Since the World Health Organization declared the global outbreak of severe acute respiratory syndrome (SARS) contained in July 2003, new cases have periodically reemerged in Asia. This situation has placed hospitals and health officials worldwide on heightened alert. In a future outbreak, rapidly and accurately distinguishing SARS from other common febrile respiratory illnesses (FRIs) could be difficult. We constructed a decision-analysis model to identify the most efficient strategies for managing undifferentiated FRIs within a hypothetical SARS outbreak in New York City during the season of respiratory infections. If establishing reliable epidemiologic links were not possible, societal costs would exceed $2.0 billion per month. SARS testing with existing polymerase chain reaction assays would have harmful public health and economic consequences if SARS made up <0.1% of circulating FRIs. Increasing influenza vaccination rates among the general population before the onset of respiratory season would save both money and lives.

Influenza A (H5N1) is endemic in poultry across much of Southeast Asia, but limited information exists on the distinctive features of the few human cases. In Thailand, we instituted nationwide surveillance and tested respiratory specimens by polymerase chain reaction and viral isolation. From January 1 to March 31, 2004, we reviewed 610 reports and identified 12 confirmed and 21 suspected cases. All 12 confirmed case-patients resided in villages that experienced abnormal chicken deaths, 9 lived in households whose backyard chickens died, and 8 reported direct contact with dead chickens. Seven were children <14 years of age. Fever preceded dyspnea by a median of 5 days, and lymphopenia significantly predicted acute respiratory distress syndrome development and death. Among hundreds of thousands of potential human cases of influenza A (H5N1) in Asia, a history of direct contact with sick poultry, young age, pneumonia and lymphopenia, and progression to acute respiratory distress syndrome should prompt specific laboratory testing for H5 influenza.

To establish whether human-to-human transmission of influenza A H5N1 occurred in the healthcare setting in Vietnam, we conducted a cross-sectional seroprevalence survey among hospital employees exposed to 4 confirmed and 1 probable H5N1 case-patients or their clinical specimens. Eighty-three (95.4%) of 87 eligible employees completed a questionnaire and provided a serum sample, which was tested for antibodies to influenza A H5N1. Ninety-five percent reported exposure to >1 H5N1 case-patients; 59 (72.0%) reported symptoms, and 2 (2.4%) fulfilled the definition for a possible H5N1 secondary case-patient. No study participants had detectable antibodies to influenza A H5N1. The data suggest that the H5N1 viruses responsible for human cases in Vietnam in January 2004 are not readily transmitted from person to person. However, influenza viruses are genetically variable, and transmissibility is difficult to predict. Therefore, persons providing care for H5N1 patients should continue to take measures to protect themselves.

Blood culture–negative endocarditis is common in Algeria. We describe the etiology of infective endocarditis in this country. Samples from 110 cases in 108 patients were collected in Algiers. Blood cultures were performed in Algeria. Serologic and molecular analysis of valves was performed in France. Infective endocarditis was classified as definite in 77 cases and possible in 33. Causative agents were detected by blood cultures in 48 cases. All 62 blood culture–negative endocarditis cases were tested by serologic or molecular methods or both. Of these, 34 tested negative and 28 had an etiologic agent identified. A total of 18 infective endocarditis cases were caused by zoonotic and arthropodborne bacteria, including Bartonella quintana (14 cases), Brucella melitensis (2 cases), and Coxiella burnetii (2 cases). Our data underline the high prevalence of infective endocarditis caused by Bartonella quintana in northern Africa and the role of serologic and molecular tools for the diagnosis of blood culture–negative endocarditis.

A flavivirus (strain 97-103) was isolated from Culex pipens mosquitoes in 1997 following floods in South Moravia, Czech Republic. The strain exhibited close antigenic relationship to West Nile virus (WNV) prototype strain Eg-101 in a cross-neutralization test. In this study, mouse pathogenicity characteristics and the complete nucleotide and putative amino acid sequences of isolate 97-103, named Rabensburg virus (RabV) after a nearby Austrian city, were determined. RabV shares only 75%–77% nucleotide identity and 89%–90% amino acid identity with representative strains of WNV lineages 1 and 2. Another RabV strain (99-222) was isolated in the same location 2 years later; it showed >99% nucleotide identity to strain 97-103. Phylogenetic analyses of RabV, WNV strains, and other members of the Japanese encephalitis virus (JEV) complex clearly demonstrated that RabV is either a new (third) lineage of WNV or a novel flavivirus of the JEV group.

Surveillance for lyssaviruses was conducted among bat populations in 8 provinces in Thailand. In 2002 and 2003, a total of 932 bats of 11 species were captured and released after serum collection. Lyssavirus infection was determined by conducting virus neutralization assays on bat serum samples. Of collected samples, 538 were either hemolysed or insufficient in volume, which left 394 suitable for analysis. These samples included the following: Pteropus lylei (n = 335), Eonycteris spelaea (n = 45), Hipposideros armiger (n = 13), and Rousettus leschennaulti (n = 1). No serum samples had evidence of neutralizing antibodies when tested against rabies virus. However, 16 samples had detectable neutralizing antibodies against Aravan virus, Khujand virus, Irkut virus, or Australian bat lyssavirus; all were specifically associated with fruit bats P. lylei (n = 15) and E. spelaea (n = 1). These results are consistent with the presence of naturally occurring viruses related to new putative lyssavirus genotypes.

The presence of the nucleic acid of the spotted fever group (SPG) and typhus group (TG) rickettsiae was investigated in 200 serum specimens seropositive for SFG rickettsiae by multiplex-nested polymerase chain reaction with primers derived from the rickettsial outer membrane protein B gene. The DNA of SFG, TG, or both rickettsiae was amplified in the 24 serum specimens, and sequence analysis showed Rickettsia conorii, R. japonica, and R. felis in the specimens. R. conorii and R. typhi were found in 7 serum specimens, which indicated the possibility of dual infection in these patients. These findings suggest that several kinds of rickettsial diseases, including boutonneuse fever, rickettsialpox, R. felis infection, and Japanese spotted fever, as well as scrub typhus and murine typhus, are occurring in Korea.

The possible presence of Pneumocystis among healthy adults was examined by detecting Pneumocystis jirovecii–specific DNA in prospectively obtained oropharyngeal wash samples from 50 persons without underlying lung disease or immunosuppression. Pneumocystis carriage, defined by detecting Pneumocystis DNA by nested polymerase chain reaction in 2 independent analyses plus successful mitochondrial large subunit ribosomal RNA typing by direct sequencing, was found in 20% of cases. All carriers were asymptomatic, anti-HIV negative, and had normal total lymphocyte and CD4+ cell counts. A second sample obtained in the 6-month follow-up was positive in 2 of 9 available carriers. Genotype analysis showed different polymorphisms; 85A/248C (40%) and 85C/248C (30%) were most frequently observed. This study provides the first evidence that P. jirovecii DNA can be frequently detected in the respiratory tract of immunocompetent adults, which agrees with the hypothesis that the general population could be a reservoir and source of this infection.

The incidence of sporadic cryptosporidiosis among 106,000 residents of 2 local government districts in northwest England before and after installation of membrane filtration of public water supplies was compared to that of 59,700 residents whose public water supplies remained unchanged. A national outbreak of foot and mouth disease in livestock during 2001 was associated with a decline in sporadic human cryptosporidiosis in all regions of the United Kingdom. In a Poisson regression model, membrane filtration was associated with an estimated 79% reduction (incidence ratio 0.207, 95% confidence intervals 0.099–0.431, p < 0.0001) after adjustment for the interval of the foot and mouth disease epidemic and the water source. Despite the confounding effect of that epidemic, membrane filtration of the public water supply was effective in reducing the risk for sporadic human Cryptosporidium infection in this population.

Our study was initiated by previous isolation of 30 imipenem-resistant, gram-negative rods from 7 of 16 U.S. rivers sampled from 1999 to 2001. Imipenem hydrolysis was detected in 22 of those isolates identified as Enterobacter asburiae. Random amplified polymorphism DNA analysis showed that these E. asburiae isolates were genetically indistinguishable. An identical clavulanic acid–inhibited β-lactamase IMI-2 was identified from each isolate that shared 99% and 97% amino acid identity with the chromosome-encoded β-lactamases IMI-1 and NmcA, respectively, from E. cloacae clinical isolates. The bla_IMI-2 gene was located on a self-transferable 66-kb plasmid. Sequence analysis of a cloned 5.5-kb DNA fragment obtained from 1 of the imipenem-resistant E. asburiae isolates identified an upstream LysR-type regulator gene that explained inducibility of IMI-2 expression. β-Lactamase IMI-2 is the first inducible and plasmid-encoded carbapenemase. Identification of clonally related E. asburiae isolates from distant rivers indicates an environmental and enterobacterial reservoir for carbapenemase genes.

We compared the rickettsial infection status of Amblyomma cajennense ticks, humans, dogs, and horses in both Brazilian spotted fever (BSF)–endemic and –nonendemic areas in the state of São Paulo, Brazil. Most of the horses and few dogs from BSF-endemic areas had serologic titers against Rickettsia rickettsii antigens. In contrast, no dogs or horses from BSF-nonendemic areas had serologic titers against R. rickettsii antigens, although they were continually exposed to A. cajennense ticks. All human serum samples and ticks from both areas were negative by serologic assay and polymerase chain reaction, respectively. Our results indicate that surveys of horse serum are a useful method of BSF surveillance in areas where humans are exposed to A. cajennense ticks. In addition, we successfully performed experimental infection of A. cajennense ticks with R. parkeri.

An obligate intracellular bacterium was isolated from urine samples from 7 (3.5%) of 202 fruit bats (Eonycteris spelaea) in peninsular Malaysia. The bacterium produced large membrane-bound inclusions in human, simian, and rodent cell lines, including epithelial, fibroblastlike, and lymphoid cells. Thin-section electron microscopy showed reticulate bodies dividing by binary fission and elementary bodies in the inclusions; mitochondria surrounded the inclusions. The inclusions were positive for periodic acid-Schiff stain but could not be stained by fluorescein-labeled anti–Chlamydia trachomatis major outer membrane protein monoclonal antibody. The bacterium was resistant to penicillin and streptomycin (MICs >256 mg/L) but susceptible to tetracycline (MIC = 0.25 mg/L) and chloramphenicol (MIC = 0.5 mg/L). Sequence analysis of the 16SrRNA gene indicated that it was most closely related to 2 isolates of Waddlia chondrophila (94% and 96% identity). The 16S and 23S rRNA gene signatures were only 91% identical. We propose this novel bacterium be called W. malaysiensis.

During the 2003 outbreak of severe acute respiratory syndrome (SARS) in Taiwan, >150,000 persons were quarantined, 24 of whom were later found to have laboratory-confirmed SARS-coronavirus (SARS-CoV) infection. Since no evidence exists that SARS-CoV is infective before the onset of symptoms and the quarantined persons were exposed but not symptomatic, we questioned the quarantine’s effectiveness. Using the SARS Taiwan quarantine data, we found that the onset-to-diagnosis time of previously quarantined confirmed case-patients was significantly shortened compared to that for those who had not been quarantined. Thus, quarantine for SARS in Taiwan screened potential infective persons for swift diagnosis and hospitalization after onset, thereby indirectly reducing infections. Full-scale quarantine measures implemented on April 28 led to a significant improvement in onset-to-diagnosis time of all SARS patients, regardless of previous quarantine status. We discuss the temporal effects of quarantine measures and other interventions on detection and isolation as well as the potential usefulness of quarantine in faster identification of persons with SARS and in improving isolation measures.

All human Ebola virus outbreaks during 2001–2003 in the forest zone between Gabon and Republic of Congo resulted from handling infected wild animal carcasses. After the first outbreak, we created an Animal Mortality Monitoring Network in collaboration with the Gabonese and Congolese Ministries of Forestry and Environment and wildlife organizations (Wildlife Conservation Society and Programme de Conservation et Utilisation Rationnelle des Ecosystèmes Forestiers en Afrique Centrale) to predict and possibly prevent human Ebola outbreaks. Since August 2001, 98 wild animal carcasses have been recovered by the network, including 65 great apes. Analysis of 21 carcasses found that 10 gorillas, 3 chimpanzees, and 1 duiker tested positive for Ebola virus. Wild animal outbreaks began before each of the 5 human Ebola outbreaks. Twice we alerted the health authorities to an imminent risk for human outbreaks, weeks before they occurred.

We reviewed historical data from 2 smallpox outbreaks in Liverpool and Edinburgh during the early and middle years of the 20th century to assess their contribution to developing modern strategies for response to a deliberate release of smallpox virus. Reports contemporaneous to these outbreaks provide detail on the effectiveness of public health interventions. In both outbreaks, extensive contact tracing, quarantine, and staged vaccination campaigns were initiated, and the outbreaks were controlled within 15 months and 3 months, respectively. In Edinburgh, the number of fatalities associated with vaccination exceeded the number of deaths from the disease. In Liverpool, ambulatory, vaccine-modified cases and misdiagnosis as chickenpox resulted in problems with outbreak control. The relatively slow spread of smallpox, as exemplified by the report from Liverpool, allowed for effective implementation of targeted intervention methods. Targeted surveillance and containment interventions have been successful in the past and should be explored as alternatives to mass vaccination.

We investigated the susceptibility to Usutu virus (Flavivirus) of 13 permanent cell lines, 3 primary cell cultures, and chicken embryos. Vero, PK-15, and goose embryo fibroblast cells developed cytopathic effects; however, viral multiplication was detected in all mammalian cell types by immunohistochemical tests. Chicken embryo fibroblast cells and chicken embryos were resistant.

From 1998 to 2002, a total of 299 bat incidents were reported at 109 children’s camps in New York; 1,429 campers and staff were involved, and 461 persons received rabies treatment. In 53.8% of the incidents, the bat was captured and samples tested negative for rabies virus, which resulted in 61.3% of persons not receiving rabies treatment.

West Nile virus (WNV) reemerged in Morocco in September 2003, causing an equine outbreak. A WNV strain isolated from a brain biopsy was completely sequenced. On the basis of phylogenetic analyses, Moroccan WNV strains isolated during the 1996 and 2003 outbreaks were closely related to other strains responsible for equine outbreaks in the western Mediterranean basin.

Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.

We compared aberration detection methods requiring historical data to those that require little background by using simulated data. Methods that require less historical data are as sensitive and specific as those that require 3–5 years of data. These simulations can determine which method produces appropriate sensitivity and specificity.

Analysis of Plasmodium falciparum isolates collected before, during, and after a 1999 malaria epidemic in Djibouti shows that, despite a high prevalence of resistance to chloroquine, the epidemic cannot be attributed to a sudden increase in parasite drug resistance of local parasite populations.

Late recognition of severe acute respiratory syndrome (SARS) was associated with no known SARS contact, hospitalization before the nosocomial outbreak was recognized, symptom onset while hospitalized, wards with SARS clusters, and postoperative status. SARS is difficult to recognize in hospitalized patients with a variety of underlying conditions in the absence of epidemiologic links.

We confirmed a bacteremic typhoid fever incidence of 3.9 episodes/1,000 person-years during fever surveillance in a Dhaka urban slum. The relative risk for preschool children compared with older persons was 8.9. Our regression model showed that these children were clinically ill, which suggests a role for preschool immunization.

We describe an outbreak of Pneumocystis jirovecii pneumonia in a pediatric renal transplant unit, likely attributable to patient-to-patient transmission. Single-strand conformation polymorphism molecular typing showed that 3 affected patients had acquired the same 2 strains of Pneumocystis, which suggests interhuman infection. An infant with mitochondriopathy was the probable index patient.