Hospital-based enhanced surveillance for West Nile virus neuroinvasive disease.

Accurate data on the incidence of West Nile virus (WNV) disease are important for directing public health education and control activities. The objective of this project was to assess the underdiagnosis of WNV neuroinvasive disease through laboratory testing of patients with suspected viral meningitis or encephalitis at selected hospitals serving WNV-endemic regions in three states. Of the 279 patients with cerebrospinal fluid (CSF) specimens tested for WNV immunoglobulin M (IgM) antibodies, 258 (92%) were negative, 19 (7%) were positive, and two (1%) had equivocal results. Overall, 63% (12/19) of patients with WNV IgM-positive CSF had WNV IgM testing ordered by their attending physician. Seven (37%) cases would not have been identified as probable WNV infections without the further testing conducted through this project. These findings indicate that over a third of WNV infections in patients with clinically compatible neurological illness might be undiagnosed due to either lack of testing or inappropriate testing, leading to substantial underestimates of WNV neuroinvasive disease burden. Efforts should be made to educate healthcare providers and laboratorians about the local epidemiology of arboviral diseases and the optimal tests to be used in different clinical situations.

Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium.

BACKGROUND: Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. METHODS: In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. RESULTS: We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. CONCLUSIONS: We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Encephalitis with thalamic and basal ganglia abnormalities: etiologies, neuroimaging, and potential role of respiratory viruses.

BACKGROUND: Encephalitis is a severe neurological syndrome with devastating consequences. Despite extensive testing, the etiology often remains unknown. Involvement of the thalamus or basal ganglia (T/BG) occurs in a subset of patients with encephalitis and may be an important etiological clue. In order to improve diagnosis of T/BG patients, we reviewed this subgroup within the California Encephalitis Project (CEP). METHODS: Data from T/BG cases enrolled in CEP were retrospectively reviewed. Cases were stratified by age and grouped by etiological classification: infectious, postinfectious, and noninfectious. Neuroimaging reports were examined and compared between etiologies. RESULTS: T/BG neuroimaging abnormalities were reported in 6% of 3236 CEP cases. An etiology was found in 76%: 37% infectious, 16% postinfectious, and 23% noninfectious. The most frequently identified infectious agents were respiratory viruses, accounting for 31%, predominantly in children. Other infections more common in the T/BG group included Creutzfeldt-Jakob disease, arbovirus, and Mycobacterium tuberculosis. Infectious and postinfectious cases had higher median cerebrospinal fluid white blood cell count than noninfectious etiologies. Notably, T/BG neuroimaging characteristics were associated with distinct etiologies. In particular, symmetric hemorrhagic abnormalities involving the thalamus were most frequently found within the respiratory virus group. CONCLUSIONS: T/BG involvement in patients with suspected encephalitis was associated with specific etiologies. In addition to agents with established predilection for the T/BG such as M. tuberculosis and arboviruses, a surprisingly high number of cases were associated with respiratory viruses, especially in children. Neuroimaging abnormalities in such patients can aid clinicians in narrowing the etiological scope and in guiding testing.

Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis.

The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.

Tuberculous meningoencephalitis in a pregnant woman presenting 7 years after removal of a cerebral granuloma.

We describe the unusual case of a young woman with a history of seizures and a granulomatous, likely tuberculous brain lesion that was surgically removed. She had an uneventful recovery without any additional therapy other than anti-epileptics. Seven years later, she presented during pregnancy with culture-confirmed tuberculous meningoencephalitis. This case highlights the spectrum of tuberculous central nervous system disease and the challenges in diagnosis.

Beyond viruses: clinical profiles and etiologies associated with encephalitis.

BACKGROUND: Encephalitis is a complex syndrome, and its etiology is often not identified. The California Encephalitis Project was initiated in 1998 to identify the causes and further describe the clinical and epidemiologic characteristics of encephalitis. METHODS: A standardized report form was used to collect demographic and clinical data. Serum, cerebrospinal fluid, and respiratory specimens were obtained prospectively and were tested for the presence of herpesviruses, arboviruses, enteroviruses, measles, respiratory viruses, Chlamydia species, and Mycoplasma pneumoniae. The association between an identified infection and encephalitis was defined using predetermined, organism-specific criteria for confirmed, probable, or possible causes. RESULTS: From 1998 through 2005, a total of 1570 patients were enrolled. Given the large number of patients, subgroups of patients with similar clinical characteristics and laboratory findings were identified. Ten clinical profiles were described. A confirmed or probable etiologic agent was identified for 16% of cases of encephalitis: 69% of these agents were viral; 20%, bacterial; 7%, prion; 3%, parasitic; and 1%, fungal. An additional 13% of cases had a possible etiology identified. Many of the agents classified as possible causes are suspected but have not yet been definitively demonstrated to cause encephalitis; these agents include M. pneumoniae (n=96), influenza virus (n=22), adenovirus (n=14), Chlamydia species (n=10), and human metapneumovirus (n=4). A noninfectious etiology was identified for 8% of cases, and no etiology was found for 63% of cases. CONCLUSIONS: Although the etiology of encephalitis remains unknown in most cases, the recognition of discrete clinical profiles among patients with encephalitis should help focus our efforts toward understanding the etiology, pathogenesis, course, and management of this complex syndrome.

Subacute sclerosing panencephalitis in the differential diagnosis of encephalitis.

The authors describe five cases of subacute sclerosing panencephalitis (SSPE) identified through the California Encephalitis Project that emphasize the importance of considering SSPE in the differential diagnosis of encephalitis, particularly among pediatric patients. SSPE was not suspected in the differential diagnosis of three of the cases until results of measles testing were known. The diagnosis of SSPE is often not considered by clinicians because of its rarity in the United States and the nonspecific clinical manifestations at onset.

Ehrlichiosis.

HGE and HME have been recognized as distinct clinical conditions for only 5 and 10 years, respectively, and much information regarding their ecology and epidemiology remains uncertain. The nonspecific character of the illness complicates this incomplete knowledge, as an unknown percentage of infections are likely misdiagnosed. Ehrlichiosis should be considered in any patient presenting with flu-like illness and history of a tick bite. Although expanding, diagnostic support for human ehrlichioses is currently limited to a few regional academic and public health laboratories. Healthcare providers should educate themselves regarding the clinical presentation of ehrlichioses and the availability of diagnostic resources in their area.

Association between Cryptosporidium infection and animal exposure in HIV-infected individuals.

Cryptosporidium causes a debilitating illness in immunocompromised individuals, yet the source of sporadic Cryptosporidium infections is unknown. Because early cases of cryptosporidiosis were associated with animals, and pets are a source of companionship to individuals with AIDS, determination of the risk of cryptosporidiosis associated with pets is important. To assess this risk, we conducted a case-control study of HIV-infected individuals with and without cryptosporidiosis. No statistically significant difference in the rate of overall pet ownership, cat ownership, or bird ownership was found between the two groups. Dog ownership reached borderline statistical significance; 15 of 48 (31%) cases owned a dog, compared with 17 of 99 (17%) controls (odds ratio [OR] = 2.19; p = .05; 95% confidence interval [CI], 0.9-5.3). No statistically significant differences between cases and controls were found in the frequency of surface water ingestion, rural exposure, travel history, or contact with diarrheic individuals. Our findings indicate that pets do not represent a major risk factor for acquisition of Cryptosporidium for HIV-infected individuals. Whether dog ownership presents a minimal risk for cryptosporidiosis needs further investigation.

Bartonella henselae prevalence in domestic cats in California: risk factors and association between bacteremia and antibody titers.

The isolation of Bartonella henselae, the agent of cat scratch disease, from the blood of naturally infected domestic cats and the demonstration that cats remain bacteremic for several months suggest that cats play a major role as a reservoir for this bacterium. A convenience sample of 205 cats from northern California was selected between 1992 and 1994 to evaluate the B. henselae antibody and bacteremia prevalences and to determine the risk factors and associations between bacteremia and antibody titers. B. henselae was isolated from the blood of 81 cats (39.5%). Forty-two (52%) of these bacteremic cats were found to be infected with > or = 1,000 CFU/ml of blood. Impounded or former stray cats were 2.86 (95% confidence interval [CI] = 1.94, 4.22) times more likely to be bacteremic than the pet cats. Young cats ( < 1 year old) were more likely than adult cats to be bacteremic (relative risk = 1.64; (95% CI = 1.19, 2.28). Bacteremic cats were more likely than nonbacteremic cats to be infested with fleas (relative risk = 1.64; 95% CI = 1.38, 1.96). No association between B. henselae infection and feline immunodeficiency virus antibody prevalence was observed. Eighty-one percent of the cats (166 of 205) tested positive for B. henselae antibodies, and titers were higher in bacteremic than in nonbacteremic cats. Multiple logistic regression analysis indicated that younger age and seropositivity for B. henselae antibodies were associated with bacteremia. Serological screening for Bartonella antibodies may not be useful for the identification of bacteremic cats (positive predictive value = 46.4%), but the lack of antibodies to B. henselae was highly predictive of the absence of bacteremia (negative predictive value = 89.7%). Seronegative cats may be more appropriate pets for immunocompromised individuals who are at increased risk for developing severe B. henselae disease.

Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir.

OBJECTIVE: To determine the reservoir and vector(s) for Rochalimaea henselae, a causative agent of bacillary angiomatosis (BA) and cat scratch disease, and to estimate the percentage of domestic cats with R henselae bacteremia in the Greater San Francisco Bay Region of Northern California. DESIGN: Hospital-based survey of patients diagnosed with BA who also had significant exposure to at least one pet cat, as well as a convenience sampling of pet or impounded cats for prevalence of Rochalimaea bacteremia. SETTING: Community and university hospitals and clinics; veterinary clinics treating privately owned or impounded cats. PATIENTS: Patients with or without human immunodeficiency virus infection, with biopsy-confirmed BA, who had prolonged exposure to pet cats prior to developing BA. MAIN OUTCOME MEASURES: Cultures and laboratory studies were performed on blood drawn from pet cats associated with patients with BA. The Rochalimaea species infecting pet cats and fleas and causing the BA lesions in human contacts of these cats was identified by culture, polymerase chain reaction-restriction fragment length polymorphism analysis, and DNA sequencing. The presence of R henselae bacteremia in pet cats was documented, and predictor variables for culture positivity were evaluated. RESULTS: Four patients diagnosed with BA who had prolonged contact with seven pet cats were identified. The Rochalimaea species causing BA lesions in these patients was determined to be R henselae. The seven pet cats were found to be bacteremic with R henselae; this bacterium was also detected in fleas taken from an infected cat by both direct culture and polymerase chain reaction. Blood samples were cultured from pet and impounded cats (N = 61) in the Greater San Francisco Bay Region, and R henselae was isolated from 41% (25/61) of these cats. CONCLUSION: We have documented that the domestic cat serves as a major persistent reservoir for R henselae, with prolonged, asymptomatic bacteremia from which humans, especially the immunocompromised, may acquire potentially serious infections. Antibiotic treatment of infected cats and control of flea infestation are potential strategies for decreasing human exposure to R henselae.

Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus.

A number of animal-associated infections occur in persons infected with the human immunodeficiency virus (HIV), including those due to Toxoplasma gondii, Cryptosporidium, Microsporida, Salmonella, Campylo-bacter, Giardia, Rhodococcus equi, Rochalimaea, and Listeria monocytogenes. Most of these infections, with the exception of those due to Rochalimaea, appear to be acquired by the immunosuppressed individual from sources other than exposure to animals. Drs. Glaser and colleagues review our current understanding of the role of exposure to animals, especially pets, in the natural history of these opportunistic infections. They suggest that the risk of zoonotic transmission is small and offer practical suggestions designed to reduce this low risk. They conclude that the benefits of animal companionship outweigh the risks to patients and that prohibition of pet ownership by individuals infected with HIV is not warranted.

Prevalence of Giardia in the feces of pups.

Fecal specimens were collected from 117 healthy pups (79 privately owned pups and 38 pups from an animal shelter) and analyzed for Giardia. Giardia cysts or trophozoites were found in 35.9% of the dog feces.

Pathology of larval Eustrongylides in the rabbit.

Three fishermen from Maryland who swallowed live bait-minnows developed severe abdominal pain within 24 hr; 2 required abdominal surgery. Larvae of the nematode Eustrongylides sp. were found in the peritoneal cavity of both (Guerin et al., 1982). In the current study, the lesions produced by Eustrongylides larvae were investigated in New Zealand white rabbits. None of these exhibited any signs of clinical illness; however, postmortem examination within 24 hr of inoculation revealed that larvae had migrated through the walls of the esophagus and stomach and viable larvae were recovered from the pleural and peritoneal cavities as well as from gastric contents. Necropsies performed at different intervals of time postinoculation showed that the migrating larvae had produced multi-focal peritonitis and multiple granulomata in the liver.

Virus detection in monkeys with diarrhea: the association of adenoviruses with diarrhea and the possible role of rotaviruses.

To explore the role of viruses in the etiology of diarrhea in colony-reared monkeys, direct electron microscopy, the fluorescent virus precipitin test and cell culture inoculation were used to examine the stools of monkeys with and without diarrhea. The animals were predominantly rhesus with a few macaques of other species, and included infants, juveniles and adults. Adenoviruses were isolated from a higher proportion of specimens from rhesus monkeys with diarrhea (73% of specimens from infants and 78% of specimens from juveniles and adults) than from control monkeys without diarrhea (22% of specimens from infants and 26% of specimens from juveniles and adults). SV 20 was the most frequently isolated simian adenovirus type; SV 17 and SV 32 also were recovered. Noncultivable adenoviruses detectable only by electron microscopy were not seen. Although adenovirus excretion was associated with diarrhea, the causal role of adenoviruses was difficult to assess. When serial specimens from animals with chronic or intermittent episodes of diarrhea were examined, sequential infections with different viruses were found to be common. Rotaviruses were detected by electron microscopy and isolated in cell cultures from two infant rhesus monkeys with diarrhea. However, the low detection rate, together with negative serologic data on 40% of infant monkeys with diarrhea, suggested that rotaviruses were not the major cause of gastroenteritis in the monkeys under study.