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MEDI-NEWS - Based on an interim safety surveillance report by L'Institut national de santé publique du Québec (INSPQ) (Funded by the Quebec Ministry of Health and Social Services) Original report in French at http://www.inspq.qc.ca/pdf/publications/1885_Vaccin_Menincogoque_SerogroupeB.pdf

September 2014

Quebec City - Invasive meningococcal disease (IMD) caused by serogroup B Neisseria meningitidis is the most common IMD in Canada today. The incidence of serogroup B disease is also highest in infants under the age of 12 months, children between the ages of 1 to 4 and adolescents between 15 and 19 years of age. In Quebec, the incidence of serogroup B IMD has been persistently higher in the region of Saguenay-Lac-Saint-Jean than in the rest of the province. For this reason, public health officials launched the country’s first large-scale vaccination campaign against serogroup B IMD starting in May of this year. Between May 5 and June 17, 2014, a total of 43,740 residents between 2 months and 20 years of age received the first dose of the multi-component vaccine—the 4CMenB vaccine—and results from an interim safety analysis monitoring adverse events following receipt of the vaccine show no worrisome safety signals in what is the largest cohort of individuals ever to receive the 4CMenB vaccine to date. Virtually all vaccine recipients indicated that they intend to receive the second dose of the serogroup B vaccine. This speaks to the high acceptability of the vaccine even in those who experienced an adverse event. 

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

An enhanced surveillance system implemented by public health officials to monitor residents who received the 4CMenB (Bexsero) vaccine for any sign of adverse events (AEs) after the first dose of the vaccine failed to identify any worrisome safety signals in a large cohort of vaccinees, an interim safety report indicates.

Initial findings are reassuring enough that officials plan to continue the campaign as scheduled and give the second dose of the vaccine to targeted residents in the Saguenay-Lac-Saint-Jean region of Quebec. At the same time, surveillance efforts will continue to ensure safety expectations are fully met.

As Dr. Gaston De Serres, lead author of the interim safety report and colleagues at the INSPQ note, transmission rates of serogroup B invasive meningococcal disease (IMD) have been persistently higher in the Saguenay-Lac-Saint-Jean health region than elsewhere in the province. In an effort to control the spread of IMD caused by serogroup B, public health officials launched a vaccination campaign against serogroup B starting in May of this year.

The program targeted residents aged 2 months to 20 years who were either residing in or attending an educational institution in this particular health region. Adverse events following vaccination were collected through active surveillance via electronic monitoring of vaccine recipients who provided a valid e-mail address as well as through passive surveillance via reporting of AEs through the provincial ESPRI registry. The ESPRI registry is already in place for all vaccines given in the province of Quebec.

AEs of particular concern were high-grade fevers, seizures and severe transient arthralgias. Public health officials also monitored vaccine recipients for high rates of absenteeism possibly due to AEs following receipt of the first dose of the 4CMenB vaccine.

Between May 5 and June 17, 2014, a total of 43,740 residents between the ages of 2 months and 20 years received the first dose of the serogroup B vaccine. Of the 27,895 vaccine recipients to whom an e-mail questionnaire was sent, 12,332 completed the electronic questionnaire. This cohort represents slightly over 28% of all individuals who received the 4CMenB vaccine during the region's targeted campaign.

Active Surveillance

Of the 12,332 participants who took part in the active surveillance, 10.9% reported a fever within 7 days of receiving the vaccine. “Onset of fever occurred within 48 hours of the vaccination in 9% of vaccinees,” the authors note, “and within 3 to 7 days in 1.9%.” Because clinical trial evidence suggested that acetaminophen reduced the risk of fever, public health officials recommended that parents use prophylactic antipyretics in children under 2 years of age who were targeted for vaccination in the region.

Children in the targeted vaccination program under 2 years of age had a higher incidence of fever at between 14 and 15% than children between 2 and 4 years of age, in whom the incidence of fever was 12%. The incidence of fever among vaccine recipients 5 years of age and older was lower at between 5 to 8%. As was found in clinical trials of the 4CMenB vaccine, the use of acetaminophen reduced the likelihood of fever onset in children under 2 years of age by about 50%.

“Overall, the mean maximum temperature was 38.9 degrees Celsius and was similar for vaccinees under 2 years of age and those in the 2 to 20-year old age group,” the authors add. Fewer than 1% of children presented with a high-grade fever of 40.5 degrees Celsius or higher following receipt of the vaccine. The median duration of fever was 2 days. Only a single case of febrile seizure was identified during this large-scale campaign and this occurred in a 1-year-old vaccine recipient.

Following active surveillance, the incidence of fever occurring within the first 48 hours was lower in children under the age of 2 who received the 4CMenB vaccine alone compared to young children who received the vaccine together with other pediatric vaccines, but the difference between the two groups was not statistically significant.

Absenteeism

Approximately 6% of individuals reported a health problem that resulted in absenteeism within 7 days post-vaccination. However, only 3.5% of absenteeism was due to AEs attributed to the 4CMen B vaccine.  The most commonly reported symptoms were general malaise, local reactions at the vaccination site, gastrointestinal and respiratory problems. No hospitalizations related to the vaccine were reported.

Estimated rates of absenteeism attributable to AEs were low, ranging from 0.9% for infants between 2 and 11 months of age to a high of 4.4% for children between the ages of 5 and 16 years.

As investigators note, the on-line questionnaire included a section for open-ended comments that was completed by 20% of respondents. The most common complaint cited by respondents was pain at the injection site. Fewer than one-third of on-line questionnaire participants reported fever and generally feeling unwell as their chief complaint.

Importantly, among all respondents to the questionnaire, 99% stated that they were likely to or definitely would receive the next dose of the vaccine whereas this proportion was 92% among individuals who reported absenteeism or a medical visit after receiving the first dose of the vaccine.

Passive Surveillance and NACI Recommendation

Under the passive surveillance reporting system, a total of 56 AEs was reported through the ESPRI program between May 5 and July 2, 2014. Of the reported cases, about half were an allergic-type reaction, around a third were fever and about 20% were local reactions.

In April 2014, the National Advisory Committee on Immunization (NACI) recommended that healthcare professionals may consider using the multi-component vaccine in infants 2 month of age and older to prevent IMD caused by serogroup B. Furthermore, NACI recommended the same vaccine be given to individuals 2 months of age and older at high risk or who have been in close contact with any person who developed IMD caused by serogroup B. 

Summary

As the authors of the interim safety report emphasize, the sheer size of the cohort involved in the enhanced surveillance program—namely 43,740 residents between 2 months and 20 years of age—is substantially greater than the total number of clinical trial subjects who received the 4CMenB vaccine during the clinical trials that led to the vacccine’s approval. Results of the regional surveillance program did confirm that local reactions, fever and general malaise do occur when the vaccine is used in a community setting. At the same time, results did not identify any concerning safety signals as a result of widespread vaccination with the 4CMenB vaccine.

The fact that virtually all vaccine recipients in the targeted region intended to receive the second required dose underscores the high acceptability of the 4CMenB vaccine and reaffirms its safety when widely used in the community.