Research Article: The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices

Date Published: March 22, 2011

Publisher: Public Library of Science

Author(s): Alice Zwerling, Marcel A. Behr, Aman Verma, Timothy F. Brewer, Dick Menzies, Madhukar Pai

Abstract: Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user
friendly Web site for TB clinicians to discern global BCG vaccination policies
and practices and improve the care of their patients.

Partial Text: Tuberculosis (TB) remains one of the major causes of infectious morbidity and
mortality globally, claiming millions of lives every year. Approximately one-third
of the world’s population is estimated to be infected with
Mycobacterium tuberculosis, giving rise to 9.4 million new
cases of active TB disease each year [1]. The majority of the TB burden exists in 22 high-burden
countries, but with immigration and global travel TB is difficult to eliminate from
any one country [1]–[4].

While most experts agree that BCG is efficacious against severe forms of childhood
TB, its efficacy against TB in adults is highly variable [7]. As a result of the uncertain
efficacy of the BCG vaccine, countries have developed very different BCG vaccination
policies. Some countries, such as the United Kingdom, have or have had universal BCG
vaccination programs, while others (including Canada and the United States) either
only recommended BCG for high-risk groups or did not advocate BCG countrywide. The
Canadian situation was further complicated by differing policies across provinces,
where some provinces underwent mass vaccination programs and others did not. In
addition, BCG vaccination policies have varied by the number of doses used, the age
at which vaccination was given, and the methods used to deliver the vaccine
(although most countries today use only the intradermal route) [8]. Vaccination practices also have
changed within and across countries over the years, reflecting changes in evidence,
health policy, public perception, increasing or decreasing TB incidence, and HIV
incidence. As a result of these changes to the BCG policies in various countries, it
is necessary to not only know the current BCG vaccination policies but also past
policies and applicable changes when dealing with adults who received BCG
vaccination in childhood.

Detailed information on past and present BCG vaccination policies and practices were
collected from as many countries as possible by one of three methods. First, short
respondent-completed questionnaires were sent out to at least two individuals in
each country. Questionnaires were sent to experts in TB research, TB control
programs, or public health/vaccination programs. Whenever possible, an attempt was
made to collect two completed questionnaires from each country in order to validate
the data. Questionnaires were available in English, French, and Spanish, and were
designed to capture both current policy and actual BCG practices, as well any
applicable changes that had occurred over the last 25 years. Detailed questions
asked for information concerning past as well as current practices, the timing and
nature of changes to the policies and or practices, repeat, multiple, or booster
shots, information concerning tuberculin skin testing in conjunction with BCG
vaccination, influence of HIV on the decision to vaccinate, and vaccine strain
differences. A total of 89 completed questionnaires were received over a 2-year
period. Second, data were abstracted from published papers, reports, and available
government policy documents retrieved through literature searches on PubMed and via
the World Wide Web. Third, we used immunization data available from the World Health
Organization Vaccine Preventable Diseases Monitoring System (http://apps.who.int/immunization_monitoring/en/globalsummary/ScheduleSelect.cfm),
which provide basic information on all vaccines currently in use in each country
[13].

The beta version of the Atlas went live in the fall of 2008 with completed
questionnaires on BCG vaccination from 62 countries. Since that time, more data have
been added and several improvements have been made. As of October 2010, we have
collected data concerning BCG vaccination policies and practices for 180 of 209
(86%) countries worldwide that we approached. The database is available as an
interactive Web site at http://www.bcgatlas.org/, where
information for a particular country’s BCG policy, along with its estimated
World Health Organization (WHO) TB incidence statistics, can be viewed alongside a
graphical map. Among the 180 countries with available data, 157 countries currently
recommend universal BCG vaccination, while the remaining 23 countries have either
stopped BCG vaccination (due to a reduction in TB incidence), or never recommended
mass BCG immunization and instead favored selective vaccination of “at
risk” groups (Figure 2).
Complete questionnaire data were available for 77 countries, while remaining data
were extracted from published sources.

The Atlas is an interactive Web site that allows users to select and view information
concerning a country’s past and current BCG vaccination policy either by
clicking on an interactive map or by selecting the country of interest from a
drop-down list (Figure 1). The
Web site is available to the public and is free of charge. Over the past year
(during its beta phase), we have recorded over 6,000 visits to the site, with a
steady increase in traffic over time.

While novel diagnostics have been developed for latent TB infection (LTBI) [15]–[19], the TST continues
to be the most widely used diagnostic test worldwide [20]. False positives can occur in
BCG-vaccinated individuals, complicating interpretation of test results [21]. However,
research suggests the timing of vaccination plays an important role [9],[10]; in a
meta-analysis, Farhat et al. found BCG vaccination at infancy has only a minimal
effect on TST specificity, particularly if the TST is done more than 10 years after
the BCG was administered, whereas BCG later in life or if given more than once led
to more frequent, larger, and pronounced TST reactions [21]. The Atlas may help clinicians
interpret TST by providing the information necessary to assess whether the TST is a
valid diagnostic tool in a particular patient, or when alternative diagnostics may
be preferable.

Recently there has been renewed interest in developing novel vaccines for TB.
According to the Global Plan to Stop TB, 2006–2015, “effective TB
vaccines will be an essential component of any strategy to eliminate tuberculosis
(TB) by 2050” [33]. In 2009, at least six different vaccine candidates
completed Phase I clinical trials, and three are currently in Phase II [18]. Novel vaccine
candidates include both live and sub-unit vaccines. Many employ a heterologous
“prime-boost” strategy that complements the existing immune response to
BCG. Either the existing BCG or a new recombinant BCG is administered first, and
then the new vaccine serves as a “booster”. Different vaccines are being
developed that could be administered in infants and young children pre-exposure, and
others as adjuvants to chemotherapy post-exposure. Given that novel vaccines may
work to complement the existing BCG, it may be relevant to know what previous BCG
vaccination individuals have had, how many and at what ages prior to administering
novel “booster vaccines”. Similarly, we may be concerned that antigens
from the primary vaccination with BCG may affect the booster vaccine. Therefore, in
countries where revaccination with BCG was practiced, we might expect higher rates
of Koch response, or delayed hypersensitivity response.

Despite nearly a century of use, the BCG vaccine continues to be controversial, and
policies and practices vary widely across the world. Many countries have experienced
major changes in regards to revaccination over the past 20 years. The BCG World
Atlas: A Database of Global BCG Vaccination Policy and Practices is an interactive
Web site that attempts to provide the clinician, researcher, and pubic health
practitioner alike with resources and information necessary to interpret current and
novel TB diagnostics and conduct fruitful research on novel vaccines. Most
critically, this is a useful resource for the TB community and is publicly available
free of charge through an easy-to-use Web site.

Source:

http://doi.org/10.1371/journal.pmed.1001012

 

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