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Volume 229, Issue 6, 15 June 2024
Editorial Commentary
Expanding the Evidence Base for Improving Sexual Health Among Transgender Communities: The Importance of Rigorous Epidemiologic Studies
Invited Perspective
Culturing the Future of Medicine: The Imperative of Strengthening the Infectious Diseases Physician-Scientist Pipeline
Viewpoint
The Costly Vicious Cycle of Infections and Malnutrition
Major Articles and Brief Reports
Bacterial Disease Pathogenesis
Prevalence of Sexually Transmitted Infections Among Transgender Women With and Without HIV in the Eastern and Southern United States
In a multicity, community-based sample of adult transgender women in the United States, the prevalence and correlates of bacterial sexually transmitted infections differed substantially by HIV status, highlighting the unique needs and risks of transgender women with and without HIV.
Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis
Oral and lesion swabs were collected from adults diagnosed with early syphilis for quantitative T. pallidum PCR testing prior to antibiotic treatment. Oral PCR positivity rates ranged from 17% in primary syphilis to 63% in early latent syphilis.
Chlamydia trachomatis T3SS Effector CT622 Induces Proinflammatory Cytokines Through TLR2/TLR4-Mediated MAPK/NF-κB Pathways in THP-1 Cells
The findings highlight the involvement of CT622, a T3SS effector protein of Chlamydia trachomatis, in inducing proinflammatory cytokines IL-6 and IL-8 through activation of the TLR2/TLR4-mediated MAPK/NF-κB pathways, which contributes to our understanding of the pathogenesis of C trachomatis.
The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis
The current study has revealed that the purine biosynthetic repressor, PurR, significantly contributes to coordinating the expression of virulence factor and in vivo persistence during VAN treatment. This finding may offer an avenue for developing novel antimicrobial targets against MRSA.
The Efficacy and Safety of an Intra-articular Dual-Acting Antibacterial Agent (TNP-2092) for Implant Infection–Associated Methicillin-Resistant Staphylococcus aureus
Intra-articular application of the novel semi-synthetic antibiotic agent TNP-2092 (rifamycin covalent bond with quinolizinone) is safe and effective in treating orthopedic implant infection caused by methicillin-resistant Staphylococcus aureus in a rat model of knee periprosthetic joint infection.
Potential Impact of Higher-Valency Pneumococcal Conjugate Vaccines Among Adults in Different Localities in Germany
Biofilm Formation by Nontypeable Haemophilus Influenzae and Resistance to Complement-Mediated Clearance
Biofilm formation contributes to the pathogenesis of Haemophilius influenzae, particularly nontypable H. influenzae isolates that were recovered from mucosal surfaces. Biofilm formation was correlated with reduced of the complement component C3b deposition on bacteria. Biofilm can be a therapeutic target.
Clinical and Bacteriological Specificities of Escherichia coli Bloodstream Infections From Biliary Portal of Entries
Escherichia coli bloodstream infections from biliary origin are clinically less severe and more likely due to strains exhibiting commensal characteristics with fewer virulence-associated genes, than either urinary or digestive nonbiliary bacteriemic strains.
Cytolethal Distending Toxin Modulates Cell Differentiation and Elicits Epithelial to Mesenchymal Transition
CDT-exposed cells lose their cell-cell junction, become individualized, and acquire a spindle-shaped morphology. They also express increased level of mesenchymal markers, as well as increased levels of key EMT transcription factors and MMP degrading activity, along with cellular motility.
COVID-2019 Disease Pathogenesis
Vaccine-Boosted CCP Decreases Virus Replication and Hastens Resolution of Infection Despite Transiently Enhancing Disease in SARS-CoV-2–Infected Hamsters
Convalescent plasma obtained from recovered COVID-19 patients vaccinated with an mRNA vaccine (Vaxplas) was infused into SARS-CoV-2–infected hamsters 24 hours after virus inoculation. Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2–infected hamsters.
Vaccination Shapes Within-Host SARS-CoV-2 Diversity of Omicron BA.2.2 Breakthrough Infection
Through intrahost SARS-CoV-2 investigation, we elucidated that vaccinees had a notable reduction of within-host diversity, accompanied by fewer inflammation-related hypermutations, suggesting the protection of vaccination against viral replication and inflammatory pathophysiology.
The Association Between Antibody Responses and Prolonged Viable Severe Acute Respiratory Syndrome Coronavirus 2 Shedding in Immunocompromised Patients: A Prospective Cohort Study
This prospective cohort study from March to November 2022 involving 62 immunocompromised COVID-19 patients revealed an enhanced clearance in viral load and culturable virus with higher neutralizing antibodies, which highlights the importance of humoral immunity through vaccination or monoclonal antibody treatments.
Hybrid Immunity to SARS-CoV-2 During Pregnancy Provides More Durable Infant Antibody Responses Compared to Natural Infection Alone
In pregnant people with prior SARS-CoV-2 infection, hybrid immunity (infection plus vaccination) before delivery provided more durable maternally derived antibody responses than infection alone in infants through 6 months of age.
Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19
We provide genetic evidence that variants of IL1RN modify the severity of SARS-CoV-2 infection. The IL1RN CTA haplotype and rs419598 C/C single-nucleotide variant are associated with lower levels of inflammatory markers and a reduction in the mortality of men.
Lung Function Trajectories in Mild COVID-19 With 2-year Follow-up
This study assessed lung function prior to mild COVID-19 infection and up to 2 years after. It revealed a significant decline in the first 6 months after infection and a slower decline thereafter, indicating lasting decline, with limited recovery.
Vγ9Vδ2 T-cells Are Potent Inhibitors of SARS-CoV-2 Replication and Represent Effector Phenotypes in Patients With COVID-19
This study aims to decipher the role of Vγ9Vδ2 T cells in COVID-19. SARS-CoV-2 mediates upregulation of BTN3A, the Vγ9Vδ2 T-cell receptor, in lung tissues/cells and mononuclear cells. Vγ9Vδ2 is differentiated and efficiently degranulated upon activation with BTN3A mAb.
HIV/AIDs
Immunologic and Virologic Parameters Associated With Human Immunodeficiency Virus (HIV) DNA Reservoir Size in People With HIV Receiving Antiretroviral Therapy
We examined correlates of HIV reservoir size in people with HIV receiving antiretroviral therapy (ART). Our data suggest that innate immunity at the time of ART initiation may play an important role in modulating the dynamics and persistence of viral reservoirs.
Magnitude of Type I Interferon Responses by Plasmacytoid Dendritic Cells After TLR7 Stimulation Is Associated With Human Immunodeficiency Virus Type 1 (HIV-1) Reservoir Sizes in Cisgender Women With HIV-1 on Antiretroviral Therapy
Stronger type I IFN responses by plasmacytoid dendritic cells in cisgender women living with HIV-1 on antiretroviral therapy correlate inversely with the size of intact and total proviral HIV-1 reservoirs, highlighting type I IFNs as potentially impacting HIV-1 reservoir dynamics.
Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy
Persons with HIV characterized as immunological nonresponders (n = 26) had higher levels of HIV RNA transcripts in addition to characteristics previously reported, including lower percentages of CD4+ naive T cells and higher percentages of CD4+ T cells expressing activation markers.
Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques
Vaginal tenofovir alafenamide fumarate/elvitegravir (TAF/EVG) inserts demonstrated efficacy of 94.4% when applied 8 hours after SHIV exposure, but 77.2% when applied at 24 hours. These findings inform further clinical development and trial design of TAF/EVG inserts as a flexible on-demand product for women.
Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes
This study assessed the prevalence and susceptibility to doravirine of the RT-V106I polymorphism in HIV-1. V106I was more common in subtypes D and F, with minimal impact on doravirine susceptibility in most cases.
Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV
Accelerated epigenetic aging was observed in women with HIV in comparison with women without HIV and was associated with lower physical function in both groups. Epigenetic aging was not associated with bone outcomes.
Viral Disease Pathogenesis
Dynamics and Clinical Significance of Cytomegalovirus-Specific Neutralizing Antibodies in Kidney Transplant Recipients Treated with T-Cell–Depleting Agents
No apparent protective role was found for CMV-specific antibodies that neutralize epithelial cell infection measured by microneutralization assay in a single-center cohort of CMV-seropositive kidney transplant recipients that had received T-cell–depleting therapy and a 3-month course of antiviral prophylaxis.
Reconsideration of Maternal Serological Testing for Predicting Congenital CMV Infection
This nested case-control study demonstrates that the value of current maternal CMV serological testing in regions with high seropositivity rates is very limited and should be reconsidered. The detection of DNAemia would be helpful in assessing risk of intrauterine transmission.
Estimating the Burden of Influenza Hospitalizations Across Multiple Seasons Using Capture-Recapture
Capture-recapture provides an alternative approach to examine the detection of cases by independent influenza surveillance systems. Our capture-recapture estimates were consistently higher across all seasons than what each surveillance system independently identified, indicating that current surveillance underestimates cases.
Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Circulating Globally in 2022–2023
Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells
Natural killer (NK) cells display robust responses against JC polyomavirus (JCPyV), a pathogen that can cause a fatal disease in immunocompromised individuals. NKG2D and its ligand ULBP2 play a key role in immune recognition of JCPyV-infected cells by NK cells.
Kinetics and Prognostic Significance of Laboratory Markers in Patients With Severe Fever With Thrombocytopenia Syndrome: Insight From a Comprehensive Analysis
We investigated the dynamic changes of laboratory markers in SFTS patients, identifying hypertension, and elevated AST, PCT, and IL-10 as independent risk factors for adverse outcomes. These biomarkers might facilitate risk assessment and early intervention for high-risk SFTS patients.
Global Health
Variability of Vaccine Responsiveness in Young Children
Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. CD4+ T-cell memory induction and antigen-presenting cell deficiencies occur in children with low vaccine response (LVR), and antibiotic exposure is associated with LVR.
Cost-Effectiveness of Community-Based Active Case Finding Strategy for Tuberculosis: Evidence From Shenzhen, China
Although ACF screening strategies incur higher costs, they are effective in reducing ATB cases and increasing QALYs. Both the basic and advanced ACF screening strategies are cost-effective, particularly in countries with a high burden of tuberculosis like China.
Impact of National Public-Private Mix and Medical Expense Support Program to Control Tuberculosis in South Korea: An Interrupted Time Series Analysis
The effectiveness of tuberculosis control programs, including the public-private mix and economic support in reducing the burden of the disease, was confirmed through interrupted time series analysis, providing valuable insights for developing effective tuberculosis control strategies globally.
Parasites
Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein–Based Vaccine Adjuvanted With Glucopyranosyl Lipid A–Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge
A Novel Ex Vivo Assay to Evaluate Functional Effectiveness of Plasmodium vivax Transmission-Blocking Vaccine Using Pvs25 Transgenic Plasmodium berghei
We developed transgenic P. berghei expressing Pvs25, a P. vivax transmission-blocking vaccine candidate (TBV), and optimized an ex vivo membrane feeding assay to facilitate evaluation of Pvs25-based TBV without dependence on P. vivax-infected patient blood from endemic areas.
Experimental Infections Reveal Acquired Zoonotic Capacity of Human Schistosomiasis Trough Hybridization
Sheep are resistant to infestation by Schistosoma haematobium, the etiologic agent of human urogenital schistosomiasis. However, when S haematobium is crossbred with Schistosoma bovis, a livestock parasite, the first-generation or backcrossed hybrids are capable to infect the animal.
Visceral Leishmaniasis–Human Immunodeficiency Virus–Coinfected Patients Are Highly Infectious to Sandflies in an Endemic Area in India
A total of 732 laboratory-reared sandflies exposed to 14 patients with visceral leishmaniasis–HIV coinfection showed 16.66% (122/732) xenodiagnosis positivity. Notably, 93% (13/14) of patients transmitted the infection to flies, as confirmed by quantitative polymerase chain reaction and/or microscopy of the sandfly midgut.
Reviews
Asymptomatic Low-Density Plasmodium falciparum Infections: Parasites Under the Host's Immune Radar?
It is unknown how the host tolerates asymptomatic Plasmodium parasitemia without clinical symptoms. In an asymptomatic state, the parasite burden is probably below the host immune system's radar and not sufficient to trigger immune reactions that result in clinical symptoms.
HIV Diagnostics and Vaccines: It Takes Two to Tango
Successful implementation of HIV-1 vaccines will require modified diagnostic tests that can distinguish vaccine-induced seropositivity/seroreactivity from true HIV-1 infection. Such tests will need to be accurate, simple, cost-effective, and developed in parallel with HIV-1 vaccines to enable global vaccine adoption.