INFECTIOUS DISEASES
CDC’s Yellow Fever Diagnostic Kit Could Mean
Faster Outbreak Response, Fewer Deaths
By Maggie Silver, MPH, Arboviral Diseases Branch, US Centers for Disease Control and Prevention
Yellow fever is one of the oldest-
recognized mosquito-borne diseases in
the world. Those who become infected
with the virus are at risk for severe liver
disease with bleeding and yellowing skin.
Between 30 to 60% of those who develop
this severe form of the disease will die.
Despite having an effective vaccine since
the 1930s, we continue to see outbreaks
occur, particularly in Africa and South
America. In 2016-17, nearly 1,000 cases
of yellow fever were confirmed in Angola
and Democratic Republic of Congo, and
around 2,700 cases have been confirmed
in Brazil since 2017. These totals are
likely much higher since many people
didn’t seek treatment or died before their
diagnosis could be confirmed.
Being able to quickly identify yellow
fever infections is crucial to stopping
an outbreak. When a yellow fever
outbreak occurs, public health officials
must mobilize quickly, as the disease
can spread rapidly within a region. Fast,
accurate identification of yellow fever
cases allows health authorities to swiftly
implement mass vaccination campaigns
that can prevent further illness. This
is why the global strategy to Eliminate
Yellow Fever Epidemics (EYE), enacted by
the World Health Organization (WHO) in
2016, includes improved diagnostic testing
and early detection as part of its strategy.
Currently, no validated commercially
available yellow fever tests exist. For
the last five years, researchers at the
US Centers for Disease Control and
Prevention (CDC) have been looking for
ways to transform the current, highly
specialized test (IgM-capture ELISA) into a
test accessible to laboratory staff working
in resource-poor countries. All those years
spent in the lab trying to streamline the
traditionally complex process have begun
to pay off. The CDC yellow fever diagnostic
research team, led by Jane Basile and
Christin Goodman, have managed to
produce a yellow fever diagnostic kit
that cuts previous processing time from
three days to just four hours. The kit is
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LAB MATTERS Winter 2020
CDC Researcher Jane Basile (center) works with attendees at the yellow fever workshop in Cameroon. Photo: CDC
CDC validated the new YF MAC-HD test kits during the 2016 Angola outbreak
and found that the method was easily transferable, and that the kit was
sensitive and specific. Now, with support from the Association of Public
Health Laboratories, CDC, WHO and Gavi, Basile and Goodman are taking
their kits on the road and teaching other laboratorians how to use them.
aptly named the “yellow fever M-antibody
capture-half day” (YF MAC-HD).
Diagnosing yellow fever can be difficult
due in part to the way symptoms occur, as
well as the lengthy, technically demanding
diagnostic test. Not only does the current
front-line yellow fever diagnostic test
take three days to complete, but it
requires highly trained laboratory staff
who must order and calibrate multiple
test components (reagents) in order to
accurately perform a test. Since most
yellow fever outbreaks occur in resource-
poor countries, where electricity, water
and even reliable shipping can be an issue,
this new diagnostic kit is a valuable tool in
combatting yellow fever outbreaks.
To address the technical challenges
of performing the existing serologic
test, Basile and Goodman created
pre-measured, calibrated test components
to allow the YF MAC-HD to be performed
easily in resource-limited settings. This
required a great deal of work producing
materials and testing complex matrices
of components before arriving at the best
combinations. The most critical of the kit
components are freeze dried to improve
stability, and the end-user simply adds
water. Each kit can test up to 24 samples
and is relatively shelf-stable—although
refrigeration is recommended.
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