Showing papers in "Clinical Microbiology Reviews in 2011"
TL;DR: The substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.
Abstract: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the "precautionary principle." Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans-directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.
1,702 citations
TL;DR: The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.
Abstract: Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.
1,107 citations
TL;DR: The authors' efforts in characterizing the molecular epidemiology of giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes.
Abstract: Summary: Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution of Giardia duodenalis genotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for some G. duodenalis genotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics of G. duodenalis in humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of various G. duodenalis genotypes, and the ecology of environmental contamination.
986 citations
TL;DR: How control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed are drawn together to show how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir.
Abstract: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.
651 citations
TL;DR: Diagnosis of fungi infections is becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of patients, and techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.
Abstract: Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.
627 citations
TL;DR: Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached and there is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB.
Abstract: SUMMARY A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.
593 citations
TL;DR: The United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century as improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic.
Abstract: Summary: Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century.
576 citations
TL;DR: The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions, which initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses.
Abstract: The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.
564 citations
TL;DR: The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs.
Abstract: SUMMARY Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program.
542 citations
TL;DR: Serological, histopathological, and molecular approaches have been recently adopted as auxiliary tools for the diagnosis of this mycotic infection and the first-choice treatment for both humans and cats is itraconazole.
Abstract: Sporotrichosis, which is caused by the dimorphic fungus Sporothrix schenckii, is currently distributed throughout the world, especially in tropical and subtropical zones. Infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Certain leisure and occupational activities, such as floriculture, agriculture, mining, and wood exploitation, are traditionally associated with the mycosis. Zoonotic transmission has been described in isolated cases or in small outbreaks. Since the end of the 1990s there has been an epidemic of sporotrichosis associated with transmission by cats in Rio de Janeiro, Brazil. More than 2,000 human cases and 3,000 animal cases have been reported. In humans, the lesions are usually restricted to the skin, subcutaneous cellular tissue, and adjacent lymphatic vessels. In cats, the disease can evolve with severe clinical manifestations and frequent systemic involvement. The gold standard for sporotrichosis diagnosis is culture. However, serological, histopathological, and molecular approaches have been recently adopted as auxiliary tools for the diagnosis of this mycotic infection. The first-choice treatment for both humans and cats is itraconazole.
486 citations
TL;DR: Several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in high-burden countries are described.
Abstract: Summary: With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network.
TL;DR: Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria, which increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing Nosocomial outbreaks due to this organism.
Abstract: Summary: Serratia species, in particular Serratia marcescens, are significant human pathogens. S. marcescens has a long and interesting taxonomic, medical experimentation, military experimentation, and human clinical infection history. The organisms in this genus, particularly S. marcescens, were long thought to be nonpathogenic. Because S. marcescens was thought to be a nonpathogen and is usually red pigmented, the U.S. military conducted experiments that attempted to ascertain the spread of this organism released over large areas. In the process, members of both the public and the military were exposed to S. marcescens, and this was uncovered by the press in the 1970s, leading to U.S. congressional hearings. S. marcescens was found to be a certain human pathogen by the mid-1960s. S. marcescens and S. liquefaciens have been isolated as causative agents of numerous outbreaks and opportunistic infections, and the association of these organisms with point sources such as medical devices and various solutions given to hospitalized patients is striking. Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria. Since many nosocomial infections are caused by multiply antibiotic-resistant strains of S. marcescens, this increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing nosocomial outbreaks due to this organism. S. marcescens, and probably other species in the genus, carries several antibiotic resistance determinants and is also capable of acquiring resistance genes. S. marcescens and S. liquefaciens are usually identified well in the clinical laboratory, but the other species are rare enough that laboratory technologists may not recognize them. 16S rRNA gene sequencing may enable better identification of some of the less common Serratia species.
TL;DR: The history, replication, genetics, characteristics, and factors involved in the pathogenesis of Mycoplasma genitalium are presented, including adhesion, the influence of hormones, motility, possible toxin production, and immunological responses.
Abstract: SUMMARY The history, replication, genetics, characteristics (both biological and physical), and factors involved in the pathogenesis of Mycoplasma genitalium are presented. The latter factors include adhesion, the influence of hormones, motility, possible toxin production, and immunological responses. The preferred site of colonization, together with current detection procedures, mainly by PCR technology, is discussed. The relationships between M. genitalium and various diseases are highlighted. These diseases include acute and chronic nongonococcal urethritis, balanoposthitis, chronic prostatitis, and acute epididymitis in men and urethritis, bacterial vaginosis, vaginitis, cervicitis, pelvic inflammatory disease, and reproductive disease in women. A causative relationship, or otherwise strong association, between several of these diseases and M. genitalium is apparent, and the extent of this, on a subjective basis, is presented; also provided is a comparison between M. genitalium and two other genital tract-orientated mollicutes, namely, Mycoplasma hominis, the first mycoplasma of human origin to be discovered, and Ureaplasma species. Also discussed is the relationship between M. genitalium and infertility and also arthritis in both men and women, as is infection in homosexual and immunodeficient patients. Decreased immunity, as in HIV infections, may enhance mycoplasmal detection and increase disease severity. Finally, aspects of the antimicrobial susceptibility and resistance of M. genitalium, together with the treatment and possible prevention of mycoplasmal disease, are discussed.
TL;DR: The genus Arcobacter has become increasingly important because its members are being considered emergent enteropathogens and/or potential zoonotic agents as well as on their virulence potential and implication in human and animal diseases.
Abstract: SUMMARY The genus Arcobacter , defined almost 20 years ago from members of the genus Campylobacter , has become increasingly important because its members are being considered emergent enteropathogens and/or potential zoonotic agents. Over recent years information that is relevant for microbiologists, especially those working in the medical and veterinary fields and in the food safety sector, has accumulated. Recently, the genus has been enlarged with several new species. The complete genomes of Arcobacter butzleri and Arcobacter nitrofigilis are available, with the former revealing diverse pathways characteristic of free-living microbes and virulence genes homologous to those of Campylobacter. The first multilocus sequence typing analysis showed a great diversity of sequence types, with no association with specific hosts or geographical regions. Advances in detection and identification techniques, mostly based on molecular methods, have been made. These microbes have been associated with water outbreaks and with indicators of fecal pollution, with food products and water as the suspected routes of transmission. This review updates this knowledge and provides the most recent data on the taxonomy, species diversity, methods of detection, and identification of these microbes as well as on their virulence potential and implication in human and animal diseases.
TL;DR: Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus, but the use of antIfungal regimens containing triazoles appears to be the best therapeutic approach.
Abstract: SUMMARY Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.
TL;DR: Current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis is reviewed.
Abstract: SUMMARY A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis.
TL;DR: The most recent views on the pathophysiology of pneumococcal meningitis are discussed, as well as potential targets for (adjunctive) therapy.
Abstract: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.
TL;DR: The biology of EBV and the host immune response are described and the characteristics and pathogenesis of infectious mononucleosis are discussed in the context of developing therapeutic and preventative strategies.
Abstract: Summary: Epstein-Barr virus (EBV) is a gammaherpesvirus that infects a large fraction of the human population. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. In some cases, primary infection can result in infectious mononucleosis. Furthermore, when host-virus balance is not achieved, the virus can drive potentially lethal lymphoproliferation and lymphomagenesis. In this review, we describe the biology of EBV and the host immune response. We review the diagnosis of EBV infection and discuss the characteristics and pathogenesis of infectious mononucleosis. These topics are approached in the context of developing therapeutic and preventative strategies.
TL;DR: The infectious diseases affecting patients with inborn errors of NF-κB-dependent TLR and IL-1R immunity are reviewed, finding that they were initially thought to be rare but have now been diagnosed in over 170 patients worldwide.
Abstract: Autosomal recessive IRAK-4 and MyD88 deficiencies predispose affected patients to recurrent invasive pyogenic bacterial infection. Both defects result in the selective impairment of cellular responses to Toll-like receptors (TLRs) other than TLR3 and of cellular responses to most interleukin-1 receptors (IL-1Rs), including IL-1R, IL-18R, and IL-33R. Hypomorphic mutations in the X-linked NEMO gene and hypermorphic mutations in the autosomal IKBA gene cause X-linked recessive and autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) syndromes. Both of these defects impair NF-κB-mediated cellular responses to multiple receptors, including TLRs, IL-1Rs, and tumor necrosis factor receptors (TNF-Rs). They therefore confer a much broader predisposition to infections than that for IRAK-4 and MyD88 deficiencies. These disorders were initially thought to be rare but have now been diagnosed in over 170 patients worldwide. We review here the infectious diseases affecting patients with inborn errors of NF-κB-dependent TLR and IL-1R immunity.
TL;DR: An overview of the epidemiology, clinical manifestations, diagnosis of, treatment of, and prognosis for unusual Mucormycetes infections (non-Rhizopus, -Mucor, and -Lichtheimia species) is provided.
Abstract: Rhizopus, Mucor, and Lichtheimia (formerly Absidia) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all cases. In contrast, Cunninghamella, Apophysomyces, Saksenaea, Rhizomucor, Cokeromyces, Actinomucor, and Syncephalastrum species individually are responsible for fewer than 1 to 5% of reported cases of mucormycosis. In this review, we provide an overview of the epidemiology, clinical manifestations, diagnosis of, treatment of, and prognosis for unusual Mucormycetes infections (non-Rhizopus, -Mucor, and -Lichtheimia species). The infections caused by these less frequent members of the order Mucorales frequently differ in their epidemiology, geographic distribution, and disease manifestations. Cunninghamella bertholletiae and Rhizomucor pusillus affect primarily immunocompromised hosts, mostly resulting from spore inhalation, causing pulmonary and disseminated infections with high mortality rates. R. pusillus infections are nosocomial or health care related in a large proportion of cases. While Apophysomyces elegans and Saksenaea vasiformis are occasionally responsible for infections in immunocompromised individuals, most cases are encountered in immunocompetent individuals as a result of trauma, leading to soft tissue infections with relatively low mortality rates. Increased knowledge of the epidemiology and clinical presentations of these unusual Mucormycetes infections may improve early diagnosis and treatment.
TL;DR: Gathering information and conducting research in a more systematic and methodical fashion through an organized research network, including zoos, veterinary practices, and rural clinics and hospitals, are needed to better define the microbiology of animal bite wound infections in humans.
Abstract: The microbiology of animal bite wound infections in humans is often polymicrobial, with a broad mixture of aerobic and anaerobic microorganisms. Bacteria recovered from infected bite wounds are most often reflective of the oral flora of the biting animal, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. Our review has focused on bite wound infections in humans from dogs, cats, and a variety of other animals such as monkeys, bears, pigs, ferrets, horses, sheep, Tasmanian devils, snakes, Komodo dragons, monitor lizards, iguanas, alligators/crocodiles, rats, guinea pigs, hamsters, prairie dogs, swans, and sharks. The medical literature in this area has been made up mostly of small case series or case reports. Very few studies have been systematic and are often limited to dog or cat bite injuries. Limitations of studies include a lack of established or inconsistent criteria for an infected wound and a failure to utilize optimal techniques in pathogen isolation, especially for anaerobic organisms. There is also a lack of an understanding of the pathogenic significance of all cultured organisms. Gathering information and conducting research in a more systematic and methodical fashion through an organized research network, including zoos, veterinary practices, and rural clinics and hospitals, are needed to better define the microbiology of animal bite wound infections in humans.
TL;DR: An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease, granulocytic anaplasmosis.
Abstract: SUMMARY Anaplasma phagocytophilum persists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum is an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum evolved the remarkable ability to hijack the regulatory system of host cells. A. phagocytophilum alters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-γ). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease.
TL;DR: The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart, suggesting that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.
Abstract: Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.
TL;DR: Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative, and few options are currently available to prevent the transmission of B. microti by blood transfusion.
Abstract: Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a variety of species or types of Babesia have been described in the literature as causing infection in humans, the rodent parasite Babesia microti has emerged as the focal point of human disease, especially in the United States. Not only has B. microti become established as a public health concern, this agent is increasingly being transmitted by blood transfusion: estimates suggest that between 70 and 100 cases of transfusion-transmitted Babesia (TTB) have occurred over the last 30 years. A recent upsurge in TTB cases attributable to B. microti, coupled with at least 12 fatalities in transfusion recipients diagnosed with babesiosis, has elevated TTB to a key policy issue in transfusion medicine. Despite clarity on a need to mitigate transmission risk, few options are currently available to prevent the transmission of B. microti by blood transfusion. Future mitigation efforts may stress serological screening of blood donors in regionalized areas of endemicity, with adjunct nucleic acid testing during the summer months, when acute infections are prevalent. However, several hurdles remain, including the absence of a licensed blood screening assay and a thorough cost-benefit analysis of proposed interventions. Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative.
TL;DR: It has been 10 years since human metapneumovirus was identified as a causative agent of respiratory illness in humans and a number of areas with key questions to be addressed in the future are identified.
Abstract: It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.
TL;DR: The experimental and field trial data which have uncovered the importance of Wolbachia symbiosis in onchocerciasis are summarized.
Abstract: The discovery of Wolbachia intracellular bacteria within filarial nematodes, including Onchocerca volvulus, the causative agent of onchocerciasis or "river blindness," has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminate Wolbachia, delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role for Wolbachia in transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae. Wolbachia has also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with the Wolbachia-mediated recruitment of mast cells, enhance infectivity. The Wolbachia activation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance of Wolbachia symbiosis in onchocerciasis.
TL;DR: This review evaluates methods for typing N. gonorrhoeae isolates and recommends various methods for different situations, and DNA sequencing of chromosomal housekeeping genes, such as multilocus sequence typing (MLST), provides a more nuanced understanding.
Abstract: SUMMARY Gonorrhea, which may become untreatable due to multiple resistance to available antibiotics, remains a public health problem worldwide. Precise methods for typing Neisseria gonorrhoeae, together with epidemiological information, are crucial for an enhanced understanding regarding issues involving epidemiology, test of cure and contact tracing, identifying core groups and risk behaviors, and recommending effective antimicrobial treatment, control, and preventive measures. This review evaluates methods for typing N. gonorrhoeae isolates and recommends various methods for different situations. Phenotypic typing methods, as well as some now-outdated DNA-based methods, have limited usefulness in differentiating between strains of N. gonorrhoeae. Genotypic methods based on DNA sequencing are preferred, and the selection of the appropriate genotypic method should be guided by its performance characteristics and whether short-term epidemiology (microepidemiology) or long-term and/or global epidemiology (macroepidemiology) matters are being investigated. Currently, for microepidemiological questions, the best methods for fast, objective, portable, highly discriminatory, reproducible, typeable, and high-throughput characterization are N. gonorrhoeae multiantigen sequence typing (NG-MAST) or full- or extended-length porB gene sequencing. However, pulsed-field gel electrophoresis (PFGE) and Opa typing can be valuable in specific situations, i.e., extreme microepidemiology, despite their limitations. For macroepidemiological studies and phylogenetic studies, DNA sequencing of chromosomal housekeeping genes, such as multilocus sequence typing (MLST), provides a more nuanced understanding.
TL;DR: No standard treatment guidelines are available, but published literature agrees that immunocompromised patients should be treated with multiple antibiotics, tailored to the disease presentation and underlying degree of immune suppression.
Abstract: Mycobacterium haemophilum is a slowly growing acid-fast bacillus (AFB) belonging to the group of nontuberculous mycobacteria (NTM) frequently found in environmental habitats, which can colonize and occasionally infect humans and animals. Several findings suggest that water reservoirs are a likely source of M. haemophilum infections. M. haemophilum causes mainly ulcerating skin infections and arthritis in persons who are severely immunocompromised. Disseminated and pulmonary infections occasionally occur. The second at-risk group is otherwise healthy children, who typically develop cervical and perihilar lymphadenitis. A full diagnostic regimen for the optimal detection of M. haemophilum includes acid-fast staining, culturing at two temperatures with iron-supplemented media, and molecular detection. The most preferable molecular assay is a real-time PCR targeting an M. haemophilum-specific internal transcribed spacer (ITS), but another approach is the application of a generic PCR for a mycobacterium-specific fragment with subsequent sequencing to identify M. haemophilum. No standard treatment guidelines are available, but published literature agrees that immunocompromised patients should be treated with multiple antibiotics, tailored to the disease presentation and underlying degree of immune suppression. The outcome of M. haemophilum cervicofacial lymphadenitis in immunocompetent patients favors surgical intervention rather than antibiotic treatment.
TL;DR: Studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro are recounted, consistent with an estrogen-fungus receptor-mediated effect on pathogenesis.
Abstract: Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. Epidemiological studies indicate a striking rarity of disease (but not infection) in females, but only during the reproductive years. This suggested a hormonal interaction between female hormones and the etiologic dimorphic fungus Paracoccidioides brasiliensis. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. This suggests an evolutionary conservation of hormonal receptor systems. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro. This block has been demonstrated to occur in vivo in animal studies. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. The fungal genes responsive to estrogen action are under study.
TL;DR: This review aims to discuss expert systems in general and how they may be used in medicine as a whole and clinical microbiology in particular (with the aid of interpretive reading) and considers rule- based systems, pattern-based systems, and data mining and introduces neural nets.
Abstract: This review aims to discuss expert systems in general and how they may be used in medicine as a whole and clinical microbiology in particular (with the aid of interpretive reading). It considers rule-based systems, pattern-based systems, and data mining and introduces neural nets. A variety of noncommercial systems is described, and the central role played by the EUCAST is stressed. The need for expert rules in the environment of reset EUCAST breakpoints is also questioned. Commercial automated systems with on-board expert systems are considered, with emphasis being placed on the "big three": Vitek 2, BD Phoenix, and MicroScan. By necessity and in places, the review becomes a general review of automated system performances for the detection of specific resistance mechanisms rather than focusing solely on expert systems. Published performance evaluations of each system are drawn together and commented on critically.