RTS,S Malaria Vaccine Results Promising

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Results from a large-scale Phase III trial, presented today in Durban, show that the most clinically advanced malaria vaccine candidate, RTS,S, continued to protect young children and infants from clinical malaria up to 18 months after vaccination. Over 18 months of follow-up, RTS,S was shown to reduce cases of clinical malaria by 46% in young children (aged 5-17 months at first vaccination) and to reduce by 27%  the malaria cases in infants (aged 6-12 weeks at first vaccination).

Based on these data, GlaxoSmithKline (GSK) now intends to submit, in 2014, a regulatory application to the European Medicines Agency (EMA). The World Health Organization (WHO) has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015 if it is granted a positive scientific opinion by EMA.

Vaccine efficacy was also assessed separately at each of the trial sites, which represent a wide range of malaria transmission settings; efficacy was found to be statistically significant at all sites in young children and at four sites in infants.

Eleven African research centres in seven African countries1 are conducting this trial, together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI.

“In Africa we experience nearly 600,000 deaths annually from malaria, mainly children under five years of age,” says Halidou Tinto, Principal Investigator from the Nanoro, Burkina Faso trial site and chair of the Clinical Trials Partnership Committee (CTPC), which oversees the RTS,S Phase III programme. “Many millions of malaria cases fill the wards of our hospitals. Progress is being made with bed nets and other measures, but we need more tools to battle this terrible disease.”

Efficacy and cases prevented

The efficacy and public health impact of RTS,S were evaluated in the context of existing malaria control measures, such as insecticide treated bed nets, which were used by 78% of children and 86% of infants in the trial. In these latest results over 18 months of follow-up, children aged 5-17 months at first vaccination with RTS,S experienced 46% fewer cases of clinical malaria, compared to children immunised with a control vaccine. An average of 941 cases of clinical malaria were prevented over 18 months of follow-up for every 1,000 children vaccinated in this age group, noting that a child can contract more than one case of malaria. Severe malaria cases were reduced by 36%; 21 cases of severe malaria were prevented over 18 months of follow-up for every 1,000 children vaccinated. Malaria hospitalisations were reduced by 42%.

Infants aged 6-12 weeks at first vaccination with RTS,S had 27% fewer cases of clinical malaria.
Over 18 months of follow-up,  444 cases of clinical malaria were prevented for every 1,000 infants vaccinated. The reduction of severe malaria cases and malaria hospitalisations by 15% and 17%, respectively, were not statistically significant.

“It appears that the RTS,S candidate vaccine has the potential to have a significant public health impact,” says Tinto. “Preventing substantial numbers of malaria cases in a community would mean fewer hospital beds filled with sick children. Families would lose less time and money caring for these children and have more time for work or other activities. And of course the children themselves would reap the benefits of better health.”

Overall, vaccine efficacy declined over time: Previous results from one year follow-up of the Phase 3 trial showed that efficacy of RTS,S was 56% against clinical malaria and 47% against severe malaria for the 5-17 month-old age group and 31% against clinical malaria and 37% against severe malaria in the 6-12 week-old age group.

Safety

RTS,S continued to display an acceptable safety and tolerability profile during the 18 month follow-up. Apart from the meningitis signal previously reported2, no other safety signal was identified. The occurrence of meningitis will be followed closely during the remainder of the trial.

Next year

Further data from 32 months follow-up and the impact of a fourth ‘booster’ dose given 18 months after the initial three doses are expected to become available in 2014.

Comments on results

Sir Andrew Witty, CEO of GSK, said: “We’re very encouraged by these latest results, which show that RTS,S continued to provide meaningful protection over 18 months to babies and young children across different regions of Africa. While we have seen some decline in vaccine efficacy over time, the sheer number of children affected by malaria means that the number of cases of the disease the vaccine can help prevent is impressive. These data support our decision to submit a regulatory application for the vaccine candidate which, if successful, would bring us a step closer to having an additional tool to fight this deadly disease. We are grateful to the scientists across Africa and GSK and to our partners who have worked tirelessly for almost 30 years to bring us to this point.”

Dr David C. Kaslow, vice president of product development at PATH, said: “Given the huge disease burden of malaria among African children, we cannot ignore what these latest results tell us about the potential for RTS,S to have a measurable and significant impact on the health of millions of young children in Africa. While we want to be careful about not getting ahead of the data, this trial continues to show that a malaria vaccine could potentially bring an important additional benefit beyond that provided by the tools already in use.”

 

About RTS,S

RTS,S is a scientific name given to this malaria vaccine candidate and represents the composition of this vaccine candidate that also contains the AS01 adjuvant system3. RTS,S aims to trigger the immune system to defend against the Plasmodium falciparum malaria parasite when it first enters the human host’s bloodstream and/or when the parasite infects liver cells. It is designed to prevent the parasite from infecting, maturing, and multiplying in the liver, after which time the parasite would re-enter the bloodstream and infect red blood cells, leading to disease symptoms. In the Phase III efficacy trial, RTS,S has been administered in three doses, one month apart. With more than US$200 million in grant monies from the Bill & Melinda Gates Foundation, MVI contributes financial, scientific, managerial, and field expertise to the development of RTS,S. GSK takes the lead in the overall development of RTS,S and has invested more than $350 million to date and expects to invest more than $260 million until development is completed.

Looking ahead

These new data support GSK’s plans to submit, in 2014, an application for a scientific opinion by the Committee for Medicinal Products for Human Use (CHMP) on RTS,S through the EMA Article 58 procedure. The EMA, in the context of cooperation with the WHO, will evaluate data on the quality, safety, and efficacy of the RTS,S vaccine candidate. A positive CHMP scientific opinion would facilitate the registration of RTS,S by national regulatory authorities in Africa. Furthermore, if the EMA gives a positive opinion, and the public health information is satisfactory, including safety and efficacy data from the Phase III programme, the WHO has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015, paving the way for decisions by African nations regarding large-scale implementation of the vaccine through their national immunisation programmes. An effective vaccine for use alongside other measures such as bed nets and anti-malarial medicines would represent a positive advance in malaria control.

The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH through an initial grant from the Bill & Melinda Gates Foundation. MVI’s mission is to accelerate the development of malaria vaccines and catalyse timely access in endemic countries. MVI’s vision is a world free from malaria. For more information, please visit www.malariavaccine.org.

PATH is an international nonprofit organization that transforms global health through innovation. PATH take an entrepreneurial approach to developing and delivering high-impact, low-cost solutions, from lifesaving vaccines, drugs, diagnostics, and devices to collaborative programs with communities. Through its work in more than 70 countries, PATH and its partners empower people to achieve their full potential. For more information, please visit www.path.org.

Source: GSK Press Rls Oct 8 2013

Malaria Threatens Penguins

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As carefree as penguins might look, torpedoing through the water or rocketing into the air like a Poseidon missile, zoo penguins are stalked by an unrelenting killer: malaria.

“It’s probably the top cause of mortality for penguins exposed outdoors,” said Dr. Allison N. Wack, a veterinarian at the Maryland Zoo in Baltimore. The avian version is not a threat to humans because mosquitoes carrying malaria and the parasites are species-specific; mosquitoes that bite birds or reptiles tend not to bite mammals, said Dr. Paul P. Calle, chief veterinarian for the Wildlife Conservation Society, which runs New York City’s zoos. And avian malaria is caused by strains of the Plasmodium parasite that do not infect humans.
[Read more…]

Malaria No More Debuts “Power of One” (Po1) Campaign to Fight Malaria

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Malaria No More announced today the debut of its most aggressive campaign to date: Power of One (Po1), where a one dollar donation provides a life-saving test and treatment for a child in Africa. The Power of One campaign uses the latest social, mobile, and e-commerce technologies to rally the global public to close malaria testing and treatment gaps in Africa, starting with Zambia. Malaria No More’s Power of One campaign is supported by some of the world’s most innovative companies, including Novartis, Alere Inc., 21st Century Fox, AHAlife.com, Causes.com, Time Warner, Twitter, Venmo and others.

A child dies every minute from malaria, making it one of the top killer diseases among children worldwide. Every dollar donated to the campaign – via the campaign’s new, mobile-friendly website Po1.org — funds a life-saving treatment for a child with malaria. The campaign aims to accelerate progress toward ending malaria deaths by closing critical treatment gaps in Africa. In 2014 and 2015, it’s estimated that over 300 million treatments are needed in Africa. Malaria No More has chosen Zambia as the first country for its Power of One campaign, as it has emerged as one of the best examples of innovation and progress in the malaria fight, and is working with the government and partners on the ground to provide 3 million treatments for children with malaria.

Power of One is using mobile phones in Africa and the U.S. in new ways to track impact and engage the public, and the campaign site, Po1.org, will leverage new tools from popular digital platforms, like Twitter and Venmo, in the coming weeks.

“It’s unacceptable that a child dies every minute for lack of malaria diagnosis and treatment, worth only a dollar,” said Martin Edlund, CEO, Malaria No More. “We’re challenging the world to help us fix that through the Power of One campaign where users can donate, track and share impact, and engage their friends using the latest mobile tools. One dollar really can save a life – and we’ll prove it.”

To debut the platform, Malaria No More will distribute 1 million “life-saving vouchers” over the next week through supporting online and physical retailers, such as AHAlife.com, as well as at high level events taking place in New York City, including Mashable’s Social Good Summit, the United Nation’s MDG Innovation Forum, and the Global Citizen Festival in Central Park. Audiences making everyday purchases will receive a ticket featuring a special code that, when redeemed on act.Po1.org, provides a test and treatment, without a donation, to save a child’s life in Zambia.

Top media partners, 21st Century Fox and Time Warner, are airing campaign PSAs and digital ads nationally this week, and ads will run across dozens of other national broadcast channels, cable networks, radio stations, popular websites, and on prominent billboards. Additionally, as a feature partner on the new platform release of Causes.com this week, the Power of One campaign is being highlighted and heavily promoted to users.

Novartis, the world’s leading provider of malaria treatments and exclusive treatment sponsor of the Power of One campaign, is donating up to three million full courses of its pediatric antimalarial drug and will support the campaign financially over the next three years. “I am proud of the significant and longstanding commitment Novartis has to the fight against malaria. For all our progress though, there’s still more work to do,” said Joseph Jimenez, CEO of Novartis. “We need more help to close the treatment gap and Power of One offers everyone a chance to engage and make a difference for children suffering from malaria.”

Alere, the world’s leading provider of rapid diagnostic tests for malaria and exclusive diagnostics partner to Malaria No More, will donate over the course of the campaign two million rapid diagnostic tests to aid point-of-care diagnosis of the disease in sub-Saharan Africa. “Accurate diagnosis of malaria significantly improves the odds in treating the disease and ending premature deaths of children,” said Ron Zwanziger, Chairman and CEO of Alere. “Alere is proud to partner with Malaria No More and to support the Power of One campaign in its goal of preventing deaths from this devastating disease.”

Every dollar donated to the Power of One campaign provides a life-saving test and treatment for a child in Africa. Thanks to our corporate partners, Power of One will be able to amplify public impact. For the first million dollars raised by the public every year, Novartis will match the global public’s contribution and donate up to an additional one million treatments and Alere will donate one million rapid diagnostic tests – this translates to two treatments and one test for every dollar donated.

For more information and to sign up to support the Power of One campaign, visit www.Po1.org.

Source: Malaria No More

Exchange Transfusion for Treatment of Severe Malaria No Longer Recommended

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The Centers for Disease Control (CDC) no longer recommends the use of exchange transfusion (ET) as an adjunct to antimalarial drugs for the treatment of severe malaria.

ET is a procedure in which a portion of blood from the infected patient is removed and replaced with uninfected blood. Previously, the rationale for the use of ET in severe malaria was that ET removed infected cells and toxic byproducts. ET has been used in countries like the United States to complement antimalarials when treating severe malaria. In fact, CDC used to recommend that ET could be considered as an adjunct to intravenous quinidine in patients with very high parasite loads (>10%), or if complications such as cerebral malaria, acute respiratory distress syndrome, or renal compromise occur. However, the use of ET has been based on limited evidence.

CDC examined the efficacy of ET as an adjunct treatment for severe malaria by analyzing data from the US National Malaria Surveillance System and reviewed the entirety of the published literature to update recommendations. Patients with severe malaria who were treated with ET were compared to those not treated with ET, and there was no significant association between ET and survival outcome. A review of the literature found that the evidence available was limited but overall showed no differences in outcome when ET was used. Adverse events due to ET were rarely reported but included acute respiratory distress syndrome, ventricular fibrillation, and hypotension. To date, this is the largest and most comprehensive study of exchange transfusion for treatment of severe malaria. Based on this evidence, adjunct ET cannot be recommended for the treatment of severe malaria.

Source: CDC

How Malaria Parasites Stick to Sides of Blood Vessels

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Malaria Test Tanzania

At the hospital in Korogwe, Tanzania, mothers are waiting in line with their young children to have the children tested for malaria. The aggressive parasite kills one million people each year of which the majority is children below the age of five. Photo: University of Copenhagen.

Researchers have identified how malaria parasites growing inside red blood cells stick to the sides of blood vessels in severe cases of malaria. The discovery may advance the development of vaccines or drugs to combat severe malaria by stopping the parasites attaching to blood vessels. The results are now published in the scientific journal Nature.

Though researchers have known for over a century that red blood cells infected with malaria parasites can kill their host by sticking to the sides of blood vessels, the binding mechanism associated with the most lethal forms of malaria was unknown. Now, in a study published in Nature, the researchers show that the parasite binds a protein in blood vessel walls called endothelial protein C receptor (EPCR), which is involved with regulating blood coagulation and the inflammatory response.

Malaria parasites grow in red blood cells and stick to the endothelial lining of blood vessels through a large family of parasite proteins called PfEMP1. This way, the parasite avoids being carried with the blood to the spleen, where it would otherwise be destroyed. One of the most aggressive forms of malaria parasite binds in brain blood vessels, causing a disease called cerebral malaria.

In 2012, three groups of researchers, including the teams at the University of Copenhagen and Seattle Biomedical Research Institute, showed that a specific type of PfEMP1 protein was responsible for cerebral binding and other severe forms of malaria infection. However, until now, the receptor to which it binds remained unknown, and the next big question was to determine which receptors the infected red blood cells were binding to.

“The first big challenge was to generate a full-length PfEMP1 protein in the laboratory,” says Assistant Professor Louise Turnerat the University of Copenhagen. “Next, we utilized a new technology developed by Retrogenix LTD in the United Kingdom to examine which of over 2,500 human proteins this PfEMP1 protein could bind to.” Of the 2,500 proteins screened, a receptor called endothelial protein C (EPCR) was the single solid hit.

“A lot of work then went into confirm this binding in the lab and not least to show that parasites from non-immune children with severe malaria symptoms in Tanzania often bound EPCR,” she continues.

“It was a true eureka moment,” says Assistant Professor Thomas Lavstsen. “Under normal conditions, ECPR plays a crucial role in regulating blood clotting, inflammation, cell death and the permeability of blood vessels. The discovery that parasites bind and interfere with this receptor´s normal function may help us explain why severe symptoms of malaria develop.”

Malaria parasites disrupt the important functions of blood vessels

Red blood cells infected with Plasmodium falciparum malaria bind to the endothelial lining of blood vessels in vital organs, such as brain, lung, and heart leading to disease complications with a high risk of deadly consequences. Source: Seattle Biomed

Red blood cells infected with Plasmodium falciparum malaria bind to the endothelial lining of blood vessels in vital organs, such as brain, lung, and heart leading to disease complications with a high risk of deadly consequences. Source: Seattle Biomed

Red blood cells infected with Plasmodium falciparum malaria bind to the endothelial lining of blood vessels in vital organs, such as brain, lung, and heart leading to disease complications with a high risk of deadly consequences. Image ourtesy of Seattle Biomed[/caption]Severe malaria symptoms such as cerebral malaria often result in minor blood clots in the brain. One of our body´s responses to malaria infection is to produce inflammatory cytokines, but too much inflammation is dangerous, describes Professor Joseph Smith, from the Seattle Biomedical Research Institute.

“ECPR and a factor in the blood called protein C act as a ‘brake’ on blood coagulation and endothelial cell inflammation and also enhance the viability and integrity of blood vessels, but when the malaria parasites use PfEMP1 to bind EPCR, they may interfere with the normal function of EPCR, and thus the binding can be the catalyst for the violent reaction,” he explains.

“Investigating this question is the next step to learn about how malaria parasites cause disease.”

Towards an intervention

The discovery that malaria parasites bind EPCR may advance vaccine and drug interventions to treat severe malaria. Dr. Matthew Higgins from the University of Oxfordexplains:

“Now that we know the pair of proteins involved, we can begin zooming further in to reveal the molecular details of how malaria parasites grab onto the sides of blood vessels. We want to know exactly which bits of the parasite protein are needed to bind to the receptor in the blood vessel wall. Then, we can aim to design vaccines or drugs to prevent this binding.”

Children who have suffered from severe malaria can experience poor hearing and reduced learning capacities later in life. Photo: University of Copenhagen.

Malaria and Hearing

Red blood cells infected with Plasmodium falciparum malaria bind to the endothelial lining of blood vessels in vital organs, such as brain, lung, and heart leading to disease complications with a high risk of deadly consequences. Image ourtesy of Seattle Biomed

Vaccine research will also benefit immediately from the discovery, since scientists can already now test the effectiveness of different vaccine candidates at preventing PfEMP1 from binding ECPR. “Over the last decade, we have come to appreciate that specific PfEMP1 proteins are associated with different severe forms of malaria,” explains Professor Thor Theander at the University of Copenhagen. “Together with The National Institute for Medical Research Tanzania, we are in the process of preparing phase I trials for a vaccine to prevent parasite binding in the placenta and malaria during pregnancy,” he explains. This new discovery holds the potential for also developing a vaccine to reduce the heavy burden malaria disease inflicts on children.  “It will be a long haul, but with these results, we can get started right away,” he says.

Source: University of Copenhagen

Drug Resistance May Make Malaria Parasite Less Resistant to Other Substances

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Malaria parasites that develop resistance to the most effective class of anti-malarial drugs may become susceptible to other treatments as a result. The discovery could reveal potential new drug options, which would be essential in the event of resistance to the best anti-malarials.

In a new study, researchers have shown how the anti-malarials artemisinins attack the malaria parasite by inhibiting the action of a crucial protein, and that genetic mutations in this protein can reduce the effect of the drugs. While demonstrating this, however, they also discovered that a mutation that gives the parasite resistance to artemisinins makes it more sensitive to attack by another substance, cyclopiazonic acid (CPA). CPA is thought to be too toxic to be a suitable anti-malarial treatment, but the findings suggest it could be worth pursuing derivatives of the acid as treatment options.

The study was led by researchers at St George’s, University of London and has been published in The Journal of Infectious Diseases.

The artemisinin group of drugs are the most effective and widely used treatments for malaria – used most powerfully with other drugs as artemisinin-based combination therapies – but little is known about their mechanism of action on the malaria parasite. There are signs that the malaria parasite is developing resistance to artemisinin-based combination therapies, meaning further understanding of the drugs could be crucial to prevent them becoming obsolete.

The St George’s researchers have now demonstrated that artemisinins work by acting on a protein within the parasite called a calcium pump. Calcium is essential for all living organisms as it is needed for vital cellular processes. The calcium pump regulates calcium levels in cells, and if it is not functioning properly the parasite dies.

In previous studies, the team had witnessed the same effect on the calcium pump in genetically engineered malaria parasites. However, in these studies the parasites’ sensitivity to artemisinins fluctuated, so they did not give a clear indication of the drugs’ mechanism of action and the findings could not be confirmed.

To provide more consistent results, the latest study used yeast cells instead of parasite cells. Yeast can be a convenient way to display and test the function of proteins from other organisms.

After confirming that artemisinins inhibited the calcium pump in the yeast model, the researchers mutated the pump to mimic three mutations previously observed to give parasites resistance to the drugs. When they did this, they saw similar resistance.

Following this, they tested whether these mutations had any effect on the action of another five substances known to have an anti-malarial effect. They found that one particular mutation that gave the pump resistance to artemisinins made it more susceptible to CPA.

Their findings also showed that the yeast model could be used to identify other drugs that harm the parasite.

Lead author Professor Sanjeev Krishna said: “CPA is a compound used in science and not in clinical practice in any way. However, it points to a proof of concept that we can look for weaknesses in the more resistant strains of the parasite. The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them.”

He added: “This new research supports our earlier work suggesting that the calcium pump is crucial for artemisinins’ action. Understanding how this lifesaving drug works on this calcium pump and how the pump can develop drug resistance will not only allow us to better understand how to use artemisinins more effectively, but it will help us contribute to the development of new drugs to counter the potentially serious effects of artemisinin resistance.”

Source: St George’s, University of London

The full journal article, “Expression in Yeast Links Field Polymorphisms in PfATP6 to in Vitro Artemisinin Resistance and Identifies New Inhibitor Classes’, is available at The Journal of Infectious Diseases.

WHO Launches Program to Counter Drug-Resistant Malaria

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On World Malaria Day, the World Health Organization has launched an emergency program in Phnom Penh to tackle a worrying regional trend – a strain of malaria that is proving resistant to the most important anti-malarial drug.

Six years ago, health researchers were worried after a strain of malaria in western Cambodia began to show resistance to the world’s key malaria treatment – Artemisinin-based Combination Therapy, known as ACT.

In response, the Cambodian government and its health partners, including the World Health Organization, put in place a program to prevent the resistant strain (falciparum malaria) from spreading within Cambodia and beyond its borders.

That program appears to have contained the resistant strain. But Thailand, Burma and Vietnam have reported pockets of artemisinin-resistant malaria strains.

The WHO malaria specialist in Phnom Penh, Stephen Bjorge, said it is likely the strains in those countries arose independently of Cambodia’s – which means the containment efforts have worked.

But because artemisinin is the standard treatment, it is important the resistant strains in all of these areas are contained and then eradicated. That is the purpose of a three-year, $400-million program the World Health Organization announced Thursday.

“The risks are significant – not only are they significant for the region in terms of having a reversal of the gains that have been made against malaria, but they are actually significant globally,” said Robert Newman, director of the WHO’s Global Malaria Program. “If history is any guide, if we were not to contain this problem then it is very likely to spread elsewhere. Especially risky is to sub-Saharan Africa, where the greatest burden still exists. And, if we were to lose the efficacy of the ACTs today, this really would be a public health catastrophe in Africa.”

The WHO-led program is being funded by the Global Fund, the Bill & Melinda Gates Foundation and by the Australian government’s development arm called AusAID.

It will cover six countries: the four where resistance has already been found, as well as two more considered to be “at risk” from the resistant strain: Laos and an area of southern China.

Newman said some of the lessons learned from Cambodia’s efforts are being used.

“This is not starting from zero,” he explained. “It is building on the experience initially on the Cambodia-Thailand border where those countries gained a lot of experience in how to reach the populations that are actually most difficult to reach – migrant and mobile populations, how to use village health care workers, how to more aggressively remove substandard medicines from the market.”

The program will distribute insecticide-treated bed nets; monitor fake drugs; ensure people have access to reliable testing and treatment; and track the disease. Migrant communities and people living in border regions will be key targets of the program.

AusAID has provided $5 million of funding for the program.

“Well, our initial funding is fixed, but the reality is Australia is part of this region,” said AusAID’s principal health advisor Ben David. “We are part of the Asia-Pacific and we see this as a critical investment to protect the poor in the region from malaria, but also to protect the interests of countries because if this problem gets out of control and we see malaria drug resistance spread in the region and beyond, then we are in to face a big set of problems.”

David says, last year, malaria killed 42,000 people in the Asia-Pacific region and more than half a million worldwide, most of them children in Africa.

Recent years have seen good progress in tackling malaria, but the WHO warns that could be undone should the resistant strains escape the current pockets in the countries of the Greater Mekong sub-region.

David believes governments will do their part to prevent the spread.

“It has actually got significant economic implications, if this problem of resistance continues. So, we really need to make the economic case to governments to continue to invest in this problem,” he added.

The chloroquine-resistant malaria strain has caused millions of deaths globally since it emerged 60 years ago from the forests of western Cambodia.

The World Health Organization warns the world cannot afford a similar repeat outbreak by allowing the new strain or strains of artemisinin-resistant malaria to escape the region.

Source: VOA News

Gene Allowing Malaria Parasite to Survive in Mosquitos ID’d

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Plasmodium gallinaceum

Malaria-causing parasites invade the mosquito midgut. Credit: NIAID

National Institute of Allergy and Infectious Diseases (NIAID) researchers have identified a gene that helps malaria-causing parasites elude the mosquito immune system, allowing the microbes to transmit efficiently to people when the insect takes a blood meal. The findings appear in the May 9, 2013, online issue of Science.

Background

Malaria is caused by a single-celled parasite from the genus Plasmodium. The parasite undergoes several developmental stages inside the mosquito. The bite of the infected insect then transmits the disease-causing parasite to people. Malaria caused by P. falciparum, one of four Plasmodium strains that commonly infect people,mostly affects young children in Africa and causes more than half a million deaths each year, according to the World Health Organization.

Certain types of mosquitoes are resistant to malaria infection. When parasites come into contact with the serum-like liquid that flows through the mosquito’s circulatory system, the insect’s immune system interacts with the surfaces of the parasites and kills them.

Several years ago, researchers noted that a particular strain of Anopheles gambiae mosquito can kill many Plasmodium species, including several P. falciparum strains. But some P. falciparum lines from West Africa survived in the resistant A. gambiae strain. More recent work attributed these striking differences in survival to interactions between the parasites and the mosquito immune system.

Results of Study

To better understand how some parasites can evade the mosquito immune system, NIAID researchers led by Carolina V. Barillas-Mury, M.D., Ph.D., in the Laboratory of Malaria and Vector Research studied genetic differences between P. falciparum lines from Brazil and Ghana. Malaria-resistant mosquitoes with healthy immune systems effectively kill the Brazil line, but when the mosquito’s immune system is disrupted, the parasites survive. In contrast, the mosquito immune system seemingly did not detect the parasites from the Ghana line.

By analyzing the offspring of a genetic cross between these two lines, the scientists identified the gene that makes some parasites invisible to the mosquito immune system.  The gene, called Pfs47, is expressed on the surface of the fertilized form of the malaria parasite. African parasites engineered to lack this key gene are readily detected by the mosquito and eliminated.

Significance

The NIAID scientists pinpointed the gene that allows P. falciparum to efficiently infect mosquitoes and be transmitted to people. The parasite’s ability to evade the mosquito immune system may contribute to the high rate of malaria transmission in some geographic areas where the disease is prevalent.  The researcher’s findings potentially could help scientists devise ways to recruit the mosquito immune system to prevent malaria transmission to people.

Next Steps

The NIAID scientists are investigating whether antibodies against the gene can block its function and allow the mosquito immune system to recognize and eliminate malaria-causing parasites.

Reference

Molina-Cruz A, Garver LS, Alabaster A, Bangiolo L, Haile A, Winikor J, Ortega C, van Schaijk BCL, Sauerwein RW, Taylor-Salmon E, Barillas-Mury C. The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system. Science DOI: 10.1126/science.1235264External Web Site Policy (2013).

Dr. Barillas-Mury’s lab page

Source: NIAID

Africa Faces $7 Billion Funding Gap to Fight Malaria

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African countries face a $7-billion funding gap to control and eliminate malaria. To discuss this issue among others, African ministers of health came together at the African Union headquarters to commemorate World Malaria Day.

Every year 660,000 people die from malaria, and 90 percent of those deaths are in Africa. Eliminating malaria by 2015 is one of the United Nations’ Millennium Development Goals. But an estimated $26.9 billion is needed in the next three years to reach the goal.

African Union Commissioner for Social Affairs Mustapha Kaloko says funding is the main challenge, when it comes to fighting malaria.

“We Africans must create [an] innovative domestic national health financing model. We cannot and should not continue to rely on external funding for health. The experience of the last few years has shown that external funding are neither predictable nor assured,” he said.

A handout photograph taken on April 15, 2013 and released 16 by the African Union-United Nations Information Support Team shows a Somali woman holding her child at a clinic run by the Burundian contingent of the African Union Mission in Somalia.A handout photograph taken on April 15, 2013 and released 16 by the African Union-United Nations Information Support Team shows a Somali woman holding her child at a clinic run by the Burundian contingent of the African Union Mission in Somalia.
Malaria costs Africa $12 billion each year in lost productivity, alone. And, a recent study conducted by the Mckinsey global consultancy company notes that every dollar invested in malaria control in Africa, generates an estimated $40 dollar in gross domestic product. But, African countries receive about 75 percent of their budget for malaria control from abroad.

Fatoumata Nafo-Traore, executive director of the Roll Back Malaria Partnership, says African countries could become less dependent, if they would prioritize malaria control:

“Malaria should come among the priorities,” she said. “If that is the case then it would become easy really to find the resources within the government budget. Malaria control interventions are not very expensive. Rapid diagnosis tests costs 50 cents and the treatment for a child costs lest than a dollar. Also, bed nets will costs between $3 to $6. If you bring all these three together, it’s less than $10 to cover one person.”

In addition to becoming less dependent on aid to pay for malaria prevention, Petrina Haingura of the Namibian Ministry of Health advises African governments to make better use of the resources that are available. She says that resources are distributed in communities, without proper education:

“We need to make them aware of these problems of malaria. And, also, some communities are using this mosquito nets by using it to catch fish. But I think we need to emphasize why we are giving them these mosquito nets is to prevent malaria,” she said.

Malaria deaths have decreased to an average of about 33 percent on the African continent. But scientists expect that shortages in funding for control interventions could quickly turn around those results.

African ministers of health are in a four-day conference of the African Union where the call to fight malaria has been renewed.

Source: VOA News

Chorangiosis Implicated in Pregnant Women Infected with Malaria

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A passing remark launched the project that will be described at the Experimental Biology 2013 conference in Boston on Monday. A poster, presented by undergraduate Ashley McMichael from Albany State University, has preliminary data that hint that there is an association between a rare pregnancy condition and malaria.

The remark that launched the project was made by a collaborator of Julie Moore, a malaria expert at the University of Georgia. Moore was visiting her collaborator, pediatric pathologist Carlos Abramowsky at Children’s Healthcare of Atlanta (affiliated with Emory University), armed with placental tissue slides collected from women living in western Kenya, a region where malaria is rampant. While viewing the slides, Moore recalls Abramowsky commenting, “Wow, this is a really interesting case of chorangiosis.” And her reaction was, “Oh, what is chorangiosis?” [Read more…]