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  • Design and Analysis of Elimination Surveys for Neglected Tropical Diseases
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-13
    Fronterre C, Amoah B, Giorgi E, et al.

    As neglected tropical diseases approach elimination status, there is a need to develop efficient sampling strategies for confirmation (or not) that elimination criteria have been met. This is an inherently difficult task because the relative precision of a prevalence estimate deteriorates as prevalence decreases, and classic survey sampling strategies based on random sampling therefore require increasingly large sample sizes. More efficient strategies for survey design and analysis can be obtained by exploiting any spatial correlation in prevalence within a model-based geostatistics framework. This framework can be used for constructing predictive probability maps that can inform in-country decision makers of the likelihood that their elimination target has been met, and where to invest in additional sampling. We evaluated our methodology using a case study of lymphatic filariasis in Ghana, demonstrating that a geostatistical approach outperforms approaches currently used to determine an evaluation unit’s elimination status.

    更新日期:2020-01-16
  • Corrigendum to: A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-09
    Kirolos A, , Manti S, et al.

    In “A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis” by Kirolos et al. [J Infect Dis 2019. doi:10.1093/infdis/jiz240], Table 1 and Figure 1 have been moved from supplementary material to the main body of the article for clarity.

    更新日期:2020-01-13
  • Prevalence and phylogenetic characterization of hepatitis C among men who have sex with men in India: limited evidence for sexual transmission
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-09
    Clipman S, Duggal P, Srikrishnan A, et al.

    BackgroundData from high-income countries suggest increasing hepatitis C virus (HCV) prevalence/incidence among HIV-infected men who have sex with men (MSM), but limited data derive from low-and-middle-income countries (LMICs). MethodsWe recruited 4,994 MSM from 5 states across India using respondent-driven sampling (RDS). Logistic regression incorporating RDS weights and machine learning feature selection were used to identify correlates of prevalent HCV, and Bayesian phylogenetic analysis was used to examine genetic clustering. ResultsMedian age was 25, HIV prevalence was 7.2% and 49.3% reported recent unprotected anal intercourse. HCV prevalence was 1.3% (95% CI: 1.0 – 1.6%; site range: 0.2 – 3.4%) and was 3.1% in HIV-positive compared to 1.1% among HIV-negative. HCV infection was significantly associated with injection drug use (OR: 177.1; 95% CI: 72.7 – 431.5) and HIV (OR: 4.34; 95% CI: 1.88 – 10.05). Machine learning did not uncover any additional epidemiologic signal. Phylogenetic analysis revealed three clusters suggestive of linked transmission; each contained at least one individual reporting injection drug use. ConclusionsWe observed a low HCV prevalence in this large sample of MSM despite high prevalence of known risk factors, reflecting either the need for a threshold of HCV for sexual transmission and/or variability in sexual practices across settings.

    更新日期:2020-01-13
  • Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-09
    Espinosa J, Marín-Moreno A, Aguilar-Calvo P, et al.

    Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]–Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.

    更新日期:2020-01-13
  • Oncostatin-M is a prognostic biomarker and inflammatory mediator for sepsis
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-13
    Gong Y, Yan X, Sun X, et al.

    BackgroundOncostatin-M (OSM) is a pleiotropic cytokine of the IL-6 family. The role of OSM in sepsis remains unknown. MethodsSerum OSM level was determined and analyzed in septic patients on day of intensive care unit (ICU) admission. Furthermore, the effects of OSM on polymicrobial sepsis induced by cecal ligation and puncture (CLP) were assessed. ResultsOn day of ICU admission, septic patients had significantly higher serum OSM levels when compared with ICU patient controls and healthy volunteers, which were related to the severity of sepsis, including parameters such as the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, procalcitonin (PCT) level, and white blood cell (WBC) number. A high serum OSM level on ICU admission was associated with 28-day mortality in septic patients. In CLP-induced polymicrobial sepsis, anti-OSM antibody decreased tissue inflammation and injury, and thus improved survival, while local and systemic bacterial dissemination was almost constant. Complementarily, supplementation with recombinant OSM protein in septic mice increased tissue injury, amplified inflammation, and worsened mortality after CLP, while it did not affect bacterial dissemination in septic mice. ConclusionsSepsis results in an increased production of OSM, which might be a potential prognostic biomarker and therapeutic target for sepsis.

    更新日期:2020-01-13
  • Persisting Antibody Response Nine Years after Bivalent HPV Vaccination in A Cohort of Dutch Women: Immune Response and the Relation with Genital HPV Infections
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-09
    Hoes J, Pasmans H, Knol M, et al.

    The bivalent HPV vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009 including 744 vaccinated and 294 unvaccinated girls (1993-1994), who provide a vaginal self-swab, serum sample and questionnaire yearly, we report a high, persisting antibody response up to nine years post-vaccination for vaccine types HPV16/18. Antibodies against non-vaccine types HPV31/33/45/52/58 were lower, but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and without HPV infections one year pre-infection (204 incident and 64 persistent infections), but observed no consistent difference in type-specific antibody levels. Having a hrHPV infection was associated with sexual risk behavior and smoking one year pre-infection. While high antibody levels are necessary for protection, our study suggests that on individual level other factors such as HPV-exposure or antibody avidity could be important.

    更新日期:2020-01-09
  • Large-scale screening and identification of novel pathogenic Staphylococcus aureus genes using a silkworm infection model
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-08
    Paudel A, Hamamoto H, Panthee S, et al.

    The regulatory network of virulence factors produced by the opportunistic pathogenStaphylococcus aureus is unclear, and the functions of many uncharacterized genes in its genome remain to be elucidated. In this study, we screened 380 genes whose function was unassigned utilizing gene-disrupted transposon mutants of the community-acquired methicillin-resistant S. aureus USA300 for pathogenicity using silkworms. We identified 10 strains with reduced silkworm killing ability. Among them, 8 displayed reduced virulence in a mouse model as evidenced by reduced colony-forming units in organs of infected mice. The role of each gene in pathogenicity was further confirmed by complementation and pathogenicity tests in silkworms, where we found that the phenotype was not restored in one strain. Additionally, some of the mutants displayed reduced hemolysis, proteolysis, pigment production, and survival in murine RAW 264.7 monocyte-macrophage cells. These newly identified genes involved in virulence will enhance our understanding of the pathogenicity of S. aureus.

    更新日期:2020-01-08
  • Erratum to: Attenuation of Helper T Cell Capacity for TH1 and TH17 Differentiation in Children With Nontuberculous Mycobacterial Infection
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-06
    Claeys T, Rosas Mejia O, Marshall S, et al.

    In “Attenuation of Helper T Cell Capacity for TH1 and TH17 Differentiation in Children With Nontuberculous Mycobacterial Infection” [J Infect Dis, Volume 220, Issue 11, 1 December 2019, Pages 1843–1847, https://doi.org/10.1093/infdis/jiz371], the author name “Don Hayes” should be “Don Hayes, Jr.”. This has been corrected online.

    更新日期:2020-01-07
  • A class II-restricted CD8ɣ13 T cell clone protects during Chlamydia muridarum genital tract infection
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-03
    Johnson R, Olivares-Strank N, Peng G.

    The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as “unrestricted” or “atypical”. We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN-ɣ and IL-13. Here we investigated the transcriptome of CD8ɣ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8ɣ13 T cell clone to determine whether either influenced bacterial clearance or immunopathology during Chlamydiamuridarum genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function.

    更新日期:2020-01-04
  • Population-level human secretor status is associated with genogroup 2 type 4 norovirus predominance
    J. Infect. Dis. (IF 5.045) Pub Date : 2020-01-04
    Arrouzet C, Ellis K, Kambhampati A, et al.

    BackgroundNoroviruses are a leading cause of acute gastroenteritis. Genogroup 2 type 4 (GII.4) has been the dominant norovirus genotype worldwide since its emergence in the mid-1990s. Individuals with a functional fucosyltransferase-2 gene, known as secretors, have increased susceptibility to GII.4 noroviruses. We hypothesized that this individual-level trait may drive GII.4 norovirus predominance at the human population level. MethodsWe conducted a systematic review for studies reporting norovirus outbreak or sporadic case genotypes and merged this with data on proportions of human secretor status in various countries from a separate systematic review. We used inverse variance-weighted linear regression to estimate magnitude of the population secretor-GII.4 proportion association. Results219 genotype and 112 secretor studies with data from 38 countries were included in the analysis. Study-level GII.4 proportion among all noroviruses ranged from 0% to 100%. Country secretor proportion ranged from 43.8% to 93.9%. We observed a 0.69% (95% CI: 0.19, 1.18) increase in GII.4 proportion for each percent increase in human secretor proportion, controlling for Human Development Index. ConclusionsNorovirus evolution and diversity may be driven by local population human host genetics. Our results may have vaccine development implications including whether specific antigenic formulations would be required for different populations.

    更新日期:2020-01-04
  • Trained immunity confers broad-spectrum protection against bacterial infections
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-31
    Ciarlo E, Heinonen T, Théroude C, et al.

    BackgroundThe innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. MethodsMice were trained and subjected to systemic infections, peritonitis, enteritis and pneumonia induced byStaphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes and hematopoietic precursors were quantified in blood, bone marrow and organs. The role of monocytes/macrophages, granulocytes and IL-1 signaling was investigated using depletion or blocking approaches. ResultsInduction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and IL-1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks. ConclusionsTrained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses.

    更新日期:2019-12-31
  • Correlations Between Human Immunodeficiency Virus (HIV) Infection and Rectal Gonorrhea Incidence in Men Who Have Sex With Men: Implications for Future HIV Preexposure Prophylaxis Trials
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-01-31
    Mullick C, Murray J.

    Using published data, we found a direct correlation between the incidence of rectal gonorrhea and human immunodeficiency virus (HIV) infection in men who have sex with men who were not using oral preexposure prophylaxis. HIV incidence was predicted using rectal gonorrhea incidence as the determinant in regression analysis. The observed correlation suggest that rectal gonorrhea incidence can potentially serve as a predictor of HIV incidence. If confirmed with additional data, a quantitative correlation for incidence of the 2 infections could be useful in active-controlled HIV prevention trials where low HIV incidence is expected. Widespread improvements in treatment as prevention and gonorrhea control can negatively impact the correlation and its utility.

    更新日期:2019-12-30
  • Novel Approaches for Development of Human Immunodeficiency Virus Preexposure Prophylaxis Agents
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-01-31
    Cohen M, Donnell D.

    HIVPrEPacquisitionpreventiontransmission

    更新日期:2019-12-30
  • Diet May Drive Influenza A Virus Exposure in African Mammals
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-03-06
    Soilemetzidou E, De Bruin E, Franz M, et al.

    BackgroundInfluenza A viruses (IAVs) represent repeatedly emerging pathogens with near worldwide distribution and an unclear nonavian-host spectrum. While the natural hosts for IAV are among waterfowl species, certain mammals can be productively infected. Southern Africa is home to diverse avian and mammalian fauna for which almost no information exists on IAV dynamics. MethodsWe evaluated 111 serum samples from 14 mammalian species from Namibia for the presence of IAV-specific antibodies and tested whether host phylogeny, sociality, or diet influence viral prevalence and diversity. ResultsFree-ranging African mammals are exposed to diverse IAV subtypes. Herbivores developed antibodies against 3 different hemagglutinin (HA) subtypes, at low prevalence, while carnivores showed a higher prevalence and diversity of HA-specific antibody responses against 11 different subtypes. Host phylogeny and sociality were not significantly associated with HA antibody prevalence or subtype diversity. Both seroprevalence and HA diversity were significantly increased in carnivores regularly feeding on birds. ConclusionsThe risk of infection and transmission may be driven by diet and ecological factors that increase contact with migratory and resident waterfowl. Consequently, wild mammals, particularly those that specialize on hunting and scavenging birds, could play an important but overlooked role in influenza epizootics.

    更新日期:2019-12-30
  • Maternal Envelope gp41 Ectodomain-Specific Antibodies Are Associated With Increased Mother-to-Child Transmission of Human Immunodeficiency Virus-1
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-29
    Naiman N, Slyker J, Nduati R, et al.

    Mother-to-child transmission of human immunodeficiency virus (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 nontransmitting 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.

    更新日期:2019-12-30
  • Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-29
    Kosloski M, Oberoi R, Wang S, et al.

    BackgroundTreatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antiviral agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved for the treatment of chronic HCV genotype 1–6 infection, including patients with HIV coinfection. MethodsA 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. Pharmacokinetics of the antiretrovirals and DAAs were characterized when administered alone and in combination to quantify changes in systemic drug exposure. ResultsGlecaprevir area under the curve increased >4-fold in the presence of ritonavir-boosted HIV protease inhibitors, while pibrentasvir concentrations were not significantly affected; elevations in alanine transaminase occurred in combination with atazanavir/ritonavir only. Exposures of glecaprevir and pibrentasvir may be significantly decreased by efavirenz. Coadministration with glecaprevir and pibrentasvir did not result in clinically significant changes in the exposure of any antiretroviral agents. ConclusionsAtazanavir is contraindicated with glecaprevir/pibrentasvir and use of boosted protease inhibitors or efavirenz is not recommended. No clinically significant interactions were observed with other studied antiretrovirals.

    更新日期:2019-12-30
  • Efficacy of Active Immunization With Attenuated α-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-26
    Tran V, Venkatasubramaniam A, Adhikari R, et al.

    Staphylococcusaureus 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 α-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 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

    更新日期:2019-12-30
  • A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-28
    Tifrea D, Pal S, de la Maza L.

    BackgroundChlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection. MethodsFemale C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with 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. ResultsImmune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1). ConclusionsThis is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

    更新日期:2019-12-30
  • Zika Virus Nonstructural Protein 1 Disrupts Glycosaminoglycans and Causes Permeability in Developing Human Placentas
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-06-27
    Puerta-Guardo H, Tabata T, Petitt M, et al.

    BackgroundDuring pregnancy, the Zika flavivirus (ZIKV) infects human placentas, inducing defects in the developing fetus. The flavivirus nonstructural protein 1 (NS1) alters glycosaminoglycans on the endothelium, causing hyperpermeability in vitro and vascular leakage in vivo in a tissue-dependent manner. The contribution of ZIKV NS1 to placental dysfunction during ZIKV infection remains unknown. MethodsWe examined the effect of ZIKV NS1 on expression and release of heparan sulfate (HS), hyaluronic acid (HA), and sialic acid on human trophoblast cell lines and anchoring villous explants from first-trimester placentas infected with ZIKV ex vivo. We measured changes in permeability in trophoblasts and stromal cores using a dextran-based fluorescence assay and changes in HA receptor expression using immunofluorescent microscopy. ResultsZIKV NS1 in the presence and absence of ZIKV increased the permeability of anchoring villous explants. ZIKV NS1 induced shedding of HA and HS and altered expression of CD44 and lymphatic endothelial cell HA receptor-1, HA receptors on stromal fibroblasts and Hofbauer macrophages in villous cores. Hyaluronidase was also stimulated in NS1-treated trophoblasts. ConclusionsThese findings suggest that ZIKV NS1 contributes to placental dysfunction via modulation of glycosaminoglycans on trophoblasts and chorionic villi, resulting in increased permeability of human placentas.

    更新日期:2019-12-30
  • What Are the Transmission Mechanisms of Influenza A Viruses in Wild Mammals?
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-03-06
    Root J.

    (See the Major Article by Soilemetzidou et al, on pages 175–82.)

    更新日期:2019-12-30
  • The Impact of Multiple Rounds of Indoor Residual Spraying on Malaria Incidence and Hemoglobin Levels in a High-Transmission Setting
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-09-06
    Zinszer K, Charland K, Vahey S, et al.

    BackgroundIndoor residual spraying (IRS) is widely used as a vector control measure, although there are conflicting findings of its effectiveness in reducing malaria incidence. The objective of this study was to estimate the effect of multiple IRS rounds on malaria incidence and hemoglobin levels in a cohort of children in rural southeastern Uganda. MethodsThe study was based upon a dynamic cohort of children aged 0.5–10 years enrolled from August 2011 to June 2017 in Nagongera Subcounty. Confirmed malaria infections and hemoglobin levels were recorded over time for each participant. After each of 4 rounds of IRS, malaria incidence, hemoglobin levels, and parasite density were evaluated and compared with pre-IRS levels. Analyses were carried out at the participant level while accounting for repeated measures and clustering by household. ResultsIncidence rate ratios comparing post-IRS to pre-IRS incidence rates for age groups 0–3, 3–5, and 5–11 were 0.108 (95% confidence interval [CI], .078–.149), 0.173 (95% CI, .136–.222), and 0.226 (95% CI, .187–.274), respectively. The mean hemoglobin levels significantly increased from 11.01 (pre-IRS) to 12.18 g/dL (post-IRS). ConclusionsOur study supports the policy recommendation of IRS usage in a stable and perennial transmission area to rapidly reduce malaria transmission.

    更新日期:2019-12-30
  • Differences in Duration and Degree of Cytomegalovirus DNAemia Observed With Two Standardized Quantitative Nucleic Acid Tests and Implications for Clinical Care
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-31
    Meesing A, Germer J, Yao J, et al.

    Cytomegalovirus (CMV) viral loads overall were 0.29 log IU/mL higher with cobas CMV for use on the cobas 6800/8800 System (cobas CMV) compared with Cobas AmpliPrep/Cobas TaqMan CMV Test (CAP/CTM CMV). Cytomegalovirus DNAemia was detected 11.5 days earlier by cobas CMV, whereas clearance was delayed by 12.8 days. Cytomegalovirus 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 retreatment (odds ratio, 0.26; 95% confidence interval, 0.04–0.99; P = .05).The use of different quantitative cytomegalovirus nucleic acid tests may affect direct patient care as a result of significant differences in reporting the degree of CMV DNAemia and the time to first detection and clearance of CMV DNAemia.

    更新日期:2019-12-30
  • Associations Between Restrictive Fluid Management and Renal Function and Tissue Perfusion in Adults With Severe Falciparum Malaria: A Prospective Observational Study
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-31
    Ishioka H, Plewes K, Pattnaik R, et al.

    BackgroundLiberal fluid resuscitation has proved harmful in adults with severe malaria, but the level of restriction has not been defined. MethodsIn 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. ResultsA total of 154 patients were studied, 41 (26.6%) of whom died. Median total fluid intake during the first 6 and 24 hours from enrollment was 3.3 (interquartile range [IQR], 1.8–5.1) mL/kg per hour and 2.2 (IQR, 1.6–3.2) mL/kg per hour, respectively. Total fluid intake at 6 hours was not correlated with changes in plasma creatinine at 24 hours (n = 116; rs = 0.16; P = .089) or lactate at 6 hours (n = 94; rs = −0.05; P = .660). Development of hypotensive shock or pulmonary edema within 24 hours after enrollment were not related to the volume of fluid administration. ConclusionsRestrictive fluid management did not worsen kidney function and tissue perfusion in adult patients with severe falciparum malaria. We suggest crystalloid administration of 2–3 mL/kg per hour during the first 24 hours without bolus therapy, unless the patient is hypotensive.

    更新日期:2019-12-30
  • Factors Associated With Hepatitis B Exposure Among People Who Report Using Methamphetamine: National Health and Nutrition Examination Survey 2009–2016
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-30
    Tressler S, Kushner T, Bhandari R.

    BackgroundWith 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. MethodsWe used 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. ResultsOverall, 847 participants met the study inclusion criteria. In multivariable logistic regression, female sex (adjusted odds ratio, 3.83; 95% confidence interval, 1.65–8.90), living below the poverty threshold (3.17; 1.39–7.21), injection drug use (4.89; 1.95–12.26), active hepatitis C virus infection (3.39; 1.10–12.26), and identifying as men who have sex with men (28.21; 5.19–153.38) were significantly associated with HBV exposure. ConclusionsThe odds of HBV exposure for female participants who reported using methamphetamine were 4 times than that for male participants. Poverty, injection drug use, and hepatitis C virus infection were also associated. As methamphetamine use increases, it is critical to identify those at risk of acquiring HBV infections in order to target testing and vaccination.

    更新日期:2019-12-30
  • Counter-Selection of Antimalarial Resistance Polymorphisms by Intermittent Preventive Treatment in Pregnancy
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-11-02
    Huijben S, Macete E, Mombo-Ngoma G, et al.

    BackgroundInnovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions. MethodsPlasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women. ResultsIn HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes. ConclusionsSelection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.

    更新日期:2019-12-30
  • Functional Human CD141+ Dendritic Cells in Human Immune System Mice
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-10-25
    Coelho-Dos-Reis J, Funakoshi R, Huang J, et al.

    BackgroundFor the purpose of studying functional human dendritic cells (DCs) in a humanized mouse model that mimics the human immune system (HIS), a model referred to as HIS mice was established. MethodsHuman immune system mice were made by engrafting NOD/SCID/IL2Rgammanull (NSG) mice with human hematopoietic stem cells (HSCs) following the transduction of genes encoding human cytokines and human leukocyte antigen (HLA)-A2.1 by adeno-associated virus serotype 9 (AAV9) vectors. ResultsOur results indicate that human DC subsets, such as CD141+CD11c+ and CD1c+CD11c+ myeloid DCs, distribute throughout several organs in HIS mice including blood, bone marrow, spleen, and draining lymph nodes. The CD141+CD11c+ and CD1c+CD11c+ human DCs isolated from HIS mice immunized with adenoviruses expressing malaria/human immunodeficiency virus (HIV) epitopes were able to induce the proliferation of malaria/HIV epitopes-specific human CD8+ T cells in vitro. Upregulation of CD1c was also observed in human CD141+ DCs 1 day after immunization with the adenovirus-based vaccines. ConclusionsEstablishment of such a humanized mouse model that mounts functional human DCs enables preclinical assessment of the immunogenicity of human vaccines in vivo.

    更新日期:2019-12-30
  • Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-10-16
    Jung A, Møller Jørgensen M, Bæk R, et al.

    BackgroundCommunity-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs). MethodsWe performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies. ResultsWe detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor–R-II, and CD16. ConclusionThe discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.

    更新日期:2019-12-30
  • High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-10-15
    Chihota B, , Wandeler G, et al.

    Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.

    更新日期:2019-12-30
  • The Impact of Actotoxumab Treatment of Gnotobiotic Piglets Infected With Different Clostridium difficile Isogenic Mutants
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-09-09
    Danz H, Lee S, Chapman-Bonofiglio S, et al.

    Nosocomial infections with Clostridium difficile are on the rise in the Unites States, attributed to emergence of antibiotic-resistant and hypervirulent strains associated with greater likelihood of recurrent infections. In addition to antibiotics, treatment with Merck anti-toxin B (TcdB) antibody bezlotoxumab is reported to reduce recurrent infections. However, treatment with anti-toxin A (TcdA) antibody actotoxumab was associated with dramatically increased disease severity and mortality rates in humans and gnotobiotic piglets. Using isogenic mutants of C. difficile strain NAPI/BI/027 deficient in TcdA (A−B+) or TcdB (A+B−), and the wild type, we investigated how and why treatment of infected animals with anti-TcdA dramatically increased disease severity. Contrary to the hypothesis, among piglets treated with anti-TcdA, those with A+B− infection were disease free, in contrast to the disease enhancement seen in those with wild-type or A−B+ infection. It seems that the lack of TcdA, through either deletion or neutralization with anti-TcdA, reduces a competitive pressure, allowing TcdB to freely exert its profound effect, leading to increased mucosal injury and disease severity.

    更新日期:2019-12-30
  • Tube Well Use as Protection Against Rotavirus Infection During the Monsoons in an Urban Setting
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-11-28
    Martinez P, Mahmud A, Yunus M, et al.

    Rotavirus, a diarrheal pathogen spread via fecal-oral transmission, is typically characterized by a winter incidence peak in most countries. Unlike for cholera and other waterborne infections, the role of sanitation and socioeconomic factors on the spatial variation of rotavirus seasonality remains unclear. In the current study, we analyzed their association with rotavirus seasonality, specifically the odds of monsoon cases, across 46 locations from 2001 to 2012 in Dhaka. Drinking water from tube wells, compared to other sources, has a clear protective effect against cases during the monsoon, when flooding and water contamination are more likely. This finding supports a significant environmental component of transmission.

    更新日期:2019-12-30
  • Matrix Metalloproteinase-13 in Atherosclerotic Plaque Is Increased by Influenza A Virus Infection
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-11-06
    Lee H, Noh J, Shin O, et al.

    BackgroundInfluenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. MethodsWe examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. ResultsWe confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. ConclusionsIn this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

    更新日期:2019-12-30
  • Risk of Severe Influenza Among Adults With Chronic Medical Conditions
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-11-04
    Walker T, Waite B, Thompson M, et al.

    BackgroundSevere influenza illness is presumed more common in adults with chronic medical conditions (CMCs), but evidence is sparse and often combined into broad CMC categories. MethodsResidents (aged 18–80 years) of Central and South Auckland hospitalized for World Health Organization-defined severe acute respiratory illness (SARI) (2012–2015) underwent influenza virus polymerase chain reaction testing. The CMC statuses for Auckland residents were modeled using hospitalization International Classification of Diseases, Tenth Revision codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity. ResultsAmong 891 276 adults, 2435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC, except for older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (incidence rate ratio [IRR] range, 4.84–13.4 across age strata), ESRD (IRR range, 3.30–9.02), CAD (IRR range, 2.77–10.7), and COPD (IRR range, 5.89–8.78) and tapered with age. ConclusionsOur findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared with those without these conditions.

    更新日期:2019-12-30
  • Corrigendum to: Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-29
    Ferreira L, Ferreira F, Nakaya H, et al.

    In this article, (“Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction” J Infect Dis, Volume 215, Issue 3, 1 February 2017, Pages 387–395, https://doi.org/10.1093/infdis/jiw540) Figure 4 has an error. The labels for validation of microarray results, depicting qRT-PCR assays of KIRD3S1 and PRF1 genes were inadvertently swapped. The correct KIR3DS1 and PRF1 qRT-PCR values are now depicted in the updated article online. This is in-line with Supplemental figure 1B, showing that KIR3DS1, and not PRF1, is the most discriminating gene between moderate and severe CCC.

    更新日期:2019-12-29
  • P. falciparum gametocyte density and infectivity in peripheral blood and skin tissue of naturally infected parasite carriers in Burkina Faso
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-26
    Meibalan E, Barry A, Gibbins M, et al.

    BackgroundPlasmodium falciparum transmission depends on mature gametocytes that can be ingested by mosquitoes taking a bloodmeal on human skin. Although gametocyte skin sequestration has long been hypothesized as important contributor to efficient malaria transmission, this has never been formally tested. MethodsIn naturally infected gametocyte carriers from Burkina Faso, we assessed infectivity to mosquitoes by direct skin feeding and membrane feeding. We directly quantified male and female gametocytes and asexual parasites in: i) finger prick blood, ii) venous blood, iii) skin biopsies, and in pools of mosquitoes that fed iv) on venous blood or, v) directly on skin. Gametocytes were visualized in skin tissue by confocal microscopy. ResultsWhilst more mosquitoes became infected when feeding directly on the skin compared to venous blood (odds ratio 2.01; 95% CI 1.21 – 3.33, p = 0.007), concentrations of gametocytes in the subdermal skin vasculature were not higher compared to other blood compartments; only sparse gametocytes were observed in skin tissue. DiscussionOur data strongly suggest that there is no significant skin sequestration of P. falciparumgametocytes. Gametocyte densities in peripheral blood are thus informative for predicting onward transmission potential to mosquitoes and can be used to target and monitor malaria elimination initiatives.

    更新日期:2019-12-27
  • Epidemiology and clinical outcomes of hospitalizations for acute respiratory or febrile illness and laboratory-confirmed influenza among pregnant women during six influenza seasons, 2010-2016
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-26
    Dawood F, , Garg S, et al.

    BackgroundPregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics. MethodsTo describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by RT-PCR in Australia, Canada, Israel and the United States during 2010-2016. ResultsOf 18,048 ARFI-coded hospitalizations, 1,064 (6%) included RT-PCR testing for influenza viruses, of which 614 (58%) were influenza-positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (IQR 1-4), 18% (95% confidence interval (CI) 15-21%) resulted in delivery, 10% (95% CI 8-12%) included a pneumonia diagnosis, 5% (95% CI 3-6%) required intensive care, 2% (95% CI 1-3%) included a sepsis diagnosis, and <1% (95% CI 0-1%) resulted in respiratory failure. ConclusionsOur findings characterize seasonal influenza hospitalizations among pregnant women and can inform assessments of the public health and economic impact of seasonal influenza on pregnant women.

    更新日期:2019-12-27
  • Screening Strategies for a Sustainable Endpoint for Gambiense Sleeping Sickness
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-26
    Castaño M, Aliee M, Mwamba Miaka E, et al.

    BackgroundGambiense human African trypanosomiasis ([gHAT] sleeping sickness) is a vector-borne disease that is typically fatal without treatment. Intensified, mainly medical-based, interventions in endemic areas have reduced the occurrence of gHAT to historically low levels. However, persistent regions, primarily in the Democratic Republic of Congo (DRC), remain a challenge to achieving the World Health Organization’s goal of global elimination of transmission (EOT). MethodsWe used stochastic models of gHAT transmission fitted to DRC case data and explored patterns of regional reporting and extinction. The time to EOT at a health zone scale (~100 000 people) and how an absence of reported cases informs about EOT was quantified. ResultsRegional epidemiology and level of active screening (AS) both influenced the predicted time to EOT. Different AS cessation criteria had similar expected infection dynamics, and recrudescence of infection was unlikely. However, whether EOT has been achieved when AS ends is critically dependent on the stopping criteria. Two or three consecutive years of no detected cases provided greater confidence of EOT compared with a single year (~66%–75% and ~82%–84% probability of EOT, respectively, compared with 31%–51%). ConclusionsMultiple years of AS without case detections is a valuable measure to assess the likelihood that the EOT target has been met locally.

    更新日期:2019-12-27
  • Chronic Disseminated Candidiasis During Hematological Maligancies: An Immune Reconstitution Inflammatory Syndrome with Expansion of Pathogen-Specific TH1 T Cells
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-27
    Candon S, Rammaert B, Foray A, et al.

    Chronic disseminated candidiasis (CDC) is a rare disease mostly occurring after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls (CANHPARI NCT01916057).Analysis of Candida-specific T cell responses using Elispot assays revealed higher numbers of IFNγ-producing T cells reactive to mp65 or candidin in 27 CDC cases as compared to 33 controls. Increased plasma levels of sCD25, IL-6, IL-1β, TNFα and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher level of CD4 and CD8 T cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ+Vδ2+ cells.The expansion of Candida-specific IFNγ-producing T cells together with features of T cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes (IRIS).

    更新日期:2019-12-27
  • Cryptosporidium parvum elongation factor 1α (CpEF1α) participates in the formation of base structure at the infection site during invasion
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-24
    Yu X, Guo F, Mouneimne R, et al.

    Cryptosporidium is a genus of apicomplexan parasites, the causative agents of cryptosporidiosis in humans and/or animals. While most apicomplexans parasitize within the host cell cytosols, Cryptosporidium resides on top of host cells, but embraced by a double-layer parasitophorous vacuole membrane (PVM) derived host cells. There is an electron-dense band to separate the parasite from host cell cytoplasm, making it as an intracellular, but extracytoplasmic parasite. In the present study, we discovered that a C. parvum translation elongation factor 1α (CpEF1α) was discharged from the invading sporozoites onto host cells, forming a crescent-shaped patch that fully resembles the electron-dense band. At the same time, host cell F-actin aggregated to form a globular shaped plug beneath the CpEF1α patch. The CpEF1α patch remained for most of the time, but became weakened and dissolved upon the completion of the invasion process. Additionally, recombinant CpEF1α protein could effectively interfere the invasion of sporozoites into host cells. These observations indicate that CpEF1α plays a role in the parasite invasion by participating in the formation of electron-dense band at the base of the parasite infection site.

    更新日期:2019-12-26
  • Dynamic, Helminth-Induced Immune Modulation Influences the Outcome of Acute and Chronic Hepatitis B Virus Infection
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-25
    Loffredo-Verde E, Bhattacharjee S, Malo A, et al.

    BackgroundChronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood. MethodsWe used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection. ResultsAlthough liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-γ secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the TH1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-γ-deficient or in TH2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV. ConclusionsThus, schistosome-induced IFN-γ had a prominent antiviral effect that outcompeted immunosuppressive effects of TH2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.

    更新日期:2019-12-26
  • Corrigendum to: Interventions in Live Poultry Markets for the Control of Avian Influenza: A Systematic Review and Meta-analysis
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-20
    Shi N, Huang J, Zhang X, et al.

    In “Interventions in Live Poultry Markets for the Control of Avian Influenza: A Systematic Review and Meta-analysis” by Shi et al [J Infect Dis 2019; https://doi.org/10.1093/infdis/jiz372], there was an error in a grant number. In the financial support section, this grant should read “Science Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention (grant numbers BE2015714, BE2017749).”

    更新日期:2019-12-23
  • Loss of Pre-Existing Immunological Memory among HIV Infected Women Despite Immune Reconstitution with Antiretroviral Therapy
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-23
    Thomas A, Hammarlund E, Gao L, et al.

    BackgroundIt is unclear if HIV infection results in permanent loss of T cell memory or if it impacts pre-existing antibodies to childhood vaccinations/infections. MethodsWe conducted a matched cohort study involving 50 pairs of HIV+ and HIV- women. Total memory T cell responses were measured after anti-CD3 stimulation or after vaccinia virus stimulation to measure T cells elicited after childhood smallpox vaccination. Vaccinia-specific antibodies were measured by ELISA. ResultsThere was no difference between HIV+ and HIV- subjects in terms of CD4+ T cell responses after anti-CD3 stimulation (P=0.19) although HIV+ subjects had significantly higher CD8+ T cell responses (P=0.033). In contrast, there was a significant loss in vaccinia-specific CD4+ T cell memory among HIV+ subjects (P=0.039) whereas antiviral CD8+ T cell memory remained intact (P=1.0). Vaccinia-specific antibodies were maintained indefinitely among HIV- subjects (half-life; infinity, 95%CI, 309 years-infinity) but declined rapidly among HIV+ subjects (half-life; 39 years, 95%CI, 24-108 years, P=0.001). ConclusionsDespite ART-associated improvement in CD4+ T cell counts (nadir CD4 <200 cells/mm3 with >350 cells/mm3 after ART), antigen-specific CD4+ T cell memory to vaccinations/infections that occurred before HIV infection did not recover after immune reconstitution and a previously unrealized decline in pre-existing antibody responses was observed.

    更新日期:2019-12-23
  • Elimination or Resurgence: Modelling Lymphatic Filariasis After Reaching the 1% Microfilaremia Prevalence Threshold
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-19
    Prada J, Davis E, Touloupou P, et al.

    The low prevalence levels associated with lymphatic filariasis elimination pose a challenge for effective disease surveillance. As more countries achieve the World Health Organization criteria for halting mass treatment and move on to surveillance, there is increasing reliance on the utility of transmission assessment surveys (TAS) to measure success. However, the long-term disease outcomes after passing TAS are largely untested. Using 3 well-established mathematical models, we show that low-level prevalence can be maintained for a long period after halting mass treatment and that true elimination (0% prevalence) is usually slow to achieve. The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (<5 years), it can still occur outside of the currently recommended postintervention surveillance period of 4–6 years. Our results highlight the need for ongoing and enhanced postintervention monitoring, beyond the scope of TAS, to ensure sustained success.

    更新日期:2019-12-20
  • Assessing the Efficacy and Safety of Liposomal Amphotericin B and Miltefosine in Combination for Treatment of Post Kala-Azar Dermal Leishmaniasis
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-19
    Ramesh V, Dixit K, Sharma N, et al.

    BackgroundNo satisfactory canonical treatment is available for post-kala-azar dermal leishmaniasis (PKDL), clinical sequela of visceral leishmaniasis. Confined treatment options and substantial increase in relapse rate after miltefosine (MIL) treatment warrant the need to adapt resilient combination therapies. In this study, we assessed the safety and efficacy of combination therapy using liposomal amphotericin B (LAmB) and MIL for treating PKDL. MethodsThirty-two PKDL patients, confirmed by microscopy or quantitative polymerase chain reaction (qPCR), were included in the study. An equal number of cases (n = 16) were put on MIL monotherapy (100 mg/day for 90 days) or MIL and LAmB combination for 45 days (3 injections of LAmB, 5 mg/kg body weight, and 100 mg/day MIL). Parasite load in slit aspirate was monitored using qPCR. ResultsPatients treated with combination therapy demonstrated a rapid decline in parasite load and achieved 100% cure, with no reports of relapse. Those treated with MIL monotherapy attained clinical cure with a gradual decrease in parasite load; however, 25% relapsed within 18 months of follow-up. ConclusionsLiposomal amphotericin B and MIL combination for treating PKDL is efficacious and safe, with high tolerability. Furthermore, this study established the utility of minimally invasive slit aspirate method for monitoring of parasite load and assessment of cure in PKDL.

    更新日期:2019-12-20
  • Ebola Patient Virus Cycle Threshold and Risk of Household Transmission of Ebola Virus
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-19
    Reichler M, Bruden D, Thomas H, et al.

    BackgroundIdentifying risk factors for household transmission of Ebola virus (EBOV) is important to guide preventive measures during Ebola outbreaks. MethodsWe enrolled all confirmed persons with EBOV disease who were the first case patient in a household from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index patients and contacts were interviewed, and contacts were followed up for 21 days to identify secondary cases. Epidemiologic data were linked to EBOV real-time reverse-transcription polymerase chain reaction cycle threshold (Ct) data from initial diagnostic specimens obtained from enrolled index case patients. ResultsCt data were available for 106 (71%) of 150 enrolled index patients. Of the Ct results, 85 (80%) were from blood specimens from live patients and 21 (20%) from oral swab specimens from deceased patients. The median Ct values for blood and swab specimens were 21.0 and 24.0, respectively (P = .007). In multivariable analysis, a Ct value from blood specimens in the lowest quintile was an independent predictor of both increased risk of household transmission (P = .009) and higher secondary attack rate among household contacts (P = .03), after adjustment for epidemiologic factors. ConclusionsOur findings suggest the potential to use Ct values from acute EBOV diagnostic specimens for index patients as an early predictor of high-risk households and high-risk groups of contacts to help prioritize EBOV disease investigation and control efforts.

    更新日期:2019-12-20
  • Persistence of Immune responses with an Inactivated Japanese Encephalitis single-dose vaccine JENVAC® and interchangeability with a live-attenuated vaccine
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-20
    Vadrevu K, Potula V, Khalatkar V, et al.

    BackgroundThis study reports immunogenicity, safety and interchangeability of a single dose, inactivated Vero-cell derived, JENVAC® to the live attenuated SA 14-14-2 vaccine in healthy children. MethodsThis phase 4, multicentre, open-label, randomized control trial enrolled 360 children who were equally randomized to receive a single dose of either JENVAC® or SA 14-14-2. Children were followed at various time points, until two years (day 720) post-vaccination, upon which a subset from each group was divided and allocated to a receive a booster dose or the other vaccine. ResultsAt all time points, immunological measures were statistically higher in the JENVAC® group. In the inter-changeability study, children receiving two doses of JENVAC® reported significantly higher response compared to two doses of SA 14-14-2. No difference in adverse events was observed. These corroborate with excellent seroprotection post the first dose of an earlier JENVAC® study. ConclusionsA single dose vaccination with JENVAC® induces protective titres that persist up to one year. We report appreciable interchangeability between both vaccines, with JENVAC®/JENVAC® combination exhibiting the highest immune response. JENVAC® is now licensed as a single dose JE vaccine. Clinical Trials Registration(CTRI/2014/02/004386 and CTRI/2016/05/006909)

    更新日期:2019-12-20
  • Potential impact and cost-effectiveness of condomless-sex-concentrated PrEP in KwaZulu-Natal accounting for drug resistance
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-18
    Phillips A, Cambiano V, Johnson L, et al.

    IntroductionOral pre-exposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation. MethodsWe calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (i) PrEP availability for adolescent-girls-and-young-women (aged 15-24; AGYW) and female sex workers (FSW), and (ii) availability for everyone aged 15-64. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programmes. ResultsIn the context of PrEP use in adults aged 15-64 there was a predicted 33% reduction in incidence, and 36% reduction in women aged 15-24. PrEP was cost effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance. ConclusionsPrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective.

    更新日期:2019-12-19
  • Control of Nipah Virus Infection in Mice by the Host Adaptors Mitochondrial Antiviral Signaling Protein (MAVS) and Myeloid Differentiation Primary Response 88 (MyD88)
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-19
    Iampietro M, Aurine N, Dhondt K, et al.

    Interferon (IFN) type I plays a critical role in the protection of mice from lethal Nipah virus (NiV) infection, but mechanisms responsible for IFN-I induction remain unknown. In the current study, we demonstrated the critical role of the mitochondrial antiviral signaling protein signaling pathway in IFN-I production and NiV replication in murine embryonic fibroblasts in vitro, and the redundant but essential roles of both mitochondrial antiviral signaling protein and myeloid differentiation primary response 88 adaptors, but not TRIF (Toll/Interleukin-1 receptor/Resistance [TIR] domain–containing adaptor–inducing IFN-β), in the control of NiV infection in mice. These results reveal potential novel targets for antiviral intervention and help in understanding NiV immunopathogenesis.

    更新日期:2019-12-19
  • Large Fecal Reservoir of Escherichia coli Sequence Type 131-H30 Subclone Strains that Are Shared within Households and Resemble Clinical ST131-H30 Isolates
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-18
    Mohamed M, Clabots C, Porter S, et al.

    BackgroundEmerging antimicrobial-resistant Escherichia coli represent mainly the nested (fluoroquinolone-resistant [FQR]) H30R and H30Rx subclones within sequence type 131 (ST131). Intestinal colonization and within-household transmission may underlie H30R's emergence. MethodsWe screened fecal samples from 741 volunteers (383 veterans, 358 household members [including pets]) for ST131 and FQR E. coli (FQREC) and used molecular profiling to resolve unique strains. Selected strains underwent PCR-based detection of phylogroups, sequence types (STs), H30, H30Rx, and 53 virulence genes (VGs). Within-household strain sharing was compared with household, host, and bacterial characteristics. Fecal isolates were compared with clinical isolates. ResultsColonization prevalence was 5.1% for H30R, 8% for ST131 (67% FQREC), and 10% for FQREC (52% ST131). ST131 isolates exhibited more VGs than non-ST131 isolates. Strain sharing (27% of multi-subject households, 18% of corresponding subjects) was associated with the elderly, FQREC, H30R, H30Rx, ST73, and specific VGs. Fecal ST131 and FQREC isolates resembled contemporaneous and historical clinical isolates according to all studied traits. ConclusionsVeterans and their human household members commonly carry and extensively share FQREC, predominantly H30R, thereby likely facilitating the ST131 pandemic. Strain sharing corresponds with multiple bacterial characteristics, including FQ resistance and specific VGs, which may promote intestinal colonization and/or host-to-host transmission.

    更新日期:2019-12-19
  • Factors Associated with ART Re-Initiation in Medicaid Recipients with HIV
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-16
    Zhang T, Wilson I, Youn B, et al.

    ObjectivesTo examine patient characteristics associated with ART re-initiation in Medicaid enrollees. MethodsThis is a retrospective cohort study, using Cox proportional hazard regression to examine the association between person-level characteristics and time from ART discontinuation to the subsequent re-initiation within 18 months. ResultsThere were 45,409 patients who discontinued ART, and 44% failed to re-initiate. More outpatient visits (3+ vs. 0 outpatient visits: adjHR 1.56; 1.45-1.67) and hospitalization (adjHR 1.18; 1.16-1.20) during follow-up were associated with re-initiation. ConclusionsFailure to re-initiate ART within 18 months was common in this sample. Care engagement was associated with greater ART re-initiation.

    更新日期:2019-12-17
  • Men and women have an equal oropharyngeal and anorectal Chlamydia trachomatis bacterial load: a comparison of three anatomic sites
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-16
    Wijers J, Dukers-Muijrers N, van Liere G, et al.

    BackgroundThe Chlamydia trachomatis(CT) bacterial load could have impact on transmission and sequelae. This is the first study to date providing a comparison of the CT bacterial load of all three anatomic sites estimated by cycle quantification (Cq) values. MethodsLaboratory data from 7,900 CT positive samples were included (2012-2018). The Cq value was used as an inversely proportional measure for CT load. Multivariable linear regression analyses were used to assess differences in mean Cq values per sample type. ResultsVaginal swabs had the lowest Cq values (31.0) followed by urine samples (32.5), anorectal swabs (34.0) and oropharyngeal swabs (36.8) (P<0.001). Men and women had similar oropharyngeal (36.4vs.37.3;p=0.13) and anorectal (34.2vs.33.9;P=0.19) Cq values. Men (32.2) and women (30.7) aged <25 years had lower urogenital Cq values than men (32.8) and women (31.9) aged ≥25 years (P<0.001). HIV positive patients (33.8) had higher urogenital Cq values than HIV negative patients (32.6) (P<0.03). ConclusionsMen and women have a similar CT load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and patients co-infected with HIV had a lower CT load suggesting exposure to previous CT infections potentially leading to some partial immunity reducing CT load.

    更新日期:2019-12-17
  • Impact of Changes in Detection Effort on Control of Visceral Leishmaniasis in the Indian Subcontinent
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-16
    Coffeng L, Le Rutte E, Muñoz J, et al.

    BackgroundControl of visceral leishmaniasis (VL) on the Indian subcontinent relies on prompt detection and treatment of symptomatic cases. Detection efforts influence the observed VL incidence and how well it reflects the underlying true incidence. As control targets are defined in terms of observed cases, there is an urgent need to understand how changes in detection delay and population coverage of improved detection affect VL control. MethodsUsing a mathematical model for transmission and control of VL, we predict the impact of reduced detection delays and/or increased population coverage of the detection programs on observed and true VL incidence and mortality. ResultsImproved case detection, either by higher coverage or reduced detection delay, causes an initial rise in observed VL incidence before a reduction. Relaxation of improved detection may lead to an apparent temporary (1 year) reduction in VL incidence, but comes with a high risk of resurging infection levels. Duration of symptoms in detected cases shows an unequivocal association with detection effort. ConclusionsVL incidence on its own is not a reliable indicator of the performance of case detection programs. Duration of symptoms in detected cases can be used as an additional marker of the performance of case detection programs.

    更新日期:2019-12-17
  • A praziquantel treatment study of immune and transcriptome profiles in Schistosoma haematobium-infected Gabonese schoolchildren
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-12-17
    Labuda L, Adegnika A, Rosa B, et al.

    Schistosoma infection has been associated with altered immune function, including hyporesponsiveness. S. haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared to uninfected controls. Cellular responses were characterised by cytokine production and flow cytometry, and in a subset of children RNA-Seq transcriptome profiling performed. Removal of S. haematobium infection resulted in increased schistosome-specific cytokine responses which were negatively associated with CD4+CD25+FOXP3+ T cells and accompanied by increased frequency of effector memory T cells. Innate responses to TLR ligation decreased with treatment and showed positive association with CD4+CD25+FOXP3+ T cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, while parasite removal with a more quiescent profile. Further analysis indicated alteration in cellular energy metabolism to be associated with S. haematobium infection and that EGR2 and EGR3, transcription factors which negatively regulate T cell activation, may play a role in adaptive immune hyporesponsiveness.

    更新日期:2019-12-17
  • The Effect of Influenza Vaccination History on Changes in Hemagglutination Inhibition Titers After Receipt of the 2015–2016 Influenza Vaccine in Older Adults in Hong Kong
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-07-06
    Ng T, Perera R, Fang V, et al.

    BackgroundImmune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same. MethodsAn observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015–2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160. ResultsParticipants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160. ConclusionsOverall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.

    更新日期:2019-12-17
  • Survivors of Ebola Virus Disease Develop Polyfunctional Antibody Responses
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-07-12
    Gunn B, Roy V, Karim M, et al.

    Monoclonal antibodies can mediate protection against Ebola virus (EBOV) infection through direct neutralization as well as through the recruitment of innate immune effector functions. However, the antibody functional response following survival of acute EBOV disease has not been well characterized. In this study, serum antibodies from Ebola virus disease (EVD) survivors from Sierra Leone were profiled to capture variation in overall subclass/isotype abundance, neutralizing activity, and innate immune effector functions. Antibodies from EVD survivors exhibited robust innate immune effector functions, mediated primarily by IgG1 and IgA1. In conclusion, development of functional antibodies follows survival of acute EVD.

    更新日期:2019-12-17
  • Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-07-27
    Lartey S, Zhou F, Brokstad K, et al.

    BackgroundInfluenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. MethodsWe collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. ResultsWe report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. ConclusionsOur data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

    更新日期:2019-12-17
  • Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on the Fitness of Contemporary Influenza A(H1N1)pdm09 and A(H3N2) Strains
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-16
    Checkmahomed L, M’hamdi Z, Carbonneau J, et al.

    BackgroundBaloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence. MethodsInfluenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR. ResultsI38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50%:50% mixture evolved to 70%:30% (WT/mutant) for A(H1N1) and 88%:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments. ConclusionThe fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.

    更新日期:2019-12-17
  • Tuberculosis Antigen-Specific T-Cell Responses During the First 6 Months of Antiretroviral Treatment
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-17
    Riou C, Jhilmeet N, Rangaka M, et al.

    The reconstitution of Mycobacterium tuberculosis antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in a high tuberculosis endemic area is described. Restoration of the antigen-specific CD4 T-cell subsets mirrored the overall CD4 T-cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known M. tuberculosis sensitization determined by interferon-γ release assay, 12/23 participants had no M. tuberculosis-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T-cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.

    更新日期:2019-12-17
  • Micronutrients, Immunological Parameters, and Dengue Virus Infection in Coastal Ecuador: A Nested Case-Control Study in an Infectious Disease Surveillance Program
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-20
    Finkelstein J, Colt S, Layden A, et al.

    BackgroundMicronutrients are known to modulate host immunity, and there is limited literature on this association in the context of dengue virus infection (DENV). MethodsUsing a nested case-control design in a surveillance program, we measured the following: anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers. We then compared these measures across 4 illness categories: healthy control, nonfebrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models. ResultsAmong 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (odds ratio [OR], 2.66; confidence interval [CI], 1.53–4.62; P = .001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR, 0.03; CI, 0.00–0.30; P = .003) and OFI (OR, 0.02; CI, 0.00–0.24; P = .003). In a subset of 71 participants, interleukin-15 levels (median fluorescent intensity) were positively associated with apparent DENV (OR, 1.09; CI, 1.03–1.14; P = .001) and negatively associated with nonfebrile DENV (OR, 0.89; CI, 0.80–0.99; P = .03) compared to healthy controls. ConclusionsAfter adjusting for the acute-phase response, serum ferritin and RBP concentrations were associated with apparent DENV and may represent biomarkers of clinical importance in the context of dengue illness.

    更新日期:2019-12-17
  • Cervical Intraepithelial Neoplasia Rates in British Columbia Women: A Population-Level Data Linkage Evaluation of the School-Based HPV Immunization Program
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-23
    Racey C, Albert A, Donken R, et al.

    BackgroundTo understand real-world human papillomavirus (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 women in British Columbia, Canada. MethodsData linkage was performed using records from provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV-vaccinated women born 1994–2005. Incidence rate, relative rate (RR), and vaccine effectiveness (VE), using unadjusted and adjusted Poisson regression of cytology (HSIL) and histopathology (CIN2, CIN3, and CIN2+) outcomes, were compared across vaccination status groups. ResultsWomen who received a complete series of vaccine on schedule between age 9 and 14 years had an adjusted RR = 0.42 (95% confidence interval [CI], 0.31–0.57) for CIN2+ over 7 years of follow-up compared to unvaccinated women, resulting in a VE of 57.9% (95% CI, 43.2%–69.0%). Adjusted RR for HSIL was 0.53 (95% CI, .43–.64), resulting in a VE of 47.1% (95% CI, 35.6%–56.7%). ConclusionWomen vaccinated against HPV have a lower incidence of cervical dysplasia compared to unvaccinated women. Immunization between 9 and 14 years of age should be encouraged. Continued program evaluation is important for measuring long-term population impact.

    更新日期:2019-12-17
  • Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus
    J. Infect. Dis. (IF 5.045) Pub Date : 2019-08-23
    Isnard S, Ramendra R, Dupuy F, et al.

    BackgroundRegenerating 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 living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. MethodsPlasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)–uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. ResultsCross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH. ConclusionsPlasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.

    更新日期:2019-12-17
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