Category: 8. Health

At first, the patient’s symptoms were a puzzle: swelling of the brain tissue and membranes as might be seen with meningitis, but without any sign of the bacteria and viruses that typically cause it.

Medical staff at the hospital on the Italian island of Sardinia excluded potential causes one by one until they were left with something unexpected. It was West Nile virus, one of several formerly tropical diseases that have become increasingly established in Europe as climate change favours the spread of the mosquitoes that carry the illnesses with their bite.

“It was practically unknown here,” recalls Dr Maria Valentina Marras of that first case in her province of Oristano in Sardinia, little more than a decade ago. “From then until now, every summer we have a West Nile emergency.”

She now leads containment efforts as head of the department of hygiene and prevention in Oristano, a region of 147,000 people that, on the day we spoke, reported its 15th case of West Nile so far this year.

The new patient was a 71-year-old man who presented at accident and emergency with the symptoms that have become familiar – high fever, confusion, neurological symptoms, encephalitis – which now trigger an automatic test for West Nile.

The detected cases indicate a much larger outbreak in reality, as 80 per cent of those who are infected show no symptoms. About 20 per cent suffer a flu, and 1 per cent are hospitalised. Older people, with conditions such as diabetes, heart or respiratory trouble, or obesity are more susceptible to severe illness due to their weakened immune response.

Each confirmed case triggers an immediate crackdown to contain the spread: the patient’s house is cordoned off, and fumigators move in with insecticides to treat the entire area around the home in a 200m radius. The disease does not spread from human to human, but only through infected mosquitos.

Despite these efforts, the spread of the virus is proving difficult to contain.

“This summer was a very hot summer, a terrible humid heat that started in June and is still going now in September,” Dr Marras says. “The mosquito found the ideal environment to reproduce, exponentially.”

Italy has detected 430 locally-transmitted cases of West Nile virus and 27 deaths so far in 2025, according to national data.

In the last week, France reported 71 new locally-acquired cases of Chikungunya, a virus that can cause chronic debilitating joint pain, bringing this summer’s record outbreak of a disease that originated in Tanzania to 227 cases across 30 clusters.

Various Mediterranean countries have reported cases of the viral infection Dengue, which is usually associated with tropical and subtropical regions of the world.

This summer’s record-breaking outbreaks of Chikungunya and West Nile virus represent a “new normal”, according to the European Centre for Disease Prevention and Control. It says climate change and increased international travel mean the tiger mosquito is established in 16 countries in Europe, and likely to spread further.

“As the mosquito-borne disease landscape evolves, more people in Europe will be at risk in the future,” the ECDC’s Dr Céline Gossner said in a statement.

With the new diseases, communities must learn to adjust. Information brochures sent to every house and pharmacy in the region of Oristano explain how West Nile virus spreads and how to prevent it. Never leave out bowls of water for pets overnight, as the mosquitos breed in the smallest amounts of stagnant water. Wear long sleeves and trousers in the evening, even if it’s hot. Avoid wearing dark clothing, which attracts them. Cover all windows with mosquito screens.

As it is a region that attracts plenty of tourists, English-language information campaigns target visitors, too.

To the local community facing the outbreak, the warnings and news reports are all a rather unpleasant reminder of a pandemic that seems very recent history.

“The community is afraid of this disease,” Dr Marras said. “Like all the world, we had Covid in 2020, so people are very scared of this disease. Even though there isn’t human-to-human transmission.

The University of Pennsylvania has developed a generative artificial intelligence (AI) model capable of designing brand new antibiotics, marking what researchers say is a major step forward in the fight against drug-resistant bacteria.

In a study published in Cell Biomaterials, engineers at Penn Engineering and colleagues across the university present AMP-Diffusion, a generative AI tool that designs antimicrobial peptides (AMPs) – short amino acid chains that kill bacteria. In animal trials, several of the AI-designed molecules worked as effectively as existing FDA-approved antibiotics and showed no detectable side effects.

For decades, scientists have warned of the looming crisis of antibiotic resistance. New drugs have proved difficult and slow to develop, leaving health systems around the world struggling to keep up. Generative AI, best known for producing images and text, could offer a radically faster approach.

“Nature’s dataset is finite; with AI, we can design antibiotics evolution never tried,” says César de la Fuente, presidential associate professor at the University of Pennsylvania, who co-led the work.

Pranam Chatterjee, assistant professor at Penn Engineering who began the project while at Duke University, adds: “We’re leveraging the same AI algorithms that generate images, but augmenting them to design potent new molecules.”

From mammoths to microbes

De la Fuente’s lab has long used AI to scour unconventional biological sources for antimicrobial properties, from the proteins of woolly mammoths to animal venoms and ancient microbes. Yet the rate at which resistance emerges has outstripped these discoveries. “Unfortunately, antibiotic resistance keeps increasing faster than we can discover new antibiotic candidates,” he says.

Chatterjee’s group, meanwhile, has focused on using AI to design peptides for hard-to-treat diseases. Their collaboration was a natural match. “It seemed like a natural fit,” says Chatterjee. “Our lab knows how to design new molecules using AI and the de la Fuente Lab knows how to identify strong antibiotic candidates using AI.”

Drug-resistant bacteria are on the rise worldwide, spreading faster than new antibiotics can be developed. The World Health Organization (WHO) calls it one of the biggest threats to global health. Credit: Saiful52/Shutterstock

A diffusion model for medicine

While large language models such as ChatGPT predict the next word in a sequence, diffusion models generate content by starting with random noise and progressively refining it into a coherent whole. This is the principle behind creative AI systems like DALL·E and Stable Diffusion.

AMP-Diffusion applies the same concept to biology. Instead of denoising pixels, it shapes amino acid sequences into plausible peptides. “It’s almost like adjusting the radio,” says de la Fuente. “You start with static and then eventually the melody emerges.”

Unlike other teams that have tried diffusion models for antibiotics, Penn’s approach leans on ESM-2, a protein language model from Meta trained on hundreds of millions of sequences. By building on an existing ‘mental map’ of how proteins fit together, AMP-Diffusion generates candidates more quickly and with a higher chance of being biologically valid.

“Instead of teaching the model the ABCs of biology, we started with a fluent speaker,” says Chatterjee. “That shortcut lets us focus on designing peptides with a real shot at becoming drugs.”

From 50,000 ideas to two winners

AMP-Diffusion generated around 50,000 peptide sequences. But testing even a fraction in the lab would be impossible. To narrow the field, the researchers turned to another AI tool, APEX 1.1, developed in de la Fuente’s lab. It ranked the candidates based on predicted bacteria-killing power, novelty and diversity. 

From this, the team synthesised 46 peptides for laboratory and animal testing. In mouse models of skin infection, two molecules stood out – performing on par with levofloxacin and polymyxin B, well-established antibiotics used against resistant bacteria. Crucially, no harmful side effects were observed.

“It’s exciting to see that our AI-generated molecules actually worked,” says Chatterjee. “This shows that generative AI can help combat antibiotic resistance.”

What’s next

The researchers see this as just the beginning. AMP-Diffusion could eventually be refined to design antibiotics for specific infections or tuned to prioritise molecules with particularly desirable drug-like properties. “We’ve shown the model works and now if we can steer it to enhance beneficial drug-like properties, we can make ready-to-go therapeutics,” says Chatterjee.

For de la Fuente, the long-term ambition is radical speed. “Ultimately, our goal is to compress the antibiotic discovery timeline from years to days,” he says.

With drug resistance now listed among the top global health threats by the World Health Organization, breakthroughs like this could prove transformative.

A rigorous new study finds that a single dose of LSD can ease anxiety and depression for months.

The study involved 198 adults with generalized anxiety disorder, or GAD, a disabling form of anxiety that affects about one in 10 people over the course of a year.

Participants who got lower doses of LSD (25 or 50 micrograms) did no better than those who got a placebo. But people who received higher doses (100 or 200 micrograms) responded quickly, a team reports in the Journal of the American Medical Association.

“By the next day, they were showing strong improvements,” says Dr. David Feifel of Kadima Neuropsyciatry Institute in San Diego, one of the 22 centers that participated in the study. “And those improvements held out all the way to the end of the study, which was 12 weeks.”

But it’s unclear whether some of the improvement was related to non-drug factors like the sensory environment in which people were treated, says Robin Carhart-Harris, a psychedelics researcher at the University of California, San Francisco who was not involved in the study.

“The safety looks good, the tolerability looks good,” he says, “but where is the depth of information about the way you delivered this product?”

Carhart-Harris, like many scientists who study psychedelics, believes that successful treatment is more likely if a person has the right mindset when beginning a trip and if the trip occurs in a place with the right sensory environment.

Not your everyday anxiety

Generalized anxiety disorder involves extreme worry or dread that interferes with a person’s ability to function.

“It’s characterized by continuous worry, inability to relax, and all the physical manifestations, racing heart rates and sweatiness,” Feifel says. It’s also frequently accompanied by depression.

Current antidepressant and antianxiety drugs are inadequate for about half of people diagnosed with GAD.

So 22 outpatient psychiatric research sites agreed to test a proprietary form of LSD called MM120, which comes from the company MindMed.

The drug is not at all like Prozac or Zoloft, which are among the usual treatments for GAD.

“This is something that has a very, very distinct subjective experience,” Feifel says, “what people might call a trip.”

MM120, like other versions of LSD, can alter a person’s perceptions and cause them to see, hear, or feel things that aren’t there.

In the study, participants were far more likely to improve if they received a dose of MM120 high enough to induce a psychedelic experience. The higher doses also were more likely to lift a person’s depression.

Non-drug factors

Psychedelic treatment often involves guides or therapists who help ensure that a patient’s psychedelic experience is safe and effective. In addition, treatment centers often provide rooms with soft lighting, a naturalistic decor, and music or other sensory stimulation.

But in this study, it’s unclear whether these environmental factors played an important role in the treatment.

The sessions were overseen by two “dosing session monitors,” who also provided an education session about the treatment. The sessions were conducted in a “private aesthetically pleasant room,” the researchers say, and participants were offered “standardized music and eyeshades.”

All of these factors could have contributed to the outcome, Carhart-Harris says, but it’s hard to tell because they weren’t specified in the study protocol and could have varied greatly from one center to another.

“To not say anything about music listening, for example, when it’s been present in virtually 100% of the trials that have been published to date on psychedelic therapy, is an obvious omission,” Carhart-Harris says.

A psychedelic future

The new research represents an emerging trend in psychedelic research: bigger, more rigorous studies that are more likely to be supported by a pharmaceutical company.

Such studies are needed to get psychedelic drugs like LSD, MDMA and psilocybin approved by the Food and Drug Administration, Feifel says. And giving doctors access to approved psychedelics could “revolutionize treatment” of psychiatric conditions ranging from depression to PTSD and addiction.

“Give it a couple of years and we’ll be seeing drugs like psilocybin [and] magic mushrooms as medicines,” Carhart-Harris says. “A whole mindset shift is going to happen around that.”

The FDA seems open to that possibility. It has already given MM120 “breakthrough therapy” status, which is meant to speed up the evaluation of promising new drugs.

MindMed, for its part, has already launched a pair of “phase 3” studies of MM120. The company expects to complete those trials in 2026.

The new Plasma Immuno Prediction Score achieves 96% accuracy in forecasting TNBC outcomes, offering laboratories a powerful tool for precision oncology.

For laboratory professionals, the latest findings in plasma proteomics underscore how the clinical laboratory is becoming central to guiding cancer treatment decisions. The discovery of blood-based protein signatures that can predict immunotherapy outcomes in triple-negative breast cancer (TNBC) demonstrates how lab-developed tests and biomarker assays can directly influence patient care, moving precision oncology forward.

A news release explained that a team of researchers in China has identified a set of plasma proteins that can reliably predict whether patients with TNBC will respond to immunotherapy, potentially transforming treatment strategies for one of the most aggressive forms of breast cancer.

The study, published July 4, 2025, in Cancer Biology & Medicine, analyzed blood samples from 195 TNBC patients. Using high-sensitivity assays, scientists at Fudan University Shanghai Cancer Center and the Shanghai Institute for Biomedical and Pharmaceutical Technologies tracked 92 immune-related proteins before, during, and after immunotherapy.

They found that three proteins in particular—arginase 1 (ARG1), nitric oxide synthase 3 (NOS3), and CD28—were strongly linked to treatment outcomes. From this, the team developed a predictive model called the Plasma Immuno Prediction Score (PIPscore), which achieved nearly 86% accuracy in forecasting responses.

“This study transforms how we approach TNBC immunotherapy,” said Yizhou Jiang, MD, co-corresponding author. “By translating complex plasma proteomics into a practical score, we’ve bridged the gap between research and clinical utility.”

Breaking the Bottleneck in TNBC

Triple-negative breast cancer accounts for about 15% of breast cancer cases worldwide and is notoriously difficult to treat because it lacks the hormonal and HER2 targets used in other subtypes. Immunotherapy has emerged as a promising option, but predicting which patients will benefit remains a challenge.

Currently, clinicians rely on biomarkers like PD-L1 expression or tumor mutational burden. However, these markers often fail to capture the complexity of immune responses, leaving doctors without reliable tools to guide decisions. Tumor biopsies, another option, are invasive and impractical for frequent monitoring.

How the Study Worked

The research team analyzed dynamic changes in plasma proteins over the course of immunotherapy. Patients who responded to treatment showed sharp rises in immune-activating proteins such as CXCL9 and interferon-gamma (IFN-γ). Those who achieved a pathologic complete response (pCR)—meaning no detectable cancer remained after treatment—had higher levels of ARG1 and CD28, but lower levels of NOS3.

According to the study, these proteins appear to regulate critical aspects of immune activation and tumor suppression. Elevated NOS3, for example, correlated with fewer CD8+ T cells in tumors, suggesting an immunosuppressive role. In contrast, ARG1’s role in arginine metabolism may boost T-cell function and strengthen immune attack on tumors.

To integrate these findings, the researchers developed the PIPscore, a composite of six proteins including ARG1, NOS3, and IL-18. This model stratified patients into high- and low-response groups with impressive precision. The area under the curve (AUC)—a common measure of predictive performance—was 0.858, indicating strong accuracy.

Perhaps most strikingly, the PIPscore predicted 12-month progression-free survival with 96% accuracy, highlighting its potential clinical value.

Linking Blood to Tumor Biology

To strengthen their conclusions, the team also used single-cell RNA sequencing to link blood protein signatures with changes in the tumor microenvironment. For example, patients with higher NOS3 levels showed reduced infiltration of CD8+ T cells into tumors, aligning blood-based findings with tissue-level biology.

“This dual approach—measuring proteins in the blood and validating them against the tumor microenvironment—offers a holistic view of how immunotherapy works,” Jiang said. “It underscores that systemic immunity, not just local tumor factors, dictates treatment success.”

Clinical Implications

The potential benefits of this approach are wide-ranging. Oncologists could use the PIPscore to determine upfront whether a TNBC patient is likely to respond to immunotherapy, sparing non-responders from ineffective treatments, unnecessary side effects, and high costs. Because the test is blood-based, it could be repeated over time, allowing clinicians to adjust treatment plans in real time.

“The PIPscore not only predicts response but also opens doors to targeting metabolic pathways like arginine deprivation to overcome resistance,” Jiang noted. “These findings underscore the importance of systemic immunity.”

Beyond TNBC, the researchers believe the method could be applied to other cancers where immunotherapy outcomes are highly variable.

In addition to plasma proteomics, the field of pharmacogenomics offers another layer of precision in cancer care by examining how genetic variations influence drug response.

When combined with tools like the PIPscore, pharmacogenomic profiling could help oncologists tailor both immunotherapy and supportive treatments to individual patients. For laboratory professionals, this integration underscores the expanding role of molecular diagnostics in personalizing therapy—ensuring patients not only receive the right drug but also the right dosage based on their genetic and immune profiles.

Next Steps

The study’s authors acknowledge that further validation is needed before the PIPscore can enter routine clinical practice. Larger, multi-center trials will be necessary to confirm its reliability across diverse patient populations. Still, experts view the findings as a major step toward more precise cancer care.

As immunotherapy adoption grows, laboratory professionals will be essential in validating, standardizing, and implementing predictive tools like the PIPscore in clinical practice. Their expertise in assay development, quality control, and biomarker interpretation ensures that discoveries at the research level can be reliably translated into real-world diagnostics, ultimately improving outcomes for patients with aggressive cancers like TNBC.

—Janette Wider

s

By grouping patients based on gene activity, scientists show that shared molecular pathways, especially immune-related ones, help explain why some diseases overlap and others diverge, offering clues for treatment and prevention.

Study: Patient stratification reveals the molecular basis of diseaseco- occurrences. Image credit: nobeastsofierce/Shutterstock.com

Using genomic and transcriptional data has greatly improved the understanding of multiple aspects of human physiology. A new paper in PNAS reports on molecular-level associations of co-occurring diseases identified by their RNA expression.

The investigators went a step further by categorizing participants by their gene expression patterns. This revealed more disease groupings, both known and potential, offering possibilities for the systematic discovery of relationships between diseases at the molecular level. This could enhance treatment approaches to such comorbidities.

Introduction

Comorbidity refers to the occurrence of two or more disease conditions in the same patient or set of patients. Specific illnesses confer a higher risk for certain other conditions. These patterns of co-occurrence help predict the course and prognosis of the diseases, as well as the odds of developing specific secondary illnesses as a result of the index condition.

Shared disease-related genes may explain these co-occurrences and can be identified using network analysis. The authors of the present paper previously showed how gene expression profiles predicted disease similarity networks, uncovering known comorbidities.

However, earlier network studies failed to identify many known comorbidities. The current study used publicly available RNA-sequencing data, which offer greater sensitivity and reproducibility than earlier methods.

The investigators built a disease similarity network, which replicated and added to associations between a much larger proportion of known comorbidities. Next, they exploited differential gene expression data to build a stratified similarity network, grouping patients by their gene expression profile.

Study findings

The networks identified direct and inverse comorbidities, that is, conditions that occur more or less often together than expected by chance. Most importantly, the stratified network recalls ~64% of epidemiologically known comorbidity pairs by analyzing patient subgroups with similar expression profiles. The results correlated with those from epidemiological studies, validating the methodological soundness of the analysis.

Identified associations include those of irritable bowel disease (IBD) and lung or liver cancer, or Kaposi’s sarcoma and HIV infection. Some less obvious associations were also identified, such as Kaposi’s sarcoma and immunological diseases like IBD.

Again, kinesin pathways were enriched in cancer but were lower than expected in Huntington’s disease. Huntington’s disease shows increased Th1/IL-12 signaling and complement activation, whereas these pathways are underexpressed in several cancers, illustrating opposite immune tendencies.

Gut-related comorbidities had the highest precision of 66.4%. Neoplasms showed the lowest precision, while mental disorders tended to have lower recall. Notably, 95.2% of DSN interactions that match epidemiology share one or more overexpressed immune pathways. More than 90% share metabolic or extracellular matrix.

Common mechanisms of comorbidities

The study suggests common underlying biological explanations for comorbidities with a strong immune component and reveals multiple deeper relationships between diseases.

Thus, common underlying mechanisms can be of three types: Both diseases share the same pathway, one condition alters pathways, causing the second condition, or a third condition causes changes that increase the risk of the other two.

Multiple combinations of these may also occur, especially with chronic medical conditions.

Therefore, not all associations between diseases reflect actual risk increases. Some mirror similarities in dysregulated pathways. Others correspond to comorbidities that have not been widely recognized, such as breast cancer with colorectal or thyroid cancer, and thyroid cancer with ulcers due to radiation treatment.

For instance, metabolic syndrome is both due to and triggers the progression of the metabolic trajectory that involves obesity, insulin resistance, diabetes, cardiovascular disease, and cancer.

Disease subtypes and comorbidities

Disease patterns and subtypes also modify comorbidity incidence as they involve distinct gene expression patterns. The current study suggests that certain breast cancer patients are more likely to have autism and bipolar disorder, though the supporting evidence is mixed or nonsignificant in some cases.

Down syndrome was also associated with a higher risk of childhood leukemia and multiple autoimmune diseases, especially celiac disease, with a sixfold higher incidence. This is associated with widespread changes in the immune system.

Conclusions

The study is based on disease similarity networks based on gene expression profiles that provided associations between comorbidities at an unprecedented scale. The networks indicate that “comorbidities have a strong molecular component that is better captured with gene expression profiles than with other molecular sources,” and provide “a systematic framework for translating disease co-occurrences into molecular patterns”.

The study clarifies the biological processes involved, helping explain how these conditions arise and why they co-occur, with a strong emphasis on immune pathways. It could perhaps guide drug repurposing and drug development efforts.

The methodology overcame earlier systemic limitations such as a biased and inadequate knowledge of disease-associated genes and disease interactions. Using uniformly processed RNA-seq with study effect adjustment improved sensitivity and reproducibility; links were further cross-checked against epidemiology and literature.

The use of patient stratification by gene expression “phenotypes” excluded non-significant pathway alterations. Finally, it identifies both positive and negative (inverse) correlations; due to data limitations, only positive links could be systematically compared with epidemiology.

Further research is required to validate the negative associations, obtain generalized epidemiological network data, and correlate demographic and treatment-related data with gene expression differences. Larger sample sizes would help achieve these goals.

Download your PDF copy now!

A rigorous new study finds that a single dose of LSD can ease anxiety and depression for months.

The study involved 198 adults with generalized anxiety disorder, or GAD, a disabling form of anxiety that affects about one in 10 people over the course of a year.

Participants who got lower doses of LSD (25 or 50 micrograms) did no better than those who got a placebo. But people who received higher doses (100 or 200 micrograms) responded quickly, a team reports in the Journal of the American Medical Association.

“By the next day, they were showing strong improvements,” says Dr. David Feifel of Kadima Neuropsyciatry Institute in San Diego, one of the 22 centers that participated in the study. “And those improvements held out all the way to the end of the study, which was 12 weeks.”

But it’s unclear whether some of the improvement was related to non-drug factors like the sensory environment in which people were treated, says Robin Carhart-Harris, a psychedelics researcher at the University of California, San Francisco who was not involved in the study.

“The safety looks good, the tolerability looks good,” he says, “but where is the depth of information about the way you delivered this product?”

Carhart-Harris, like many scientists who study psychedelics, believes that successful treatment is more likely if a person has the right mindset when beginning a trip and if the trip occurs in a place with the right sensory environment.

Not your everyday anxiety

Generalized anxiety disorder involves extreme worry or dread that interferes with a person’s ability to function.

“It’s characterized by continuous worry, inability to relax, and all the physical manifestations, racing heart rates and sweatiness,” Feifel says. It’s also frequently accompanied by depression.

Current antidepressant and antianxiety drugs are inadequate for about half of people diagnosed with GAD.

So 22 outpatient psychiatric research sites agreed to test a proprietary form of LSD called MM120, which comes from the company MindMed.

The drug is not at all like Prozac or Zoloft, which are among the usual treatments for GAD.

“This is something that has a very, very distinct subjective experience,” Feifel says, “what people might call a trip.”

MM120, like other versions of LSD, can alter a person’s perceptions and cause them to see, hear, or feel things that aren’t there.

In the study, participants were far more likely to improve if they received a dose of MM120 high enough to induce a psychedelic experience. The higher doses also were more likely to lift a person’s depression.

Non-drug factors

Psychedelic treatment often involves guides or therapists who help ensure that a patient’s psychedelic experience is safe and effective. In addition, treatment centers often provide rooms with soft lighting, a naturalistic decor, and music or other sensory stimulation.

But in this study, it’s unclear whether these environmental factors played an important role in the treatment.

The sessions were overseen by two “dosing session monitors,” who also provided an education session about the treatment. The sessions were conducted in a “private aesthetically pleasant room,” the researchers say, and participants were offered “standardized music and eyeshades.”

All of these factors could have contributed to the outcome, Carhart-Harris says, but it’s hard to tell because they weren’t specified in the study protocol and could have varied greatly from one center to another.

“To not say anything about music listening, for example, when it’s been present in virtually 100% of the trials that have been published to date on psychedelic therapy, is an obvious omission,” Carhart-Harris says.

A psychedelic future

The new research represents an emerging trend in psychedelic research: bigger, more rigorous studies that are more likely to be supported by a pharmaceutical company.

Such studies are needed to get psychedelic drugs like LSD, MDMA and psilocybin approved by the Food and Drug Administration, Feifel says. And giving doctors access to approved psychedelics could “revolutionize treatment” of psychiatric conditions ranging from depression to PTSD and addiction.

“Give it a couple of years and we’ll be seeing drugs like psilocybin [and] magic mushrooms as medicines,” Carhart-Harris says. “A whole mindset shift is going to happen around that.”

The FDA seems open to that possibility. It has already given MM120 “breakthrough therapy” status, which is meant to speed up the evaluation of promising new drugs.

MindMed, for its part, has already launched a pair of “phase 3” studies of MM120. The company expects to complete those trials in 2026.

New details have emerged about a San Francisco child infected with H5N1 bird flu late last year, one in a string of U.S. cases since 2023. Unlike most of those, this infection had no clear source, raising questions about where the virus is persisting, particularly in urban environments, and how human exposures occur.

The case, described by the San Francisco Department of Public Health and CDC in the Morbidity and Mortality Weekly Report on September 4, 2025, involved a school-aged child who fell ill in December 2024.

Their illness looked like an ordinary flu: fever, abdominal pain, muscle aches, conjunctivitis. Symptoms lasted about a week, and by the time H5N1 was flagged through enhanced surveillance—weekly batch testing of samples to identify virus subtypes—the child was already better.

Authorities traced 67 close contacts—including household members, classmates, and health care providers—but found no evidence that the child had transmitted to anyone else. Although only a small fraction of contacts were tested, all samples were negative. That caveat leaves open the possibility that very mild or asymptomatic infections could have been missed, though no evidence points to onward spread.

What makes this case stand out is the missing link. The child hadn’t traveled, hadn’t visited farms, and hadn’t been around poultry or wild birds. The family had purchased poultry from a live bird market, a major risk factor in other outbreaks, but it was cooked and eaten well before the illness began and the child had not been to the market.

Genetic sequencing showed the virus belonged to a group of viruses known as clade 2.3.4.4b, genotype B3.13, which is the same lineage driving the California dairy outbreak and showing up in cats and wild birds. Crucially, the genetic sequence lacked mutations thought to enable efficient human-to-human transmission. Still, the fact that the child was infected without a clear exposure highlights how much we don’t yet understand about the environmental reservoirs or transmission pathways of this virus in urban settings.

This case is one of 70 that have been confirmed in the U.S. since 2023. Most have been linked to dairy cattle or poultry, but in three—including this one—investigators were unable to identify a source of exposure.

So far, American cases have mostly been mild, though there has been one death. That contrasts sharply with the global history of H5N1, where many infections in Asia, the Middle East, and Africa have been fatal. Virologists caution that although American strains mostly lack key mutations for sustained person-to-person transmission, adaptation to mammals has occurred elsewhere, including in marine mammals including sea lions in South America and in mink, foxes, and raccoon dogs on fur farms in Europe.

The report is a reminder of both the potential and the limits of current surveillance. Batch testing caught the infection, but only after the illness was over—too late for isolation or antiviral treatment, and too late to understand exposures in real time.

While it is fortunate that the child’s case was mild, the questions that remain about how the child became infected in the first place underscore how much there is still to learn about the epidemiology of bird flu in North American and the importance of surveillance, rapid diagnostic capacity, and protection for people in contact with potentially infected animals.

It seems to me that the real challenge for public health is how to accurately assess risk to the public—the CDC currently rates it as “low”—when there is still much that remains unknown.