Research news and online first at the MJA

Hepatitis B virus found in Bronze Age tissue samples

Two studies by researchers from the University of Cambridge, in the UK have sequenced the genomes of Bronze Age humans and revealed evidence of hepatitis B virus (HBV) in 25 of the 304 individuals studied, suggesting that humans throughout Eurasia were infected with HBV for thousands of years. In the first study, published in Nature, the researchers sequenced the genomes of 137 ancient humans from the Eurasian steppes — a vast region spanning about 8000 km from Hungary to northeastern China — covering a period of about 4000 years. They also studied genomic data from 502 individuals from present-day self-reported ancestries across Central Asia, Altai, Siberia and the Caucasus. The findings shed light on the population history of the region, suggesting a gradual transition from Bronze Age pastoralists of Eurasian ancestry towards mounted warriors with primarily East Asian ancestry. In the second study, also published in Nature, they analysed ancient DNA sequences from 304 central and western Eurasian humans, who lived between about 2000 and 7000 years ago. They reported evidence of HBV infections in 25 individuals, spanning a period of almost 4000 years. The authors recovered 12 full or partial HBV genomes — including genotypes that are now extinct — that they analysed together with contemporary human and non-human primate HBV genomes. They showed the existence of ancient HBV genomes in regions incongruent with their present-day distribution, and at least one now-extinct genotype. Discovery of further ancient viral sequences may provide a clearer picture of the true origin and early history of HBV, and aid the understanding of the contributions of natural and cultural changes to disease burden and mortality.

Early antibiotic use: does it reduce vaccine effectiveness?

Researchers from the South Australian Health and Medical Research Institute at Flinders University have shown that in preclinical models, antibiotic exposure in infant mice impairs their responses to five important, routine vaccines that are administered daily around the world, including vaccines against meningitis, pneumonia, tuberculosis and whooping cough. Published in Cell Host and Microbe Today, the study showed that “it appears that antibiotics in the first year of life change the way the body builds immunity and responds to vaccination”, according to lead author Associate Professor David Lynn. His team has established a clinical study at the Women’s and Children’s Hospital in Adelaide to identify whether this phenomenon also happens in human infants, and to explore how the healthy gut microbiome influences the effectiveness of vaccination.

HPV vaccine safe and effective, says Cochrane review

New evidence published in the Cochrane Library shows that human papilloma virus (HPV) vaccines protect against cervical lesions in young women, particularly in those who are vaccinated between the ages of 15 years and 26 years. A team of Cochrane researchers summarised results of 26 studies in 73 428 women conducted across all continents over the past 8 years. Most women in the studies were under the age of 26 years, although three trials recruited women aged between 25 and 45 years. The studies were well designed, randomly allocating the women to either HPV vaccine or a placebo. The review evaluated evidence for two vaccines: the bivalent vaccine targeting HPV16 and 18, and the quadrivalent vaccine targeting HPV16/18 and two low risk HPV types causing genital warts. The newer vaccine that targets nine HPV types was not included in the review since it has not been compared against a placebo in a randomised controlled trial. The review looked at two groups of people: women who were free of high risk HPV at the time of vaccination, and all women regardless of HPV status at vaccination. As none of the studies followed up participants for long enough to detect an effect on cervical cancer, the effects of the vaccine were measured as pre-cancer associated with HPV16/18 and pre-cancer irrespective of HPV type. The review looked at data from ten trials assessing cervical lesion data at between 3.5 to 8 years after vaccination. They found that in young women who did not carry HPV, vaccination reduced the risk of developing cervical pre-cancer from about 164 per 10 000 women in the placebo arm to about 2 per 10 000 women in the vaccine arm. In data from all enrolled women aged 15–26 years irrespective of HPV status at vaccination, vaccines reduced the risk of cervical pre-cancer associated with HPV16/18 from 341 to 157 per 10 000. HPV vaccination reduced also the risk for any pre-cancer lesions from 559 to 391 per 10 000. In older women vaccinated between 25 to 45 years, the HPV vaccine does not appear to work as well, possibly because older women are more likely to have been already exposed prior to vaccination. The evidence also shows that the vaccines do not appear to increase the risk of serious side effects which was about 7% in both HPV vaccinated or control groups. The researchers did not find increased risk of miscarriage in women who became pregnant after vaccination. However, they emphasised that more data are required to provide greater certainty about very rare side effects and the effect vaccines have on rates of stillbirth, and babies born with abnormalities in those who became pregnant around the time of vaccination.

Bone density treatment slows leukaemia

Researchers from the Telethon Kids Institute may have unlocked a vital key to reducing the progression of leukaemia in children, potentially prompting a change in thinking around the best way to target treatment. In research published in Leukemia, a team led by Dr Laurence Cheung described how they had identified the mechanism of bone loss that occurred during the development of leukaemia – which, when treated, was able to reduce leukaemia progression. The team’s study focused on the most common form of leukaemia in children, a subtype of acute lymphoblastic leukaemia (ALL) known as pre-B ALL. “When we created a pre-clinical model replicating this kind of leukaemia, we witnessed substantial bone loss during the development of the cancer,” Dr Cheung said. The researchers wanted to discover what was causing the bone loss, and identified a signal produced by the leukaemia cells which instructed cells in the microenvironment – osteoclasts – to eat away at the bone. They used a commercially available drug called zoledronic acid – already known to be safe for children and used to treat brittle bone disease – to target the cells in the microenvironment around the leukaemia cells. Dr Cheung said that the findings, although pre-clinical, were promising and suggested that targeting the microenvironment around leukaemia cells could not only help fight leukaemia, but simultaneously provide relief for one of its most common and painful side effects: bone loss. “Importantly, we found that this not only compensated for the leukaemia-dependent bone fragility, but also reduced leukaemia progression,” Dr Cheung said. “Our finding that the cells surrounding the leukaemia cells can contribute to treatment failure or success has led to a paradigm shift. It means this potentially could be a powerful adjuvant therapy. It’s not going to replace chemotherapy, but we propose that using chemotherapy and treating the microenvironment at the same time will have more benefit than just the chemotherapy by itself.”

What’s online first at the MJA

14 May Research: Psychological distress in remote mining and construction workers in Australia
Bowers et al; doi: 10.5694/mja17.00950
Psychological distress is significantly more prevalent in the remote mining and construction workforce than in the overall Australian population … OPEN ACCESS permanently.

14 May Podcast with Dr Jennifer Bowers, Managing Director of Rural and Remote Mental Health … OPEN ACCESS permanently.

14 May Research: RedUSe: reducing antipsychotic and benzodiazepine prescribing in residential aged care facilities
Westbury et al; doi: 10.5694/mja17.00857
A multi-strategic, interdisciplinary intervention can reduce inappropriate prescribing of psychotropic agents … OPEN ACCESS permanently.

14 May Podcast with Dr Juanita Westbury, senior lecturer in Dementia Care at the Wicking Dementia Research and Education Centre … OPEN ACCESS permanently.

14 May Research: Effects of post-discharge management on rates of early re-admission and death after hospitalisation for heart failure
Huynh et al; doi: 10.5694/mja17.00809
Early re-admission rates after hospitalisation for heart failure are primarily explained by differences in post-discharge management … OPEN ACCESS permanently.

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