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Diagnostic stewardship is a novel concept related to modifying the process of ordering, testing, and reporting with the goal of decreasing unnecessary testing and treatment, working upstream and synergistically with antimicrobial stewardship principles.

Diagnostic Stewardship: Beyond Managing Bloodstream Infections

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

Presented at ASM Microbe 2025, a bioinformatics-driven study has identified nine human microRNAs (miRNAs) with strong complementary binding to both hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV), supporting their potential use as targeted antiviral therapeutics.

HCV, a positive-sense single-stranded RNA virus in the Flaviviridae family, is a major cause of liver cirrhosis and hepatocellular carcinoma. Despite the availability of direct-acting antivirals (DAAs), challenges persist due to drug resistance and lack of a prophylactic vaccine. BVDV, a related pestivirus, is an established model for studying HCV due to its similar genomic structure.

Researchers from Diné College used multiple computational tools, NCBI BLAST-n, miRBase, and miRDB, to conduct over 36,400 sequence alignments. The objective was to identify human miRNAs with high sequence complementarity to the BVDV nucleocapsid gene and the HCV capsid gene across all six major genotypes.

Nine miRNAs demonstrated strong dual-binding affinity:

Each candidate aligned to both viral targets with two complementary sequence locations, suggesting potential for simultaneous inhibition of viral replication pathways in both BVDV and HCV. This multi-target interaction highlights their potential utility in developing a dual-acting therapeutic strategy.

The therapeutic concept relies on miRNAs’ ability to regulate gene expression post-transcriptionally by targeting viral mRNA. In this study, bioinformatics alignment confirmed that selected miRNAs can theoretically suppress viral protein synthesis by binding to conserved genomic regions.

The findings are especially relevant given the global burden of HCV, which affects an estimated 58 million people worldwide, and the continuing emergence of resistant viral strains. A miRNA-based antiviral could provide a nontraditional therapeutic approach that complements or enhances existing DAA regimens.

The investigators emphasized the need for preclinical validation to assess antiviral efficacy, off-target effects, delivery mechanisms, and safety profiles in both in vitro and in vivo models. This study provides foundational data for future development of miRNA-based antiviral therapies and reinforces the value of computational methods in early-stage therapeutic discovery.

Cayatineto HW, Hakim S. Interaction between candidate miRNAs, bovine viral diarrhea virus (BVDV) nucleocapsid gene and hepatitis C virus (HCV) capsid gene: a promising antiviral therapeutic approach. Abstract AAR-IDS-202. Presented at ASM Microbe 2025. June 19-23, 2025. Los Angeles, CA.

Presented at ASM Microbe 2025, a bioinformatics study highlights 9 human miRNAs capable of binding and potentially inhibiting both hepatitis C and bovine viral diarrhea viruses.

Conferences

Dual-Targeting miRNAs Identified as Potential Therapeutics Against HCV and BVDV

Malaria elimination progress in Africa has stalled despite scale-up of standard control interventions. Mass drug administration (MDA) shows promise for reducing transmission, but evidence is limited for low-to-moderate transmission settings. To inform clinical practice, we interviewed study authors Michelle Hsiang, MD, MS, and Michelle E Roh, PhD, for expert insights on their recent trial.

Coverage of MDA improved across rounds, with 74%, 79%, and 81% of eligible participants receiving treatment in cycles one through three. No serious adverse events were reported, confirming safety. The adjusted reduction in malaria incidence was approximately 55% (95% CI, 28 to 71) during the intervention year but declined to 26% (95% CI, –17 to 53) post-intervention. Malaria incidence during the post-intervention transmission season remained 126 cases per 1000 population in the intervention arm versus 146 cases per 1000 in controls.

This open-label, cluster-randomized controlled trial in southeast Senegal randomized 60 villages with moderate-to-low seasonal malaria transmission (60–160 cases per 1000) to either three cycles of MDA with dihydroartemisinin–piperaquine plus single low-dose primaquine at 6-week intervals or standard seasonal malaria chemoprevention (SMC) with sulfadoxine–pyrimethamine plus amodiaquine every 4 weeks. The primary endpoint was 

 incidence in the post-intervention season (July–December 2022). Safety, coverage, and incidence during the intervention year were secondary outcomes.


Hsiang and Roh emphasized that “in our study setting, where malaria transmission was moderate-to-low and highly seasonal and coverage of standard malaria control interventions (eg, vector control, surveillance, case management) was high, three rounds of MDA with dihydroartemisinin-piperaquine and single low-dose primaquine rapidly reduced malaria incidence by ~55%.” Although, “this effect was not sustained upon discontinuation of MDA, with none of the villages reaching pre-elimination levels (<5 cases per 1000 population) in the subsequent transmission season.”

Regarding future malaria control strategies, they recommend: “Ensure that the number of MDA rounds administered covers the full transmission season. It is likely that, in our study, partial coverage of the transmission season contributed to the weak sustained effect in the post-intervention year.” Furthermore, programs should “aim to reach >80% coverage of the population (supported by WHO recommendations), which may require strong community acceptance and engagement by the local health and administrative officials.” They also noted, “MDA is costly and resource-intensive and may require sustained commitment over several years to maximize benefits.”

On challenges to sustaining MDA’s impact, their recommendations include: “MDA will likely need to be repeated annually over several years until malaria incidence drops to low levels, at which point programs can consider transitioning to more targeted strategies such as focal MDA.” They stress that “to effectively reduce the parasite reservoir, the timing and frequency of MDA rounds should cover the entire transmission season.” Finally, “community sensitization and engagement are critical to reaching high coverage,” with additional efforts needed “to engage groups who may be less likely to participate in standard chemoprevention campaigns, including adults, adolescents, and highly mobile populations.”


The study’s open-label design and geographic focus limit generalizability. The diminished effect after cessation of MDA highlights the challenges of achieving sustained malaria control with limited intervention rounds.


MDA with dihydroartemisinin–piperaquine plus single low-dose primaquine is safe and reduces malaria incidence significantly during active administration in a moderate-to-low transmission African setting. Although, Hsiang and Roh conclude, “MDA will likely need to be repeated annually over several years until malaria incidence drops to low levels, at which point programs can consider transitioning to more targeted strategies such as focal MDA.” Successful malaria control via MDA requires optimized timing, full seasonal coverage, and strong community engagement to maintain gains.

1.Effect of mass drug administration on malaria incidence in southeast Senegal during 2020–22: a two-arm, open-label, cluster-randomised controlled trial. Ba, El-hadji Konko Ciré et al. The Lancet Infectious Diseases, Volume 25, Issue 6, 656 – 667. June 2025. Accessed July 7, 2025.

2.Brady OJ, Slater HC, Pemberton-Ross P, et al. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. 

. 2017;5(7):e680-e687. doi:10.1016/S2214-109X(17)30220-6

Significant short-term impact of MDA with dihydroartemisinin–piperaquine plus primaquine in a moderate-to-low transmission setting, highlighting the need for full seasonal coverage and community engagement to sustain gains.

Mass Drug Administration Reduces Malaria Incidence but Requires Sustained Effort in Southeast Senegal

In a 6–3 decision, the US Supreme Court ruled in 

 to uphold the constitutionality of the Affordable Care Act (ACA) provision mandating that insurers cover certain preventive services without cost sharing.¹ The ruling reaffirms the authority of the US Preventive Services Task Force (USPSTF), the Advisory Committee on Immunization Practices (ACIP), and the Health Resources and Services Administration (HRSA) in determining the scope of covered services.

The case stemmed from a lawsuit brought by four individuals and two Christian-owned businesses in Texas, who objected to providing insurance that covers services such as HIV prevention medication (PrEP), the HPV vaccine, and contraceptives. The plaintiffs argued that the mandate violated their religious beliefs and that the USPSTF’s volunteer-led structure breached the Constitution’s Appointments Clause.²

The US Court of Appeals for the Fifth Circuit previously held that the USPSTF’s structure was unconstitutional and restricted the federal government from enforcing its recommendations. The Supreme Court reversed that ruling, reinstating the ACA’s full preventive services requirement.²

In response, Carl Schmid, executive director of the HIV+Hepatitis Policy Institute, issued a statement supporting the decision, stating, “This is a great victory for healthcare in our country and for everyone who believes in prevention... We are very pleased the Court upheld the coverage requirement.”¹

He emphasized the continuing need for oversight and compliance, particularly with the expansion of long-acting forms of HIV PrEP, and expressed concern about proposed federal budget cuts to CDC prevention programs.¹

The HIV+Hepatitis Policy Institute, along with 19 other public health organizations, filed an amicus brief supporting the federal government’s position. Their brief highlighted the public health significance of routine screenings and preventive medications, including their role in identifying infectious diseases and linking individuals to treatment.¹

The ACA, passed in 2010, delegates to USPSTF, ACIP, and HRSA the authority to define which services must be covered at no cost by private insurers. Since then, these bodies have recommended coverage for services such as PrEP (2019), the HPV vaccine (2007), and contraceptives (2011).²

The ruling ensures that insured individuals nationwide will continue to have access to preventive services such as HIV testing, cancer screenings, immunizations, and contraceptive care without cost-sharing requirements.

In our interview, Schmid discussed the ongoing Supreme Court case 

, which challenges the Affordable Care Act’s preventive services coverage requirement. Schmid emphasized the critical role this mandate plays in ensuring access to HIV prevention tools like PrEP, as well as testing for HIV and hepatitis, all at no cost to insured individuals.

The Case for HIV Prevention and Screening: Pay Today or Pay Tomorrow

He explained that without this requirement, insurers might stop covering these services, especially newer, long-acting PrEP treatments that are expected to come to market soon. Schmid noted, “The beauty of the preventive services requirement from the Affordable Care Act is that they not only have to cover the drug… and then the second aspect of the law is that it has to be at no cost to the consumer.”

Schmid also highlighted the broader implications for public health, pointing out that these preventive services reduce long-term healthcare costs by preventing infections and linking people to care early. He urged a unified approach beyond just HIV prevention to maintain coverage for all preventive health services, emphasizing collaboration among advocacy groups.

1.Supreme Court upholds preventive services coverage requirements. June 27, 2025. Accessed June 27, 2025. https://hivhep.org/press-releases/supreme-court-upholds-preventive-services-coverage-requirements/  

2.Kennedy v. Braidwood Management, Inc. (n.d.). 

. Retrieved June 27, 2025, from https://www.oyez.org/cases/2024/24-316


6–3 ruling preserves no-cost insurance coverage for preventive services such as HIV PrEP, contraceptives, and screenings.

Supreme Court Affirms ACA Preventive Care Mandate in Kennedy v Braidwood

 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.

MANDEE NOVAL, PHARMD*

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