The n e w e ng l a n d j o u r na l of m e dic i n e

edi t or i a l s

A Vaccine for Malaria

Nicholas J. White, F.R.S.

Its been a long time coming, and indeed we are were enrolled. The report describes vaccine ef-
still not there yet, but it is becoming increasingly ficacy against P. falciparum malaria in the first 6000
clear that we really do have the first effective vac- of 8923 children in the older age category, together
cine against a parasitic disease in humans. If there with an evaluation of the first 250 cases of severe
are no unforeseen disasters, the RTS,S/AS01 Plas malaria from the two age groups. It is not usual
modium falciparum malaria vaccine should become practice to publish the results of trials in pieces,
available in just over 3 years. The World Health and there does not seem to be a clear scientific
Organization (WHO) has already taken the un- reason why this trial has been reported with less
usual step of indicating that it could recommend than half the efficacy results available. The target
this first malaria vaccine for use in some African population for this vaccine is young infants who
countries as early as 2015, depending on the full would receive the malaria vaccine together with
phase 3 trial results that will become available in routine immunizations, but the critical efficacy
2014.1 The vaccine has been developed by a public results in this subgroup will not be reported for
private partnership between GlaxoSmithKline and another year. Even then, only results on short-term
the Program for Appropriate Technology in Health efficacy will be available, findings that will be
(PATH) Malaria Vaccine Initiative, supported by the insufficient to assess the public health role of
Bill and Melinda Gates Foundation, primarily for this vaccine.
use in infants and young children in sub-Saharan The interim results are broadly in line with
Africa. RTS,S/AS01 is a hybrid construct of the those reported previously in extended phase 2
hepatitis B surface antigen fused with a recom- studies.3-5 Protective efficacy against P. falciparum
binant antigen derived from part of the circum- malaria (55% protection against all malaria epi-
sporozoite protein. This is the protein coat of the sodes) was at the upper end of expectations from
sporozoite, the parasite stage that is inoculated earlier studies, whereas the overall reduction in
by the feeding anopheline mosquito, which then severe malaria (35% protection) was slightly less
invades liver cells and multiplies there before en- than anticipated.
tering the bloodstream. Keys to the success of the Trials often throw up unexpected findings.
vaccine are the immunogenic polymeric nature of In this trial, there were significantly more cas-
RTS,S particles and the proprietary adjuvant AS01. es of meningitis among children receiving the
A large number of other potential malaria vac- RTS,S/AS01 vaccine than among those receiv-
cines are in various stages of development, but ing the comparator vaccines. There seems to
the RTS,S/AS01 vaccine is considerably further be no plausible explanation for this, and it
along the path to registration and potential de- may well turn out to be a chance finding, but
ployment than the others. it cannot be ignored. On the other hand, the
In this issue of the Journal, the RTS,S Clini- increased risk of febrile reactions or seizures
cal Trials Partnership provides an interim re- among RTS,S/AS01 recipients may be real, re-
port of a large, multicenter phase 3 trial of this flecting the reactogenicity of this highly im-
vaccine.2 A total of 15,460 children in two age munogenic vaccine. Such questions highlight
categories 6 to 12 weeks and 5 to 17 months the importance of phase 4 studies of both safety

1926 n engl j med 365;20 nejm.org november 17, 2011

The New England Journal of Medicine

Downloaded from nejm.org on March 20, 2017. For personal use only. No other uses without permission.
Copyright 2011 Massachusetts Medical Society. All rights reserved.
 editorials

and effectiveness with active surveillance if this recommend that the inclusion of RTS,S/AS01 in
vaccine is deployed. the multipronged attack against malaria is justi-
What does this vaccine mean for the future fied. The key question of how long the protection
of the control and elimination of malaria? The against malaria lasts, particularly in the antici-
considerable increase in global funding is paying pated context of declining malaria transmission,
dividends. In places where effective interven- remains open. An assessment of an 18-month
tions (insecticide-treated bed nets, insecticides, and booster dose will not be available until 2014.
artemisinin-combination treatments) are being in- Another key issue is whether efficacy varies ac-
tensively deployed, malaria morbidity and mortal- cording to the intensity of transmission. We also
ity are falling. Several new, simple, affordable in- do not know yet how much the vaccine will cost.
terventions, such as seasonal chemoprevention All these factors are essential components of the
among young children in areas of seasonally objective assessments of cost-effectiveness that
high malaria transmission and the use of artesu- should form the basis of future global and na-
nate in patients with severe malaria, can also pro- tional policy decisions.
vide substantial reductions in mortality. The very Disclosure forms provided by the author are available with the
full text of this article at NEJM.org.
low rate of death from malaria in this large trial
(only 10 deaths directly attributed to malaria) From the Faculty of Tropical Medicine, Mahidol University,
Bangkok, Thailand.
testifies to the benefits of providing early diagno-
sis and effective antimalarial treatment. But there This article (10.1056/NEJMe1111777) was published on Octo-
ber 18, 2011, at NEJM.org.
are real dangers ahead. How will the necessary
funding be sustained in the face of a global eco- 1. Malaria: initiative for vaccine research (IVR). Geneva: World
Health Organization (http://www.who.int/vaccine_research/
nomic downturn, along with a reduction in politi- Malaria/en/index.html).
cal pressure associated with declining mortality 2. The RTS,S Clinical Trials Partnership. First results of
from malaria? In addition, artemisinin resistance phase 3 trial of RTS,S/AS01 malaria vaccine in African children.
N Engl J Med 2011;365:1863-75.
in malaria parasites and pyrethroid resistance 3. Bejon P, Lusingu J, Olotu A, et al. Efficacy of RTS,S/AS01E
in anopheline mosquito vectors pose very serious vaccine against malaria in children 5 to 17 months of age. N Engl
threats. J Med 2008;359:2521-32.
4. Asante KP, Abdulla S, Agnandji S, et al. Safety and efficacy of
All the investigators who have labored long the RTS,S/AS01(E) candidate malaria vaccine given with expanded-
and hard in the development and evaluation of programme-on-immunisation vaccines: 19 month follow-up of
this malaria vaccine deserve congratulations. It is a randomised, open-label, phase 2 trial. Lancet Infect Dis 2011;
11:741-9.
a great achievement and an important advance, 5. Olotu A, Lusingu J, Leach A, et al. Efficacy of RTS,S/AS01E
but they know that this partially protective vac- malaria vaccine and exploratory analysis on anti-circumsporozo-
cine is not the sole solution to the control and ite antibody titres and protection in children aged 5-17 months
in Kenya and Tanzania: a randomised controlled trial. Lancet
elimination of malaria. After registration, the de- Infect Dis 2011;11:102-9.
finitive WHO guidance, expected in 2015, may Copyright 2011 Massachusetts Medical Society.

Childhood Obesity and Coronary Heart Disease

Albert P. Rocchini, M.D.

Obesity is the most common nutritional problem creased incidence of atherosclerosis in adulthood.
among children in both developed and under- Postmortem studies have shown that obesity in
developed countries. Despite efforts over the past childhood and adolescence is associated with in-
decade to prevent and control obesity, data from creased evidence of atherosclerosis at autopsy, es-
the 20032006 National Health and Nutrition Ex- pecially in males.2 Epidemiologic studies involving
amination Surveys (NHANES) show that 16.3% children have documented a strong association
of children and adolescents, 2 to 19 years of age, between the major known atherosclerosis risk fac-
are obese (i.e., have a body-mass index [BMI] above tors (elevated blood pressure, dyslipidemia, in-
the 95th percentile for age and sex).1 flammatory markers, and insulin resistance) and
There is strong epidemiologic evidence that childhood obesity.3 Baker et al.,4 using data on
obesity in childhood is associated with an in- childhood BMI z scores and information from

n engl j med 365;20 nejm.org november 17, 2011 1927

The New England Journal of Medicine
Downloaded from nejm.org on March 20, 2017. For personal use only. No other uses without permission.
Copyright 2011 Massachusetts Medical Society. All rights reserved.