Early diagnosis of SARS: lessons from the Toronto SARS outbreak

The clinical presentation of SARS is nonspecific and diagnostic tests do not provide accurate results early in the disease course. Initial diagnosis remains reliant on clinical assessment. To identify features of the clinical assessment that are useful in SARS diagnosis, the exposure status and the prevalence and timing of symptoms, signs, laboratory and radiographic findings were determined for all adult patients admitted with suspected SARS during the Toronto SARS outbreak. Findings were compared between patients with laboratory-confirmed SARS and those in whom SARS was excluded by laboratory or public health investigation. Of 364 cases, 273 (75%) had confirmed SARS, 30 (8%) were excluded, and 61 (17%) remained indeterminate. Among confirmed cases, exposure occurred in the healthcare environment (80%) or in the households of affected patients (17%); community or travel-related cases were rare (<3%). Fever occurred in 97% of patients by the time of admission. Respiratory findings including cough, dyspnea and pulmonary infiltrates evolved later and were present in only 59, 37 and 68% of patients, respectively, at admission. Direct exposure, fever on the first day of illness, and elevated temperature, pulmonary infiltrates, lymphopenia and thrombocytopenia at admission were associated with confirmed cases. Rhinorrhea, sore throat, and an elevated neutrophil count at admission were associated with excluded cases. In the absence of fever or significant exposure, SARS is unlikely. Other clinical, laboratory and radiographic findings further raise or lower the likelihood of SARS and provide a rational basis for estimating the likelihood of SARS and directing initial management.     

Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.

Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 ± 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.     

Nosocomial infections and risk factors in intensive care unit of a university hospital in Turkey

The aim of this study was to determine the types nosocomial infections (NIs) and the risk factors for NIs in the central intensive care unit (ICU) of Trakya University Hospital. The patients admitted to the ICU were observed prospectively by the unit-directed active surveillance method based on patient and the laboratory over a 9-month-period. The samples of urine, blood, sputum or tracheal aspirate were taken from the patients on the first and the third days of their hospitalization in ICU; the patients were cultured routinely. Other samples were taken and cultured if there was suspicion of an infection. Infections were considered as ICU-associated if they developed after 48 hours of hospitalization in the unit and 5 days after discharge from the unit if the patients had been sent to a different ward in the hospital. The rate of NIs in 135 patients assigned was found to be 68%. The most common infection sites were lower respiratory tract, urinary tract, bloodstream, catheter site and surgical wound. Hospitalization in ICU for more than 6 days and colonization was found to be the main risk factor for NIs. Prolonged mechanical ventilation and tracheostomy, as well as frequently changed nasogastric catheterization, were found to be risk factors for lower respiratory tract infections. For bloodstream infections, both prolonged insertion of and frequent change of arterial catheters, and for urinary tract infections, female gender, period and repeating of urinary catheterization were risk factors. A high prevalence rate of nosocomial infections was found in this study. Invasive device use and duration of use continue to greatly influence the development of nosocomial infection in ICU. Important factors to prevent nosocomial infections are to avoid long hospitalization and unnecessary device application. Control and prevention strategies based on continuing education of healthcare workers will decrease the nosocomial infections in the intensive care unit.     

The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, ³H-FX or ³H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given ³H-FX, but mainly via the feces in mice given ³H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of ³H-FX or ³H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in ³H-FX-administered than ³H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with ³H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.     

Immunogenicity of measles vaccine from a hospital based and outreach programme in rural Kenya.

Data on efficacy of rural immunization programmes are scarce. We investigated the seroconversion rate following measles vaccination in an outreach programme in Kakamega District, Kenya. Of 170 children, 120 (71%) showed seroconversion after vaccination. Haemagglutination inhibition test was performed on paired blood samples before and 30 days or more (mean 46, range 30-70 days) after vaccination. These results are comparable to results found by other studies in developing countries. Geometrical mean titres before vaccination of children in the age group above 14 months were significantly lower than in the younger age groups (P less than 0.001). This investigation indicates that seroconversion rate studies are feasible in remote rural areas.