Part C

In this part of the test, there are two texts about different aspects of healthcare. For questions 1-8, choose the
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answer (A, B, C or D) which you think fits best according to the text. B
C
Fill the circle in completely. Example: D

Text 1: The BCG vaccine

The bacillus Calmette-Guérin vaccine (BCG), which provides effective protection against tuberculosis (TB), is the
oldest vaccine in the world that is still in use. Albert Calmette and Camille Guérin began developing it in 1900, and

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by 1921 they had a stable, nonvirulent strain of TB which could be used to protect against the disease. In the midst
of this progress, it was discovered that BCG seemed to provide benefits beyond protection against TB. A 1927 trial

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in Sweden showed that the vaccine reduced early-life mortality, and that this benefit could not be explained simply
by the reduction in TB deaths. The researcher who reported these results, Carl Naeslund, suggested that BCG

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might trigger some ‘nonspecific immunity’, through unknown means. In the ensuing century, studies, surveys and
clinical trials have documented that these nonspecific effects appear to be real and robust. Other live vaccines,
such as the measles vaccine, also show nonspecific effects, though the best-studied ones are for BCG.

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In North America, Europe and Australia, where TB is no longer a major concern, the BCG remains of interest

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because of its potential to reduce the risk of diabetes, cancer, Alzheimer’s, allergic diseases and other conditions.
Physician-epidemiologist Christine Stabell Benn and researcher Nigel Curtis have conducted clinical trials in

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Denmark and Australia, respectively, showing that BCG vaccination at birth reduces the risk of eczema—especially
in babies who are predisposed to eczema because one or both parents had it. However, before BCG can be
recommended for this purpose, certain barriers will have to be overcome. Regulatory agencies will have to review
the evidence and approve BCG for a new condition. Also, the vaccine will have to become broadly available, which
is not currently the case in North America, Europe or Australia.

Many African countries vaccinate children with BCG, but only 50 percent of children receive the vaccine within the
first month of life, when they are extremely vulnerable to other infections. Neonatal mortality remains high in Africa,
even as child mortality has declined. Because BCG is given for TB and children rarely die of TB in their first few
months, ‘there’s no incentive for vaccination programs to improve coverage early on in life,’ Stabell Benn explains.
But her clinical trials in Guinea-Bissau have shown that receiving the vaccine at birth can reduce neonatal mortality
by about a third. ‘In coming too late with the vaccine, you lose a lot of potential for doing a lot of good,’ she says.
‘My dream would be that we repurpose BCG as a vaccine against neonatal mortality, because that would really
change how it’s being used.’

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[CANDIDATE NO.] READING QUESTION PAPER PARTS B & C 08/16

 The body of evidence on BCG’s off-target effects is now substantial enough that researchers and health policy
makers have recently convened international workshops to evaluate whether there is sufficient evidence to
recommend policy changes to childhood vaccinations schedules. ‘If we want to be sure we have the perfect
information,’ Stabell Benn says, ‘we will never get going. So this is about finding that cut-off, where you can
start and say, ‘We have enough now to move to policy and be reasonably sure that it will really truly benefit most
recipients.’

Still, the idea of using BCG’s nonspecific effects to treat a host of diseases is not universally accepted. ‘I’ve never
come across a topic that’s more polarizing,’ says Curtis. Although there is no question that live vaccines—in

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particular, BCG—have immune effects beyond their main target, ‘the bit that remains controversial is to what extent

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those changes in the immune system are translated to clinically apparent effects,’ he explains. In other words, in
which populations, and for which conditions, can these off-target effects meaningfully help patients?

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As the patent on BCG expired long ago, pharmaceutical organisations aren’t gearing up for the trials necessary to
obtain regulatory approval for other uses. ‘The challenges we face are not really scientific,’ says Jaykumar Menon,

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chair of a non-profit organisation attempting to develop affordable therapeutics. ‘It’s a story of market failure.’ The
solution might be to gain better insight into the mechanisms of BCG’s off-target effects. Then companies could

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improve on the existing vaccine to create a new one for which they could seek patents, says immunologist and
infectious disease clinician, Mihai Netea.

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Netea’s group has identified chemical components on the cell wall of BCG that induce trained immunity and
developed a nanoparticle on whose surface the BCG-derived components could be placed. In animal experiments,
the researchers have shown that the nanoparticle could stimulate trained immunity. Netea envisions that the
patentable nanoparticle technology could be the basis for a wholly new vaccine for treating cancer patients—a
population for which the live BCG vaccine is usually too risky due to immunosuppression.

The ‘holy grail’ of the research that scientists in this area are conducting is not just to understand how vaccines
have these effects, Curtis says, but also to use that understanding to design better vaccines and compounds that
would target specific conditions, ranging from diabetes to cancer.

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[CANDIDATE NO.] READING QUESTION PAPER PARTS B & C 09/16