Journal of Infectious Diseases

BACKGROUND: The country of Georgia initiated its hepatitis C virus (HCV) elimination program in 2015, at which point a serosurvey showed the adult prevalence of HCV antibody (anti-HCV) and HCV RNA to be 7.7% and 5.4%, respectively. This analysis reports hepatitis C results of a follow-up serosurvey conducted in 2021, and progress towards elimination. METHODS: The serosurvey used a stratified, multi-stage cluster design with systematic sampling to include adults and children (aged 5-17 years) providing consent (or assent with parental consent)...

BACKGROUND: ALPK1 agonist has recently been reported to demonstrate anti-HBV efficacy via activating NF-κB signaling, which is crucial for maximizing interferon responses. Here, we investigated the impact of ALPK1 on HBV replication, and explored ALPK1 variants for predicting PegIFNα treatment response. METHODS: The potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out and their correlations with PegIFNα treatment response were assessed in 945 HBeAg-positive chronic hepatitis B (CHB) patients...

Infection with intestinal whipworms (Trichuris spp.) causes widespread morbidity and may alter responses to enteric and extraintestinal co-infections. Here, we show that Trichuris muris infection in mice increases co-infection with two evolutionary divergent enteric pathogens, the bacterium Citrobacter rodentium and the helminth Heligmosomoides polygyrus. Co-infection caused reduced weight gain and promoted type-1-biased inflammation. In contrast, T. muris-infected mice were more resistant to migrating Ascaris suum larvae in the lungs...

We analyzed same-gender couples discordant in their HIV status. The HIV+ partner was homozygous for CCR5 while his receptive HIV- partner was a CCR5Δ32 heterozygote with a C20S missense mutation in his CCR5 allele. The cells from the HIV- partner showed significant resistance to R5 fusion/infection and had no chemotactic response to CCL4 (MIP-1β). We demonstrated abundant CCR5-specific RNA in the HIV- partner's cells but no detectable CCR5 protein. CCR5 promoter region cloned from each partner's DNA indicated no significant impact on RNA transcription...

BACKGROUND: Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, by a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts by mathematical modeling. METHODS: We screened approved 132 drugs using an MPXV infection cell system...

BACKGROUND: SARS-CoV-2 genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by RT-qPCR in specimens from 3,204 individuals hospitalized with COVID-19 at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression...

Long-term consequences of HIV are likely the result of persistent inflammation and immune dysfunction of which CMV is a known contributor. We leveraged two ACTG clinical trials exploring effects of immune modulators (ruxolitinib and sirolimus) on inflammation in people with HIV on ART to determine if these interventions affected CMV shedding at various mucosal sites. Analyzing 635 mucosal samples collected, we found no significant difference in CMV levels across study arms or time points. Men had more CMV shedding than women...

BACKGROUND: The emerged SARS-CoV-2 Omicron variants BA.1, BA.2 and BA.4/5 demonstrate higher transmission and infection compared to previous variants of concern. To evaluate effectiveness of heterologous and homologous booster vaccination, we directly compared cellular and humoral immune responses as well as neutralizing capacity against replication-competent SARS-CoV-2 wild type, Delta and Omicron variants BA.1, BA.2, BA.4/5. METHODS: For this, peripheral blood mononuclear cells (PBMCs) and serum samples of 137 participants divided into three major groups were investigated...

Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in COVID-19 pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify SARS-CoV-2 virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton's tyrosine kinase (BTK)-induced pyroptosis and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells...

The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal non-human primate (NHP) at high-biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all four infected marmosets. Three developed pulmonary edema and hemorrhage as well as multi-focal hemorrhagic lymphadenopathy, while one recapitulated neurologic clinical manifestations and cardiomyopathy on gross pathology...

BACKGROUND: Human papillomavirus (HPV) vaccination coverage remains suboptimal in the U.S., underscoring the importance of monitoring trends in vaccine hesitancy. METHODS: Cross-sectional data from the 2011-2020 National Immunization Survey-Teen were used to assess trends in provider-verified HPV vaccination initiation (≥1 dose) among 13-17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy. RESULTS: Among all sex and race and ethnicity groups, prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%)...

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in U.S. military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained Spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7...

Modified vaccinia virus Ankara (MVA) is used as a vaccine against monkeypox virus (MPXV) and as a viral vaccine vector. MVA-MERS-S is a vaccine candidate against Middle East respiratory syndrome- associated coronavirus (MERS-CoV). Here, we report that cross-reactive MPXV nAbs were detectable in only a single subject after the first dose, 3 out of 10 after the 2nd dose, and in 10 out of 10 after the 3rd dose of MVA-MERS-S vaccine.

BACKGROUND: The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes. METHODS: Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with TNF concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality...

Multisystem inflammatory syndrome in children (MIS-C) is a complication of SARS-CoV-2 infection; in the U.S., reporting of MIS-C after COVID-19 vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on October 29, 2021. Covering a period when ∼7 million children received vaccine, surveillance for MIS-C ≤90 days post-vaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence...

BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL), a dermal form of the disease, occurs in some of the visceral leishmaniasis (VL) patients following treatment. The PKDL disease mechanism is yet not clearly understood. OBJECTIVES: Here we have studied the role of dermal fibroblasts in VL and PKDL disease mechanism. METHODS: Dermal fibroblasts were grown from skin biopsy explants collected from individual VL & PKDL patients and healthy controls...

Staphylococcus aureus (S. aureus) causes a broad range of infections. TLR2 senses the S. aureus lipoproteins in S. aureus infections. Aging raises the risk of infection. Our aim was to understand how aging and TLR2 impact the clinical outcomes of S. aureus bacteremia. Four groups of mice (Wild type/young, Wild type/old, TLR2-/-/young, and TLR2-/-/old) were intravenously infected with S. aureus, and the infection course was followed. Both TLR2 deficiency and aging enhanced the susceptibility to disease. Increased age was the main contributing factor to mortality and changes in spleen weight, whereas other clinical parameters such as weight loss and kidney abscess formation were more TLR2 dependent...

BACKGROUND: SARS-CoV-2 control on college campuses is challenging given communal living and student social dynamics. Understanding SARS-CoV-2 transmission among college students is important for the development of optimal control strategies. METHODS: SARS-CoV-2 nasal swabs were collected from University of Pittsburgh students for symptomatic testing and asymptomatic surveillance from August 2020 through April 2021 from three campuses. Whole-genome sequencing (WGS) was performed on 308 samples and contact tracing information collected from students was used to identify transmission clusters...

BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. COVID mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD...

OBJECTIVES: We quantified the quality-adjusted life-years (QALYs) lost attributable to chlamydia, gonorrhea, and trichomoniasis in the US, by sex and age group. METHODS: We adapted a previous probability-tree model to estimate the average number of lifetime QALYs lost due to genital chlamydia, gonorrhea, and trichomoniasis, per incident infection and at the population level, by sex and age group. We conducted multivariate sensitivity analyses to address uncertainty around key parameter values...