University of Michigan. US: Combining insecticide-treated bed nets with vaccines and other
control measures may provide the best chance at eliminating malaria,
which killed nearly 600,000 people worldwide in 2013, most of them
African children.
More than 20 malaria vaccine candidates are in different stages of
development, but none are licensed for use. So no one knows for sure
what will happen when vaccines and bed nets are used together.
A University of Michigan-led research team used a mathematical model
of malaria transmission to find out. The researchers examined potential
interactions between the two control measures and found that—in some
cases—the combination of bed nets and a vaccine actually makes the
problem worse.
"The joint use of bed nets and vaccines will not always lead to
consistent increases in the efficacy of malaria control. In some cases,
the use of vaccines and bed nets may actually make the situation worse,"
said Mercedes Pascual, a professor in the U-M Department of Ecology and
Evolutionary Biology.
"Specifically, our study suggests that the combined use of some
malaria vaccines with bed nets can lead to increased morbidity and
mortality in older age classes."
Pascual is co-author of a paper scheduled for online publication Jan.
19 in Proceedings of the National Academy of Sciences. The first author
is Yael Artzy-Randrup of the University of Amsterdam, a former
postdoctoral researcher in Pascual's lab. The other author is Andrew
Dobson of Princeton University.
The malaria vaccines under development fall into three categories,
each focusing on a different stage of the malaria life cycle. That cycle
involves human hosts and Anopheles mosquitoes infected with Plasmodium
parasites.
Preerythrocytic vaccines, or PEVs, aim to reduce the chances that a
person will be infected when bitten by a disease-carrying mosquito.
Blood-stage vaccines, or BSVs, don't block infection but try to reduce
the level of disease severity and the number of fatalities.
Transmission-blocking vaccines, or TBVs, don't protect vaccinated
individuals against infection or illness. But they prevent mosquitoes
from spreading the disease to others after biting a vaccinated person.
Because TBV vaccines provide no protection to the vaccinated person
but potentially reduce the rate at which others are infected, they are
commonly called altruistic vaccines.
Pascual and her colleagues found that the combination of treated bed
nets and TBV vaccines achieves the most efficient control, resulting in
fewer cases of malaria while increasing the probability of eliminating
the disease.
"Ironically, the vaccines that work best with bed nets are the ones
that do not protect the vaccinated host—the bed net does that—but
instead block transmission of malaria in mosquitoes that have found an
opportunity to bite vaccinated hosts," Artzy-Randrup said.
In contrast, both BSV and PEV malaria vaccines, when combined with
bed nets, actually increased the number of malaria cases seen in the
modeling study. Interactions between the bed nets and those vaccines
reduced levels of natural immunity in the population, increasing
morbidity in older age classes.
Unraveling the interactions between bed nets and vaccines is
especially challenging due to the complex and transient nature of
malaria immunity.
A child's first malaria infection can result in severe, sometimes
fatal, illness. If the child survives, he or she will gain partial
immunity that reduces the risk of severe illness in the future.
Additional bites from infected mosquitoes can help the child retain
that immunity, which would otherwise wane after one to two years. But
the combination of bed nets and certain vaccines can undermine that
natural immunity.
"This complexity is at the heart of why it has been so hard to develop any sort of malaria vaccine," said co-author Dobson.
In 2013, there were an estimated 198 million malaria cases worldwide,
including 584,000 deaths, according to the World Health Organization.
Most deaths occur among children living in Africa, where a child dies
every minute from malaria, according to WHO.
Between 2000 and 2013, access to insecticide-treated bed nets
increased substantially. In 2013, almost half of all people at risk of
malaria in sub-Saharan Africa had access to an insecticide-treated net, a
marked increase from just 3 percent in 2004, according to WHO.
Funding for the modeling study was provided by the Fogarty
International Center, the National Institutes of Health, a James
McDonnell Foundation award, and Princeton University Grand Challenges.
Pascual is an investigator of the Howard Hughes Medical Institute.