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The list of research areas and treatments under analysis mentioned in various sources for Malaria includes:
Some of the more recent treatments for Malaria include:
Treatments to consider for Malaria may include:
Mutation of human gene provides protection against Malaria: New research conducted by scientists at the University of Toronto has suggested that not everyone develops life threatening health problems when bitten by a malaria-infected mosquito. Malaria causes an estimated 500 million clinical cases worldwide with symptoms ranging from headache, high fevers and nausea to more than 1 million deaths annually. Malaria has had a major effect on the evolution of the human species. Mutations occurring in the human genome that have helped us survive this infection have been selected for over tens of 1,000s of years of co-existing with this parasite. Understanding the mechanism of these mutations in making us more resistant to malaria can help in designing innovative new strategies to prevent or treat severe malaria in places such as sub-Saharan Africa. The research showed that people who have an enzyme deficiency called pyruvate kinase, which is required for energy production in the body or those who carry the gene trait for this deficiency may be protected from severe and fatal malaria. These findings could lead to the design of new novel therapies to treat and prevent severe and fatal malaria through enhancing the body's protective pathways instead of drowning the body with drugs.
Enzymes called "proteases," which are involved in hemoglobin digestion by malaria parasites, are attractive targets for developing new inhibitors. Another potential set of drug targets is contained within the apicoplast, an intracellular organelle of the malaria parasite that has recently been discovered to be related to chloroplasts in plants. (Source: excerpt from Malaria Research, NIAID Fact Sheet: NIAID)
NIAID also supports research to determine the mechanism of action of currently available drugs and to understand how drug resistance develops. One mechanism by which chloroquine and some other antimalarial drugs appear to function is through interfering with the parasite's ability to detoxify products of the hemoglobin digestion process that would be harmful to the parasite. A genetic cross between chloroquine-sensitive and chloroquine-resistant strains of P. falciparum is being systematically analyzed to identify the gene(s) responsible for resistance to this once most useful antimalarial drug. Because of increasing chloroquine resistance, antifolate-sulfa drug combinations like Fansidar™ are becoming increasingly important in treating falciparum malaria. Minute mutations in the parasite's dihydrofolate reductase gene, however, lead to resistance to the antifolate drugs. By identifying the genetic basis of drug resistance, scientists should be able to design better treatment strategies. In addition, this research is providing molecular markers of drug resistance that will be helpful in determining the best therapy for individual patients, as well as for the national surveillance efforts of countries where malaria is endemic. (Source: excerpt from Malaria Research, NIAID Fact Sheet: NIAID)
Mosquito Control
Scientific
investigators now realize the best approach to malaria control will
involve integrated methods that consider the biological,
epidemiological, and ecological factors that influence disease
transmission in a given area. Many NIAID-sponsored studies are aimed
at understanding the biology of the mosquito vector, as well as its
interaction with both the parasite and people. This information is
critical to identifying accessible targets for alternative control
strategies. Some NIAID-supported scientists are working to identify
new environmentally safe insecticides. Researchers also are using
satellite-based remote sensing technology to understand the effects
of climate change on transmission of malaria and other vector-borne
diseases. This may allow prediction of changing patterns of malaria
distribution, including the appearance of epidemics.
As a
long-term approach, scientists are using molecular biology to invent
new ways of modifying the mosquito so it cannot transmit malaria.
They are working to sequence the genome of the Anopheles
gambiae mosquito, the most efficient of the malaria vectors.
This work should help ongoing efforts to identify genes controlling
critical stages of parasite development within the mosquito. Other
investigators have made important progress in finding ways to
introduce new genes into the mosquito, such as those that produce
substances toxic to the parasite. Together, these studies could lead
to the development of mosquitoes that cannot support parasite
growth. In addition, field studies of mosquito population dynamics
in endemic regions are under way, which will provide a basis for
understanding how introduction of such "vector-incompetent"
mosquitoes might control or stop malaria transmission.
Vaccines
During the 1960s and
1970s, early clinical studies showed that experimental vaccination
with weakened malaria parasites could effectively immunize patients
against a subsequent malaria infection. Because vaccines based on
live, inactivated or killed malaria parasites are not currently
economically or technically feasible, much of the research on
vaccines focuses on identifying specific components or antigens of
the malaria parasite that can start a protective immune response.
Scientists encounter difficult obstacles in attempting to develop
malaria vaccines, in terms of parasite biology, human immune
responses, and both preclinical and clinical evaluation. Although
four different species of protozoan parasites cause human malaria,
most vaccine efforts have been directed toward falciparum malaria
because of its severity.
Parasite of the same species but
isolated from different geographic locations may be genetically and
immunologically distinct, so vaccines that protect against one
geographic isolate may not protect against another. In addition,
malaria parasites have complex life cycles with multiple distinct
developmental stages creating potentially thousands of different
antigens that could serve as targets of an immune response. Finally,
because protection appears to require both antibody-mediated and
cell-mediated immune responses, identifying delivery systems and
formulations that stimulate all the aspects of immune reactivity
represents an enormous technical challenge.
A sporozoite
vaccine would protect against the infectious form injected into a
person by a mosquito. But if a single sporozoite were to escape the
body's immune defenses, it could eventually lead to full-blown
disease. A merozoite (blood-stage) vaccine, in addition to
safeguarding against that possibility, could prevent or diminish
symptoms in persons already infected. A gametocyte (sexual stage)
vaccine does not protect the person being vaccinated, but instead
interrupts the cycle of transmission by inhibiting the further
development of gametocytes once they-along with antibodies produced
in response to the vaccine-are ingested by the mosquito. Although a
sporozoite vaccine could be useful for protecting tourists or other
persons exposed only briefly, the vaccine best suited for malarious
parts of the world may well be a "cocktail" combining antigens from
several parasite forms, and perhaps also from two or more species.
A number of candidate vaccine antigens have been identified
from different developmental stages of the parasite, and some have
advanced to the point of preliminary clinical evaluation.
Researchers have largely focused on candidate vaccine antigens that
are expressed on the parasite surface and/or are involved in some
critical aspect of parasite development or disease. For example, the
circumsporozoite (CS) protein is the dominant surface antigen of the
sporozoite stage, and is believed to interact with receptors on the
hepatocyte (human liver cell) surface during the initial infection.
Several antigens have been identified that are involved in
binding merozoites to the human red blood cell or in the
cell-invasion process. One, a merozoite surface protein (MSP-1),
repeatedly has been found to elicit protective immunity in rodent
and monkey models of malaria. Inhibition of such crucial steps in
parasite growth would form a good strategy for a vaccine.
Other studies have identified a parasite-derived molecule
(PfEMP1) on the surface of infected red blood cells that mediates
their binding to endothelial cells and other red cells. The
parasite, however, has developed ways to prevent the immune system
from attacking the infected red cell by regularly changing the
structure of such surface proteins-a process known as antigenic
variation. Recent studies of the P. falciparum genome have
revealed two major families of variant genes, known as "var"
(including PfEMP1) and "rif," in P. falciparum expressed at
different times during the course of an infection. Better
understanding of antigenic variation may help scientists identify
new strategies to interfere with parasite development.
Researchers are also investigating the immune mechanisms
involved in severe malaria disease. For example, recent studies
indicate that binding of plasmodium-infected red cells to a molecule
found on the surface of cells within the placenta contributes to the
adverse outcomes associated with malaria during a woman's first
pregnancy, and may provide the basis for developing a vaccine to
prevent this aspect of pathology. A few vaccine candidates, mostly
based on sporozoite antigens, have undergone clinical trials. A
vaccine made up of a combination of CS antigen and hepatitis B
surface antigen showed sufficient protective efficacy in a small
clinical trial to justify further testing in an endemic area. Only
one candidate vaccine, Spf66, based on antigens from both merozoite
and sporozoite stages, has undergone extensive field trials. It
showed efficacy in early clinical trials in South America, but
results from subsequent trials in Africa and Southeast Asia were not
as promising. Other vaccine candidates derived from multiple
parasite life cycle stages are currently being prepared for Phase I
human safety trials. NIAID is working with African scientists to
expand the capability to conduct clinical trials of new malaria
vaccines. (Source: excerpt from Malaria Research, NIAID Fact Sheet: NIAID)
NIAID investigators are planning the first human trial of a vaccine designed specifically to block the transmission of malaria parasites from infected people. The trial will take place at the NIH Clinical Center in Bethesda, Md. (Source: excerpt from Malaria, NIAID Fact Sheet: NIAID)
Designer drugs based on a successful herbal treatment for malaria used in traditional Chinese medicine have cured the disease, even drug-resistant forms, in NIAID-supported studies. In the absence of effective vaccines, drugs are the best way to prevent disease and treat patients with malaria. New drugs are urgently needed because of the emergence and spread of drug-resistant malaria parasites, especially among P. falciparum.
The investigators developed a synthetic, simpler version of artemisinin, derived from the Artemisia annua herb (qinghaosu) used in traditional Chinese medicine to cure people with malaria. Having a synthetic version would allow for easier, cheaper production of drugs than either relying on natural supplies or chemically creating complete artemisinin or its derivatives. (Source: excerpt from Malaria, NIAID Fact Sheet: NIAID)
The following medical news items are relevant to medical research for Malaria:
Some of the clinical trials for Malaria include:
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