Significant step taken in search for new malaria vaccine

Researchers from the Walter and Eliza Hall Institute of Medical Research have taken a significant step toward developing a new vaccine for malaria, revealing for the first time an “atomic-scale” blueprint of how the parasite invades human cells. Using the Nobel Prize-winning technology cryo-EM (cryo-electron microscopy), the researchers mapped the previously hidden first contact between Plasmodium vivax malaria parasites and the young red blood cells they invade to begin the parasites’ spread throughout the body. Their research, published in Nature, solves the mystery of the molecular machinery the parasite uses to latch on to red blood cells. This essential step in the malaria lifecycle is the beginning of the classical symptoms associated with malaria – fever, chills, malaise, diarrhoea and vomiting – which can last weeks or even longer. “We’ve now mapped, down to the atomic level, exactly how the parasite interacts with the human transferrin receptor,” said Associate Professor Wai-Hong Tham. Guided by the 3D map, the team was able to tease out the precise details of the parasite–host interaction, identifying its most vulnerable spots. The team also “solved” how antimalarial antibodies bind to and block P. vivax parasites to stop them from invading red blood cells, using x-ray crystallography facilities at the Australian Synchrotron. “With this crystal map, we have identified additional ‘weak spots’ that could be exploited as therapeutic targets,” the researchers said. “The information allows us to go back to the parasite and pull out the part of the protein that will make the best possible vaccine.”

New way to reverse drug resistance in some cancers

University of Queensland (UQ) researchers have discovered how to reverse drug resistance in skin and mouth squamous cell carcinomas. Associate Professor Nicholas Saunders, from UQ Diamantina Institute, said squamous cell carcinomas were curable when diagnosed early but difficult to eradicate once the cancer spread. “The drugs used to treat squamous cell carcinomas that have spread to other parts of the body only work for a small fraction of patients. In our study, we successfully added a new drug to an existing treatment to make squamous cell carcinomas responsive to treatment.” Researchers found that a protein called E2F7 was controlling drug resistance in the affected cells. “More than 80% of squamous cell carcinomas we examined had a unique defect in the protein,” Associate Professor Saunders said. “In normal cells, E2F7 stays within the nucleus of a cell and blocks drug resistance. We discovered that in most squamous carcinomas, E2F7 is pumped out of the nucleus, meaning it can no longer stop drug resistance occurring. By administering a drug that helps to keep E2F7 in the nucleus, the cancer cells become sensitive to existing chemotherapeutics.” The study was published in Science Translational Medicine.

Penicillin allergies linked to greater risk of superbug infections

Patients who have a penicillin allergy recorded in their medical records are at an increased risk of developing the drug resistant “superbug” infection MRSA (methicillin-resistant Staphylococcus aureus) and health care-associated infection Clostridium difficile, according to US research published in The BMJ. To evaluate the public health consequences of a penicillin allergy label, researchers at Massachusetts General Hospital in Boston examined the relation between penicillin allergy and development of MRSA and C. difficile. Using data from the Health Improvement Network, an electronic medical record database of 11 million UK patients, they identified 64 141 adults with a documented penicillin allergy and 237 258 matched adults of similar age and sex, with recent penicillin exposure but without a penicillin allergy. None of the participants had any history of MRSA and C. difficile infection and were followed up for an average of 6 years, during which time use of antibiotics and cases of doctor-diagnosed MRSA and C difficile were recorded. A total of 1345 participants developed MRSA and 1688 developed C. difficile over the follow-up period. After adjusting for several known risk factors, the researchers found that a penicillin allergy label was associated with a 69% increased risk of MRSA and a 26% increased risk of C. difficile. The results show that increased use of broad spectrum antibiotics accounted for more than half (55%) of the increased MRSA risk and more than one third (35%) of the increased C. difficile risk among patients with a listed penicillin allergy. The researchers argued that addressing penicillin allergies “may be an important public health strategy to reduce the incidence of MRSA and C. difficile among patients with a penicillin allergy label.” Penicillin allergy is the most commonly documented drug allergy, reported by about 10% of patients. However, previous studies have shown that more than 90% of patients with listed penicillin allergies can be safely treated with penicillin.

What’s new online at the MJA

2 July Podcast with Professor Geoffrey Thompson, Deputy Medical Editor at the MJA, talking about the MJA’s Indigenous issue … OPEN ACCESS permanently.

2 July Podcast with Dr Deborah Randall, from the Centre for Big Data Research in Health, and Professor Sandra Eades, from the Sax Institute and Baker IDI Heart and Diabetes Institute … OPEN ACCESS permanently.

2 July Podcast with Associate Professor James Ward, Head of the Aboriginal Health, Infectious Diseases at the South Australian Health and Medical Research Institute … OPEN ACCESS permanently.

2 July Podcast with Adjunct Professor Garry Egger, board member of the Australian Society for Lifestyle Medicine, and Conjoint Professor Bob Morgan, from the Wollotuka Institute at the University of Newcastle … OPEN ACCESS permanently.

 

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