Sean P. Elliott

Rat Bite Fever and Streptobacillus moniliformis

SUMMARY Rat bite fever, caused by Streptobacillus moniliformis, is a systemic illness classically characterized by fever, rigors, and polyarthralgias. If left untreated, it carries a mortality rate of 10%. Unfortunately, its nonspecific initial presentation combined with difficulties in culturing its causative organism produces a significant risk of delay or failure in diagnosis. The increasing popularity of rats and other rodents as pets, together with the risk of invasive or fatal disease, demands increased attention to rat bite fever as a potential diagnosis. The clinical and biological features of rat bite fever and Streptobacillus moniliformis are reviewed, providing some distinguishing features to assist the clinician and microbiologist in diagnosis.

The Spectrum and Presentation of Disseminated Coccidioidomycosis

PURPOSE Extrapulmonary dissemination of Coccidioides species is associated with significant morbidity and mortality. The clinical manifestations vary widely according to the host, the severity of illness, and location of dissemination. The morbidity and mortality can be reduced by early recognition and treatment, which in turn depends on understanding the spectrum and presentation of disease. METHODS We performed a retrospective analysis of 150 cases with extrapulmonary nonmeningeal disease seen from 1996 to 2007 at a referral medical center in an endemic region. RESULTS Hematogenous dissemination was associated with high mortality and occurred primarily in immunocompromised patients, but only 30% of patients with more limited forms of dissemination were immunocompromised. In keeping with prior studies, there was a preponderance of males (nearly 2:1) and people of African or Asian (especially Pacific Islanders) descent. In contrast, Hispanics and diabetics were not at increased risk. Serology was frequently negative in immunocompromised patients, but the diagnosis could be established by isolation of the organism in culture, or in histologic or cytologic specimens. CONCLUSIONS Although coccidioidomycosis is a great imitator, the diagnosis can usually be made readily if a high level of suspicion is maintained and appropriate diagnostic testing is performed. In most patients, that will include serologic testing in addition to cultures and histology or cytology of appropriate samples.

Characterization of the Human Forssman Synthetase Gene AN EVOLVING ASSOCIATION BETWEEN GLYCOLIPID SYNTHESIS AND HOST-MICROBIAL INTERACTIONS

Differences in glycolipid expression between species contribute to the tropism of many infectious pathogens for their hosts. For example, we demonstrate that cultured human and monkey urinary epithelial cells fail to bind a canine Escherichia coli uropathogenic isolate; however, transfection of these cells with the canine Forssman synthetase (FS) cDNA enables abundant adherence by the same pathogen, indicating that addition of a single sugar residue to a glycolipid receptor has marked effects on microbial attachment. Given the contribution of glycolipids to host-microbial interactions, we sought to determine why human tissues do not express Forssman glycolipid. Query of the GenBankTM data base yielded a human sequence with high identity to the canine FS cDNA. Reverse transcription polymerase chain reaction and Northern blotting demonstrated the presence of FS mRNA in all tissues examined. A human FS cDNA was characterized, revealing identities with the canine FS gene of 86 and 83% at the nucleotide and predicted amino acid sequences, respectively. In contrast to the canine FS cDNA, transfection of COS-1 cells with the human FS cDNA resulted in no detectable FS enzyme activity. These results suggest that variability in glycolipid synthesis between species is an important determinant of microbial tropism. Evolutionary pressure from pathogenic organisms may have contributed to diversity in glycolipid expression among species.

Forssman Synthetase Expression Results in Diminished Shiga Toxin Susceptibility a Role for Glycolipids in Determining Host-Microbe Interactions

ABSTRACT Forssman glycolipid (FG), the product of Forssman synthetase (FS), is widely expressed among nonprimate mammalian species. Here, we describe a molecular and genetic relationship between FG expression and Shiga toxin (Stx) susceptibility. We have isolated the FS cDNA from human, canine, and murine cells. Whereas the murine and canine FS genes express a functional enzyme, the human FS cDNA was found to express a protein that lacks FS activity, despite a high degree of sequence identity with the enzymatically active murine and canine FS genes. In order to examine the relationship between FG expression and Stx susceptibility, Vero cells were transfected with the three FS orthologues or a vector control. Complementation with the human FS cDNA had no effect on Stx susceptibility, whereas stable expression of the canine and murine FS resulted in markedly decreased susceptibility to toxin. Among individual cells, an inverse correlation between FG expression and Stx binding was demonstrated. Moreover, only strongly FG-reactive cells were capable of growing in the presence of Stx. These cells were found to have high levels of FG expression and a correspondingly diminished GbO3 content. We conclude that expression of a functionally active FS modifies Stx receptor glycolipids to FG and results in markedly decreased susceptibility to toxin. We speculate that inactivation of the FS gene during primate evolution may account, at least in part, for the marked susceptibility of human cells to Stx.

Rat Bite Fever: Three Case Reports and a Literature Review

Rat bite fever is a systemic illness classically characterized by abrupt onset of fever, rash, and arthralgias, which carries a mortality rate of 13% if left untreated.1 We believe our experience has been unusual, as we diagnosed 3 cases between the months of July and October 2001. Since the presentation of rat bite fever may be nonspecific, a high potential for misdiagnosis exists with potentially fatal complications. We therefore describe our patients’ presentations and review existing literature to help practitioners recognize this infectious illness.

Staphylococcus lugdunensis: an emerging cause of ventriculoperitoneal shunt infections.

Staphylococcus lugdunensis, a coagulase-negative staphylococcus first described in 1988, has gained recognition as an organism with considerable pathogenic capability in adults. In contrast to the indolent presentation characteristic of other coagulase-negative staphylococci, S. lugdunensis infections resemble the aggressive behavior of Staphylococcus aureus. Although the organism has been isolated from a wide variety of infections in adults, it is a very rare cause of pediatric infections. We describe the first two pediatric patients who developed ventriculoperitoneal shunt infections caused by S. lugdunensis. These cases suggest that coagulase-negative staphylococci should be identified to the species level and that, if S. lugdunensis is identified, greater morbidity compared to that associated with other coagulase-negative staphylococcal shunt infections should be anticipated. A longer course of therapy is recommended for S. lugdunensis infections.

Enteroviral encephalitis leading to a locked-in state.

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Although enteroviruses are a common cause of community-acquired aseptic meningitis, enteroviral meningitis usually has a benign course. We describe a 14-year-old patient with enteroviral meningoencephalitis diagnosed by polymerase chain reaction. Her level of consciousness declined rapidly after hospital admission and resulted in a locked-in state. Although she experienced slow neurologic improvement, residual neurologic deficits remain. Although there is a general awareness of the characteristics of enteroviral encephalitis, this case report is significant in presenting a case of unusual severity and sequelae. To our knowledge, this is the first published report of an enterovirus encephalitis leading to a locked-in-state. (J Child Neurol 2001;16:864—866).

Congenital Cytomegalovirus Infection: An Overview

Cytomegalovirus (CMV) remains the most common cause of congenitally-acquired infection in the United States and is a leading infectious cause of sensorineural hearing loss, cognitive delay, and permanent neurologic sequelae. Although most cases of congenital CMV infection are asymptomatic, significant morbidity and mortality exist for symptomatic infants and may also occur in asymptomatic ones. Diagnosis remains relatively straightforward, but treatment options are limited and associated with some toxicity. Efforts at prevention via vaccination, screening, and improved epidemiology deserve high priority to limit the impact of this common infection.

Cat Scratch Disease and Arthropod Vectors: More to it than a Scratch?

Purpose: Cat scratch disease is a common infection, particularly in children, and clinicians need to be aware of its potential transmission to humans by arthropod vectors such as fleas and ticks in addition to animal bites and scratches. The absence of a vertebrate bite or scratch does not preclude infection with Bartonella henselae. Methods:Literature regarding arthropod transmission of B. henselae was reviewed. Results:B. henselae and related bacterial species are transmitted among cats and dogs by arthropod vectors. In the absence of these vectors, disease does not spread amongst the animals. On the other hand, disease can be spread to humans by bite and scratch as well as by arthropod vectors. Animals commonly infected with B. henselae and arthropod vectors are discussed. Conclusions:Clinicians should be aware that a common illness, cat scratch disease, can be transmitted by arthropod vectors and a history of an animal scratch or bite is not necessary for disease transmission.

Challenges in the Management of Infections due to Carbapenem-Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) infections are increasing and are associated with considerable morbidity and mortality. Members of the Emerging Infections Network treating CRE encountered difficulties in obtaining laboratory results and struggled with limited treatment options. In addition, many treated patients experienced an alarming degree of drug toxicity from CRE therapies.