1/30/2018 CDC - Malaria - Tools for Tomorrow - CDC’s Research Contributions

CDC’s Research Contributions

Over the past three decades, CDC has contributed to the world’s knowledge of
malaria, especially the burden of malaria in areas of high malaria transmission in
children and pregnant women and the impact of drug resistance. CDC has
contributed to the development and evaluation of prevention and control
interventions recommended by the World Health Organization and used by
programs worldwide to fight malaria: insecticide-treated bed nets (ITNs), intermittent
preventive treatment in pregnancy (IPTp), and artemisinin-based combination
therapies (ACTs).

Having completed the research that has informed the current generation of malaria
control interventions, CDC is well-positioned to refine malaria interventions as well
as develop new interventions to stay ahead of the curve—and contribute to
achieving the ambitious global goals of malaria elimination and ultimately
eradication.

CDC’s Research Highlights

In the last decades, CDC has contributed to our knowledge and understanding of
these areas:

Understanding the impact of malaria

Monitoring drug resistance
Developing and evaluating interventions
Antimalarial drug use, diagnosis, and non-falciparum malarias
Malaria in travelers

Understanding the impact of malaria

CDC work in Malawi and Kenya established the role of malaria in infant and
early childhood mortality in high transmission settings and documented the
public health importance of severe malaria-related anemia as a major cause of
death in such populations.
CDC studies in Malawi and Kenya determined the risk of malaria-associated low
birth weight, one of the adverse effects of malaria infection during pregnancy.
CDC has also made substantial contributions to efforts to quantify the burden of
malaria mortality in African children and the burden of malaria in pregnancy.

Toolkit Helps Assess the Burden of Malaria during Pregnancy

CDC, WHO, and other partners developed a toolkit to help

assess the burden of malaria during pregnancy in countries
without recent data. Safe and effective interventions can help
prevent adverse consequences of malaria in pregnancy.
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1/30/2018 CDC - Malaria - Tools for Tomorrow - CDC’s Research Contributions

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Monitoring drug resistance

Beginning in the late 1950s, resistance to the most commonly used antimalarial
drug, chloroquine, began to appear almost simultaneously in Southeast Asia and
South America.

Starting in the 1980s, CDC called attention to the impact of antimalarial drug
resistance in Africa. CDC and colleagues documented the public health impact
of chloroquine resistance and helped countries in sub-Saharan Africa establish
malaria drug resistance monitoring networks.
In the early to mid-1990s, CDC and WHO developed and implemented standard
protocols for assessing the therapeutic efficacy of drugs and changing
antimalarial drug treatment guidelines. CDC helped develop standard
techniques that use molecular techniques for discerning reinfection from
recrudescence to assess drug efficacy outcomes in high transmission settings.
As a result of the findings from CDC-assisted drug efficacy testing, first-line
antimalarial drug policy changed from chloroquine to sulfadoxine-pyrimethamine
(SP) in Malawi, Zambia, Kenya, Tanzania, and the Democratic Republic of
Congo. CDC contributed to economic evaluations of the costs associated with
changing antimalarial drug policies.
CDC continued to contribute to the knowledge of drug resistance by determining
the origin and distribution of SP-resistance alleles across Africa. CDC and
KEMRI documented the SP "killer" gene mutation 164 in Africa, which signaled
the end of the useful lifetime for this class of malaria treatment drugs.

Developing and evaluating interventions

CDC conducted groundbreaking work to develop and evaluate IPTp, to evaluate
ITNs in areas of high malaria transmission, and to define how best to manage
malaria cases in children. CDC is also working on evaluating new technologies for
malaria control.

Intermittent Preventive Treatment for Pregnant Women (IPTp)

CDC determined that intermittent preventive treatment of malaria during

pregnancy (IPTp)—the delivery of curative doses of effective antimalarial drugs
as part of routine prenatal care—reduced the risk that malaria-infected pregnant
women would have babies with low birth weight, a contributing factor to infant
death.
To benefit from treatment, pregnant women who are HIV-positive need more
doses of IPTp with the drug sulfadoxine-pyrimethamine (SP) or, in some cases,
a different drug.

Insecticide-treated Bed Nets (ITNs)

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1/30/2018 CDC - Malaria - Tools for Tomorrow - CDC’s Research Contributions

CDC and the Kenya Medical Research Institute (KEMRI) completed one of the
first studies to demonstrate that ITNs could reduce malaria-related illness and
death in an area of very intense, year-round malaria transmission. Prior to these
findings, all of the evidence of bed net efficacy in Africa had been collected in
settings where transmission was only moderate or exclusively seasonal.

This study also broke ground by showing that if enough people in a malaria-
endemic community were protected with ITNs, the absolute numbers of
mosquitoes would be reduced and even individuals in neighboring households
without ITNs could be protected from infection (the "community effect").
CDC studies also allayed concerns that continued use of bed nets would simply
cause children at risk of malaria-related death to die at slightly older ages. Use
of regularly maintained ITNs for an additional 2 - 4 years showed that continued
protection for infants did not shift mortality to older children.
Pregnant women also were shown to benefit from ITNs. When pregnant women
slept under ITNs, malaria infections and the malaria-associated ill effects in
pregnancy were reduced. In addition, severe malarial anemia was reduced by
47% and the delivery of low-birth-weight infants decreased by 28%.

CDC’s "X-Ray Gun" Measures Insecticide on Nets

A CDC scientist has adapted an x-ray fluorescence

analyzer to quickly measure the level of the
insecticide deltamethrin on insecticide-treated bed
nets (ITNs).

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Use of Both ITNs and Indoor Residual Spraying

In a 2008–2009 study in Rachuonyo District, Kenya, CDC determined that the

use of both ITNs and IRS reduced malaria infections by 62% (and by 67%
among those 6 months to 4 years, the most vulnerable) compared with use of
ITNs alone. IRS also reduced the numbers of anopheline mosquitoes. These
data suggest for the first time that by using both interventions together, people
living in areas that receive both interventions benefit considerably.

Case Management

Most of the deaths caused by malaria are in young children under 5 years of
age. CDC helped establish the clinical basis for the Integrated Management of
Childhood Illnesses (IMCI) strategy and assessed components of its
implementation. IMCI is an approach developed by WHO and the United Nations
Children's Fund (UNICEF) that promotes accurate identification of childhood
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illnesses in outpatient settings, ensures appropriate combined treatment of all
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major illnesses, strengthens caretaker counseling, and speeds referral of

severely ill children.
After resistance developed to sulfadoxine-pyrimethamine, which had replaced
chloroquine for first-line treatment, artemesinin-containing combination therapies
(ACTs) were widely adopted; CDC contributed to establishing valid techniques
for measuring adherence to ACTs.

Intermittent Preventive Treatment of Infants (IPTi)

CDC contributed to understanding the role of intermittent preventive treatment of

infants (IPTi) in reducing malaria illness. Similar to IPTp, IPTi consists of
treatment doses of sulfadoxine-pyrimethamine (SP), delivered to children
regardless of malaria infection or symptoms at their first 3 routine vaccinations.
Studies have demonstrated that IPTi can reduce the incidence of clinical malaria
by a little more than 30%.

Antimalarial drug use, diagnosis, and non-falciparum malarias

Antimalarial Drug Issues

In many countries substandard and counterfeit drugs present a problem.

CDC-developed a colorimetric test for counterfeit artesunates, an important ACT.

The test can be used by workers in the field to determine whether the packaged
drug contains the antimalaria drugs.
CDC and Ifakara Health Institute completed the only study of malaria infection
among clients at retail shops and contributed to the first nationally representative
study of antimalarial drug quality in the retail sector.
CDC contributed to testing new drug candidates and vaccine components in
nonhuman primates.

CDC’s Dye Test Detects Counterfeit Antimalarials

A colorimetric test developed at CDC to assess the

quality of artesunate requires only a small portion of an
artesunate tablet (1%). After the material is exposed to a
strong base and then treated with a reagent, a distinct
yellow color is produced if artesunate is present.

More

Diagnosis

CDC collaborated with local research institutions in Kenya and Tanzania to learn
more about how best to use recently available rapid diagnostic tests (RDTs) for
malaria, which can provide diagnosis in as little as 15 minutes.

Recent CDC supported research in Tanzania demonstrated that health

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workers at rural health facilities can successfully use RDTs to improve
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patient care when supported by appropriate supervision and RDT quality

control. In response to these studies, the Tanzanian National Malaria Control
Program is exploring options for providing adequate supervision and quality
control to deliver malaria RDTs nationwide. Better diagnostics and
appropriate treatment will result in fewer malaria-related complications and
deaths and provide a more accurate way of measuring the impact of malaria
control.

Recent CDC-supported research on RDTs in Kenya showed that these tests

were underutilized, but when they were used, the results were followed
properly by health workers.

CDC helped demonstrate that many malaria parasites in South America do not
produce a specific protein product, which will preclude the use of many RDTs for
malaria in endemic regions on this continent.

Non-Falciparum Malarias

CDC contributed to the understanding that P. vivax , long thought to be much

less lethal than P. falciparum , could be quite virulent.

CDC helped document that a 5th malaria parasite, P. knowlesi , which was
recently recognized as a cause of human malaria disease, had been imported
into North America by a traveler.

Malaria in travelers
CDC contributes to research of malaria in U.S. citizens who acquire malaria
elsewhere by establishing rates of failure and adverse reactions for U.S.
travelers and Peace Corps volunteers taking chloroquine, sulfadoxine-
pyrimethamine, and mefloquine for malaria prevention.

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