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Bird flu has been spreading undetected in US cattle for months

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Jaime Guevara-Aguirre (back left), Valter Longo (back right), and several of the Laron study participants at the USC Leonard Davis School of Gerontology in Los Angeles.

Jaime Guevara-Aguirre (back left) and Valter Longo (back right) pose with several of the Laron study participants.Credit: Courtesy Jaime Guevara-Aguirre & Valter Longo

People with Laron syndrome — a growth-hormone-receptor condition — seem to be at lower risk of developing cardiovascular disease than relatives who do not have the syndrome. Laron syndrome had already been linked to health benefits including protection against diabetes, cancer and cognitive decline. “They seem to be protected from all the major age-related diseases,” says biogerontologist Valter Longo, a co-author on the cardiovascular study. It’s unclear if people with Laron syndrome live longer on average than those without it, but mice with a similar condition live for about 40% longer than do control animals.

Nature | 6 min read

Reference: Med paper

The H5N1 strain of avian influenza has been spreading undetected in US cattle for months, according to a preliminary analysis of genomic data released by the US Department of Agriculture. The outbreak is likely to have begun when the virus jumped from an infected bird into a cow, probably around late December or early January. But the publicly released data do not include critical information that would shed light on the outbreak’s origins and evolution. “In an outbreak response, the faster you get data, the sooner you can act,” says genomic epidemiologist Martha Nelson. “Whether we’re not too late, to me, that’s kind of the million dollar question.”

Nature | 5 min read

On the outskirts of Beijing, researchers from all over the world have come together at the Synergetic Extreme Condition User Facility to push matter to its limits with extreme magnetic fields, pressures and temperatures, and examine it in new ways with extremely precise resolution in time. One particularly tantalizing goal for many researchers using this US$220-million toolbox is to discover new superconductors, materials that conduct electricity without resistance. Nature reporter Gemma Conroy steps inside to take a look.

Nature | 6 min read

Features & opinion

Climate change is completely reshaping the ecosystem in one of the best-studied Arctic fjords, on the northwest side of the Norwegian archipelago Svalbard. Since the inlet stopped freezing over during the winter, Arctic mammals such as beluga whales have left and more southerly animals including Atlantic puffins have moved in. New habitats have popped up along the shoreline where sea ice once suffocated plant growth. “It’s incredible that I — in my time — have been able to see such dramatic changes,” says ecotoxicologist Geir Wing Gabrielsen.

Nature | 7 min read

“Lots of our members call us ‘the magic money tree’,” says Alison Baxter, head of communications for the Authors’ Licensing and Collecting Society (ALCS), a UK agency that compensates authors when their works are copied or shared after publication. Such societies also collect royalties on behalf of scientists, for example when their paper is printed out and distributed to students. Anyone with publications to their name (and to which they own the copyright) can join a collecting society — though many people don’t, because of the misconception that it might be a scam. For those who do join, the rewards can be welcome: for example, each ALCS member received an average of around £450 this year.

Nature | 7 min read

The debate between physicists Niels Bohr and Albert Einstein over what quantum mechanics ‘really means’ has evolved into a long-standing myth, writes science writer Jim Baggott. Einstein rejected the possibility of some of the quantum weirdness implied by the theory, such as ‘spooky action at a distance’. Bohr’s ‘Copenhagen interpretation’ has been interpreted by some as ‘shut up and calculate’. But the idea that Bohr and his followers heavy-handedly imposed his view as a dogmatic orthodoxy doesn’t hold water, argues Baggott. In reality, “by the 1950s, the physics community had become broadly indifferent…. Quantum mechanics worked. Why worry about what it meant?” Nevertheless, the myth had a role in motivating the singular personalities that challenged it, laying the foundations for quantum computing.

Nature | 13 min read

Working as a scientist at an environmental non-profit organization can be similar to academic research, but requires a change of mindset: studies must always address real-world challenges. Jobs are usually advertised on job boards or LinkedIn, and it’s important for applicants to emphasize soft skills alongside scientific achievement. “It’s the same educational background and the same research, but just the way that I describe things had to shift completely,” says ecologist Kenneth Davidson. For early-career scientists who make the leap, non-profits can provide more job security and flexibility than academia.

Nature | 9 min read

Where I work

Matthew Nitschke guides a pipette filled with brown liquid over some bleached corals in a tank

Matthew Nitschke is a senior research scientist at the Australian Institute of Marine Science, and a research fellow at Victoria University of Wellington, New Zealand.Credit: Giacomo d’Orlando for Nature

For ten years, Matthew Nitschke and his colleagues at the Australian Institute of Marine Science have been growing coral symbionts in the laboratory while gradually raising the heat. “Each time the symbionts adapt, we push the temperature up a bit,” says Nitschke. “They can now survive a constant 31 °C.” The goal is to develop corals able to survive waters warmed by climate change. “Studying marine conservation is hard,” says Nitschke. “Marine ecosystems are degrading. Coral reefs are bleaching: by 2060, without significant emissions reductions, mass coral bleaching on the Great Barrier Reef could be an annual event.” The next step is small-scale field trials out on the reef. (Nature | 3 min read)

Our award-winning ‘Where I Work’ series is now on display as a beautiful large-scale photography exhibition near the Nature offices in King’s Cross, London. If you’re near, do drop by (it’s free). Otherwise, check out the virtual exhibition online.

QUOTE OF THE DAY

Computational biologist Jitao David Zhang says his misconceptions about vocational training were demolished when he experienced first-hand the apprenticeship culture in Germany and Switzerland. (Nature | 7 min read)

On Friday, Leif Penguinson was hiding among the lush mangroves in Ujung Kulon National Park, Indonesia. Did you find the penguin? When you’re ready, here’s the answer.

Thanks for reading,

Flora Graham, senior editor, Nature Briefing

With contributions by Katrina Krämer and Smriti Mallapaty

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Bird flu virus has been spreading in US cows for months, RNA reveals

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A Robotic milker, milks Jersey dairy cows in the milking parlor at the Twin Brook Creamery August 6, 2019 in Lynden, Washington, USA.

A cow is milked in Washington State.Credit: USDA Photo/Alamy

A strain of highly pathogenic avian influenza has been silently spreading in US cattle for months, according to preliminary analysis of genomic data. The outbreak is likely to have begun when the virus jumped from an infected bird into a cow, probably around late December or early January. This implies a protracted, undetected spread of the virus — suggesting that more cattle across the United States, and even in neighbouring regions, could have been infected with avian influenza than currently reported.

These conclusions are based on swift and summary analyses by researchers, following a dump of genomic data by the US Department of Agriculture (USDA) into a public repository earlier this week. But to scientists’ dismay, the publicly released data do not include critical information that would shed light on the outbreak’s origins and evolution. Researchers also express concern that the genomic data wasn’t released until almost four weeks after the outbreak was announced.

Speed is especially important for fast-spreading respiratory pathogens that have the potential to spark pandemics, says Tulio de Oliveira, a bioinformatician at Stellenbosch University in South Africa. The cattle outbreak is not expected to allow the virus to gain the ability to spread between people, but researchers say it is important to be vigilant.

“In an outbreak response, the faster you get data, the sooner you can act,” says Martha Nelson, a genomic epidemiologist at the National Center for Biotechnology Information (NCBI) in Bethesda, Maryland. Nelson adds that with every week that goes by, the window for controlling the outbreak narrows. “Whether we’re not too late, to me, that’s kind of the million dollar question.”

Single spillover

Federal officials announced on 25 March that a highly pathogenic bird-flu strain had been detected in dairy cows. The USDA has since confirmed infections with the strain, named H5N1, in 34 dairy herds in nine states. In late March and early April, the USDA posted a handful of viral sequences from cows sampled in Texas and a sequence from a human case, on the widely used repository GISAID.

On 21 April, the USDA posted more sequencing data on the Sequence Read Archive (SRA), a repository maintained by the NCBI. The latest upload included some 10 gigabytes of sequencing information from 239 animals, includings cows, chickens and cats, says Karthik Gangavarapu, a computational biologist at Scripps Research in La Jolla, who processed the raw data.

Analysis of the genomes suggests that the cattle outbreak probably began with a single introduction from wild birds in December or early January. “It’s good news that there’s only been one jump that we can discern so far. But bad news, in many ways that it has been spreading for probably several months already,” says Michael Worobey, an evolutionary biologist at the University of Arizona in Tucson, who has analysed the genomes.

“This virus is clearly transmitting among cows in some way,” says Louise Moncla, an evolutionary virologist at the University of Pennsylvania in Philadelphia, who has studied the genomic data.

Nelson, who is analysing the data, says she was most surprised by the extent of the genetic diversity in the virus infecting cattle, which indicates that the virus has had months to evolve. Among the mutations are changes to a viral-protein section that scientists have linked to possible adaptation to spread in mammals, she says.

The data also show occasional jumps back from infected cows to birds and cats. “This is a multi-host outbreak,” says Nelson.

A single jump, many months ago, is “the most reliable conclusion you can make,” based on the available data, says Eric Bortz, a virologist at the University of Alaska Anchorage. But an important caveat is that it isn’t clear what percentage of infected cows the samples represent, he says.

Fill in the blank

That’s only one of many data gaps. Scientists lack information about each sample’s precise collection date and the state where it was collected. Such gaps are “very abnormal,” Nelson says.

The missing ‘metadata’ make it harder to answer many open questions, such as how the virus is transmitted between cows and herds, and make it tricky to pin down exactly when the virus jumped to cows. These insights could help to control further viral spread, and protect workers on cattle farms “who can least afford to be exposed,” says Worobey.

Worobey, Gangavarapu and their colleagues are now racing to analyse some metadata uncovered through online sleuthing by Florence Débarre, an evolutionary biologist at the French national research agency CNRS in Paris. Gangavarapu says dates and geographic information for 152 of the 239 samples have been extracted from a USDA presentation posted on YouTube on 26 April.

Researchers also want more swabbing of cattle and wild birds to gain more insights into the outbreak’s exact origin and to decipher another puzzle. The genomic data reveal that the viral genome sequenced from the infected person does not include some of the signature mutations observed in the cattle. “That is a mystery to everyone,” says Nelson.

One possibility is that the person was infected by a separate viral lineage, which infected cattle that have not been swabbed. Another less likely scenario, which can’t be ruled out, says Nelson, is that the person was infected directly from a wild bird. “It raises just a whole slew of questions about what black box of samples we are missing.”

Shilo Weir, a public affairs specialist at the USDA, says the agency decided to post the unanalysed sequence data on the SRA to make it public as soon as possible. Weir says the agency will “work as quickly as possible” to publish curated files on GISAID with relevant epidemiological information, and will continue to make raw data available on the SRA on a rolling basis.

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Fungal diseases are spreading undetected

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Two people wearing surgical gowns, face masks, and hair coverings, stand on either side of a patient (lying down in centre of image), performing surgery

Surgeons operate to remove ‘black fungus’ from a person’s lung.Credit: Prakash Singh/AFP via Getty

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In mid-2021, a deadly fungal disease called mucormycosis began surging in India’s crowded hospitals. Often referred to as ‘black fungus’, and caused by various common mould species, mucormycosis typically invades structures in the face and brain. But during the Indian outbreak, thousands of people in hospital — most of them undergoing steroid treatment for severe COVID-19 — developed fungal infections that festered unseen in the lungs1. “We missed a lot of pulmonary mucormycosis during COVID,” says microbiologist Arunaloke Chakrabarti, director of the Doodhadhari Burfani Hospital and Research Institute in Haridwar, India. The expertise and tests needed to diagnose the condition were frequently unavailable, Chakrabarti says, and many people died before they could be treated.

India’s experience with mucormycosis reflects a broader diagnostic predicament: many low- and middle-income countries (LMICs) lack even the most basic tools for detecting the fungal diseases that kill an estimated 2.5 million people each year2. Misdiagnosis often leads to incorrect treatment, and, because people who are immunocompromised are particularly at risk, expanding use of steroids and other immune-suppressing drugs is contributing to the growth of vulnerable populations. People with HIV, cancer and respiratory diseases are especially at risk, particularly where poor sanitation and over-crowding aids the spread of fungal pathogens3.

As fungal disease rates rise steadily, efforts to shore up the ability of LMICs to diagnose the conditions have taken on a new urgency. In 2022, the World Health Organization (WHO) released its first-ever ranking of fungal health threats, with the aim of strengthening the global response to infections. The report emphasized that expanded access to diagnostics will help policymakers to better assess the burden of fungal diseases, so that resources and attention can be allocated more appropriately.

A global problem

Surveys of diagnostic capacity in LMICs over the past few years reveal a dire situation. Methods in many places are limited to conventional microscopy and fungal culture, both of which have shortcomings. Microscopy, for example, requires the expertise of people who can identify fungal pathogens by their appearance. Such specialists are typically unavailable in remote settings. And it can take up to one month to culture a sufficient quantity of fungal cells for microscopic analysis. That’s too long for people who are acutely ill, such as those “with fungal sepsis or fungal meningitis, who need a more immediate diagnosis”, says Marcio Louenco Rodrigues, a mycologist at the Oswaldo Cruz Foundation, a research institute in Curtiba, Brazil. Certain pathogens, including Pneumocystis jirovecii, which causes pneumonia, can’t be cultured at all.

In the absence of a diagnosis, physicians will often treat suspected infections on the basis of symptoms. But that approach comes with risks. Some fungal pathogens, including Mucorales, Histoplasma and Aspergillus cause lethal pulmonary infections that can be easily confused with tuberculosis, which is a bacterial disease4. Fungal infections don’t respond to antibiotics. And by the time people who are initially misdiagnosed with tuberculosis receive antifungal therapy, “many are already dying”, says Claudia Banda, an infectious-disease specialist at Cayetano Heredia University in Lima, Peru.

A key step towards boosting diagnostic capacity is to broaden access to simple, point-of-care assays that can be used cheaply in remote settings. “This is what developing countries really want,” says David Denning, a research clinician at the University of Manchester, UK. Denning was the founding president of the Global Action Fund for Fungal Infections (GAFFI), a non-governmental advocacy group headquartered in Geneva, Switzerland. GAFFI played a key part in selecting tests for fungal diseases for the WHO’s list of essential diagnostics, which was first released in 2018.

Topping that list are lateral flow assays that generate fast diagnostic results and cost less than US$5 each. These sorts of assay will be familiar to many as home-test kits for COVID-19. They detect microbial antigens or immune antibodies in blood and other fluids and have already been standardized for several fungal pathogens. For example, the WHO recommends screening people with HIV who have critically low white blood cell counts for cryptococcal antigen, which would indicate the presence of a harmful fungal infection that can cause meningitis5.

Lateral flow assays detect Cryptococcus with high accuracy. But in Africa — which is home to around 65% of people in the world with HIV — only around 25% of the population has access to the test, according to a survey funded by GAFFI3. And Latin American countries have similar shortages. In 2023, Banda and her colleagues surveyed Peru’s public hospitals, and found that only 13% of them could provide cryptococcal antigen testing (unpublished data).

A push to expand access

Uptake is thwarted by a lack of awareness of fungal infections, says Rodrigues, adding that for many fungal pathogens, there are no lateral flow tests. Cost is also a barrier, because although the price per test is low, rolling them out at scale would impose substantial burdens on already stretched health-care systems.

Image on left: black and white brain image with orange area to the right of centre. Image on Right: green spherical fungus particles of varying sizes, on dark background

A brain scan reveals cryptococcal meningitis, which can be caused by the fungus Cryptococcus neoformans (right).Credit: Cultura Creative RF/Alamy; Dennis Kunkel Microscopy/SPL

Routine use of the assay could save many lives — Cryptococcus kills nearly 150,000 people a year2. However, Banda points out that the main drug therapy for cryptococcal meningitis, amphotericin B, is also exceedingly toxic, “so we like to have some definitive evidence of the disease before we start treatment”.

Broadening diagnostics for other fungi that can cause serious illness, such as Aspergillus and Histoplasma, could also save lives. According to Denning, as many as 10% of people with suspected tuberculosis actually have chronic pulmonary aspergillosis. “So, all tuberculosis clinics around the world should be testing for it,” he says. Denning’s research on the global incidence of fungal diseases found that more than 2 million people each year develop invasive aspergillosis2, which occurs when the fungi spreads through the body. Histoplasmosis is also endemic in many LMICs, and if left untreated, mortality in people with HIV is 100%, Banda says.

Banda’s fungal-disease work in Peru, which is funded by the US Centers for Disease Control and Prevention, shows that histoplasmosis is endemic among people with HIV, cancer and other immune-suppressing conditions who live in and around the country’s coastal jungles. Bat droppings in these areas are a ready source of the fungus spores. Accurate estimates of the number of people affected are unavailable, however, owing to the lack of access to diagnostic testing, Banda says. She cites a similar need for access for chronic pulmonary aspergillosis and Candida auris — a hospital scourge that’s notoriously difficult to eliminate or control. The fungus C. auris, in particular, is an emerging global-health threat; some strains resist all antifungals and incur death rates as high as 70%. In Peru, the pathogen emerged several years ago, “and not all our microbiology labs are adequately prepared for it”, Banda says.

Advocates are calling for lateral flow assays to be developed for a broader array of fungal diseases. Along those lines, researchers at the University of Exeter, UK, are developing an assay specific to Rhizopus arrhizus6 — a fungal spore responsible for most human cases of mucormycosis, the disease that plagued India during the COVID-19 pandemic.

But lateral flow assays can’t solve the diagnostic shortages on their own. The tests are valuable as screening indicators that reveal whether a given pathogen is — or was — present in the body, but they don’t measure the extent of a fungal infection, or “how well a patient responds to treatment”, says Amir Seyedmousavi, a clinical microbiologist at the National Institutes of Health Clinical Center, in Bethesda, Maryland. Patient monitoring requires more advanced analytical techniques, Seyedmousavi says, such as polymerase chain reaction (PCR) sequencing and other molecular tests. The laboratory capacity needed for these technologies, however, is often unavailable in resource-poor areas.

Seyedmousavi chairs the Fungal Diagnostic Working Group of the International Society for Human and Animal Mycology. The group is working to standardize and improve affordable diagnostic tests — especially for LMICs. And it aims to create international networks for knowledge sharing and education. Chakrabarti, meanwhile, is working to establish diagnostic reference centres across India that offer a range of standardized diagnostics — not just at the hospitals at which they are based, but also at the clinics that serve as the first point of contact for health care. The reference centres provide training to boost laboratory workforces, Chakrabarti says, and staff there conduct epidemiology studies to map the distribution of fungal diseases throughout the country.

Person seated in room below window, wearing a face mask. To the right, person standing wearing PPE looking at MRI

During the peak of the COVID-19 pandemic, mucormycosis cases surged in India.Credit: Prakash Singh/AFP via Getty

GAFFI is sponsoring similar approaches in other parts of the world. In partnership with the non-profit organization the Asociacion de Salud Integral in Guatemala City, for instance, GAFFI sponsored a diagnostic demonstration that focused on a number of fungal diseases, including histoplasmosis and cryptococcosis. In 2023, GAFFI reported that mortality from fungal infections in people with HIV could be substantially reduced with readily available diagnostics and treatment.

Efforts to expand access to diagnostic tests face complex challenges. Because clinical awareness of fungal diseases is low in LMICs, physicians don’t request diagnostic tests often enough to create a market that could make the tests more readily available. In the absence of better information on prevalence — especially outside urban areas — health systems in low-income countries have failed to prioritize fungal diseases, Banda says, creating a vicious cycle of neglect.

Health-care financing poses extra hurdles. In some LMICs, people have to pay for fungal diagnostic tests out of their own pocket. “People don’t want to pay for a test that might be negative,” Denning says. “They just want the doctor to make a judgement about treatment. For the life-threatening fungal diseases — the ones that cause meningitis or sepsis or pneumonia — that can be tough.”

Denning argues that teaching hospitals in LMICs should have access to every test on the WHO’s list of essential fungal diagnostics, and that the tests should also be made freely available to people at the point of use. If hospitals don’t improve their capacity to detect and treat fungal diseases correctly, he warns, “then acquired microbial resistance and inappropriate use of all these antimicrobials just becomes rife”. Fortunately, diagnostic tests are steadily becoming cheaper, “so it should be possible to provide them at low-cost around the world,” Denning adds. “The big need is just to get them into everybody’s hands.”

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