Genetically Modified Fungus Could Fight Malaria

Bacteria use for producing anti-body against malaria are seen through a microscope at Westminster University in London, Tuesday, March 15, 2011. In a cramped London laboratory filled with test tubes, bacteria and mosquitoes, scientists are trying to engineer a new weapon in the battle against malaria: a mutant fungus. For years, Angray Kang at Westminster University and colleagues have been testing whether they could genetically tweak a fungus to kill the malaria parasite carried by mosquitoes.

NPR

In a cramped London laboratory filled with test tubes, bacteria and mosquitoes, scientists are trying to engineer a new weapon in the battle against malaria: a mutant fungus.

For years, Angray Kang at Westminster University and colleagues have been testing whether they could genetically tweak a fungus to kill the malaria parasite carried by mosquitoes.

Now they’ve found that in lab experiments, mosquitoes exposed to the fungus show a sharp drop in levels of the parasite. If it works that way in the wild, that should make it harder for the disease to infect people.

Kang said the mutant fungus could be sprayed onto walls and bednets like insecticides and could be made for a comparable cost.

He said the same process of genetic modification could also be used to target other insect-spread diseases like dengue and West Nile virus. The research was done together with scientists at the Johns Hopkins School of Public Health and was funded by the U.S. National Institutes of Health. Early results were published recently in the journal Science.

“This is very exciting research,” said Andrew Read, director of the Center for Infectious Disease Dynamics at Pennsylvania State University. He has worked on similar projects but was not involved with the fungus research. “It tells us that if you can’t find something in nature to do what you want, you can just make it.”

Read said using the souped-up fungus might be less environmentally invasive than other genetic approaches. Some critics have warned that competing biological approaches, like scientists creating mutant mosquitoes, could wreak havoc to ecosystems if billions of the insects are released into the wild.

With the fungus, “you just spray it on the wall and it does its job,” Read said. “You don’t have to worry about generation after generation of the stuff.”

He also said the fungus technology could be a new way of dealing with insecticide-resistant mosquitoes, an increasing problem that has meant the return of effective but controversial sprays like DDT. “With the (mutant) fungi, you wouldn’t have chemical residues hanging around,” he said. “It would just be a fungus very similar to what is already found in nature.”

In laboratory tests, Kang and colleagues found mosquitoes exposed to the mutated fungus had malaria parasite levels about 85 percent lower than normal. When they added a scorpion toxin to the mix, levels dropped by 97 percent. No tests have shown whether using the fungus would curb human malaria cases, but experts think fewer malaria parasites should translate into fewer cases.

“If the strategy works and there are fewer parasites, this could change how malaria is spread and reduce transmission to humans,” said George Christophides, an infection expert at Imperial College London who was not associated with the research.

Kang’s experiment involved inserting a human antibody against malaria into a fungus commonly found in soil and plants worldwide. Spores made by the fungus burrow into the mosquito, invading its circulatory system. When the malaria-causing parasite multiplies inside the insect, the antibody keeps the parasites from reaching the mosquito’s salivary glands. That theoretically stops the disease’s spread.

“The mosquito can be infected by malaria, but it can’t pass it onto humans,” Kang said. The mutated fungus then eats away at the mosquito from the inside, killing the insect after a couple of weeks. That’s long enough for the mosquito to reproduce, which should lessen its incentive to evolve resistance to it.

The same fungus — minus the genetic modifications — is already produced in industrial quantities to squash locust outbreaks in Australia. The fungus is naturally lethal to locusts, so no genetic modification is needed.

If Kang and colleagues can get enough funding, they hope to test the mutant fungus in malaria-endemic countries like Burkina Faso, Kenya or Tanzania.

Other experts doubted whether the laboratory experiment could be replicated in the wild. “It’s a neat scientific idea, but there are questions about (the mutated fungus’s) stability and formulation,” said Janet Hemingway, director of the Liverpool School of Tropical Medicine. She said the mutant fungus would have to survive being shipped to Africa and then be viable for another three to six months in stifling heat once it’s sprayed onto walls or bednets.

One group that campaigns against genetically modified organisms warned the mutant fungus could skew behaviors of other wildlife.

“The release of any genetically modified organism into the environment runs the risk that it may have wider impacts than just its target,” said Pete Riley, campaign director of GM Freeze, a U.K.-based advocacy group. He said the modified fungus could have unintended consequences which might be impossible to reverse. “Nature has a pretty cunning way of getting around everything we throw at it,” he said.

Kang acknowledged that simply having a new mutant fungus would not stop malaria. “We still need better drugs and other interventions,” he said. “But malaria kills about a million people every year so we have to try whatever may work.”

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Canadians Make Malaria Breakthrough

Mother and daughter sleep under mosquito net to prevent bites from the parasite carrying mosquito

Lana Haight, Postmedia News

SASKATOON — Scientists in Saskatoon have developed an inexpensive malaria treatment that will help the million people who die every year from the infection.

“This is the most important drug in the treatment of malaria today. The World Health Organization says it should be the first line of defence,” said Patrick Covello, a senior research officer at the National Research Council in Saskatoon.

Covello and his team figured out a way to produce a difficult-to-cultivate chemical needed to build effective malaria drugs.

The breakthrough was announced Friday at the National Research Council Plant Biotechnology Institute.

The best drugs available to fight malaria are made with artemisinin, a compound derived from the sweet wormwood plant found in parts of Asia and Africa. But cultivating and harvesting the plant and then extracting artemisinin is time-consuming and labour intensive, says Covello. And the supply of the natural compound is also dependent on weather and growing conditions.

In 2003, Covello began work to identify the genes in the wormwood plant that produce the protein that leads to artemisinin.

“We identified four genes in what we call the pathway to artemisinin in the plant,” he said in an interview.

Meanwhile, University of California at Berkley researchers found they could develop a precusor to artemisinin by introducing chemicals into yeast.

Covello contacted Amyris Technologies, a spinoff company from the Berkeley research group, to suggest it use the genes his group had identified in the wormwood plant. When two of the genes identified in Saskatoon were introduced to the yeast compound developed at Berkeley, the production of artemisinin doubled.

The Institute for OneWorld Health, the American-based organization that has led the project to develop the semi-synthetic artemisinin, and pharmaceutical company Sanofi-aventis jointly announced on Friday that the drug company is preparing to ramp up production using the genes identified in Saskatoon.

The Bill & Melinda Gates Foundation, which has already contributed $42.6 million toward the American research, is also supporting the production of the drug to ensure it will be available on a not-for-profit basis for the developing world.

“The idea is to provide the developing world with antimalarial drugs at the lowest possible cost and, in addition, to provide a very stable supply because this yeast-fermentation process is shorter term and more reliable than growing the plants themselves,” said Covello.

Covello understands that Sanofi-aventis will begin commercial-scale production in 2012.

The federal government has spent $869,000 over eight years to support the Saskatoon research.

“Our government is committed to improving the health of women and children in developing countries,” said Gary Goodyear, minister of state for science and technology, in a government news release.

“This new development in the production of a malaria treatment represents a major development in the fight against the disease. It will strengthen Canada’s position as a world leader in health research and provide a reliable and affordable solution.”

The Vancouver Sun
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African Leaders Pledge to End Malaria by 2015

Ted Purlain

The United Nations envoy tasked with coordinating efforts against malaria has reported that African leaders are at the forefront of a landmark initiative to end unnecessary deaths from the disease by 2015.

The African Leaders Malarial Alliance was recently formed and tasked with ensuring that more than 240 million insecticide-treated bed nets were distributed, according to PressTrust.com.

Malaria is believed to kill almost one million Africans every year and to affect over 200 million more. Most of those that succumb are pregnant women and children under the age of five. At least $12 billion of costs through lost development and opportunity are thought to be lost annually.

Launched at United Nations Headquarters in New York, ALMA is a high-level forum set up to oversee the efficient procurement and utilization of malaria control measures.

“Malaria is borderless,” Ray Chambers, the secretary-general’s special envoy for malaria, said, according to PressTrust.com. “Therefore, we need an organization that transcends borders. This is ALMA.”

Chambers said that the actions of ALMA can go a long way towards saving one million lives every year as it works to end deaths, enhance health infrastructures and grow economies.

U.N. Secretary-General Ban Ki-moon sent a message to the launch that supported the mutual engagement of Africa’s heads of state and government, as well as the support of the international community.

Last year, the international community spent $3 billion on the overall campaign against malaria.

World Health Organization Director-General Margaret Chan called the launch of ALMA a critical step in the fight against malaria in Africa, PressTrust.com reports.

Ted Purlain Vaccine NewsDaily
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Cuts That Kill: The Senate Must Restore Global Health Funding

Joanne Carter
Executive director of RESULTS/RESULTS Educational Fund (REF)

Last week Congress approved a two-week extension of federal funding to avoid a looming government shutdown. The vote postpones — but does not resolve — potentially devastating cuts to global health programs. The House-proposed bill for the balance of 2011 proposes deep cuts to some of the most effective investments the US makes globally, including a drastic 40 percent reduction for the Global Fund to Fight AIDS, Tuberculosis and Malaria.

In a recent interview Michael Gerson, a former speechwriter and advisor to President George W. Bush, called the cuts “irrelevant and destructive.” He’s right on both counts, and there’s still time for Congress to reverse course.

The cuts are irrelevant to the deficit problem that members of Congress are ostensibly trying to solve. Our entire foreign aid portfolio amounts to little more than a rounding error in the federal budget. Foreign aid focused on health, education, economic opportunity, and other anti-poverty programs account for less than 1 percent of federal spending. Even if Americans believed that erasing these programs was a good idea — and they don’t, as public opinion polls consistently reveal — it wouldn’t put a dent in the deficit.

These cuts are destructive because they would be measured in human lives.

With the U.S. as a leading donor, the Global Fund has helped save more than six million lives, and in just a decade has fundamentally altered our ability to fight AIDS, TB, and malaria, among the biggest killers on the planet. If the House proposal to slash $450 million from the Global Fund were adopted it would mean six million treatments for malaria would not be administered. More than 400,000 people won’t be provided with antiretroviral medication to treat AIDS, and nearly 60,000 women won’t receive the drugs they need to prevent transmission of HIV to their newborn children. More than 370,000 people won’t be tested and treated for tuberculosis, the world’s leading curable infectious killer of adults.

This budget crunch comes just as new tools are available to transform the fight against infectious diseases. A new way to diagnosis TB using a machine called Xpert is one such breakthrough. The current method of identifying TB bacteria under a microscope was developed nearly 130 years ago and is still used throughout the developing world. This method often fails to detect TB in people living with HIV/AIDS and in children, cannot detect drug resistance, and is frustratingly slow. Patients must take time off from work and family to return to a clinic and submit multiple specimens over several days — often an impossible demand in very poor communities. Although TB is curable, correctly and rapidly diagnosing the disease has been a major stumbling block.

Xpert has the potential to change that. It’s fast, accurate and easy to use. About the size of an espresso machine, it relies on DNA technology to diagnose TB, detects drug-resistant strains of the disease, and returns the results in about 90 minutes. That may not grab headlines, but in the world of TB control it’s nothing short of revolutionary.

Other breakthroughs abound. The promising trial results for a microbicide gel to prevent HIV transmission electrified the HIV/AIDS community in search of new prevention methods. Vaccines to help prevent pneumonia and diarrhea — the two leading killers of young children — are newly available in poor countries through the GAVI Alliance, an international partnership to expand access to childhood immunizations.

The question for Congress is whether global health policy and funding will keep up with global health evidence and opportunity.

The innovations in global health now at our fingertips are not just new drugs, vaccines, and diagnostics, but also the means of financing and delivering them. For example, The Global Fund to Fight AIDS, Tuberculosis and Malaria has led the way in changing the business model for how aid is delivered. Last week the conservative-led UK government released an exhaustive multilateral aid review of 43 development institutions which rated the Global Fund as one of nine organizations with an “excellent track record” for delivering results. Global Fund proposals are developed by the countries who implement them, they are evaluated by an independent review panel, and continued funding is awarded according to performance. Project documents — everything from glowing reports to unforgiving audits — are made publicly available on the Fund’s website.

That may sound like common sense, but it’s not necessarily common practice among global health and development aid donors.

As a board member of the Global Fund, I see the Fund’s challenges up close, and I also see its ground-breaking model, its impact and the even greater potential it represents. The proven success of the Global Fund allows us to think about seizing the next set of opportunities presented by modern medicine and break the backs of the world’s greatest epidemics.

Congress faces unenviably tough budget decisions this year, but funding for these programs is not a close call. The Senate should reverse the House’s proposed cuts to global health for 2011, and restore this sliver of the federal budget that delivers unparalleled results. To do otherwise would be irrelevant and destructive.

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Fighting Malaria With Nets Nets, Mandy Moore

Mandy Moore
Singer-songwriter, actress and PSI Ambassador
Mandy Moore, Singer-songwriter, actress and PSI Ambassador

I’m extremely grateful to be invited to share my voice alongside all these incredible women on International Women’s Day. As an ambassador for the global health organization PSI (Population Services International), I’ve been fortunate to have traveled to places like the Central African Republic and Southern Sudan where I have met amazing women who rival the likes of the women on this site today.

Last fall, I traveled to the Central African Republic — a country where malaria is responsible for approximately half of all hospital visits. I was there to help launch a United Nations Foundation’s Nothing But Nets campaign that would provide a net to every family in need in the country.

As part of the trip, I visited a local health clinic in a rural part of the capital city, Bangui. There, I met a woman named Sophie who was with her husband and newborn baby. Her baby was inconsolable, crying from pain and hot to touch with a high fever. This was the second time Sophie had been at the clinic with her daughter. The first time her daughter she was only mildly ill, but the health clinic didn’t have any anti-malaria treatment in stock. So they referred her to the local hospital, which was an expensive bus ride away. When Sophie arrived at the hospital she realized that they couldn’t afford the medication. So she took the little remaining money she had and purchased syringes. Then she walked back to the rural health clinic and begged the doctor there to give them the medication for free. Sophie was willing to inject her daughter herself if she thought it could save her life.

Mandy Moore in the Central African Republic

That’s when I met them. The health clinic had no medication, Sophie had no money, and her daughter’s fever was worsening by the minute. Luckily, in her case, we were able to give her the money needed to return to the hospital by cab and purchase the right treatments.

That was the last time I saw Sophie and her baby. I often think of them and hope that they’re okay. But I can’t help but wonder what will happen the next time her daughter is bitten by a malaria-carrying mosquito, when there’s no group of Westerners at the clinic willing to pay her way.

Thankfully, there’s hope for mothers like her. Long-lasting, insecticide-treated mosquito nets are one of the most cost-effective and cost-efficient ways of preventing malaria. Nets can prevent malaria transmission by up to 90 percent, and through the Nothing But Nets campaign that I helped launch, the government of Central African Republic and its partners at PSI and UNICEF were able to distribute nearly 1 million mosquito nets — one for every family in need.

At the same time, thanks to a grant from the Global Fund to Fight AIDS, Tuberculosis and Malaria, the local health clinic where I met Sophie is now able to provide preventative malaria treatment to pregnant women, free of charge. Malaria contributes to the deaths of an estimated 10,000 pregnant women and 200,000 infants each year in Africa, so early and effective treatment can prevent a great majority of deaths.

But tackling malaria in a country like the Central African Republic is a huge uphill battle, and my experiences there have been a healthy dose of reality, fueling my own sense of urgency to do my part in reducing the preventable suffering of the incredible women I met. This year, I will be attending the Clinton Global Initiative University, a meeting for students and national youth organizations to tackle pressing global issues. I am excited about being a part of this growing community of young leaders who don’t just discuss the world’s challenges, but take real, concrete steps toward solving them — real, concrete steps to empower women like Sophie to protect herself and her family.

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Genetically Modified Fungi Prevent Parasite Development in Malaria Mosquitoes

spores of Metarhizium anisopliae in an oil formulation germinating on locust cuticle

K. Amponsah-Manager

A team of scientists in the UK and US have genetically modified a fungus that prevents the development of malaria-causing parasites in the mosquitoes.  The study which has been published in the journal Science showed that the fungus can eliminate up to 90% of the parasite in the vector that carry it, the female anopheles mosquito.

The scientists inserted the genes of human antibodies or scorpion toxins into a fungus called Metarhizium anisopliae and infected mosquitoes with the fungus. This conferred onto mosquitoes infected with the fungus the ability to block the development of malaria-causing parasites in mosquitoes.

The female Anopheles mosquitoes are the vectors for the malaria parasite, Plasmodium, which develop inside the body of mosquitoes. The mosquito simply helps to shuttle the parasite between infected person and healthy people and therefore the ability to deprive the parasite of its taxi service is key to fighting the illness.

Due to the environmental hazards of using pesticides to fight the malaria mosquitoes and the development of resistance to many anti-malarial products, recent years scientists have focused their attention on finding natural and environmental friendly methods to fight the disease. The fungus Metarhizium anisopliae naturally kills mosquitoes but unlike parasites, it takes day to accomplish that. The advantage of the Fungi’s patience is that because the mosquitoes can mate and do their usual chores, they have less reason to develop resistance.

Results of the study showed that malaria parasite survived in the salivary glands of 25 percent of the mosquitoes sprayed with the genetically modified organism, compared to 87 percent of those sprayed with an unmodified strain of the fungus, and to 94 percent of those that were not sprayed at all.

The good news from the study is the possibility that spraying malaria-transmitting mosquitoes with the genetically-modified fungus, also known as transgenic fungus, could one day become a feasible method to significantly reduce the transmission of the disease to humans.

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Vaccine-Delivering Nanoparticles May Help Fight HIV, Malaria

Engineers at MIT have come up with a new type of nanoparticle that could safely and effectively deliver vaccines for diseases such as HIV and malaria.

The new particles consist of concentric fatty spheres that can carry synthetic versions of proteins normally produced by viruses. These synthetic particles elicit a strong immune response – comparable to that produced by live virus vaccines – but should be much safer, says Darrell Irvine, author of the paper and an associate professor of materials science and engineering and biological engineering.

Such particles could help scientists develop vaccines against cancer as well as infectious diseases. In collaboration with scientists at the Walter Reed Army Institute of Research, Irvine and his students are now testing the nanoparticles’ ability to deliver an experimental malaria vaccine in mice.

Vaccines protect the body by exposing it to an infectious agent that primes the immune system to respond quickly when it encounters the pathogen again. In many cases, such as with the polio and smallpox vaccines, a dead or disabled form of the virus is used. Other vaccines, such as the diphtheria vaccine, consist of a synthetic version of a protein or other molecule normally made by the pathogen.

When designing a vaccine, scientists try to provoke at least one of the human body’s two major players in the immune response: T cells, which attack body cells that have been infected with a pathogen; or B cells, which secrete antibodies that target viruses or bacteria present in the blood and other body fluids.

For diseases in which the pathogen tends to stay inside cells, such as HIV, a strong response from a type of T cell known as “killer” T cell is required. The best way to provoke these cells into action is to use a killed or disabled virus, but that cannot be done with HIV because it’s difficult to render the virus harmless.

To get around the danger of using live viruses, scientists are working on synthetic vaccines for HIV and other viral infections such as hepatitis B. However, these vaccines, while safer, do not elicit a very strong T cell response.

Importantly, the particles also elicit a strong antibody response. Niren Murthy, associate professor at Georgia Institute of Technology, says the new particles represent “a fairly large advance,” though he says that more experiments are needed to show that they can elicit an immune response against human disease, in human subjects. “There’s definitely enough potential to be worth exploring it with more sophisticated and expensive experiments,” he says.

The work has been described in the Feb. 20 issue of Nature Materials. (ANI)

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George Clooney Gives Malaria Hollywood Buzz

Clooney contracted malaria while in Sudan to monitor the election

George Clooney is used to creating a buzz no matter where he goes. However, on a recent trip to Sudan he experienced a buzz he could have done without.

‘I was so sick with malaria, I didn’t care if I lived or died’

The Hollywood heartthrob was bitten by a mosquito and contracted malaria while in Africa working on his Enough project, in a bid to put an end to genocide.

“I guess the mosquito in Juba looked at me and thought I was the bar,” he quipped. But while Clooney ironically joked catching malaria “was good fun” the disease is deadly and often fatal. In fact, it is the fifth-leading cause of death around the world, according to the US-based Centre For Disease Control And Prevention.

The 49-year-old is not the first celebrity to pick up malaria. Chelsea footballer Didier Drogba recently fell foul of the disease when in the Ivory Coast, while Cheryl Cole contracted it on a trip to Tanzania. The Girls Aloud singer and X Factor star was originally misdiagnosed and ended up in hospital after collapsing on a shoot.

“I am pretty much evangelised now when it comes to warning people of the dangers of malaria,” says Joe Kearns from Dublin, who picked up the disease while working for Concern in Ethiopia.

Like Cheryl Cole, Kearns was also misdiagnosed and ended up in hospital in a critical condition.

“The first thing is it feels very like a flu,” he says. “You get aches and pains in your bones and you have a temperature and you feel crap. It was almost two years since I had come home from the zone that had malaria so it didn’t trigger any alarm bells.”

While the symptoms usually take a period of between two weeks and several months to appear, in extreme cases can appear up to 30-40 years later.

“I went into hospital and they sent me home with no idea what was wrong with me,” says Kearns. “I was getting sicker and sicker and after about 10 days I was hospitalised again. My wife was told they didn’t think I would live. I had had three blood transfusions, I was unable to eat and I weighed 8.5 stone – I normally weigh about 11 stone. I was so sick I actually didn’t care whether I lived or died.”

Luckily, his brother, a doctor, had a tissue sample sent to the Tropical Medicine Clinic in the Lourdes Hospital in Drogheda after recalling Joe had been in Africa. That is when he was finally diagnosed as suffering from malaria.

“Basically speaking, Irish-trained doctors are not sufficiently trained in considering tropical medicine in their consultations, and that’s the same whether they are GPs or a hospital doctor,” says Dr Graham Fry, Medical Director at the Tropical Medical Bureau. “It takes an exceptional doctor to consider outside a box and consider a person’s geographical history.”

The symptoms of the mosquito-born infectious disease, widespread in parts of the Americas, Asia and Africa, include fever and headache, but in severe cases can lead to hallucinations, coma and death.

Indeed, former No Frontiers presenter Kathryn Thomas experienced “hellish visions” and couldn’t feel her legs after catching malaria while filming an adventure special in Papua New Guinea.

But just like George Clooney, Cheryl Cole, Kathryn Thomas and many others who catch the disease, Joe Kearns had taken what he thought were the proper precautions.

“I went out to Africa for two years and beforehand got a lot of medical advice from Concern,” he says. “We were told to take tablets while we were there and I was very diligent about making sure I took my tablets. I was not sick at all with malaria when I was in Africa. But the tablets don’t guarantee that you won’t get it, as in my case. The only way to be sure you don’t get it is to ensure you don’t get bitten. If you take the tablets you are improving your chances but it is only improving your chances.”

In fact, according to Dr Fry of the Tropical Medical Bureau, tablets only offer 95% protection.

In Africa, it is estimated that two children die from malaria every minute. Every year there are about 250 million malaria cases and nearly one million deaths, according to the World Health Organisation. But malaria is also a growing phenomenon in Ireland.

The National Surveillance Centre report on Notifiable Diseases issued earlier this year shows 82 reported cases of malaria in 2010 in comparison to 90 cases for the previous 12 months.

“Up until four or five years ago there was only about 20 cases every year in Ireland,” says Dr Fry. “However, over the last five years that has shot up into the 80s and 90s.

“Over half of these are from people who have come to live in Ireland over the last 10 years from Africa. They have had a couple of children they have settled in to Ireland and they now want to go back to their home country in West Africa to visit family and friends.

“They don’t think they are going to be at risk because they are going home, but they are not. Ireland is now their home so they have lost the antibodies that protect them.”

With the numbers of malaria cases on the rise, the Tropical Medical Bureau is urging Irish travellers to be more cautious and to acquire the appropriate vaccinations before travelling to malaria-prone areas.

“I don’t think Irish people are aware of the risks,” says Dr Fry. “Reading about George Clooney or Cheryl Cole people think they must have done something really odd and it is never going to happen to them. People never think it is going to happen to them, because it always happen to someone else.”

George Clooney and Cheryl Cole also probably thought it always happens to someone else, but like an increasing number of people they were wrong. Luckily for them the disease was diagnosed early enough before they ended up being dead wrong. – Irish Independent

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