H5N1

The Lancet Commission on 21st-Century Global Health Threats

Via The Lancet, December 15, 2022: The Lancet Commission on 21st-Century Global Health Threats. 

The world has lived through an extraordinary global health threat, the COVID-19 pandemic, leading to nearly 20 million deaths, staggering economic losses, a generational decline in human capital, and the first decline in global life expectancy since 1950 (the first year when UN estimates were published). Another major threat, climate change, now has broad scientific, political, and social recognition. The spectre of nuclear confrontation has re-emerged as a serious threat during the ongoing Russian invasion of Ukraine. 

The three Cs—COVID-19, climate change, and conflict—highlight that the steady global health progress of the past 70 years will not necessarily continue in the next 70 years. But there are many other threats beyond the three Cs that threaten to undermine future global health progress, including rising antimicrobial resistance, increasing obesity, inverted population pyramids, eroding sexual and reproductive rights for women, food insecurity, and fraying multilateralism. How global health advances or retreats will depend crucially on the multiplicity of these threats and how they intersect. 

The global community and many nations have launched commissions, task forces, and panels to draw lessons from the COVID-19 pandemic. The Pan-European Commission on Health and Sustainable Development explored the post-pandemic world for Europe and made far-reaching recommendations based on a One Health lens. The Independent Panel for Pandemic Preparedness and Response and the G20 High Level Independent Panel on Financing the Global Commons for Pandemic Preparedness and Response called for the creation of new institutions and financing mechanisms to prepare the world for new pandemics and other threats. 

Multiple commissions, task forces, and panels have addressed climate change, including two Lancet Commissions, and the Intergovernmental Panel on Climate Change produces regular multistakeholder assessments. These global convenings have been mirrored by multiple national reviews. Although there are high-profile initiatives for pandemics and climate change, other threats have received less widespread attention or have been debated largely in academic subdisciplines.  

Governments, international organisations, and local communities will need to manage multiple threats at the same time. Many of these threats interact and lead to complex health, economic, social, and geopolitical consequences. Climate change, population growth, and political fragility may coincide leading to large-scale migration. Food systems can be designed to improve health, reduce poverty, and slow climate change, or the reverse.  

Specific and cross-cutting technologies and policies are needed to reduce the risk of emerging threats or to decrease the harms from threats as they unfold. The most important strategies for risk and harm reduction are unlikely to emerge if each threat is examined in isolation from the others.  

We have established the Lancet Commission on 21st-Century Global Health Threats to examine the broad set of threats facing the world over the rest of the century. This long perspective is needed since threats such as climate change, food systems, antimicrobial resistance, or inverted population pyramids require many decades for actions to alter future trajectories. The Sustainable Development Goal focus on 2030 is an important motivator for immediate policy action, but a longer-term perspective is needed to fully assess and respond to emerging threats.

This Commission's work will be informed by diverse expertise. The Commission members are drawn from many distinct groups: current and former heads of state, intergovernmental organisation leaders, leaders of public health institutions, global health funders, global health thought leaders, and civil society and youth organisations. The Commission represents a diverse group with gender parity and regional balance so that many perspectives are brought to bear on finding cross-cutting tools and solutions for future threats. The Commission will meet over the next 2 years to assess the evidence produced by various working groups and will release its analysis and recommendations by the end of 2024.

With all eyes on Covid-19, drug-resistant infections crept in

Via The New York Times: With All Eyes on Covid-19, Drug-Resistant Infections Crept In.

As Covid-19 took hold over the last year, hospitals and nursing homes used and reused scarce protective equipment — masks, gloves, gowns. This desperate frugality helped prevent the airborne transfer of the virus. 

But it also appears to have helped spread a different set of germs — drug-resistant bacteria and fungi — that have used the chaos of the pandemic to grow opportunistically in health care settings around the globe. 

These bacteria and fungi, like Covid-19, prey on older people, the infirm and those with compromised immune systems. They can cling tenaciously to clothing and medical equipment, which is why nursing homes and hospitals before the pandemic were increasingly focused on cleaning rooms and changing gowns to prevent their spread. 

That emphasis all but slipped away amid an all-consuming focus on the coronavirus. In fact, experts warn, the changes in hygiene and other practices caused by the Covid-19 fight are likely to have contributed to the spread of these drug-resistant germs.  

“Seeing the world as a one-pathogen world is really problematic,” said Dr. Susan S. Huang, an infectious disease specialist at the University of California at Irvine Medical School, noting that the nearly singular focus on the pandemic appears to have led to more spread of drug-resistant infection. “We have every reason to believe the problem has gotten worse.”  

A few data points reinforce her fears, including isolated outbreaks of various drug-resistant infections in Florida, New Jersey and California, as well as in India, Italy, Peru and France. Overall figures have been hard to track because many nursing homes and hospitals simply stopped screening for the germs as resources were diverted to Covid-19.  

When even modest screening picked up again early in the summer, the results suggested that certain drug-resistant organisms had taken root and spread. Particularly troublesome have been growing case counts of a fungus called Candida auris, which authorities had tried to fight before the pandemic with increased screening, isolation of infected patients and better hygiene.

ECDC: Antimicrobial consumption - Annual Epidemiological Report for 2018

ECDC has published Antimicrobial consumption - Annual Epidemiological Report for 2018. The executive summary:

• In 2018, the average total consumption (community and hospital sector combined) of antibacterials for systemic use (ATC group J01) in the EU/EEA was 20.1 DDD per 1 000 inhabitants per day (country range: 9.7–34.0). During the period 2009–2018, no statistically significant change was observed for the EU/EEA overall. However, statistically significant decreasing trends were observed for 11 countries. Statistically significant increasing trends were observed for four countries. 

• The average consumption of antivirals for systemic use (ATC group J05) in both sectors (community and hospital sector combined) was 2.2 DDD per 1 000 inhabitants per day (country range: 0.51–6.78).   

• Twenty-eight countries – 26 EU Member States and two EEA countries (Iceland and Norway) – reported data on antimicrobial consumption for 2018. Twenty-four countries reported both community and hospital consumption, three countries reported only community consumption, and one country reported total consumption for both sectors but without differentiating between them. 

• Antimicrobial consumption is expressed as the number of defined daily doses (DDDs) per 1 000 inhabitants per day. The Anatomical Therapeutic Chemical (ATC) DDD Index 2019 was used for the analysis of 2018 data as well as of historical data in order to assess 10-year trends.   

• The most recent data on antimicrobial consumption are available from the public ESAC-Net interactive database (data for 1997‒2018) on the ECDC website. 

ECDC: Surveillance of antimicrobial resistance in Europe 2018

ECDC has published Surveillance of antimicrobial resistance in Europe 2018. Excerpt from the executive summary: 

As in previous years, the AMR situation in Europe displays wide variations depending on bacterial species, antimicrobial group and geographical region. For several bacterial species–antimicrobial group combinations, a north-to-south and west-to-east gradient is evident. In general, lower resistance percentages were reported by countries in the north while higher percentages were reported in the south and east of Europe. The high variability in AMR across EU/EEA countries reinforces the scope for significant reductions through investments to strengthen current best practice.   

In 2018, more than half of the Escherichia  coli isolates reported to EARS-Net and more than a third of the Klebsiella pneumoniae isolates were resistant to at least one antimicrobial group under regular surveillance, and combined resistance to several antimicrobial groups was frequent. Resistance percentages were generally higher in K. pneumoniae than in E. coli. While carbapenem resistance remained rare in E. coli, several countries reported carbapenem resistance percentages above 10% for K. pneumoniae. 

Carbapenem resistance was also common in Pseudomonas  aeruginosa and Acinetobacter species, and at higher percentages compared with K. pneumoniae. For all four gram-negative bacteria, the countries reporting the highest carbapenem resistance percentages were also among the countries reporting the highest resistance percentages for other antimicrobial groups. For most gram-negative bacterial species–antimicrobial group combinations, changes in resistance percentages between 2015 and 2018 were moderate, and resistance remained at previously reported high levels.  

For Streptococcus pneumoniae, the resistance situation appeared stable, but with large inter-country variations. For Staphylococcus aureus, the decline in the percentage of methicillin-resistant (i.e. MRSA) isolates reported in previous years continued in 2018. Nevertheless, MRSA remains an important pathogen in the EU/EEA, as the levels of MRSA were still high in several countries, and combined resistance to other antimicrobial groups was common. 

FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs

A news release from the US Food and Drug Administration: FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs. Excerpt:

The U.S. Food and Drug Administration today approved Pretomanid Tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs. 

“The threat of antimicrobial-resistant infections is a key challenge we face as a public health agency,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D. 

“The bacterium that causes tuberculosis can develop resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections. 

"This approval also marks the second time a drug is being approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway, advanced by Congress, to spur development of drugs targeting infections that lack effective therapies. We hope we continue to see more development of antibacterial drugs for treating serious or life-threatening infections in limited populations of patients with unmet medical needs.”  

Pretomanid in combination with bedaquiline and linezolid is approved for treating a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary TB. Multidrug-resistant TB and extensively drug-resistant TB are difficult to treat due to resistance to available therapies. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.  

The safety and effectiveness of Pretomanid, taken orally in combination with bedaquiline and linezolid, were primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs). Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of extensively drug resistant TB.

The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes (transaminases and gamma-glutamyltransferase), indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.  

Pretomanid used in combination with bedaquiline and linezolid should not be used in patients with hypersensitivity to bedaquiline or linezolid.

Scientists discover new cure for the deadliest strain of tuberculosis

Here's how The New York Times reported on today's good news: Scientists Discover New Cure for the Deadliest Strain of Tuberculosis. Excerpt:

TSAKANE, South Africa — When she joined a trial of new tuberculosis drugs, the dying young woman weighed just 57 pounds. 

Stricken with a deadly strain of the disease, she was mortally terrified. Local nurses told her the Johannesburg hospital to which she must be transferred was very far away — and infested with vervet monkeys. 

“I cried the whole way in the ambulance,” Tsholofelo Msimango recalled recently. “They said I would live with monkeys and the sisters there were not nice and the food was bad and there was no way I would come back. They told my parents to fix the insurance because I would die.” 

Five years later, Ms. Msimango, 25, is now tuberculosis-free. She is healthy at 103 pounds, and has a young son.

The trial she joined was small — it enrolled only 109 patients — but experts are calling the preliminary results groundbreaking. The drug regimen tested on Ms. Msimango has shown a 90 percent success rate against a deadly plague, extensively drug-resistant tuberculosis. 

On Wednesday, the Food and Drug Administration effectively endorsed the approach, approving the newest of the three drugs used in the regimen. Usually, the World Health Organization adopts approvals made by the F.D.A. or its European counterpart, meaning the treatment could soon come into use worldwide. 

Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the so-called XDR strain is the ultimate in lethality. It is resistant to all four families of antibiotics typically used to fight the disease. 

Only a tiny fraction of the 10 million people infected by TB each year get this type, but very few of them survive it. 

There are about 30,000 cases in over 100 countries. Three-quarters of those patients die before they even receive a diagnosis, experts believe, and among those who get typical treatment, the cure rate is only 34 percent.

Climate crisis seriously damaging human health, report finds

Via The Guardian: Climate crisis seriously damaging human health, report finds. Excerpt:

A report by experts from 27 national science academies has set out the widespread damage global heating is already causing to people’s health and the increasingly serious impacts expected in future. 

Scorching heatwaves and floods will claim more victims as extreme weather increases but there are serious indirect effects too, from spreading mosquito-borne diseases to worsening mental health. 

“There are impacts occurring now [and], over the coming century, climate change has to be ranked as one of the most serious threats to health,” said Prof Sir Andrew Haines, a co-chair of the report for the European Academies’ Science Advisory Council (Easac).

However, there were also great benefits from action to cut carbon emissions, the report found, most notably cutting the 350,000 early deaths from air pollution every year in Europe caused by burning fossil fuels. “The economic benefits of action to address the current and prospective health effects of climate change are likely to be substantial,” the report concluded. 

The World Health Organization director general, Tedros Adhanom Ghebreyesus, warned in November that climate breakdown was already a health crisis. “We cannot delay action on climate change,” he said. “We cannot sleepwalk through this health emergency any longer.” In December, a WHO report said tackling the climate crisis would save at least a million lives a year, making it a moral imperative to act.

The new Easeac report, The Imperative of Climate Action to Protect Human Health in Europe, assessed the scientific evidence of the effects of global heating on health. Extreme weather such as heatwaves, floods and droughts have direct short-term impacts but also affect people in the longer term. “Mental health effects include post-traumatic stress disorder, anxiety, substance abuse and depression,” the report said.

The scientists were also concerned by the effect of extreme weather on food production, with studies showing a 5-25% cut in staple crop yields across the Mediterranean region in coming decades. But the report said even small cuts in meat eating could lead to significant cuts in carbon emissions, as well as benefits to health. 

The report anticipates the spread of infectious diseases in Europe as temperatures rise and increase the range of mosquitoes that transmit dengue fever and ticks that cause Lyme disease. Food poisoning could also rise, as salmonella bacteria thrived in warmer conditions, the report said. It even found research suggesting antibiotic resistance in E coli increases in hotter conditions.  

“We are exposing the whole of the world population to changes in climate, and this is clearly very concerning as we are moving to some extent into uncharted territory,” said Haines, professor of environmental change and public health at the London School of Hygiene and Tropical Medicine.

World's rivers 'awash with dangerous levels of antibiotics'

Via The Guardian: World's rivers 'awash with dangerous levels of antibiotics'. Excerpt:

Hundreds of rivers around the world from the Thames to the Tigris are awash with dangerously high levels of antibiotics, the largest global study on the subject has found.  

Antibiotic pollution is one of the key routes by which bacteria are able develop resistance to the life-saving medicines, rendering them ineffective for human use. “A lot of the resistance genes we see in human pathogens originated from environmental bacteria,” said Prof William Gaze, a microbial ecologist at the University of Exeter who studies antimicrobial resistance but was not involved in the study. 

The rise in antibiotic-resistant bacteria is a global health emergency that could kill 10 million people by 2050, the UN said last month.

The drugs find their way into rivers and soil via human and animal waste and leaks from wastewater treatment plants and drug manufacturing facilities. “It’s quite scary and depressing. We could have large parts of the environment that have got antibiotics at levels high enough to affect resistance,” said Alistair Boxall, an environmental scientist at the University of York, who co-led the study. 

The research, presented on Monday at a conference in Helsinki, shows that some of the world’s best-known rivers, including the Thames, are contaminated with antibiotics classified as critically important for the treatment of serious infections. In many cases they were detected at unsafe levels, meaning resistance is much more likely to develop and spread. 

Samples taken from the Danube in Austria contained seven antibiotics including clarithromycin, used to treat respiratory tract infections such as pneumonia and bronchitis, at nearly four times the level considered safe. 

The Danube, Europe’s second-largest river, was the continent’s most polluted. Eight per cent of the sites tested in Europe were above safe limits.  

The Thames, generally regarded as one of Europe’s cleanest rivers, was contaminated, along with some of its tributaries, by a mixture of five antibiotics. One site on the river and three on its tributaries were polluted above safe levels. Ciprofloxacin, which treats infections of the skin and urinary tract, peaked at more than three times safe levels. 

Even rivers contaminated with low levels of antibiotics are a threat, Gaze said. “Even the low concentrations seen in Europe can drive the evolution of resistance and increase the likelihood that resistance genes transfer to human pathogens,” he says.

What superbug hunters know that we don’t

Via The New York Times, an opinion piece by Dr. Matt McCarthy: What Superbug Hunters Know That We Don’t. Excerpt:

Antibiotic-resistant superbugs are everywhere. If your hospital claims it doesn’t have them, it isn’t looking hard enough. 

Hospitals are losing an important public relations battle over the expanding threat of superbugs, including the deadly fungus Candida auris. Though states are tasked with conducting outbreak investigations, they aren't required to disclose their findings to the Centers for Disease Control and Prevention (and in many cases they haven’t). Grieving families are pushing for more transparency, while patient advocates smell a cover-up, likening the scenario to a restaurant failing to report an outbreak of food poisoning. In the midst of all this mistrust, hospital spokesmen are declining to comment. This is a mistake. 

I hate to be the bearer of bad news, but these microbes are in our homes, cars and grocery stores. One study found that even after the use of disinfectant, more than half of hospital rooms still contain a superbug. Nurses and doctors carry these things around, too. Roughly 5 percent of health care workers are colonized with MRSA, a bacterium that kills thousands of people in the United States every year, and another study found that 10 percent of patients entering a hospital had a multidrug-resistant species on their hands. You don’t want to know what’s hiding on a handkerchief.  

Here’s the thing: You almost certainly don’t need to worry about any of this. Potentially deadly bacteria and fungi live harmlessly on our hands, feet, and faces, and may never cause a problem. There are trillions of bacteria living inside all of us. Why are we pretending they aren’t on our gurneys, blood pressure cuffs and X-ray machines? 

Demanding that hospitals release lists of every superbug they find within their walls, however, as many transparency advocates want, is not the answer. The irony is that the hospitals that see the most superbugs are often the best ones we have, for the simple reason that they have the most sophisticated diagnostic platforms, the most powerful antibiotics and the experts to administer them.  

Compelling a world-class hospital like Massachusetts General Hospital, where I saw my first superbug as a medical student, to reveal a microbe list would only freak patients out. It wouldn’t explain where the microbes came from, whether any patients were infected, and how they were cured. 

In a worst-case scenario, more transparency could lead to patients avoiding medical care out of a misplaced fear of encountering drug-resistant bacteria. Hospitals might start refusing patients with certain infections, especially those coming from nursing facilities where these microbes are common, out of a concern that the patient’s bacteria could be added to the list. This would do everyone a disservice: Patients wouldn’t receive optimal care and superbugs would multiply.  

But hospital administrators and government officials do need to be honest about the microbes in our medical centers and explain what is really going on. No comment will no longer suffice. People have questions and this story is not going away. To ensure that patients are well-informed, hospitals should train spokesmen to address these issues and states should revisit their reluctance to disclose information. Above all, health care workers and administrators should speak openly about the measures their hospitals are already employing to keep people safe.  

I’m not particularly interested in the microbes that dwell inside of a given hospital; what matters is whether its employees follow the strict protocols that prevent these organisms from going where they shouldn’t.

UK: Teenager recovers from near death in world-first GM virus treatment (updated)

Via The Guardian: Teenager recovers from near death in world-first GM virus treatment. Excerpt:

A British teenager has made a remarkable recovery after being the first patient in the world to be given a genetically engineered virus to treat a drug-resistant infection. 

Isabelle Holdaway, 17, nearly died after a lung transplant left her with an intractable infection that could not be cleared with antibiotics. After a nine-month stay at Great Ormond Street hospital, she returned to her home in Kent for palliative care, but recovered after her consultant teamed up with a US laboratory to develop the experimental therapy.  

The scientists behind the breakthrough have said bacteria-killing viruses, known as phages, have the potential to be used as an alternative treatment to counter the growing crisis of resistance to antibiotics.  

Isabelle’s mother, Jo, who made the initial suggestion of phage therapy to doctors at Great Ormond Street after reading about it online, said her daughter was “the luckiest child on earth” to have received the treatment in time. 

“It’s incredible medical science. It’s been a miracle,” she said. 

Isabelle has cystic fibrosis, a genetic disease that results in frequent infections clogging up the lungs with mucus. By summer 2017, her lungs had less than a third of their normal function and she had been plagued by two stubborn bacterial strains for eight years. She and her doctors decided a double lung transplant was the best option, even though it meant her existing infections could spread.

After the transplant, this fear became a reality: a bacterial strain similar to TB took hold, colonising her surgical wound, then her liver, until eventually pockets of bacteria known as nodules began pushing through the skin on her arms, legs and buttocks. 

“She lost so much weight. She was literally like a skeleton,” Jo said. “The bacteria was just coming through her skin. There was nothing they could do to make her comfortable. It was horrific.” 

She searched the internet for alternative treatments and on reading about phage therapies asked Isabelle’s consultant, Helen Spencer, whether this might be an option.  

By chance, a Great Ormond Street colleague was in touch with Prof Graham Hatfull, a scientist who had spent more than three decades amassing a collection of phages, stored in 15,000 frozen vials at the University of Pittsburgh. Hatfull agreed to help find a treatment for Isabelle and another teenage patient at Great Ormond Street who had a life-threatening infection. 

Phages work by infecting bacteria cells and killing them, but they are very specific in which infections they can target. Hatfull and colleagues identified dozens of phages known to infect bacterial relatives of the patients’ strains, and tested thousands of combinations of them in petri dishes to see which wiped out the patients’ bacteria.

Update: For details on this case, see this excellent article by Ed Yong in The Atlantic.