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News Article | April 12, 2016
Site: http://www.biosciencetechnology.com/rss-feeds/all/rss.xml/all

A team of scientists led by Oxford University have made a discovery that could improve our chances of developing an effective vaccine against Tuberculosis. The researchers have identified new biomarkers for Tuberculosis (TB) which have shown for the first time why immunity from the widely used Bacillus Calmette-Guérin (BCG) vaccine is so variable. The biomarkers will also provide valuable clues to assess whether potential new vaccines could be effective. TB remains one of the world's major killer diseases, causing TB disease in 9.6 million people and 1.5 million deaths in 2014. The only available vaccine, Bacillus Calmette-Guérin (BCG), works well (estimated 50 percent effective) to prevent severe disease in children but is very variable (0 percent to 80 percent effective) in how well it protects against lung disease, particularly in countries where TB is most common. While BCG is one of the safest and most widely used vaccines worldwide, there is one key issue: It is currently very difficult to determine whether it will work or not. This also makes it really hard to determine if any new vaccines might work. For many vaccines, medics and scientists can use what are called immune correlates or biomarkers, typically in the blood, which can be measured to determine whether a vaccine has successfully induced immunity. Not only are these correlates useful in measuring the success of existing vaccination programmes, they are also invaluable in assessing whether potential new vaccines could be effective. With a pressing need for a TB vaccine that is more effective than BCG, a research team drawn from a number of groups at Oxford University, working with colleagues from the South African Tuberculosis Vaccine Initiative at the University of Cape Town and the London School of Hygiene & Tropical Medicine, set out to identify immune correlates that could facilitate TB vaccine development. The team, funded by the Wellcome Trust and Aeras, and led by Professor Helen McShane and Dr. Helen Fletcher, studied immune responses in infants in South Africa who were taking part in a TB vaccine trial. Professor McShane said: "We looked at a number of factors that could be used as immune correlates, to try and find biomarkers that will help us develop a better vaccine." The team carried out tests for twenty-two possible factors. One - levels of activated HLA-DR+CD4+ T-cells - was linked to higher TB disease risk. Meanwhile, BCG-specific Interferon-gamma secreting T-cells indicated lower TB risk, with higher levels of these cells directly linked to greater reduction of the risk of TB. Antibodies to a TB protein, Ag85A, were also identified as a possible correlate. Higher levels of Ag85A antibody were associated with lower TB risk. However, the team cautions that other environmental and disease factors could also cause Ag85A antibody levels to rise and so there may not be a direct link between the antibody and TB risk. Professor McShane said: "These are useful results which ideally would now be confirmed in further trials. They show that antigen-specific T cells are important in protection against TB, but that activated T cells increase the risk". Dr. Helen Fletcher from the London School of Hygiene & Tropical Medicine, said: "For the first time we have some evidence of how BCG might work, and also what could block it from working. Although there is still much work to do, these findings may bring us a step closer to developing a more effective vaccine for TB." Dr. Tom Scriba from the South African Tuberculosis Vaccine Initiative said: "TB is still a major international killer, and rates of TB disease in some areas of South Africa are among the highest in the world. These findings provide important clues about the type of immunity TB vaccines should elicit, and bring us closer to our vision, a world without TB." The team is continuing its work to develop a TB vaccine, aiming to protect more people from the disease. The paper was published in the jounral Nature Communications.


Van Griensven J.,Institute of Tropical Medicine | Carrillo E.,Institute Salud Carlos III | Lopez-Velez R.,Tropical Medicine | Lynen L.,Institute of Tropical Medicine | Moreno J.,Institute Salud Carlos III
Clinical Microbiology and Infection | Year: 2014

Leishmaniasis is a vector-born chronic infectious disease caused by a group of protozoan parasites of the genus Leishmania. Whereas most immunocompetent individuals will not develop disease after Leishmania infection, immunosuppression is a well-established risk factor for disease. The most severe form is visceral leishmaniasis (VL), which is typically fatal if untreated. Whereas human immunodeficiency virus (HIV) co-infection (VL-HIV) was initially mainly reported from southern Europe, it is now emerging in other regions, including East Africa, India, and Brazil. VL has also been found in a wide range of non-HIV-related immunosuppressive states, mainly falling under the realm of transplantation medicine, rheumatology, haematology, and oncology. Clinical presentation can be atypical in immunosuppressed individuals, being easily misdiagnosed or mistaken as a flare-up of the underlying disease. The best diagnostic approach is the combination of parasitological and serological or molecular methods. Liposomal amphotericin B is the drug of choice. Treatment failure and relapse rates are particularly high in cases of HIV co-infection, despite initiation of antiretroviral treatment. Primary prophylaxis is not recommended, but secondary prophylaxis is recommended when the patient is immunosuppressed. Cutaneous leishmaniasis can have a number of particular features in individuals with immunosuppression, especially if severe, including parasite dissemination, clinical polymorphism with atypical and often more severe clinical forms, and even visceralization. Mucosal leishmaniasis is more common. Treatment of cutaneous and mucosal leishmaniasis can be challenging, and systemic treatment is more often indicated. With globally increased travel and access to advanced medical care in developing countries, the leishmaniasis burden in immunosuppressed individuals will probably continue to rise, warranting increased awareness and enhanced surveillance systems. © 2014 European Society of Clinical Microbiology and Infectious Diseases. Source


News Article
Site: http://www.nature.com/nature/current_issue/

As soon as the rain stops, mosquitoes flood the guard house of an upscale tourist resort near Cuba’s Bay of Pigs. Without hesitation, one of the guards reaches under his desk to pull out a device that looks like a very large hair dryer. “Mosquito gun,” he says. He walks around, spraying a thick, white cloud of fumigant that engulfs the booth. Slowly, the mosquitoes disappear. It’s not uncommon to see clouds of pesticide wafting through Cuba’s houses and neighbour­hoods. It is largely because of such intensive measures by ordinary citizens that the country has been among the last in the Caribbean to succumb to local transmission of Zika. As of 11 August, Cuba has recorded three people who were infected by local mosquitoes rather than contracting the illness abroad, compared with 8,766 confirmed cases in nearby Puerto Rico (see ‘Zika in the Caribbean’). Although scientists and public-health officials are disappointed that Zika has finally arrived in Cuba, they are not surprised. “It’s not easy to avoid an introduction, because a lot of people are coming to Cuba from a lot of places,” says Maria Guzmán, head of virology at the Pedro Kourí Tropical Medicine Institute in Havana. The country has recorded about 30 confirmed imported cases. Zika is especially insidious because most people who have it show either no symptoms or only common ones such as fevers, which could be attributed to other illnesses. Yet, with the exception of one locally acquired case in March, Cuba mostly managed to keep Zika out until this month. That success was the result of its excellent health-care system and an extensive surveillance programme for vector-borne diseases that the government set up 35 years ago, says Ileana Morales, director of science and technology at Cuba’s public-health ministry. In 1981, Cuba saw the first outbreak of haemorrhagic dengue fever in the Americas, with more than 344,000 infections. “We turned that epidemiological event into an opportunity,” says Morales. The country sent medical workers to affected areas and began intensively spraying pesticides to eradicate the Aedes aegypti mosquito that carries the disease. It also created a national reporting system, as well as a framework for cooperation between government agencies and public-education campaigns to encourage spraying and self-monitoring for mosquito bites, even among children. One of the most effective measures was a heavy fine for people found to have mosquitoes breeding on their property, says Duane Gubler, an infectious-disease researcher at Duke–NUS Medical School in Singapore. With all these measures in place, Cuba eliminated the dengue outbreak in four months. Now, when another outbreak threatens, “it’s no problem for us to reinforce our system” and intensify such efforts, says Morales. In February, before any Zika cases had been detected in Cuba, the government dispatched 9,000 soldiers to spray homes and other buildings, while workers killed mosquito larvae in habitats such as waterways. Airport officials screened visitors arriving from Zika-infected countries and medical workers went from door to door looking for people with symptoms. The health-care system already conducts extensive prenatal examinations, so it is primed to detect Zika-caused birth defects such as microcephaly. Cristian Morales, head of the Cuba office of the Pan American Health Organization (PAHO), says that it is probably unrealistic for other countries to simply copy Cuba’s mosquito-control programmes. The country’s health-care network is one of the best in the developing world, and the decades-long stability of its government has ensured policy continuity and enforcement of measures such as fines. He adds that the most important aspects of a response, for any country, include collaboration between government sectors and increased surveillance. “Cuba probably does a better job of controlling mosquitoes than any other country in the Americas, but it hasn’t been totally effective,” says Gubler. This is partly due to dips in funding. A resurgence of dengue in 1997 was probably exacerbated by the fall of the Soviet Union, Cuba’s major trading partner, which decimated the economy and weakened health funding. Another disadvantage stems from the 56-year-old US trade embargo, which prevents Cuba from acquiring drugs and medical supplies that include components made in the United States. It must instead buy them from other countries, such as China, often at higher cost. Yet success has come despite these issues. According to PAHO, health workers have intensified efforts to spray pesticides and eradicate standing water — where mosquitoes can breed — within 150 metres of the homes of each of the two most recent people to get Zika, in the southeastern province of Holguin. Workers are also searching houses for infected people and collecting mosquitoes for study. Guzmán adds that Cuban researchers have begun to plan work on a Zika vaccine. She says that international cooperation will be important in helping Cuba and others to address Zika. “It’s a problem of everybody. It’s a new challenge for the world.”


News Article
Site: http://www.nature.com/nature/current_issue/

A decades-long push to make Guinea-worm disease the first parasitic infection to be wiped out is close to victory. But a mysterious epidemic of the parasite in dogs threatens to foil the eradication effort. “If we’re going to be aggressive and achieve this, we have to eliminate the infection in dogs,” says David Molyneux, a parasitologist at Liverpool School of Tropical Medicine, UK. The Carter Center in Atlanta, Georgia, is leading the global campaign to eradicate Guinea worm. Next week, it will announce that case numbers for the excruciatingly painful infection are at a record low, with approximately 25 cases reported in 2015 in just 4 countries: Chad, Ethiopia, Mali and South Sudan. But infections in dogs are soaring in Chad, where officials will meet at the end of January to grapple with the canine epidemic. The central African nation recorded more than 450 cases of Guinea worm in domestic dogs last year — an all-time high (see ‘Canine comeback’). Researchers and officials strongly suspect that dogs are spreading the infection to humans; now the race is on to understand how this might happen, as well as how dogs acquire the infection in the first place. The World Health Organization is unlikely to declare Guinea worm eradicated until the parasite has stopped spreading in dogs, says Molyneux, who is part of the commission that will make that decision. In 1986, when the Carter Centre joined the Guinea-worm eradication campaign, there were an estimated 3.5 million infections annually, mostly due to poor sanitation and lack of access to clean water. When people drink unfiltered water, they can swallow microscopic freshwater crustaceans called copepods, which Guinea-worm larvae infect. The copepods die, releasing the larvae, which mature and mate in the human intestine. Male worms die after mating, but adult females — approximately 80 centi­metres in length — survive and slowly migrate out of the gut. About a year after infection, they burrow through their host’s skin, usually around the legs and feet, sometimes taking weeks to fully escape. To cope with the searing pain, many people bathe in rivers and lakes, contaminating the water with the next generation of larvae. Although rarely fatal, Guinea worm can debilitate people for months and keep children out of school. There is no vaccine against the parasite and no effective treatment, so eradication efforts have focused on providing clean water and changing people’s behaviour, says Donald Hopkins, a special adviser at the Carter Center who is leading its Guinea-worm eradication efforts. People in areas in which the parasite was once rife have learnt to filter their water using cloths and to avoid re-contaminating water supplies. Even the most out-of-the-way villages now quickly contain cases and report them to health officials. Chad was on the cusp of being declared free of Guinea worm in the late 2000s: no case had been recorded in the previous decade. But starting in April 2010, increased surveillance turned up a handful of human infections, and around 60 cases have been recorded since then. The cases are unusually sporadic and isolated from one another, says Mark Eberhard, a parasitologist who consults on Guinea-worm eradication for the Carter Center. More typically, cases occur in clusters and recur in the same village year after year. “There was no increase or explosion of cases as one would expect,” he says. Shortly after these observations, officials began to hear rumours of Guinea-worm-infected dogs in Chad. Researchers have known for decades that dogs, leopards and other mammals occasionally acquire Guinea-worm-like infections, but they assumed that these cases stemmed from distinct species of Dracunculus, the nematode worm that causes the disease, or were rare examples of infections that had somehow spilt over from an outbreak in humans. But in Chad, researchers now think that dogs are spreading the worms to humans — not the other way around. Between January and October 2015, officials recorded 459 canine infections from 150 villages in the central African nation — an unprecedented volume. And genome sequencing has confirmed that dogs in Chad are infected by the same nematode worms (Dracunculus medinensis) that plague humans (M. L. Eberhard et al. Am. J. Trop. Med. Hyg. 90, 61–70; 2014). To better understand the situation, a team led by James Cotton and Caroline Durrant, genome scientists at the Wellcome Trust Sanger Institute in Hinxton, UK, is now sequencing the genomes of more Guinea worms collected from dogs and humans in Chad to confirm that dogs are indeed transmitting the disease to people. And Eberhard, who is convinced that this is the case, is trying to determine how dogs become infected in the first place. They are unlikely to contract the worms from drinking water, he says, because dogs tend to scare away copepods when they lap. Most of Chad’s cases have occurred among fishing communities along the Chari River, and Eberhard suspects that dogs are eating the entrails of gutted, copepod-eating fish. Dogs then pass the worms to humans by reintroducing the larvae into water. Researchers, including Eberhard, are testing aspects of this hypothesis in ferrets, a common animal model in disease research, but eradication officials in Chad are not waiting for the results before taking action. Since February 2015, they have offered the equivalent of US$20 to people who report Guinea-worm cases in dogs and tie up the animals to prevent them from contaminating water sources. They are also encouraging villagers to bury fish entrails to keep dogs from eating them. And a trial is ongoing to test whether a drug used to treat heartworm — a roundworm parasite common in dogs — has any effect on Guinea worm. Because of Guinea worm’s one-year incubation time, it should be clear before the end of 2016 whether these interventions have worked. Older residents from villages along the Chari River say that their fishing practices have not changed, according to Hopkins, and they cannot recall dogs becoming infected with Guinea worm in the past. But Molyneux says that the dearth of humans transmitting the disease could explain the parasite’s jump to dogs. “If you were Guinea worm and there were only 100 of you left in the world,” he says, “what would you do? You’d get the hell out of the host that’s being targeted and move to something else.”


News Article
Site: http://www.scientificamerican.com

Just about every topic, from eminent domain to “hand” size, has scuttled onto the debate stage this election cycle. But the presidential candidates have uttered little about science policy “It’s been conspicuous by its absence,” says Dr. Peter J. Hotez, Dean of the National School of Tropical Medicine at Baylor College of Medicine. Nonetheless, the Republican frontrunner, Donald Trump, has made public remarks that give voters a glimpse into what some of his scientific policies might be. We asked some science and policy experts to discuss Trump’s stances, and what that could mean for Americans in the future. Go slow on climate action: Trump has tweeted that climate change is a Chinese-driven hoax, though he later called the Tweet a joke. In an interview with Fox and Friends, he called climate change “just a very, very expensive form of tax” and “very hard on business.” Sizing up the science: “There’s been a misperception that either you get a good economy or you protect the environment,” says Peter LaPuma, an associate professor in the Milken Institute School of Public Health at George Washington University. LaPuma, who worked as a sustainable energy consultant for Booz Allen Hamilton before joining George Washington, says many companies have found that sustainable practices actually boost their bottom lines. For example, IT companies like Apple have begun using renewable energy to power their data centers, a switch that often saves money because the cost of energy sources like solar has dropped so much. Immediate action to combat climate change has immediate benefits, according to LaPuma. “Climate change is not just polar bears 100 years from now,” he says. Replacing a coal-fired power plant with a solar farm can benefit health immediately, as well as clearing the air for better views of the country’s natural landscape. Cut the EPA: Trump has said he would cut funding for the Environmental Protection Agency and return environmental protection responsibilities to the states. He claims the agency hurts business, and in an interview with The Wall Street Journal, called the EPA “the laughingstock of the world.” Sizing up the science: “There would be serious repercussions” by 2020 if the EPA were severely downsized or abolished, according to Rice University’s Baker Institute for Public Policy professor Neal F. Lane, who directed the National Science Foundation and later the White House Office of Science and Technology Policy under President Clinton. Lane says the EPA plays a critical role in protecting clean air and drinking water, and that its regulations have helped rehabilitate polluted water bodies like Lake Erie, which was pronounced “dead” in the 1960s. “This is not just a bunch of regulators hugging trees,” he adds. Though states do have a part to play in regulation, the country needs a federal regulating body, according to Lane, because contaminated water and air can cross state borders. That’s not to say citizens shouldn’t weigh in on the agency’s proposed rules. “There will always be a healthy debate between the private sector and the federal government on these regulations,” says Lane. For this reason, he said, the EPA solicits public comment before making new rules. If Congress supported Trump in slashing funds for the EPA or changing the law to remove the agency’s power to regulate, Lane predicts there would be an outcry from overwhelmed governors and “reasonable people who care about their families, their children and their life style.” Alter vaccination schedules to avoid autism: Trump says he favors vaccines, but giving children smaller doses over a longer period of time. He has blamed vaccines for causing autism in children. Sizing up the science: “I remember wanting to throw something at the TV when I heard it,” Hotez says of Trump’s debate statement linking vaccinations and autism. Hotez, who develops vaccinations and also has a daughter with autism, says studies have found no link between autism and vaccination. “The anti-vaxxers keep moving the goalposts,” he says. After scientific studies debunked accusations against specific vaccinations, Hotez says those against vaccinations started a different fad: arguing to change the vaccination schedule to protect children. But infants’ immune systems face up to hundreds of new antigens every day, according to Hotez. Adding a few more in the form of a vaccination does not harm infants. He says changing the FDA’s approved vaccination schedule without clinical testing about immune response could decrease vaccines’ efficacy. To imagine what a future with fewer or less effective vaccines might look like, Hotez suggests voters think of California’s recent outbreak of measles, a true threat to children’s health. “It’s one of the great killers of children in the world,” he says. “One hundred thousand children die every year of measles.” Defund Planned Parenthood: Although Trump says Planned Parenthood does a lot of good for women’s health, he says he would defund its clinics because of their abortion services. Sizing up the science: “The good thing is that he doesn’t think [Planned Parenthood] is evil,” says Amy Tsui, a professor at Johns Hopkins Bloomberg School of Public Health. But, she says, no federal funding has gone to abortion since the Hyde Amendment of 1976 (though Medicaid can fund abortion in the case of rape, incest, or endangerment of the mother’s life). If Trump defunds all Planned Parenthood clinics, even those that don’t perform abortions, then he’ll be “throwing the baby out with the bathwater,” according to Tsui. She says Planned Parenthood’s low-cost care and urban clinic locations, helps low-income women in particular. In fact, Leighton Ku, Director of the Center for Health Policy Research at George Washington University, says that decreased access to Planned Parenthood’s contraception services could increase the rate of unwanted pregnancies and possibly cause a spike in abortions. Abolish and replace the Affordable Care Act: Trump recently released his healthcare plan to replace the Affordable Care Act. Highlights include promises to lower American healthcare cost by allowing insurer bids across state lines, make health insurance tax deductible, and remove barriers to prescription drugs entering from outside the country. Sizing up the science: George Washington’s Ku says the number of Americans without health insurance is at its lowest in recent recorded history, and has reached that point without ballooning healthcare costs. He says he’s concerned that repealing the Affordable Care Act might leave 13 million people insured under the plan without coverage. Allowing insurers to compete across state lines could potentially lower cost, but Ku points out that state insurance standards differ, and Trump has not clarified which state’s rules would apply in interstate deals. Ku also views tax deductibility as a red herring: Low-income Americans, who struggle the most to get insured, already pay little to no taxes on care. Lowering barriers to imported medicine could decrease prices, but Ku warns that pharmaceutical manufacturers will likely try to raise prices outside the U.S. if imports grow more common. This might cut into some of Americans’ savings. Restrictions on some countries, like China, should continue, he says, because of issues with counterfeited pharmaceuticals. Even so, the FDA would need more resources to monitor imports. Regardless, Ku doubts a Republican Congress would go along with Trump’s proposal. In summary, Trump’s proposals have not won over the scientists we consulted. Hotez expressed hope that Trump will bring experts onboard to make more informed proposals if he becomes the Republican nominee. But Lane says he’s skeptical even of that. “Who would he recruit to his science team?” asks Lane. “How capable would they be of providing advice? Of course, I don’t have the answer to that. But it’s a question voters should have in their minds.”

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