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1.  How to treat severe infections in critically ill neutropenic patients? 
BMC Infectious Diseases  2014;14:512.
Severe infections in neutropenic patient often progress rapidly leading to life-threatening organ dysfunction requiring admission to the Intensive Care Unit. Management strategies include early adequate appropriate empirical antimicrobial, early admission to ICU to avoid any delay in the diagnostic and therapeutic management of organ dysfunction. This review discusses the main clinical situations encountered in critically ill neutropenic patients. Specific diagnostic and therapeutic approaches have been proposed for acute respiratory failure, shock, neutropenic enterocolitis, catheter-related infections, cellulitis and primary bacteriemia. Non anti-infectious agents and recent advances will also be discussed. At present, most of large-scale studies and recommendations in neutropenic patients stem from hematological patients and will need further validation in ICU patients.
doi:10.1186/1471-2334-14-512
PMCID: PMC4289060  PMID: 25431154
2.  How to treat VAP due to MDR pathogens in ICU patients 
BMC Infectious Diseases  2014;14:135.
Background
The increasing occurrence of multidrug resistant (MDR) bacteria arises at a time when there is a lack of antibiotics active against these pathogens and few new antimicrobials are in the pipelines of the pharmaceutical industry. Treatment of ventilator-associated pneumonia (VAP) caused especially by MDR Gram-negative bacilli (GNB) represents a real challenge due to the dearth of treatment options.
Methods
We searched the medical literature relevant about management of ventilator-associated pneumonia caused by multi-drug resistant pathogens including GNB and methicillin-resistant S. aureus.
Results
Empirical therapy should be prescribed based on the local pattern of susceptibilities. Colistin and tigecycline are in many cases the unique options for the treatment of many episodes of VAP caused by MDR-GNB. Tigecyline (not licensed for treatment of pneumonia) should be used with an initial bolus of 200 mg followed by 100 mg every 12 h. The need for a loading dose and the administration of high doses of colistin (9 million IU/day in two or three doses) is currently accepted. Vancomycin has been considered the treatment of choice for pneumonia due to MRSA although linezolid may provide higher rate of clinical cure for MRSA VAP with a good safety profile. The initial antibiotic treatment must be reassessed and simplify in accordance of culture results.
Conclusions
Empirical treatment of VAP due to MDR pathogens should be based on knowledge of local ecology. A strategy combining early high doses of effective agents with subsequent simplification in the light of microbiologic information is recommended.
doi:10.1186/1471-2334-14-135
PMCID: PMC4289192  PMID: 25430700
3.  How to approach and treat viral infections in ICU patients 
BMC Infectious Diseases  2014;14:321.
Patients with severe viral infections are often hospitalized in intensive care units (ICUs) and recent studies underline the frequency of viral detection in ICU patients. Viral infections in the ICU often involve the respiratory or the central nervous system and can cause significant morbidity and mortality especially in immunocompromised patients. The mainstay of therapy of viral infections is supportive care and antiviral therapy when available. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host proteins that regulate immunity and are involved in the viral life cycle. These novel treatments need to be further validated in animal and human randomized controlled studies.
doi:10.1186/1471-2334-14-321
PMCID: PMC4289200  PMID: 25431007
4.  How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients? 
BMC Infectious Diseases  2014;14:288.
High mortality and morbidity rates associated with severe infections in the critically ill continue to be a significant issue for the healthcare system. In view of the diverse and unique pharmacokinetic profile of drugs in this patient population, there is increasing use of therapeutic drug monitoring (TDM) in attempt to optimize the exposure of antibiotics, improve clinical outcome and minimize the emergence of antibiotic resistance. Despite this, a beneficial clinical outcome for TDM of antibiotics has only been demonstrated for aminoglycosides in a general hospital patient population. Clinical outcome studies for other antibiotics remain elusive. Further, there is significant variability among institutions with respect to the practice of TDM including the selection of patients, sampling time for concentration monitoring, methodologies of antibiotic assay, selection of PK/PD targets as well as dose optimisation strategies. The aim of this paper is to review the available evidence relating to practices of antibiotic TDM, and describe how TDM can be applied to potentially improve outcomes from severe infections in the critically ill.
doi:10.1186/1471-2334-14-288
PMCID: PMC4289211  PMID: 25430961
TDM; Antibiotic; Pharmacokinetics; Pharmacodynamics
5.  Treatment of gram - positive infections in critically ill patients 
Gram-positive bacteria to include methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), and enterococci, to include vancomycin-resistant enterococci (VRE), display a remarkable array of resistance and virulence factors, which have contributed to their prominent role in infections of the critically ill. Over the last three decades infections with these pathogens has increased as has their overall resistance to available antimicrobial agents. This has led to the development of a number of new antibiotics for the treatment of Gram-positive bacteria. At present, it is important that clinicians recognize the changing resistance patterns and epidemiology of Gram-positive bacteria as these factors may impact patient outcomes. The increasing range of these pathogens, such as the emergence of community-associated MRSA clones, emphasizes that all specialties of physicians treating infections should have a good understanding of the infections caused by Gram-positive bacteria in their area of practice. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has traditionally been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for alternative agents demonstrating efficacy in this role. Similarly, the expansion of VRE as a pathogen in the ICU setting has required the development of agents targeting this important pathogen.
doi:10.1186/1471-2334-14-92
PMCID: PMC4289239  PMID: 25431211
Gram-positive cocci; Antibiotics; Staphylococcus aureus; Enterococci; Resistance
6.  Treatment of bloodstream infections in ICUs 
BMC Infectious Diseases  2014;14:489.
Bloodstream infections (BSIs) are frequent in ICU and is a prognostic factor of severe sepsis. Community acquired BSIs usually due to susceptible bacteria should be clearly differentiated from healthcare associated BSIs frequently due to resistant hospital strains. Early adequate treatment is key and should use guidelines and direct examination of samples performed from the infectious source. Previous antibiotic therapy knowledge, history of multi-drug resistant organism (MDRO) carriage are other major determinants of first choice antimicrobials in heathcare-associated and nosocomial BSIs. Initial antimicrobial dose should be adapted to pharmacokinetic knowledge. In general, a high dose is recommended at the beginning of treatment.
If MDRO is suspected combination antibiotic therapy is mandatory because it increase the spectrum of treatment. Most of time, combination should be pursued no more than 2 to 5 days.
Given the negative impact of useless antimicrobials, maximal effort should be done to decrease the antibiotic selection pressure. De-escalation from a broad spectrum to a narrow spectrum antimicrobial decreases the antibiotic selection pressure without negative impact on mortality. Duration of therapy should be shortened as often as possible especially when organism is susceptible, when the infection source has been totally controlled.
doi:10.1186/1471-2334-14-489
PMCID: PMC4289315  PMID: 25431091
Bloodstream infection; Healthcare associated infections; Bacterial resistance; Intensive care unit
7.  How to treat infections in a surgical intensive care unit 
BMC Infectious Diseases  2014;14:193.
The management of infections in surgical intensive care unit patients poses specific challenges. Although the overall approach to the patient is no different from other patients, diagnosis is often problematic. As in other infections, multidrug resistance is increasingly described, and changes in pharmacokinetics may require different dosing strategies. Also the need for source control adds a level of complexity to the management of the patient. Whereas source control was a purely surgical issue before, percutaneous drainage has emerged as an important alternative. Appropriate timing of source control often remains difficult to determine, but in most severe infections source control should not be delayed. But also the need for a multidisciplinary approach can make the decision making difficult. New concepts such as dedicated source control teams may further assist in selecting the most appropriate treatment strategy and further improve outcome of surgical severe sepsis patients.
doi:10.1186/1471-2334-14-193
PMCID: PMC4289346  PMID: 25430804
8.  How to avoid microaspiration? A key element for the prevention of ventilator-associated pneumonia in intubated ICU patients 
BMC Infectious Diseases  2014;14:119.
Microaspiration of subglottic secretions through channels formed by folds in high volume-low pressure poly-vinyl chloride cuffs of endotracheal tubes is considered a significant pathogenic mechanism of ventilator-associated pneumonia (VAP). Therefore a series of prevention measures target the avoidance of microaspiration. However, although some of these can minimize microaspiration, benefits in terms of VAP prevention are not always obvious. Polyurethane-cuffed endotracheal tubes successfully reduce microaspiration but high quality data demonstrating VAP rate reduction are lacking. An analogous conclusion can be made regarding taper-shaped cuffs compared with classic barrel-shaped cuffs. More clinical data regarding these endotracheal tube designs are needed to demonstrate clinical value in addition to in vitro-based evidence. The clinical usefulness of endotracheal tubes developed for subglottic secretions drainage is established in multiple studies and confirmed by meta-analysis. Any change in cuff design will fail to prevent microaspiration if the cuff is insufficiently inflated. At least one well-designed trial demonstrated that continuous cuff pressure monitoring and control decrease the risk of VAP. Gel lubrication of the cuff prior to intubation temporarily hampers microaspiration through sludging the channels formed by folds in high volume-low pressure cuffs. As the beneficial effect of gel lubrication is temporarily, its potential to reduce VAP risk is probably nonsignificant. A minimum positive end-expiratory pressure of at least 5 cmH2O can be recommended as it reduces the risk of microaspiration in vitro and in vivo. One randomized controlled study demonstrated a reduced risk of VAP in patients ventilated with PEEP (5–8 cmH2O). Regarding head-of-bed elevation, it can be recommended to avoid supine positioning. Whether a 45° head-of-bed elevation is to be preferred above 25-30° head-of-bed elevation remains unproven. Finally, the routine monitoring of gastric residual volumes in mechanically ventilated patients receiving enteral nutrition cannot be recommended.
doi:10.1186/1471-2334-14-119
PMCID: PMC4289393  PMID: 25430629
Ventilator-associated pneumonia; Pneumonia; Micro-aspiration; Prevention; Infection
10.  Hepatitis C in European prisons: a call for an evidence-informed response 
BMC Infectious Diseases  2014;14(Suppl 6):S17.
Globally, over 10 million people are held in prisons and other places of detention at any given time. People who inject drugs (PWID) comprise 10-48% of male and 30-60% of female prisoners. The spread of hepatitis C in prisons is clearly driven by injection drug use, with many infected prisoners unaware of their infection status. Risk behaviour for acquisition of hepatitis C via common use of injecting equipment is widespread in many prison settings.
In custodial settings, effective and efficient prevention models applied in the community are very rarely implemented. Only approximately 60 out of more than 10,000 prisons worldwide provide needle exchange. Thus, HCV prevention is almost exclusively limited to verbal advice, leaflets and other measures directed to cognitive behavioural change. Although the outcome of HCV antiviral treatment is comparable to non-substance users and substance users out of prison, the uptake for antiviral treatment is extremely low.
Based on a literature review to assess the spread of hepatitis C among prisoners and to learn more about the impact for the prison system, recommendations regarding hepatitis C prevention, screening and treatment in prisons have been formulated in this article.
doi:10.1186/1471-2334-14-S6-S17
PMCID: PMC4178549  PMID: 25252822
11.  Update on different aspects of HCV variability: focus on NS5B polymerase 
BMC Infectious Diseases  2014;14(Suppl 5):S1.
The study of hepatitis C virus (HCV) genotypes/subtypes, quasispecies and recombinants obtained by virus genome sequencing are important for epidemiological studies, to trace the source of infection, for development of new direct acting antivirals (DAAs) therapy and for understanding antiviral selection pressures. The HCV NS5B gene encodes a polymerase, which is responsible for virus replication and is a potential target for the development of antiviral agents. Many studies for classification of HCV use a particular segment of the NS5B gene, in addition to other specific regions, and phylogenetic analysis. Actually, some nucleoside/nucleotide analogues and non-nucleoside inhibitors target NS5B protein. This review focuses on HCV variability, phylogenetic analysis and the role of NS5B in the virus-host interactions.
doi:10.1186/1471-2334-14-S5-S1
PMCID: PMC4160895  PMID: 25234810
12.  Update on epidemiology of HCV in Italy: focus on the Calabria Region 
BMC Infectious Diseases  2014;14(Suppl 5):S2.
The epidemiological profile of HCV infection is evolving in Europe, as well as in Italy. We have previously showed genotype distributions and their dynamics in 2,153 HCV RNA positive patients living in Calabria, Southern Italy, over 11 years. In this study, we extend and update this information by evaluating a hospital-based cohort of 945 HCV RNA positive patients attending five hospitals in the Calabria Region from January 2011 to August 2013. We assessed rates of HCV genotypes according to age and gender and the dynamics of HCV genotype distribution over the 3-year period studied. Data showed that genotype 1b is the most prevalent, followed by subtypes 2a/2c and genotype 3. Genotype 4 exhibited an increase between 2011 and 2013. Also, we found a significant decrease in the median age of subjects infected with HCV genotype 3 and 4 during the period studied. Since HCV genotypes are important in epidemiology, pathogenesis and response to antiviral therapy, a continuous epidemiological surveillance is needed.
doi:10.1186/1471-2334-14-S5-S2
PMCID: PMC4160896  PMID: 25236184
13.  Molecular diagnostics in the management of chronic hepatitis C: key considerations in the era of new antiviral therapies 
BMC Infectious Diseases  2014;14(Suppl 5):S8.
Molecular tests that detect and/or quantify HCV RNA are important in the diagnosis and management of patients with chronic hepatitis C (CHC) undergoing anti-viral therapy. The primary goal of anti-HCV therapy is to achieve a sustained virologic response (SVR) defined as "undetectable" Hepatitis C Virus (HCV) RNA in the serum or plasma at 12 to 24 weeks following the end of treatment.
HCV RNA viral load (VL) monitoring is used to guide treatment duration where decisions can be made on-therapy and to determine whether or not to stop therapy. In addition, clinicians determine treatment regimen and duration based on the HCV genotype (1-6) as well as the kinetics of HCV RNA levels.
As direct acting antivirals (DAA) have revolutionized hepatitis C treatment, they have also lead to new HCV RNA VL result interpretations. Further, the clinical decisions were different for pegylated-interferon/ribavirin (PEGα/RBV)+ boceprevir or telaprevir-containing regimens approved in 2011 (e.g. one requiring an additional 4 week "lead-in" with PEGα/RBV), each having different HCV RNA values for futility rules, created complexity in clinical decisions.
The future pegylated-interferon free DAA- regimens promise significantly improved cure rates along with fixed durations and simpler treatment rules. The intent of this article is to discuss the role of HCV RNA real-time PCR tests used in the management of CHC patients in the past and how this is likely to change in the era of interferon free DAA regimens.
doi:10.1186/1471-2334-14-S5-S8
PMCID: PMC4160902  PMID: 25236936
14.  How to approach and treat VAP in ICU patients 
BMC Infectious Diseases  2014;14:211.
Background
Ventilator-associated pneumonia (VAP) is one of the most frequent clinical problems in ICU with an elevated morbidity and costs associated with it, in addition to prolonged MV, ICU-length of stay (LOS) and hospital-length of stay. Current challenges in VAP management include the absence of a diagnostic gold standard; the lack of evidence regarding contamination vs. airway colonization vs. infection; and the increasing antibiotic resistance. We performed a Pubmed search of articles addressing the management of ventilator-associated pneumonia (VAP). Immunocompromised patients, children and VAP due to multi-drug resistant pathogens were excluded from the analysis. When facing a patient with VAP, it’s important to address a few key questions for the patient’s optimal management: when should antibiotics be started?; what microorganisms should be covered?; is there risk for multirresistant microorganisms?; how to choose the initial agent?; how microbiological tests determine antibiotic changes?; and lastly, which dose and for how long?. It’s important not to delay adequate treatment, since outcomes improve when empirical treatment is early and effective. We recommend short course of broad-spectrum antibiotics, followed by de-escalation when susceptibilities are available. Individualization of treatment is the key to optimal management.
doi:10.1186/1471-2334-14-211
PMCID: PMC4304084  PMID: 25430899
Ventilator-associated pneumonia; Nosocomial pneumonia; Treatment; Antibiotic; Management
15.  Tuberculosis in childhood: a systematic review of national and international guidelines 
BMC Infectious Diseases  2014;14(Suppl 1):S3.
Background
Paediatric tuberculosis (TB) represents a major public health concern worldwide. About 1 million children aged less than 15 years develop TB each year, contributing to 3-25% of the total TB caseload. The aim of this review is to evaluate national and international guidelines concerning tuberculosis in childhood and compare them in terms of diagnosis and treatment strategies.
Methods
A literature search of the Pubmed database was performed from January 2000 to August 2013, using the terms “tuberculosis” and “children”. The search was limited to guidelines and consensus conferences, human species and full text availability, with no language restrictions.
Results
Twenty-seven national and international guidelines are identified. Several discrepancies on the diagnosis workup of TB are underlined. The main points of disagreement are represented by the interpretation of tuberculin skin test (TST) result and the recommendations on the use of TST and/or interferon-gamma release assay (IGRA) for the diagnosis of TB infection. Otherwise, all guidelines are in agreement that a microbiological confirmation should always be sought. Similarly, susceptibility drug testing and genotyping should be performed whenever it is possible on the basis of resources availability. On the contrary, the use of nucleic acid amplification tests (NAATs) for the M. tuberculosis detection is still controversial. A general consensus exists, otherwise, on TB treatment and only minor discrepancies are evidenced, such as the recommendations on daily or intermittent treatment regimens.
Conclusions
Despite advances in TB diagnostic tools have been reached during the last decade, a lack of uniformity in their availability, indication and interpretation has relevant consequences for clinical practice. Further studies need to be performed to clarify this issue and identify a reliable and reproducible diagnostic workup. Moreover, future studies should analyze the drug metabolism and the efficacy of intermittent dosing regimes in childhood, as well as new treatment regimens in order to improve the therapy compliance.
doi:10.1186/1471-2334-14-S1-S3
PMCID: PMC4015175  PMID: 24564378
16.  Clinical peculiarities of tuberculosis 
BMC Infectious Diseases  2014;14(Suppl 1):S4.
The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults.
doi:10.1186/1471-2334-14-S1-S4
PMCID: PMC4015485  PMID: 24564419
17.  Reflections on the immunology of tuberculosis: will we ever unravel the skein? 
BMC Infectious Diseases  2014;14(Suppl 1):S1.
Many and large dumps exist in our knowledge about Mycobacterium tuberculosis infection and disease in infants and children. We still do not understand why some individuals do acquire and others do not acquire the infection in the presence of the same risk factors. We do not understand why some individuals convert from latent to active tuberculosis and why other individuals convert from active to inactive tuberculosis even without treatment.
As a matter of fact the immune system mounts a bouncing, robust and polyedral defence against Mycobacterium tuberculosis, but the bacillus is so much artful and dextrous that it has ahead from this immunological fierce accoutrements. Mycobacterium tuberculosis survival, multiplication, and transmission are largely favoured by the immune mechanisms. The granuloma itself is more bacillus- than host-protective.
These abilities make Mycobacterium tuberculosis one of more successful human pathogens, but dumps in our knowledge and the counterproductive immunity hinder development of new diagnostics, therapies and vaccines. This occurs in front of an infection which engages one third of the world population and a disease which kills in a year about 1.5 million individuals worldwide.
Understanding mechanisms and meaning of immune response in tuberculosis marks out the foundations of strategies with a view to prepare effective vaccines and reliable diagnostic tools as well as to build up therapeutic weapons. To gain these objectives is vital and urgent considering that tuberculosis is a common cause of morbidity and is a leading cause of death.
doi:10.1186/1471-2334-14-S1-S1
PMCID: PMC4015689  PMID: 24564297
18.  Vaccine against tuberculosis: what’s new? 
BMC Infectious Diseases  2014;14(Suppl 1):S2.
Background
one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued.
Method
a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and ClinicalTrial.gov websites.
Results
100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed.
Conclusions
Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050.
doi:10.1186/1471-2334-14-S1-S2
PMCID: PMC4015960  PMID: 24564340
19.  Tuberculosis and HIV co-infection in children 
BMC Infectious Diseases  2014;14(Suppl 1):S5.
HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.
Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.
Conclusion
Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.
doi:10.1186/1471-2334-14-S1-S5
PMCID: PMC4016474  PMID: 24564453
20.  Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update 
BMC Infectious Diseases  2014;14(Suppl 1):S6.
Background
Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.
Methods
We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.
Results
Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).
Conclusions
Both IGRAs showed no better performance than TST in low income countries.
doi:10.1186/1471-2334-14-S1-S6
PMCID: PMC4016555  PMID: 24564486
21.  Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests 
Background
Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests.
Methods
We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail.
Results
Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification.
Conclusions
Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.
doi:10.1186/1471-2334-13-37
PMCID: PMC3579720  PMID: 23347408
Bacteria; Clinical microbiology; Diagnosis; Digestive disorders; Gastroenterology; Helminths; Intestinal protozoa; Persistent diarrhoea; Virus
22.  Epidemiological features and specificities of HCV infection: a hospital-based cohort study in a university medical center of Calabria region 
BMC Infectious Diseases  2012;12(Suppl 2):S4.
The epidemiological status of HCV in Europe, and in particular in Mediterranean countries, is continuously evolving. The genotype distribution is related to improvement of healthcare conditions, expansion of intravenous drug use and immigration. We review and characterize the epidemiology of the distribution of HCV genotypes within Calabria, an area of Southern Italy. We focus on the pattern of distinct HCV genotype changes over the last 16 years; particularly subtype 1b and genotype 4. We collected data by evaluating a hospital-based cohort of chronic hepatitis C patients; in addition, we report an update including new patients enrolled during last eight months.
doi:10.1186/1471-2334-12-S2-S4
PMCID: PMC3495624  PMID: 23173638
23.  Natural history and clinical response: “It’s the virus, stupid, or is it the host?” 
BMC Infectious Diseases  2012;12(Suppl 2):S6.
Summary
A major goal of modern medicine is the application of personalized therapies, consisting of decisions and practices tailored to the individual patient. Information about genetic variants, either mutant or polymorphic, represents the basis for the development of this clinical approach. Recently, several independent genome-wide association studies (GWAS) have identified two single nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV containment, spontaneous clearance, treatment response, and disease progression. In this minireview we will concisely discuss some critical genetic concepts that may have possible implications for clinical decisions in the treatment of HCV infection.
doi:10.1186/1471-2334-12-S2-S6
PMCID: PMC3495625  PMID: 23173731
24.  Future research and collaboration: the “SINERGIE” project on HCV (South Italian Network for Rational Guidelines and International Epidemiology) 
BMC Infectious Diseases  2012;12(Suppl 2):S9.
The SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology) project is intended to set up a collaborative network comprising virologists, clinicians and public health officials dealing with patients affected by HCV disease in the Calabria Region. A prospective observational data-base of HCV infection will be developed and used for studies on HCV natural history, response to treatment, pharmaco-economics, disease complications, and HCV epidemiology (including phylogenetic analysis). With this approach, we aim at improving the identification and care of patients, focusing on upcoming research questions. The final objective is to assist in improving care delivery and inform Public Health Authorities on how to optimize resource allocation in this area.
doi:10.1186/1471-2334-12-S2-S9
PMCID: PMC3495626  PMID: 23173812
25.  Chronic HCV infection: epidemiological and clinical relevance 
BMC Infectious Diseases  2012;12(Suppl 2):S2.
Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated acute and chronic hepatitis in 1989, plays a major role as a cause of chronic liver injury, with potential for neoplastic degeneration. It is mainly transmitted by the parenteral route. However, although with lower efficiency, it may be also transmitted by sexual intercourses and by the mother-to-child route. Epidemiological evidence shows that a wave of infection occurred in the 1945-65 period (baby boomers) in western countries. After acute infection, as many as 50-85% of the patients fail to clear the virus resulting in chronic liver infection and/or disease. It is estimated that, on a global scale, about 170 million people are chronically infected with HCV, leading to about 350.000 deaths yearly. Among western countries southern Europe, and particularly Italy, is among the most affected areas. The impact on the public health systems is noteworthy, with high number of hospitalizations due to chronic liver disease, cirrhosis or hepatocellular carcinoma. While waiting for a safe and effective vaccine to be made available, new promising direct-acting antiviral (DAA) drugs offer a better therapeutic scenario than in the past even for the poor responder genotypes 1 and 4, provided that effective screening and care is offered. However, the long and aspecific prodromic period before clinical symptoms develop is a major obstacle to early detection and treatment. Effective screening strategies may target at-risk groups or age specific groups, as recently recommended by the CDC.
doi:10.1186/1471-2334-12-S2-S2
PMCID: PMC3495628  PMID: 23173556

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