Showing papers in "Current Opinion in Infectious Diseases in 2015"
TL;DR: It is clear that there is a complicated bidirectional relationship between the intestinal microbiota and host which is vital to health and an enhanced understanding of this relationship will be critical not only to maximize and maintain human health but also to shape the understanding of disease and to foster new therapeutic approaches.
Abstract: Purpose of reviewA diverse array of microbes colonizes the human intestine. In this review, we seek to outline the current state of knowledge on what characterizes a ‘healthy’ or ‘normal’ intestinal microbiome, what factors modify the intestinal microbiome in the healthy state and how the intestinal
136 citations
TL;DR: Early and rapid detection of suspected infected patients with communicable diseases along with appropriate infection control practice, education, national and global preparedness guidelines would help to prevent disease transmission to HCPs.
Abstract: PURPOSE OF REVIEW Several viral diseases have emerged and impacted healthcare systems worldwide. Healthcare personnels (HCPs) are at high risk of acquiring some emerging infections while caring for patients. We provide a review of risk factors, evidence of infection in HCPs, and prevention strategies with Middle East respiratory syndrome coronavirus, Ebola virus disease (Ebola), severe acute respiratory syndrome (SARS), and avian influenza. RECENT FINDINGS HCP-related infections with Middle East respiratory syndrome coronavirus, Ebola, and SARS have been reported among 1-27%, 2.5-12%, and 11-57% of total cases, respectively. The case fatality rate of Ebola in HCPs has been reported up to 73%. The WHO guidelines for the global surveillance of SARS were developed in 2004 and used as a template for other emerging diseases preparedness. Risks to HCPs with emerging diseases are related to inappropriate and insufficient infection control measures during an initial encounter, at the beginning of outbreak and with an overwhelming number of patient cases. To date, there are no reports of avian influenza transmission to HCPs from affected cases. SUMMARY Early and rapid detection of suspected infected patients with communicable diseases along with appropriate infection control practice, education, national and global preparedness guidelines would help to prevent disease transmission to HCPs.
124 citations
TL;DR: It is proposed that the neonate immune system and maternal milk represent an entity necessary to ensure not only appropriate function in early life but also long term immune homeostasis.
Abstract: Purpose of reviewThis article aims to review the evidence that breast milk can actively shape neonate gut immune system development toward a mature immune system capable of responding appropriately to encountered antigens.Recent findingsRecent findings in the adult have demonstrated the critical rol
100 citations
TL;DR: Improved molecular diagnostics and genetic sequence analysis are beginning to reveal the complex dynamics of individual serotypes and genotypes, and their contribution to recent outbreaks of enterovirus-associated disease, however, the biological mechanisms underlying their emergence and transmission dynamics remain elusive.
Abstract: Purpose of reviewThere are over 100 serotypes of human enteroviruses, which cause a spectrum of illnesses, including meningitis, encephalitis, paralysis, myocarditis and rash. Increasing incidence of hand-foot-and-mouth disease in the Asia-Pacific region and recent outbreaks of enterovirus-associate
97 citations
TL;DR: A retrospective study of visceral leishmaniasis in organ transplant patients suggests that there may be a role for secondary prophylaxis after treatment akin to HIV coinfection recommendations, and the pros and cons of oral therapy with miltefosine are discussed.
Abstract: Purpose of reviewThis review summarizes recent important and interesting articles investigating the challenging treatment of the parasitic infection, leishmaniasis. In addition, it compares and contrasts leishmaniasis clinical practice treatment guidelines.Recent findingsStudies show that, in contra
95 citations
TL;DR: Clinical and epidemiological investigations are urgently needed to stop the further spread of artemisinin resistance, monitor the efficacy of ACTs where K13 mutations are prevalent, identify currently-available drug regimens that cure ACT failures, and rapidly advance new antimalarial compounds through preclinical studies and clinical trials.
Abstract: Purpose of reviewThe emergence of artemisinin resistance in Southeast Asia (SEA), where artemisinin combination therapies (ACTs) are beginning to fail, threatens global endeavors to control and eliminate Plasmodium falciparum malaria. Future efforts to prevent the spread of this calamity to Africa w
85 citations
TL;DR: Resource-poor countries should closely monitor the epidemiology of Hav infection and periodically undertake cost-effectiveness analyses of HAV immunization strategies to allow timely identification of epidemiologic transition and introduction of preventive strategies before HAV infection becomes a public health problem.
Abstract: Purpose of reviewTransmission of hepatitis A virus (HAV) infection is primarily fecal–oral. Symptomatic hepatitis, severe disease, and death are more likely to occur when infection occurs at an older age. Improvements in socioeconomic and hygienic conditions have led to a change in its epidemiology
81 citations
TL;DR: Increased recognition and understanding of the disease pathogenesis, its uncommon clinical manifestations, complications and particular therapeutic strategies are the cornerstone for the optimal outcome of this often fatal condition.
Abstract: Purpose of review Cryptococcosis among solid organ transplant (SOT) recipients is a source of significant morbidity. Its pathogenesis, the etiology of immune reconstitution syndrome, and the optimal therapy in this setting are still not well defined. Herein, we review the epidemiology, the latest findings on pathogenesis, unique clinical manifestations, and the treatment of Cryptococcosis in this specific vulnerable population. Recent findings Cryptococcosis is a common fungal complication among SOT recipients. It follows in frequency only to aspergillosis and candidiasis. Cryptococcal infection carries a high mortality, up to 27% during the first year posttransplantation. Host factors, environmental factors, medications, and the type of transplant all play a role in the clinical presentation and severity of infection. Clinical manifestations can be atypical among SOT recipients, and therefore, clinical suspicion and diagnostic evaluation must consider cryptococcal central nervous system disease. During meningitis treatment, measurement of Flucytosine levels is recommended to increase safety and optimize the therapeutic effect. Summary Cryptococcosis among SOT recipients is an evolving field. Increased recognition and understanding of the disease pathogenesis, its uncommon clinical manifestations, complications and particular therapeutic strategies are the cornerstone for the optimal outcome of this often fatal condition.
81 citations
TL;DR: A major role of reactivation of latent infection in the pathogenesis of toxoplasmosis in this patient population is confirmed, and universal prophylaxis with TMP/SMX in allo pre-HCTSP patients should be implemented by all transplant programmes.
Abstract: Purpose of reviewToxoplasmosis in haematopoietic cell transplant (HCT) recipients is associated with high morbidity and mortality rates. Prophylaxis following HCT is recommended for high-risk pre-HCT toxoplasma-seropositive (pre-HCTSP) recipients. However, there is no agreement or consistency among
79 citations
TL;DR: HIV-infected PWUDs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care and a comprehensive strategy that encompasses evidence-based prevention and treatment interventions that target the individual, family, healthcare system, legal and societal structure is required.
Abstract: Purpose of review
HIV management in PWUD is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care. In this review we describe the individual, health systems and societal barriers to HIV treatment access and care retention for people who use drugs. Additionally the clinical management of HIV infected PWUD is often complicated by the presence of multiple infectious and non-infectious comorbidities.
78 citations
TL;DR: Eliminating HCV through scaling up treatment is a theoretical possibility, but empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.
Abstract: Purpose of Review
The majority of HCV infections in UK and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk – such as people who inject drugs (PWID) – irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID.
TL;DR: Microscopy and rapid diagnostic tests provide effective surveillance for malaria control and strategies that detect a reservoir of submicroscopic infection must be developed and standardized to guide malaria elimination.
Abstract: Purpose of reviewLimitations of blood smear microscopy contributed to failure of the 1950–1960s WHO Global Programme to Eliminate Malaria. All diagnostic methods encounter limits of detection (LOD) beyond which it will not be possible to identify infected individuals. When this occurs, it becomes di
TL;DR: New developments in the molecular and cellular basis of T. vaginalis pathobiology combined with data on the urogenital tract microbiota and immunology have enriched knowledge on human–microbe interactions that will contribute to increasing the capacity to prevent and treat T. vaginais and other sexually transmitted infections.
Abstract: Purpose of review To integrate a selection of the most recent data on Trichomonas vaginalis origins, molecular cell biology and T. vaginalis interactions with the urogenital tract microbiota with trichomoniasis symptoms and clinical management. Recent findings Transcriptomics and proteomics datasets are accumulating, facilitating the identification and prioritization of key target genes to study T. vaginalis pathobiology. Proteins involved in host sensing and cytoskeletal plasticity during T. vaginalis amoeboid transformation were identified. T. vaginalis was shown to secrete exosomes and a macrophage migration inhibitory factor-like protein that both influence host-parasite interactions. T. vaginalis co-infections with Mycoplasma species and viruses were shown to modulate the inflammatory responses, whereas T. vaginalis interactions with various Lactobacillus species inhibit parasite interactions with human cells. T. vaginalis infections were also shown to be associated with bacterial vaginosis. A broader range of health sequelae is also becoming apparent. Diagnostics for both women and men based on the molecular approaches are being refined, in particular for men. Summary New developments in the molecular and cellular basis of T. vaginalis pathobiology combined with data on the urogenital tract microbiota and immunology have enriched our knowledge on human-microbe interactions that will contribute to increasing our capacity to prevent and treat T. vaginalis and other sexually transmitted infections.
TL;DR: Although microbial invasion is responsible for inflammatory bone disorders, except for an autoinflammatory origin, the underlying and detailed mechanisms in the pathogenesis of osteomyelitis are not yet fully understood and represent an absolute precondition for the development of effective causal treatment strategies in the future.
Abstract: Purpose of reviewThe term osteomyelitis covers a wide range of inflammatory bone disorders caused by microbial invasion or due to autoinflammatory processes, but furthermore osteomyelitis also occurs at different ages and at preferred localizations in the human skeleton. This article aims to give an
TL;DR: The incidence of SSI after surgery is not falling and some advances might be included into these care bundles, but more research is needed together with improved compliance with care bundles.
Abstract: Purpose of review: surgical site infection (SSI) is a common health care associated infection and complicates up to 10-20% of operations with considerable health care resources Apart from the widely adopted use of appropriate hair removal, antibiotic prophylaxis, avoidance of hypothermia and peri-operative glycaemic control to reduce SSIs this review has considered new research and systematic reviews, and whether their findings should be included in guidelines
Recent findings: The efficacy of preoperative bathing/showering, antibiotic prophylaxis for clean surgery and perioperative oxygen supplementation to reduce the risk of SSI is still in doubt By contrast, the use of 2% chlorhexidine in alcohol skin preparation, postoperative negative pressure wound therapy and antiseptic surgical dressings do show promise Antimicrobial sutures in independent meta-analyses were found to reduce the risk of SSI after all classes of surgery (except dirty) whereas the use of wound guards, or diathermy skin incision (compared with scalpel incision), did not
Summary: The incidence of SSI after surgery is not falling Based on this review of published trials and evidence-based systematic reviews some advances might be included into these care bundles More research is needed together with improved compliance with care bundles
TL;DR: Technical advancements can enhance the accurate and timely genotypic detection of drug resistance and treatments for drug-resistant CMV and their genetic barriers to resistance.
Abstract: Purpose of review
updated information on diagnosis of CMV drug resistance, treatments for drug-resistant infection and potential uses of experimental antiviral compounds.
TL;DR: It is time to start using genetics in UTI-prone patients, to improve diagnosis and to assess the risk for chronic sequels such as renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation.
Abstract: Urinary tract infections (UTIs) are common, dangerous and interesting. Susceptible individuals experience multiple, often clustered episodes, and in a subset of patients, infections progress to acute pyelonephritis (APN), sometimes accompanied by uro-sepsis. Others develop asymptomatic bacteriuria (ABU). Here, we review the molecular basis for these differences, with the intention to distinguish exaggerated host responses that drive disease from attenuated responses that favour protection and to highlight the genetic basis for these extremes, based on knock-out mice and clinical studies.
TL;DR: The management of P. aeruginosa respiratory infection in CF remains a challenging area, especially in the setting of multidrug resistance, and the role of inhaled antibiotics continues to be expanded.
Abstract: The current guidelines and recent clinical research in the management of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF) are reviewed. Areas where further research is required will also be highlighted.
P. aeruginosa is a key respiratory pathogen in CF. Inhaled tobramycin or colistin is recommended for early eradication to prevent establishment of chronic infection. Other antibiotic options are currently being investigated. The long-term success of eradication strategies is also now being assessed. The use of inhaled antibiotics in the management of chronic P. aeruginosa infection is an area of active investigation. Acute pulmonary exacerbations are still a major cause of morbidity and mortality. Guidelines continue to recommend combination intravenous therapy but further research is required to clarify the advantage of this approach. Multidrug resistance is common and potentially more effective antipseudomonal antibiotics may soon become available.
The management of P. aeruginosa respiratory infection in CF remains a challenging area, especially in the setting of multidrug resistance. The role of inhaled antibiotics continues to be expanded. Further research is required in the key areas of eradication and management of chronic infection and acute pulmonary exacerbations to identify those treatments that optimize long-term, clinical benefits.
TL;DR: Echinocandins remain preferred agents against invasive Candida infections and Susceptibility testing and FKS genotypic testing do not have roles in routine clinical practice, but may be useful in newly-diagnosed patients who are echinoc andin-experienced or those who have not responded to echinokandin treatment.
Abstract: Purpose of reviewWe review and offer our clinical perspectives on the emergence of echinocandin-resistant Candida.Recent findingsCandida FKS gene mutations attenuate echinocandin activity, but overall mutation rates among clinical isolates remain low (Candida glabrata, ∼4%; other species, <1%). Rate
TL;DR: The potent and broad antiviral function of the immune system can be exploited by the development of immune-modulating BSAA, which will be a key aim of antiviral research in the coming decades.
Abstract: Purpose of reviewPotent antivirals are successfully used for the treatment of infections with herpesviruses, hepatitis B and C viruses, HIV, and with some success for influenza viruses. However, no selective inhibitors are available for a multitude of medically important viruses, most of which are (
TL;DR: Robust surveillance systems are essential to combat antibiotic resistance, and need to emphasize a ‘one health’ approach, an overview of contemporary surveillance programs, with emphasis on gram-negative bacteria.
Abstract: Purpose of Review
It is widely accepted that infection control, advanced diagnostics, and novel therapeutics are crucial to mitigate the impact of antibiotic-resistant bacteria. The role of global, national and regional surveillance systems as part of the response to the challenge posed by antibiotic resistance is not sufficiently highlighted. We provide an overview of contemporary surveillance programs, with emphasis on Gram-negative bacteria.
TL;DR: The aim is to examine the safety and feasibility of antibiotic de-escalation in critically ill patients providing practical tips about how to accomplish this strategy in the critical care setting.
Abstract: Purpose of reviewAn antimicrobial policy consisting of the initial use of wide-spectrum antimicrobials followed by a reassessment of treatment when culture results are available is termed de-escalation therapy. Our aim is to examine the safety and feasibility of antibiotic de-escalation in criticall
TL;DR: It is important to utilize the available referenced guidelines, along with the practical experiences of biocontainment units, to optimize the care provided to patients with EVD while strictly adhering to infection control principles.
Abstract: Purpose of reviewThis review details infection control issues encountered in the management of patients with Ebola virus disease (EVD), with emphasis on how these issues were confronted in two biocontainment patient care units in the United States.Recent findingsThere is a notable paucity of medical
TL;DR: Clinicians should be aware of testing strategies employed by their laboratories to ensure optimal sensitivity and specificity and local available T. pallidum PCR assays may improve the diagnosis of early disease and inform antibiotic choice.
Abstract: Purpose of reviewThe past 15 years have seen a dramatic increase in syphilis diagnoses in several regions including China, North America, Western Europe and Australia. Worldwide, the disease remains prevalent, contributing to substantial adult morbidity and neonatal mortality. Testing and treatment
TL;DR: Maternal immunization with an immunogenic vaccine has the potential to substantially impact the morbidity and mortality of RSV-associated lower respiratory tract illness in infants worldwide.
Abstract: Purpose of reviewRespiratory syncytial virus (RSV) remains an important cause of serious and sometimes fatal acute lower respiratory tract disease in infants, yet no effective antiviral treatment or vaccine for the prevention of RSV in early life is available. Vaccination of women during pregnancy i
TL;DR: Posaconazole has been tested in humans showing activity against T. cruzi, but not enough to reach cure by itself, and open a window to new strategies as combination therapies or even sequential treatments.
Abstract: PURPOSE OF REVIEW The current therapeutic scenario against Chagas disease has been recently updated with the use of the triazoles in clinical trials and several experimental assays (in-vitro and in-vivo models) which are bringing novel and promising evidence for the treatment of Chagas diseases, mainly in its chronic phase. We pretend to analyze all the evidence extracted from the in-vitro and in-vivo assays, and try to understand the poor outcome of posaconazole (POS) in the clinical experience. RECENT FINDINGS POS is the drug with more advanced development in both experimental model and clinical trial. Despite the promising results initially obtained in the animal model, the clinical trial did not meet expectations. Nevertheless, it has documented the activity against Trypanosoma cruzi either in the animal model or in humans. Also new treatment strategies, combination or sequential schemes, have been evaluated in the animal model. SUMMARY POS has been tested in humans showing activity against T. cruzi, but not enough to reach cure by itself. Those results represent one of the most important breakthroughs in the treatment of Chagas disease, and open a window to new strategies as combination therapies or even sequential treatments.
TL;DR: There is theoretical plausibility for sexual transmission of Ebola virus but there has been no evidence of this occurring and recommendations are that those recovering from Ebola virus disease should abstain from all sexual intercourse, or if this is not possible, use condoms, for 3 months after the onset of symptoms.
Abstract: Purpose of review: The ongoing Ebola virus epidemic in West Africa is a major global health challenge. The main mode of transmission is through contact with bodily fluids and skin of those infected or who have died. This review was undertaken to consider the evidence for transmission by contact with bodily fluids occurring through sexual activity. Recent findings: No cases in the previous 20 outbreaks or the current outbreak in West Africa have been shown to be sexually transmitted although other types of viral haemorrhagic fever have had sexual transmission implicated. Ebola virus is found in sites and fluids associated with sexual activity but this occurs at different stages of the disease. Persistence in the convalescent period occurs in rectum vagina and semen with persistence in semen being longest of up to at least 101 days. Recommendations based on this data are that those recovering from Ebola virus disease should abstain from all sexual intercourse or if this is not possible use condoms for 3 months after the onset of symptoms. Summary: There is theoretical plausibility for sexual transmission of Ebola virus but there has been no evidence of this occurring. Further research is needed to consider if sexual activity contributes to the epidemic in order to inform individuals with regard to avoiding acquisition or transmission by those recovering from Ebola virus disease.
TL;DR: This review discusses the expanding noncanonical functions of CRISPR-Cas systems, including their roles in virulence, focusing mainly on their relationship to the cell envelope.
Abstract: Purpose of review: CRISPR-Cas systems are prokaryotic immune systems against invading nucleic acids that adapt as new environmental threats arise There are emerging examples of CRISPR-Cas functions in bacterial physiology beyond their role in adaptive immunity This highlights the poorly understood, but potentially common, moonlighting functions of these abundant systems We propose that these noncanonical CRISPR-Cas activities have evolved to respond to stresses at the cell envelope
Recent findings: Here, we discuss recent literature describing the impact of the extracellular environment on the regulation of CRISPR-Cas systems, and the influence of CRISPR-Cas activity on bacterial physiology These described noncanonical CRISPR-Cas functions allow the bacterial cell to respond to the extracellular environment, primarily through changes in envelope physiology
Summary: This review discusses the expanding noncanonical functions of CRISPR-Cas systems, including their roles in virulence, focusing mainly on their relationship to the cell envelope We first examine the effects of the extracellular environment on regulation of CRISPR-Cas components, and then discuss the impact of CRISPR-Cas systems on bacterial physiology, concentrating on their roles in influencing interactions with the environment including host organisms
TL;DR: The scope of TDM is broadening from the traditional focus on prevention of toxicity, to include optimization of antibiotic exposure thereby improving patient outcomes, however, the evidence relating TDM practice with improved clinical outcome remains limited.
Abstract: Purpose of reviewRecent studies suggest that contemporary antibiotic dosing is unlikely to achieve best outcomes for critically ill patients because of extensive pharmacokinetic variability and altered pharmacodynamics. Dose adaptation is considered quite challenging because of unpredictable dose-exposure relationships. Consequently, individualization of antibiotic dosing has been advocated. Herein, we describe recent developments in the optimization of antibiotic dosing in the critically ill.Recent findingsConventional doses of many antibiotics frequently result in sub or supratherapeutic exposures in the critically ill. Clinical studies continue to illustrate that dose-exposure relationships are highly variable in severely ill patients. Dose optimization based on pharmacokinetic/pharmacodynamic principles can effectively improve antibiotic exposure. Therapeutic drug monitoring (TDM) with adaptive feedback is likely to be the most robust approach to optimize dosing for individual patients. This more accurate approach to dosing is made possible with the user-friendly dosing software that is emerging.SummaryThe scope of TDM is broadening from the traditional focus on prevention of toxicity, to include optimization of antibiotic exposure thereby improving patient outcomes. However, the evidence relating TDM practice with improved clinical outcome remains limited. Well designed, multicentre, randomized controlled studies are warranted.
TL;DR: D diagnosis and management of encephalitis is challenging in immunocompromised individuals, in part because of atypical clinical presentations and the presence of uncommon or novel infectious agents.
Abstract: Purpose of reviewThis article describes recent advances in the diagnosis and management of encephalitis in immunocompromised individuals.Recent findingsHerpes simplex virus (HSV) and varicella zoster virus (VZV) are common causes of encephalitis in immunocompromised individuals, although clinical ma