Research news in brief

Dengue-carrying mozzies engineered to resist

American researchers have reported in PLOS Neglected Tropical Diseases that the mosquitoes that carry dengue virus (DENV) can be genetically engineered to have an increased resistance to infection by the virus. When a mosquito bites a person infected with DENV, the virus has to complete its lifecycle in the mosquito’s gut, eventually infecting its salivary glands, before it can infect another person. Previous studies have shown that mosquitoes rely on a molecular pathway, dubbed JAK/STAT, to try to fight DENV infection and stop this cycle. Proteins known as Dome and Hop are involved in turning on the JAK/STAT when the mosquito is infected with DENV. The researchers from Johns Hopkins University genetically engineered Aedes aegypti mosquitoes to turn on expression of either Dome or Hop, in the fat body (a dynamic tissue that plays a major role in the metabolic functions of insects), earlier in infection — immediately after ingesting blood — and make more of the proteins. Mosquitoes with engineered versions of Dome or Hop that were then infected with DENV had 78.18% (Dome) and 83.63% (Hop) fewer copies of the virus in their guts, as well as significantly less virus in their salivary glands. Mosquitoes with the altered genes had normal lifespans, but produced fewer eggs than normal mosquitoes. When the researchers repeated the experiments with Zika virus and chikungunya virus, no impact was seen on infection, suggesting that the importance of the JAK/STAT pathway in the fat body tissue is unique to DENV. However, the researchers believe that it may be possible to achieve improved or total resistance to dengue and other viruses by promoting expression of additional transgenes in multiple tissues.

Gastric acid suppressants linked to hospitalisation

Research out of the Australian National University has found a link between popular heartburn drugs and an increase in the risk of infectious gastroenteritis – an illness that results in 13.1 million lost days of work in Australia a year. The study, published in PLOS ONE, was based on data from the Sax Institute’s 45 and Up Study, and found that people who take proton pump inhibitors (PPIs) had a 70% increase in the risk of being admitted to hospital with infectious gastroenteritis. The research examined cases of infectious gastroenteritis in Australians aged over 45 years. “[We found that taking] PPIs … increased [the] risk of infectious gastroenteritis hospitalization,” the authors wrote, and commented that one potential explanation is increased colonisation and proliferation of pathogens secondary to acid suppression. The association was not seen for H₂ receptor antagonist users. The authors also found that among PPI users, there was a dose–response relationship between the average daily dose dispensed and infectious gastroenteritis hospitalisation (P_trend < 0.001). PPIs are one of the world’s most commonly used gastric acid suppressants, with more than 19 million scripts prescribed annually in Australia. The research builds on a report by the ANU National Centre for Epidemiology and Population Health which found 15.1 million gastroenteritis cases in Australia in 2010.

Amygdala links stress to heart disease and stroke

Heightened activity in the amygdala – a region of the brain involved in stress – is associated with a greater risk of heart disease and stroke, according to a study published in The Lancet that provides new insights into the possible mechanism by which stress can lead to cardiovascular disease in humans. The researchers from Massachusetts General Hospital and Harvard Medical School in the United States suggested that these findings could eventually lead to new ways to target and treat stress-related cardiovascular risk. In this study, 293 patients were given a combined positron emission tomography and computed tomography scan. Resting amygdala metabolic activity, bone marrow activity and arterial inflammation were assessed using validated methods. The patients were then tracked for an average of 3.7 years to see if they developed cardiovascular disease. In this time, 22 patients had cardiovascular events including heart attack, angina, heart failure, stroke and peripheral arterial disease. Those with higher amygdala activity had a greater risk of subsequent cardiovascular disease, and were also found to have increased bone marrow activity and arterial inflammation. The increased risk of cardiovascular disease seemed to be mediated by the increased bone marrow activity and arterial inflammation. The authors suggested a possible biological mechanism, whereby the amygdala signals to the bone marrow to produce extra white blood cells, which in turn act on the arteries causing them to develop plaques and become inflamed, which may then cause heart attack and stroke. A small substudy of 13 patients who had a history of post-traumatic stress disorder also had psychometric testing to assess their stress levels. In this group, perceived stress was associated with amygdala activity, arterial inflammation and C-reactive protein. The researchers noted that increased bone marrow activity and arterial inflammation only partly account for the association between amygdala activity and cardiovascular disease, and there are likely to be additional contributory mechanisms. They also acknowledged that more research and larger studies are needed to confirm the mechanism.

Gut bug check could save heart attack victims

Researchers from the Lerner Research Institute in the US have found that measuring the levels in the blood of a molecule called trimethylamine N-oxide (TMAO), which is produced by the gut bacteria from components of red meat, eggs and dairy products, could give them a quick and reliable way of assessing the risk of death and other major heart problems in patients who arrive at hospital emergency departments with chest pain. Moreover, TMAO levels could predict this risk not only in the short term (over the first 30 days), but also the risk of death in the longer term (up to 7 years later). The study, published in the European Heart Journal, found that TMAO levels predicted higher risks of serious heart problems and death even in patients who did not have elevated troponin T levels. The researchers examined TMAO levels in the blood of 530 patients, aged over 18 years, arriving at the emergency department of the Cleveland Clinic (Ohio, US) with chest pains, and 1683 patients who had coronary angiography within 5 days after being admitted to one of four university hospitals in Switzerland (Zurich, Bern, Lausanne and Geneva) with chest pains. The patients were followed up for several years to monitor for outcomes such as death from any cause, death from heart and blood vessel problems, heart attack, stroke or revascularisation – collectively termed “major adverse cardiovascular events” (MACE). They found that the Cleveland patients with higher TMAO levels were more likely to experience MACE at 30 days, 6 months and 7 years after their admittance to hospital. After adjusting for risk factors, such as age, smoking, diabetes cholesterol levels and blood pressure, when compared with patients with the lowest TMAO levels, those with levels in the top 25% were around six times more likely to die, have a heart attack or stroke or require revascularisation at 30 days and 6 months, and nearly twice as likely to die within 7 years. Even in patients who did not appear to have elevated levels of troponin T when they first arrived at hospital, those with the TMAO levels in the top 25% still had a nearly six-fold higher risk of MACE. Co-author, Dr Slayman Obeid, junior consultant at the University Heart Centre, Zurich, said: “TMAO offers a better understanding of the clinical impact that our daily diet has on the cardiovascular system, specifically in patients presenting with acute coronary syndrome. This opens the way for new preventive measures, such as encouraging patients to switch from a diet rich in red meat, dairy products and eggs to a Mediterranean diet rich in green leafy vegetables and fibre. In addition, drugs could be developed that target the process by which bacteria in the gut interact with food to make TMAO”.

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