download - Wellcome Trust

34 | DEVELOPING PEOPLE
A neglected
malaria
Once considered benign, vivax malaria is actually
far from innocuous.
Go with
the flow
Blood flow to the brain is carefully
controlled – but in a surprising way.
1
As well as P. falciparum, other
Plasmodium species can cause
malaria, including P. vivax. Vivax
malaria has been considered relatively
harmless, but as Career Development
Fellow Ric Price has discovered, it is
common, serious and, with drugresistant
forms appearing, a growing
threat to health in South-east Asia.
Malaria remains a serious problem in
South-east Asia, accounting for 40 per
cent of the world’s cases. Unlike Africa,
where falciparum malaria predominates,
South-east Asia faces infections from
both P. falciparum and P. vivax.
To test whether P. vivax really is ‘benign’,
Dr Price at the Menzies School of Health
Research in Australia, working with the
Wellcome Trust’s South-east Asia
Programme, set out to assess the impact
of the two malarias in Papua, Indonesia.
An analysis of hospital admissions over a
four-year period revealed that 64 per cent
of patients with malaria had P. falciparum,
24 per cent P. vivax and 10.5 per cent
mixed infections. In children under one,
however, P. vivax accounted for nearly
half of all malaria admissions. Across all
ages, the death rate for P. vivax, 1.6 per
cent, was comparable to the overall
death rate from malaria (2 per cent).
A community study revealed similar
patterns. More than half of the population
can expect to experience falciparum
malaria each year and nearly a third vivax
malaria. Again, the prevalence of vivax
malaria was higher in young children.
Moreover, vivax can also be harmful
during pregnancy. In a separate study, Dr
Price found that the fever and anaemia
associated with vivax as well as
falciparum malaria raised the risk of
premature labour and stillbirth in
pregnant women.
In part, P. vivax has been neglected
because drug resistance has been less of
a problem – it first appeared as recently
as 1989. Now, though, drug-resistant
forms of P. vivax are spreading across
much of South-east Asia and more
recently in South America. Cure rates for
standard treatments have fallen below
half for both P. falciparum and P. vivax.
On the brighter side, effective treatments
are available for multidrug-resistant
malaria. Indeed, a clinical trial of two
artemisinin combination therapies (ACT)
confirmed that they were clinically
effective for treating multidrug-resistant
falciparum and vivax malaria in Papua.
A study of the impact of widespread
deployment of ACT on P. vivax is now
underway.
References for this article can be found at
www.wellcome.ac.uk/annualreview.
The brain is a major consumer of
energy, and the harder it works the
more energy it needs. As a result,
brain activity is tightly coupled to
blood flow, which delivers the glucose
and oxygen needed to generate
energy. But as new Sir Henry
Wellcome Postdoctoral Fellow Clare
Howarth has discovered, this wellknown
phenomenon is controlled in
an unexpected way.
After a course on magnetic resonance
imaging (MRI) fired her interest during a
physics degree at Imperial College
London, Dr Howarth was accepted onto
University College London’s highly
competitive Wellcome Trust-funded
Four-year PhD Programme. There her
focus turned to energy consumption by
the brain.
Standard brain imaging techniques,
such as functional MRI, make use of the
fact that regions of brain activity are
marked by increased blood flow. This
blood flow was thought to be regulated
by smooth muscle surrounding arterioles
carrying blood to areas of the brain, but
Dr Howarth discovered that although
smaller vessels, capillaries, lack smooth
muscle, they are sheathed in contractile
cells known as pericytes. And it is
contraction of these cells that controls
capillary diameter and regulates regional
blood flow in the brain.
Images
1 In South-east Asia, Plasmodium vivax as well as P. falciparum
causes serious malaria.
2 Colour-coded image of blood flow in the brain.