Volume 230, Issue 2, 15 August 2024

Little is known about the targets of effector T cells during human syphilis. Herein we show that Treponema pallidum infection elicits antigen-specific CD4⁺ T-cell responses in blood and skin that persist in both compartments long after curative therapy.

This study uncovers the pivotal role of noncanonical pyroptosis in lethal sepsis progression. Inhibiting pyroptosis alone improves the survival of septic mice. HMGB1 A box suppresses noncanonical pyroptosis, offering potential therapeutic strategies to ameliorate lethal sepsis.

Engineered lysin CF-370, which demonstrated broad-spectrum in vitro activity against multiple clinically relevant gram-negative pathogens and in vivo efficacy in an animal model of invasive multisystem infection, showed therapeutic potential as systemic treatment for infections with antibiotic-resistant pathogens.

Among soldiers stationed at Fort Liberty, North Carolina, between 1991 and 2019, the seroprevalence of tick-borne rickettsiosis decreased, while that of Ehrlichia nearly doubled, likely reflecting the geographic expansion of lone star tick populations.

Heparin-binding hemagglutinin (HBHA) effectively inhibits macrophage autophagy and ultimately promotes the intracellular survival of Mycobacterium. The TLR4-dependent PI3K-AKT-mTOR signaling pathway is a crucial mediator of HBHA's inhibitory effects on autophagy. Additionally, HBHA plays a pivotal role in driving M2 polarization of macrophages.

The study probes early immune responses to Mycobacterium tuberculosis, highlighting NF-κB signaling. The absence of IKK2 in CD11c⁺ myeloid cells enhances early M tuberculosis resistance, triggering proinflammatory responses. IKK2 abrogation in MRP8-expressing neutrophils has no impact on disease pathology or M tuberculosis control.

Nasal administration of the human commensal Haemophilus haemolyticus improved recovery from influenza and prevented development of nontypeable Haemophilus influenzae otitis media in mice. This represents an important finding as new therapies to prevent respiratory infections and otitis media are needed.

Elevated body mass index is associated with mucosal viral persistence and prolonged symptoms after SARS-CoV-2 infection. Low serum anti-S IgG levels were associated with reinfection risk, and higher peak anti-S and anti-NC antibody levels were associated with persistent symptoms.

Overall sensitivity and specificity were 53.0% and 98.8%, respectively, but varied by clinical and temporal factors. Sensitivity increased 4–7 days after illness onset (70.1%) and when repeated ≥2 (68.5%) and ≥4 (75.8%) days after initial Ag-RDT negative, supporting serial testing recommendations.

We investigated a SARS-CoV-2 outbreak affecting several modules of a penitentiary center, finding a single origin (B.1.1.7). Contact tracing identified plausible transmission vectors between modules, and prison lockdown most probably averted additional cases.

Our study shows that annual COVID-19 vaccination is net cost-saving from the adult individual perspective over the course of a year, and thus provides support for individuals to get the COVID-19 vaccine, even if they must pay out-of-pocket.

Prediabetes and diabetes are prevalent in people living with HIV. Glycated hemoglobin and fasting blood glucose are sufficient tests for screening. Risk factors include traditional causes such as age and body mass index, HIV-associated features including drug exposures and nadir CD4, and microbiome predictors.

We examined the association of mt-DNA haplogroups with weight/BMI gain 96 weeks after ART initiation in treatment-naive patients. A significant association was found between major UK mtDNA haplogroup and lower weight/BMI increase, highlighting mitochondrial genetics’ role in posttreatment weight dynamics.

Our study in naturally recovered long-term Sudan virus survivors revealed durable polyfunctional humoral and cellular memory immune responses with distinctive gene expression signatures, which may provide long-lasting protective immunity and help to define the ebolavirus correlate of protection.

Hamsters infected with NiV develop antibodies against the nucleoprotein and glycoprotein. While neutralizing antibodies do not develop until late in infection, early nonneutralizing antibodies possess Fc-mediated effector functions such as antibody-dependent complement deposition and antibody-dependent phagocytosis.

This trial confirmed that an Advax-adjuvanted trivalent seasonal influenza vaccine was safe and well tolerated in high-risk individuals with chronic disease or older age, with positive impacts on their anti-influenza antibody responses.

The mRNA-1647 human cytomegalovirus vaccine elicited polyfunctional and durable antibody responses in humans. While the mRNA-1647–elicited glycoprotein B (gB)–specific IgG responses were lower than those of the moderately effective gB/MF59 vaccine, the pentameric complex–specific IgG responses were robust.

This study provides evidence that respiratory syncytial virus, a common respiratory virus, causes neurotoxic infection of dorsal root ganglia peripheral nerves innervating the lungs and spinal cord and could cause release of replicating virus into the central nervous system, triggering monocyte infection, chemokine-induced neuroinflammation, and neurologic dysfunction.

Costs of lower respiratory tract illness due to respiratory syncytial virus are high in commercially insured and Medicaid-insured infants, especially among the youngest and those born prematurely.

In Bagamoyo, Tanzania, roughly two-thirds of asymptomatic malaria in >5 year-olds is submicroscopic, only detectable by polymerase chain reaction. Submicroscopic carriage and the proportion of submicroscopic carriers who later develop patent malaria are correlated with local village-level malaria prevalence.

Ugandan refugees newly arrived from South Sudan and the Democratic Republic of Congo were frequently infected with malaria parasites, with prevalences of markers of drug resistance remarkably different depending on the refugee country of origin.

Rezafungin (Rezzayo) has been approved by the FDA to treat candidemia and invasive candidiasis in adults who have limited or no alternative treatment options. In this article, we describe the rationale for approval and important considerations during the review process.

Neutrophil extracellular traps (NETs) aid in the clearance of pathogens, but their overproduction may drive massive inflammatory responses, contributing to morbidity and mortality. Despite the importance of NETs in the pathophysiology of infections, many clinicians are unaware of these processes.

Cloaking antibodies (cAbs) paradoxically protect bacteria from serum killing. Here we show that cAbs are prevalent in patients with Pseudomonas aeruginosa BSIs and allow survival of otherwise serum-sensitive bacteria. Generation of cAbs may increase susceptibility to bloodstream infections.

Lung disease due to Mycobacterium avium complex shows response rates in only 40% of patients treated with the standard-of-care combination regimen. Ceftriaxone, an old drug, demonstrated better efficacy and is predicted to shorten therapy duration in patients 2.4-fold.

Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex.

In this study on the host-response biomarker BV score and its subanalytes TRAIL, IP-10, and CRP, children with Mycoplasma pneumoniae community-acquired pneumonia have atypically low levels of the BV score, resembling a viral infection.

Although autochthonous (non-travel-related) typhoid cases in Santiago, Chile, are currently rare compared to the 1977–1991 hyperendemic era, 5 of 16 recent cases (2017–2019) were linked to 4 elderly female chronic carriers by household investigations and whole genome sequencing of isolates.

Host immune signatures to diagnose tuberculosis show promise, but have not been investigated in tuberculous meningitis. We demonstrate the ability of a whole-blood 3-gene host signature to discriminate tuberculous meningitis from other brain infections, including individuals with HIV.

XBB.1.5-containing messenger RNA-1273 vaccines administered as fifth doses to adults elicited potent and diverse neutralizing responses against Omicron XBB and other recent severe acute respiratory syndrome coronavirus 2 variants, supporting authorization and approval of monovalent XBB.1.5-containing vaccines for 2023-2024 immunizations.

Higher variant-specific IgA, but not IgG, antibody response at 1 month after booster vaccination was associated with infection risk, where individuals, who remained uninfected over the follow-up period of at least 8 months, had higher variant-specific IgA than individuals who became infected.

In our study of >6000 people with HIV, no HIV-specific factors were correlated with SARS-CoV-2 susceptibility. High prepandemic human coronavirus antibodies independently lowered SARS-CoV-2 risk, highlighting the importance of local immune factors in susceptibility.

This article explores underlying mechanisms of the multisystem inflammatory syndrome in children (MIS-C) and provides novel insights into T-cell and myeloid cell fates contributing to MIS-C pathology.

This study shows that autoantibodies against type I interferon covary with cellular alterations, in particular reduced immune cell numbers, while they have limited effect on the soluble and adaptive immune response in critical COVID-19.

This study reports for the first time the identification of a Middle East respiratory syndrome coronavirus (MERS-CoV) spike-specific CD8⁺ T-cell epitope in an HLA-A*03/HLA-B*35-positive individual following MVA-MERS-S vaccination. This contributes to the limited understanding of T-cell immunity against MERS-CoV.

We conducted a genome-wide association study (GWAS) to investigate the association between the severity of RSV infection and genetic markers. Despite this being the largest GWAS of severe RSV infection, we did not detect any genome-wide significant loci.

RSV cases in US adults aged ≥60 years were estimated to contribute a total annual cost of $6.6 billion (95% uncertainty interval, $3.1–$12.9 billion), including $2.9 billion in direct costs and $3.7 billion in indirect costs.

This respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) vaccine was tolerable when coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) in healthy nonpregnant women, and induced robust immune responses.

Human seasonal coronaviruses (HCoVs) were prevalent among children and adults with mild and severe acute respiratory illness (SARI) in Malawi between 2011 and 2017. 229E and OC43 were associated with SARI, and NL63 with influenza-like illness. Individual HCoVs had distinct seasonality.

Respiratory syncytial virus (RSV) and influenza vaccines would ideally be coadministered in adults ≥65 years. Coadministration of an RSV vaccine candidate (Ad26.RSV.preF/RSV preF protein) and Fluzone-HD had an acceptable safety profile and did not hamper the immunogenicity of either vaccine.

In influenza treatment, oral favipiravir failed to consistently reach target plasma concentrations and showed wide interindividual variability in concentrations associated with differences in favipiravir's metabolism and body weight. Higher oral doses and in seriously ill patients intravenous dosing require study.

We report results of HIV vaccine trial HVTN 120, which evaluated ALVAC-HIV (vCP2438) boosted with MF59 or AS01_B adjuvanted with gp120 at 2 doses. The highest CD4⁺ T-cell and binding antibody responses were in the lower dose gp120/AS01_B regimen.

This study demonstrates the striking suppression of nonclassical antigen presentation molecule CD1d by varicella zoster virus (VZV). In identifying a novel VZV immunoevasive strategy, we also demonstrate preliminary investigations in the mechanisms underpinning the VZV-mediated downregulation of CD1d.

In this study, we explore the complex relationship between cytomegalovirus infections and clinical outcomes in transplant recipients and propose strategies for monitoring viral dynamics to optimize treatment and prevent failure to respond to antiviral therapies.

Torque teno virus (TTV) load relates to CD4⁺ T-cell count and human pegivirus load in treatment-naive HIV patients and shows a strong property as a biomarker for immunodeficiency (CDC stages 1–3) but not for human pegivirus load or AIDS-defining events.

This study reports that the early bactericidal activity of a bedaquiline-based second-line regimen for drug-resistant tuberculosis (TB) is similar to that of the standard rifampin-based first-line regimen for drug-sensitive TB.

Wellcome Trust and the International AIDS Vaccine Initiative convened international experts developing tuberculosis human infection studies to discuss the status of each model and the key enablers to progress these, with a focus around accelerating their use for testing tuberculosis vaccines.

In this retrospective of 333 patients with Ebola virus disease (Democratic Republic of the Congo, 2019), rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2–3.8]; P = .0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03–2.9]; P = .037).

We performed integrative analyses of multiple cohorts spanning >1500 transcriptome samples to uncover gene signatures that discriminate malaria from healthy controls, enteric fever, and sepsis or that distinguish cerebral malaria from other clinical phenotypes.

Full- and fractional-dose regimens of the RTS,S/AS01_E malaria vaccine have similar vaccine efficacy against clinical malaria. With a fixed supply of vaccine, more children can be vaccinated and thus more cases prevented by using fractional- rather than full-dose regimens.

Clinical and real-world evidence studies suggest that mRNA-based boosters induce increased reactogenicity compared with the Novavax protein-based COVID-19 vaccine, NVX-CoV2373. Pain/tenderness, swelling, fatigue, headache, muscle pain, and fever are less common for NVX-CoV2373 versus mRNA boosters.