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Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention
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Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2016) | Viewed by 167091

Special Issue Editor

Prof. Dr. Susanna Esposito

E-Mail Website
Guest Editor
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
Interests: respiratory tract infections; emerging infections; vaccines; antibiotic therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The International Journal of Molecular Sciences (IJMS) is planning to run a Special Issue regarding the topic, “Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention”.

Infectious diseases are extremely frequent in children and adults and novel diagnostic methods have permitted to increase our knowledge on their epidemiology and pathophysiology. Emerging pathogens have appeared in these last years, raising alerts among health authorities. Moreover, new antinfective treatments have been discovered, and it is extremely important to know when to use them avoiding abuse and misuse of these new drugs with possible negative outcomes on antimicrobial resistance. Furthermore, new vaccines appeared on the market and it is extremely relevant to be informed of their impact on public health.

This Special Issue will include manuscripts on different aspects of infectious diseases, covering childhood and adult ages, as well as different pathogens. Moreover, papers on host immune response’s role in infectious diseases will be more than welcome.

Prof. Dr. Susanna Esposito
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • antinfective therapy
  • diagnostic test
  • emerging pathogens
  • immune response
  • infectious diseases
  • invasive bacterial infection
  • pediatric infectious diseases
  • prevention
  • vaccines

Published Papers (23 papers)

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Editorial

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169 KiB  
Editorial
Infectious Diseases: Pathophysiology, Diagnostics and Prevention
by Susanna Esposito
Int. J. Mol. Sci. 2016, 17(9), 1464; https://doi.org/10.3390/ijms17091464 - 02 Sep 2016
Cited by 10 | Viewed by 5714
Abstract
Infectious diseases occur very frequently in children and adults. Novel diagnostic methods have permitted us to expand our knowledge on their epidemiology and pathophysiology [1].[...] Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)

Research

Jump to: Editorial, Review, Other

337 KiB  
Article
Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis
by Luisa Galli, Laura Lancella, Chiara Tersigni, Elisabetta Venturini, Elena Chiappini, Barbara Maria Bergamini, Margherita Codifava, Cristina Venturelli, Giulia Tosetti, Caterina Marabotto, Laura Cursi, Elena Boccuzzi, Silvia Garazzino, Pier Angelo Tovo, Michele Pinon, Daniele Le Serre, Laura Castiglioni, Andrea Lo Vecchio, Alfredo Guarino, Eugenia Bruzzese, Giuseppe Losurdo, Elio Castagnola, Grazia Bossi, Gian Luigi Marseglia, Susanna Esposito, Samantha Bosis, Rita Grandolfo, Valentina Fiorito, Piero Valentini, Danilo Buonsenso, Raffaele Domenici, Marco Montesanti, Filippo Maria Salvini, Enrica Riva, Icilio Dodi, Francesca Maschio, Luisa Abbagnato, Elisa Fiumana, Chiara Fornabaio, Patrizia Ballista, Vincenzo Portelli, Gabriella Bottone, Nicola Palladino, Mariella Valenzise, Barbara Vecchi, Maria Di Gangi, Carla Lupi, Alberto Villani and Maurizio De Martinoadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2016, 17(6), 960; https://doi.org/10.3390/ijms17060960 - 17 Jun 2016
Cited by 34 | Viewed by 8645
Abstract
Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large [...] Read more.
Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

598 KiB  
Article
Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing
by Alex Vorsters, Severien Van Keer, Samantha Biesmans, Annick Hens, Ilse De Coster, Herman Goossens, Margareta Ieven and Pierre Van Damme
Int. J. Mol. Sci. 2016, 17(5), 750; https://doi.org/10.3390/ijms17050750 - 17 May 2016
Cited by 17 | Viewed by 5327
Abstract
The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. [...] Read more.
The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

501 KiB  
Article
Exchange Transfusion in the Treatment of Neonatal Septic Shock: A Ten-Year Experience in a Neonatal Intensive Care Unit
by Lorenza Pugni, Andrea Ronchi, Bianca Bizzarri, Dario Consonni, Carlo Pietrasanta, Beatrice Ghirardi, Monica Fumagalli, Stefano Ghirardello and Fabio Mosca
Int. J. Mol. Sci. 2016, 17(5), 695; https://doi.org/10.3390/ijms17050695 - 09 May 2016
Cited by 23 | Viewed by 6782
Abstract
Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the [...] Read more.
Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06–0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

686 KiB  
Communication
Varicella Skin Complications in Childhood: A Case Series and a Systematic Review of the Literature
by Elena Bozzola, Mauro Bozzola, Andrzej Krzysztofiak, Alberto Eugenio Tozzi, May El Hachem and Alberto Villani
Int. J. Mol. Sci. 2016, 17(5), 688; https://doi.org/10.3390/ijms17050688 - 06 May 2016
Cited by 9 | Viewed by 5388
Abstract
Even if varicella is generally considered a harmless disease in childhood, severe complications may occur. We examined varicella skin complications (VSCs) in hospitalized immunologically healthy children, over a nine-year period. We also systematically analyzed previous reports to calculate the rate of VSCs in [...] Read more.
Even if varicella is generally considered a harmless disease in childhood, severe complications may occur. We examined varicella skin complications (VSCs) in hospitalized immunologically healthy children, over a nine-year period. We also systematically analyzed previous reports to calculate the rate of VSCs in the literature. VSCs occurred in 16.4% of children hospitalized for varicella. This figure is in accordance with the literature, as the range of VSCs was 2.6%–41.2%. Skin complications may represent determinants of hospitalization and of other indirect costs in young children. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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2646 KiB  
Article
The Molecular Epidemiology and Evolutionary Dynamics of Influenza B Virus in Two Italian Regions during 2010–2015: The Experience of Sicily and Liguria
by Fabio Tramuto, Andrea Orsi, Carmelo Massimo Maida, Claudio Costantino, Cecilia Trucchi, Cristiano Alicino, Francesco Vitale and Filippo Ansaldi
Int. J. Mol. Sci. 2016, 17(4), 549; https://doi.org/10.3390/ijms17040549 - 13 Apr 2016
Cited by 21 | Viewed by 5335
Abstract
Molecular epidemiology of influenza B virus remained poorly studied in Italy, despite representing a major contributor to seasonal epidemics. This study aimed to reconstruct the phylogenetic relationships and genetic diversity of the hemagglutinin gene sequences of 197 influenza B strains circulating in both [...] Read more.
Molecular epidemiology of influenza B virus remained poorly studied in Italy, despite representing a major contributor to seasonal epidemics. This study aimed to reconstruct the phylogenetic relationships and genetic diversity of the hemagglutinin gene sequences of 197 influenza B strains circulating in both Southern (Sicily) and Northern (Liguria) Italy between 2010 and 2015. Upper respiratory tract specimens of patients displaying symptoms of influenza-like illness were screened by real-time RT-PCR assay for the presence of influenza B virus. PCR-positive influenza B samples were further analyzed by sequencing. Neighbor-joining phylogenetic trees were constructed and the amino-acid alignments were analyzed. Phylogenetic analysis showed clusters in B/Victoria clade 1A/1B (n = 29, 14.7%), and B/Yamagata clades 2 (n = 112, 56.8%) and 3 (n = 56, 28.4%). Both influenza B lineages were found to co-circulate during the study period, although a lineage swap from B/Victoria to B/Yamagata occurred in Italy between January 2011 and January 2013. The most represented amino-acid substitutions were N116K in the 120-loop (83.9% of B/Yamagata clade 3 strains) and I146V in the 150-loop (89.6% of B/Victoria clade 1 strains). D197N in 190-helix was found in almost all viruses collected. Our findings provide further evidence to support the adoption of quadrivalent influenza vaccines in our country. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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448 KiB  
Article
The Impact of Specific Viruses on Clinical Outcome in Children Presenting with Acute Heart Failure
by Maria Giulia Gagliardi, Alessandra Fierabracci, Mara Pilati, Marcello Chinali, Carlo Bassano, Francesca Saura, Isabella Giovannoni and Paola Francalanci
Int. J. Mol. Sci. 2016, 17(4), 486; https://doi.org/10.3390/ijms17040486 - 01 Apr 2016
Cited by 15 | Viewed by 4680
Abstract
The presence and type of viral genomes have been suggested as the main etiology for inflammatory dilated cardiomyopathy. Information on the clinical implication of this finding in a large population of children is lacking. We evaluated the prevalence, type, and clinical impact of [...] Read more.
The presence and type of viral genomes have been suggested as the main etiology for inflammatory dilated cardiomyopathy. Information on the clinical implication of this finding in a large population of children is lacking. We evaluated the prevalence, type, and clinical impact of specific viral genomes in endomyocardial biopsies (EMB) collected between 2001 and 2013 among 63 children admitted to our hospital for acute heart failure (median age 2.8 years). Viral genome was searched by polymerase chain reaction (PCR). Patients underwent a complete two-dimensional echocardiographic examination at hospital admission and at discharge and were followed-up for 10 years. Twenty-seven adverse events (7 deaths and 20 cardiac transplantations) occurred during the follow-up. Viral genome was amplified in 19/63 biopsies (35%); PVB19 was the most commonly isolated virus. Presence of specific viral genome was associated with a significant recovery in ejection fraction, compared to patients without viral evidence (p < 0.05). In Cox-regression analysis, higher survival rate was related to virus-positive biopsies (p < 0.05). When comparing long-term prognosis among different viral groups, a trend towards better prognosis was observed in the presence of isolated Parvovirus B19 (PVB19) (p = 0.07). In our series, presence of a virus-positive EMB (mainly PVB19) was associated with improvement over time in cardiac function and better long-term prognosis. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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2057 KiB  
Article
Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors
by Tiziana Latronico, Claudia Mascia, Ilaria Pati, Paola Zuccala, Fabio Mengoni, Raffaella Marocco, Tiziana Tieghi, Valeria Belvisi, Miriam Lichtner, Vincenzo Vullo, Claudio Maria Mastroianni and Grazia Maria Liuzzi
Int. J. Mol. Sci. 2016, 17(4), 455; https://doi.org/10.3390/ijms17040455 - 26 Mar 2016
Cited by 30 | Viewed by 5354
Abstract
An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated [...] Read more.
An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

214 KiB  
Article
Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy
by Emanuele Focà, Paola Magro, Davide Motta, Silvia Compostella, Salvatore Casari, Andrea Bonito, Nigritella Brianese, Alice Ferraresi, Paola Rodari, Maria Chiara Pezzoli, Eugenia Quiros-Roldan and Francesco Castelli
Int. J. Mol. Sci. 2016, 17(4), 434; https://doi.org/10.3390/ijms17040434 - 24 Mar 2016
Cited by 22 | Viewed by 4899
Abstract
Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were [...] Read more.
Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD—standard deviation—3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
5000 KiB  
Article
Immunogenicity and Cross-Protective Efficacy Induced by Outer Membrane Proteins from Salmonella Typhimurium Mutants with Truncated LPS in Mice
by Qiong Liu, Qing Liu, Xinxin Zhao, Tian Liu, Jie Yi, Kang Liang and Qingke Kong
Int. J. Mol. Sci. 2016, 17(3), 416; https://doi.org/10.3390/ijms17030416 - 22 Mar 2016
Cited by 32 | Viewed by 10303
Abstract
Lipopolysaccharide (LPS) is a major virulence factor present in the outer membrane of Salmonella enterica serovar Typhimurium (S. Typhimurium). Outer membrane proteins (OMPs) from Salmonella show high immunogenicity and provide protection against Salmonella infection, and truncated LPS alters the outer membrane composition [...] Read more.
Lipopolysaccharide (LPS) is a major virulence factor present in the outer membrane of Salmonella enterica serovar Typhimurium (S. Typhimurium). Outer membrane proteins (OMPs) from Salmonella show high immunogenicity and provide protection against Salmonella infection, and truncated LPS alters the outer membrane composition of the cell wall. In our previous study, we demonstrated that Salmonella mutants carrying truncated LPS failed to induce strong immune responses and cross-reaction to other enteric bacteria, due to their high attenuation and low colonization in the host. Therefore, we plan to investigate whether outer membrane proteins from Salmonella mutants with truncated LPS resulting from a series of nonpolar mutations, including ∆waaC12, ∆waaF15, ∆waaG42, ∆rfaH49, ∆waaI43, ∆waaJ44, ∆waaL46, ∆wbaP45 and ∆wzy-48, affect immunogenicity and provide protection against diverse Salmonella challenge. In this study, the immunogenicity and cross-protection efficiency of purified OMPs from all mutants were investigated to explore a potential OMP vaccine to protect against homologous or heterologous serotype Salmonella challenge. The results demonstrated that OMPs from three Salmonella mutants (∆waaC12, ∆waaJ44 and ∆waaL46) induced higher immune responses and provided good protection against homologous S. Typhimurium. The OMPs from these three mutants were also selected to determine the cross-protective efficacy against homologous and heterologous serotype Salmonella. Our results indicated that the mutant ∆waaC12 can elicit higher cross-reactivity and can provide good protection against S. Choleraesuis and S. Enteritidis infection and that the cross-reactivity may be ascribed to an antigen of approximately 18.4–30 kDa. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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1684 KiB  
Article
Dried Saliva Spots: A Robust Method for Detecting Streptococcus pneumoniae Carriage by PCR
by Cassandra L. Krone, Anna E. Oja, Kirsten Van de Groep, Elisabeth A. M. Sanders, Debby Bogaert and Krzysztof Trzciński
Int. J. Mol. Sci. 2016, 17(3), 343; https://doi.org/10.3390/ijms17030343 - 05 Mar 2016
Cited by 14 | Viewed by 5385
Abstract
The earliest studies in the late 19th century on Streptococcus pneumoniae (S. pneumoniae) carriage used saliva as the primary specimen. However, interest in saliva declined after the sensitive mouse inoculation method was replaced by conventional culture, which made isolation of pneumococci [...] Read more.
The earliest studies in the late 19th century on Streptococcus pneumoniae (S. pneumoniae) carriage used saliva as the primary specimen. However, interest in saliva declined after the sensitive mouse inoculation method was replaced by conventional culture, which made isolation of pneumococci from the highly polymicrobial oral cavity virtually impossible. Here, we tested the feasibility of using dried saliva spots (DSS) for studies on pneumococcal carriage. Saliva samples from children and pneumococcus-spiked saliva samples from healthy adults were applied to paper, dried, and stored, with and without desiccant, at temperatures ranging from −20 to 37 °C for up to 35 days. DNA extracted from DSS was tested with quantitative-PCR (qPCR) specifically for S. pneumoniae. When processed immediately after drying, the quantity of pneumococcal DNA detected in spiked DSS from adults matched the levels in freshly spiked raw saliva. Furthermore, pneumococcal DNA was stable in DSS stored with desiccant for up to one month over a broad range of temperatures. There were no differences in the results when spiking saliva with varied pneumococcal strains. The collection of saliva can be a particularly useful in surveillance studies conducted in remote settings, as it does not require trained personnel, and DSS are resilient to various transportation conditions. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Review

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484 KiB  
Review
Pneumococcus and the Elderly in Italy: A Summary of Available Evidence Regarding Carriage, Clinical Burden of Lower Respiratory Tract Infections and On-Field Effectiveness of PCV13 Vaccination
by Andrea Orsi, Filippo Ansaldi, Cecilia Trucchi, Roberto Rosselli and Giancarlo Icardi
Int. J. Mol. Sci. 2016, 17(7), 1140; https://doi.org/10.3390/ijms17071140 - 15 Jul 2016
Cited by 17 | Viewed by 4864
Abstract
Streptococcus pneumoniae is currently the leading cause of community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) in adults, elderly and high-risk subjects worldwide. The clear benefits of pneumococcal conjugate vaccination in childhood have been accompanied by a decrease of vaccine-serotype invasive diseases [...] Read more.
Streptococcus pneumoniae is currently the leading cause of community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) in adults, elderly and high-risk subjects worldwide. The clear benefits of pneumococcal conjugate vaccination in childhood have been accompanied by a decrease of vaccine-serotype invasive diseases among adults in several countries, mainly due to the herd effect mediated by the reduction of vaccine-serotype nasopharyngeal colonization in both age groups, but this reduction in the incidence of pneumonia has not been observed. The “Community Acquired Pneumonia Immunization Trial in Adults” (CAPITA) study provided conclusive evidence about 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing CAP in adults and led Western countries to issue new recommendations for pneumococcal immunization targeting subjects >50 years and high-risk groups, with marked differences with respect to age and/or risk groups immunized, eligibility for reimbursement and national, regional or local implementation. Several Italian regions implemented PCV13 immunization programs in adults and interesting data have been come available in the last years, especially from Liguria, a Northern region with a high and long-lasting pneumococcal vaccine immunological pressure in infants. In this review, currently available evidence from Italy and Liguria regarding pneumococcal carriage, burden of CAP and LRTI, and on-field effectiveness of PCV13 immunization in adults and elderly will be summarized. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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199 KiB  
Review
Dismantling the Taboo against Vaccines in Pregnancy
by Maurizio De Martino
Int. J. Mol. Sci. 2016, 17(6), 894; https://doi.org/10.3390/ijms17060894 - 07 Jun 2016
Cited by 18 | Viewed by 7229
Abstract
Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest [...] Read more.
Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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203 KiB  
Review
Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis
by Luca Castellazzi, Marco Mantero and Susanna Esposito
Int. J. Mol. Sci. 2016, 17(6), 855; https://doi.org/10.3390/ijms17060855 - 01 Jun 2016
Cited by 116 | Viewed by 13420
Abstract
Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based [...] Read more.
Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
402 KiB  
Review
Campylobacter jejuni Fatal Sepsis in a Patient with Non-Hodgkin’s Lymphoma: Case Report and Literature Review of a Difficult Diagnosis
by Maria Teresa Gallo, Enea Gino Di Domenico, Luigi Toma, Francesco Marchesi, Lorella Pelagalli, Nicola Manghisi, Fiorentina Ascenzioni, Grazia Prignano, Andrea Mengarelli and Fabrizio Ensoli
Int. J. Mol. Sci. 2016, 17(4), 544; https://doi.org/10.3390/ijms17040544 - 12 Apr 2016
Cited by 10 | Viewed by 5600
Abstract
Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. [...] Read more.
Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. Here, we report a case of a fatal sepsis caused by C. jejuni in a 76-year-old Caucasian man with non-Hodgkin’s lymphoma. After chemotherapeutic treatment, the patient experienced fever associated with severe neutropenia and thrombocytopenia without hemodynamic instability, abdominal pain, and diarrhea. The slow growth of C. jejuni in the blood culture systems and the difficulty in identifying it with conventional biochemical phenotyping methods contributed to the delay of administering a targeted antimicrobial treatment, leading to a fatal outcome. Early recognition and timely intervention are critical for the successful management of C. jejuni infection. Symptoms may be difficult to recognize in immunocompromised patients undergoing chemotherapy. Thus, it is important to increase physician awareness regarding the clinical manifestations of C. jejuni to improve therapeutic efficacy. Moreover, the use of more aggressive empirical antimicrobial treatments with aminoglycosides and/or carbapenems should be considered in immunosuppressed patients, in comparison to those currently indicated in the guidelines for cancer-related infections supporting the use of cephalosporins as monotherapy. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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208 KiB  
Review
Infectious Discitis and Spondylodiscitis in Children
by Nicola Principi and Susanna Esposito
Int. J. Mol. Sci. 2016, 17(4), 539; https://doi.org/10.3390/ijms17040539 - 09 Apr 2016
Cited by 55 | Viewed by 10105
Abstract
In children, infectious discitis (D) and infectious spondylodiscitis (SD) are rare diseases that can cause significant clinical problems, including spinal deformities and segmental instabilities. Moreover, when the infection spreads into the spinal channel, D and SD can cause devastating neurologic complications. Early diagnosis [...] Read more.
In children, infectious discitis (D) and infectious spondylodiscitis (SD) are rare diseases that can cause significant clinical problems, including spinal deformities and segmental instabilities. Moreover, when the infection spreads into the spinal channel, D and SD can cause devastating neurologic complications. Early diagnosis and treatment may reduce these risks. The main aim of this paper is to discuss recent concepts regarding the epidemiology, microbiology, clinical presentation, diagnosis, and treatment of pediatric D and SD. It is highlighted that particular attention must be paid to the identification of the causative infectious agent and its sensitivity to antibiotics, remembering that traditional culture frequently leads to negative results and modern molecular methods can significantly increase the detection rate. Several different bacterial pathogens can cause D and SD, and, in some cases, particularly those due to Staphylococcus aureus, Kingella kingae, Mycobacterium tuberculosis, Brucella spp., the appropriate choice of drug is critical to achieve cure. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

245 KiB  
Review
Recurrent Fever in Children
by Sofia Torreggiani, Giovanni Filocamo and Susanna Esposito
Int. J. Mol. Sci. 2016, 17(4), 448; https://doi.org/10.3390/ijms17040448 - 25 Mar 2016
Cited by 15 | Viewed by 9555
Abstract
Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever [...] Read more.
Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Review
Carbapenems to Treat Multidrug and Extensively Drug-Resistant Tuberculosis: A Systematic Review
by Giovanni Sotgiu, Lia D’Ambrosio, Rosella Centis, Simon Tiberi, Susanna Esposito, Simone Dore, Antonio Spanevello and Giovanni Battista Migliori
Int. J. Mol. Sci. 2016, 17(3), 373; https://doi.org/10.3390/ijms17030373 - 12 Mar 2016
Cited by 77 | Viewed by 7087
Abstract
Background: Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No [...] Read more.
Background: Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems. Methods: A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews. Results: Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%. Conclusions: The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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2045 KiB  
Review
Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?
by Marta Di Pasquale, Stefano Aliberti, Marco Mantero, Sonia Bianchini and Francesco Blasi
Int. J. Mol. Sci. 2016, 17(3), 287; https://doi.org/10.3390/ijms17030287 - 25 Feb 2016
Cited by 28 | Viewed by 10129
Abstract
Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor [...] Read more.
Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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239 KiB  
Review
Mycobacterium tuberculosis: Manipulator of Protective Immunity
by Vanessa C. Korb, Anil A. Chuturgoon and Devapregasan Moodley
Int. J. Mol. Sci. 2016, 17(3), 131; https://doi.org/10.3390/ijms17030131 - 25 Feb 2016
Cited by 63 | Viewed by 13680
Abstract
Mycobacterium tuberculosis (MTB) is one of the most successful pathogens in human history and remains a global health challenge. MTB has evolved a plethora of strategies to evade the immune response sufficiently to survive within the macrophage in a bacterial-immunological equilibrium, yet causes [...] Read more.
Mycobacterium tuberculosis (MTB) is one of the most successful pathogens in human history and remains a global health challenge. MTB has evolved a plethora of strategies to evade the immune response sufficiently to survive within the macrophage in a bacterial-immunological equilibrium, yet causes sufficient immunopathology to facilitate its transmission. This review highlights MTB as the driver of disease pathogenesis and presents evidence of the mechanisms by which MTB manipulates the protective immune response into a pathological productive infection. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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210 KiB  
Review
Critical Overview of the Risk Scoring Systems to Predict Non-Responsiveness to Intravenous Immunoglobulin in Kawasaki Syndrome
by Donato Rigante, Laura Andreozzi, Michele Fastiggi, Benedetta Bracci, Marco Francesco Natale and Susanna Esposito
Int. J. Mol. Sci. 2016, 17(3), 278; https://doi.org/10.3390/ijms17030278 - 24 Feb 2016
Cited by 62 | Viewed by 5848
Abstract
Kawasaki syndrome (KS) is the most relevant cause of heart disease in children living in developed countries. Intravenous immunoglobulin (IVIG) has a preventive function in the formation of coronary artery abnormalities and a poor strictly-curative action in established coronary damage. More than two [...] Read more.
Kawasaki syndrome (KS) is the most relevant cause of heart disease in children living in developed countries. Intravenous immunoglobulin (IVIG) has a preventive function in the formation of coronary artery abnormalities and a poor strictly-curative action in established coronary damage. More than two decades ago, the Harada score was set to assess which children with KS should be subject to administration of IVIG, evaluating retrospectively a large cohort of patients with regard to age, sex and laboratory data. Nowadays, high dose IVIG is administered to all children with a confirmed diagnosis of KS, but a tool for predicting non-responsiveness to the initial infusion of IVIG has not been found. The prediction of IVIG resistance is a crucial issue, as recognising these high-risk patients should consent the administration of an intensified initial treatment in combination with IVIG in order to prevent coronary injuries. Few reports have focused on factors, referring to both clinical parameters and laboratory data at the onset of KS, in order to predict which patients might be IVIG non-responsive. We have analysed three different risk scores which were formulated to predict IVIG resistance in Japanese children with typical KS, but their application in non-Japanese patients or in those with incomplete and atypical patterns of the disease has been studied in a fragmentary way. Overall, our analysis showed that early and definite ascertainment of likely IVIG non-responders who require additional therapies reducing the development of coronary artery involvement in children with KS is still a challenge. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Review
Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review
by Antonio Ieni, Valeria Barresi, Luciana Rigoli, Francesco Fedele, Giovanni Tuccari and Rosario Alberto Caruso
Int. J. Mol. Sci. 2016, 17(1), 109; https://doi.org/10.3390/ijms17010109 - 15 Jan 2016
Cited by 29 | Viewed by 6097
Abstract
Innate and adaptive immunity are both involved in acute and chronic inflammatory processes. The main cellular players in the innate immune system are macrophages, mast cells, dendritic cells, neutrophils, eosinophils, and natural killer (NK), which offer antigen-independent defense against infection. Helicobacter pylori ( [...] Read more.
Innate and adaptive immunity are both involved in acute and chronic inflammatory processes. The main cellular players in the innate immune system are macrophages, mast cells, dendritic cells, neutrophils, eosinophils, and natural killer (NK), which offer antigen-independent defense against infection. Helicobacter pylori (H. pylori) infection presents peculiar characteristics in gastric mucosa infrequently occurring in other organs; its gastric colonization determines a causal role in both gastric carcinomas and mucosa-associated lymphoid tissue lymphoma. In contrast, an active role for Epstein-Barr virus (EBV) has been identified only in 9% of gastric carcinomas. The aim of the present review is to discuss the role of cellular morphological effectors in innate immunity during H. pylori infection and gastric carcinogenesis. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Graphical abstract

Other

183 KiB  
Brief Report
Identification of Human Adenovirus in Respiratory Samples with Luminex Respiratory Virus Panel Fast V2 Assay and Real-Time Polymerase Chain Reaction
by Susanna Esposito, Alessia Scala, Sonia Bianchini, Alberto Zampiero, Emilio Fossali and Nicola Principi
Int. J. Mol. Sci. 2016, 17(3), 297; https://doi.org/10.3390/ijms17030297 - 26 Feb 2016
Cited by 14 | Viewed by 4144
Abstract
In order to compare the last version of the Respiratory Virus Panel (RVP) Fast assay for human Adenovirus (hAdv) detection with a specific real-time polymerase chain reaction (qPCR), which is considered the gold standard for hAdv detection, nasopharyngeal samples collected from 309 children [...] Read more.
In order to compare the last version of the Respiratory Virus Panel (RVP) Fast assay for human Adenovirus (hAdv) detection with a specific real-time polymerase chain reaction (qPCR), which is considered the gold standard for hAdv detection, nasopharyngeal samples collected from 309 children (age range, four months to eight years) with respiratory tract infection were tested using the RVP Fast v2 assay (Luminex Molecular Diagnostics, Inc., Toronto, ON, Canada) and a specific TaqMan qPCR to identify hAdv DNA. The RVP Fast v2 assay detected 30/61 (49.2%) hAdv infections that had been identified by real-time qPCR, demonstrating a significantly lower detection rate (p < 0.001). The sensitivity of the RVP Fast v2 assay in comparison to qPCR was lower in younger children (42.9% vs. 57.7%; Cohen’s kappa coefficient, 0.53); in samples with co-infections (40.0% vs. 56.7%; Cohen’s kappa coefficient, 0.52); and in samples with hAdv type C (45.9% vs. 57.1%; Cohen’s kappa coefficient, 0.60). Samples with lower viral loads were associated with a significantly lower sensitivity of the RVP Fast v2 assay (35.1% vs. 68.2%, p = 0.01; Cohen’s kappa coefficients, 0.49). The RVP Fast v2 assay has important limitations for the detection of hAdv and cannot be used to evaluate whether hAdvs are the main etiologic agent responsible for an outbreak or when epidemiological studies are performed. Full article
(This article belongs to the Special Issue Infectious Diseases: Pathophysiology, Diagnostics, Therapies, and Prevention)
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