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Rowley is the clinical director of the Division of Infectious Diseases at the Beth Israel Deaconess Medical School and an assistant professor of Medicine at Harvard Medical School in Boston. His clinical and research interests include HIV, sexually transmitted infections, and infections in individuals with opioid use disorder.

Ocular Syphilis and Neurosyphilis in a Patient  Living With HIV

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

Atea Pharmaceuticals is going to provide its full phase 2 data, which will show it met its primary endpoints at the upcoming EASL Congress in May. It will present the data in a poster titled, Efficacy and Safety of Bemnifosbuvir and Ruzasvir after 8 Weeks of Treatment in Patients with Chronic Hepatitis C Virus (HCV) Infection.

“Following our successful phase 2 study and the recent initiation of our global phase 3 program, we look forward to delivering the regimen of bemnifosbuvir and ruzasvir which we believe has the potential to increase the number of HCV patients that are treated and cured,” Atea CEO Jean-Pierre Sommadossi, PhD, said in a statement. “Untreated chronic HCV can have a profound impact on patients’ lives, as well as the associated healthcare and hospitalization costs, as the disease progresses in some cases to liver cancer.”

Earlier this month, the company announced it had dosed its first patient. It’s C-BEYOND trial will be conducted in the US and Canada, the company is concurrently conducting its C-FORWARD, an international trial. Each trial will enroll approximately 880 treatment-naïve patients, including those with and without compensated cirrhosis.

The regimen of bemnifosbuvir and ruzasvir will be administered orally once-daily for 8 weeks (in patients without cirrhosis) or 12 weeks (in patients with compensated cirrhosis) while the regimen of sofosbuvir and velpatasvir will be administered orally once-daily for 12 weeks for all patients with or without compensated cirrhosis.

The primary endpoint for each trial is HCV RNA < lower limit of quantitation (LLOQ) at 24 weeks from the start of treatment and encompasses sustained virologic response 12 weeks post-treatment (SVR12) in each arm. Measurement at 24 weeks from the start of treatment is to ensure the primary endpoint occurs at the same relative timepoint from the start of treatment in all patients. While C-BEYOND and C-FORWARD are both open-label trials, Atea has put measures and processes in place that are designed to blind Atea personnel to patient treatment assignments.

At last year’s The Liver Meeting, Atea presented a poster that demonstrated the combination therapy achieved a 97% sustained virologic response at 12 weeks post-treatment (SVR12) in a phase 2 lead-in cohort. According to the investigators, the analysis supported a short 8-week treatment with bemnifosbuvir and ruzasvir for chronic HCV.

The modeling results provided insight on the mechanism of action and demonstrated that the combination of bemnifosbuvir and ruzasvir was highly effective in blocking both viral replication and viral assembly/secretion in HCV-infected patients, independent of genotype, age, sex, or fibrosis score.

 studies to be approximately 10-fold more active than sofosbuvir (SOF), against a panel of laboratory strains and clinical isolates of HCV GT 1–5. 

 studies have also demonstrated bemnifosbuvir remained fully active against SOF resistance-associated substitutions (S282T), with up to 58-fold more potency than SOF.

The pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV. Bemnifosbuvir has been shown to have a low risk for drug-drug interactions. Bemnifosbuvir has been administered to over 2,200 subjects and has been well-tolerated at doses up to 550 mg for durations up to 12 weeks in healthy subjects and patients.

The other half of the combination, ruzasvir, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. Ruzasvir has been administered to over 1,500 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The PK profile of ruzasvir supports once-daily dosing.



References
1.Atea Pharmaceuticals to Present New Data Showcasing Potential Best-in-Class Regimen of Bemnifosbuvir and Ruzasvir for Treatment of Hepatitis C Virus at EASL Congress 2025. Atea Pharmaceuticals press release. April 23, 2025. Accessed April 24, 2025.
2. Atea Pharmaceuticals Announces Dosing of First Patient in C-BEYOND, Phase 3 Study Evaluating Regimen of Bemnifosbuvir and Ruzasvir for Treatment of Hepatitis C Virus. Atea Pharmaceuticals press release. April 9, 2025. Accessed April 9, 2025.
3. Ribeiro R. Multiscale Modeling of Lead-in Results from a Phase 2 Study of an 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection. Poster #1467 presented at The Liver Meeting. November 15-19, 2024. San Diego, CA



Atea Pharmaceuticals will present the full clinical study at the upcoming EASL Congress in May. 

HCV Combination Therapy Meets Phase 2 End Points, Will Present Data at Conference

Scientists have created the first transgenic nonhuman primate model susceptible to hepatitis B virus (HBV), potentially enabling preclinical testing of curative therapies. The study used PiggyBac transposon technology to insert a liver-specific human sodium-taurocholate cotransporting polypeptide (hNTCP) expression cassette into rhesus macaque embryos.

Two macaque offspring were born from surrogate mothers after zygote modification. Both express hNTCP in the liver. Hepatocytes isolated from the macaques were shown to be susceptible to HBV infection, confirming functional expression of the viral receptor.

HBV is limited by strict species specificity, which has slowed the development of immunocompetent animal models. Prior work showed that vector-mediated expression of hNTCP in macaques permits infection. This study expands on that approach by producing a transgenic model capable of persistent liver-specific expression.

The findings offer a new platform for testing curative therapies for HBV and studying host-virus interactions in a preclinical setting.

In an email Q&A, Ben Burwitz, PhD, associate professor at Oregon Health & Science University’s Oregon National Primate Research Center, discussed the significance of the new model, the advantages of germline hNTCP expression over vector-based methods, and the technical process behind creating the transgenic macaques. He also outlined how the model could support antiviral development while acknowledging its current limitations as a developing research tool.

Contagion: Can you explain the significance of creating a transgenic rhesus macaque model for HBV research, and how does it address the challenges of studying HBV in nonhuman primates?

“One of the major barriers to the study of curative HBV therapies is the lack of a translational, immunocompetent model of HBV infection. HBV has a narrow host range, infecting only humans and chimpanzees. Chimpanzee research was halted in 2012 by the NIH, and this left a huge gap in the field. Very early on we showed that rhesus macaque hepatocytes could be infected with HBV in vitro if you artificially expressed the HBV receptor on their surface. This was the first data showing that the only block to HBV infection in rhesus macaques was the viral entry step. From there, we created viral vectors (e.g., Ad5 and AAV) that expressed the HBV receptor and could be given to rhesus macaques in vivo. These animals became susceptible to HBV infection, which drove our desire to make transgenic rhesus macaques expressing the HBV receptor naturally from the germline.”

Contagion: What specific advantages does the liver-specific expression of the human NTCP receptor provide for studying HBV infection in this model, and how does it replicate the natural susceptibility of human hepatocytes?

 “Rhesus macaques expressing human NTCP (HBV receptor) from the germline have several advantages over creating HBV susceptible rhesus macaques through viral vectors:

2) Not all hepatocytes are transduced by viral vectors, limiting HBV spreading

3) The viral vector genomes and hNTCP expression can be lost during cell division. Therefore, an optimal rhesus macaque HBV model would have transgenic, hepatocyte-specific hNTCP expression to overcome these challenges.”

 “In terms of replicating the HBV susceptibility of human hepatocytes, all measures of HBV replication that we have looked at thus far in vitro in rhesus macaque hepatocytes expressing human NTCP look identical to human infection.”

Contagion: Could you expand on the methodology used in this study, particularly the use of PiggyBac transposon technology to create the transgenic macaques? What are the key steps involved in generating these animals?

 “PiggyBac is a transposon. Transposons, also known as ‘jumping genes’, were first discovered by Barbara McClintock in the 1940s while studying maize. There are two components of the system. First, the transposon is the genetic element that can be moved from one genomic location to another (in our case, moving human NTCP from a circular DNA template to the rhesus macaque genome). Second, there is an enzyme called a transposase that facilitates the moving of the transposon. Therefore, we needed to inject single-cell rhesus macaque embryos (called zygotes) with both our transposase and our transposon.”

 “To be honest, the genetic engineering components of the project were far more straightforward than the Assisted Reproductive Technologies components. The Assisted Reproductive Technologies core at the Oregon National Primate Research Center capitalizes on decades of rhesus macaque reproductive and developmental science (the repro division was the first and only division upon the opening of the Oregon National Primate Research Center) to finally bring to bear our ability to make transgenic rhesus macaques. This core is second to none at in vitro fertilization, microinjection of single cell embryos, and biopsies and cryopreservation of transgenic embryos. My lab does none of this, we were just along for the amazing ride and had a good idea on how to use the technology.”

Contagion: What implications do these transgenic macaques have for the development of HBV therapies, and how do you envision this model being used in future drug development and therapeutic testing?

 “There has been a successful HBV vaccine since the early 1980s, yet many parts of the world continue to have high rates of HBV transmission. The vast majority of people living with chronic HBV infection (i.e., an infection that their body was unable to clear naturally) were infected at the time of birth. Therefore, the most relevant way we can use our model is to study the critical aspects of vertical transmission (mother-to-child at birth) that lead to chronicity, as well as to study new drugs that can eliminate HBV from the liver at different times in life. Humans living with chronic HBV live for decades, and therefore we have a lot of time to study these models if we can show that they also maintain chronic HBV infection indefinitely.”

Contagion: Are there any challenges or limitations in using this model, and how might researchers overcome them as they move forward with HBV-related studies?

 “In the end, no matter what manipulations we make to rhesus macaques, they are still not natural carriers of HBV infection. Therefore, there may still be barriers to the use of this model that we cannot anticipate. For instance, there may be immune responses to HBV in rhesus macaques that are not present in humans, simply because HBV has co-evolved with humans for over 10,000 years. We are excited about our new model, but there is still (and always seems to be) a lot of work left ahead of us.”

This new transgenic rhesus macaque model is the first immunocompetent nonhuman primate system naturally susceptible to hepatitis B virus. While it still requires further validation, it provides a useful tool for studying chronic infection, vertical transmission, and testing potential curative therapies in a biologically relevant setting.

Rust LN, Wettengel JM, Biswas S, Ryu J, Piekarski N, Yusova S, Lutz SS, Naldiga S, Hinrichs BJ, Sullivan MN, Lo JO, Protzer U, Smedley JV, Sacha JB, Hanna CB, Bimber BN, Hennebold JD, Burwitz BJ. Liver-specific transgenic expression of human NTCP in rhesus macaques confers HBV susceptibility on primary hepatocytes. Proc Natl Acad Sci U S A. 2025 Feb 18;122(7):e2413771122. doi: 10.1073/pnas.2413771122. Epub 2025 Feb 12. PMID: 39937851; PMCID: PMC11848295

Q&A with Ben Burwitz, PhD, on the significance of the new hepatitis B virus (HBV)-susceptible primate model and its potential to advance hepatitis B research and therapeutic development.

New Transgenic Rhesus Macaque Model Paves Way for HBV Therapy Development

During a hepatitis E outbreak in 2022 in South Sudan at the Bentiu refugee camp, the Hecolin HEV vaccine was shown to be highly protective. The results were published in 

“In the primary analysis we estimated an unadjusted two-dose vaccine effectiveness of 67.8% (95% CI –28.6 to 91.9), and a 2-dose vaccine effectiveness of 84.0% (–2085 to 992) after adjustment for potential confounders,” the investigators wrote. “The bias indicator analysis suggested that test-negative cases might have been more likely to have been vaccinated than their matched community controls due to different health care seeking behaviors, potentially meaning underestimation of effectiveness estimates. The test-negative design, which uses facility-matched controls, led to an adjusted two-dose effectiveness of 89.4% (564 to 98.0).”

The camp was an environment that enabled outbreak conditions. “The Bentiu camp in South Sudan, home to more than 100,000 people who have been displaced due to civil war, is a regular victim of hepatitis E and other waterborne disease outbreaks, likely due to the poor sanitation conditions and frequent flooding,” study senior author Andrew Azman, PhD, epidemiologist, UNIGE-HUG Centre for Emerging Viral Diseases, Médecins Sans Frontières

, and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, said in a statement.

The investigators identified 859 patients with suspected HEV. Of this group, 201 met the eligibility criteria and 21 cases had laboratory confirmed hepatitis E. Among the confirmed cases, 10 (48%) were unvaccinated compared with 33 (27%) of 121 matched controls, between May 10 and Dec 30, 2022.

Along with its protection, the study confirmed the protection provided by 2 doses during an epidemic, and the reduction of the disease. ‘‘Our results combined with others helped lead to recent approval by WHO’s International Coordinating Group (ICG) on Vaccine Provision of a stockpile of hepatitis E vaccines for emergencies,” Azman said. “This stockpile has the potential to save many lives and we’re looking forward to seeing it in action. These results have also already contributed to the WHO recommendations on the use of a 2-dose schedule,”

Developed in China, the Hecolin vaccine was approved in the country in 2011. It is a recombinant protein-subunit hepatitis E vaccine (HEV239) developed by Xiamen Innovax Biotech Co. It is recommended for adults aged 16 and older, particularly those at high risk of HEV infection. The World Health Organization (WHO) has recommended using the Hecolin vaccine in disease outbreak settings.

According to the Centers for Disease Control and Prevention (CDC), hepatitis E (HEV) is more common in many parts of the world where sanitation is poor and people have limited access to clean drinking water.

It is more rare in the US, but it is a leading cause of acute viral hepatitis, particularly in Asia and Africa.

 Approximately 20 million people worldwide are infected annually with HEV, according to the WHO. The virus is especially dangerous for pregnant women and people with chronic illnesses, with a mortality rate of up to 10%-50%.

1.Nesbitt RC, Kinya Asilaza V, Alvarez C, et al. The effectiveness of two doses of recombinant hepatitis E vaccine in response to an outbreak in Bentiu, South Sudan: a case-control and bias indicator study. 

. 2025;25(5):537-547. doi:10.1016/S1473-3099(24)00657-1
2.Hepatitis E vaccination is effective in an epidemic. Eurkealert. January 14, 2025. Accessed April 30, 2025.


https://www.eurekalert.org/news-releases/1070407


3. Hecolin Hepatitis E Vaccine.Vax Before Travel. last reviewed Janaury 25, 2025. Accessed April 30, 2025. 
https://www.vax-before-travel.com/vaccines/hecolin-hepatitis-e-vaccine
4.Hepatitis E Basics. CDC. May 14, 2024. Accessed April 30, 2025. https://www.cdc.gov/hepatitis-e/about/index.html



The Hecolin hepatitis E virus vaccine was delivered with a reduced 2-dose schedule to people living in a refugee camp to try to reduce an outbreak.  

Hepatitis E Vaccine Demonstrates High Efficacy in Outbreak Setting  

Atea’s investigational combination treatment of bemnifosbuvir and ruzasvir showed these results after an 8-week treatment regimen.

HCV Therapy Demonstrates 98% Sustained Virologic Response at 12 Weeks Post-Treatment

At the ongoing European Association for the Study of the Liver (EASL) Congress 2025, Atea Pharmaceuticals announced the full results from its phase 2 clinical trial, which showed a 98% sustained virologic response rate at 12 weeks post-treatment (SVR12) in 210 of 215 participants with the regimen in the “Per-Protocol Treatment-Adherent Population,” using an 8-week treatment duration. Additionally, the SVR12 rate was 95% in 245 of 259 trial participants in the “Per-Protocol Regardless of Adherence Population” which included patients who were not treatment adherent (17%).

“If you look at the more expanded population—that wasn't the primary endpoint—there was a 259 patients, which includes patients that were less compliant to therapy, and still, despite suboptimal compliance, had a 95% cure rate,” said Eric Lawitz, MD, clinical professor of medicine at The Texas Liver Institute, University of Texas Health, San Antonio.

In addition, he explains a majority of hepatitis C patients are different from previous years, and that the Atea trial showed promising results for this population.

“Of the 181 non cirrhotics, 180 were cured…this is really important in 2025 because the burden of hepatitis C is really emerging in the young people who are non cirrhotic and just need an effective treatment,” Lawitz said.

The phase 2 study was conducted in treatment-naïve, chronic HCV-infected patients across genotypes either without cirrhosis (n=238) or with compensated cirrhosis (n=37). Results demonstrated 99% of treatment-adherent patients who were non-cirrhotic and infected with genotypes 1-4 achieved SVR12, demonstrating robust pan-genotypic potency and supporting an 8-week treatment duration in non-cirrhotic patients in the phase 3 program. A 100% SVR12 rate was observed in non-cirrhotic, treatment-adherent patients infected with genotype 3, a historically difficult genotype to treat and cure.

Last month, the company announced it had begun its phase 3 trial program, and this will incorporate its C-BEYOND trial, which will be conducted in the US and Canada, and its C-FORWARD trial, an international study. Each trial will enroll approximately 880 treatment-naïve patients, including those with and without compensated cirrhosis.

“As you look at hepatitis C antiviral drug development over the years, phase 3 tends to reproduce phase 2 data. Ultimately, you get bigger numbers and statistical significance,” Lawitz said. “Of course, in this phase 2 trial, this was an open label and not a placebo or active, controlled study. In the phase 3 trial, we would expect an active control study, and so my expectations would be that we would see very similar results with bigger numbers.”

1. Atea Pharmaceuticals Announces Full Results from Phase 2 Study of Regimen of Bemnifosbuvir and Ruzasvir for Treatment of Hepatitis C Virus (HCV) Presented at EASL Congress 2025. May 7, 2025. Accessed May 8, 2025.
https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-announces-full-results-phase-2-study
2. Atea Pharmaceuticals Announces Dosing of First Patient in C-BEYOND, Phase 3 Study Evaluating Regimen of Bemnifosbuvir and Ruzasvir for Treatment of Hepatitis C Virus. Atea Pharmaceuticals press release. April 9, 2025. Accessed May 8, 2025.
https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-announces-dosing-first-patient-c-beyond




Atea Pharmaceuticals' investigational combination treatment of bemnifosbuvir and ruzasvir showed these results after an 8-week treatment regimen.

HCV Therapy Demonstrates 98% Sustained Virologic Response at 12 Weeks Post Treatment

A recent study of the highly pathogenic avian influenza A(H5N1) virus isolated from a dairy farm worker in Michigan has revealed concerning findings about its transmission capabilities. The virus, A/Michigan/90/2024 (MI90), was shown to transmit via airborne particles in a controlled ferret model and cause moderate disease, suggesting a possible shift in the virus’s capacity to infect humans and spread in mammalian populations. These results, published in 

, underscore the growing concerns about the virus’s potential to cause a future pandemic.

The Michigan dairy farm worker, who was diagnosed with conjunctivitis following exposure to infected animals, is part of a larger multistate outbreak of H5N1 that has been impacting US dairy cattle since 2024.1 As of May 6, 2025, the CDC has reported 70 confirmed and probable human cases of H5N1 in the U.S. since 2024, with 41 of those linked to dairy cattle and 24 to poultry operations. Also, there was a first US death associated with H5N1 occurred in Louisiana. Despite these human infections, no evidence of sustained human-to-human transmission exists.

In a controlled study, ferrets were inoculated with the MI90 virus to evaluate its ability to transmit through direct contact and respiratory droplets. All 18 infected ferrets survived the 21-day trial, although moderate illness was observed. Symptoms included a mean weight loss of 9.8 percent, transient fever (1.8°C above baseline), lethargy, and respiratory and ocular symptoms between days 4 and 9 post-infection. The highest virus titers were detected in the ethmoid turbinates (7.4 log10 PFU/mL), with limited brain and gastrointestinal tract detection.

Transmission was confirmed in both contact models:

: All 6 naive ferrets shed the virus and seroconverted, demonstrating a 100 percent transmission rate.

: 3 out of 6 naive ferrets shed the virus (peak 2.6 to 4.8 log10 PFU/mL) between days 9 and 11 post-contact, confirming a 50 percent airborne transmission rate.

Airborne virus sampling indicated that ferrets infected with MI90 released infectious particles, peaking at day 3 with up to 133 PFU/hour detected by cyclone-based aerosol samplers. These findings suggest that the virus is capable of transmitting via respiratory droplets, further raising concerns about its potential for wider spread.

When compared to a genetically distinct H5N1 virus isolated from a dairy worker in Texas, the MI90 strain demonstrated reduced virulence. The Texas virus contains the E627K mutation in the PB2 protein, which is associated with enhanced mammalian adaptation. MI90 encodes 627E and carries the M631L mutation, also linked to adaptation in mammals. Despite these genetic differences, both strains transmitted efficiently in ferrets and produced detectable airborne virus.

The CDC continues to closely monitor the outbreak through its national influenza surveillance systems, which have tested over 186,000 specimens without detecting unusual flu activity. More than 16,600 individuals exposed to infected animals have been monitored, and targeted surveillance has identified 64 positive cases.

The CDC’s latest update highlights ongoing widespread animal infections. Over 1,000 dairy herds in 17 states, nearly 13,000 wild birds, and over 169 million poultry have been affected by H5N1. Health officials urge continued vigilance, especially in agricultural settings, as these viruses continue to evolve and adapt.

In a separate assessment using the Influenza Risk Assessment Tool (IRAT), the CDC evaluated two avian influenza A(H5N1) viruses, A/California/147/2024 and A/Washington/239/2024. The assessment found that both viruses posed a moderate public health risk due to their genetic characteristics, zoonotic potential, and limited but concerning spillover into humans. The IRAT results align with the recent Texas case report, reinforcing the need for continued surveillance, particularly in environments where animal-to-human transmission remains a concern.

The findings from this study and the ongoing outbreak emphasize the importance of continued monitoring and risk assessment as H5N1 viruses evolve. While the current risk to humans remains low, these developments highlight the need for heightened awareness and preparedness in both agricultural and healthcare settings.

1. Brock N, Pulit-Penaloza JA, Belser JA, Pappas C, Sun X, Kieran TJ, et al. Avian influenza A(H5N1) isolated from dairy farm worker, Michigan. Emerg Infect Dis. 2025 June [date cited]. 

2. CDC. H5 Bird Flu: Current Situation. May 6, 2025. Accessed May 7, 2025. 

https://www.cdc.gov/bird-flu/situation-summary/index.html#:~:text=What%20to%20know,70%20cases

3. CDC. Results of Influenza Risk Assessment Tool. May 2, 2025. Accessed May 7, 2025. 

https://www.cdc.gov/pandemic-flu/php/monitoring/irat-virus-summaries.html

Michigan dairy worker's infection is linked to widespread H5N1 outbreaks, as new findings suggest increased transmission risk and moderate disease in mammals.

Christopher F. Rowley, MD, MPH

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