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Emily Hadley is a statistician and research data scientist at RTI International 

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

Exploring the challenges and strategies for combating MDR Pseudomonas aeruginosa infections, as discussed with Jason Pogue, PharmD, BCPS, BCIDP

Emerging Resistance in Pseudomonas Treatment: Key Insights from the CACTUS Study

, compared the effectiveness of ceftolozane-tazobactam (CT) and ceftazidime-avibactam (CZA) in treating multidrug-resistant (

 infections. The study found that both treatments had similar clinical outcomes. Of the 234 patients treated with CT, 

, compared to 55% for those treated with CZA. The 30-day mortality rates were also similar: 20% for CT and 19% for CZA.

In the final part of our interview with Jason M Pogue, PharmD, BCPS, BCIDP, clinical professor at the University of Michigan and investigator of the study, we discussed the high rates of emergent resistance observed in Pseudomonas treatments. Resistance developed in 1 in 5 patients, regardless of the treatment arm. Pogue noted that 

 resistance is driven by upregulated chromosomal mechanisms, rather than by transferable beta-lactamases. This type of resistance is more common in clinical settings where traditional agents like cefepime, meropenem, and piperacillin-tazobactam (piptazo) are not used, as these drugs often contribute to elevated resistance levels.

When asked about the high rates of resistance observed, Pogue emphasized the nature of 

 as a particularly challenging pathogen. He explained that the resistance seen with newer agents like CT and CZA is not unexpected, given the bacteria's ability to upregulate chromosomal resistance mechanisms.

“When we sat and looked at these results, when we first got them, we started thinking through them. This is what jumped out to us first: Regardless of what treatment arm you were in, you're giving this novel, or I guess at least novel-ish, since they're like, 10 years old now, novel agents for resistant 

, and one out of every five times in both arms, you're seeing resistance development.”

 is a jerk. I don't know how else to say this—it's kind of the nature of 

He further explained the biological mechanisms behind this resistance, "What's unique about 

 is a lot of the beta-lactam resistance that we see is driven by upregulation of chromosomal mechanisms of resistance. So, rather than passing beta-lactamases from one to another, the resistance is in the chromosome of the organism. And in the presence of certain things, notably antibiotics, you can see upregulation of these resistance mechanisms.”

Building on this, he clarified why resistance development should be viewed in the context of treatment settings, "It’s not shocking that this happens because, when you're using these drugs, you're already in a situation where resistance is present in the background. You’re just kind of taking it to the next level with these agents. And I think it’s important for us to think about the fact that this happens 1 out of 5 times. That’s kind of the nature of Pseudomonas.”

Pogue’s insight reveals why resistance remains a challenge even with newer agents like CT and CZA: 

’s ability to adapt and upregulate its resistance mechanisms makes it difficult to achieve long-term success with many treatments.

 resistance is not new, nor is it specific to the newer beta-lactam agents. Historically, carbapenems have been associated with resistance development in about 20% of patients, and there is limited data on the resistance patterns seen with piptazo and cefepime.


“If you look historically at the carbapenems, they cause resistance in 20% of patients. Not a lot of good data out there on piptazo and cefepime, but just as a clinician, those of you watching know that it’s not shocking when you treat a patient for 

 and they develop resistance. That’s kind of the nature of the beast,” This emphasizes that 

resistance is a longstanding issue in clinical practice, and resistance development remains common even with first-line antibiotics.

Despite the high rates of resistance observed in the study, Pogue emphasized that strategies exist to help mitigate its emergence. He discussed potential avenues for improving treatment outcomes, including dose optimization, combination therapy, and exploring adjunctive therapies.
"One of the things we’ll want to do moving forward, and as a community, we need to do, is ask: “Are there strategies that can limit the emergence of resistance?” Whether that’s dose optimization, whether that’s robustly comparing combination therapy to monotherapy, or some sort of adjunctive therapy, I think those are next steps. And it just shows you the need for continued drug development in this space as well.”

Pogue’s focus on exploring these strategies highlights the importance of finding new ways to manage and reduce resistance. He also stressed that continued innovation in antibiotic development is essential for staying ahead of evolving bacterial threats like 

The findings of the CACTUS Study offer valuable insights into the challenges of treating MDR 

 infections, highlighting the ongoing issue of resistance. While the clinical success rates for CT and CZA were similar, the development of resistance in 1 in 5 patients remains a key concern. Pogue’s recommendations to optimize dosing, explore combination therapies, and continue drug development will be crucial for addressing these issues moving forward.

Part 1 of our interview introducing The CACTUS study: 

CACTUS Study Compares Ceftolozane-Tazobactam vs. Ceftazidime-Avibactam for MDR Pseudomonas

Part 2 of our interview discussing ceftolozane tazobactam’s effectiveness over ceftazidime avibactam: 

Ceftolozane Tazobactam Linked to Increased Clinical Success in Pneumonia

Shields RK, Abbo LM, Ackley R, et al. 1109. A multicenter, observational study to compare the effectiveness of Ceftazidime-Avibactam versus Ceftolozane-Tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the United States (CACTUS). Open Forum Infect Dis. 2023;10(Suppl 2):ofad500.082. Published 2023 Nov 27. doi:10.1093/ofid/ofad500.082

In 2024, there were many news updates in the world of respiratory infections, ranging from updates in vaccinations to new data on the long-term effects of some of these illnesses on patients. The 

 team followed it all, and spent our time speaking with experts from major institutions, pharmaceutical companies, and the federal agencies who are working together to push medical science forward.

Here, we'll be providing a list of stories that resonated with our audience in 2024 in the area of respiratory infections. As expected, a number of COVID-related updates made their way into this list, among other news items that were of interest to readers. 

Click the headlines to read more from these stories.

During the Pandemic, 75% of Hospitalized COVID-19 Patients Received Antibiotics, Despite Only a Minority Needing Them

In the early days of the pandemic when hospital ICUs were filling up with severe COVID-19 patients, clinicians had no therapeutic agents, and no one had any form of immunity to fight the virus, thus health care turned to a familiar form of treatment: antibiotics.

New data from the WHO offers further information on the scope of this treatment challenge that happened in the first years of the pandemic.

Although only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, 75% of patients were treated with antibiotics ‘just in case’ they helped, according to the WHO research. The highest rate of antibiotic use was seen among patients with severe or critical COVID-19...

COVID-19 Vaccination Associated with Reduced Risks of Thromboembolic, Cardiovascular Complications

One of the ongoing concerns of COVID-19 vaccines has been reports around thromboembolic and cardiovascular events. There have been reports of blood clots following adenovirus-based COVID-19 vaccines, with an association that was further assessed in observational studies. Later on, mRNA-based vaccines were found to be associated with the risk of rare myocarditis events. Contrary to these past associations, a new study published in the journal, 

, reported there was a major reduction of risk (45–81%) for post-acute COVID-19 venous thromboembolism (VTE), arterial thrombosis/thromboembolism (ATE) and heart failure (HF) in patients who had been vaccinated...

Healthcare Workers Who Received Additional Vaccine Dose Had Lower Odds of Symptoms at 6 Weeks

The early days of the Omicron predominant period continued to see high incidence rates of COVID-19 that included severe infections, hospitalizations, and mortality. For their part, healthcare workers (HCWs) were always in close proximity to patients with severe infection, and consequently in harm’s way. As such, HCWs saw a large incidence rate of active infection as a population.

According to 1 study done in the early period of the pandemic beginning from the time no vaccines were authorized, and extending through until nearly a year after the vaccines had been initially rolled out (December 2020), HCWs took up a large percentage of confirmed cases...

The US Will Transition to Trivalent Vaccines for Next Year's Influenza Season

The FDA’s Vaccines and Related Biological Products Advisory Committee recommended that all US flu vaccines transition from quadrivalent to trivalent vaccines for the 2024-2025 flu season. The trivalent vaccines’ formula will still contain the influenza A(H1N1), A(H3N2), and B/Victoria-lineage vaccine virus, but omit the influenza B/Yamagata virus because it is no longer actively circulating.

“FDA has been engaging and interacting with manufacturers of FDA-approved seasonal flu vaccines and providing scientific and regulatory advice to them to facilitate the timely availability of approved safe and effective trivalent seasonal flu vaccines for the 2024-2025 US flu season,” said the FDA in a news release...

COVID-19 Vaccination During Early Pandemic Years Shown to Reduce Risk for Heart Attacks, Strokes

The incidence rates for both heart attacks and strokes (arterial thromboses) were lower after COVID-19 vaccination than before or without vaccination during the earlier years of the pandemic, according to a new study from England.

Heart attacks and strokes were up to 10% lower in the 13 to 24 weeks after the first dose of a COVID-19 vaccine. And post-second dose, the incidence was up to 27% lower after receiving the AstraZeneca vaccine and up to 20% lower after the Pfizer/Biotech vaccine...

Japan Approves Updated Self-Amplifying mRNA COVID-19 Vaccine

Japan has approved the CSL and Arcturus Therapeutics' Updated self-amplifying (SA) mRNA COVID-19 Vaccine, ARCT-154 (Kostaive). The updated vaccine is targeted to protect against the JN1 lineage of omicron subvariants for adults 18 years of age and older. "We are pleased to receive the updated approval from Japan's Ministry of Health, Labor and Welfare, and remain on track to distribute Kostaive in time for the October COVID-19 vaccination campaign," Emmanuelle Lecomte-Brisset, senior vice president and head of Global Regulatory Affairs, CSL, said in a statement...

In a retrospective cohort study published in 

 investigators evaluated the incidence of certain symptoms and conditions associated with long COVID, potentially indicative of PASC, within 31 to 150 days after a SARS-CoV-2 test in both adults and children, comparing those with positive and negative results. Individuals infected with SARS-CoV-2, particularly those who required hospitalization, faced an increased risk of being diagnosed with specific symptoms and conditions following their acute infection phase.

Following adjustments for baseline covariates, adults and children who were hospitalized and tested positive showed higher odds of receiving a diagnosis of ≥1 symptom...

CDC Updated COVID-19 and Influenza Vaccination Guidelines for 2024-2025 Season

During the CDC's Advisory Committee on Immunization Practices (ACIP) meeting held on June 27, 2024, voting members recommended the authorized 2024-2025 COVID-19 vaccines for those 6 months of age and older and reaffirmed the influenza vaccination guidelines. The CDC discussed that the 2023-2024 COVID-19 vaccination has proven effective in protecting against various aspects of the virus, including asymptomatic SARS-CoV-2 infections, COVID-19-related visits to emergency departments and urgent care facilities, and hospitalizations. While showing waning patterns over time, it continues to provide notable protection against illness...

Internal Tremors: Adding to the List of Long COVID Symptoms

Long COVID has a laundry list of symptoms — and a lesser-known but troubling one is the sensation of having internal tremors, often with no outward evidence that this is happening. In a new, Yale-based Long COVID study, over one-third of participants report experiencing this strange symptom, which feels as if tremors are occurring 

Long COVID remains one of the most poorly-understood aspects of the SARS-CoV-2 pandemic. Since shortly after the pandemic began in 2020, health professionals have had to come to terms with the fact that some patients who overcome their initial COVID-19 infection never completely recover. People with Long COVID have developed a variety of symptoms that range from gastrointestinal issues to chronic fatigue...

As 2024 winds to a close, take a look back on some of the biggest stories Contagion was following around respiratory infections.

Contagion's 2024 Top Stories: Respiratory Infections

New research suggests the sympathetic nervous system (SNS) or flight or fight response can shape the severity of 

 infection. In an animal study, a group of investigators found if they disrupted specific receptor activity in the sympathetic nervous system, a significant reduction in both intestinal inflammation and mortality was seen.

The affected portion of the SNS is the alpha 2-adrenergic receptors (α2-ARs) which are cell surface-based, and play a role in fight or flight responses including blood pressure, anxiety and stress, and inflammation.

“The discovery of the α2AR as a major driver of disease was somewhat unexpected, considering that the α2AR is a well-known negative regulator of sympathetic activity,” the investigators wrote in their study, which was published in 

“Neurons are the first responders that coordinate defenses against toxic attacks. Sometimes those responders don’t recruit the right size and kind of artillery and that can make things worse,” said study author David Tyus, PhD, a neuroscience graduate student at University of Virginia (UVA), in a news release. “Interestingly, the receptor we identified as important in 

 infection [the alpha 2 adrenergic receptor] has also been linked to irritable bowel syndrome.

Tyus and study author William A. Petri Jr., MD, PhD, of UVA's Health’s Division of Infectious Diseases and International Health, evaluated the role of SNS in 

 the study's authors explain that blockade of alpha 2-adrenergic receptors downstream may stop disease progression of 

Can you explain the concept of using therapies to quiet the “fight or flight” response to potentially prevent a severe case of C difficile?
Petri and Tyus:

 Our results suggest that sympathetic nervous system activity contributes to the severity of disease in 

infection. Part of that determination was observing that blockade of specific receptors downstream of the sympathetic nervous system could curb disease progression 

infected mice. Theoretically, receptor blockade in patients could do the same but further study is needed to determine whether this approach could be safely applied prophylactically or after symptoms occur.

What are the important takeaways from your study?
Petri and Tyus:

The biggest takeaway from the study is that the sympathetic nervous system seems to be an important part of the disease process when one is infected with 

With the backdrop of many studies in the field focusing on barrier and immune functions, this study is a new example of neuronal contributions to 

What would you like to see in terms of next steps for your research?
Petri and Tyus:

 We would like to determine which cells downstream of the sympathetic nervous system mediate its effects in the hopes of finding more resolved mechanisms and therapeutic targets. Additionally, we would like to test the role of the sympathetic nervous system in recurrent disease, a hallmark issue of 

There are a number of reasons to study recurrent infection, including the possibility of a patient's diminished quality of life as well as mortality. Factors such as advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulance are some reasons people infected have more severe bouts or even recurrence with 

“We are very excited to think about how our findings translate to clinic and how the sympathetic nervous system might play a role in recurrent infection. I hope that this study sets the foundation for future findings of how neurons affect the course of 

infection outcomes,” Petri said in a news release. 

References
1. Tyus D, Leslie JL, Naz F, Uddin MJ, Thompson B, Petri WA Jr. The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection. 

. 2024;5(10):101771. doi:10.1016/j.xcrm.2024.101771
2. Belfer I, Buzas B, Hipp H, et al. Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene. 

. 2005;50(1):12-20. doi:10.1007/s10038-004-0211-y
3. Zhang SJ, Lai G, Griffis CA, Schiltz M, Aroke EN. α

-Adrenergic Receptor Agonist, an Attractive but Underused ERAS Component in Improving Fast-Track Recovery and Surgical Outcomes. 

. 2021;89(6):529-537.
4. Faulty ‘Fight or Flight’ Drives Deadly C. Difficile. UVA News release. 


https://newsroom.uvahealth.com/2024/10/10/faulty-fight-or-flight-drives-deadly-c-difficile/

 Infection: Risk Factors, Treatment, and Prevention. 

Investigators at the University of Virginia are examining the potential link between the “sympathetic” nervous system and the role of the seriousness of the infection.  

Could the Flight or Fight Response Trigger Severe C difficile?

Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, and his team discovered the klebsiella pneumoniae variant, KPC-31, 

Identifying a Novel Variant of Klebsiella Pneumoniae 

Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, medical director for the microbiology laboratory at AdventHealth in Orlando, FL has a unique perspective. As someone who has been both a practicing physician in the past and a current laboratorian, he is able to utilize both his clinical and diagnostic experiences and apply them to individual cases. This dual professional experience helped him earlier this year when he and his lab team at AdventHealth were able to diagnose a novel variant of 

, called KPC-31, in a patient which was possibly the first case ever diagnosed in the state of Florida.

The detection of this mysterious and unusual pathogen was discovered utilizing various diagnostics tools including whole genome sequencing (WGS) as well as multi-locus sequence typing (MLST).

Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, and his team discovered the klebsiella pneumoniae variant, KPC-31, in a patient by sequencing the entire genome through a series of different diagnostics, which not only led to identifying the strain, but to a greater understanding of its antimicrobial susceptibility. 

Emily Hadley

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