Journal of Infectious Diseases

BACKGROUND: Dengue virus (DENV) can cause life-threatening disease characterized by endothelial dysfunction and vascular leakage. DENV nonstructural protein 1 (NS1) induces human endothelial hyperpermeability and vascular leak in mice, and NS1 vaccination confers antibody-mediated protective immunity. We evaluated the magnitude, cross-reactivity, and functionality of NS1-specific IgG antibody responses in sera from a phase II clinical trial of Takeda's live-attenuated tetravalent dengue vaccine candidate (TAK-003)...

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BACKGROUND: Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early and late onset disease and maternal complications potentially could be addressed. METHODS: Capsular polysaccharide conjugate vaccine GBS6 was designed using Whole Genome Sequencing surveillance data of recent, global GBS isolates responsible for invasive neonatal GBS disease...

We analyzed the virulence of pandemic H1N1 2009 influenza A viruses in vivo and in vitro. Selected viruses isolated in 2009, 2010, 2014, and 2015 were assessed using an aerosol-mediated high-dose infection model for pigs as well as air-liquid interface cultures of differentiated airway epithelial cells. Using a dyspnea score, rectal temperature, lung lesions, and viral load in the lung as parameters, the strains from 2014-2015 were significantly less virulent than the strains isolated in 2009-2010. In vitro, the viruses from 2009-2010 also differed from the 2014-2015 viruses by increased release of infectious virus, a more pronounced loss of ciliated cells, and a reduced thickness of the epithelial cell layer...

We report a case of sexual transmission of human immunodeficiency virus (HIV) that occurred during treatment discontinuation in a therapeutic vaccine trial, following oral sex. Transmission occurred even though the index participant was an HIV/AIDS activist, particularly well informed about the risks and modalities of transmission. This case report highlights the risk of secondary transmission of HIV during cessation of treatment in HIV cure-related trials.

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BACKGROUND: Histo blood group antigens (HBGAs) such as fucosyltransferase FUT2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. METHODS: In three community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. qPCR panels tested 3,663 diarrheal and 18,148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n=520) and mothers' (n=519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens...

Zika virus (ZIKV) is a clinically important flavivirus that can cause neurological disturbances in newborns. Here, we investigated comparatively the outcome of in vitro infection of newborn monocytes by ZIKV. We observed that neonatal cells show defective production of IL-1β, IL-10 and MCP-1 in response to ZIKV, albeit they are as efficient as adult cells in supporting viral infection. Although CLEC5A is a classical flavivirus immune receptor, it is not essential for cytokine response, but regulates the viral load only in adult cells, not in newborns...

Background: Scale-up of direct-acting antiviral(DAA) therapy is expected to abate HCV incidence among HIV-positive men-who-have-sex-with-men(MSM). Treatment programs in neighbouring countries may influence each other's outcomes through international transmission. We aimed at classifying HCV infections in HIV-positive MSM as either domestically or internationally acquired, and at estimating how this classification changed over time. Methods: HCV subtype 1a (the most frequent subtype among MSM) genomes from 99 persons enrolled in the Swiss-HIV-Cohort-Study(SHCS) and diagnosed with replicating HCV infections between 1999 and 2016, were sequenced...

Background: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. Methods: We investigated in-vitro and in-vivo effects of metformin in humans. Results: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in-vitro cellular metabolism whilst inhibiting the mammalian target of rapamycin (mTOR) targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation, and increased phagocytosis...

In 2015-2016, a Zika virus (ZIKV) outbreak occurred in the Americas. In 2017, we conducted a ZIKV serosurvey in Suriname in which 770 participants were recruited from one urban area and two rural villages in the tropical rainforest. All collected samples were tested for presence of ZIKV antibodies using a ZIKV IgG ELISA and a virus neutralisation assay. We found that 35.1% of the participants had neutralizing antibodies against ZIKV. In one remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across Suriname...

Background: Genital infection with herpes simplex virus type-2 (HSV-2) is common, and increases risk of HIV transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 Study. Methods: We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blind, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 pre-exposure prophylaxis...

The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not...

A respiratory outbreak associated with adenovirus-7 (HAdV-7) occurred among unvaccinated officer candidates attending initial military training. Respiratory infections associated with HAdV-7 can be severe resulting in significant morbidity. Genomic sequencing revealed HAdV-7d, a genome type recently remerging in the US as a significant respiratory pathogen, following reports from Southeast Asia. Twenty-nine outbreak cases were identified; this likely represents an underestimate. Although the HAdV-4 and -7 vaccine is currently given to US military enlisted recruit trainees, it is not routinely given to officer candidates...

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Background: Women-specific factors exist that increases vulnerability to drug-related harms from injecting drug use including bloodborne viruses (BBV), but gender differences in BBV prevalence have not been systematically examined. Methods: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically-confirmed HIV, hepatitis C (anti-HCV) and hepatitis B (HBsAg) prevalence in people who inject drugs (PWID) by gender. Gender differences in BBV (relative risks, RR in women vs men) were regressed on country-level prevalence and inequality measures...

Background: Few studies have studied relative cross-protection between different groups of viruses through studies of sequential infections in humans. We aimed to investigate presence of short-lived relative cross-protection between specific prior viral infections and subsequent febrile respiratory illness (FRI). Methods: Basic Military Training (BMT) intakes between December 2009 and December 2014 were recruited, with the first FRI as the entry point. ResPlex II assays and real-time PCR assays were used to detect viral pathogens in the samples collected, followed by survival analyses to determine if infection with particular viruses conferred short-lived relative cross-protection against FRI...

The diversity of Trypanosoma cruzi parasites infecting humans is still poorly understood. We used deep sequencing to analyze this diversity in Chagasic patients from Mexico. Such information is crucial to understand transmission cycles, and identify determinants for epidemiological and clinical characteristics of the infection. We analyzed parasite mini-exon spliced leader sequences following PCR amplification from blood DNA and deep sequencing. Chagasic patients presented a diverse assemblage of parasite haplotypes covering TcI, TcII, TcV and TcVI DTUs, with 3...

Background: The tryptophan-kynurenine-NAD+ pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in CNS infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers. Methods: We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 220 cerebrospinal fluid samples from patients with bacterial and viral (herpes simplex, varicella zoster, enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (anti-NMDA-R encephalitis, multiple sclerosis), and noninflamed controls (Bell's palsy, normal pressure hydrocephalus, Tourette syndrome)...