| 1. |
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| 2. |
- Ali, Abukar, 1988, et al.
(författare)
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CTLA4-Ig but not anti-TNF therapy promotes staphylococcal septic arthritis in mice.
- 2015
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:8, s. 1308-1316
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Tidskriftsartikel (refereegranskat)abstract
- The development of biologics has greatly increased the quality of life as well as the life expectancy of many RA patients. However, a large number of these patients are at an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-TNF versus CTLA4-Ig treatment on both immunological response and host defense in a murine model of septic arthritis.
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| 3. |
- Alkaitis, Matthew S., et al.
(författare)
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Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria
- 2016
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 214:12, s. 1840-1849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion.METHODS: We used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene. Heavy isotope-labeled tracers measured by quadrupole time-of-flight liquid chromatography-mass spectrometry were used to quantify the in vivo rate of appearance and interconversion of plasma arginine, ornithine, and citrulline in infected mice.RESULTS: Children with cerebral malaria and P. berghei-infected mice demonstrated depletion of plasma arginine, ornithine, and citrulline. Knock out of Plasmodium arginase did not alter arginine depletion in infected mice. Metabolic tracer analysis demonstrated that plasma arginase flux was unchanged by P. berghei infection. Instead, infected mice exhibited decreased rates of plasma arginine, ornithine, and citrulline appearance and decreased conversion of plasma citrulline to arginine. Notably, plasma arginine use by nitric oxide synthase was decreased in infected mice.CONCLUSIONS: Simultaneous arginine and ornithine depletion in malaria parasite-infected children cannot be fully explained by plasma arginase activity. Our mouse model studies suggest that plasma arginine depletion is driven primarily by a decreased rate of appearance.
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| 4. |
- Anantharajah, Ahalieyah, et al.
(författare)
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Inhibition of the injectisome and flagellar type III secretion systems by INP1855 impairs Pseudomonas aeruginosa pathogenicity and inflammasome activation
- 2016
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 214:7, s. 1105-1116
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Tidskriftsartikel (refereegranskat)abstract
- With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent inflammasome activation, which induces interleukin 1 beta (IL-1 beta) release and reduces interleukin 17 (IL-17) production and bacterial clearance. fT3SS ensures bacterial motility, attachment to the host cells, and triggers inflammation. INP1855 is an iT3SS inhibitor identified by in vitro screening, using Yersinia pseudotuberculosis. Using a mouse model of P. aeruginosa pulmonary infection, we show that INP1855 improves survival after infection with an iT3SS-positive strain, reduces bacterial pathogenicity and dissemination and IL-1 beta secretion, and increases IL-17 secretion. INP1855 also modified the cytokine balance in mice infected with an iT3SS-negative, fT3SS-positive strain. In vitro, INP1855 impaired iT3SS and fT3SS functionality, as evidenced by a reduction in secretory activity and flagellar motility and an increase in adenosine triphosphate levels. As a result, INP1855 decreased cytotoxicity mediated by toxins and by inflammasome activation induced by both laboratory strains and clinical isolates. We conclude that INP1855 acts by dual inhibition of iT3SS and fT3SS and represents a promising therapeutic approach.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Berg, Aase, et al.
(författare)
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Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria
- 2015
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Ingår i: The Internet Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1528-8366 .- 0022-1899 .- 1537-6613. ; 212:11, s. 1835-1840
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Tidskriftsartikel (refereegranskat)abstract
- The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent.
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| 10. |
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| 11. |
- Birse, Kenzie D., et al.
(författare)
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Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices
- 2017
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 215:4, s. 590-598
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Tidskriftsartikel (refereegranskat)abstract
- Background. Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods. Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results. We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P =.009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions. These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.
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| 12. |
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| 13. |
- Burbelo, P. D., et al.
(författare)
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Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 217:7, s. 1024-1032
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Methods Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Results Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P >.0001) and blood antibodies by 7-fold (P =.0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. Conclusions To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.
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| 14. |
- Carey, Alison J., et al.
(författare)
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Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection
- 2016
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 213:4, s. 659-668
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Tidskriftsartikel (refereegranskat)abstract
- Background. CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods. We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14-/- mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results. UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14-/- mice. Exacerbation of infection in Cd14-/- mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions. This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.
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| 15. |
- Chauhan, SB, et al.
(författare)
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Interleukin 2 is an Upstream Regulator of CD4+ T Cells From Visceral Leishmaniasis Patients With Therapeutic Potential
- 2019
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 220:1, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- Control of visceral leishmaniasis (VL) caused by Leishmania donovani requires interferon-γ production by CD4+ T cells. In VL patients, antiparasitic CD4+ T-cell responses are ineffective for unknown reasons. In this study, we measured the expression of genes associated with various immune functions in these cells from VL patients and compared them to CD4+ T cells from the same patients after drug treatment and from endemic controls. We found reduced GATA3, RORC, and FOXP3 gene expression in CD4+ T cells of VL patients, associated with reduced Th2, Th17, and FOXP3+CD4+ T regulatory cell frequencies in VL patient blood. Interleukin 2 (IL-2) was an important upstream regulator of CD4+ T cells from VL patients, and functional studies demonstrated the therapeutic potential of IL-2 for improving antiparasitic immunity. Together, these results provide new insights into the characteristics of CD4+ T cells from VL patients that can be used to improve antiparasitic immune responses.
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| 16. |
- Connolly-Andersen, Anne-Marie, et al.
(författare)
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Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients
- 2015
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 212:7, s. 1061-1069
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Tidskriftsartikel (refereegranskat)abstract
- Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.
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| 17. |
- Cook, Jackie, et al.
(författare)
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Mass Screening and Treatment on the Basis of Results of a Plasmodium falciparum-Specific Rapid Diagnostic Test Did Not Reduce Malaria Incidence in Zanzibar
- 2015
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Ingår i: The Internet Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1528-8366 .- 0022-1899 .- 1537-6613. ; 211:9, s. 1476-1483
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission.METHODS: Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission.RESULTS: Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas.CONCLUSIONS: Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase.
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| 18. |
- Cunningham, Anthony L., et al.
(författare)
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Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:11, s. 1750-1760
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Tidskriftsartikel (refereegranskat)abstract
- Background. The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01(B) Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods. Participants (ZOE-50: >= 50; ZOE-70: >= 70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing >= 2 of 4 activation markers assessed (CD4(2+)) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results. After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD4(2+) T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained >= 5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.
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| 19. |
- Depledge, D. P., et al.
(författare)
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High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:10, s. 1592-1601
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Tidskriftsartikel (refereegranskat)abstract
- Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.
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| 20. |
- Edén, Arvid, 1975, et al.
(författare)
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Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 214:12, s. 1822-1825
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Tidskriftsartikel (refereegranskat)abstract
- We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips.
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| 21. |
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| 22. |
- Elkington, Paul, et al.
(författare)
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In Vitro Granuloma Models of Tuberculosis: Potential and Challenges
- 2019
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Ingår i: Journal of Infectious Diseases. - : OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 219:12, s. 1858-1866
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Forskningsöversikt (refereegranskat)abstract
- Despite intensive research efforts, several fundamental disease processes for tuberculosis (TB) remain poorly understood. A central enigma is that host immunity is necessary to control disease yet promotes transmission by causing lung immunopathology. Our inability to distinguish these processes makes it challenging to design rational novel interventions. Elucidating basic immune mechanisms likely requires both in vivo and in vitro analyses, since Mycobacterium tuberculosis is a highly specialized human pathogen. The classic immune response is the TB granuloma organized in three dimensions within extracellular matrix. Several groups are developing cell culture granuloma models. In January 2018, NIAID convened a workshop, entitled "3-D Human in vitro TB Granuloma Model" to advance the field. Here, we summarize the arguments for developing advanced TB cell culture models and critically review those currently available. We discuss how integrating complementary approaches, specifically organoids and mathematical modeling, can maximize progress, and conclude by discussing future challenges and opportunities.
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| 23. |
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| 24. |
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| 25. |
- Franck, Kristina Træholt, et al.
(författare)
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Norovirus Genotypes in Hospital Settings - Differences between Nosocomial and Community-Acquired Infections.
- 2015
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:6, s. 881-888
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Tidskriftsartikel (refereegranskat)abstract
- Norovirus is a major cause of gastroenteritis and hospital outbreaks, leading to substantial morbidity and direct healthcare expenses as well as indirect societal costs. The aim of the study was to estimate the proportion of nosocomial norovirus infections among inpatients tested positive for norovirus in Denmark, 2002-2010, and to study the distribution of norovirus genotypes among inpatients with nosocomial and community-acquired norovirus infections, respectively.
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| 26. |
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| 27. |
- Geremariam Welearegay, Tesfalem, et al.
(författare)
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Diagnosis of Human Echinococcosis via Exhaled Breath Analysis : A Promise for Rapid Diagnosis of Infectious Diseases Caused by Helminths
- 2019
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 219:1, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human echinococcosis is a neglected infectious disease affecting more than 1 million people globally. Its diagnosis is expensive and difficult because of lack of adequate resources in low-resource locations, where most cases occur.Methods: A group of volunteers diagnosed with the 2 main types of echinococcosis and corresponding control groups were recruited from hospitals in Tunisia (32 patients with cystic echinococcosis and 43 controls) and Poland (16 patients with alveolar echinococcosis and 8 controls). Breath samples were collected from all patients and analyzed by gas chromatography coupled to mass spectrometry, and a specifically developed electronic nose system.Results: The chemical analysis revealed statistically different concentrations of 2 compounds in the breath of patients with cystic echinococcosis compared to controls, and statistically different concentrations of 7 compounds in the breath of patients with alveolar echinococcosis compared to controls. The discrimination accuracy achieved by the electronic nose system was 100% for cystic echinococcosis and 92.9% for alveolar echinococcosis, while the discrimination accuracy between these 2 patient groups was 92.1%.Conclusion: Here we advocate a noninvasive, fast, easy-to-operate and nonexpensive diagnostic tool for the diagnosis of human echinococcosis disease through exhaled breath analysis, suitable for early diagnosis and population screening.
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| 28. |
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| 29. |
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| 30. |
- Goncalves, Adriana, et al.
(författare)
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Innovative and New Approaches to Laboratory Diagnosis of Zika and Dengue : A Meeting Report
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:7, s. 1060-1068
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Tidskriftsartikel (refereegranskat)abstract
- Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostic tools to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostic tools, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programs. The rate-limiting step to bringing new diagnostic tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory-response consortium for flaviviruses with a decentralized biobank of well-characterized samples to facilitate assay validation. Access to proficiency panels are needed to ensure quality control, in additional to in-country capacity building.
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| 31. |
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| 32. |
- Howard, Jennifer, et al.
(författare)
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The Antigen-Presenting Potential of V gamma 9V delta 2 T Cells During Plasmodium falciparum Blood-Stage Infection
- 2017
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 215:10, s. 1569-1579
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Tidskriftsartikel (refereegranskat)abstract
- During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human V gamma 9V delta 2 T cells can act in vitro as antigen-presenting cells (APCs) and induce alpha beta T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because V gamma 9V delta 2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P. falciparum-infected patients, V gamma 9V delta 2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, V gamma 9V delta 2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive alpha beta T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8(+) T cells. Our findings qualify V gamma 9V delta 2 T cells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.
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| 33. |
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| 34. |
- Ivaska, LE, et al.
(författare)
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No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients
- 2019
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 220:4, s. 589-593
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Tidskriftsartikel (refereegranskat)abstract
- Human bocavirus 1 (HBoV1) can persist in nasopharynx and tonsils. Using HBoV1 serology, reverse-transcription polymerase chain reaction (PCR) for detecting messenger RNA (mRNA) and quantitative PCR for HBoV1 genome load count, we studied to what extent the HBoV1 DNA loads in nasopharynx correlate with acute infection markers. Tonsillar tissue, nasopharyngeal aspirate, and serum were obtained from 188 elective adeno-/tonsillectomy patients. Relatively high loads of HBoV1 DNA were detected in the nasopharynx of 14 (7%) primarily asymptomatic subjects with negative mRNA and/or serodiagnostic results. Quantitative HBoV1 DNA PCR may have lower specificity than HBoV1 mRNA detection for diagnosing symptomatic infection.
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| 35. |
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| 36. |
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| 37. |
- Kubler, Andre, et al.
(författare)
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Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis
- 2016
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 213:4, s. 618-627
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Tidskriftsartikel (refereegranskat)abstract
- Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).
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| 38. |
- Kwiecinski, Jakub, 1985, et al.
(författare)
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Staphylokinase controls Staphylococcus aureus biofilm formation and detachment through host plasminogen activation.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 213:1, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In this study, we investigated the contribution of fibrin and staphylokinase to biofilm formation. Both in clinical S. aureus isolates and in laboratory strains, high staphylokinase-producing strains formed less biofilm than strains that lacked staphylokinase, suggesting that staphylokinase prevents biofilm formation. Additionally, staphylokinase induced detachment of mature biofilms. This effect depended on plasminogen activation by staphylokinase. Host-derived fibrin, the main substrate cleaved by staphylokinase-activated plasminogen, was a major component of biofilm matrix and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Staphylokinase also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for staphylokinase-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.
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| 39. |
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| 40. |
- Luna, Brian, et al.
(författare)
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In Vivo Prediction of Tuberculosis-Associated Cavity Formation in Rabbits
- 2015
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 211:3, s. 481-485
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Tidskriftsartikel (refereegranskat)abstract
- The presence of cavitary lesions in patients with tuberculosis poses a significant clinical concern due to the risk of infectivity and the risk of antibiotic treatment failure. We describe 2 algorithms that use noninvasive positron emission tomography (PET) and computed tomography (CT) to predict the development of cavitary lesions in rabbits. Analysis of the PET region of interest predicted cavitary disease with 100% sensitivity and 76% specificity, and analysis of the CT region of interest predicted cavitary disease with 83.3% sensitivity and 76.9% specificity. Our results show that restricting our analysis to regions with high [(18)F]-fluorodeoxyglucose uptake provided the best combination of sensitivity and specificity.
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| 41. |
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| 42. |
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| 43. |
- Na, Manli, et al.
(författare)
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Lack of Receptor for Advanced Glycation End products leads to less severe staphylococcal skin infection but more skin abscesses and prolonged wound healing.
- 2018
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 218:5, s. 791-800
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Tidskriftsartikel (refereegranskat)abstract
- Lack of Receptor for Advanced Glycation End products (RAGE) ameliorates several infections including Staphylococcus aureus (S. aureus) pneumonia. We sought to investigate the role of RAGE in staphylococcal skin infection in mice.Wild-type (WT) and RAGE deficient (RAGE-/-) mice were subcutaneously inoculated with S. aureus SH1000 strain in abscess forming dose or necrotic dose. Clinical signs of dermatitis, along with histopathological changes, were compared between the groups.The skin lesion size was smaller in RAGE-/- mice. Infected RAGE-/- mice expressed lower pro-inflammatory cytokines in local skins compared to control mice. Low dose of bacteria caused more abscess formation in RAGE-/- mice compared to skin necrosis that was more often observed in WT mice. As a result of more abscess formation, the wound healing was prolonged in RAGE-/- mice. Importantly, RAGE-/- mice had lower bacterial loads in the skin than controls, which is correlated with higher local levels of myeloperoxidase before skin infection. In vitro, enhanced phagocytic capacity of neutrophils and macrophages obtained from RAGE-/- mice compared to control mice was observed.RAGE deficiency up-regulates phagocytic capacity of phagocytes, resulting in lower bacterial burden in local skin and milder skin lesions in mice with staphylococcal skin infection.
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| 44. |
- Nathavitharana, RR, et al.
(författare)
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Guidance for Studies Evaluating the Accuracy of Tuberculosis Triage Tests
- 2019
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 220:220 Suppl 3, s. S116-S125
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 3.6 million cases of active tuberculosis (TB) go potentially undiagnosed annually, partly due to limited access to confirmatory diagnostic tests, such as molecular assays or mycobacterial culture, in community and primary healthcare settings. This article provides guidance for TB triage test evaluations. A TB triage test is designed for use in people with TB symptoms and/or significant risk factors for TB. Triage tests are simple and low-cost tests aiming to improve ease of access and implementation (compared with confirmatory tests) and decrease the proportion of patients requiring more expensive confirmatory testing. Evaluation of triage tests should occur in settings of intended use, such as community and primary healthcare centers. Important considerations for triage test evaluation include study design, population, sample type, test throughput, use of thresholds, reference standard (ideally culture), and specimen flow. The impact of a triage test will depend heavily on issues beyond accuracy, primarily centered on implementation.
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| 45. |
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| 46. |
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| 47. |
- Pettersson-Kymmer, Ulrika, et al.
(författare)
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HLA and KIR Associations of Cervical Neoplasia
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 218:12, s. 2006-2015
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB3*9901 (OR=1.24, P=2.49×10-9), HLA-DRB5*0101 (OR=1.29, P=2.26×10-8), HLA-DRB5*9901 (OR=0.77, P=1.90×10-9) and HLA-DRB3*0301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
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| 48. |
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| 49. |
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| 50. |
- Rahimy, Elham, et al.
(författare)
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Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.
- 2017
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 215:7, s. 1132-1140
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Tidskriftsartikel (refereegranskat)abstract
- We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART).The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance.The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance.The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection.
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