Vaccine vigilance in Canada: Is it as robust as it could be?

Canada has been known to have one of the better vaccine safety surveillance capacities in the world, but in the early 2000s, it was noted there was still room for improvement. How has Canada done over the last decade and is there more to be done? Canada has done well. First, there has been significant progress made by the Vaccine Vigilance Working Group to enhance the passive vaccine safety monitoring system and address potential issues arising from the review of surveillance data and cases or clusters of concern. Second, there has been an increased investigative capacity for clusters of adverse events and other vaccine safety issues, including an assessment and referral system for individuals with adverse events following immunizations (AEFIs). Third, the use of the Brighton Collaboration definitions and other international standards has facilitated international collaboration and represents the best standard of practice. Despite all these improvements, however, there is more that could be done. The sensitivity of Canada's passive surveillance system still varies from one province and territory to another. The timeliness of the data exchange flow could improve. The AEFI Signal Response Protocol, which identifies the processes and required actions for timely management of any newly detected or emerging vaccine safety signals, is a critical piece of a robust vaccine safety system but it is still in the making. It is commendable that Canada has decided to expand its focus on evaluation research from influenza vaccines to vaccine-preventable diseases more broadly, with the establishment of the Canadian Immunization Research Network (CIRN). CIRN's newly developed Provincial Collaborative Network and the move toward record linkages is excellent. These new investments are welcome in light of the rich vaccine development pipeline, the increased pool of available vaccines, and the growing set of technologies for vaccines production, delivery, and safety monitoring. What would round this all out would be a stronger capacity to monitor the implementation of vaccination programs and vaccine coverage, and better documentation of the reduction of the disease burden attributable to vaccination programs. Canada's investment in vaccines for the health of all deserves no less.

Developing evidence-based immunization recommendations and GRADE.

The Strategic Group of Advisory Experts (SAGE) on immunization is an independent advisory committee with a mandate to advise the World Health Organization (WHO) on the development of vaccine and immunization related policies. SAGE working groups are established on a time-limited basis to review and provide evidence-based recommendations, together with their implications, for open deliberation and decision-making by SAGE. In making its recommendations, SAGE takes into consideration: the epidemiologic and clinical characteristics of the disease; vaccine and immunization characteristics; economic analysis; health system considerations; the existence of and interaction with other intervention and control strategies; costing and social impacts; and legal and ethical concerns. Since 1998, WHO has produced evidence-based vaccine position papers for use primarily by national public health officials and immunization programme managers. Since April 2006 all new or updated position papers have been based on SAGE recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach has been adopted by WHO and, since 2008, GRADE tables that rate the quality of evidence have been produced in support of key recommendations. SAGE previously expressed concern that GRADE was not ideally suited to many immunization-specific issues such as the vaccine population level effect and the inclusion of surveillance system data, particularly for vaccine safety. Extensive productive interactions with various advisory groups including the US Advisory Committee on Immunization Practices, the European Centres for Disease Control, the German Standing Committee on Vaccination (STIKO), WHO's Global Advisory Committee on Vaccine Safety and the GRADE working group resulted in key enhancements to accommodate vaccine-relevant evidence. This facilitated integration and acceptability of the GRADE approach in the development of immunization related SAGE and WHO recommendations. Ongoing utilisation should result in further fine-tuning of the approach to ensure that recommendations are based on the full range of appropriate evidence.

Safe injection practices in a primary health care setting in Oman.

We conducted a national survey of injection practices in 78 government health facilities in Oman in 2001. Data were obtained by interview and observation. The overall standards were good and the stock of disposable equipment was adequate. Recapping of needles was only observed in 1 facility but in 28%, waste disposal boxes contained recapped needles and 17.9% reported needle-stick injuries in the past year. In 9% of the institutions, sharps were observed around the facility, in 12.8% unsupervised disposal containers were seen and in 11.5% unsafe storage of full boxes was observed. While disposal of the used waste was done away from the health facility, only 33.3% disposed of it by correct incineration.

Safe injection practices in a primary health care setting in Oman

We conducted a national survey of injection practices in 78 government health facilities in Oman in 2001. Data were obtained by interview and observation. The overall standards were good and the stock of disposable equipment was adequate. Recapping of needles was only observed in 1 facility but in 28%, waste disposal boxes contained recapped needles and 17.9% reported needle-stick injuries in the past year. In 9% of the institutions, sharps were observed around the facility, in 12.8% unsupervised disposal containers were seen and in 11.5% unsafe storage of full boxes was observed. While disposal of the used waste was done away from the health facility, only 33.3% disposed of it by correct incineration

Injection practices in Burkina Faso in 2000.

BACKGROUND: Unsafe delivery and overuse of injections can result in the spread of hepatitis B virus, hepatitis C virus, and HIV. The aim of the present survey was to estimate the frequency of safe injection practices in Burkina Faso. METHOD: Using the new standardized World Health Organization tool to assess injection practices, we selected 80 primary health facilities with a two-stage cluster sampling method, collected information using structured observations and provider interviews, and analyzed the data using Epi-Info software. RESULTS: We observed 116 injections in 52 facilities. In 50 facilities [96%; 95% confidence interval (CI) 85-99%] injections were given with a new, single-use syringe and needle. In 29 facilities (56%; 95% CI 36-74%), staff recapped needles using two hands. All 80 facilities visited had a stock in the community to provide new, single-use syringes and needles. In 61% (95% CI 54-79%) of facilities, staff reported needlestick injuries in the last 12 months. Used needles were discarded in open containers in 66 facilities (83%; 95% CI 55-96%) and observed in the surroundings of 46 facilities (57%; 95% CI 32-80%). CONCLUSIONS: In 2000, most of the health facilities in Burkina Faso were using sterile injection equipment. However, practices were still observed that could expose patients, health care workers, and communities to risks, and that required specific interventions.

How best to estimate the global burden of pertussis?

In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. Good estimates are needed to help set priorities for vaccination programmes. We aimed to develop a simple, reliable, and explicit method for estimating pertussis cases and deaths for children under 15 years to calculate the global disease burden in 1999. We estimated the proportion of susceptible children becoming infected in countries with poor vaccination coverage (<70%) in 1999 at 30% by 1 year, 80% by 5 years, and 100% by 15 years of age and for countries with good coverage (> or =70%) at 10% by 1 year, 60% by 5 years, and 100% by 15 years. Vaccine efficacy was estimated at 80% for preventing infection and 95% for preventing deaths. We used UN population estimates and vaccination coverage reported to WHO (adjusted for specific survey data if available). Case fatality ratios for countries with high and low child mortality were derived from published and unpublished work. For some countries with good vital events registration we used reported deaths adjusted for underascertainment. In 1999 there were an estimated 48.5 million pertussis cases in children worldwide. Deaths from pertussis were estimated at 390000 and at 295000 after adjustment for local data sources. Based on this approach, disability-adjusted life years from pertussis (12.7 million) in 2000 exceeded those of other preventable diseases such as lung cancer (11.4 million) and meningitis (5.8 million). This simple approach yields estimates that can be used for setting vaccination programme priorities. Better data are needed on the public health importance of pertussis in high mortality countries, the benefits of incomplete vaccination, and the harm from delayed vaccination.

Investigation into a cluster of infant deaths following immunization: evidence for methanol intoxication.

A cluster of infant deaths due to severe metabolic acidosis following immunization was reported in a prosperous farming village in Egypt. Fears that more deaths might occur, and of a deleterious effect on national immunization programs prompted an urgent investigation by national and international partners. The deaths, and other previously unrecognized illness following immunization, were associated with excessive topical application of methanol. Methanol was employed as an anti-pyretic and anti-inflammatory agent following injections. Fear of adverse reactions to vaccine had encouraged increasing use of methanol for these purposes. Local physicians and nurses were unaware of the toxicity of methanol and did not consider it in the differential diagnosis, and thus did not offer appropriate life-saving therapy. The interaction of traditional practices and modern medical interventions can have clinically important consequences, and should be considered when programs are introduced and as they are monitored.

Ensuring vaccine safety in immunization programmes--a WHO perspective.

Ever since vaccines were firstly used against smallpox, adverse events following immunization have been reported. As immunization programmes expand to reach even the most remote communities in the poorest countries, it is likely that many more events will be temporally linked with vaccine administration. Furthermore, the profound shift in the general public and media interest in adverse events may lead to undue concerns and allegations which may ultimately jeopardize immunization programmes world-wide. While the health professional has understood this issue for some time, the public and the media have now also become all too aware of the significance of vaccine-related adverse events. The familiar vaccines, well-tested over decades, have not changed--but the perception regarding their safety has shifted. Claims outrageous or reasonable are being made against both the old and the newly-introduced vaccines. At the same time, the immunological and genetic revolution of the last decade may well bring to our notice some hypothetical risks that need to be addressed at pre-clinical level. WHO has been at the leading edge to guarantee vaccine safety for the last 30 years and will continue to do so. The Organization's plans for the next decade and beyond include the Safe Injection Global Network (SIGN), the development and introduction of safer technologies, and the prevention, early detection and management of AEFIs. The new technologies include needle-containing injection devices such as the autodisable syringe, as well as mucosal and transcutaneous immunization. Training will continue to be at the centre of WHO's efforts, limiting human error to a minimum. Mechanisms have been set in place to detect and respond to new and unforeseen events occurring. Above all, there is a willingness to respond to new climates and new technologies so that the Organization is in the best position to ensure safe immunization for all the world's children.

Immunisation safety: a priority of the World Health Organization's Department of Vaccines and Biologicals.

In 1999, the World Health Organization (WHO) Department of Vaccines and Biologicals launched the Immunisation Safety Priority Project to boost its activities in this area, with the aim of establishing a comprehensive system to ensure the safety of all immunisations given in national immunisation programmes. Countries are the primary focus of this project. The WHO has a role to play not only because of its technical and normative role but also because of its privileged relationship with country authorities and other partners, its global vision and mandate, and because it is perceived as free from conflicts of interest. There are four areas of focus in the project: quality control and assessment tools to ensure vaccine safety from clinical trials up to and including the point of use;research and development of safer and simpler delivery systems; access to safer and more efficient systems for vaccine delivery and sharps waste management; and mechanisms to respond promptly and effectively to vaccine safety concerns. The project emphasises the importance of advocating safety and developing necessary infrastructure and human resource to properly deal with immunisation related safety issues at a national level.

The Immunization Monitoring Program Active (IMPACT) prospective five year study of Canadian children hospitalized for chickenpox or an associated complication.

BACKGROUND: Varicella vaccine was approved for use in Canada in 1998. A major goal of universal varicella vaccine programs is to reduce severe infection and associated complications. Baseline data are essential against which to judge the effectiveness of routine childhood immunization. OBJECTIVE: To describe morbidity and mortality among children hospitalized for chickenpox. Methods. From January 1, 1991, to March 31, 1996, chickenpox admissions to 11 pediatric referral centers were actively identified. Patient and illness characteristics were compared for 3 subgroups defined by prior health: healthy; unhealthy but immunocompetent; immunocompromised. RESULTS: Of 861 cases 488 (56.7%) were healthy, 75(8.7%) were unhealthy and 298 (34.6%) were immunocompromised. The immunocompromised children differed from healthy/unhealthy cases in mean age (6.4 vs. 4.0/4.6 years, respectively, P < 0.0001); median interval from rash onset to admission (2 vs. 5/5 days, P < 0.0001); complication rate (20% vs. 90%/79%; P = 0.001); and rate of acyclovir therapy (98% vs. 24%/39%; P = 0.001). Unhealthy vs. healthy cases had a higher frequency (P < 0.01) of intensive care (13.3% vs. 4.7%), ventilation (9.3% vs. 2.0%) and death (4% vs. 0.2%). CONCLUSION: These data provide a baseline for morbidity/mortality resulting from chickenpox before varicella vaccine use in Canada.

Developing a national system for dealing with adverse events following immunization.

Although vaccines are among the safest of pharmaceuticals, the occasional severe adverse event or cluster of adverse events associated with their use may rapidly become a serious threat to public health. It is essential that national monitoring and reporting systems for vaccine safety are efficient and adequately coordinated with those that conventionally deal with non-vaccine pharmaceuticals. Equally important is the need for an enlightened and informed national system to be in place to deal with public concerns and rapid evaluation of the risk to public safety when adverse events occur. Described in this article is the outcome of efforts by the WHO Global Training Network to describe a simple national system for dealing with vaccine safety and with emergencies as they arise. The goals of a training programme designed to help develop such a system are also outlined.