On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital’s response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin.

The healthcare setting was important in the early spread of severe acute respiratory syndrome (SARS) in both Toronto and Taiwan. Healthcare workers, patients, and visitors were at increased risk for infection. Nonetheless, the ability of individual SARS patients to transmit disease was quite variable. Unrecognized SARS case-patients were a primary source of transmission and early detection and intervention were important to limit spread. Strict adherence to infection control precautions was essential in containing outbreaks. In addition, grouping patients into cohorts and limiting access to SARS patients minimized exposure opportunities. Given the difficulty in implementing several of these measures, controls were frequently adapted to the acuity of SARS care and level of transmission within facilities. Although these conclusions are based only on a retrospective analysis of events, applying the experiences of Toronto and Taiwan to SARS preparedness planning efforts will likely minimize future transmission within healthcare facilities.

Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.

To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients.

To evaluate multidrug-resistant strains of Salmonella enterica Typhimurium, including definitive type 104 (DT104) in the United States, we reviewed data from the National Antimicrobial Resistance Monitoring System (NARMS). In 1997–1998, 25% (703) of 2,767 serotyped Salmonella isolates received at NARMS were S. Typhimurium; antimicrobial susceptibility testing and phage typing were completed for 697. Fifty-eight percent (402) were resistant to >1 antimicrobial agent. Three multidrug-resistant (>5 drugs) strains accounted for 74% (296) of all resistant isolates. Ceftriaxone resistance was present in 3% (8), and nalidixic acid resistance in 1% (4), of these multidrug-resistant strains. By phage typing, 37% (259) of S. Typhimurium isolates were DT104, 30% (209) were of undefined type and 15% (103) were untypable. Fifty percent (202) of resistant (>1 drug) isolates were DT104. Multidrug-resistant S. Typhimurium isolates, particularly DT104, account for a substantial proportion of S. Typhimurium isolates; ceftriaxone resistance is exhibited by some of these strains.

Disease transmission forecasts can help minimize human and domestic animal health risks by indicating where disease control and prevention efforts should be focused. For disease systems in which weather-related variables affect pathogen proliferation, dispersal, or transmission, the potential for disease forecasting exists. We present a seasonal forecast of St. Louis encephalitis virus transmission in Indian River County, Florida. We derive an empirical relationship between modeled land surface wetness and levels of SLEV transmission in humans. We then use these data to forecast SLEV transmission with a seasonal lead. Forecast skill is demonstrated, and a real-time seasonal forecast of epidemic SLEV transmission is presented. This study demonstrates how weather and climate forecast skill verification analyses may be applied to test the predictability of an empirical disease forecast model.

An acute tick-borne rickettsiosis caused by Rickettsia heilongjiangensis was diagnosed in 13 patients from the Russian Far East in 2002. We amplified and sequenced four portions of three rickettsial genes from the patients' skin biopsy results and blood samples and showed that the amplified rickettsial genes belong to R. heilongjiangensis, which was recently isolated from Dermacentor sylvarum ticks in nearby regions of China. This rickettsia, belonging to subgroup of R. japonica, was previously suggested to be pathogenic for humans on the basis of serologic findings. We tested serum samples with different rickettsial antigens from 11 patients and confirmed increasing titers of immunoglobulin (Ig) G and IgM to spotted fever group rickettsiae, including R. heilongjiangensis. Clinical and epidemiologic data on these patients show that this disease is similar to other tick-borne rickettsioses.

Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.

The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription–polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%–40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.

We present a stochastic model for the spread of smallpox after a small number of index cases are introduced into a susceptible population. The model describes a branching process for the spread of the infection and the effects of intervention measures. We discuss scenarios in which ring vaccination of direct contacts of infected persons is sufficient to contain an epidemic. Ring vaccination can be successful if infectious cases are rapidly diagnosed. However, because of the inherent stochastic nature of epidemic outbreaks, both the size and duration of contained outbreaks are highly variable. Intervention requirements depend on the basic reproduction number R₀, for which different estimates exist. When faced with the decision of whether to rely on ring vaccination, the public health community should be aware that an epidemic might take time to subside even for an eventually successful intervention strategy.

We present an analysis of strain and patient factors associated with the development of bloody diarrhea and hemolytic uremic syndrome (HUS) among Shiga toxin-producing Escherichia coli (STEC) patients registered in Denmark in a 6-year period. Of 343 STEC patients, bloody diarrhea developed in 36.4% and HUS in 6.1%. In a multivariate logistic regression model, risk factors for bloody diarrhea were the eae and stx₂ genes, O groups O157 and O103, and increasing age. Risk factors for HUS were presence of the stx₂ (odds ratio [OR] 18.9) and eae (OR undefined) genes, being a child, and having bloody diarrhea. O group O157, although associated with HUS in a univariate analysis (OR 4.0), was not associated in the multivariate analysis (OR 1.1). This finding indicates that, rather than O group, the combined presence of the eae and stx₂ genes is an important predictor of HUS.

Seroepidemiologic studies of Pneumocystis pneumonia (PCP) in humans have been limited by inadequate reagents. We have developed an enzyme-linked immunosorbent assay (ELISA) using three overlapping recombinant fragments of the human Pneumocystis major surface glycoprotein (MsgA, MsgB, and MsgC) for analysis of antibody responses in HIV-positive patients and healthy blood donors. HIV-positive patients had significantly higher antibody levels to all Msg fragments. Furthermore, HIV-positive patients who experienced a previous episode of PCP (PCP-positive) had higher level of antibodies to MsgC than patients who never had PCP. A significant association was found between ELISA antibody level and reactivity by Western blot in HIV-positive patients, especially those who were PCP-positive. Thus, this ELISA will be useful in studying serum antibody responses to Pneumocystis in different human populations.

Methicillin-resistant Staphylococcus aureus (MRSA) with reduced vancomycin susceptibility (VISA, vancomycin-intermediate S. aureus) has been reported from many countries. Whether resistance is evolving regularly in different genetic backgrounds or in a single clone with a genetic predisposition, as early results suggest, is unclear. We have studied 101 MRSA with reduced vancomycin susceptibility from nine countries by multilocus sequence typing (MLST) and characterization of SCCmec (staphylococcal chromosomal cassette mec) and agr (accessory gene regulator). We found nine genotypes by MLST, with isolates within all five major hospital MRSA lineages. Most isolates (88/101) belonged to two of the earliest MRSA clones that have global prevalence. Our results show that reduced susceptibility to vancomycin has emerged in many successful epidemic lineages with no clear clonal disposition. Increasing antimicrobial resistance in genetically distinct pandemic clones may lead to MRSA infections that will become increasingly difficult to treat.

The New York City Department of Health and Mental Hygiene has established a syndromic surveillance system that monitors emergency department visits to detect disease outbreaks early. Routinely collected chief complaint information is transmitted electronically to the health department daily and analyzed for temporal and spatial aberrations. Respiratory, fever, diarrhea, and vomiting are the key syndromes analyzed. Statistically significant aberrations or “signals” are investigated to determine their public health importance. In the first year of operation (November 15, 2001, to November 14, 2002), 2.5 million visits were reported from 39 participating emergency departments, covering an estimated 75% of annual visits. Most signals for the respiratory and fever syndromes (64% and 95%, respectively) occurred during periods of peak influenza A and B activity. Eighty-three percent of the signals for diarrhea and 88% of the signals for vomiting occurred during periods of suspected norovirus and rotavirus transmission.

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.

We assessed the quantitative contribution of pig farming to antimicrobial resistance in the commensal flora of pig farmers by comparing 113 healthy pig farmers from the major French porcine production areas to 113 nonfarmers, each matched for sex, age, and county of residence. All reported that they had not taken antiimicrobial agents within the previous month. Throat, nasal, and fecal swabs were screened for resistant microorganisms on agar containing selected antimicrobial agents. Nasopharyngeal carriage of Staphylococcus aureus was significantly more frequent in pig farmers, as was macrolide resistance of S. aureus from carriers. Nongroupable streptococci from the throat were more resistant to the penicillins in pig farmers. The intestinal isolation of enterococci resistant to erythromycin or vancomycin was not significantly higher in pig farmers in contrast to that of enterobacteria resistant to nalidixic acid, chloramphenicol, tetracycline, and streptomycin. Prevalence of resistance in predominant fecal enterobacteria was also significantly higher in pig farmers for cotrimoxazole, tetracycline, streptomycin, and nalidixic acid. We determined a significant association between pig farming and isolation of resistant commensal bacteria.

Since Venezuelan equine encephalitis virus (VEEV) was isolated in Peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the Amazon region. To investigate genetic relationships among the Peru VEEV isolates and between the Peru isolates and other VEEV strains, a fragment of the PE2 gene was amplified and analyzed by single-stranded conformation polymorphism. Representatives of seven genotypes underwent sequencing and phylogenetic analysis. The results identified four VEE complex lineages that cocirculate in the Amazon region: subtypes ID (Panama and Colombia/Venezuela genotypes), IIIC, and a new, proposed subtype IIID, which was isolated from a febrile human, mosquitoes, and spiny rats. Both ID lineages and the IIID subtype are associated with febrile human illness. Most of the subtype ID isolates belonged to the Panama genotype, but the Colombia/Venezuela genotype, which is phylogenetically related to epizootic strains, also continues to circulate in the Amazon basin.

Pogosta disease is a mosquito-borne viral disease in Finland, which is clinically manifested by rash and arthritis; larger outbreaks occur in 7-year intervals. The causative agent of the disease has been suspected of being closely related to Sindbis virus (SINV). We isolated SINV from five patients with acute Pogosta disease during an outbreak in fall 2002 in Finland. One virus strain was recovered from a whole blood sample and four other strains from skin lesions. The etiology of Pogosta disease was confirmed by these first Finnish SINV strains, which also represent the first human SINV isolates from Europe. Phylogenetic analysis indicates that the Finnish SINV strains are closely related to the viral agents isolated from mosquitoes and that cause clinically similar diseases in nearby geographic areas.

This study found infrequent transmission of severe acute respiratory syndrome (SARS) coronavirus to healthcare workers involved in the care of the first five case-patients in Taiwan, despite a substantial number of unprotected exposures. Nonetheless, given that SARS has been highly transmissible on some occasions, we still recommend strict precautions.

We obtained 475 nucleotides of the DNA polymerase gene of a novel human herpesvirus 8 homolog sequence in a gibbon. The finding of this new gibbon virus, which clusters with a related chimpanzee virus in the rhadinovirus 2 genogroup, suggests the existence of a novel γ-2-herpesvirus in humans.

Dengue fever is a reportable disease in Germany. Surveillance data from 2001 and 2002 were analyzed and compared to travel patterns. Imported dengue fever increased strongly in this time. Most infections were acquired in Southeast Asia, specifically Thailand. The 2002 epidemic in Brazil was also reflected in these data.

We evaluated cloacal swab, vascular pulp of flight feather, and kidney and spleen pool samples from carcasses of members of the family Corvidae as sources of West Nile virus (WNV). The cloacal swab, kidney and spleen pool, and feather pulp, respectively, were the source of WNV in 38%, 43%, and 77% of the carcasses.

We report a fatal case of rickettsiosis in a woman from the United States living in Kenya, who had a history of tick exposure. Immunohistochemical staining of skin, kidney, and liver demonstrated spotted fever group rickettsiae. The clinical findings, severity, and fatal outcome are most consistent with Rickettsia conorii infection.

SARS coronavirus injected intratracheally into chickens, turkeys, geese, ducks, and quail, or into the allantoic sac of their embryonating eggs, failed to cause disease or replicate. This finding suggests that domestic poultry were unlikely to have been the reservoir, or associated with dissemination, of SARS coronavirus in the animal markets of southern China.

In April 1947, during a smallpox outbreak in New York City (NYC), >6,000,000 people were vaccinated. To determine whether vaccination increased cardiac death, we reviewed NYC death certificates for comparable periods in 1946 and 1948 (N = 81,529) and calculated adjusted relative death rates for the postvaccination period. No increases in cardiac deaths were observed.

Five Mycobacterium tuberculosis complex isolates in California were identified as M. africanum by spoligotyping, single nucleotide polymorphisms, a deletion mutation, and phenotypic traits, confirming it as a cause of tuberculosis in the United States. Three of the five patients from whom M. africanum was isolated had lived in Africa.

Dementia developed in a patient with widespread neurologic manifestations; she died within 5 months. Pathologic findings showed granulomatous inflammation with caseation necrosis, foreign body–type giant cells, and proliferative endarteritis with vascular occlusions. Broad-range polymerase chain reaction identified Mycobacterium neoaurum as the possible pathogen. Central nervous system infection by M. neoaurum may result in rapidly progressive dementia.

A comparison of New York’s traditional communicable disease surveillance system for diarrhea-associated hemolytic uremic syndrome with hospital discharge data showed a sensitivity of 65%. Escherichia coli O157:H7 was found in 63% of samples cultured from hemolytic uremic syndrome patients, and samples were more likely to be positive when collected early in illness.

An outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium infections occurred in Pennsylvania and New Jersey. A case-control study implicated pasteurized milk from a dairy, and an inspection indicated the potential for contamination after pasteurization. Dairy cattle are the likely reservoir, and milk may be an important vehicle of Salmonella transmission to humans.

We describe the first case of Neisseria meningitidis W135 meningitis in Turkey. The strain was genotypically unrelated to the clone (W)ET-37, isolated from Hajj pilgrims in 2000.

During the summer and fall of 2002, an epidemic (223 cases) and epizootic of West Nile virus infections occurred in Chicago. Retrospective spatial analysis demonstrated that age-adjusted human case rates were three times higher inside geographic areas with high early-season crow deaths than outside these areas.

We report an outbreak of 235 community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections among military recruits. In this unique environment, the close contact between recruits and the physical demands of training may have contributed to the spread of MRSA. Control measures included improved hygiene and aggressive clinical treatment.

To evaluate the importance of human exposure to Rift Valley fever virus in Chad, investigations were carried out to determine specific antibody prevalence in domestic ruminants during the 2002 rainy season. Results highlighted recent, substantial, active transmission of this virus.

Bats submitted to the Texas Department of Health (1996–2000) were speciated and tested for rabies virus antigen by direct immunofluorescence microscopy. Antigenic analysis of rabies virus–positive specimens was performed with monoclonal antibodies against the nucleoprotein of the virus; atypical or unexpected results were confirmed by genetic analysis of nucleoprotein sequence.

We describe a case of acquired infection of a strain of hepatitis E virus (HEV)with a 100% amino acid identity to the analogous region in strains of HEV circulating in a United Kingdom pig herd. This case further supports the theory that autochthonous HEV infection in industrialized countries is zoonotic.