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How has treating infections changed with the availability of experimental vaccines and therapeutics, and how can we apply this to COVID-19 today? 

What the 2018 DRC Ebola Epidemic Taught Us About Outbreak Response and Experimental Countermeasures

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

 support the use of a simple, noninvasive diagnostic algorithm for predicting advanced liver fibrosis in patients with chronic hepatitis B (CHB), offering a practical alternative to liver biopsy, especially in primary care and resource-limited settings. This prospective, multicenter cross-sectional study included 602 patients with CHB who underwent liver biopsy: 408 in a training cohort from 2 centers and 194 in an external validation cohort from a third center. 

One decision rule (rule No. 1) identified advanced fibrosis (F3-F4) using criteria of platelet count less than 185 × 10⁹/L, age less than or equal to 38 years, and γ-glutamyltransferase (GGT) greater than or equal to 27 IU/L. This rule applied to 60 patients (14.7%) in the training cohort, correctly classifying 41 as F3-F4, with a sensitivity of 53.9%, specificity of 94.3%, positive predictive value (PPV) of 68.3%, and negative predictive value (NPV) of 89.9%. Another rule (rule No. 2), which incorporated all 5 variables, identified patients without significant fibrosis (F0-F1) and demonstrated strong diagnostic performance, with a sensitivity of 90.1%, specificity of 74.7%, and both PPV and NPV of 83.8%. This rule applied to 260 patients (63.7%) in the cohort.

Researchers developed a decision tree algorithm based on 5 routinely available variables: platelet count, alanine aminotransferase, aspartate aminotransferase, GGT, and patient age. This algorithm provides a noninvasive, cost-effective tool for accurately staging liver fibrosis in CHB, thereby enhancing clinical decision-making, particularly where advanced diagnostics are scarce.

In findings from a separate CHB study published concurrently, a novel extracorporeal immunoadsorption therapy using anti–hepatitis B surface antigen (HBsAg) monoclonal antibody-coated agarose beads showed significant removal of HBsAg in a preclinical rabbit model, also published in 

. The system achieved a mean reduction of 76.4% in serum HBsAg and a 66.2% decrease in HB virus DNA levels in rabbits injected with HBsAg-positive serum. These results address a critical hurdle in achieving functional cure for CHB, defined by sustained HBsAg clearance, a goal rarely met by current antiviral therapies. Although immunoadsorption therapy offers a novel adjunctive approach by directly removing HBsAg, further clinical studies are needed to evaluate its safety, tolerability, and efficacy in humans.

To develop the system, researchers screened 6 monoclonal antibodies and selected the most effective for coupling to agarose beads. The resulting immunosorbent was validated for adsorption efficiency and structural integrity using scanning electron microscopy and energy-dispersive spectrometry. In vitro cytotoxicity testing with V79 lung fibroblasts confirmed no adverse effects on cell viability. The immunosorbent exhibited strong static and dynamic HBsAg-binding capacity in vitro, which supported its testing in an extracorporeal circulation system in vivo.

Together, these studies highlight 2 promising, science-driven advances in CHB management: a validated, noninvasive fibrosis staging algorithm that leverages routine laboratory tests for risk stratification and an innovative immunoadsorption system offering a mechanistically novel method to clear HBsAg, an essential step toward functional cure. Clinical trials are warranted to confirm the safety, tolerability, and therapeutic benefit of these approaches in human patients.

1. Nana J, Bosson JL, Skaare K, et al. Diagnostic performance of a new algorithm combining simple, non-invasive and inexpensive tests for predicting the presence of advanced liver fibrosis in patients with chronic hepatitis B. 

2. Wang M, Zhou Q, Wu H, et al. Efficacy of extracorporeal immunoadsorption therapy for removal of HBsAg. 

Findings from recent studies published in BMC Gastroenterology highlight practical diagnostic tools and novel therapeutic strategies to improve management of chronic hepatitis B.

New Advances in Chronic Hepatitis B: Noninvasive Fibrosis Algorithm and Immunoadsorption Therapy

In 2023, the United States reported 2770 cases of nationally notifiable arboviral diseases, with West Nile virus (WNV) accounting for 95% of those cases, according to a Centers for Disease Control and Prevention (CDC) report published in 

. These infections resulted in 2022 hospitalizations (73%) and 208 deaths (8%), with the majority of illnesses occurring from July through September.

Among the year’s most significant findings was the first US human infection with a novel WNV lineage 3 (L3), a strain previously detected only in mosquitoes in Central Europe. The patient was coinfected with both L3 and the more common lineage 1 (L1) and became severely ill, requiring advanced diagnostic testing.

“This was the first time WNV lineage 3 has been associated with human disease and identified in the United States,” said Hannah Padda, DVM, CDC epidemic intelligence service officer, in an email interview with 

. “CDC described the case in a paper published in 2024 in the 

 journal, reporting that the patient was coinfected with both L3 and the very common lineage 1.”

Although the exact role of L3 in the illness remains unclear, Padda emphasized the need for expanded surveillance: “It is not clear what role L3 played in the patient’s illness, if any, because the person was infected with both lineages. We also do not know how widely L3 is distributed in the United States or how many WNV infections might be associated with L3.”

Current molecular surveillance tools do not routinely detect or differentiate WNV lineages: “The L3 detection in the United States highlights the importance of conducting WNV surveillance, including for human disease and vectors. Current surveillance methods for WNV disease do not include tests that detect L3 by molecular methods or differentiate L3 from L1 through blood testing.”

Padda stressed the importance of continued research to assess any impact on public health guidance: “More research is needed to better understand the public health impact of L3 WNV to inform any potential changes to clinical, diagnostic, vector control, or prevention recommendations. In the meantime, CDC guidance remains the same for all WNV lineages: People can take steps to help protect themselves from mosquito bites and communities can implement mosquito control.”

Powassan virus disease ranked second in reported arboviral infections in 2023, with 49 cases, an increase from 2022's record high. La Crosse virus, meanwhile, was the most common cause of arboviral illness among children, with many cases classified as neuroinvasive.

The report also documented 3 WNV transmissions through organ transplantation, reinforcing the need for vigilance in donor screening. “WNV transmission from an infected organ donor is rare,” Padda said. “There are currently no required donor screening protocols for WNV, but most living donors and some deceased donors are screened for evidence of WNV infection. Health authorities and blood and organ donation organizations monitor and update their protocols to ensure the safety of the blood and organ supply.”

Given the underreporting of arboviral illnesses due to asymptomatic infections and limited testing, improved case detection remains a CDC priority. “CDC works to increase patient and provider awareness of arboviral diseases because understanding the seasonal and geographic distribution and characteristics of arboviral diseases in the United States is essential to detect and report cases,” said Padda.

She outlined several strategies to enhance detection and reporting

“People with flu-like or neurologic symptoms—such as neck stiffness, muscle weakness, numbness, disorientation, or sudden vision loss—should see their health care provider and discuss any recent exposure to mosquito or tick bites.”

“Health care providers should consider arboviral testing for patients with acute febrile or neurologic illnesses when ticks and mosquitoes are active and regularly talk to their patients about preventing mosquito and tick bites.”

“Health care providers should also inform their state or local health department of patients with suspected arboviral infections.”

“State and local health departments should continue to report cases to CDC to inform arboviral disease surveillance.”

As the geographic range and diversity of arboviruses evolve, the CDC urges clinicians and public health practitioners to remain alert. Preventive measures, including personal protection, mosquito control, and enhanced testing, remain the cornerstone of reducing morbidity and mortality.

1. Padda H, Jacobs D, Gould CV, et al. West Nile virus and other nationally notifiable arboviral diseases — United States, 2023. 

2. Davis E, Velez J, Hamik J, et al. Evidence of lineage 1 and 3 West Nile virus in person with neuroinvasive disease, Nebraska, USA, 2023. 

. 2024;30(10):2090-2098. doi:10.3201/eid3010.240595

3. West Nile and organ transplantation. Centers for Disease Control and Prevention. May 14, 2024. Accessed June 26, 2025. 

https://www.cdc.gov/west-nile-virus/causes/organ-transplantation.html

4. West Nile: symptoms, diagnosis, & treatment. Centers for Disease Control and Prevention. May 15, 2024. Accessed June 26, 2025. 

https://www.cdc.gov/west-nile-virus/symptoms-diagnosis-treatment/index.html

Centers for Disease Control and Prevention report underscores need for improved surveillance, donor screening, and public awareness as rare WNV strain emerges and Powassan virus cases hit new high.

West Nile Virus Dominated Arboviral Cases in 2023, as CDC Reports First US Infection With Lineage 3 Strain

Invivyd recently announced its phase 3 CANOPY trial evaluating monoclonal antibody, pemivibart (Pemgarda), against COVID-19 has been published in the journal 

Pemivibart showed a 84% relative risk reduction of symptomatic COVID-19 vs placebo during the 6-month on-drug period and 74% relative risk reduction sustained through a 6-month off-drug follow-up, highlighting durable protection even at low residual drug levels.

And in an evolving regulatory environment, Invivyd’s CANOPY results suggest a potential shift in how monoclonal antibody therapies might be considered for infectious disease prevention.

One of the patient groups being studied in the CANOPY trial is immunocompromised individuals. This group has had limited efficacy in terms of COVID-19 vaccine protection, so there is a need for additional immunization, especially in a patient base with major medical issues, and these individuals can be at a higher risk for severe disease, including hospitalization and mortality.

 sat down to speak with Cameron Wolfe, MBBS, of Duke University School of Medicine, principal investigator for the trial, and Mark Wingertzahn, PhD, senior vice president of clinical development and medical affairs at Invivyd, to discuss the results of the trial.

 I wanted to begin by discussing the relative risk reduction. Can you elaborate on the significance of the 84% risk reduction observed during the 6-month on-drug period in the CANOPY trial?

 The CANOPY study was unique in several ways. We had a placebo-controlled cohort where an 84% relative risk reduction was observed after 2 study drug doses—that corresponds to the 6-month time point. There was also an off-drug period, or what we might think of as a washout period, which continued from month 6 through month 12.

That 84% relative risk reduction observed in the immunocompetent cohort offered a couple of key insights. First, it demonstrated that there are still highly effective and well-tolerated options beyond vaccines. Second, it showed a significant level of protection, particularly important given that this is the only monoclonal antibody currently available that has retained efficacy even after the emergence of Omicron.

So we’re looking at a very contemporary drug evaluated in a modern patient population—the only study done to date with a monoclonal antibody that still retains activity. The results demonstrated robust protection against a composite end point of RT-PCR [reverse transcription polymerase chain reaction]–confirmed COVID-19 cases, hospitalization, and death.

An important component of this trial is that it included participants who are immunocompromised. Can you talk about the challenges this patient population faces with COVID-19 and any key takeaways for them from this study?

 As I was preparing for this interview, I reflected on how I personally felt during the height of COVID-19. I was living in a high-rise in downtown Boston at the time, and I remember how empty and eerie the streets were; barely anyone was out. It felt isolating, unsettling, and frightening.

I think many of us with intact immune systems have since forgotten those feelings. But for immunocompromised individuals, that sense of isolation still persists. They still can’t safely enter crowded spaces like grocery stores, concerts, or malls. They continue to live in a very insular and cautious way.

They have to think carefully about when and how they can see family—whether it has to be outside rather than indoors, for instance. Unlike those of us with fully functioning immune systems, immunocompromised patients still live with that heightened caution and risk, which impacts their quality of life and social connectedness.



 In looking at the antibody safety profile, can you offer some insights on it during this trial?

 I am glad that post marketing, we haven't seen anything on the allergic and anaphylactic side. That's reassuring. And I think, frankly, [that] would be more consistent with what we knew from monoclonals in lots of other spaces. I think that's reassuring. The patients in whom you use these are complex patients with lots of medical issues and lots of risk, and I think the safety profile when balanced against what you're trying to achieve with the drug actually stands out really well.

And how does the trial position this form of prevention as a viable option for PrEP?

We've learned a lot in the last 4 or 5 years about who's at risk, who responds well to vaccines, and who gets more severe COVID-19. And I think what this trial does is builds on experience with other monoclonals really to highlight an effort for people who are still getting severe COVID-19 and who have not been able to mount a sufficient response. The fact that this product maintains efficacy against current variants is its other strength there.

Results from Invivyd’s pemivibart (Pemgarda) phase 3 trial show it had a significant PrEP effect during the 6-month on-drug period for both immunocompromised and immunocompetent populations.

Monoclonal Antibody Shows 84% Relative Risk Reduction of Symptomatic COVID-19 vs Placebo

: TGD Cuts, LLC, of Jessup, Maryland, recalled fresh cucumbers and related products containing cucumbers from Bedner Growers, Inc, due to potential 

 contamination. These items, with use-by dates from May 19 to 28, 2025, were distributed across Maryland, Virginia, Pennsylvania, New Jersey, and North Carolina. The products are believed to be past their shelf life, and no illnesses have been reported.

: August Egg Company in Hilmar, California, recalled approximately 1.7 million dozen brown cage-free and organic eggs due to possible contamination with 

enteritidis. Distributed between February 3 and May 15, 2025, these eggs bore plant codes P-6562 or CA-5330 and were sold in multiple western and midwestern states, including at major retailers such as Walmart and Safeway. The company ceased sales of fresh shell eggs and redirected eggs to pasteurization facilities.

: Fuentes Farms LLC of McAllen, Texas, recalled 71 boxes of fresh cucumbers (Lot 357) potentially contaminated with 

. Distributed through flea markets in McAllen and Alamo, Texas, between May 31 and June 3, these cucumbers were packaged in 40-lb boxes with Fuentes Farm labels. No illnesses were reported. This recall was prompted by an FDA routine sample detecting the bacteria.

 infections can cause fever, diarrhea, nausea, vomiting, and severe complications, especially in young children, older people, and immunocompromised individuals.

: Bornstein Seafoods, Inc, of Bellingham, Washington, recalled 44,550 lb of cooked and peeled ready-to-eat coldwater shrimp due to potential 

 contamination. Distributed mainly in the Pacific Northwest and British Columbia, these products were pulled after routine testing. No illnesses were reported.

: Hofood99 Inc of Brooklyn, New York, recalled 200-g packages of enoki mushrooms nationwide following detection of 

 by Michigan state authorities. Packaged in green plastic bags, these mushrooms are marked with UPC 6 976532 310051. Consumers were advised to destroy or return the product.

 Face Rock Creamery of Bandon, Oregon, is voluntarily recalling 2 lots of its Vampire Slayer Garlic Cheddar Curds sold at Trader Joe’s in Northern California and Northern Nevada due to potential contamination with 

, which can cause serious illness, especially in vulnerable populations. No illnesses have been reported. Consumers are urged not to eat the product and to return it for a full refund. The recall follows routine testing that detected the bacteria, and the company is working with regulators to address the issue.

 poses serious risks to young children, older people, pregnant women, and immunocompromised individuals, causing symptoms such as high fever, headache, nausea, and, in pregnant women, miscarriage or stillbirth.

: P East Trading Corp in Bronx, New York, recalled uneviscerated salted, smoked split herring sold in New York, New Jersey, and Connecticut due to possible contamination with 

. The product, packaged in 18-lb wooden boxes and made in Canada, was found to be over 5 inches long and improperly eviscerated, increasing botulism risk. 

 produces a toxin that causes botulism, a severe and potentially fatal illness characterized by symptoms including muscle weakness, dizziness, double vision, difficulty speaking or swallowing, and respiratory failure. Consumers were warned not to consume the product regardless of appearance or odor.

: Medtech Products Inc of Tarrytown, New York, announced a nationwide recall of 5 lots of Little Remedies Honey Cough Syrup due to contamination with 

. Distributed from December 2022 through June 2025, these syrups can cause foodborne illness with nausea, vomiting, and diarrhea; though typically mild, high exposure can be fatal.

References
1. Company announcement: Tgd Cuts, LLC initiated voluntary recall of cucumber from Bedner Growers Inc., which had the potential to be contaminated with Salmonella. FDA. June 4, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/tgd-cuts-llc-initiated-voluntary-recall-cucumber-bedner-growers-inc-which-had-potential-be

2. Company announcement: August Egg Company recalls shell eggs because of possible health risk. FDA. June 6, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/august-egg-company-recalls-shell-eggs-because-possible-health-risk

3. Company announcement: Fuentes Farms, LLC recalls product because of possible health risk. FDA. June 16, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/fuentes-farms-llc-recalls-product-because-possible-health-risk

4. Company announcement: Bornstein Seafoods Inc recalls cooked & peeled ready-to-eat coldwater shrimp meat because of possible health risk. FDA. June 10, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/bornstein-seafoods-inc-recalls-cooked-peeled-ready-eat-coldwater-shrimp-meat-because-possible-health

4. Company announcement: Hofood99 Inc recalls enoki mushroom due to possible health risk. FDA. June 11, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/hofood99-inc-recalls-enoki-mushroom-due-possible-health-risk

5. Face Rock Creamery voluntarily recalls Vampire Slayer Garlic Cheddar Curds due to potential Listeria contamination. FDA. June 21, 2025. Accessed June 30, 2025. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/face-rock-creamery-voluntarily-recalls-vampire-slayer-garlic-cheddar-curds

6. Company announcement: P. East Trading Corp Distributors issues alert on uneviscerated 'salted smoked split herring' due to potential Clostridium botulinum contamination. FDA. June 10, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/p-east-trading-corp-distributors-issues-alert-uneviscerated-salted-smoked-split-herring-due

7. Company announcement: Medtech Products Inc. issues nationwide recall of Little Remedies® Honey Cough Syrup due to microbial contamination. FDA. June 18, 2025. Accessed June 30, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/medtech-products-inc-issues-nationwide-recall-little-remediesr-honey-cough-syrup-due-microbial

Several companies nationwide, with FDA oversight, recalled food products due to potential bacterial contamination, issuing consumer warnings to prevent foodborne illness.

KRUTIKA KUPPALLI, MD

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