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CEO Lori Tremmel Freeman discusses NACCHO's capacity-building programs and strategies to strengthen local health departments in addressing evolving public health threats.

NACCHO's Efforts to Combat Healthcare-Associated Infections and Antimicrobial Resistance

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 “skip phenomenon” (SP) refers to a clinical pattern in which blood cultures intermittently test positive before eventually clearing. A recent study sheds light on the fact that one-third of patients with Staphylococcus lugdunensis infective endocarditis (

 IE) experience the SP, and these patients tend to face prolonged bacteremia, extended hospital stays, and a higher 1-year mortality rate. In an exclusive email interview, Patrick D Crowley, DO, from the Mayo Clinic’s Division of Public Health, Infectious Disease, and Occupational Medicine, discussed the significance of this phenomenon, its impact on clinical practice, and the implications for patient care.

Contagion: Could you explain the "skip phenomenon" (SP) in simple terms and why it’s significant in the context of 

"'Skip Phenomenon' occurs in patients with positive blood cultures who are receiving antibiotics. One set of their blood cultures are negative for 24 hours, but the blood cultures turn positive the next day. This one day of negative cultures is the “skip”. This SP has only been described in 

, until now with Staphylococcus lugdunensis infective endocarditis."

Contagion: How can clinicians identify and interpret the skip phenomenon in patients, and what implications does this have for treatment and monitoring?

: "The first step to identifying SP is to know that it can occur. Previously, if a set of blood cultures had no bacterial growth, the team would not repeat cultures and would treat the patient like there was not bacteria in their blood anymore. If SP happens and the bacteremia recurs in the blood the next day, that puts patients at risk for an infection in central lines or surgically implanted material. Thus, if a patient has bacteremia with 

, we suggest waiting until there are two consecutive days of negative blood cultures prior to placing central lines or surgically implanted material to reduce risk."

Contagion: Your study found that patients with the SP had a longer duration of bacteremia and hospital stay. What factors do you think contribute to these longer durations, and how can they be managed more effectively?

: "Skip phenomenon may indicate either that patients are more vulnerable - sicker, frailer, older - or that 

 infection is more severe or has spread to a location not identified - such as the spine, large muscles, joints, or brain. If SP occurs, clinicians should consider whether the patient has an infection somewhere else. They should ask about new joint pain, back pain, check for confusion, and consider whether other imaging - such as a brain or spinal MRI or PET-CT is needed. Infective endocarditis is a difficult disease to diagnose and treat, and should be managed by an Infectious Diseases specialist."

Contagion: Given the higher 1-year mortality rate in patients with the SP, what do you believe are the key drivers of this increased mortality, and how can early detection and intervention impact long-term outcomes?

: "I think the mortality is higher in the patients with SP due to patient and disease factors outlined above. 

 infective endocarditis is a disease with high mortality. Over one fourth of patients without SP died as well. However, it is worth noting that we had a small study sample and it would be helpful to look into a larger number of cases to describe mortality rates and whether there are other contributing factors that we can address."

 IE presents unique challenges for clinicians, with implications for treatment, monitoring, and patient outcomes. Crowley’s insights underscore the importance of awareness in managing these patients, particularly as they are at greater risk for prolonged infection and higher mortality rates. The findings also highlight the need for further research to understand these dynamics better and improve clinical interventions.

Crowley P, Gasca L, Katragadda S, et. al. Identification of the Skip Phenomenon Among Patients with Staphylococcus lugdunensis Infective Endocarditis: A Retrospective Review, Open Forum Infectious Diseases, 2025;, ofaf015, https://doi.org/10.1093/ofid/ofaf015

Patrick D Crowley, DO explains the impact of the "skip phenomenon" in Staphylococcus lugdunensis infective endocarditis, linking it to longer hospital stays and higher mortality rates.





The "Skip Phenomenon" in Blood Infections

There are high infection rates in this population, but limited opportunities to bring about awareness has been a difficult factor to overcome. 

Black Women and HIV: Breaking Down Barriers

In 2024, the Centers for Disease Control and Prevention released its surveillance report that showed that despite Black women in the United States making up just 13% of the overall female population, they accounted for 50% of HIV diagnoses among women.

Barriers for Black women getting HIV prevention and care include access, economic, and cultural, which contribute to the disparity, and underscore an urgent need that demands focused action.

In trying to overcome these barriers and limited educational opportunities, ViiV Healthcare has been looking to meet women where they are. For example, last fall they sponsored a panel session at the Beautycon conference titled, “State of Beauty: Real Talk on the Intersection of Beauty, Self-Care and Sexual Health.” One of the featured panelists was Alftan Dyson, PharmD, AAHIVP, FNPhA, regional medical Lead & US DEI medical engagement lead at ViiV Healthcare.

“I think that's a key," Dyson said. "Showing up in nontraditional spaces to have this conversation, because that really breaks down the stigma, right?”

Dyson explains this is all part of a community-focused approach. One specific initiative involved in the approach is the 

 program, which was developed by ViiV Healthcare, and aims to increase awareness and access to HIV prevention and care for Black women by changing the conversation.

“How do we shift the conversation from talking about risk? So, reframing risk to talk about reasons, particularly motivating reasons for prevention and care,” Dyson said. “And so Risk to Reasons is one of those initiatives where you bring in community, you listen to and work with community to create this initiative. And it's really the first multimillion dollar philanthropic investment that was dedicated to black women's needs.”

Reference
1. HIV Surveillance Report: Diagnoses, Deaths, and Prevalence of HIV in the United States and 6 Territories and Freely Associated States, 2022. May 21, 2024. Accessed January 15, 2025.
https://stacks.cdc.gov/view/cdc/156509

There are high infection rates in this population, but limited opportunities to bring about awareness and education. However, a newer program sponsored by ViiV Healthcare looks to engage these women and bring about a better understanding behind transmission and care.   

Black Women and HIV: Breaking Down Barriers, Having Conversations in the Communities

In the second part of our conversation, Abdulwhab Shremo Msdi, PharmD, discusses using this methodology for this dosing technique and if he has a preference. 

Estimating the AUC for Vancomycin Using Non Trapezoidal Equations 

In the first part of the interview with Msdi, he discussed AUC-based monitoring for vancomycin and its adoption by institutions and its value in dosing. 

Looking at the Slow Adoption of AUC-Based Monitoring for Vancomycin

In this segment, Msdi talks about using a unique approach that estimates the AUC for vancomycin using non trapezoidal equations. He says the equations are not novel but rather uncommon and he discovered them during his fellowship. 

“I think it's an attention issue—not complexity—because they are not very complex to do, but there is just not much published for us pharmacists to see how to use them," Msdi said. 

He also likes this approach as it helps describe drug kinetics.

Back in the fall, Msdi coauthored an article on the topic and provided information on this approach. 

Optimizing Vancomycin Therapy: A Review of AUC Calculation Techniques

In the second part of our conversation, Abdulwhab Shremo Msdi, PharmD, discusses using this methodology. 

CEO Larry Sutton discusses SIDIPREV, a novel oxygen-based therapy aimed at preventing C difficile infections, with a focus on high-risk elderly patients and regulatory strategies to accelerate access.

Fighting C difficile Before It Starts: Lopoxy Therapeutics Approach

, Inc has acquired assets from Xeno Biosciences Inc. to advance its therapy SIDIPREV for preventing 

) infections in hospitalized patients. The acquisition includes regulatory filings, FDA correspondence, CMC data, intellectual property, and data from Phase I and Ib clinical trials showing the safety of the active pharmaceutical ingredient. This deal allows LPOXY to begin a Phase II study of SIDIPREV under the FDA’s Limited Population Pathway for Antibacterial and Antifungal Development (LPAD).

Larry Sutton, MD, PhD, physician scientist and CEO of Lopoxy Therapeutics, is leading efforts to address this growing health crisis. In our interview with Sutton, he shares the science behind their innovative therapeutic, SIDIPREV, and how it could transform the way we combat this difficult-to-treat, highly recurrent infection.

Larry Sutton begins by explaining that Lopoxy's mission is not simply to treat 

, but to prevent it from ever happening. “There have been some people that have tried this,” he says. “Sanofi and Pfizer both tried to prevent 

 by making vaccines, but they didn’t work in phase three. Most of the other people are just kind of resigned to the fact that you have to get it and then try to treat it. But the problem is, it’s highly recurrent, and it’s difficult to treat.”

Lopoxy believes the solution is to intervene before the infection has a chance to develop. “We think that through our technology, through raising the oxygen concentration in the gut—which is toxic to these anaerobic pathogens—we will prevent them from happening in the first place,” Sutton said.

SIDIPREV is a metered-dose oxygen delivery system specifically designed to be co-administered with antibiotics, which is the number one risk factor for developing 

 infections. “You take these at the same time, and that increased concentration of oxygen, which is toxic to 

, will prevent it from causing an infection,” Sutton said.

“Anybody of any age on any antibiotic can get this infection, because it’s a spore-forming organism. We breathe in and swallow spores from fungi, pollen, and other things every day. But elderly patients are more likely to get it, not necessarily as an independent risk factor, but because the older we get, the sicker we get, and the more vulnerable we are," Sutton said.

He continued, “So the most urgent need is in hospitalized elderly patients, and that’s what we’re targeting first. There’s no other therapy to prevent these infections in this group.” Their initial clinical trials will focus on elderly patients hospitalized with pneumonia—an infection that increases the likelihood of contracting a secondary 

 infection, especially when combined with antibiotic use.

Although, Sutton also points out that the risk extends beyond the hospital. “There are antibiotics out in the community that cause this too,” he says. “For example, like clindamycin, there’s 16% of people on clindamycin who will get 

 infections. It’s a very high risk, and it’s a great antibiotic—it’s on the WHO’s essential medicines list—but physicians are a little reluctant to prescribe it because of the risk for 

An important step in bringing SIDIPREV to market involves navigating the regulatory process. Sutton highlights the FDA’s Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) as an important strategy for getting this innovative treatment into the hands of those who need it most. “LPAD is for situations like this, where there’s a high-risk group of people who don’t have any other therapeutic options,” Sutton said. “It’s a way to do a pivotal clinical trial and get a limited label for these high-risk people.”

If successful in their clinical trials, Sutton’s team would secure approval for SIDIPREV, but only for the specific population it’s designed to protect. “For example, if we are successful with this in elderly patients with community-acquired pneumonia who are on fluoroquinolones or ceftriaxone, we wouldn’t get a label to give it to anybody. We could only give it to those people, because they’re the high-risk ones,” Sutton explained. “But at least it gets it out there and begins to protect people.”

While the approval would be limited at first, Sutton sees this as a critical step forward. “It doesn’t stop us from going on and developing it in the more traditional way through Phase III trials,” he added. “We will do that for broader indications. But the LPAD pathway gets a way to get something on the market quickly to protect people.”

Stay tuned for part 2 of our interview coming soon.

LPOXY Therapeutics, Inc. Acquires Key Assets from Xeno Biosciences Inc. to Advance C difficile Prevention Therapy. January 4, 2024. Accessed January 10, 2024. 

https://firstwordpharma.com/story/5925021

CEO Larry Sutton, MD, PhD, discusses SIDIPREV, a novel oxygen-based therapy aimed at preventing C difficile infections.

The fall and winter months signal an increase in viral infections circulating among children and families, including influenza, COVID-19, and respiratory syncytial virus (RSV). Although RSV is a public health concern for individuals of all ages, infants and toddlers, especially those born prematurely or with compromised immune systems, and older individuals have particular vulnerability to severe complications. Each year, RSV accounts for more than 2.1 million outpatient visits in children younger than 5 years and more than 60,000 hospitalizations, making it the most common cause of hospital admission in children younger than 1 year.¹ In vulnerable groups, RSV can lead to severe conditions such as bronchiolitis, often resulting in emergency department visits and hospitalization. 

In an effort to protect these populations with high risk, the US Food and Drug Administration approved nirsevimab-alip (Beyfortus) in July 2023. Nirsevimab-alip is a monoclonal antibody administered as a preventive measure for all infants younger than 8 months whose mothers did not receive an RSV vaccine during pregnancy.² Despite recent advances in RSV prevention, effective antiviral treatments remain unavailable. Current treatment guidelines emphasize supportive care, such as oxygen supplementation, fluid management, and nutritional support when needed. Although aerosolized ribavirin is available, its use is limited by significant drawbacks. Ribavirin requires prolonged administration, is expensive, and raises safety concerns for health care providers due to potential teratogenic effects. Consequently, its role in clinical practice is minimal. These limitations highlight the urgent need for more practical and effective antiviral therapies in RSV management, extending beyond preventive options.

Ziresovir (AK0529) is a potent, selective RSV F protein inhibitor aimed at reducing the severity and duration of respiratory symptoms, leading to shorter hospital stays and fewer complications.³ Ziresovir is dosed based on body weight, with a minimum dose of 2 mg/kg necessary to achieve the suggested trough concentration of at least 130 ng/mL, which has been shown to correlate with improvements in clinical symptom scores and reduced viral loads.⁴ A recent phase 3 trial conducted in China evaluated the efficacy and safety of ziresovir therapy in children hospitalized with RSV infection. 

This randomized, double-blind, placebo-controlled trial was conducted across 28 hospitals in China. Participants were children aged 1 to 24 months hospitalized with confirmed RSV infection within 36 hours prior to receiving their first dose of ziresovir or placebo. Infants were excluded if they had positive test results for HIV, were coinfected with influenza or bacterial pneumonia, or had a known or suspected immunodeficiency. Participants were randomly assigned 2:1 to receive either ziresovir (n = 164) or placebo (n = 80), with both treatments administered every 12 hours for 5 days. Doses ranged from 10 to 40 mg, depending on body weight. The primary efficacy end point was assessed using the Wang Bronchiolitis Severity Score, which evaluates symptoms such as wheezing, respiratory rates, and the child’s general condition, from baseline to day 3. Secondary end points included reductions in RSV viral loads, symptom remission, and length of stay in the intensive care unit, if applicable. The trial was divided into 2 parts: The first focused on safety and pharmacokinetics, whereas the second evaluated efficacy. The safety analysis (part 1) included 302 participants, whereas the efficacy portion of the trial (part 2) evaluated 244 participants. Part 2 of the trial was initiated after part 1 was completed. Participants received ziresovir or placebo for 5 days, with a 9-day safety follow-up period. 

Findings from the phase 3 trial demonstrated that ziresovir had significant efficacy compared with placebo, offering a promising therapeutic option for infants and toddlers hospitalized with RSV (TABLE). The adverse event profile of ziresovir was minimal and comparable to that of placebo, suggesting a favorable safety profile (adverse event occurrences, 61% vs 53%). Additionally, resistanceassociated mutations were identified in the ziresovir treatment group. However, no correlation was observed between these mutations and viral rebound, indicating that the presence of resistance mutations did not affect viral load recurrence in these patients. 

There are some limitations to the study worth noting. First, there was a lack of multinational enrollment, with approximately 89% of the intention-to-treat population identifying as Han Chinese. This may warrant further studies across diverse global populations to ensure the broader applicability of the findings. Second, a common end point for assessing treatment response, time to discontinuation of supplemental oxygen, was not included whereas end points such as change in Wang bronchiolitis score and viral load were included. The former is not yet validated for RSV infection, and the latter is not regularly used in clinical practice. 

Given these limitations, readers should interpret the findings with caution regarding applicability across diverse patient populations and should consider that an alternative clinical scoring tool might have provided a more optimal measure of treatment response. However, the variables assessed are intuitive and frequently used in clinical practice, lending relevance to the study’s findings. Ultimately, these data contribute promising insights toward the development of more effective RSV treatment options, an area of critical need. Considering that the median time from symptom onset to the first dose was 4 days—when viral load is naturally declining—the timing of intervention is a critical factor in interpreting the efficacy of the antiviral. 

Like most antivirals, earlier administration is generally associated with greater effectiveness, as early intervention can actively inhibit viral replication before substantial immune response and viral decline occur. Given the delayed dosing in this study, it raises the question of whether the observed antiviral effect was due to the treatment itself or was partially attributable to the natural course of infection. Therefore, readers should consider that although promising, these results might reflect the antiviral’s potential in later stages rather than its full efficacy if administered earlier, underscoring the need for further studies exploring optimal timing of treatment initiation. 

As the use of nirsevimab-alip continues to grow for RSV prevention, the development and approval of an effective antiviral treatment, such as ziresovir, would be a significant advancement in managing severe cases. Although further research is necessary to confirm the efficacy and safety of ziresovir in more diverse populations, findings from this trial highlight its potential as a valuable therapeutic option in the fight against RSV.

1.Surveillance of RSV. Centers for Disease Control and Prevention. Accessed October 15, 2024. http://www.cdc.gov/rsv/php/surveillance/index.html
2.Dalton M. Respiratory syncytial virus (RSV). National Foundation for Infectious Diseases. September 14, 2024. Accessed October 15, 2024. http://www.nfid.org/infectious-disease/rsv/
3.Zheng X, Gao L, Wang L, et al. Discovery of ziresovir as a potent, selective, and orally bioavailable respiratory syncytial virus fusion protein inhibitor. 

. 2019;62(13):6003-6014. doi:10.1021/acs.jmedchem.9b00654
4.Zhao S, Shang Y, Yin Y, et al; AIRFLO Study Group. Ziresovir in hospitalized infants with respiratory syncytial virus infection. 

. 2024;391(12):1096-1107. doi:10.1056/nejmoa2313551

Findings from a recent phase 3 trial show promising results for
the approval of ziresovir in the treatment of respiratory syncytial virus in infants.

Lori Tremmel Freeman

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