Plasmodium falciparum Archives

October 10, 2013October 10, 2013

Hope for Malaria Vaccine by 2015

British drug maker GlaxoSmithKline is seeking regulatory approval for the world’s first malaria vaccine after trial data showed that it had cut the number of cases in African children.

Experts say that they are optimistic about the possibility of the world’s first vaccine after the trial results.

Malaria, a mosquito-borne parasitic disease, kills hundreds of thousands of people worldwide every year.

Scientists say an effective vaccine is key to attempts to eradicate it.

The vaccine known as RTS,S was found to have almost halved the number of malaria cases in young children in the trial and to have reduced by about 25% the number of malaria cases in infants.

GlaxoSmithKline (GSK) is developing RTS,S with the non-profit Path Malaria Vaccine Initiative (MVI), supported by funding from the Bill & Melinda Gates Foundation.

“Many millions of malaria cases fill the wards of our hospitals,” said Halidou Tinto, a lead investigator on the RTS,S trial from Burkina Faso.

“Progress is being made with bed nets and other measures, but we need more tools to battle this terrible disease.”

The malaria trial was Africa’s largest-ever clinical trial involving almost 15,500 children in seven countries.

The findings were presented at a medical meeting in Durban, South Africa.

“Based on these data, GSK now intends to submit, in 2014, a regulatory application to the European Medicines Agency (EMA),” GSK said in a statement.

The company has been developing the vaccine for three decades.

The statement said that the hope now is that the Geneva-based World Health Organization (WHO) may recommend the use of the RTS,S vaccine from as early as 2015 if EMA drugs regulators back its licence application.

Testing showed that 18 months after vaccination, children aged five to 17 months had a 46% reduction in the risk of clinical malaria compared to unvaccinated contemporaries.

But in infants aged six to 12 weeks at the time of vaccination, there was only a 27% reduction in risk.

A spokeswoman for GSK told the AFP news agency that the company would file its application to the EMA under a process aimed at facilitating new drugs for poorer countries.

UK politician Lynne Featherstone, International Development Minister, said: “Malaria is not just one of the world’s biggest killers of children, it also burdens health systems, hinders children’s development and puts a brake on economic growth. An effective malaria vaccine would have an enormous impact on the developing world.

“We welcome the scientific progress made by this research and look forward to seeing the full results in due course.”

August 12, 2013

Malaria Vaccine Shows Early Promise in Clinical Trials

By Rebecca Morelle, BBC Science

A malaria vaccine has shown promising results in early stage clinical trials, according to researchers.

Researchers found the vaccine, which is being developed in the US, protected 12 out of 15 patients from the disease, when given in high doses.

The method is unusual because it involves injecting live but weakened malaria-causing parasites directly into patients to trigger immunity.

The research is published in the journal Science.

Lead author Dr Robert Seder, from the Vaccine Research Center at the National Institutes of Health, in Maryland, said: “We were excited and thrilled by the result, but it is important that we repeat it, extend it and do it in larger numbers.” Continue reading “Malaria Vaccine Shows Early Promise in Clinical Trials”

April 7, 2012

Fight Against Malaria Compromised by Resistance Spread

Scientists have found new evidence that resistance to the front-line treatments for malaria is increasing.

They have confirmed that resistant strains of the malaria parasite on the border between Thailand and Burma, 500 miles (800km) away from previous sites.

Researchers say that the rise of resistance means the effort to eliminate malaria is “seriously compromised”.

The details have been published in The Lancet medical journal.

For many years now the most effective drugs against malaria have been derived from the Chinese plant, Artemisia annua. It is also known as sweet wormwood.

In 2009 researchers found that the most deadly species of malaria parasites, spread by mosquitoes, were becoming more resistant to these drugs in parts of western Cambodia.

This new data confirms that these Plasmodium falciparum parasites that are infecting patients more than 500 miles away on the border between Thailand and Burma are growing steadily more resistant.

The researchers from the Shoklo Malaria Research Unit measured the time it took the artemisinin drugs to clear parasites from the bloodstreams of more than 3,000 patients. Over the nine years between 2001 and 2010, they found that drugs became less effective and the number of patients showing resistance rose to 20%.

Prof Francois Nosten, who is part of the research team that has carried out the latest work, says the development is very serious.

“It would certainly compromise the idea of eliminating malaria that’s for sure and will probably translate into a resurgence of malaria in many places,” he said.

‘Untreatable malaria’

Another scientist involved with the study is Dr Standwell Nkhoma from the Texas Biomedical Research Institute.

“Spread of drug-resistant malaria parasites within South East Asia and overspill into sub-Saharan Africa, where most malaria deaths occur, would be a public health disaster resulting in millions of deaths.”

The scientists cannot tell if the resistance has moved because mosquitoes carrying the resistant parasites have moved to the Burmese border or if it has arisen spontaneously among the population there. Either way the researchers involved say it raises the spectre of untreatable malaria.

“Either the resistance has moved and it will continue to move and will eventually reach Africa. Or if it has emerged, now that artemisinin is the standard therapy worldwide then it means it could emerge anywhere,” Prof Nosten told the BBC.

“If we were to lose artemisinin then we don’t have any new drugs in the pipeline to replace them. We could be going back 15 years to where cases were very difficult to treat because of the lack of an efficacious drug.”

Artemisinin is rarely used on its own, usually being combined with older drugs to help fight the rise of resistance. These artemisinin based combination therapies are now recommended by the World Health Organization as the first-line treatment and have contributed substantially to the recent decline in malaria cases in many regions.

Prof Nosten says the current spread of resistance could be similar to what happened in the 1970s with chloroquine, a drug that was once a front-line treatment against the disease.

“When chloroquine resistance reached Africa in the middle of the 1970s it translated into a large increase in the number of cases and the number of children who died increased dramatically.”

In a separate paper published in the journal Science researchers have identified a region of the malaria parasite genome that is linked to resistance to artemisinin.

Dr Tim Anderson, from Texas Biomed who led this study, says that while mapping the geographical spread of resistance can be challenging it may be hugely beneficial.

“If we can identify the genetic determinants of artemisinin resistance we should be able to confirm potential cases of resistance more rapidly. This could be critically important for limiting the further spread of resistance.”

According to the World Malaria Report 2011 malaria was responsible for killing an estimated 655,000 people in 2010 – more than one every minute. A majority of these were young children and pregnant women.

The BBC Science Reporter

February 10, 2011January 3, 2013

Malaria: What is it and Why I Believe Our Generation Can Defeat it

By Kwabena Amponsah-Manager

What is Malaria?

Malaria is a tropical disease that is caused by the bite from the female Anopheles mosquito. The parasite is known as Plasmodium. Globally about 22 countries are plagued by malaria, most of them in the tropical regions and a few sub-tropical countries.

Symptoms of Malaria:

The symptoms of malaria include fever, anemia, chills, lost of appetite, general body weakness, nausea, convulsions and headache. The most characteristic symptom of malaria is the cycle of sudden chills followed by fever and sweating.

Occurrence:

There are more than 400 million cases of malaria annually. If not treated, the infection can be fatal, especially in infants, pregnant mothers and seniors. Malaria kills between one and three million people, the majority of whom are young children in sub-Saharan Africa, where 90% of malaria-related deaths occur.

The most serious form of the disease is caused by Plasmodium falciparum which is one of several species of the parasite that cause the disease. A milder form of the disease results from the species Plasmodium vivax, Plasmodium ovale and Plasmodium malariae.

Prevention and Treatment of Malaria:

The most effective means of preventing the disease is to prevent the bite from the mosquito. Insecticide treated mosquito nets and insect repellents are first line preventive measures. Mass preventive measures such as spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs are also employed by governments and institutions.

Currently there is no effective vaccine against malaria though a few are in development (GSK is a leader in this aspect). A variety of antimalarial medications are available. In the last 5 years, treatment of P. falciparum infections in endemic countries has been altered by the use of combinations of drugs containing an artemisinin derivative. Severe malaria is treated with intravenous or intramuscular quinine or, increasingly, the artemisinin derivative artesunate. Several drugs are also available to prevent malaria in travelers to malaria-endemic countries (prophylaxis). An example of prophylactic malaria drug is Malarone. Chloroquine used to be most commonly prescribed medicine against malaria but the parasite developed resistance to the drug. It is still being used to treat and prevent malaria though not as effective as it used to be. In places where drug resistance parasites have not yet been confirmed, such as Central America and parts of the Middle East, Chloroquine is still the drug of choice prevent and treat P. falciparum and P. vivax infections.

For reasons not fully understood, a number of diseases appear to provide some resistance to malaria. Notable ones include sickle cell disease, thalassaemias, glucose-6-phosphate dehydrogenase, Duffy antigens. Some people have red blood cells that lack proteins called Duffy antigens on their surface. Duffy antigens act as receptors for Plasmodium vivax merozoites, so people without Duffy antigens are resistant to infection from this parasite. Again, individuals who live in malaria-endemic regions acquire immunity to malaria through natural exposure to malaria parasites. In fact, naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from the disease.

Even though malaria has not received the global attention required for a killer of such profile, wealthy foundations, some private companies, and smart governments across the world are beginning to wake and make malaria a priority. However, there are still skeptics who doubt humans’ ability to eradicate malaria. Early November of 2010 a series of papers published in a respected scientific journal, the Lancet cast a gloomy cloud over any hope of dealing with malaria, at least in our lifetime. The papers concluded by urging governments, donor agencies and foundations to focus more on minimizing the prevalence of malaria and not on eradicating the killer.

Generally speaking, and not necessarily referring to the Lancet papers, considering mankind’s quest to conquer the universe, occupy Space, and pursue every kind of technology to make life easier and better, it would be intellectuality dishonest and morally criminal for humans to accept the theory that malaria is ineradicable.

A few decades ago, significant portion of North America was plagued with malaria in the same fashion as African countries are going through. In fact, it was not until the late 1890′s that scientists even learnt that the disease is caused by a parasite and that it is a mosquito that transmits the parasite from person to person. The assumption in those days was that malaria was caused by some environmental factors. The word malaria actually comes from the Italian “mala aria”, meaning “bad air” because it was generally believed that malaria was caused by breathing in bad or foul air and vapors emanating from swamps, marshy lands and latrines.

It is important to remember that 70 to 80 years ago, Americans traveling to the Eastern Tennessee Valleys had the same fear they now have when traveling to Togo or Ivory Coast because of malaria. With the creation of the U.S. Tennessee Valley Authority (TVA) in 1933 which established an organized malaria control program, the doubts began to fade. At the time, malaria affected 30 percent of the population in the region where the TVA was incorporated. After implementing aggressive research and control operations, the disease was essentially eradicated in the TVA region by 1947.

The US did not win the battle over malaria overnight. Efforts to control malaria became national focus as far back as the early 20th century during the occupation of American military in Cuba and the construction of the Panama Canal. It is recorded that malaria (and yellow fever) caused significant number of deaths among the workers of the canal. This triggered an aggressive program of malaria control which in 10 years had already made remarkable progress.

Malaria can be defeated, albeit, not overnight. The funding available for anti-malaria campaigns, and research and development is tiny compared to the challenges.

In the long run, I believe that prevention of malaria is the cost-effective route to take rather than treatment of the disease. However, for preventive measures to make the required impact, funding would have to be ramped up.

Current statistics show that in many of the malaria endemic countries, funding is less than US$1 per capita, and in fact it is less than US$0.5 in 16 malaria endemic countries, making up about 710 million people.

Much as I wanted this to be educational rather than political, I cannot help but state that malaria could be eradicated from the earth at negligible percentage of the cost of the Iraq war. It has been estimated by Economist Jeffrey Sachs that malaria can be controlled for US$3 billion in aid per year. (The cost of the Iraq war stands at $774 billion at the time of writing this article)

Our generation must stand trial for genocide for inaction on a problem that kills a child every 30-40 seconds. It is every 30-40 seconds!

Caught in The Act: Imaging Microscopy Catches Malaria Parasite Invading Blood Cells

Australian scientists using new image and cell technologies have for the first time caught malaria parasites in the act of invading red blood cells. The researchers, from the Walter and Eliza Hall Institute in Melbourne, Australia, and the University of Technology, Sydney (UTS), achieved this long-held aim using a combination of electron, light and super resolution microscopy, a technology platform new to Australia.

The detailed look at what occurs as the parasite burrows through the walls of red blood cells provides new insights into the molecular and cellular events that drive cell invasion and may pave the way for developing new treatments for malaria. Institute researchers Dr Jake Baum, Mr David Riglar, Dr Dave Richard and colleagues from the institute’s Infection and Immunity division led the research with colleagues from the i3 institute at UTS.

Dr Baum said the real breakthrough for the research team had been the ability to capture high-resolution images of the parasite at each and every stage of invasion, and to do so reliably and repeatedly. Their findings are published in today’s issue of the journal Cell Host & Microbe.

“It is the first time we’ve been able to actually visualise this process in all its molecular glory, combining new advances developed at the institute for isolating viable parasites with innovative imaging technologies,” Dr Baum said.

“Super resolution microscopy has opened up a new realm of understanding into how malaria parasites actually invade the human red blood cell. Whilst we have observed this miniature parasite drive its way into the cell before, the beauty of the new imaging technology is that it provides a quantum leap in the amount of detail we can see, revealing key molecular and cellular events required for each stage of the invasion process.”

The imaging technology, called OMX 3D SIM super resolution microscopy, is a powerful new 3D tool that captures cellular processes unfolding at nanometer scales. The team worked closely with Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull from the i3 institute at UTS to capture these images.

“This is just the beginning of an exciting new era of discoveries enabled by this technology that will lead to a better understanding of how microbes such as malaria, bacteria and viruses cause infectious disease,” Associate Professor Whitchurch said.

Dr Baum said the methodology would be integral to the development of new malaria drugs and vaccines. “If, for example, you wanted to test a particular drug or vaccine, or investigate how a particular human antibody works to protect you from malaria, this imaging approach now gives us a window to see the actual effects that each reagent or antibody has on the precise steps of invasion,” he said.

Malaria is caused by the Plasmodium parasite, which is transmitted by the bite of infected mosquitoes. Each year more than 400 million people contract malaria, and as many as a million, mostly children, die.

“Historically it has been very difficult to both isolate live and viable parasites for infection of red blood cells and to employ imaging technologies sensitive enough to capture snapshots of the invasion process with these parasites, which are only one micron (one millionth of a metre) in diameter,” Dr Baum said.

He said one of the most interesting discoveries the imaging approach revealed was that once the parasite has attached to the red blood cell and formed a tight bond with the cell, a master switch for invasion is initiated and invasion will continue unabated without any further checkpoints.

“The parasite actually inserts its own window into the cell, which it then opens and uses to walk into the cell, which is quite extraordinary,” Dr Baum said. “Visually tracking the invasion of Plasmodium falciparum into a red blood cell is something I’ve been aiming at ever since I began at the Walter and Eliza Hall Institute in 2003; it’s really thrilling to have reached that goal. This technology enables us to look at individual proteins that we always knew were involved in invasion, but we never knew what they did or where they were, and that, we believe, is a real leap for malaria researchers worldwide

This work was supported by the National Health and Medical Research Council, The University of Melbourne, Canadian Institutes of Health, the University of Technology, Sydney, and the Australian Research Council.

This image is a composite showing the behavior of different parts of the malaria parasite as it invades a red blood cell, at nanometer scales. The three components of the malaria parasite are labeled with fluorescent proteins (blue = parasite nucleus, red = secretory organelle, green = tight junction). The red blood cell is superimposed on the image for context. Image 1 (Attachment): The parasite is about to invade the red blood cell (unseen to the right of the picture). The tight junction (green) is like a window that the parasite brings with it and inserts into the red blood cell to gain entry. Image 2 (Invasion): This image is mid-invasion, the first time this step has even been visualized. The parasite "opens" the window it has inserted into the cell, and walks through. The secretory organelle (red) secretes its contents through the tight junction (green) and creates a vacuole which the parasite lives within in the red blood cell. In this image we see the parasite nucleus (blue) moving through the ‘window’ into the cell. Image 3 (Sealing): The parasite has completed invasion and is within a vacuole inside the host red blood cell. The window has been closed again, and will break down at a later stage. The parasite is now enclosed within its vacuole (red), the nucleus (blue) showing the parasite safely inside.

Penny Fannin

fannin@wehi.edu.au

January 17, 2011January 17, 2011

Global Action on Malaria Resistance Urgent, WHO

The WHO has launched a worldwide ‘call to action’ to governments, agencies, researchers and non-governmental organisations over the malaria parasite’s growing resistance to the most potent weapon against it — the drug, artemisinin.

If recently discovered resistance spreads, said the WHO, the formidable successes of anti-malaria campaigns in recent years will be threatened. Artemisinin lies at the heart of malaria treatment worldwide and has no obvious successor.

“The consequences of widespread resistance to artemisinins would be catastrophic,” WHO director-general Margaret Chan told a press conference held after the launch of the ‘Global plan for artemisinin resistance containment’ yesterday (12 January).

“We need to maintain this medicine. What is at stake it is not just the goals on malaria but, frankly, the whole related Millennium Development Goals”, said Robert Newman, director of the WHO Global Malaria Programme.

Resistance to artemisinin was identified in the Plasmodium falciparum parasite on the Cambodia–Thailand border in studies conducted between 2001 and 2009. It is now reported in other areas of the Greater Mekong Subregion and some fear that the resistance will spread to Africa, where most malaria deaths occur.

GPARC calls for increased surveillance of resistance and improved access to diagnostics and treatment with artemisinin combination therapies (ACTs), and for more research on topics ranging from new methods for containing resistance to mathematical modelling of its spread.

“We don’t have all the knowledge and tools we need,” said Newman, adding that finding a quick way of testing for resistance should be a priority.

“We need a molecular marker for drug resistance that will allow us to know much earlier where this problem may be emerging.”

“The research community must be engaged in the development of new classes of antimalarial medicines that would not fall into the same trap of resistance that we have with ACTs,” he added.

But it will not be easy to pin down the parasite’s genes responsible for resistance, according to Pascal Ringwald, coordinator of the drug resistance and containment unit of the WHO Global Malaria Programme.

“It took 30 years to find the gene related to chloroquine resistance,” he told SciDev.Net. “There are thousands of mutant genes in the parasite and the problem is to find which mutation could be related to artemisinin resistance.”

“Now we have better molecular tools,” he said. “I don’t think it’s going to take another 30 years, but it is very difficult and also very expensive.”

Call for action also aims to bring in new funds to bridge the estimated US$175 million funding gap for the project. So far, the UK’s Department for International Development (DFID) has agreed to fund a project to improve surveillance and map the extent of resistance.