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Researchers found the experimental vaccine could potentially inhibit severe diarrhea and pseudomembranous colitis by inducing a functional antibody response that can neutralize the two main disease-causing toxins (toxin A or B) produced by C. difficile.

Pfizer's C. difficile Vaccine Succeeds in Phase II Study

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

) was first identified in a single case in Japan where a man had it appear in his ear. According to the Centers for Disease Control and Prevention (CDC), a retrospective review of 

strain collections found that the earliest known strain of the fungus dated back further to 1996 in South Korea.

In the ensuing years, the fungal pathogen has been mysterious in appearing very quickly in places and then disappearing almost as quickly. Earlier this year, two outbreaks were made public with one happening at a nursing home in Washington, DC, and the other at 2 hospitals in the Dallas area.

During this outbreak, a cluster of 101 cases was detected in the Washington, DC, nursing home and a cluster of 22 cases was detected in 2 Dallas areas hospitals from January to April.

According to reports, some of these patients infected with 

did not show any clinical improvement after being treated with all 3 major classes of the antifungals. In fact, in 5 patients who were fully resistant to treatment, 3 of them died.

 does not appear to have a high incidence rate, the infection presents some serious challenges to clinicians. It is especially troublesome as the CDC has outlined 3 main concerns about it, including:

It being a newer, emerging fungus, it can be challenging for labs to diagnose with standard laboratory methods, which can lead to misidentification and in turn lead to the incorrect treatment and management;

And lastly, it can quickly lead to outbreaks in health care facilities.

 fungal infection is still relatively rare, when it occurs in the 

, it can quickly take hold and become an outbreak if infection prevention measures are not taken.

 clinical isolates are resistant to one of the 3 classes of antifungals that we have to treat invasive infections,” Jeffrey Rybak, PharmD, PhD, instructor, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, said. Rybak has been conducting research on 

 in trying to identify novel targets for therapy, apply next-generation sequencing technologies, and develop molecular tools to advance the study of the fungus.

Rybak also points out that isolates might become resistant while someone is on therapy. “Even while it might be susceptible upfront, after a week or two of therapy, we may find that the patient has an infection now caused by an isolate of the same 

 that has become resistant to the echinocandins and we are really left with nothing else.”

Rybak says these investigational agents show promise against the infection, but that they need to see more clinical trials to see their full treatment utility.

 spoke to Rybak about the challenges of multidrug resistance with 

uris, how diagnosing it is evolving, the merits of monotherapy over combination therapy, what to consider in seeing resolution of symptoms, and some of the big picture public health concerns associated with this infection.

With the unpredictability of when it will appear, and its propensity to be multidrug-resistant, this particular pathogen is challenging to diagnose and treat.  

Candida Auris: An Enigmatic and Difficult-to-Treat Fungal Pathogen

With the different modes of transmission and the variability in their incidence rates, infectious disease outbreaks can be difficult to manage once they appear. 

The introduction of COVID-19 reaffirmed how quickly an infectious disease can take hold and how dangerous a viral pathogen can be to a larger, global population.

Ebola, on the other hand, has had very bad regional outbreaks in various countries within Africa. And while its mode of transmission is different (through body fluids), the fear it could spread to other areas in the world remains intense due to the disease’s harmful effects and potential mortality. Ebola’s 

 according to the World Health Organization, but there is also great variability with rates ranging from 25% to 90% from past individual outbreaks. 

is a mysterious fungal infection and not much is fully known for why outbreaks appear. It remains highly contagious in health care settings and is often multidrug resistant. Similar to Ebola, the mortality rates for 

 vary greatly according to Jeffrey Rybak, PharmD, PhD, instructor, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital.

Outside of a smattering of cases in Europe and the US, Ebola outbreaks have remained on the African continent. Conversely, 

 has had outbreaks in several continents occurring simultaneously, according to Rybak.

In the second installment of an interview with 

Rybak discusses outbreaks across different geographic locations including one where there was a high incidence rate of COVID-19, 

 mortality rates, and whether it has enough durability that will provide it with a sense of permanency and therefore remain a concern in public health for years to come.

The emergence of this fungal infection remains mysterious as the world experiences more outbreaks. 

Considering Candida Auris Outbreak Behavior

 continues to be a concerning fungal infection in health care settings. Outbreaks can appear without warning almost anywhere in the world and disappear quickly as well.

First discovered in Japan in 2009, this enigmatic yet emerging fungal infection remains a concern for health care personnel as they try to understand outbreaks but also determine treatment protocols. 

AdventHealth Orlando, a large hospital system in central Florida, wanted to study 

 susceptibility patterns. The investigators recovered 5 

 isolates from clinical samples over the course of a year in 2021. They performed susceptibility testing included flucytosine, isavuconazole, voriconazole, amphotericin B, itraconazole, posaconazole, anidulafungin, micafungin and fluconazole.

“All five isolates from AdventHealth Orlando have been resistant to fluconazole and based on our results, this agent should be avoided as part of the treatment optimization when an infection by 

 is confirmed,” the study authors wrote.

The study, “Susceptibility Pattern of Five 

 Strains Isolated from Clinical Samples at AdventHealth Central Florida Division, South,” was presented at the 

24th Annual Making a Difference in Infectious Disease (MAD-ID) Meeting 2022,

 spoke to costudy investigator Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, director, Microbiology/Virology/Immunology Laboratories, AdventHealth at the meeting who provided insights on the study and the challenges of testing for this elusive fungal infection.

AdventHealth Orlando studied a small number of these fungal isolates to examine treatment resistance patterns. 

Conferences

Examining Candida Auris Susceptibility Patterns 

remains a mysterious fungal infection. Since it was first identified in Japan back in 2009, it has been spreading in localized outbreaks across 6 continents.

Most recently, the state of Mississippi reported in January that there were 6 total cases of 

 with 2 deaths and 37 people colonized with the fungus since November 2022. The cases were traced back to long term acute care facilities (LTAC) in the central part of the state.

According to the Centers for Disease Control and Prevention (CDC), a retrospective review of 

 collections found that the earliest known strain of the fungus dated back further to 1996 in South Korea. So, it has been with us for a number of years now, but thus far, there have been no definitive answers as to why these outbreaks occur.

“It is not entirely clear why we are seeing more 

 outbreaks,” David S. Perlin, PhD, chief scientific officer and executive vice president, 

Center for Discovery and Innovation (CDI) Hackensack Meridian Health

, said. “One possibility is that there is a much broader use of antifungal agents around the world for both treating human disease as well as for controlling fungal outbreaks in agriculture. This may well be selecting for organisms for 

, which can persist in the environment and readily adapt to stress situations induced by antifungal agents hence resulting in antifungal drug resistance.”

Interestingly, Perlin does see some parallels between fungal and bacterial infections and MDR.

“There are clades of 

, for example, that have mono resistance, or mild resistance, or moderate resistance…during therapy you can see selection of a kind of canonical resistance,” Perlin stated.

CDC has outlined 3 main concerns about 

 infection, including: It is often multidrug-resistant; It can be challenging for labs to diagnose with standard laboratory methods, which can lead to misidentification and in turn lead to the incorrect treatment and management; and lastly, it can quickly lead to outbreaks in health care facilities. This last component, is especially concerning because 

 typically appears in hospitals and long-term facilities, affecting older patients and those who might already be diagnosed with serious health problems and might be prone to infections.

Perlin is an expert in drug discovery and drug resistance mechanisms, and he has helped develop novel therapeutics and diagnostics against high-threat bacteria, viruses, and fungi. He has published more than 320 papers and book chapters and has co-authored two books.

Perlin leads CDI, and his team has been involved in multiple studies involving 

 research. His laboratory is supported by multiple grants from the National Institutes of Health, pharmaceutical and biopharmaceutical sectors. Perlin and his group at CDI was among the first to develop a molecular diagnostic for 

. “The key in developing a molecular diagnostic for 

 as it is for any organism is to identify those genetic signatures that distinguish it from other organisms.”

He said it was challenging for the existing commercial testing systems to distinguish the other species of 

 and were confusing the existing commercial tests.




The mortality rate for this form of infection is high and that is due in part to the high level of multidrug resistance.

 found in the United States have been susceptible to echinocandins although reports of echinocandin- or pan-resistant cases are increasing. This organism appears to develop resistance quickly. Patients on antifungal treatment should be carefully monitored for clinical improvement. Follow-up cultures and repeat susceptibility testing should be conducted. Both recurrent and persistent 

 bloodstream infections have been documented," the CDC stated on its website.

Back in November, Jersey City, NJ-based Scynexis was awarded a grant to study the potential of their agent, SCY-247, for treatment of 

SCY-247 is a second generation fungerp, a triterpenoid class of antifungals, which represents the first new class of antifungal compounds since 2001, and is under development as a potential systemic therapeutic option. During that time, the company anticipated that the FDA may grant SCY-247 Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of the agent.

The first generation fungerp, ibrexafungerp, formerly known as SCY-078, was 

 in December to treat vulvovaginal candidiasis (VVC) and prevent recurrent VVC.



 spoke to Perlin who offered some insights into his lab’s research on 

their development of a molecular assay, various therapies, and the hope of further collaboration between laboratory professionals and clinicians.



A prominent researcher offers some insights on this emerging fungal infection.



Candida auris: Understanding the Mystery Behind Outbreaks

is spreading rapidly throughout the United States, according to the Centers for Disease Control and Prevention (CDC).

is an emerging fungus that, troublingly, is displaying antimicrobial resistance. The superbug is spreading in health care facilities across the country, with high fever and chills as the most common initial symptoms.

 has been steadily spreading in the US. However, a new 

incidence, with cases doubling from 2019 to 2021.

The study utilized CDC national surveillance data from individuals with any specimen that tested positive for 

. A total of 3270 clinical cases and 7413 screening cases of 

 were reported in the US through December 31, 2021. Each year, the percentage of clinical cases increased, with a 44% increase in 2019 and a 95% increase in 2021.

Additionally, 2021 saw an 80% increase in colonization screening volume and a more than 200% increase in screening cases. From 2019-2021, 17 states all identified their first-ever 

Echinocandins are a class of antifungals widely used to treat invasive candidiasis, primarily indicated for critically ill and neutropenic patients. Concerningly, this report found that the number of 

cases with echinocandins resistance in 2021 had tripled in each of the preceding 2 years.

One limitation of these findings is that the identification of screening cases directly relies on the basis of need and available resources, which determine when screening is conducted. Because screening is not conducted uniformly across the country, the true burden of 

The investigators note that the rise in echinocandin-resistant cases and evidence of transmission are particularly alarming. “These findings highlight the need for improved detection and infection control practices to prevent spread of 

Candida auris fungal infections increased 95% in 2021, and drug-resistant cases are continuing to spread across the US.

Amy Jacob

Articles

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