How can malaria be controlled?

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QUESTION:

What is malaria? How can it be controlled?

ANSWER:

Malaria is a disease caused by a single-celled parasite called Plasmodium. There are four species that regularly infect humans: P. falciparum (which causes the most severe form of the disease, and is responsible for 90% of the annual 700,000 fatalities caused by malaria, mainly in Africa), P. vivax, P. ovale and P. malariae. A fifth species, P. knowlesi, has recently also been reported in a small number of cases in south-east Asia, where prevalence appears to be increasing.

Despite it’s wide geographic range and potentially severe consequences, there are actually several effective strategies for controlling malaria, many of which have been successful of reducing the burden of the disease, and especially the number of deaths, in various regions. The first step towards control is prevention. This has largely been achieved through the distribution of long-lasting insecticide treated bednets, which prevent people from being bitten by infected mosquitoes as they sleep at night. While this has drastically reduced the number of cases of malaria in some settings, and particularly in certain high risk groups such as children under five and pregnant women, some worrying new data just was published which suggested that in high transmission zones, bednets may actually exacernate re-infection rates for older children and adults, and lead to insecticide resistance in mosquitoes. As such, while bednets clearly are still a key prevention strategy, their effect should be closely monitored.

Secondly, there is diagnosis and treatment. These go hand in hand, as they usually require the availability of health services or health professionals. If malaria infections are rapidly and accurately diagnosed, appropriate treatment can be swiftly given, preventing the progression of the disease and allowing the patient to recover. Appropriate administration of medication, as well as adherence to the full course of the drugs, can also help to prevent drug-resistance from emerging.

Finally, there are on-going research initiatives looking to find new ways to tackle malaria. For example, many scientists are involved in the search for a malaria vaccine, which, if safe, effective, and sufficiently cheap, could transform the way we think about fighting malaria. Similarly, due to the unfortunate circumstance of ever-increasing drug-resistance, particularly in Plasmodium falciparum, new types of medication are constantly being tested and trialled. The combination of all these efforts has managed to reduce the mortality of malaria greatly over the past few years; the aim now, espoused by organisations such as Malaria No More, is to get to a point where deaths from malaria are eliminated by the year 2015.

New Malaria Vaccine Passes Safety Test

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Most malaria vaccines under development work by including genetically engineered versions of just a handful of the thousands of proteins of the Plasmodium parasite. Those modified proteins are designed to trigger an immune response to Plasmodium, after it’s passed into the host’s bloodstream by the bite of an infected mosquito.

In contrast, says researcher Robert A. Seder of the U.S. National Institute of Allergy and Infectious Diseases, this new vaccine includes a deactivated version of the entire parasite. [Read more…]

Malaria Vaccine from Mosquito Saliva

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One of the more promising avenues of creating a vaccine for malaria involves going inside mosquitoes’ bodies — typically the source of the disease’s spread — to develop the key component of the vaccine.

Research published online in the journal Science today shows the barriers and future direction for that vaccine. A clinical trial of such a vaccine showed that it was safe, but that it didn’t confer immunity to enough of the study participants.

Read more, via My Health News Daily.

IDRI, USAID to Collaborate on Malaria Vaccine Development

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The Infectious Disease Research Institute (IDRI) today announced a new Memorandum of Understanding with the United States Agency for International Development (USAID), focused on support of a collaboration with the Walter Reed Army Institute of Research (WRAIR) for the development of a new vaccine against malaria. The collaboration is for the development of a novel malaria vaccine, which combines WRAIR’s malaria antigen CelTOS with IDRI’s potent GLA-SE adjuvant.

Preclinical studies to date have shown that the combination of CelTOS and GLA-SE in a vaccine candidate produces potent immune responses in small animals, resulting in a protective immune response during the infectious mosquito-stage of malaria parasites.

Because of the conserved nature of the CelTOS antigen, immunized mice are protected against other distantly related malaria strains as well. USAID provided funds for WRAIR’s preclinical studies of this antigen, and the Bill & Melinda Gates Foundation funded IDRI’s CelTOS-specific adjuvant development activities. A phase I clinical trial with human malaria challenge is being funded by USAID, the WRAIR, and the Gates Foundation grant awarded to IDRI.

Malaria is a devastating parasitic disease transmitted through the bite of infected Anopheles mosquitoes. The WHO estimates that more than two billion people live in malarious areas of the world in Africa, Asia, Oceania, and Latin America. The emergence and spread of drug resistance, production and availability of counterfeit medications, and mosquito resistance to insecticides make the development of a safe, effective, and affordable malaria vaccine critical as an adjunct to other preventive measures. Because CelTOS is essential for establishing parasite infections in both the human and mosquito hosts, IDRI, USAID, and WRAIR are hopeful that the development of the CelTOS – GLA-SE malaria vaccine will provide a significant new approach to a human malaria vaccine, targeting prevention of both human disease and transmission of the parasite back to the mosquito.

“The collaboration with WRAIR illustrates again the broad utility of GLA-SE as a vaccine adjuvant,” Dr. Steven G. Reed, IDRI’s Founder, President and Chief Scientific Officer, stated. “We are very excited to be moving this important project ahead and particularly pleased with the validating interest from USAID.”

“The Walter Reed Army Institute of Research is pleased that both IDRI and USAID have partnered with us in helping support the development of malaria vaccines to prevent infection in children worldwide and to protect our men and women serving in uniform in areas of the world where malaria is still a major infectious disease,” said COL Christian Ockenhouse, Director of WRAIRs’ Malaria Vaccine Development Program.

Dr. Carter Diggs, Senior Technical Advisor for the USAID Malaria Vaccine Development Program added that, “In spite of dramatic progress in malaria control, the disease is still a major killer of children in the developing world. USAID is very pleased with this collaboration, which combines exploration of the vaccine potential of an untested, but promising malaria antigen with this leading edge adjuvant system.”

Source: PRNewswire

Scientists Offer 2020 Vision of Vaccines for Malaria, TB & HIV/AIDS

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Collectively, malaria, TB & HIV/AIDS cause more than five million deaths per year – nearly the entire population of the state of Washington – and represent one of the world’s major public health challenges as we move into the second decade of the 21st century. In the May 26, 2011, edition of the premier scientific journal Nature, Seattle BioMed Director Alan Aderem, Ph.D., along with Rino Rappuoli, Ph.D., Global Head of Vaccines Research for Novartis Vaccines & Diagnostics, discuss recent advances in vaccine development, along with new tools including systems biology and structure-based antigen design that could lead to a deeper understanding of mechanisms of protection. This, in turn, will illuminate the path to rational vaccine development to lift the burden of the world’s most devastating infectious diseases.

According to Aderem, a systems biology pioneer who recently joined Seattle BioMed to incorporate that approach with the Institute’s infectious disease research, new conceptional and technological advances indicate that it will be possible to develop vaccines for the “big three” infectious diseases within the next 10 years. “Success will be largely dependent on our ability to use novel approaches such as systems biology to analyze data sets generated during proof-of-concept trials,” he explained. “This will lead to new insights such as the identification of correlates of protection or signatures of immunogenicity and the acceleration of large-scale clinical trials.” Aderem added that innovative, new clinical and regulatory approaches will also accelerate the pathway to much-needed vaccines.

The article discusses the strengths and criticisms of the systems biology approach, with the key strength of the approach lying in its ability to capture and integrate massive amounts of biological data to visualize emergent properties that are not demonstrated by their individual parts and cannot be predicted from the parts alone. “The power of systems biology comes from its capacity to predict the behavior of an entire biological system,” Aderem said. “From there, we can optimize vaccine candidates and predict whether a drug or vaccine candidate can work before it moves into large scale, very expensive clinical trials.”

Systems biology can also be used to speed the often lengthy clinical trial experience. Aderem and Rappuoli estimate that in trials of new vaccines for malaria, TB and HIV/AIDS, only one hypothesis has been tested every eight years in the past three decades. “We cannot afford this approach if we want to have an impact on disease in a reasonable timeframe,” Aderem said. “We can accelerate clinical development by performing more efficacy trials and by improving their design using systems biology approaches to test several hypotheses in parallel and having an adaptive design to expand the outcomes that prove most promising.”

Aderem and Rappuoli also debunk one of the key criticisms of systems biology – that it is overly reliant on computation. “Much of this comes from a misunderstanding on the role of computers in systems biology,” Aderem explained. “Computers are not expected to come up with biological insights from the outset, but are meant to facilitate an integration of discovery science with hypothesis-driven science to yield a holistic description of a biological system.”

While progress has been made over the past few years in the development of novel vaccines against the three most challenging infectious diseases in the world, Aderem and Rappuoli conclude that innovative design of clinical trials, testing several vaccines in parallel and getting early information using systems biology approaches will accelerate vaccine development and increase understanding of the human immune system.

Source: Seattle Biomedical Research Institute (Seattle BioMed)

New Biomarkers Study Could Lead to Improved Malaria Vaccines

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In the first study of its type in the malaria field, Seattle BioMed has been awarded an $8.9 million grant from the Bill & Melinda Gates Foundation to identify biomarkers that will allow malaria vaccine design based on robust predictors of protective immunity.

According to Ruobing Wang, M.D., Ph.D., the goal of the study is to identify and validate biomarkers that correlate with vaccine-induced protective immunity against malaria infection.

“In order to bring the burden of malaria under control – with the ultimate goal of eradicating the pathogens that cause disease – we know we need a highly efficacious anti-infection vaccine,” she explained. “But, without reliable biomarkers of anti-infection immunity, the development and testing of malaria vaccines is a slow and expensive process.” Biomarkers will be used for prediction and monitoring the vaccine efficacy in clinical trials and to select optimal vaccine candidates for development.

To conduct this research, the company will call upon its areas of expertise and knowledge – vaccine and immunology studies in animal models of malaria, the ability to grow human malaria parasites in mosquitoes for research and clinical studies, and its ability to develop genetically attenuated parasite strains for human trials. It will also begin full-scale trials in its Malaria Clinical Trials Center, and employ its newfound expertise in the area of systems biology.

Seattle BioMed scientists have developed genetically attenuated whole parasite vaccine strains that have proven successful in rodent malaria models and have moved into human studies. “In this new study, we will use genetically attenuated parasite strains as probes to determine whether host correlates of immunity can be identified during vaccination in mice,” explained Seattle BioMed’s Stefan Kappe, Ph.D. “These model vaccines provide an opportunity to discriminate biomarkers associated with complete, long-lasting protection from those associated with partial, short-lived or lack of protection.”

Researchers at Seattle BioMed will then apply the knowledge gained in mouse models to human studies. “Through studies conducted at Seattle BioMed’s Malaria Clinical Trials Center, we’ll evaluate whether biomarkers of protection identified in the rodent models will predict protective immunity in humans,” explained Wang.

Seattle BioMed researchers will employ network analysis of transcriptional responses to predict protection in both mice and humans to determine if they can find universal markers that will allow them to optimize vaccine candidates. According to Alan Aderem, Ph.D., the power of systems biology lies in its capacity to predict the behavior of a biological system.  “If we have the ability to predict whether a vaccine candidate for malaria will work before it goes into large scale clinical trials, we could move away from today’s typical ‘trial and error’ method toward a more powerful predictive approach to vaccine discovery and development,” he said.

Through these integrated studies, Seattle BioMed researchers will deliver a set of candidate immune biomarkers associated with protection against malaria infection that can be used for monitoring vaccine efficacy. “This will facilitate future malaria vaccine trials with the ultimate goal of accelerating the development of a highly effective malaria vaccine that has the potential to save millions of lives,” said Wang.

Wang is leading the study – Seattle BioMed’s first to include the integration of its recently announced systems biology approach to infectious disease research – with a team that includes Seattle BioMed’s Stefan Kappe, Ph.D., and Alan Aderem, Ph.D., along with Patrick Duffy, M.D., of the National Institutes of Health, Jonathan Derry, Ph.D., of Sage Bionetworks, and Xiaowu Liang, Ph.D., of Antigen Discovery Inc. (ADi).

Source: PR Newswire

Liquidia Technologies Gets $10M from Gates Foundation for Malaria Vaccine

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The Bill & Melinda Gates Foundation invested $10 million in Liquidia Technologies, a closely held biotechnology company developing vaccines, as part of a $400 million initiative to fund activities to help poorer countries.

Liquidia is developing a seasonal flu vaccine and has an agreement with the PATH Malaria Vaccine Initiative to use its technology to work on new malaria vaccines, the Research Triangle Park, North Carolina-based company said today in an e- mailed statement. [Read more…]

Sanaria Wins $3M Grant for Development of Malaria Vaccine

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Sanaria has won a three-year, $3 million phase 2 Small Business Research Innovation grant from the National Institutes of Health to further develop its malaria vaccine.

The money will support research by scientists at the Rockville company and its partner, Columbia University, according to Sanaria information. The new grant continues earlier NIH-supported efforts at Sanaria and Columbia to develop genetically modified strains of the human malaria parasite Plasmodium falciparum that do not cause disease, but stimulate protective immunity when administered as a live, whole parasite malaria vaccine.

“There is considerable excitement about whole parasite malaria vaccines, and research towards developing genetically modified strains for such vaccines is at the cutting edge of this field,” said Christian Loucq, director of the Malaria Vaccine Initiative with PATH-Program for Appropriate Technology in Health, in a statement.

The parasites have been weakened by exposure to radiation and confer high-level protection against malaria when introduced by the bite of infected mosquitoes, according to Sanaria. These parasites invade host tissues, but cannot complete differentiation and do not replicate or cause disease.

“Sanaria is uniquely positioned at this time to expand the pipeline of candidate sporozoite vaccines to include vaccines based on precisely gene-altered parasites that are highly potent in inducing protective immunity against malaria and are unable to cause disease,” said Stephen L. Hoffman, Sanaria’s founder and chief scientist, in the statement.

Professor Working on Malaria Vaccine that Will Inoculate Mosquitos When They Bite People

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The same menace that spreads malaria – the mosquito bite – could help wipe out the deadly disease, according to researchers working on a new vaccine at Tulane University.

The PATH Malaria Vaccine Initiative(MVI), established in 1999 through a grant from the Bill & Melinda Gates Foundation, announced today a collaboration with Tulane University School of Public Health and Tropical Medicine and India’s Gennova Biopharmaceuticals Ltd. to produce and test a novel vaccine that aims to inoculate mosquitoes when they bite people. [Read more…]