scholarly journals Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1299
Author(s):  
Neil Foster ◽  
Ying Tang ◽  
Angelo Berchieri ◽  
Shizhong Geng ◽  
Xinan Jiao ◽  
...  
Keyword(s):  
Host Response ◽  
Reproductive Tract ◽  
Acute Infection ◽  
Carrier State ◽  
Immune Clearance ◽  
Host Genetic ◽  
Specific Igg ◽  
Number Of Individuals ◽  
Type Response ◽  
Disease Free

One characteristic of the few Salmonella enterica serovars that produce typhoid-like infections is that disease-free persistent infection can occur for months or years in a small number of individuals post-convalescence. The bacteria continue to be shed intermittently which is a key component of the epidemiology of these infections. Persistent chronic infection occurs despite high levels of circulating specific IgG. We have reviewed the information on the basis for persistence in S. Typhi, S. Dublin, S. Gallinarum, S. Pullorum, S. Abortusovis and also S. Typhimurium in mice as a model of persistence. Persistence appears to occur in macrophages in the spleen and liver with shedding either from the gall bladder and gut or the reproductive tract. The involvement of host genetic background in defining persistence is clear from studies with the mouse but less so with human and poultry infections. There is increasing evidence that the organisms (i) modulate the host response away from the typical Th1-type response normally associated with immune clearance of an acute infection to Th2-type or an anti-inflammatory response, and that (ii) the bacteria modulate transformation of macrophage from M1 to M2 type. The bacterial factors involved in this are not yet fully understood. There are early indications that it might be possible to remodulate the response back towards a Th1 response by using cytokine therapy.

scholarly journals Zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection†

2020 ◽  
Vol 103 (5) ◽  
pp. 1030-1042 ◽  
Author(s):  
Jenna K Schmidt ◽  
Katherine D Mean ◽  
Riley C Puntney ◽  
Eric S Alexander ◽  
Ruth Sullivan ◽  
...  
Keyword(s):  
Pilot Study ◽  
Rhesus Macaque ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Acute Infection ◽  
Viral Rna ◽  
Viral Reservoir ◽  
Computer Assisted ◽  
Male Reproductive Tract ◽  
The Impact

Abstract Although sexual transmission of Zika virus (ZIKV) is well-documented, the viral reservoir(s) in the male reproductive tract remains uncertain in humans and immune-intact animal models. We evaluated the presence of ZIKV in a rhesus macaque pilot study to determine persistence in semen, assess the impact of infection on sperm functional characteristics, and define the viral reservoir in the male reproductive tract. Five adult male rhesus monkeys were inoculated with 105 PFU of Asian-lineage ZIKV isolate PRVABC59, and two males were inoculated with the same dose of African-lineage ZIKV DAKAR41524. Viremia and viral RNA (vRNA) shedding in semen were monitored, and a cohort of animals were necropsied for tissue collection to assess tissue vRNA burden and histopathology. All animals exhibited viremia for limited periods (1–11 days); duration of shedding did not differ significantly between viral isolates. There were sporadic low levels of vRNA in the semen from some, but not all animals. Viral RNA levels in reproductive tract tissues were also modest and present in the epididymis in three of five cases, one case in the vas deferens, but not detected in testis, seminal vesicles or prostate. ZIKV infection did not impact semen motility parameters as assessed by computer-assisted sperm analysis. Despite some evidence of prolonged ZIKV RNA shedding in human semen and high tropism of ZIKV for male reproductive tract tissues in mice deficient in Type 1 interferon signaling, in the rhesus macaques assessed in this pilot study, we did not consistently find ZIKV RNA in the male reproductive tract.

scholarly journals Concurrent Immune Suppression and Hyperinflammation in Patients With Community-Acquired Pneumonia

2020 ◽  
Vol 11 ◽  
Author(s):  
Xanthe Brands ◽  
Bastiaan W. Haak ◽  
Augustijn M. Klarenbeek ◽  
Natasja A. Otto ◽  
Daniël R. Faber ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Suppression ◽  
Host Response ◽  
Cell Activation ◽  
Acute Infection ◽  
Community Acquired Pneumonia ◽  
Endothelial Cell Activation ◽  
Blood Leukocytes ◽  
Tnf Α ◽  
Neutrophil Degranulation

BackgroundThe nature and timing of the host immune response during infections remain uncertain and most knowledge is derived from critically ill sepsis patients. We aimed to test the hypothesis that community-acquired pneumonia (CAP) is associated with concurrent immune suppression and systemic inflammation.MethodsBlood was collected from 79 CAP patients within 24 h after hospitalization and 1 month after discharge; 42 age- and sex-matched subjects without acute infection served as controls. Blood leukocytes were stimulated with lipopolysaccharide (LPS) or Klebsiella pneumoniae, and cytokines were measured in supernatants. Fifteen plasma biomarkers reflective of key host response pathways were compared between CAP patients with the strongest immune suppression (lowest 25% blood leukocyte tumor necrosis factor (TNF)-α production in response to LPS) and those with the least immune suppression (highest 25% of LPS-induced TNF-α production).ResultsBlood leukocytes of CAP patients (relative to control subjects) showed a reduced capacity to release TNF-α, interleukin (IL)-1β, IL-6 and IL-10 upon stimulation with LPS or K. pneumoniae, with a concurrently enhanced ability to release the anti-inflammatory mediator IL-1 receptor antagonist, irrespective of the presence of sepsis (18.9% of cases). Low (relative to high) TNF-α producers displayed higher plasma levels of biomarkers reflecting systemic inflammation, neutrophil degranulation, endothelial cell activation, a disturbed vascular barrier function and coagulation activation.ConclusionCAP replicates a common feature of immune suppression in sepsis. The coexistence of immune suppression and hyperinflammation in CAP argues against the theory of two distinct phases during the host response to sepsis.

scholarly journals Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors

AIDS ◽  
2017 ◽  
pp. 1 ◽  
Author(s):  
Saheli Sadanand ◽  
Jishnu Das ◽  
Amy W. Chung ◽  
Matthew K. Schoen ◽  
Sophie Lane ◽  
...  
Keyword(s):  
Temporal Variation ◽  
Acute Infection ◽  
Igg Subclass ◽  
Specific Igg ◽  
Chronic Progressors

scholarly journals A 29-mRNA host response test from blood accurately distinguishes bacterial and viral infections among emergency department patients

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asimina Safarika ◽  
James W. Wacker ◽  
Konstantinos Katsaros ◽  
Nicky Solomonidi ◽  
George Giannikopoulos ◽  
...  
Keyword(s):  
Emergency Department ◽  
Host Response ◽  
Viral Infections ◽  
Acute Infection ◽  
Chronic Obstructive ◽  
Infection Status ◽  
Suspected Sepsis ◽  
Response Test ◽  
Cell Counts ◽  
Rule Out

Abstract Background Whether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections. Methods The PROMPT trial is a prospective, non-interventional, multi-center clinical study that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status. Results Subject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90–0.99) and 0.90 (95% CI 0.83–0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95% CI 0.79–0.96) for PCT, 0.80 (95% CI 0.72–89) for CRP and 0.78 (95% CI 0.69–0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (> 0.5 µg/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out). Conclusions InSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship. Registration number at Clinicaltrials.gov NCT 03295825.

scholarly journals Dynamics of Human Immunodeficiency Virus-1 Genetic Diversification During Acute Infection

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Hongshuo Song ◽  
Meera Bose ◽  
Suteeraporn Pinyakorn ◽  
Eric Sanders-Buell ◽  
Anne Marie O’Sullivan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
Acute Infection ◽  
Viral Dynamics ◽  
Virus Envelope ◽  
Acute Infections ◽  
Human Immunodeficiency Virus Envelope ◽  
Immunodeficiency Virus ◽  
Host Genetic ◽  
Human Immunodeficiency Virus 1

Abstract We analyzed human immunodeficiency virus envelope diversity in 98 acute infections. The within-host genetic diversity, divergence from transmitted/founder (T/F) strain, and the observed frequency of multiple T/F infections increased with Fiebig stage. These data identify rapid viral dynamics during acute infection with implications for clinical trials conducted in this setting.

scholarly journals Human cryptosporidiosis: detection of specific antibodies in the serum by an indirect immunofluorescence

1996 ◽  
Vol 30 (5) ◽  
pp. 395-402
Author(s):  
Lúcia M.A. Braz ◽  
Vicente Amato Neto ◽  
Clara I.L. Ferrari ◽  
Maria C.A. Palhares ◽  
Valdir S. Amato ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Indirect Immunofluorescence ◽  
Population Studies ◽  
Acute Infection ◽  
Hiv Positive ◽  
Humoral Immune ◽  
Immunodeficiency Virus ◽  
Cryptosporidium Oocysts ◽  
Indirect Immunofluorescence Technique ◽  
Specific Igg

Cryptosporidium sp., a coccidian parasite usually found in the faeces of cattle, has been recently implicated as an agent of human intestinal disease, mainly in immunocompromised patients. In the study realized, by an indirect immunofluorescence technique, specific immunoglobulins (IgG and IgM) have been demonstrated in human serum against Cryptosporidium oocysts. Purified oocysts were used as antigens in the indirect immunofluorecence assay. After analyzing this test in sera from selected groups of patients, the frequency of both specific IgG and IgM of immunocompetent children who were excreting oocysts in their faeces was 62% and in children with negative excretion of oocysts was 20% and 40%, respectively. In adults infected with the human immunodeficiency virus (HIV) and who were excreting Cryptosporidium in their stools, the frequency was 57% for IgG but only 2% for IgM. Twenty three percent of immunocompromised adults with not determined excretion of oocysts in their stools had anti-Cryptosporidium IgG in their sera. Children infected with human immunodeficiency virus had no IgM and only 14% had IgG detectable in their sera. The indirect immunoflorescence assay, when used with other parasitological techniques appears to be useful for retrospective population studies and for diagnosis of acute infection. The humoral immune response of HIV positive patients to this protozoan agent needs clarification.

scholarly journals Mathematical Analysis of Malaria-Schistosomiasis Coinfection Model

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
E. A. Bakare ◽  
C. R. Nwozo
Keyword(s):  
Numerical Simulations ◽  
Endemic Equilibrium ◽  
Model Parameters ◽  
Asymptotically Stable ◽  
Reproduction Numbers ◽  
Mathematical Techniques ◽  
Parameter Values ◽  
The Impact ◽  
Number Of Individuals ◽  
Disease Free

We formulated and analysed a mathematical model to explore the cointeraction between malaria and schistosomiasis. Qualitative and comprehensive mathematical techniques have been applied to analyse the model. The local stability of the disease-free and endemic equilibrium was analysed, respectively. However, the main theorem shows that if RMS<1, then the disease-free equilibrium is locally asymptotically stable and the phase will vanish out of the host and if RMS>1, a unique endemic equilibrium is also locally asymptotically stable and the disease persists at the endemic steady state. The impact of schistosomiasis and its treatment on malaria dynamics is also investigated. Numerical simulations using a set of reasonable parameter values show that the two epidemics coexist whenever their reproduction numbers exceed unity. Further, results of the full malaria-schistosomiasis model also suggest that an increase in the number of individuals infected with schistosomiasis in the presence of treatment results in a decrease in malaria cases. Sensitivity analysis was further carried out to investigate the influence of the model parameters on the transmission and spread of malaria-schistosomiasis coinfection. Numerical simulations were carried out to confirm our theoretical findings.

Anin vivomodel for the study of chemotaxis induced by Schistosomula ofSchistosoma mansoni

Parasitology ◽  
1986 ◽  
Vol 92 (1) ◽  
pp. 117-132 ◽  
Author(s):  
L. P. Chao ◽  
J. T. Jones ◽  
J. R. Kusel
Keyword(s):  
Schistosoma Mansoni ◽  
Intraperitoneal Injection ◽  
Primary Infection ◽  
Host Response ◽  
Immune Status ◽  
Macrophage Response ◽  
The Third ◽  
Specific Igg

SUMMARYPeritoneal leucocytosis, with an increased percentage of eosinophils, was found in mice which had been infected withSchistosoma mansonifor 7 weeks or longer. Specific IgG against worm and egg antigens increased in peritoneal fluids and their corresponding sera respectively 5 and 7 weeks after infection. An intraperitoneal challenge with schistosomula elicited neutrophilia in all mice regardless of immune status, as well as infiltration of eosinophils and macrophages in infected mice. The secondary eosinophilia occurred in mice previously infected for 1 week or longer, whereas the infiltration of macrophages occurred only after worms from the primary infection had started laying eggs. Unlike the eosinophilia the macrophage response required infection with bisexual populations of cercariae. Injection of previously infected mice withEscherichia, TrichinellaorToxocarafailed to increase the proportions of eosinophils and macrophages. Schistosomula-induced eosinophilia could be elicited in passively sensitized mice. Intraperitoneal injection of PBS extract of adult worms elicited eosinophilia in infected mice and neutrophilia in normal mice. Two chromatographic fractions induced eosinophilia and the third only neutrophilia. The relevance of these observations to host response toS. mansoniinfections is discussed.

scholarly journals Gene Expression: the Key to Understanding HIV-1 Infection?

2020 ◽  
Vol 84 (2) ◽  
Author(s):  
Melinda Judge ◽  
Erica Parker ◽  
Denise Naniche ◽  
Peter Le Souëf
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Host Response ◽  
Acute Infection ◽  
Cell Types ◽  
Tissue Type ◽  
Full Potential ◽  
Cell Tissue ◽  
Gene Expression Dysregulation ◽  
Living With Hiv

SUMMARY Gene expression profiling of the host response to HIV infection has promised to fill the gaps in our knowledge and provide new insights toward vaccine and cure. However, despite 20 years of research, the biggest questions remained unanswered. A literature review identified 62 studies examining gene expression dysregulation in samples from individuals living with HIV. Changes in gene expression were dependent on cell/tissue type, stage of infection, viremia, and treatment status. Some cell types, notably CD4+ T cells, exhibit upregulation of cell cycle, interferon-related, and apoptosis genes consistent with depletion. Others, including CD8+ T cells and natural killer cells, exhibit perturbed function in the absence of direct infection with HIV. Dysregulation is greatest during acute infection. Differences in study design and data reporting limit comparability of existing research and do not as yet provide a coherent overview of gene expression in HIV. This review outlines the extraordinarily complex host response to HIV and offers recommendations to realize the full potential of HIV host transcriptomics.

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