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Clinical implications of emerging pathogens in haemophilia: the variant Creutzfeldt-Jakob disease experience.

The impact of variant Creutzfeldt-Jakob disease (vCJD) on the clinical practice of haemophilia in the UK is coloured by the haemophilia community's experience of hepatitis C virus and human immunodeficiency virus (HIV) transmission via plasma-derived therapies in the 1980s, when the delay in recognizing and acting on the potential risks cost many patients their lives and left others to manage another chronic disease. This crisis prompted organisations such as the United Kingdom Haemophilia Centre Doctors' Organisation to advocate for the introduction of haemophilia therapies that would not be susceptible to contamination with blood-borne pathogens. After the identification of vCJD in 1996, a number of public health measures were taken in response to a government-sponsored vCJD risk assessment, and following reports of transfusion-transmission of vCJD, additional guidelines have been developed to prevent person-to-person transmission, some of which may impact the quality and availability of medical and surgical care. Variant CJD has had a significant negative effect on the UK haemophilia community, shaking patient confidence in the therapies they have received over the last 21 years, affecting the quality of care and creating the risk of stigmatizing the community as it was in the 1980s. As with HIV and vCJD, emerging blood-borne infectious agents will likely affect blood and blood-derived therapies well before we become aware of its presence. As a result, only therapies with the lowest level of risk should be used for care of patients with haemophilia.

Animals↗

Increasing incidence of Mycobacterium xenopi at Bellevue hospital: An emerging pathogen or a product of improved laboratory methods?

STUDY OBJECTIVES: To investigate the dramatic rise in number of Mycobacterium xenopi isolates identified in our mycobacteriology laboratory, and to determine if this increase was due to emerging clinical pathology or to changes in culture technique. DESIGN: Retrospective chart and laboratory review. SETTING: University-affiliated tertiary-care city hospital. PATIENTS: Eighty-one patients with a single culture positive for M xenopi from 1975 to 1994 (period 1), and 47 patients with two or more cultures positive from 1994 to 1998 (period 2). INTERVENTIONS: The Bellevue mycobacteriology laboratory changed the culture medium from solid Lowenstein-Jensen medium (used from 1975 to 1990) to the Septi-Check AFB System (Becton-Dickinson; Glencoe, MD; used from 1991 to 1994), to the Mycobacteria Growth Indication Tube (MGIT; Becton-Dickinson; used from 1995 to 1998). MEASUREMENTS AND RESULTS: We recovered 29 M xenopi isolates from 1975 to 1990, 12 isolates from 1991 to 1994, and 381 isolates from 1995 to 1998. We subsequently identified and reviewed the medical records of all 81 patients who were culture positive for M xenopi from 1975 to 1994 (period 1), and 46 patients who had two or more isolates culture positive for M xenopi from 1995 to 1998 (period 2). For period 1, 75% of the subjects were male, 80% were minority, and at least 43% were HIV positive. Only one patient had clinical M xenopi lung disease during this period. For period 2, 79% of the subjects were male, 83% were minority, and at least 58% were HIV positive; two additional patients were identified who had clinical M xenopi lung disease. CONCLUSIONS: The dramatic increase in M xenopi isolates noted in our hospital was due to a more sensitive laboratory isolation technique, rather than a true increase in clinical disease. Other hospitals utilizing MGIT systems for mycobacterial recovery should interpret positive M xenopi cultures with caution.

AIDS-Related Opportunistic Infections↗

Ehrlichia chaffeensis: a prototypical emerging pathogen.

Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and perhaps several vertebrate reservoir hosts. The moderate to severe disease caused by E. chaffeensis in humans, first identified in 1986 and reported for more than 1,000 patients through 2000, represents a prototypical "emerging infection." Knowledge of the biology and natural history of E. chaffeensis, and of the epidemiology, clinical features, and laboratory diagnosis of the zoonotic disease it causes (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded considerably in the period since its discovery. In this review, we summarize briefly the current understanding of the microbiology, pathogenesis, and clinical manifestations associated with this pathogen but focus primarily on discussing various ecological factors responsible for the recent recognition of this important and potentially life-threatening tick-borne disease. Perhaps the most pivotal element in the emergence of HME has been the staggering increases in white-tailed deer populations in the eastern United States during the 20th century. This animal serves as a keystone host for all life stages of the principal tick vector (Amblyomma americanum) and is perhaps the most important vertebrate reservoir host for E. chaffeensis. The contributions of other components, including expansion of susceptible human populations, growth and broadening geographical distributions of other potential reservoir species and A. americanum, and improvements in confirmatory diagnostic methods, are also explored.

Animals↗

Trichosporon pullulans infection in 2 patients with chronic granulomatous disease: an emerging pathogen and review of the literature.

BACKGROUND: Chronic granulomatous disease is a genetically determined primary immunodeficiency disease in which phagocytic cells are unable to kill certain bacteria and fungi after ingestion. Manifestations include recurrent pyogenic infections caused by catalase-positive microbes. Trichosporon species are emerging as opportunistic agents that cause systemic disease in immunocompromised patients. Typically disease has been described in association with T beigelii in patients with secondary immunodeficiency, such as underlying malignancy. OBJECTIVE: The objective was to report the first 2 cases of T pullulans infection in 2 male children with chronic granulomatous disease. METHODS: The records of the 2 patients were reviewed. In addition, all cases of T pullulans infection reported in the English language literature are presented. RESULTS: This report brings to 7 the total number of cases of T pullulans reported and the first in patients with chronic granulomatous disease, one with invasive pneumonia and the other with an infected paronychium and localized cellulitis. In the 5 additional cases malignancy was the principal risk factor. CONCLUSION: T pullulans has rarely been reported as a fungal pathogen. The most prominent risk factor for the development of trichosporonosis is immunocompromise, most notably with neutropenia. Abnormally functioning neutrophils, such as with chronic granulomatous disease, may also predispose individuals to this opportunistic pathogen.

Child↗

Echinococcus multilocularis: an emerging pathogen in Hungary and Central Eastern Europe?

Echinococcus multilocularis, the causative agent of human alveolar echinococcosis, is reported for the first time in Red Foxes (Vulpes vulpes) in Hungary. This parasite may be spreading eastward because the population of foxes has increased as a consequence of human interventions, and this spread may result in the emergence of alveolar echinococcosis in Central Eastern Europe.

Animals↗

Rational monoclonal antibody development to emerging pathogens, biothreat agents and agents of foreign animal disease: The antigen scale.

Many factors influence the choice of methods used to develop antibody to infectious agents. In this paper, we review the current status of the main technologies used to produce monoclonal antibodies (mAbs) from the B cells of antigen-sensitized animals. While companies are adopting advanced high-throughput methods, the major technologies used by veterinary and medical research laboratories are classical hybridoma fusion and recombinant library selection techniques. These methods have inherent advantages and limitations but have many common aspects when using immunized rodents. Laboratories with expertise in both methods of antibody development have a distinct advantage in their ability to advance mAb technology. New and re-emerging infectious threats in today's world emphasize the need for quality immunoreagents and the need to maintain expertise in mAb development. We provide examples of some common applications for mAb reagents used to identify pathogens such as the SARS-coronavirus (SARS-CoV), Bacillus anthracis, and foot-and-mouth disease (FMD) virus. We also outline a framework for investigators to make rational decisions concerning which method to use to develop mAbs based upon characteristics of the pathogen under study and the intended downstream application. Lastly, we provide parameters for the immunisation of mice and a classification system which describes the expected outcome for mAb development strategies when using classes of immunogens to generate mAbs with desired activities.

Animal Diseases↗

Viral encephalitis: familiar infections and emerging pathogens.

Significant advances have been made in our understanding of the natural history and pathogenesis of viral encephalitides. The development of PCR has greatly increased our ability to diagnose viral infections of the central nervous system, particularly for herpes and enteroviral infections. Advancing knowledge has led to the recognition that some encephalitides can be reliably prevented by vaccination (eg, Japanese encephalitis and rabies). For other pathogens such as the arboviruses, the focus has been on prevention by vector control. Finally, effective therapy has been established for a very limited number of viral infections (eg, acyclovir for herpes simplex encephalitis). Other potentially useful treatments, such as pleconaril for enteroviral meningoencephalitis are under clinical evaluation. We review current understanding of viral encephalitides with particular reference to emerging viral infections and the availability of existing treatment regimens.

Adult↗

Infections with the chlamydia-like microorganism Simkania negevensis, a possible emerging pathogen.

Although evidence for the existence of numerous chlamydia-like microorganisms has been discovered in both environmental samples and clinical specimens, very few have been grown in vitro, and little is known of their pathogenic potential. Of all such organisms, Simkania negevensis is probably the most extensively studied. This review summarizes current knowledge about this intracellular bacterium, focusing especially on human infections.

Chlamydiaceae Infections↗

Combating Gram-positive pathogens: emerging techniques to identify relevant virulence targets.

Recent progress in microbial genome sequencing, along with functional genomics technologies based on gene expression, proteomics and genetics have facilitated the identification of significant numbers of Gram-positive virulence genes. These genes represent a novel and heterogeneous class of targets for antimicrobial drug development. This review will concentrate of the contribution of two functional genomics technologies, in vivo expression technology (IVET) based on gene expression and signature-tagged mutagenesis (STM), a genetics based technology to the identification of virulence genes in Gram-positive pathogens.

Journal Article↗

Streptococcus pneumoniae, an emerging pathogen in mycotic aneurysms?

Two patients are described with a mycotic aneurysm caused by streptococcus pneumoniae infection. The patients presented with back pain and fever, and had an antecedent history of lower respiratory tract infection; neither of them were suffering from endocarditis. Mycotic aneurysms are a rare disorder with, over the years, a changing spectrum of presentation, localisation and bacterial aetiology. S. pneumoniae infection has only very rarely been reported as a cause of mycotic aneurysms. Since 1986, 14 patients with a mycotic aneurysm were treated at the Leiden University Hospital. Of these patients, 5 had mycotic aneurysms caused by S. pneumoniae infection. The mortality in these patients was high. In this communication, we would like to draw attention to S. pneumoniae infections as an emerging cause of mycotic aneurysms.

Aged↗

Nocardia veterana, a new emerging pathogen.

Nocardia veterana is a newly described species named after the veteran's hospital where it was first isolated. This initial type strain was not thought to be clinically significant. We describe three cases of pulmonary disease attributable to N. veterana: two cases in patients presenting with multiple pulmonary nodules in a setting of immunocompromise and one case of exacerbation of chronic pulmonary disease. The isolates were susceptible to ampicillin, imipenem, gentamicin, amikacin, and trimethoprim-sulfamethoxazole and had reduced susceptibilities to ceftriaxone, cefotaxime, minocycline, and ciprofloxacin. The MICs of amoxicillin-clavulanate were higher than that of ampicillin alone, and the bacteria produced a beta-lactamase detectable only after induction with clavulanic acid. Phenotypically, the isolates could not be characterized beyond the Nocardia genus level. All three isolates were definitively identified as N. veterana by PCR and sequencing of the 16S rRNA gene. On the basis of their susceptibility and restriction enzyme analysis profiles, our findings indicate that they could potentially be misidentified as N. nova. These cases illustrate the pathogenic potential of this newly described species and emphasize the importance of accurate identification of Nocardia isolates to the species level by integrated use of phenotypic and genotypic methods.

Adult↗

Enterococcus: an emerging pathogen in hospitals.

Enterococci remain an important cause of nosocomial infection, particularly among the critically ill. Nationwide, the incidence of enterococcal infections is rising, with an increasing proportion caused by resistant organisms. The spread of vancomycin-resistant enterococci (VRE) within hospitals has been well studied and helps to explain the proliferation of enterococcal disease. After hospital admission of an individual carrying VRE, persistent colonization contributes to the development of a reservoir of colonized inpatients. VRE is usually spread patient to patient by health care workers caring for colonized individuals. To interrupt this phenomenon, infection control efforts including improved hand hygiene, use of gloves and cover gowns, and antibiotic control measures have been promoted. Prospective data concerning the relative benefit of each intervention are limited, and no consensus has emerged regarding the optimal strategy for limiting the dissemination of VRE. Appropriate treatment of an individual patient infected with VRE depends upon successful interpretation of the antibiotic susceptibility profile of the infecting strain. For the critically ill patient, an aggressive approach to diagnosis and therapy is essential. However, even the newest agents available to treat resistant enterococci are limited because of emerging resistance and toxicity.

Journal Article↗

[Enterobacter sakazakii: an emerging pathogen!].

E Sakazakii is a cause of invasive infection with high death rates in neonates. This report summarizes the investigation of infections associated with the presence of the organism in commercial powdered formula fed to the infant. The organism was detected in either prepared formula, the environment in wich it was prepared, or unopened products. Clinicians should be aware of the potential risk for infection from use of nonsterile formula in the neonatal health-care setting.

Communicable Diseases, Emerging↗

Mycobacterium lentiflavum, an emerging pathogen?

Three cases of infection due to Mycobacterium lentiflavum, a recently described species characterized by multiple resistance to anti-mycobacterial drugs, are reported here. While one case simply adds to the number of cervical lynphadenitis reported in literature, the others concern the first isolations from pleural effusions, in a young boy with leukaemia and in an elderly patient with lung disease, respectively.

Adolescent↗

Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy.

We characterized 27 episodes of fungemia in 22 children infected with the human immunodeficiency virus (HIV). Fungemia in these patients presented as a community-acquired infection in the setting of outpatient total parenteral nutrition or intravenous antibiotic therapy through a chronically indwelling central venous catheter (CVC). Fungemia developed only in patients with CVCs (P < .001). Non-albicans Candida species, Torulopsis glabrata, Rhodotorula rubra, and Bipolaris spicifera constituted 52% of all causes. Fungemia was detected early, within a median of 2.4 days after the onset of new fever, which permitted prompt administration of amphotericin B (mean dosage, 0.7 mg/[kg.day]; median duration, 19 days). CVCs were removed in 23 (85%) of the episodes. We conclude that fungemia in HIV-infected children often presents as a community-acquired infection, is frequently due to newly emerging opportunistic fungi, and can be managed, with a high level of success (95% survival with no posttherapeutic sequelae), by early diagnosis, prompt initiation of amphotericin B therapy, and removal of the CVC.

Antifungal Agents↗

Human monocytic ehrlichiosis: an emerging pathogen in transplantation.

BACKGROUND: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

Animals↗