Journal of Infectious Diseases

BACKGROUND: Keratin 8/18 (K8/18) are the exclusively expressed keratins intermediate filaments pair in hepatocytes that protect against liver injuries and viral infection. We aimed to explore the genetic link between keratin variants and chronic hepatitis B virus (CHB) infection in a large cohort from a high epidemic area. METHODS: Genomic DNA was isolated from patients, and sanger sequencing was applied to analyze variations in exon regions of K8/18. Biochemical and functional analysis of novel mutations was also performed...

The incidence of sexually transmitted infections (STIs) including gonorrhea, syphilis, chlamydia, and trichomoniasis, is increasing by over 1 million new cases daily and represents a global public health crisis. There is an alarming increase of gonorrhea and syphilis among men who have sex with men and bisexual men, two key populations also at high risk for human immunodeficiency virus (HIV). A refocused, dedicated, and intensive biomedical research program is needed that targets the development of innovative diagnostics, safe and effective vaccines, and new and improved therapeutics for STIs...

BACKGROUND: Mycobacterium bovis (M. bovis) persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon beta (IFN-β) is one of these critical strategies. The mitochondrial transcription factor A (TFAM), plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-β production in response to viral infection. However, the role of TFAM in the production of IFN-β by M. bovis has not been elucidated...

Nosocomial infections with Clostridium difficile are on the rise in the USA, attributed to emergence of antibiotic resistant and hypervirulent strains associated with greater likelihood of recurrent infections. In addition to antibiotics, treatment with Merck anti-TcdB antibody Bezlotoxumab reported to reduce recurrent infections. However, treatment with anti-TcdA antibody Actotoxumab had dramatically increased disease severity and mortality rates in humans and gnotobiotic piglets. Utilizing isogenic mutants of C...

BACKGROUND: Liberal fluid resuscitation has proved harmful in adults with severe malaria, but the level of restriction has not been defined. METHODS: In a prospective observational study in adults with severe falciparum malaria, restrictive fluid management was provided at the discretion of the treating physician. The relationships between the volume of fluid and changes in renal function or tissue perfusion were evaluated. RESULTS: A total of 154 patients were studied, of whom 41 (26...

Cytomegalovirus viral loads overall were 0.29 log IU/ml higher with cobas® CMV for use on the cobas® 6800/8800 System (cobas CMV) when compared to Cobas® AmpliPrep/Cobas® TaqMan® CMV Test (CAP/CTM CMV). CMV DNAemia was detected 11.5 days earlier by cobas CMV, while clearance was delayed by 12.8 days. CMV remained detectable by cobas CMV in 44.2% of patients at the time of viral clearance as determined by CAP/CTM CMV. Undetectable viral load by cobas CMV at end of treatment was associated with reduced risk for re-treatment (odds ratio, 0...

BACKGROUND: With the nation's focus on the opioid crisis, methamphetamine has made a comeback, potentially increasing risk for hepatitis B. We examined factors associated with hepatitis B virus (HBV) exposure among people who reported ever using methamphetamine in a nationally representative survey. METHODS: We utilized the National Health and Nutrition Examination Survey to examine factors associated with HBV exposure among participants who reported ever using methamphetamine using bivariate and multivariable logistic regression...

BACKGROUND: Treatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antivirals agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and a NS5A inhibitor approved for the treatment of chronic HCV genotype 1-6 infection, including patients with HIV coinfection. METHODS: A series of Phase 1 studies was conducted to evaluate potential interactions of glecaprevir and pibrentasvir with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, abacavir/dolutegravir/lamivudine, raltegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/emtricitabine/tenofovir disoproxil fumarate...

BACKGROUND: BCG appears to reduce acquisition of Mycobacterium tuberculosis (Mtb) infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of Mtb infection in adults. METHODS: We conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression...

Mother-to-child transmission of HIV occurs in the setting of maternal and passively-acquired antibodies, providing a unique window into immune correlates of HIV risk. We compared plasma antibody binding to HIV antigens between 51 non-transmitting mother-infant pairs and 21 transmitting mother-infant pairs. Plasma antibody binding to a variety of gp41 ectodomain-containing antigens was associated with increased odds of transmission. Understanding the reasons why gp41 ectodomain-targeting antibodies are associated with transmission risk will be important in determining whether they can directly enhance infection or whether their presence reflects a redirecting of the humoral response away from targeting more protective epitopes...

BACKGROUND: Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a Ct recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection. METHODS: Female C3H/HeN mice were vaccinated by mucosal and systemic routes with Ct serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with Ct serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43) or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants...

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Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all three toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S...

BACKGROUND: Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. METHODS: We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at five clinical time points and by HIV-coinfection and IFNL4 genotype...

Follicular helper T cells (Tfh), CD4 lymphocytes critical for efficient antibody responses, have been shown to be key HIV-1 reservoirs. HIV-2 infection represents a unique naturally-occurring model for investigating Tfh role in HIV/AIDS, given its slow rate of CD4 decline, low to undetectable viremia and high neutralizing antibodies titers throughout the disease course. We investigated here, for the first time, Tfh susceptibility to HIV-2 infection by combining in vitro infection of tonsillar Tfh with the ex vivo study of circulating Tfh from HIV-2-infected patients...

Despite the benefits of yearly influenza vaccination, accumulating evidence suggests that diminished vaccine efficacy may be related to repeated vaccination. Although studied at the level of B cell responses, CD4 T cell responses have not yet been examined. Here, we analyze CD4 T cell responses to influenza vaccination in subjects who differ in their vaccine history. We find a striking disparity in their responses, with previously vaccinated subjects exhibiting significantly blunted CD4 T cell responses and diminished antibody responses...

BACKGROUND: To understand real-world HPV vaccine impact, continuous evaluation using population-based data is critical. We evaluated the early impact of the school-based HPV immunization program on cervical dysplasia in females in British Columbia (BC), Canada. METHODS: Data linkage was performed using records from the provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV vaccinated females born in 1994-2005...

BACKGROUND: Regenerating islet-derived protein-3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People with HIV (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation and development of non-AIDS co-morbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. METHODS: Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 HIV-uninfected controls were assessed...

BACKGROUND: Accurate quantification of female and male gametocytes and sex-ratios in low-density malaria infections are important for assessing the transmission potential of asymptomatic infections. Gametocytes often escape detection even by molecular methods, therefore ultra-low gametocyte densities were quantified in large blood volumes. METHODS: Female and male gametocytes were quantified in 161 PCR-positive Plasmodium falciparum (Pf) infections from a cross-sectional survey in Papua New Guinea...

BACKGROUND: Streptococcus pneumonia meningitis (PM) is a major cause of childhood neurological deficits. Although the Notch1 signalling pathway regulates neurogenesis and neuroinflammation, we know little about its expression or influence on hippocampal neurogenesis and gliogenesis during PM. METHODS: We used immunofluorescence and western blots to detect Notch1 signalling expression during experimental PM. Through double-labelling immunofluorescence, we investigated proliferation and differentiation in the dentate gyrus (DG) in PM before and after treatment with exogenous Notch1 activator (Jagged1) and inhibitor (IMR-1)...