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The virulent pathogen has significant individual and public health implications.
 

Exploring the Threat of MDR-TB in the United States

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

In the second installment of our COVID-19 pandemic series, Robert Hopkins Jr, MD, the medical director of the National Foundation for Infectious Diseases (NFID), discusses the paradox that has risen from the COVID-19 vaccines 

Withthe the Rise of Vaccines, a Greater Public Mistrust

One of the biggest lingering effects that has arisen from the pandemic is vaccine hesitancy and antivaccine beliefs. What started out as a major achievement with the development of new vaccines to protect against COVID-19 in record time, morphed into disinformation and misinformation campaigns about the COVID-19 vaccines and expanded the public’s already existing mistrust against childhood immunizations that stemmed years before around autism and the measles mumps and rubella (MMR) vaccine.

This vaccine mistrust continues to spread today, and can be seen in the childhood vaccination rates.

“Nationally, 2-dose MMR coverage was 92.7% (range = 79.6% [Idaho] to 98.3% [West Virginia]), with coverage ≥95% reported by 11 jurisdictions and <90% by 14 jurisdictions (Table). Five-dose DTaP coverage was 92.3% (range = 79.5% [Idaho] to 98.4% [West Virginia]); with coverage ≥95% reported by 12 jurisdictions and <90% by 15,” investigators wrote in the Centers for Disease Control and Prevention’s (CDC) 

. Four-dose polio vaccination coverage was 92.6% (range = 80.1% [Idaho] to 98.4% [West Virginia]), with coverage ≥95% reported by 12 jurisdictions and <90% by 13. Two-dose VAR vaccination coverage was 92.4% (range = 79.1% [Idaho] to 99.7% [West Virginia]), with 10 jurisdictions reporting coverage ≥95% and 15 reporting <90% coverage. During the 2023–24 school year, coverage with each of the vaccines decreased in most states compared with that during the 2022–23 school year.” 

This nationwide decline in immunization rates has been a troubling trend for several years. It is important to note that once local immunization rates fall below 95%, populations in those areas become vulnerable to outbreaks. We are witnessing this now with the current measles outbreak occurring in 3 states and scattered cases in several others.

Record Time: The Development of COVID-19 Vaccines

When the US went into shutdown mode in March 2020, the government had already been working on mRNA technology, which helped accelerate the development of vaccines in less than a year.

“While a great deal of the foundational work was completed following the SARS and MERS outbreaks, and technologies were developed to facilitate mRNA and other vaccine platforms, the rapid development of a process—and then the evaluation of that compressed vaccine timeline—did not miss or change any critical scientific and regulatory steps,” said Robert Hopkins Jr, MD, medical director of the National Foundation for Infectious Diseases (NFID). “The incredible financial investment by the government, academia, industry, and the dedication of thousands of scientists, staff, and trial participants to get the vaccines to the finish line is just absolutely incredible. We then saw a huge vaccine rollout that was also unprecedented, along with the expansion of a new tool in our vaccine safety platform—the V-SAFE program. It really was an incredible and unprecedented series of events.”

The Toll of Disinformation and Misinformation

Initially, COVID-19 vaccines were viewed as a major scientific accomplishment. However, the rise of disinformation and misinformation influenced public opinion, turning many away from the vaccines. These antivaccine beliefs have since expanded to include immunizations on the childhood vaccine schedule. Diseases previously considered nearly extinct in the US—such as measles—are making a comeback.

mRNA COVID-19 Vaccines and Turbo Cancer: The Latest Myth That Won’t Disappear

first disinformation campaign around the MMR vaccine

 and autism nearly 30 years ago to the rise of antivaccine organizations and spokespeople, the pandemic only fueled the flames of this existing undercurrent. It exacerbated the vitriol and cemented these erroneous beliefs for many.

"I think there was fractured trust from the already challenged place we were in back in 2019. Add to that the mandates put in place—done with the very positive goal of protecting the health and safety of society. That good intent, unfortunately, was met with backlash,” Hopkins said. “The backlash—the chafing and outright rebellion against what to do—further fractured the fabric of our society. In the search for solutions to prevent COVID-19, several highly vocal advocates promoted unproven compounds like hydroxychloroquine, ivermectin, and others, which were trumpeted as solutions by some leaders and segments of society, despite evidence to the contrary.”

Reference
1. Seither R, Yusuf OB, Dramann D, et al. Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2023-24 School Year. 

. 2024;73(41):925-932. Published 2024 Oct 17. doi:10.15585/mmwr.mm7341a3




In the second installment of our COVID-19 pandemic series, Robert Hopkins Jr, MD, the medical director of the National Foundation for Infectious Diseases (NFID), discusses the paradox that has arisen from the COVID-19 vaccines that in spite of their development in record time, what remains is a deeper mistrust in immunizations overall.   

With the Rise of COVID-19 Vaccines, a Greater Public Mistrust of Immunizations Has Taken Hold

gepotidacin (Blujepa), was approved by the FDA. It is is indicated for uncomplicated urinary tract infections in female patients aged at least 12 years and weighing at least 40 kg.

“I think with this recent approval, it gives another option. I think to infectious disease hospitalists and family medicine this really helps identify and treat uncomplicated UTI. We know this is something that is evident across the board, whether it's in family practice or in the hospitals. And so there still is a high unmet need,” said Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of pharmacy at Emory Healthcare and Winship Cancer Institute. It's a new mechanism of action and I think that's what's exciting about this treatment.”


The approval is based on positive results from the pivotal phase 3 EAGLE-2 and EAGLE-3 trials which demonstrated non-inferiority to nitrofurantoin, one of the leading current standard of care options for uUTI, in female adults (≥40 kg) and paediatric patients (≥12 years, ≥40 kg) with a confirmed uUTI. In EAGLE-2, gepotidacin demonstrated non-inferiority in therapeutic success which occurred in 50.6% (162/320) of participants compared to 47.0% (135/287) for nitrofurantoin (covariate-adjusted treatment difference 4.3%, 95% CI (-3.6, 12.1)).


In EAGLE-3, gepotidacin demonstrated statistically significant superiority versus nitrofurantoin (one-sided p-value 0.0003). Therapeutic success occurred in 58.5% (162/277) of participants compared to 43.6% (115/264) for nitrofurantoin (covariate-adjusted treatment difference 14.6%, 95% CI (6.4, 22.8)).

The safety and tolerability profile of gepotidacin in the EAGLE-2 and EAGLE-3 phase III trials was consistent with previous trials. The most commonly reported adverse events (AEs) in gepotidacin participants were gastrointestinal (GI). Diarrhea was the most common (16% of participants), followed by nausea (9%). Of the participants who reported GI AEs in the gepotidacin group, the most common maximum severity was mild (69% Grade 1) and moderate (28% Grade 2). Participants with Grade 3 GI events accounted for 3% of all patients with GI events and occurred in <1% of all participants. There was one drug-related serious adverse event in each treatment arm (

 and nitrofurantoin) across the 2 trials.

"I think the exciting thing here is we still have nitrofurantoin, we still have fluoroquinolones, but how can we use this new option that might have a different side effect profile and leverage that for specific patient populations, then we can decrease resistance," Haumschild said. "We can add another option, if patients do progress on therapy or somehow are unresponsive." 

GSK is planning a US commercial launch in the second half of 2025.





Reference
Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and olderGSK. March 25, 2025. Accessed March 25, 2025.
https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/

This is the first in a new class of oral antibiotics for uncomplicated urinary tract infections (uUTIs) in nearly 30 years.

FDA Approves Gepotidacin (Blujepa) for Uncomplicated Urinary Tract Infections 

Sesh Sundararaman, MD, PhD, discusses his findings and how this approach can be triggered to minimize undesirable treatment features and open the door to newer treatment possibilities.  

How a Prodrug Approach May Aid In Antimalarial Development

Antimalarial treatments continue to face resistance in both Asia and Africa—2 continents devastated by this vector-borne disease. Sesh Sundararaman, MD, PhD, an attending physician with the Division of Infectious Diseases at the Children’s Hospital of Philadelphia (CHOP), points out that not only is resistance growing with existing artemisinin-based combination therapies (ACTs), but a particular strain can be much more severe.

“We know that it's occurring in a few countries in Africa. It's a big risk because the majority of cases of falciparum malaria, which is the deadliest form of malaria, occur in Sub-Saharan Africa,” Sundararaman said. “So if we lose our ability to treat patients with those drugs, we will see an increase in mortality and morbidity.”

Developing new therapies can be challenging because they are either poorly absorbed in the gastrointestinal tract or absorbed and eliminated from the body too rapidly. One potential strategy for drug development is the use of prodrugs, which are designed to improve a drug’s ability to be absorbed or to reach its target. Prodrugs work like a Trojan horse, offering a more targeted attack against infections and diseases once they reach the appropriate tissues or cells. However, prodrugs are inactive and must be activated, typically by an enzyme, to achieve their desired effect.

Sundararaman and colleagues at CHOP studied how antimalarial prodrugs are activated, with the goal of identifying a way to more effectively treat malaria.

“Prodrugging is really a way to help our drugs get to where they need to go,” Sundararaman said. “And prodrugs are actually used very commonly in the pharmaceutical industry. The main reason is that we have drugs that may have properties making them poorly absorbed. One of the things chemists can do is attach these prodrug groups that mask those properties, making a poorly absorbed drug better absorbed.”

Sundararaman and his team found that a human enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme for multiple antimalarial prodrugs known as lipophilic ester prodrugs. The APEH enzyme is normally found in red blood cells. However, in the case of malaria, the enzyme is taken into the parasite’s cytoplasm, where APEH retains its activity. The researchers’ findings suggest that APEH activates antimalarial prodrugs within the parasite, greatly increasing the potency of the lipophilic ester prodrugs.

“It seems that at least 2 different pivaloxymethyl (POM) prodrugs—the 'POM' group being the focus of this paper—are activated by the enzyme, which suggests that other prodrugs could also be activated by the same human enzyme that is taken up by the parasite,” Sundararaman said.

Their findings were recently published in the journal 

Proceedings of the National Academy of Sciences

1.Children’s Hospital of Philadelphia Researchers Use a “Trojan Horse” Approach to Develop New Antimalarial Drugs. CHOP. March 5, 2025. Accessed March 21, 2025.
https://www.chop.edu/news/childrens-hospital-philadelphia-researchers-use-trojan-horse-approach-develop-new-antimalarial



The Miami-based Jackson Health System, a nonprofit academic medical organization, saw significant increases in the fungal infection 

 every year over a 5-year period (2019–2023).¹ They experienced their largest percentage increase from 2019 to 2020, going from 5 cases in 2019 to 29 cases in 2020. This represents a 590% increase. The health system saw increases every year thereafter, with 71 cases in 2021 (a 145% increase compared to 2020), 107 cases in 2022 (a 51% increase compared to 2021), and 115 cases in 2023 (a 7% increase compared to 2022).¹

This was a retrospective observational study, and its results were published in the 

. The investigators included clinical cultures with 

 but did not include surveillance cultures. Specimens were processed through routine methods, and identification was performed using mass spectrometry. Whole-genome sequencing was performed on select specimens.¹

The predominant source was blood cultures, but the investigators noted that specimens originating from soft tissue and bone infections saw a large increase in 2022 and 2023.¹

“The volumes of clinical cultures with 

 have rapidly increased, accompanied by an expansion in the sources of infection,” the investigators wrote.¹

They also noted that all the sequenced isolates belonged to clade III (South African) and were found to be resistant to fluconazole but susceptible to echinocandins and amphotericin B.¹

 continues to increase nationwide. The most recent year of surveillance is 2023, and the Centers for Disease Control and Prevention (CDC) reported 4,514 cases of 

 in the US during that year. The agency also noted that the number of clinical cases has continued to increase since the first US case was reported in 2016. The CDC emphasizes that case numbers and trends vary by state.²

 often appears in clusters or small outbreaks within hospitals or long-term care facilities. Three states—Florida (568), California (642), and Nevada (599)—reported the highest number of cases nationwide, followed by Texas (492), Illinois (477), and New York (413). Several Mountain and New England states reported no new cases in 2023.

The CDC explains that state and local health departments submit clinical case count data to the agency. The agency also notes that case counts on some state and local health department websites may differ from federal numbers. For example, the CDC’s webpage currently shows data for clinical cases only, while some states report both clinical and screening cases.

“Differences in counts may also occur because of differences in how cases are counted (such as by case, specimen, or patient; reported date versus specimen collection date; or where the patient lives versus where the patient's sample was collected),” the CDC writes on its website.

1. Rosa R, Baptista RP, Tran TT, et al. Changing Trends in the Sources and Volumes of Clinical Cultures with Candida auris at a Large Health System, 2019-2023. 

. Published online March 17, 2025. doi:10.1016/j.ajic.2025.03.013
2. Tracking C. auris. CDC. December 9, 2024. Accessed March 21, 2025.
https://www.cdc.gov/candida-auris/tracking-c-auris/index.html?2023=2023

Examined over a 5-year period, the Jackson Health System in Florida reported large volumes of positive cultures for the fungal infection every year and that infection sources expanded over time.

Large Hospital System Experiences Significant Increases in Candida auris 

David Berman, MD, PhD, discusses promising signs of dose-dependent viral control and reduction in active HIV reservoir in Phase 1/2 STRIVE trial data

Title: Immunocore Reports 2/5 Participants Achieve Viral Control and HIV Reservoir Reduction Across 3 Dose Cohorts of IMC-M113V

Immunocore Holdings plc presented early findings from the multiple ascending dose (MAD) phase of its Phase 1/2 STRIVE trial for IMC-M113V at CROI 2025 in San Francisco, California. The data suggest that IMC-M113V, a T-cell receptor bispecific therapy, is well tolerated and demonstrates signs of dose-dependent viral control after antiretroviral treatment (ART) interruption.

The trial included 16 participants living with HIV (PLWH) who were stable on ART. David Berman, MD, PhD, executive vice president of research and development at Immunocore, explained the significance of the study, stating, “Our platform is essentially, we create these off-the-shelf, soluble bispecific proteins, where you have a targeting end to target a specific cell, and then the other end is an effector, which brings T-cells close to the target cell, so close that it actually can kill the target cell. So it acts as a bridge.”

No serious adverse events were observed, and mild cytokine release syndrome (CRS) was noted in some participants at higher doses. The highest dose cohort (300 mcg) showed a dose-dependent increase in T-cell-derived cytokines. “With our cancer programs, we see evidence that you're activating T-cells. So when T-cells get activated, you see cytokines being released in the blood, and that leads to something called cytokine release syndrome. So it's fully expected, and essentially that is typically begins with fever,” Berman explained. “Now with repeated dosing, it doesn't appear to be any other adverse event, so it is very well tolerated.”

Three participants showed delayed viral rebound and subsequent viral control during ART interruption. Viral load in these individuals decreased to approximately 200 copies/mL, a result not commonly seen in untreated PLWH. The trial’s aim is to assess IMC-M113V’s ability to reduce the HIV reservoir and control viral replication after ART interruption. Berman commented, “What we saw, quite remarkably, is a dose-dependent evidence of antiviral reduction, and that's manifest as three of these people living with HIV during the ATI had an increase in their virus initially, and then it seems like the immune system was activated and the virus came under control, and the virus went back down to around 200 copies per million.”

The initial results also show a reduction in CD4+ T-cell-associated HIV Gag RNA in some participants, suggesting a reduction in the active viral reservoir. Berman explained the importance of targeting the viral reservoir, “The viral reservoir, as you point out, was the first measure. And there, it's important to remember that a majority of the viral and the analog I give is the iceberg. If you think of the iceberg, only the tip of the iceberg above the water, the tip of the viral reservoir will actually produce replication competent virus.”

Preliminary data also indicate a trend toward reduced intact HIV DNA in patients treated at the two highest doses. IMC-M113V works by targeting an HLA-A*02:01-Gag complex on HIV-infected cells, using an anti-CD3 effector to recruit T-cells that destroy HIV-infected CD4+ cells. Berman elaborated on how the therapy targets HIV, stating, “We identified a protein in HIV called gag that is chopped up inside the cell, and small peptides are presented on the surface by HLA, and we developed the targeting end of the bispecific to recognize that gag peptide.”

The trial is continuing with higher doses being evaluated, and additional expansion cohorts are planned. Berman emphasized that while the results are promising, further investigation is needed: “We need to continue dose escalating, and then we can, you know, correlate that with clinical outcome.”

The next steps for the treatment involve evaluating the antiviral activity of IMC-M113V in larger cohorts, focusing on correlating the reduction in the viral reservoir with clinical outcomes. Berman noted, “The immediate next steps for us is to continue dose escalating, because if we can, it’s very well tolerated with higher doses, we may even see further reductions. And then we would want to look at correlations between the reservoir reduction and antiviral activity.”

As the trial continues, Immunocore is working to determine whether the antiviral activity can be sustained beyond 12 weeks, with the ultimate goal of achieving a functional cure. “The goal here is functional cure. It's not a 12-week interruption of the treatment,” Berman said. “We wanted to go to the harder population, because you can see a signal. So everyone in our trial started ART later, they're less likely to spontaneously control."

Immunocore Holdings plc. Immunocore presents initial multiple ascending dose data for HIV functional cure candidate in an oral presentation at CROI 2025. 

. March 10, 2025. Accessed March 17, 2025. https://www.immunocore.com/investors/news/press-releases/detail/112/immunocore-presents-initial-multiple-ascending-dose-data-for-hiv-functional-cure-candidate-in-an-oral-presentation-at-croi-2025

David Berman, MD, PhD, discusses signs of dose-dependent viral control and reduction in active HIV reservoir in Phase 1/2 STRIVE trial data.


JENNIFER BAILEY, PHARMD, BCPS, AAHIVP

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