Annual Report 2008 - 2009 - Liverpool School of Tropical Medicine

PROFESSOR BERNARD BRABIN MB ChB MSc PhD FRCPCH
HEAD OF THE CHILD AND REPRODUCTIVE HEALTH GROUP
PROFESSOR IN TROPICAL PAEDIATRICS
Bernard is Head of the Child and Reproductive Health Group. He holds a personal Chair in
Tropical Paediatrics at the University of Liverpool and the Foundation Chair in International
Child Health at the Academic Medical Centre, University of Amsterdam. His research focuses
on maternal and child health in low resource settings with particular emphasis on malaria,
and nutrition and infection interactions. He also undertakes research in Merseyside on the
effects of maternal smoking on child health.
DEVELOPMENT OF APPROPRIATE
AGE-BASED DOSING REGIMENS
Many febrile episodes in malaria endemic areas
are treated with over-the-counter antimalarial
drugs or by first-line health care providers
in settings where patient weights are not
known. In these situations drug doses are
determined by a patient’s age as a proxy of
their weight, but because of the considerable
natural variation in weight this means that
some patients may receive too much or too
little drug. This is a particular concern with
drugs that have a narrow therapeutic margin
and with dosing in early childhood and
adolescence, times of rapid growth and large
variations in bodyweight by age. Sub-optimal
dosing is a major cause of treatment failure,
particularly in young children who may have
insufficient immunity to clear any persistent
parasitaemia, and may drive the development
of drug resistance in populations. Overdosing
on the other hand may have potentially
fatal consequences for the individual and
may negatively affect the reputation of an
otherwise highly efficacious antimalarial.
There are no standardised procedures to devise
age-based proxies for bodyweight as part of
the normal regulatory drug developmental
process, yet malaria control programs need
dose recommendations that are based on both
weight and age. The lack of clear guidance
on the design of age-based dosing regimens
has resulted in considerable variation in the
available dose recommendations, some
resulting in poor, but widely-used, regimens.
To address this,
LSTM Child and
Reproductive
Health group
scientists
developed
a method in
collaboration
with WHO TDR
and Drugs for
Neglected
Diseases initiative (DNDi) to determine practical
age-based dose regimens for both children
and adolescents that would result in the
smallest number of patients receiving doses
above or below the effective dose range. A
weight-for-age reference data set was compiled
specifically for this purpose using data from
over 35 malaria endemic countries, to develop
a model that reflects the variation in weight by
age of populations in malaria endemic regions
of Africa, Asia-Pacific and Latin America and
can therefore provide the optimal translation of
weight-based to age-based dosing regimens.
It has become increasingly clear that there are
similar needs for age-based dosing regimens
with other drugs. To address this, the team from
LSTM has started work with DNDi and others
this year to explore practical opportunities for
work on drugs for other neglected diseases,
and improve the availability of evidence-based,
safe, effective age-based dosing regimens for
populations with limited access to health care.
WHO COLLABORATING CENTRE AT
LSTM REDESIGNATED FOR ANOTHER
4 YEARS
The World Health Organization Collaborating
Centre for the Prevention of Deafness, directed
by LSTM’s Dr Ian Mackenzie, is based in the
Child and Reproductive Health Group. Deafness
is often a hidden disability, leading to poor
education and social skills in children and the
severe restriction of occupational prospects
for adults. It is estimated that up to 4% of the
world’s population have disabling hearing loss,
a situation which is becoming worse worldwide
as the average population age increases.
Over the last few years the Centre has
conducted hearing prevalence studies in
Myanmar, Sri Lanka, India and West Java, for use
by WHO’s global burden of disease database.
The Centre has long standing experience
with studies related to the management of
chronic suppurative otitis media (runny ear),
a common preventable cause of deafness in
low resource countries. Our initial research
indicated that WHO guidelines and policy
required revision. This research in Kenya was
funded by The Wellcome Trust and showed
the cost-effectiveness of antibiotic eardrops.
We are now extending this work through a
grant from the US Thrasher Foundation to
include studies on how the nutritional status
of children influences their risk for ear infection.
We are particularly interested in the effects
of zinc supplementation on recovery rates
from ear infection. We have also examined
the relationship of deafness to HIV/AIDS in
children in western Kenya and work last year
in Peshawar, Pakistan confirmed the high
rate of deafness in children in this area which
paralleled a similar pattern in the Pakistani
community in Oldham, England.
Globally the management of deafness is
expensive and hearing aids and the recurring
costs of batteries are beyond the means of
most in poorer communities. By representing
WHO at international hearing and disability
meetings in China, Philippines, Thailand, USA,
India, France, Holland and Australia over the
last 2 years, we have highlighted the need
to translate these high standards in hearing
initiatives in a more equitable way.
Dr K Phiri recording from a child their auditory
brainstem responses and otoacoustic emissions
in a Malawian village.
The Centre at LSTM provides technical support
to WHO in Geneva as well as supporting several
teaching initiatives on deafness both overseas
and in the UK. The efforts of Dr Mackenzie have
been recognised through the re-designation of
the Centre by WHO for a further four years.
LSTM ANNUAL REPORT 9