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Volume 230, Issue 1, 15 July 2024
Editorial Commentary
New Publishing Strategy at JID
Perspective
Escape Velocity—the Launch of Microbiome Therapies
FDA approval of the first microbiota therapeutics raises new questions about the future role of fecal microbiota transplantation (FMT). The authors explore these questions and suggest that FMT has unique value for research and to support patient access.
Major Articles and Brief Reports
COVID-2019 Disease Pathogenesis
Cytotoxic Lymphocyte-Monocyte Complex Reflects the Dynamics of Coronavirus Disease 2019 Systemic Immune Response
Cytotoxic lymphocytes attach to CD14+ monocytes with high inflammasome assembly capability and elevated antigen-presenting potential in COVID-19 progression and convalescent stages, representing a dynamic systemic immune response upon SARS-CoV-2 infection.
Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia
Individuals with lymphoma were at risk for reduced or absent vaccine response, even when untreated. Normal circulating immunoglobulins increased the likelihood of response. CART-19 did not permanently impair response, with the presence of Tfh and B cells predicting receptor-binding domain–specific IgG.
Regulatory T and CXCR3+ Circulating Tfh Cells Concordantly Shape the Neutralizing Antibody Responses in Individuals Who Have Recovered from Mild COVID-19
In this study, we demonstrated that Treg cells and CXCR3+ cTfh cells concordantly shape the nAb responses in people who have recovered from mild but not severe COVID-19. Treg cells limit the nAb responses by limiting CXCR3+ cTfh cells function.
Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison
The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. However, in the Netherlands, a comparison accounting for population differences shows that the Spanish flu of 1918–1920 was deadlier than COVID-19 in 2020–2022.
Anti–SARS-CoV-2 Antibody Levels Associated With COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu Vaccine Effectiveness Network, October 2021–June 2022
From October 2021 to June 2022, we assessed the association between antibody concentration and COVID-19 illness among patients enrolled in a test-negative study in 7 US states. We found that higher anti–receptor-binding domain antibodies in patients were associated with protection against symptomatic COVID-19.
HIV/AIDS
Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France
Among 410 men having sex with men living with human immunodeficiency virus and undergoing annual anal cytology and high-resolution anoscopy, 33% had high-grade anal lesions detected within 2 years; strongest determinants were baseline positivity for human papillomavirus 16 and p16/Ki67.
Effect of Vaginal Microecological Disorders on the Increased Risk of Abnormal Cervical Cytology Among Women With Human Immunodeficiency Virus in China
Predicting abnormal cervical cytology based on vaginal microecological disorders helps clinicians in the early identification of women with HIV, who are at a higher risk of cervical cancer, and this might be a primary prevention strategy.
Signals From Inflamed Perivascular Adipose Tissue Contribute to Small-Vessel Dysfunction in Women With Human Immunodeficiency Virus
Perivascular adipose tissue surrounding small subcutaneous vessels from women with HIV has oxidative stress, inflammation, and reduced adiponectin that may contribute to enhanced contractility and microvascular disease.
HIV Immunocapture Reveals Particles Expressed in Semen Under Integrase Strand Transfer Inhibitor-Based Therapy Are Largely Myeloid Cell-Derived and Disparate
Under potent INSTI-based therapy, HIV was observed to maintain residual expression below the detection of standard clinical testing, uncovering nonlymphoid-derived viruses in the male genital tract that were highly divergent and distinct from lymphoid-derived variants present in blood.
Impact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes
Carrying the drug resistance mutation K103N at either low or high frequency when starting a nonnucleoside reverse transcriptase inhibitor antiretroviral therapy regimen increases treatment failure risk.
Viral Disease Pathogenesis
Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection
Different subtypes in chronic active Epstein-Barr virus infection demonstrated specific clinical features. Generally, patients with CD8+ T-cell type had a poor prognosis.
Trends for Syndromic Surveillance of Norovirus in Emergency Department Data Based on Chief Complaints
This study aimed to determine if emergency department (ED) data could reflect norovirus trends. A significant correlation was found between reported cases, especially in children, and specific ED visit complaints. ED data can help detect infectious disease trends early.
Cutavirus Infection in Large-Plaque Parapsoriasis, a Premalignant Condition of Mycosis Fungoides
This study reports preferential detection of high levels of cutavirus DNA with the expression of viral mRNA in large-plaque parapsoriasis. This suggests a potential role for cutavirus in the pathogenesis of the disorder, a premalignant condition of mycosis fungoides.
Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression
Influenza infection releases adenosine triphosphate that primes peripheral neutrophils and causes their excessive activation after they infiltrate the lungs. Thus, adenosine triphosphate–induced neutrophil priming may be a therapeutic target to reduce lung tissue damage in severe influenza cases.
The Potential Benefits of Delaying Seasonal Influenza Vaccine Selections for the Northern Hemisphere: A Retrospective Modeling Study in the United States
With expedited vaccine production, reconsidering existing timelines for seasonal influenza vaccine selection could result in substantial epidemiological advantages, especially when additional data could enhance the antigenic alignment between vaccine and prevalent viruses.
Influenza Vaccine Effectiveness Against Influenza A–Associated Emergency Department, Urgent Care, and Hospitalization Encounters Among US Adults, 2022–2023
Among US adults, including older adults and persons with high-risk medical conditions, influenza vaccination provided moderate protection against influenza A–associated emergency department or urgent care encounters (vaccine effectiveness [VE], 44%) and hospitalizations (VE, 35%) during the 2022–2023 influenza season.
Global Health
Hemagglutination Inhibition Antibody Titers as Mediators of Influenza Vaccine Efficacy Against Symptomatic Influenza A(H1N1), A(H3N2), and B/Victoria Virus Infections
Hemagglutination inhibition antibody titers mediate 20%–40% of inactivated influenza vaccine efficacy against influenza A(H1N1), A(H3N2), and B/Victoria virus infections.
Assessment of the Zoonotic Potential of Atypical Scrapie Prions in Humanized Mice Reveals Rare Phenotypic Convergence but Not Identity With Sporadic Creutzfeldt-Jakob Disease Prions
Humanized mice exposed to a panel of animal atypical scrapie prions showed very low susceptibility, suggesting a limited zoonotic potential. However, 1 isolate adapted into prions phenotypically resembling those causing human sporadic Creutzfeldt-Jakob disease. Further characterization dismissed a causal link.
Parasites
Antileishmanial Activity of Cathelicidin and its Modulation by Leishmania donovani in a cAMP Response Element Modulator-Dependent Manner in Infection
Developing novel therapeutics for visceral leishmaniasis is a pressing need. We demonstrated that the antimicrobial peptide cathelicidin, administered externally, has an antileishmanial effect. However, infection downregulates endogenous cathelicidin by exploiting host protein CREM, which could be a potential drug target.
Spliced-Leader RNA as a Dynamic Marker for Monitoring Viable Leishmania Parasites During and After Treatment
Comprehensive in vitro and in vivo experiments and analyses in patients with visceral leishmaniasis identify spliced-leader RNA (SL-RNA) as a parasite viability marker. An optimized protocol allows the versatile detection of SL-RNA and other molecular markers for individualized patient management.
Bacterial Disease Pathogenesis
Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling
This study revealed that SspA-1 of the highly virulent Streptococcus suis 2 strain induces an excessive inflammatory response via TLR2 endosomal and type I IFN signaling, unveiling a novel role of type I IFN in S. suis infection.
Ectopic Expression of C-Type Lectin Mincle Renders Mice Susceptible to Staphylococcal Pneumonia
This study characterized the 2 glycolipids of Staphylococcus aureus, Glc-DAG and Glc2-DAG, acting as molecular patterns with opposing activities in Mincle-dependent lung anti-staphylococcal immunity in mice.
In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection
Disruption of the capsule biosynthesis gene wcaJ evolved in a patient with recurrent Klebsiella pneumoniae carbapenemase–producing K pneumoniae bloodstream infections. Loss of function in wcaJ led to resistance to complement-mediated killing as well as increased complement binding and osponophagocytosis.
Characteristic Profiling of Soluble Factors in the Cerebrospinal Fluid of Patients With Neurosyphilis
Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in the cerebrospinal fluid (CSF), which are correlated with immune status and neuronal damage. Moreover, CSF biomarker panels were identified that may accurately discriminate neurosyphilis at different stages.
Genomes & Microbiome
Unearthing New ccr Genes and Staphylococcal Cassette Chromosome Elements in Staphylococci Through Genome Mining
Twelve novel ccr genes were identified in staphylococci and mammaliicocci, forming 12 novel ccr gene complexes and 10 novel SCC elements. The biological activity of 5 groups of novel Ccr recombinases were further demonstrated.
Minimal Impact on the Resistome of Children in Botswana After Azithromycin Treatment for Acute Severe Diarrheal Disease
This study compared azithromycin treatment for bacterial diarrhea in children in Botswana to the usual care to evaluate its impact on antibiotic resistance in the gut microbiome. In both treatment groups, azithromycin resistance genes increased in prevalence at 60 days.
Review
Chlamydia trachomatis Seroassays Used in Epidemiologic Research: A Narrative Review and Practical Considerations
This narrative review summarizes the “state of the science” for Chlamydia trachomatis seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.
Babesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies
This review focuses on the B. duncani ICIM model, which serves as a promising resource for advancing research into the biology, pathogenicity, and virulence of intraerythrocytic parasites, as well as a tool to evaluate new drugs, vaccines, and diagnostic tests.
Correspondence
A Planned Trial to Evaluate the Safety and Efficacy of Tafenoquine + Atovaquone/Azithromycin in Hospitalized Patients With Babesiosis
Reply to Dow and Smith
Online-Only Articles
Perspectives
How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks
Synergies between funders within the medical countermeasure life cycle are critical to ensure long-term sustainment and availability of vaccines, therapeutics, and diagnostics.
Major Articles and Brief Reports
COVID-2019 Disease Pathogenesis
Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial
The Omicron BA.1 variant–specific vaccine NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with the prototype vaccine, NVX-CoV2373, when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.
Delayed Mucosal Antiviral Responses Despite Robust Peripheral Inflammation in Fatal COVID-19
Fatal COVID-19 is associated robust peripheral inflammation; however, early interferon-led responses in the respiratory mucosa are delayed relative to those that will survive severe SARS-CoV-2 infection.
Deficient Generation of Spike-Specific Long-Lived Plasma Cells in the Bone Marrow After Severe Acute Respiratory Syndrome Coronavirus 2 Infection
By studying the bone marrow aspiration samples of 20 individuals with prior coronavirus disease 2019, we showed deficient generation of spike-specific long-lived plasma cells in bone marrow as the major contributor to the nondurable humoral immune response to this infection.
HIV/AIDS
Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials
CAB + RPV LA is effective in the maintenance of HIV-1 virologic suppression in adults regardless of BMI category, with longer-length needles (≥2 inches) recommend for those with BMI ≥30 kg/m2 to accommodate individual body habitus and ensure appropriate administration.
Prevotella timonensis Bacteria Associated With Vaginal Dysbiosis Enhance Human Immunodeficiency Virus Type 1 Susceptibility Of Vaginal CD4+ T Cells
Exposure to Prevotella timonensis, a bacterium associated with vaginal dysbiosis, increased uptake, fusion, and production of HIV-1 by vaginal CD4+ T cells, thereby enhancing HIV-1 susceptibility. Pre-exposure of CD4+ T cells to antiretroviral inhibitors abolished P timonensis–enhanced HIV-1 infection.
Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study
Viral Disease Pathogenesis
Levels of Angiopoietin 2 Are Predictive for Mortality in Patients Infected With Yellow Fever Virus
Markers of endothelial cell activation were measured in patients with yellow fever virus infection at the time of presentation. Extremely increased levels of angiopoietin 2 were detected in nonsurvivors vs survivors, suggesting that angiopoietin 2 could serve as a predictive marker for mortality.
The Clinical and Economic Burden of Antibiotic Use in Pediatric Patients With Varicella Infection: A Retrospective Cohort Analysis of Real-World Data in England
This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.
Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011–2014
We estimated the effect of rotavirus vaccination on duration and quantity of rotavirus shed during rotavirus gastroenteritis in Bangladesh. Virus quantity was lower in symptomatic vaccinated children compared to symptomatic unvaccinated children, but differences in episode duration were small.
Effectiveness of Influenza Vaccination During Pregnancy Against Laboratory-Confirmed Seasonal Influenza Among Infants Under 6 Months of Age in Ontario, Canada
Influenza vaccination during pregnancy was protective against influenza infection and influenza hospitalization among infants <6 months of age. Because influenza vaccines are not available for this age group, vaccination during pregnancy can offer passive protection to young infants.
RSV Neutralizing Antibodies in Dried Blood
Neutralizing antibodies against respiratory syncytial virus in serum and dried blood are highly correlated, are stable in dried blood for 6 months, and can withstand temperature variation. Dried blood samples are a patient-centered and logistical solution for clinical trials.
Immunogenicity and Safety Following 1 Dose of AS01E-Adjuvanted Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults: A Phase 3 Trial
One dose of prefusion F protein–based vaccine for older adults administered to ≥60-year-olds induced humoral and cell-mediated immune responses that remained above pre–dose 1 levels for at least 1 year. The vaccine was well tolerated with an acceptable safety profile.
Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021–2022 Bronchiolitis Season in England, Scotland, and Ireland
The BronchStart study collected data on 17 899 presentations in children aged <2 years with serious respiratory disease following the lifting of lockdown measures. For infant admissions, 51.3% were not associated with RSV; the majority were in previously healthy term infants.
Global Health
The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study
Modelling study shows that the decline in mpox cases among MSM in the Netherlands was primarily due to infection-induced immunity among those with high sexual activity levels and accelerated by behavioral adaptions. The outbreak could have faded even without vaccination.
High-Resolution Geospatial Mapping of Zero-Dose and Underimmunized Children Following Nigeria's 2021 Multiple Indicator Cluster Survey/National Immunization Coverage Survey
Nigeria has the highest number of children missing out on all routine immunization vaccinations—“zero-dose children.” Geospatial models can predict areas with zero-dose and underimmunized children for targeted interventions to achieve the Immunization Agenda 2030 goals.
Estimating the Potential Public Health Value of BCG Revaccination
Adolescent/adult targeted BCG revaccination assumed to prevent sustained Mycobacterium tuberculosis infection may have a positive health impact and be cost-effective in India and South Africa, even if associated with up to 50% increased risk of progression to disease.
Parasites
Quantifying Replication Slippage Error in Cryptosporidium Metabarcoding Studies
DNA repeat regions differentiate subtypes and track Cryptosporidium outbreaks but have high replication slippage rates. Using synthesized DNA, we demonstrate that slippage rates increase with the length of repeat region and can contribute to error rates of up to 20%.
Bacterial Disease Pathogenesis
Steroid Drugs Inhibit Bacterial Respiratory Oxidases and Are Lethal Toward Methicillin-Resistant Staphylococcus aureus
Computational and microbiological techniques were used to identify the steroid drug quinestrol as an inhibitor of cytochrome bd respiratory complexes from Escherichia coli and Staphylococcus aureus. This drug was bacteriostatic toward both species but was only lethal toward S. aureus.
Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes
Gardnerella Species and Their Association With Bacterial Vaginosis
Prevalence and concentrations of 4 Gardnerella species groups as measured by quantitative PCR were significantly associated with bacterial vaginosis (BV). Detection of multiple Gardnerella species was a risk factor for BV development, and none were a specific marker for BV.
Evidence of Reduced Virulence and Increased Colonization Among Pneumococcal Isolates of Serotype 3 Clade II Lineage in Mice
Pneumococcal serotype 3 clinical isolates display variable and clade-dependent biological characteristics in a mouse model of pneumococcal invasive disease and carriage.
Clonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction
A ST700-GPSC10 serotype 3 Streptococcus pneumoniae lineage, currently restricted to the African continent, is characterized by the absence of 6 genes from the capsular polysaccharide locus and decreased susceptibility to opsonophagocytosis, which may explain the spread of this lineage.
Review
The Burden of Hepatitis A Outbreaks in the United States: Health Outcomes, Economic Costs, and Management Strategies
Ongoing hepatitis A outbreaks in the United States are associated with a substantial clinical and economic burden. Prevention strategies and efforts to increase awareness and vaccination coverage are needed to reduce the burden of hepatitis A and prevent future outbreaks.