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Guideline Updates for Infective Endocarditis, HAP, and VAP

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

The combination of the antiviral agents islatravir and lenacapavir demonstrates both efficacy and safety, leading to advancement into Phase 3 trials.

Gilead and Merck Report Successful Phase 2 Results for Investigational Once-Weekly HIV Treatment

Gilead Sciences and Merck have announced promising Phase 2 clinical trial results for an investigational weekly oral combination regimen of islatravir and lenacapavir, demonstrating sustained viral suppression in adults living with HIV after 48 weeks. This innovative regimen could become the first once-weekly oral treatment for HIV.

In the study presented at IDWeek, 94.2% of participants who switched from a daily regimen of Biktarvy to the new treatment maintained viral suppression, defined as HIV-1 RNA levels below 50 copies/mL. Importantly, no participants had detectable viral loads at this benchmark.

In our interview with Jared Baeten, Gilead’s Senior Vice President of Virology, he stated, “The study showed promising results for maintaining viral suppression in individuals with HIV. The primary outcome at week 48...indicated that the regimen is poised to advance to Phase 3 trials.” This underscores the significance of the trial's findings, highlighting that the treatment not only achieved its primary outcome but also sets the stage for further clinical evaluation in Phase 3 trials, a critical step toward potential approval.

The open-label study involved 104 virologically suppressed adults randomized to either the once-weekly regimen (n=52) or continued daily Biktarvy (n=52). Participants' median age was 40, with diverse representation. Secondary endpoints showed comparable rates of viral suppression between the two groups.

Baeten emphasizes the effectiveness of the investigational regimen by stating, “The study showed promising results for maintaining viral suppression in individuals with HIV. The primary outcome at week 48...indicated that the regimen is poised to advance to Phase 3 trials.” This underscores the significance of the trial's findings, highlighting that the treatment not only achieved its primary outcome but also sets the stage for further clinical evaluation in Phase 3 trials, which is a critical step toward potential approval.

Adverse events were reported in 19.2% of the islatravir-lenacapavir group, primarily mild, with dry mouth and nausea being the most common. In contrast, only 5.8% of participants on Biktarvy reported treatment-related adverse events, and no severe events related to the study drugs occurred. Baeten notes, “This combination demonstrated a favorable safety and tolerability profile, further supporting its progression.”

This combination regimen is under further investigation in two Phase 3 studies aimed at evaluating its safety and efficacy in a broader population of virologically suppressed individuals. Both islatravir and lenacapavir remain investigational compounds, with ongoing studies assessing their long-term potential as treatment options.

Baeten stated, “Additionally, the collaboration with Merck reinforces the development and potential commercialization of this HIV treatment regimen, with both organizations dedicated to advancing new and effective options for HIV treatment.” This highlights the strategic partnership between Gilead and Merck, essential for the successful development and commercialization of the treatment, addressing public health challenges. As HIV continues to pose public health challenges, these developments offer hope for more flexible and accessible treatment solutions for those living with the virus.

Press Release. Gilead and Merck Announce Phase 2 Data Showing a Treatment Switch to an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression in Adults at Week 48. 

October 19, 2024. Accessed November 4, 2024. 

https://www.gilead.com/news/news-details/2024/gilead-and-merck-announce-phase-2-data-showing-a-treatment-switch-to-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral-suppression-in-adu

Conferences

Despite advances in understanding and treating Long COVID, many questions about its mechanisms, susceptibility, and varied recovery patterns remain unresolved, underscoring the need for continued research.

EP 5: What We Know But Still Have to Learn About Long COVID

Since the start of the COVID-19 pandemic, the persistence or appearance of neurologic symptoms after clearance of SARS-CoV-2 infection has become a serious health challenge for patients and clinicians worldwide. The effects of postacute sequelae of SARS-CoV-2 infection (PASC), commonly known as 

, can be debilitating and persist for months after infection. Some of these symptoms can include fatigue, neuropsychiatric sequelae, sleep disturbances, sensorimotor symptoms, cognitive impairment/brain fog, hypoguesia/hyposmia, hearing loss, and ocular symptoms.

As emphasized by the research and experts in the field, currently there are no specific tests for the diagnosis of Long COVID, and clinical features such as laboratory findings and biomarkers may not specifically relate to the condition. It is important to develop and validate biomarkers for the prediction, diagnosis, and prognosis of Long COVID and its response to therapeutics. Regardless of age or preexisting health conditions, Long COVID can affect anyone, highlighting that this condition is not restricted to any specific demographic and does not discriminate, even against the healthiest individuals.

Recently, we conducted a Long COVID roundtable in collaboration with 

to continue our roundtable video series where we delve into important clinical neurological disease topics with a comprehensive discussion with clinicians in the field. Despite growing knowledge about Long COVID, many questions remain unanswered. In this last episode, experts acknowledged the significant progress in recognizing and studying this condition, particularly in areas like endothelial and neuroinflammatory changes. 

In this discussion, the panel highlighted how advances such as the use of AI for drug repurposing and proteomics may offer hope for new treatments. However, much is still unknown, including the exact mechanisms of Long COVID, who is most susceptible, and why recovery varies widely among patients. The pandemic has spotlighted long-standing post-infectious syndromes, driving further research into how infections impact neuroinflammation, neurodegeneration, and public health.

Ravindra Ganesh, MD, MBBS, FACP, Dip ABOM, general medicine doctor at the 

, clinical associate professor of neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, director of the Dysautonomia Clinic.

 physical medicine and rehabilitation physician, professor, and chair of rehabilitation medicine at UT Health, leader of the Long COVID clinic.

 I think the more we've learned about Long COVID, the more questions I’ve had. It’s been extremely validating to have an infection-associated chronic illness taken seriously by the government, the NIH, and larger academic bodies. It’s been good to see funding coming in and great to see the data supporting what we’ve suspected for years—that there are endothelial changes, neuroinflammatory changes, and that testing, along with all of this research, is being used to better delineate a pathophysiology that, honestly, has been pretty mystifying for the last 40-50 years as we’ve studied these diseases. Some of the things we’re seeing, such as the application of AI to repurpose orphan drugs and the proteomics research for Long COVID, are promising. Hopefully, this will lead to therapeutic trials that can help our patients.

What do we need to learn? Everything. We have a clinical definition, but we don’t have a unified pathophysiology. We don’t have clear delineations—like, this is what it looks like if you have Long COVID with an endothelial predominance or Long COVID with both endothelial and neuroinflammatory components—and how to treat them. We also don’t know exactly who is susceptible. We have ideas based on hypermobility, family history, and responses to previous infections, but we don’t yet have a genetic signature that could predict who will be at high risk after exposure to SARS-CoV-2. We also don’t know how long each person’s illness will last. I still don’t understand how I can have two patients in my clinic, both six months post-infection and equally sick, but one recovers in a year while the other remains chronically ill for four years, with nothing making them better.

I think this has raised more questions than answers, but the attention and the amount of data we’ve collected are incredibly encouraging.

: I still think we don’t know what we don’t know. It’s one of those Dunning-Kruger effects—there’s still so much we don’t understand, even for people like us who care for these patients regularly.

 I agree with my colleagues. COVID has uncovered longstanding issues with post-acute infectious syndromes that have existed for decades, if not centuries, but were never properly studied or addressed. We pushed these patients aside. Now, with the Long COVID pandemic affecting millions, we’re saying, “What do we do now?”

The silver lining of this pandemic, which is truly a human disaster, is that we can finally address these unknown pathophysiologies. We’re uncovering that not only does SARS-CoV-2 impact the brain, but so do multiple viral or bacterial infections, leading to both neuroinflammation and neurodegeneration. New science now tells us that even multiple sclerosis has a causative link to the Epstein-Barr virus. I was taught during my residency that EBV was too common to cause multiple sclerosis, but this understanding has shifted.

There’s going to be a whole new field focused on how infections impact human health and disease, particularly the brain. We’ll need to study the genetic predispositions that make some individuals more susceptible to these adverse outcomes. We’ve always had cases of post-acute Lyme syndrome, post-mono syndrome, and post-flu syndrome. Now, we’re also seeing similar symptoms after vaccinations in some cases. All of these unknowns are coming to light, and we are being forced to study them.

Before, we could ask, “How many of these patients are there, really?” Now we know that millions of people are affected. Even if you apply the smallest estimate—3.5% to 4% of those with long COVID, even with Omicron—that still means millions of people worldwide are impacted. These are young people who are unable to work or go to school. The impact is enormous, affecting public health, disease management, and the economy.

The silver lining is that we may finally get some answers. But I don’t think we’re going to like what we learn. What we do with that information will be critical. In the past, it was easier to remain in the unknown—it’s like the saying, “What you don’t know can’t hurt you.” But now, we’ll know, and we’ll have to act on that, likely at both a public health and policy level.

What We Know But Still Have to Learn About Long COVID

Clinicians discuss the complexities of diagnosing Long COVID, emphasizing the need for improved biomarkers and diagnostic technologies to better serve affected patients.

Addressing the Diagnostic Gap in Long COVID Care

In Episode 4 of our Long COVID roundtable collaboration with 

, clinicians noted that diagnosing Long COVID often relies on strategies used for other chronic illnesses, reflecting the challenges and limitations.

Ravindra Ganesh, MD, MBBS, FACP, Dip ABOM, general medicine doctor at the Mayo Clinic and leader of their Long COVID clinic.

Svetlana Blitshteyn, MD, FAAN, clinical associate professor of neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, director of the Dysautonomia Clinic.

Monica Verduzco-Gutierrez, MD, physical medicine and rehabilitation physician, professor, and chair of rehabilitation medicine at UT Health, leader of the Long COVID clinic.

Verduzco-Gutierrez and Blitshteyn discuss the gap between research on Long COVID and the clinical tests currently available. Verduzco-Gutierrez mentions studies showing abnormal vascular markers and gene methylation patterns associated with Long COVID but notes these tests are not accessible in practice. Blitshteyn highlights the need for validated immunologic tests for clinicians and emphasizes the importance of thorough clinical evaluations. They both call for advancements in diagnostic technologies, including functional MRIs and tests for hypercoagulability, to better identify patients with Long COVID. Ganesh adds that functional testing can reveal physiological issues not seen in standard scans, highlighting the need for improved diagnostic tools.

: “Are we still talking about our wish list? Because that would be mine. We don’t have these tests available yet. But there are so many studies showing that Long COVID is real. We know that there's pathophysiology involved. In a recent preprint from 

, it was shown that there are abnormal vascular markers associated with vascular inflammation. Patients with neuropsychiatric Long COVID symptoms and cognitive changes were the ones who had these abnormalities, compared to those who did not develop Long COVID. Of course, I’m wondering if I can check any of these labs in real life. Unfortunately, they’re not available through common labs like Labcorp or Quest, so they’re not readily accessible. But at least we’re seeing differentiating factors.”

“There was another study that looked at methylation patterns of people’s genes. It gives us a clue, if certain genes methylate in specific ways, those individuals are more likely to develop Long COVID. But again, we don’t all have big labs to analyze gene methylation after infection. We also know that the complement system and inflammation are impacted in people with Long COVID. It’s nice to see we’re getting closer to having tests that show there’s abnormal pathobiology. Now, we need to make these into accessible biomarkers.”

: “I agree. There’s always a huge gap between the tests available for researchers and those available for clinicians. We need to find a cost-effective way to bridge this gap. I would love to have cytokine panels and T-cell type tests available, ones we could apply to our patients. That’s been long overdue. Even before the COVID pandemic, there was a shortage of good, accessible, and validated immunologic tests, including antibody tests for autoimmune disorders that don’t show up on standard autoimmune panels. We need these tests to be available to clinicians. They need to be validated, from certified labs, and informative.”

“At the end of the day, waiting for these tests to legitimize or treat these disorders may not be practical. We’ve already dealt with other autoimmune inflammatory conditions with poor markers. For example, there’s rheumatoid arthritis with negative rheumatoid factor, and Sjogren's syndrome with negative antibodies. It’s going to be important to categorize by subtypes, positive Long COVID patients versus negative ones. But I think ultimately, we’ll have to rely on clinical features and stratify patients based on their clinical presentations.”

: “Right now, we have the National Academy of Medicine’s definition of Long COVID, which is a clinical definition. Listen to your patients, get the timeline, and see how long their symptoms have been going on. Of course, work them up, don’t just do the basics. Be as thorough as possible, as we discussed earlier. Right now, it’s all about listening to them and taking a thorough clinical history. It’s a clinical diagnosis, and we’re going to have to accept that for the time being.”

: “I think Long COVID presents a great opportunity to develop other technologies and modalities for clinical use. We need to make specialized neuroimaging and MRI sequences more available, accessible, and affordable. Functional MRI should be cheaper and more widely used. We also need tests that can identify hypercoagulability visible on MRI. Right now, when we do a 3 Tesla MRI of the brain, we often don’t see much. We do see increased white matter changes in some patients with Long COVID, but that’s not enough. We need to go further.”

“Wouldn't it be great if this "shadow pandemic" of Long COVID spurred the development of these new technologies in clinical practice for both clinicians and patients? I’m thinking about MR spectroscopy, PET scans, spinal taps, lumbar punctures, and autoimmune profiles of cerebrospinal fluids, which we don’t typically get. "How do we assess venous outflow in the brain to check for hypercoagulability or stenosis?" Maybe the CSF isn’t draining properly in many patients. "What about the glymphatic system?" There’s so much in neuroscience we can apply in clinical practice now.”

: “I think most of our patients look fine on anatomical scans, but when we challenge their physiology, when we stress them, that’s when we start to see the deficits. The changes show up. Functional MRIs might be one of the best approaches because patients are generally fine at baseline. But as they experience cognitive, physical, or emotional stress, that’s when their energy diminishes, and their symptoms worsen. That’s where the physiological issues often become apparent.”

“The only quote-unquote "reliable marker" for ME/CFS is the two-day CPET. I don’t like doing it because you’re essentially inducing a crash to show that the patient had a crash. I’ve done it twice in my life, both times because insurance required it for disability evaluation. But the testing in both the neurological and immunological realms is really lacking, and that’s what we’re seeing in our patients. It’s definitely high on my wish list.”

Clinicians discussed the complexities of diagnosing Long COVID, emphasizing the need for improved biomarkers and diagnostic technologies to better serve affected patients.

Sohab Asghar, MBBS, MD, highlights the role of socio-economic factors and demographic disparities in HIV mortality from 1999 to 2023.

Examining Disparities in HIV Mortality That Remain Underexamined

Despite advances in HIV management, mortality trends in the U.S. population remain insufficiently studied, hindering evidence-based interventions. This analysis examines HIV-related mortality across demographic factors—age, gender, race/ethnicity, urbanization, and U.S. Census Regions—using state and county-level Age-Adjusted Mortality Rates (AAMR).

At IDWeek, Muhammad Sohaib Asghar (Sohaib), MBBS, MD, resident physician at AdventHealth Sebring discussed key factors identified that contributed to the trends in HIV mortality, and how might these insights guide future public health strategies, “There are many known risk factors for HIV mortality, such as male gender and African American race, but a significant recent factor is socio-economic determinants. States like Florida, Georgia, and Louisiana have higher prevalence rates, which directly correlate with increased mortality. Understanding these factors is crucial for guiding future public health strategies.”

From 1999 to 2023, there were 271,568 HIV-related deaths (AAMR=3.4 per 100,000; 95% CI: 3.3-3.5). Overall mortality decreased at an annual rate of -4.66% (95% CI: -4.96, -4.43). However, trends showed increases among males (2018-2021), individuals aged 65-84, Non-Hispanic American Indian or Alaskan Natives (2017-2023), and in all regions (2018-2021). Top affected states included the District of Columbia, Florida, Maryland, Louisiana, New York, and Georgia. Notably, Union and Miami-Dade Counties in Florida reported high rates, while Mississippi exhibited the slowest decline.

Asghar discussed the strengths and limitations of using the CDC WONDER Database for this study and how they influenced findings. “CDC Wonder is a very large database, very comprehensive. We have many socio-demographic variables that we can use to stratify the data... The only drawback that I found from the CDC Wonder database is that it is based on the Billing Coding System, so lots of times we don't have specific underlying cause of death.”

Data were sourced from the CDC WONDER Database, utilizing ICD-10 codes (B20-B24) to identify HIV-related deaths from 1999 to 2023. Trends were evaluated via Joinpoint regression for annual percent changes (APC), with urbanization classified per the NCHS 2013 scheme.

Asghar discussed recommendations for policymakers and clinicians to enhance HIV prevention and treatment efforts in the US, “Targeted intervention should be at primary care level. Primary care providers should be able to take care of these patients, provide the supply kits, not all of the patients are able to take care of them or be preventive about them. Going back to restrategize at community-based levels would surely make sure that we end this endemic throughout the country.”

While overall HIV mortality decreased from 1999 to 2023, disparities exist across demographics and regions. Enhanced public health surveillance is necessary to identify high-risk groups for targeted interventions.

HIV Mortality Trends among the United States Population from 1999-2023: A Retrospective Study using the CDC Wonder Database. Poster 390 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

Sohaib Asghar, MBBS, MD, highlights the role of socio-economic factors and demographic disparities in HIV mortality from 1999 to 2023.

, commonly known as bird flu, has had an increase in human cases in the United States recently, particularly among poultry and dairy workers. H5N1 has primarily circulated in the Midwest, with these cases raising concerns about potential human transmission and broader public health implications. Understanding the current landscape of H5N1, including recent data and prevention strategies, is essential as health officials monitor the situation.

The CDC is monitoring influenza data at national, state, and local levels. As of October 9, 2024, 18 human cases of H5N1 have been reported in the US since 2022. Since February 2022, more than 15,500 individuals have been monitored after exposure to infected animals, with 590 tested for novel influenza A. Recently, approximately 6100 individuals have been monitored, including 3350 exposed to dairy cows and 2800 to birds and other animals.

Currently, CDC surveillance systems indicate no unusual flu activity related to H5N1. In the week ending October 19, 2024, public health laboratories reported no positive tests for novel influenza A, and wastewater monitoring detected H5 at only 1 out of 320 sites.

CDC continues to collaborate with the USDA, FDA, and state health officials using the One Health approach to monitor the situation. The agency has deployed a multilingual epidemiological field team to assist local health departments with outreach and surveillance efforts. To date, more than 5100 individuals exposed to potentially infected animals have been monitored, and more than 54,000 specimens have been tested for H5N1viruses.

 marked the 14th reported case this year and was the first without documented occupational exposure. Identified through seasonal flu surveillance, the patient was hospitalized but has since recovered. Experts suggest that transmission routes may include incidental contact with infected animals, indicating a need for further research into risk factors.

Meghan Davis, DVM, PhD, MPH, an associate professor at Johns Hopkins Bloomberg School of Public Health, discussed potential alternative transmission routes for avian influenza, highlighting the Missouri case as an example of variable exposure routes beyond direct animal contact. “What the case in Missouri really highlights is that the transmission routes are quite variable. It's not just occupational contact with live animals; it could also be from incidental contact with animals, and we don't yet fully recognize what those risk factors might be for people,” she said.

The serological testing methods used in the CDC's investigation of the Missouri H5N1 case included several assays. The primary method was the Microneutralization (MN) assay, which identifies influenza virus-specific antibodies in blood sera by measuring the ability of these antibodies to neutralize the virus. The Hemagglutinin Inhibition (HI) assay was employed to detect antibodies to the hemagglutinin of specific influenza viruses; this test assesses the ability of antibodies to agglutinate red blood cells, using multiple types of red blood cells for detection.

Another method used was the Multiplex Antibody Detection Assay (MIADA), which looks for antibody binding to multiple influenza antigen targets (28-plex) and measures total immunoglobulin responses, including IgG, IgM, and IgA. A Seasonal Influenza Serum Absorption step was included to remove antibodies against seasonal influenza viruses to reduce cross-reactivity, enhancing the specificity of the H5N1 testing.

The CDC also developed 2 Reverse Genetics (RG) viruses that mirrored the antigenic changes found in the H5N1 virus from the Missouri case. This allowed for precise serological testing. Together, these methods provided a comprehensive assessment of immune responses and potential previous exposure or infection with H5N1 in the individuals tested.

, the Department of Public Health confirmed 7 probable cases of H5N1 linked to dairy farm outbreaks. Most infections have occurred among farm workers, with mild symptoms reported.

To continue, the CDC confirmed H5 infections in two of four poultry cullers from 

 state, marking the state's first cases. Despite the confirmed cases, public health officials maintain that the risk to the public remains low, although those with occupational exposure to sick animals face a higher risk.

Despite the rise in cases, Davis said, “The good news, however, is that despite the human cases linked to poultry outbreaks and dairy cow infections primarily affecting workers, no human-to-human transmission has been identified yet. This is an important aspect to monitor closely.”

One Health: An Approach Bridging Human, Animal, and Environmental Health

The One Health approach is a collaborative framework that recognizes the interconnectedness of human, animal, and environmental health. It advocates for a multidisciplinary strategy to address health challenges, particularly zoonotic diseases, by integrating expertise from fields like medicine, veterinary science, and environmental science to promote holistic solutions and sustainable ecosystems.

Davis is a proponent of the One Health approach. She said, “One Health is foundational to many infectious diseases that are zoonotic. What is recognized with highly pathogenic avian influenza is that it has been present for a considerable period. Like seasonal influenza in humans, there are influenza strains that predominantly affect birds. These include reservoirs—types of birds that carry the virus but don't get very sick themselves—such as waterfowl like ducks. On the other hand, there are birds that can become severely ill and die, including domestic poultry like broiler chickens, layer chickens (for meat and eggs), turkeys, and other species kept by humans.”

According to the CDC spokesperson, “CDC’s One Health approach recognizes the interconnection between people, animals, plants, and their shared environment, which is highly relevant in our surveillance and response strategies for H5N1.”

Current Status of Human Vaccine Developments for H5N1

According to the CDC’s October 11, 2024, update, the CDC has allocated more than 100,000 doses of seasonal flu vaccine for farm workers in 12 states with positive H5 cases to mitigate the risk of spread. Although the vaccine does not protect against H5N1, the CDC noted that it can reduce severe illness from seasonal flu as well as aid in the identification of potential H5N1 cases.

Additionally, the CDC is testing existing candidate vaccines for effectiveness against current H5N1 strains. Recent studies suggest that licensed adjuvanted H5N1 vaccines may generate cross-neutralizing antibodies against circulating variants, aiding in pandemic preparedness.

They are also genetic sequencing of the H5N1 viruses from infected individuals has shown no significant mutations associated with increased infectivity or reduced susceptibility to available antiviral treatments. This is important for understanding the current vaccine landscape, as it suggests that the current vaccines may still be relevant.

 in July 2024 found the stockpiled adjuvanted H5N1 vaccines demonstrate potential effectiveness against H5N1 clade 2.3.4.4b, highlighting their importance in pandemic preparedness efforts. The study assessed the binding, hemagglutination inhibition, and neutralizing antibody responses in adults vaccinated with three licensed H5N1 vaccines derived from earlier strains (A/Vietnam, clade 1; A/Indonesia, clade 2.1) with and without adjuvants.

Vaccination with the 2 adjuvanted H5N1 vaccines resulted in cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates ranged from 60% to 95% after 2 doses of the AS03-adjuvanted A/Indonesia vaccine or 3 doses of the MF59-adjuvanted A/Vietnam vaccine.

 is the primary antiviral, prescribed at 75 mg twice daily for 5 days for outpatients, and should be given promptly to hospitalized patients, regardless of illness onset. For immunocompromised patients, combination therapy may help prevent antiviral resistance. Treatment should not be delayed while awaiting lab results, and duration may be extended for severely ill patients based on clinical judgment.

Intravenous peramivir is an alternative for those who cannot take oral medications, recommended for at least 5 days. Higher doses of oseltamivir have not shown additional benefits, so healthcare providers should consult CDC resources for dosing guidance. Treatment with antivirals like oseltamivir is recommended for suspected H5N1 cases. Healthcare providers are advised to start treatment without delay, even before laboratory confirmation. Monitoring for antiviral resistance, especially in hospitalized patients, is important.

Safety Measures for Veterinary Professionals and Clients

As avian influenza continues to rise as a threat to animals and the safety of veterinary professionals, it is becoming crucial for teams to understand the disease and how to protect patients, clients, and themselves—especially since avian influenza has now been transmitted to different species, including humans.

 In Spring 2024, Texas reported the detection of the disease in dairy farms and in other animals such as dolphins.

The CDC advises that it is currently unlikely humans can become infected through an infected stray, wild, feral, or domestic cat, but human infection can be possible if there is prolonged unprotected exposure to infected animals in individuals not wearing personal protective equipment.

“If you have an animal that has a fever, is lethargic, maybe [they are] having some discharge from the eyes or nose, coughing, trouble, breathing, wheezing, and especially an elevated body temperature, any of those flu-like symptoms will be things that you'll want to be thinking about as potential symptoms of avian influenza,” Kemba Marshall, MPH, DVM, DABVP (Avian), SHRM-CP, founder of Marshall Recruiting Consortium, explained.

“Now, specifically, let’s turn our attention towards backyard poultry. Chickens can do the same things, they can still cough, wheeze, and have discharged from the eyes and nose. Their comb, the skin that you see on the top of their head, you may see that become discolored. Affected laying hens may have an abnormally shaped eggs, which may be kind of lumpy, bumpy, or what we just call like a misshapen egg,” she continued.

Veterinary and public health officials share the important roles of surveillance and prevention strategies, insights on the virus's transmission pathways, historical context, the One Health approach, and highlights effective precautionary measures to mitigate H5N1 risks.

Elizabeth Leung, PharmD, BCPS-AQ ID

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