Around the Globe

Predictions Upended Down Under, While Fighting Zika
Richard Day
Professor of Clinical Pharmacology
University of New South Wales

irst, I must “eat my hat!” My confident prediction, and the prediction of many others (including all the polls), that we would have a new Prime Minister and change of Government was wrong. Prime Minister Scott Morrison surprised all of us (and possibly himself) by winning the “un-winnable” election on 18 May 2019. So the proposal, forecast by then shadow health minister Catherine King in her National Press Club presentation on 13 February 2019, for “structural reform for healthcare” driven by a bipartisan Health Reform Commission and widely welcomed across the health sector is now “off the agenda.” The incumbent’s plans for our health system, which is considered by many to be in need of reform, are awaited with interest.

Emerging Zika Hazard

Disturbingly, Zika virus has emerged as a significant hazard around the world for pregnant women and their unborn children. The Aedes aegypti mosquito transmits the virus when taking a blood meal from a human host. This has become a concern in Australia as the mosquito is now resident in Far North Queensland, likely migrating from nearby New Guinea and Indonesia where the virus is present.

Scientists at the Commonwealth Science Innovation Research Organisation (CSIRO), the national science organization, have collaborated with colleagues at the University of California San Diego to introduce an anti-ZikV gene into mosquito embryos. One copy of the mutated gene results in almost complete suppression of viral transmission; two copies produced complete suppression. Mosquitos with the anti-ZikV gene are easily identified by their red eyes due to the simultaneous introduction of a second, “red eye” gene. This innovative strategy aimed at the Aedes aegyptii mosquito will be welcome in the more than 80 countries where Chikungunya virus New Guinea is transmitted by this mosquito. Similar approaches will be needed for other viruses/mosquitos that march southward in Australia as the climate heats up. Other emerging concerns in Australia driven by climate change are the arthritogenic chikungunya virus and dengue virus, both also carried by Aedes aegypti and endemic now in Indonesia and New Guinea.

2019 Australian Trial of the Year

On a more positive note, the Australian Clinical Trials Alliance (ACTA) has chosen the best Australian developed, led, and published clinical trials for 2019. Promoting the highest standard clinical trials is key to advancing medical care and ACTA is committed to promoting Australia’s contribution to global health through high quality clinical trials that address important clinical questions. The ASPREE (ASPirin in Reducing Events in the Elderly) study took top honours as the 2019 Australian national trial of the year. Conceived and developed by Professor John McNeil, clinical pharmacologist and epidemiologist of Monash University, Victoria ASPREE was an international, multicentre trial which examined whether daily low-dose aspirin prevented or delayed age-related conditions including cardiovascular disease, dementia, depression, and some cancers in the apparently healthy elderly. The placebo-controlled trial, published in the New England Journal of Medicine in October 2018, was the biggest primary prevention aspirin study to-date, with almost 20,000 healthy seniors over 70 years participating. The study had a huge impact, showing there was no clinical benefit but significant harm, especially bleeding, liberating the elderly from taking aspirin to prevent disease.

The other finalists for best Australian clinical trial of the year, similarly published in NEJM, were large, randomized controlled trials addressing important clinical questions using rigorous methodology. ADRENAL (ADjunctive CorticosteRoid TrEatment iN CriticAlly ilL patients with septic shock) showed parental adrenocorticosteroids (hydrocortisone), used extensively in Intensive Care Units for patients with septic shock on ventilators, did not reduce mortality at 90 days compared to placebos. RELIEF (REstrictive versus LIbEral Fluid Therapy for Major Abdominal Surgery) showed that recommended fluid restriction around abdominal surgery not only did not deliver better outcomes than liberal fluid replacement but resulted in higher rates of acute kidney injury.

All three Australian studies have translated immediately to better and safer care of hundreds of thousands of people around the world; and, importantly, they have set the standard for asking critical questions and investing in undertaking high quality clinical trials to definitively answer these questions.