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Hantavirus: emergency department response to a disaster from an emerging pathogen.

In May 1993, the appearance of critically ill patients with unexplained respiratory distress was noted in the Four Corners area formed by New Mexico, Arizona, and Colorado. This epidemic was ultimately linked to a hantavirus, an emerging pathogen. The impact on the emergency department of a new infectious disease with respiratory distress is described. A model is proposed to manage infectious disease disasters. Emerging infections that are important to emergency physicians are discussed. Recommendations that focus on disaster management and prevention of the spread of an unknown pathogen are developed.

Bunyaviridae Infections↗

Protecting the blood supply from emerging pathogens: the role of pathogen inactivation.

Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid-containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.

Anti-Infective Agents↗

Rapid identification of emerging pathogens: coronavirus.

We describe a new approach for infectious disease surveillance that facilitates rapid identification of known and emerging pathogens. The process uses broad-range polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry for accurate mass measurements of PCR products, and base composition signature analysis to identify organisms in a sample. We demonstrate this principle by using 14 isolates of 9 diverse Coronavirus spp., including the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). We show that this method could identify and distinguish between SARS and other known CoV, including the human CoV 229E and OC43, individually and in a mixture of all 3 human viruses. The sensitivity of detection, measured by using titered SARS-CoV spiked into human serum, was approximate, equals1 PFU/mL. This approach, applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens, is capable of automated analysis of >900 PCR reactions per day.

Animals↗

Identification and characterization of an RTX toxin in the emerging pathogen Kingella kingae.

Kingella kingae is an emerging bacterial pathogen that is increasingly recognized as the causative agent of a variety of pediatric diseases, including septic arthritis and osteomyelitis. The pathogenesis of K. kingae disease is believed to begin with colonization of the upper respiratory tract. In the present study, we examined interactions between K. kingae and cultured respiratory epithelial cells and observed potent cytotoxicity, detected by both microscopy and lactic acid dehydrogenase (LDH) release assays. Experiments with synovial and macrophage cell lines revealed cytotoxicity for these cell types as well. Using mariner mutagenesis and a screen for loss of cytotoxicity, a genetic locus encoding an RTX toxin system was identified. Disruption of the K. kingae RTX locus resulted in a loss of cytotoxicity for respiratory epithelial, synovial, and macrophage cell lines. DNA sequence analysis demonstrated that the RTX locus is flanked by insertion elements and has a reduced G+C content compared to that of the whole genome. Two relatively less invasive Kingella species, K. oralis and K. denitrificans, were found to be noncytotoxic and to lack the RTX region, as determined by LDH release assays and Southern blotting. We concluded that K. kingae expresses an RTX toxin that has wide cellular specificity and was likely acquired horizontally. The possible roles for this toxin in the pathogenesis of K. kingae disease include breaching of the epithelial barrier and destruction of target tissues, such as synovium (joint lining).

Animals↗

Stenotrophomonas maltophilia: antimicrobial resistance and molecular typing of an emerging pathogen in a Turkish university hospital.

Despite its limited pathogenicity, Stenotrophomonas maltophilia is an emerging nosocomial pathogen. This study investigated the isolation frequency, antimicrobial resistance and genotypic relationships of 205 S. maltophilia isolates from 188 patients in a university hospital between 1998 and 2003. Susceptibility profiles for 11 antimicrobial agents were determined by the NCCLS agar dilution method for non-fermentative bacteria, while enterobacterial repetitive intergenic consensus sequence (ERIC)-PCR and pulsed-field gel electrophoresis (PFGE) were used for genotyping of the isolates. Of the 205 isolates, 56.1% were isolated in the last 2 years of the study. The risk of S. maltophilia isolation was higher in intensive care units, S. maltophilia was isolated mostly (86.8%) after hospitalisation for >or= 48 h, and 90.4% of the patients had underlying diseases. Resistance levels were>60% for all antimicrobial agents tested except co-trimoxazole. High genetic diversity was found among the S. maltophilia isolates, and cross-infection with S. maltophilia was not common. Although ERIC-PCR revealed fewer genotypes than PFGE, it proved to be a rapid and easy method for S. maltophilia genotyping, and was more economical than PFGE.

Anti-Bacterial Agents↗

E. coli O157:H7 is an emerging pathogen in Missouri.

Dramatic media reports of recent outbreaks of illness caused by Escherichia coli O157:H7 have drawn national attention to this emerging pathogen. In 1993, a widely publicized outbreak of over 500 culture-confirmed cases was traced to fast-food hamburgers in Washington, Idaho, Nevada and California. Closer to home, the first (and still the largest) reported waterborne outbreak of this disease occurred in Cabool, Missouri in 1989. That outbreak affected 243 people, of whom 32 were hospitalized, 2 had hemolytic uremic syndrome, and 4 died. E. coli O157:H7 was added to the list of reportable diseases in Missouri in mid-1992, but its importance is still not widely recognized. This article reviews the results of state and national surveillance for the disease, and suggests methods for improving diagnosis and reporting.

Adolescent↗

Transfusion-transmitted infections: existing and emerging pathogens.

In general, the risk of transfusion-transmitted infections has been greatly reduced today. However, blood-borne bacterial and parasitic infections and emerging infections transmitted through transfusion are an area of increasing concern. Implementation of stringent donor eligibility criteria, improved donor screening and more sophisticated as well as sensitive methods of antibody, antigen and viral genome detection, have virtually eliminated transfusion transmitted infection in developed countries. In developing countries like India, the risk of transfusion-transmitted infections is still considerable. A comprehensive MEDLINE search and review of relevant transfusion medicine literature were carried out and the data extracted and studied with particular reference to emerging pathogens transmitted through blood transfusion and posing a huge threat.

Animals↗

Emerging Pathogens Associated with Infectious Diarrhea.

In recent years, emerging microbial pathogens associated with infectious diarrhea have caused significant morbidity and mortality. Although sporadic cases of infectious diarrhea have occurred worldwide in the past, recent outbreaks in the United States traced to contaminated water or food have raised concerns about the safety of the water supply and the adequacy of surveillance of the food supply and foodborne diseases. In 1993, Cryptosporidium parvum, an important cause of unrelenting diarrhea and severe weight loss in AIDS patients, was associated with the largest outbreak of infectious diarrhea caused by contaminated municipal water that has ever been reported in the U.S. During the early summer of 1996, a major outbreak of Cyclospora cayetanensis that infected approximately 1,500 persons in 20 states, Washington, D.C. and two Canadian provinces was reported from North America. The suspected food vehicle in this outbreak was contaminated raspberries imported from Guatemala. In addition to these coccidian protozoa,Escherichia coli 0157:H7, first recognized in 1982 as a cause of hemorrhagic colitis, has recently been responsible for a multi-state outbreak in the U.S. due to contamination of commercial ground beef, and an outbreak in Japan that infected over 9,500 persons, two-thirds of whom were children. The contaminated food vehicle in the latter outbreak, although suspected to be radish sprouts, remains unknown. These recent massive outbreaks underscore the importance of a well-established public health infrastructure and an effective surveillance system for the early identification and reporting of infected patients that will lead to appropriate epidemiologic investigations and the rapid detection of contaminated vehicles.

Journal Article↗

Emerging pathogen Cyclospora cayetanensis infection in Nepal.

Cylospora cayetanensis, an emerging parasitic pathogen of human is being increasingly recognized throughout the world, however the means of transmission and the possibility of a reservoir host remain an enigma. A longitudinal study on cyclosporiasis in different parts of Nepal was carried out from April, 1995 until November, 2000. Fecal specimens were collected from symptomatic and asymptomatic patients. The data shows a distinct seasonality with the highest infection rates occurring during the summer and rainy season of the year. Attempts have been made to determine the sources of infection and possible reservoir hosts. Stools were examined from nearly 700 animals such as chickens, pigs, buffalos, cows, dogs, cats, monkeys, rats, mice and pigeons. In addition, vegetable farms around the Kathmandu Valley were examined during the seasonal high and low periods of transmission. C. cayetanensis-like oocysts were found in sewage water and from vegetable washings on five occasions during June, July, August, October, and November. Similarly, C. cayetanensis-like oocysts were recovered from mice, rats, chickens, and dogs. These results suggest that these sources may be important in the transmission of this parasitosis. However, further studies will be required to obtain definitive answers on transmission.

Adolescent↗

Enterobacteria of emerging pathogenic significance from clinical cases in man and animals and detection of toads and wall lizards as their reservoirs.

A total of 416 samples comprising faecal samples from diarrhoeic cases of man, calves, sheep and goats, and urine samples from patients with urinary tract infections, were examined for the presence of enterobacteria of emerging pathogenic significance. Citrobacter freundii from 20, C. intermedius biotype-a from four, Serratia marcescens (serotype 05:H13, bactericin type 16) from one and Erwinia herbicola from two human stool samples were isolated. Only two urine samples yielded C. freundii. Citrobacter freundii was isolated from 10 and C. intermedius biotype-a from two calves. From sheep and goats, two isolates of C. freundii and three of C. intermedius biotype-a were obtained. None of these samples yielded Edwarsiella tarda or Yersinia enterocolitica. The examination of 99 toads and 145 wall lizards revealed that toads were reservoirs for C. freundii, C. intermedius biotype-a and Salmonella brijbhumi, whereas wall lizards were reservoirs for C. freundii, C. intermedius biotype-a, E. herbicola, Enterobacter cloacae and Salmonella spp. These bacteria were present in the range of 2.0 x 10(6) to 6.0 x 10(11) organisms per gram of intestinal contents. In addition, toads were carriers for Edwardsiella tarda (new serotypes 04167:H1 and 05159: non-motile). None of the toads and wall lizards proved positive for C. intermedius biotype-b (C. koseri), S. marcescens and Y. entercolitica. C. freundii, C. intermedius biotype-a, E. herbicola and S. marcescens were resistant to penicillin and erythromycin whereas E. tarda isolates were also resistant to gentamycin, neomycin, colistin and sulfamethaxazole.

Animal Diseases↗

Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.

Animals↗

Comparison of the E-test with the NCCLS M38-P method for antifungal susceptibility testing of common and emerging pathogenic filamentous fungi.

The National Committee for Clinical Laboratory Standards (NCCLS) M38-P method describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds). The present study evaluated the in vitro fungistatic activities of itraconazole and amphotericin B by the E-test and the NCCLS M38-P microdilution method against 186 common and emerging pathogenic molds (123 isolates of Aspergillus spp. [five species], 16 isolates of Fusarium spp. [two species], 4 Paecilomyces lilacinus isolates, 5 Rhizopus arrhizus isolates, 15 Scedosporium spp., 18 dematiaceous fungi, and 5 Trichoderma longibrachiatum isolates). The agreement between the methods for amphotericin B MICs ranged from 70% for Fusarium solani to > or =90% for most of the other species after the first reading; agreement was dependent on both the incubation time and the species being evaluated. Major discrepancies between the amphotericin B MICs determined by the E-test and the NCCLS M38-P method were demonstrated for three of the five species of Aspergillus tested and the two species of Fusarium tested. This discrepancy was more marked after 48 h of incubation; the geometric mean MICs determined by the E-test increased between 24 and 48 h from between 1.39 and 3.3 microg/ml to between 5.2 and >8 microg/ml for Aspergillus flavus, Aspergillus fumigatus, and Aspergillus nidulans. The agreement between the itraconazole MICs determined by the E-test and the NCCLS M38-P method ranged from 83.3% for A. nidulans to > or =90% for all the other species tested; the overall agreement was higher (92.7%) than that for amphotericin B (87.9%). The agreement was less dependent on the incubation time. Clinical trials need to be conducted to establish the role of the results of either the E-test or the NCCLS M38-P method in vitro for molds with the two agents as predictors of clinical outcome.

Amphotericin B↗

Emerging pathogens for pneumonia in Singapore.

The death rate from pneumonia in Singapore has increased steadily over the past decade. The emerging respiratory pathogens may have contributed to this increased mortality. New challenges have arisen from changes in the characteristics of the host and the susceptibilities of the various pathogens to antibiotics. There has been a 60-fold increase in the incidence of penicillin resistance in Streptococcus pneumoniae, the major pathogen for community-acquired pneumonia (CAP). Gram-negative bacilli are the major pathogens in severe CAP with Klebsiella pneumonia being the most frequently isolated organism. There has been a small increase in the number of cases of Legionnaire's disease and a marked increase in the incidence of melioidosis. While the overall incidence of tuberculosis has been unchanged, the number of non-residents with tuberculosis has doubled in the past 5 years. The rising prevalence of human immunodeficiency Virus infection is reflected in an increasing number of apparently healthy young men who present with CAP caused by Pneumocystis carinii. There is increasing resistance to antibiotics among gram-negative bacilli and Staphylococcus aureus, the dominant pathogens in hospital-acquired pneumonia. New strategies are urgently needed to prevent the emergence of pathogens in the hospital environment which may be resistant to all known antibiotics.

AIDS-Related Opportunistic Infections↗

Enterohemorrhagic Escherichia coli: a family of emerging pathogens.

Enterohemorrhagic Escherichia coli (EHEC) have emerged over the last decade as important enteric pathogens because of their potential to induce both hemorrhagic colitis and fatal hemolytic uremic syndrome (HUS). HUS following EHEC colitis has become the leading cause of pediatric renal failure requiring kidney transplant in North America. The ability for EHEC to induce disease is dependent upon their ability to adhere to the intestinal mucosa in an intimate fashion, and to produce potent cytotoxins. These virulence factors (toxin production and enteroadherence) have been implicated in the pathogenesis of EHEC-induced disease. In this review we will discuss the symptomatology, epidemiology, laboratory diagnosis, pathogenesis, complications, treatment, and prevention of EHEC disease. We will review HUS with emphasis on treatment and prevention. Finally we will review animal models for EHEC infection in order to discuss their role in developing new strategies for the treatment and prevention of EHEC-associated diseases.

Animals↗

Pyogenic liver abscess: Klebsiella as an emerging pathogen.

Patients with pyogenic liver abscesses often present to the emergency department with fever of unknown origin. After the appropriate clinical evaluation, cross-sectional imaging may be performed in the emergent setting to aid in localization of fever source. On computed tomography imaging, pyogenic liver abscesses may present as inflammatory masses in the liver, with Escherichia coli as the most common pathogen. We report an emerging hepatic pathogen as the cause, Klebsiella pneumoniae.

Aged↗

Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus.

Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.

Animals↗

[Methicillin-resistant Staphylococcus aureus (MRSA) in veterinary medicine: a "new emerging pathogen"?].

The problem of nosocomial infections is of increasing importance in veterinary medicine. As an example, this review summarizes current knowledge regarding methicillin-resistant Staphylococcus aureus (MRSA) as a typical example, as these pathogens are the most important agents of nosocomial infections in human medicine worldwide and are being increasingly reported in veterinary medicine. MRSA are classified by their ability to be resistant against oxacillin/methicillin, this feature being confered by mecA, a gene which was acquired by horizontal gene transfer of the staphylococcal gene cassette (SCCmec). It is this genetic information that enables MRSA to be resistant against all penicillins, cehalosporins and carbapenems. In addition, MRSA are often resistant against a variety of other antiinfectives, i.e. aminoglycosides, macrolides, lincosamide, streptomycins, tetracyclin, chloramphenicol, but also against fluorquinolones and rifampicin. Presumably, these highly adapted strains are particularly able to acquire resistance genes located on plasmids or transposons. They are also able to develop point mutations, further leading to resistant phenotypes. If these pathogens are leading to infectious diseases, veterinarians may be confronted with a worst-case scenario, being left without any antiinfective therapeutic. As Staphylococcus aureus is highly tenacid, professional hygiene management is of utmost importance. The increasing number of published sporadic MRSA infections, MRSA-infectious diseases as well as MRSA outbreaks in veterinary medicine justifies their recognition as a "New Emerging Pathogen". So far, horses and dogs are mostly affected by MRSA. Although transmission between humans and animals has been reported occasionally, the sources, routes of transmission or the epidemiological relevance of MRSA infections in animals are far from being understood. Therefore, epidemiological investigations utilizing molecular typing tools are mandatory. Typing tools like multilocus-sequence-typing (MLST), pulsefield-gelelectrophoresis (PFGE), sequence analysis of the gene encoding protein A (spa-typing) as well as SCCmec-typing are all at hand.

Animals↗

Rhodococcus equi: an emerging pathogen.

More than 100 cases of Rhodococcus equi infection have been reported since the first description of human disease caused by this organism. The vast majority of patients infected with R. equi are immunocompromised, and two-thirds have human immunodeficiency virus infection. The clinical manifestations of R. equi infection are diverse, although 80% of patients have some pulmonary involvement. The organism is easily cultured from specimens of infected tissue or body fluid, but it may be misdiagnosed as a contaminant. Treatment is often prolonged, and relapses at distant sites are common. This article summarizes the history, diagnosis, clinical features, and treatment of infection with this emerging pathogen.

Actinomycetales Infections↗