria – proteins or sugars that are recognised by the body’s immune system and may therefore be important antigens for use in vaccines. It was an understanding of the importance of this genetic diversity that stimulated Professor Martin Maiden’s studies of Neisseria meningitidis, which began more than 25 years ago, and which have generated breakthrough discoveries about how vaccines work against the disease.

In the 1990s serogroup C bacteria (MenC) caused outbreaks of invasive disease worldwide, with the UK particularly affected. This resulted in the accelerated introduction of a new vaccine (meningococcal conjugate C, or MCC) into the UK, the first country to use such vaccines. Maiden’s group led a multicentre study of meningococcal carriage (the numbers of people carrying the bacteria in their throats) before and after the introduction of the vaccine, with the aim of determining the effect the vaccine had on the meningococcal bacteria population; for example, there were concerns that suppression of one serogroup through vaccination might lead to an increase in another serogroup.

Maiden’s studies showed no such effect, but instead demonstrated that, after the MenC vaccine was introduced, there was a dramatic fall in carriage of meningococcal bacteria, leading to protection even of people who had not been vaccinated. Moreover, it was the MenC serogroup that was particularly affected, resulting in a dramatic reduction of transmission of this strain. This explained the great success of the immunisation campaign, which included all individuals up to the age of 18. Maiden and his colleagues had directly demonstrated a herd immunity effect: vaccination of individuals reduced transmission of the epidemic bacteria and conferred protection on the population as a whole.

A map of the sub-Saharan Meningitis Belt in Africa.
Credit: PATH/David Simpson. Courtesy of PATH. All rights reserved.

These findings were highly influential in the recent implementation of a novel vaccine in the African Meningitis Belt – an area where 450 million people are at risk of meningococcal disease, particularly that caused by the serogroup A bacteria (MenA). Recognising the need for an affordable and effective vaccine to tackle this serogroup, the Bill and Melinda Gates foundation and the WHO established the Meningitis Vaccine Project, led by Dr Mark LaForce, to develop an affordable MenA vaccine, MenAfriVac, which was licensed in 2010 and has been successfully rolled out across the Meningitis Belt. Building on experience with MCC vaccines, MenAfriVac was used to immunise all individuals under the age of 29, to maximise the transmission reduction effects that Maiden had demonstrated in the UK. As part of efforts to understand this vaccine, the African Meningococcal Carriage Consortium (MenAfriCar) was established to study the impact of the new vaccine on MenA transmission across the belt. MenAfriCar carriage studies involving several thousand people in Chad before and after the vaccination campaign, combined with disease incidence data, showed conclusively that MenAfriVac had reduced the incidence of MenA virtually to zero in the study areas, even amongst non-vaccinated individuals, consistent with the findings of the UK research.

Maiden’s group made another important contribution to the study by devising novel high-throughput genomic methods that could rapidly detect and identify the meningococcal strains present in the population. Without these, it would have been impossible to screen the thousands of samples collected by the MenAfriCar studies.

The group has also been involved in capacity-building work, setting up exchange programmes with young scientists from the Meningitis Belt and training them in the new molecular analysis techniques. One of them, Kanny Diallo, who participated in the genomic analysis of the MenAfriCar samples, has recently been awarded a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine to undertake a DPhil on the topic. In the long term, these activities will contribute to the further development of centres for this kind of research within the Meningitis Belt itself, strengthening the ability of countries like Chad to combat the diseases that most affect them. Maiden’s group has also played a leading role in the development of the Welcome Trust’s successful Advanced Training Course ‘Molecular Approaches to Clinical Microbiology in Africa’ which trains microbiologists from across Africa.

Research funded by the Wellcome Trust.

MenAfriVac is a registered trademark of Serum Institute of India Ltd.

Links

Professor Maiden’s research group - http://maidenlab.zoo.ox.ac.uk/

Read the paper about this study in the Lancet - http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961612-8/fulltext?_eventId=login