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PRIORITY PRESS - Family Medicine Forum 2011

Montréal, Quebec / November 3-5, 2011

Montréal - Recent surveys suggest poor control of symptoms and disease is endemic among patients with asthma and chronic obstructive pulmonary disease. There are numerous reasons for this finding, including lack of awareness of the characteristics of good control, insufficient knowledge about disease management, and poor compliance with therapy. These problems often result from a lack of dialogue between patients and their physicians. Several sessions here were devoted to detection, monitoring and management of respiratory disease and practical measures for improving patients’ symptoms, quality of life and longer-term outcomes. As speakers told delegates, earlier and more consistent use of recommended therapies reduces symptoms, inflammation and deterioration in lung function. Self-management education, including training in appropriate inhaler use, requires regular reinforcement.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Most patients (or the parents of young patients) have little knowledge about meningitis and its potentially devastating impact, commented Dr. Marla Shapiro, Associate Professor, Family and Community Medicine, University of Toronto, Ontario. Family physicians can counter some of the pervasive misinformation about vaccines and explain their importance in preventing infection with meningococcus, she told delegates.

Incidence Varies by Province

The causes of bacterial meningitis have evolved over time, indicated Dr. John Yaremko, Assistant Professor of Paediatrics, McGill University, Montréal, Quebec. Haemophilus influenzae and Pneumococcus are seen less frequently now than 20 years ago, largely due to the success of vaccination. Neisseria meningitidis continues to present an important risk, especially to infants, adolescents and young adults. Five major serogroups of N. meningitidis— A, B, C, Y and W-135, as distinguished by their polysaccharide capsules—are responsible for most cases of disease worldwide. According to Dr. Yaremko, “There is more than one strain causing meningitis and there is room for improvement in terms of prevention.”

Large-scale vaccination programs introduced as a result of outbreaks over the last 2 decades have significantly reduced the prevalence of serogroup C meningococcus. Currently, 54% of all cases of invasive meningococcal disease (IMD) are caused by serogroup B. For reasons that remain unclear, prevalence varies by province in the general population of Canada; for example, in Quebec, serogroup B accounted for at least 90% of cases in 2008-2010. In many other countries as well, serogroup B is now the most important pathogen, causing 80% to 90% of disease, Dr. Yaremko noted.

Disease Is Aggressive

Transmission of N. meningitidis occurs through direct contact or exposure to respiratory secretions. Asymptomatic carriage rates may reach 35% in winter and spring, especially in adolescents and young adults, Dr. Yaremko reported. The incubation period is 2 to 10 days.

Infants under 1 year of age are 8 times more likely than the general population to develop IMD, as a result of their immature immune systems and loss of maternal antibodies. Serogroup B represents 82% of the IMD cases in infants under 1 year of age while serogroup B is responsible for 72% of IMD cases in children 1 to 4 (Canada Communicable Disease Report, April 2009). Also at high risk are adolescents and young adults, who are 2 to 5 times more likely than average to develop the disease. In this age group, 68% of IMD cases are caused by serogroup B. “A lot of this is because of their lifestyle,” Dr. Yaremko explained: people in these age groups are highly social and often spend a great deal of time in relatively crowded conditions (e.g. schools, locker rooms, university dormitories, bars). Smoking and an underlying respiratory tract infection also increase the risk of IMD.

Once N. meningitidis infection occurs, acute illness develops rapidly. The progression from nonspecific symptoms to death can take as little as 24 hours. “In the first 4 to 8 hours it looks very much like a viral illness with myalgias, loss of appetite, fever and irritability in younger kids. At 12 to 15 hours, we start seeing meningococcal symptoms and signs of bacteremia, such as hypoperfusion, meningismus and photophobia. [At] 15-24 hours, patients [may present] with confusion, seizures, loss of consciousness, signs of sepsis and multisystem failure... 60% of individuals who have IMD will have been sick for less than 24 hours by the time they are admitted to the ICU,” he told delegates.

Mortality from IMD is 10% to 15%, Dr. Yaremko adding that teens and young adults have the highest mortality rates. Among survivors, 10% to 30% will have sequelae.

While all body systems may be affected, neurologic sequelae such as hearing loss, blindness, seizure disorders and neuropsychiatric syndromes are the most common. “Children younger than 2 years of age are much more likely to have sequelae than older kids and adults, no matter the serogroup. Kids aged 2 to 19 are more likely to have sequelae than adults... Any individual with serogroup C is more likely to have complications than those with other serogroups,” Dr. Yaremko said.

Innovative Vaccine Development

A vaccine against serogroup B N. meningitidis has been “a holy grail,” according to Dr. Marina Salvadori, Associate Professor of Paediatrics and infectious diseases consultant, University of Western Ontario, London. In contrast with other serogroups, the polysaccharide capsule of serogroup B so closely resembles fetal neural tissue that experimental vaccines employing conjugate technology failed to induce an adequate immune response. A vaccine targeting a single subcapsular protein is also unlikely to be broadly effective, given the worldwide diversity of strains. As a consequence, a revolutionary process known as “reverse vaccinology” was employed to identify 4 proteins essential to all strains of serogroup B and to which antibodies could be developed; these are the basis of the new vaccine.

The immunogenicity and safety of the 4CMenB vaccine have been studied extensively in populations at risk for serogroup B infection, Dr. Salvadori noted. “Currently we think the vaccine protects against about 75% of strains in infants and about 85% of strains in adolescents and adults.” For example, in infants, doses at 2, 4 and 6 months with boosting at 12 months led to high levels of bactericidal antibodies (Vesikari et al. International Pathogenic Neisseria Conference 2010, Poster 180). Additional studies indicate that in both infants and toddlers, the 4CMenB vaccine can safely and effectively be given concomitantly with other routine immunizations, she added.

Immunogenicity has also been demonstrated in adolescents given 1-3 doses of the vaccine, Dr. Salvadori reported, with 2 doses providing optimal results (Santolaya et al. ESPID 2011, Poster P905). “We get really good antibody titres that are felt to be cidal, or killing, to all the different antigens... And it looks like the antibodies persist for at least 6 months, if not a bit longer.” The exact duration of immunogenicity must still be ascertained, she added. It is likely that boosting will be necessary for any meningococcal vaccine because the incubation period for the disease is so short. “You have to have high levels of antibody at all times to immediately clamp onto the bacteria and get rid of it,” Dr. Salvadori told delegates.

Studies conducted in infants, toddlers and teens have also demonstrated the safety/reactogenicity of the vaccine. Patients or their parents may be told that arm soreness and redness may occur and is a sign of a good immune response, Dr. Salvadori indicated. Fever (usually less than 39º C) has been observed several hours to 2 days after the vaccine. Prophylactic acetaminophen can reduce the likelihood of fever and of return office visits by worried parents, she noted.

Summary

Surveillance data show that serogroup B N. meningitidis is currently the most likely pathogen in IMD. Although this illness is rare, its substantial morbidity and mortality necessitate consideration of vaccination in young patients at risk. As reported here, the 4CMenB vaccine has been submitted for review by Health Canada and could be available within a year. ?

Based on: “Achieving Broad Protection Against Serogroup B: On the Cusp of the First Broadly Protective Meningitis B Vaccine.” Family Medicine Forum 2011, Friday, November 4, 12:00-13:00, Palais des congrès de Montréal, Room 710A.

This program meets the accreditation criteria of The College of Family Physicians of Canada and has been accredited for up to 1 Mainpro-M1 credits.

Note: At press time, the 4CMenB vaccine is not approved in Canada.