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New public health perspectives on aspergillosis, sporotrichosis, histoplasmosis, and coccidioidomycosis.

Four Fungal Horsemen: Emerging Trends in Fungal Disease Epidemiology

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

Part 2 with James F Cummings, MD, as he discussed the need for a stronger response to emerging variants, the importance of protecting high-risk populations, and the potential to reduce vaccine hesitancy through easier administration.

Evaluating Safety and Efficacy of Vaxart's Oral Vaccine's Impact on COVID-19 Variants

Vaxart has announced the start of a sentinel cohort for its Phase 2b clinical trial, which will evaluate the safety, immunogenicity, and effectiveness of its oral COVID-19 vaccine candidate in comparison to an approved mRNA vaccine. This trial, valued at up to $456 million under Project NextGen, seeks to tackle ongoing challenges related to COVID-19. The study will examine various factors, including effectiveness against symptomatic and asymptomatic COVID-19, immune responses, and the occurrence of adverse events. The primary goal will be to assess the relative efficacy of Vaxart’s vaccine in preventing symptomatic disease, with results expected 12 months after vaccination.

In discussing the broader implications of the trial with James F. Cummings, MD, chief medical officer of Vaxart, he noted the initial successes in COVID-19 vaccine development, highlighting the role of significant investments in improving capabilities and technologies. He stated, “One key aspect of the response to COVID-19 has been the initial vaccine efforts, which were impressive given we started from scratch. This was made possible by significant investments from the government and various institutions in improving capabilities and technologies, along with effective biosurveillance to identify the issues and convert that data into actionable information for solutions. However, while it was a strong start, it wasn't the best approach moving forward. We know the virus mutates several times a year, so we need a more durable and broader response. For instance, if a vaccine is administered today, it should still be effective against strains that emerge six months later. This is where mucosal immunity comes into play.”

The first phase of the trial will enroll 400 participants, with 200 receiving Vaxart’s oral vaccine candidate and 200 receiving the approved mRNA vaccine. After a 30-day safety assessment by an independent Data and Safety Monitoring Board (DSMB) and the FDA, the trial will proceed to a second phase, which aims to enroll an additional 10,000 participants to ensure diverse demographic representation, including at least 25% of participants over the age of 65.

Cummings expressed enthusiasm about the next generation of vaccines, noting the logistical advantages of developing a vaccine that does not require complex refrigeration infrastructure. “We aim to create a vaccine for everyone, especially focusing on protecting those at highest risk. In our trial, 25% of participants will be over 65 or at higher risk for severe disease. Historical data from past COVID-19 infections shows that these individuals are at the greatest risk, so we want to assess how well the vaccine prevents symptomatic disease and infections, as well as how effectively it triggers a strong immune response.”

He added that their platform has demonstrated no immune decline in older adults, with similar immune responses observed in both older and younger participants. “This is encouraging because older adults often require higher doses or additional boosters to achieve a robust immune response, but our platform doesn’t show that age-related decline.”

Cummings also addressed the importance of making vaccines accessible and easy to administer. “One significant issue is vaccine hesitancy; many people, including some in my family, are hesitant because they don’t like needles. Our approach could eliminate that concern, as it may be suitable for home use, similar to some vaccines already approved for home administration.” One significant issue is vaccine hesitancy; many people, including some in my family, are hesitant because they don’t like needles. Our approach could eliminate that concern, as it may be suitable for home use, similar to some vaccines already approved for home administration.”

All in all, Vaxart's Phase 2b trial aims to develop an oral COVID-19 vaccine. The study will assess safety and efficacy by comparing its candidate to an approved mRNA vaccine. This effort could improve public health and address vaccine hesitancy in the fight against COVID-19.

Watch part 1 of Cummings interview here: 

https://www.contagionlive.com/view/vaxart-initiates-phase-2b-study-of-oral-covid-19-vaccine

Press Release. Vaxart Announces Initiation of Sentinel Cohort for Phase 2b Study Evaluating Its COVID-19 Oral Pill Vaccine Candidate. VAXART. September 30, 2024. Accessed October 4, 2024.

Part 2 with James F Cummings, MD, as he discusses the need for a stronger response to emerging variants, the importance of protecting high-risk populations, and the potential to reduce vaccine hesitancy through easier administration.

James F Cummings, MD, discussed the trial's goals, highlighting the vaccine's potential to generate mucosal immunity and its advantages in logistics and administration.

Vaxart Initiates Phase 2b Study of Oral COVID-19 Vaccine

Vaxart has announced the initiation of a sentinel cohort for its Phase 2b clinical trial, evaluating the safety, immunogenicity, and efficacy of its oral COVID-19 vaccine candidate compared to an approved mRNA vaccine. Valued at up to $456 million under Project NextGen, this trial aims to address ongoing challenges posed by COVID-19. The study will assess factors such as efficacy against symptomatic and asymptomatic COVID-19, immune responses, and the incidence of adverse events. The primary endpoint will focus on the relative efficacy of Vaxart’s vaccine for preventing symptomatic disease, with analysis expected 12 months post-vaccination.

James F Cummings, MD, chief medical officer of Vaxart, he highlighted the significance of this milestone, stating, “Initiating the sentinel cohort is a strong step toward Vaxart’s goal of developing a vaccine that may bring us closer to a sustainable solution to the persistent threat of COVID-19. We continue to progress toward our goal of conducting the Phase 2b study and look forward to the results of our mucosal technology’s first head-to-head comparison against an approved mRNA vaccine for this virus.”

The first phase will enroll 400 participants: 200 receiving Vaxart’s oral vaccine candidate and 200 receiving the approved mRNA vaccine. Following a 30-day safety review by an independent Data and Safety Monitoring Board (DSMB) and the FDA, the trial will advance to a second phase aiming to enroll an additional 10,000 participants, ensuring demographic representation, including at least 25% of those over 65 years of age.

In the first part of our two-part interview with Cummings, he discussed how the oral COVID-19 vaccine enhances immune response compared to traditional injections and shared insights on its potential benefits for public health. He noted, “Another one is the fact that the way our vaccine works, it exhibits a mucosal immune response as well as a serum response,” emphasizing the significance of mucosal immunity in providing a first line of defense against pathogens.

Cummings also emphasized the advantages of their oral vaccine platform, “It's a pretty neat idea, and that we have a pill-based form that’s thermally stable. This is something that has stability at room temperature and doesn’t require a needle, syringe, or any medical professional to administer. From start to finish, it’s a very economical way of fielding a vaccine for global health,” he said.

Additionally, Cummings highlighted the logistical benefits, stating, “having something that could be as easy as sending them in the mail or ubering it to someone, or however you would want to deliver it, I think makes distribution, the logistics of vaccine delivery a lot easier. I think that's one of the benefits of the platform.”

Stay tuned for part two of our interview, where we will explore the key safety and effectiveness measures that will be evaluated in the trial, their relevance to current needs in the fight against COVID-19, and how the trial will ensure representation of various age groups and health conditions. We will also discuss what the results could imply for future vaccines.

Funding for this initiative is provided by Project NextGen, an effort led by BARDA and NIAID to accelerate the development of next-generation COVID-19 vaccines and therapeutics. Vaxart stands out as the first US company to complete a Phase 2 clinical trial for an oral COVID-19 vaccine, showcasing its leadership in oral vaccine development. The company is also advancing oral vaccines for norovirus and influenza, as well as a therapeutic vaccine for human papillomavirus.

Press Release. Vaxart Announces Initiation of Sentinel Cohort for Phase 2b Study Evaluating Its COVID-19 Oral Pill Vaccine Candidate. VAXART. September 30, 2024. Accessed October 3, 2024.

Part 1 of James F Cummings, MD interview, discusses the trial's goals and highlights the vaccine's potential to generate mucosal immunity, its logistical advantages and ease of administration.





The benefits, challenges, and prospects of wastewater data in enhancing public health strategies against AMR.

Transformative Potential of Wastewater Surveillance in Monitoring Antimicrobial Resistance

Valerie Morley, PhD, senior scientist at Ginkgo Bioworks, recently delivered a presentation at the World AMR Congress on the role of wastewater surveillance in monitoring antimicrobial resistance (AMR) across diverse environments, including healthcare settings and agricultural sites. Her talk focused on drawing valuable public health insights from wastewater surveillance for AMR.

She highlighted the benefits of wastewater surveillance for obtaining population-level data, which complements cultured clinical isolates.“Wastewater surveillance is a cost-effective way to get population-level data that can be very targeted. We can look at wastewater coming from a single ward or unit in a hospital, or it can be very broad. We can look at municipal-level wastewater that's coming from an entire community, and importantly, wastewater allows us to get data from the community setting as well as healthcare settings.”

Morley identified technical challenges in associating resistance genes with bacterial organisms and the complexity of interpreting metagenomic data. “One of the big examples that comes to mind for me is that with metagenomic data, we often can't make associations between the resistance genes that we're detecting and the bacterial organisms that they're associated with.”

Morley noted that these challenges stem from limitations in current sequencing approaches but highlighted ongoing efforts to improve accuracy through new methodologies. “That's just kind of a limitation of most types of sequencing approaches, and that's a place where, if we can start to make those associations more accurately, that's really valuable. We're working on that both, there's new approaches coming out that help us to do that. On the wet lab side, they're expensive right now compared to other sequencing methods, and there's also ways to potentially get better at doing that bioinformatically and from a statistical perspective, to make those predictions.”

She underscored the importance of collaborating with end-users to extract meaningful insights and discussed the potential of wastewater surveillance to inform public health strategies. This includes reducing healthcare-associated infections and guiding antimicrobial stewardship through large-scale pilots and data correlation with electronic health records.

“We're really excited about the idea that wastewater surveillance could help hospitals to reduce healthcare-associated infections and to make decisions regarding antimicrobial stewardship. ... This could help to inform when hospitals might want to turn on heightened infection control procedures or more targeted surveillance methods like sequencing or testing swabs, for example.”

In conclusion, Morley highlights wastewater surveillance as a promising tool for monitoring AMR in both healthcare and community settings. While this approach provides valuable population-level data that complements traditional methods, it faces challenges in data interpretation and accuracy. Advances in technology and data integration are expected to enhance its effectiveness, potentially improving infection control and antimicrobial stewardship.

World Anti-Microbial Resistance Congress

Conferences

In a world that has become skeptical of vaccine safety and efficacy, a new modeling study from England demonstrates the continued high efficacy of the MMR vaccine. According to a new study published in 

, the MMR vaccine remains highly protective against measles for life, and sees a very small decrease in protection over time.

According to the investigators, for a person who was born in 1995 who received a full immunization (2 doses) of the MMR vaccine before age of 5 and gained full protection from the vaccine, a waning of about 0.04% each year would mean vaccine effectiveness remains on average:

A Small Uptick in Measles Cases Among Fully Vaccinated

In England in 2011, 20 individuals who were double-vaccinated were infected with measles (1.9% of all cases) compared to 989 unvaccinated people (93% of all cases). In the same country in 2019, 57 individuals vaccinated twice had measles (7.2% of all cases) compared to 666 unvaccinated people (84% of all cases). This shows a slight uptick in cases in the fully vaccinated, but the investigators write that the slight decreases in individual protection over time are only apparent because outbreaks are happening as a result of reductions in vaccine coverage, and highlight that the best way to protect everyone from the disease is to maintain high levels of vaccine coverage in the population

“Although our results suggest that a slight waning of immunity from the MMR vaccine over time explains why we are seeing an increase in the proportion of measles cases in double-vaccinated people in England, it’s important to note that the biggest risk factor for measles outbreaks by far is low vaccination rates,” study investigator Alexis Robert, PhD, The London School of Hygiene & Tropical Medicine, said in a statement. “The MMR vaccine remains highly effective and receiving two doses will protect you and those around you against measles infection. Even if you are one of the small number of people who get an infection after two doses of MMR vaccine, previous studies suggest measles symptoms in people who have been vaccinated are milder than in people who have not had a vaccine.”



More than 95% of individuals gain immunity after a single dose of MMR vaccine. This means that after 2 doses, a small proportion of vaccinated people (less than 1%) may be infected because of a lack of immune response.

Transmissibility and The Seriousness of Missing Childhood Immunizations


Measles is spread by breathing in contaminated air or touching an infected surface then touching the eyes, noses, or mouths. According to the Centers for Disease Control and Prevention (CDC), the measles virus can live up to 2 hours in airspace after an infected person leaves an area and can linger on surfaces for hours. And, if you put a person with measles in a room with 10 people who have not been vaccinated or have not previously contracted measles, 9 of those people will also get the disease.

“Measles is the most contagious and easily transmittable virus we know—far more than COVID or influenza,” said Patricia A. Stinchfield, RN, MS, CPNP, president, National Foundation for Infectious Diseases (NFID) in an interview with 

Considered one of the most successful immunizations, the MMR vaccine has done much for public health for years. However, there has been a continuing downward trend of childhood immunizations here in the United States.

 that over the last 2 school years, the national coverage for childhood state-required vaccines among kindergarten students declined from 95% to approximately 93%. During the 2020-21 school year, vaccinations dropped to 94% and during the 2021-22 school year it dropped again to approximately 93%.

And while this does not sound like a large number, it still represents thousands of young children not getting their vaccinations. It is also a disturbing trend as some families may feel they do not need them or are fearful of vaccines.

“Compared with the 2020–21 school year, vaccination coverage decreased 0.4–0.9 percentage points for all vaccines. Although 2.6% of kindergartners had an exemption for at least 1 vaccine, an additional 3.9% who did not have an exemption were not up to date with MMR,” the investigators wrote in an 

This is the lowest rate of vaccination in over a decade, the CDC states. And the MMWR report said that as many as 250,000 kindergartners are not protected against measles.

The reduction in the number of fully vaccinated children can only lead to more cases. In local communities this can present a real problem explains, NFID's Stinchfield.

“When those rates go below 95%—and this is really about in a specific community, what is the rate in the daycare? What is the rate in a high school? In a city? In a state?” Stinchfield explained. “To just take a big global number and say that's pretty high, we're good, is not okay. When a local community gets below 95%, that gives measles an ability to make an entrance and spread in that community.”

She also makes the point that there are people who are vulnerable to measles including babies who are too young to be immunized, those who are immunocompromised, and people who are on various therapies that might make them more susceptible to the disease.



This should give families who are reluctant to get childhood immunizations something to consider in thinking about others.

1.Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study. Lancet Public Health. September 26, 2024. Accessed September 26, 2024.


https://www.thelancet.com/journals/lanpub/article/PIISS2468-2667(24)00181-6/fulltext


2.Measles. Transmission. CDC. Last reviewed November 5, 2020. Accessed September 26, 2024.


https://www.cdc.gov/measles/transmission.html


3. Parkinson J. Measles Outbreak in Philadelphia Prompts Caution, Calls for MMR Vaccination. 

 January 8, 2024. Accessed September 26, 2024.


https://www.contagionlive.com/view/measles-outbreak-in-philadelphia-prompts-caution-calls-for-mmr-vaccination


4. Parkinson J. A Comprehensive Look at Measles. 

March 13, 2024. Accessed September 26, 2024.
https://www.contagionlive.com/view/a-comprehensive-look-at-measles

An English modeling study suggests level of protection decreases only very slightly over time and reminds parents to have their children up to date on all vaccinations.

Though MMR Vaccine Remains Highly Protective Against Measles, Some Waning Immunity Can Lead to Outlier Cases 

One of the ongoing challenges for clinicians is determining if infections are either bacterial or viral. Their presentation can be similar, and testing to determine if infections are the former or the latter can be time consuming. Clinicians want to make sure their patients are getting some type of intervention, so broad-spectrum antibiotics can often be prescribed in these cases.

A novel assay, the MeMed BV test, can distinguish between bacterial and viral infections in 15 minutes. The test received a FDA 510(k) clearance last year and also has the European CE Mark.

A new study, the JUNO trial, was conducted by the manufacturer and demonstrated a 62% relative reduction in unnecessary antibiotic prescription rates—33% in the control group versus 13% in the MeMed BV (MMBV) group (p=0.003). Importantly, follow-up data indicated no significant increase in the rate of return emergency departments (EDs) and urgent care centers (UCCs) visits within 7 days, with 4.7% in the control group compared to 3.8% in the MeMed BV group. The data was presented at the ongoing ACEP24 Scientific Assembly by Adam Singer, MD, vice chairman for Research and Professor, Department of Emergency Medicine, Renaissance School of Medicine, Stony Brook University, New York.

The JUNO trial is a randomized controlled trial conducted across 11 EDs and UCCs in the US and Israel. It enrolled 260 adult patients with clinical suspicion of lower respiratory tract infection (LRTI). The first small-scale analysis of data from the trial, which focused on a subgroup of 160 patients.

“These preliminary results underscore the potential of MeMed BV to significantly influence antibiotic stewardship, reducing unwarranted antibiotic prescriptions while enhancing patient outcomes. We are now recruiting for a larger randomized controlled trial, which will further solidify the clinical value of the test," Singer said in a statement.

These infections are particularly challenging for clinicians especially as antimicrobial resistance continues to be an ongoing issue. Patients in some treatment environments, such as long-term care settings, may be delayed in getting diagnosed, and often patients can be given broad-spectrum antibiotics that may be limited in efficacy and leads to switching antibiotics and more exposure to these therapies and the possibility of antimicrobial resistance (AMR). One of the more important, emerging concepts is the Time-to-Treat paradigm, which is essential to getting patients antimicrobials with susceptibility to infections in an efficient time span.

Addressing gram-negative antimicrobial resistant infections has been a significant issue, and the Infectious Diseases Society of America (IDSA) decided to update treatment guidance this year. Back in August, the organization 

 for managing antimicrobial resistant infections, including those caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), difficult-to-treat 

 (DTR P. aeruginosa), carbapenem-resistant 

The MeMed BV test's manufacturer, Haifa Israel-based, MeMed, is planning to continue with studies. "The results of this trial build on a decade-long series of studies involving thousands of patients, demonstrating the high performance of the MeMed BV technology,” MeMed's co-founder and CEO Dr. Eran Eden, said in a statement. “This trial marks a significant step forward by generating interventional data and showcasing the test's actual impact on patients. We are committed to further expanding on these findings, with several additional utility and real-world studies underway. We are deeply grateful to Diasorin and BARDA for supporting this trial and for advancing the host-response field."

1.MeMed BV Test Demonstrates Antibiotic Overuse Reduction in First US Interventional Trial. MeMed. September 30, 2024. Accessed September 30, 2024. 

https://www.prnewswire.com/news-releases/memed-bv-test-demonstrates-antibiotic-overuse-reduction-in-first-us-interventional-trial-302260001.html

2. Infectious Diseases Society of America. IDSA 2024 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Published Clinical Infectious Diseases July 12, 2024. Accessed August 7, 2024. 

https://www.idsociety.org/practice-guideline/amr-guidance/

A novel test is looking to ascertain this diagnostic information quickly to aid clinicians in making a determination of infections and more efficiently prescribe antimicrobials.   

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