From 1937 until 1999, West Nile virus (WNV) garnered scant medical attention as the cause of febrile illness and sporadic encephalitis in parts of Africa, Asia, and Europe. After the surprising detection of WNV in New York City in 1999, the virus has spread dramatically westward across the United States, southward into Central America and the Caribbean, and northward into Canada, resulting in the largest epidemics of neuroinvasive WNV disease ever reported. From 1999 to 2004, >7,000 neuroinvasive WNV disease cases were reported in the United States. In 2002, WNV transmission through blood transfusion and organ transplantation was described for the first time, intrauterine transmission was first documented, and possible transmission through breastfeeding was reported. This review highlights new information regarding the epidemiology and dynamics of WNV transmission, providing a new platform for further research into preventing and controlling WNV disease.

West Nile virus (WNV) causes epidemics of febrile illness, meningitis, encephalitis, and flaccid paralysis. Since it was first detected in New York City in 1999, and through 2004, 16,000 WNV disease cases have been reported in the United States. Over the past 5 years, research on WNV disease has expanded rapidly. This review highlights new information regarding the virology, clinical manifestations, and pathology of WNV disease, which will provide a new platform for further research into diagnosis, treatment, and possible prevention of WNV through vaccination.

Brucellae are class 3 organisms and potential agents of bioterrorism. Because of effective public health measures, brucellosis has become a rare disease in industrialized countries, and clinical microbiology laboratories are frequently unfamiliar with the genus. A low index of suspicion by physicians or failure to notify the laboratory, equivocal Gram-stain results, misidentification of the organism by commercial systems, unsafe laboratory practices, and laboratory accidents have been responsible for numerous cases of exposure to the organism and laboratory-acquired disease in recent years. Discovery of a laboratory exposure to brucellae should prompt an exhaustive investigation of the event and its circumstances, definition of the population at risk, enforcement of safe laboratory practices, and antimicrobial drug prophylaxis for exposed persons. Inadvertent exposures to brucellae in the clinical laboratory indicate a widespread lack of preparedness to cope with eventual biologic threats involving use of the organism.

In July 2004, an outbreak of influenza A (H3N2) was detected at 3 Bhutanese refugee camps in southeastern Nepal. Hemagglutination inhibition showed that ≈40% of the viruses from this outbreak were antigenically distinct from the A/Wyoming/3/03 vaccine strain. Four amino acid differences were observed in most of the 26 isolates compared with the A/Wyoming/3/2003 vaccine strain. All 4 substitutions are located within or adjacent to known antibody-binding sites. Several isolates showed a lysine-to-asparagine substitution at position 145 (K145N) in the hemagglutinin molecule, which may be noteworthy since position 145 is located within a glycosylation site and adjacent to an antibody-binding site. H3N2 viruses continue to drift from the vaccine strain and may remain as the dominant strains during the 2005–2006 influenza season. Thus, the 2005–2006 Northern Hemisphere vaccine strain was changed to A/California/7/2004, a virus with all 4 amino acid substitutions observed in these Nepalese isolates.

Sickle cell anemia patients have 600 times the risk for invasive pneumococcal disease than their healthy peers. High-level cephalosporin resistance was described in the 1990s in healthy children from Tennessee, but its prevalence in sickle cell disease patients is unknown. Pneumococcal isolates from sickle cell disease patients from Tennessee were subjected to multilocus sequence typing to characterize antimicrobial drug–resistant strains. Twenty-one percent of strains were resistant to cefotaxime and penicillin. Of the 14 cephalosporin-resistant strains, 9 were sequence types previously described as highly cephalosporin resistant, while resistance was found for the first time in 3 clones: Maryland^6B, ST660, and a novel clone, ST1753. High-level cephalosporin resistance exists in more settings than initially recognized, and its high prevalence in sickle cell disease patients may decrease the efficacy of third-generation cephalosporins in invasive pneumococcal disease.

Few long-term multicenter investigations have evaluated the relationships between aggregate antimicrobial drug use in hospitals and bacterial resistance. We measured fluoroquinolone use from 1999 through 2003 in a network of US hospitals. The percentages of fluoroquinolone-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) were obtained from yearly antibiograms at each hospital. Univariate linear regression showed significant associations between a hospital's volume of fluoroquinolone use and percent resistance in most individual study years (1999–2001 for P. aeruginosa, 1999–2002 for S. aureus). When the method of generalized estimating equations was used, a population-averaged longitudinal model incorporating total fluoroquinolone use and the previous year's resistance (to account for autocorrelation) did not show a significant effect of fluoroquinolone use on percent resistance for most drug-organism combinations, except for the relationship between levofloxacin use and percent MRSA. The ecologic relationship between fluoroquinolone use and resistance is complex and requires further study.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has generated considerable concern among medical and public health professionals. We used a statewide, population-based antimicrobial resistance surveillance system to examine epidemiologic trends for MRSA from outpatients and inpatients in Hawaii. Pediatric and adult patient populations were compared to assess characteristics of MRSA isolates specific for each group. From 2000 to 2002, 8,206 (26%) of 31,482 total S. aureus isolates were MRSA. During this period, the proportion of MRSA isolates increased in both outpatient and inpatient clinical settings (p<0.01). When stratified by age, annual trends showed a significant increase in the proportion of MRSA in adult patients (from 24% to 30%, p<0.01) but not in pediatric patients (from 25% to 27%, p>0.05). Although MRSA isolates from adults demonstrated high resistance to most non–β-lactams, most MRSA isolates from pediatric outpatients remained susceptible to most non–β-lactams.

Coxiella burnetii is a strict intracellular bacterium with potential as a bioterrorism agent. To characterize different isolates of C. burnetii at the molecular level, we performed multispacer sequence typing (MST). MST is based on intergenic region sequencing. These regions are potentially variable since they are subject to lower selection pressure than the adjacent genes. We screened 68 spacers in 14 isolates and selected the 10 that exhibited the most variation. These spacers were then tested in 159 additional isolates obtained from different geographic areas or different hosts or were implicated in different manifestations of human disease caused by C. burnetii. The sequence analysis yielded 30 different allelic combinations. Phylogenic analysis showed 3 major clusters. MST allows easy comparison and exchange of results obtained in different laboratories and could be a useful tool for identifying bacterial strains.

War wound infection and osteomyelitis caused by multidrug-resistant (MDR) Acinetobacter species have been prevalent during the 2003–2005 military operations in Iraq. Twenty-three soldiers wounded in Iraq and subsequently admitted to our facility from March 2003 to May 2004 had wound cultures positive for Acinetobacter calcoaceticus-baumannii complex. Eighteen had osteomyelitis, 2 burn infection, and 3 deep wound infection. Primary therapy for these infections was directed antimicrobial agents for an average of 6 weeks. All soldiers initially improved, regardless of the specific type of therapy. Patients were followed up to 23 months after completing therapy, and none had recurrent infection with Acinetobacter species. Despite the drug resistance that infecting organisms demonstrated in this series, a regimen of carefully selected extended antimicrobial-drug therapy appears effective for osteomyelitis caused by MDR Acinetobacter spp.

The human coronavirus NL63 (HCoV-NL63) was first identified in the Netherlands, and its circulation in France has not been investigated. We studied HCoV-NL63 infection in hospitalized children diagnosed with respiratory tract infections. From November 2002 to April 2003, we evaluated 300 respiratory specimens for HCoV-NL63. Of the 300 samples, 28 (9.3%) were positive for HCoV-NL63. The highest prevalence was found in February (18%). The main symptoms were fever (61%), rhinitis (39%), bronchiolitis (39%), digestive problems (33%), otitis (28%), pharyngitis (22%), and conjunctivitis (17%). A fragment of the spike protein gene was sequenced to determine the variety of circulating HCoV-NL63. Phylogenetic analysis indicated that strains with different genetic markers cocirculate in France.

We studied HIV genetic diversity in a cohort of 127 pregnant, HIV-infected women who received prenatal care at Sainte-Justine Hospital in Montreal, Canada, between 1999 and 2003. Clade assignments were derived by phylogenetic analysis of amplified pol sequences. Genotyping was successful in 103 of 127 women, 59 (57.3%) of whom were infected with clade B HIV-1, and 44 (42.7%) with nonclade B viruses, including subtypes A, C, D, F, G, and H. Four sequences remained unassigned. Forty-three of 44 women infected with non-clade B viruses were newcomers from sub-Saharan Africa, and subtype identity was consistent with those circulating in their countries of origin. These results highlight the epidemiologic importance of non-B HIV-1 in antenatal populations in a large North American urban center, underscore the influence of population movements on clade intermixing, and identify a group of patients who could be targeted for surveillance and drug therapy followup.

In 1999 and 2000, 3 state health departments reported 4 outbreaks of gastrointestinal illness due to Salmonella enterica serotype Typhimurium in employees, clients, and client animals from 3 companion animal veterinary clinics and 1 animal shelter. More than 45 persons and companion animals became ill. Four independent investigations resulted in the testing of 19 human samples and >200 animal samples; 18 persons and 36 animals were culture-positive for S. Typhimurium. One outbreak was due to multidrug-resistant S. Typhimurium R-type ACKSSuT, while the other 3 were due to multidrug-resistant S. Typhimurium R-type ACSSuT DT104. This report documents nosocomial transmission of S. Typhimurium and demonstrates that companion animal facilities may serve as foci of transmission for salmonellae between animals and humans if adequate precautions are not followed.

We evaluated the clinical usefulness of spoligotyping, a polymerase chain reaction–based method for simultaneous detection and typing of Mycobacterium tuberculosis strains, with acid-fast bacilli–positive slides from clinical specimens or mycobacterial cultures. Overall sensitivity and specificity were 97% and 95% for the detection of M. tuberculosis and 98% and 96% when used with clinical specimens. Laboratory turnaround time of spoligotyping was less than that for culture identification by a median of 20 days. In comparison with IS6110-based restriction fragment length polymorphism typing, spoligotyping overestimated the number of isolates with identical DNA fingerprints by ≈50%, but showed a 100% negative predictive value. Spoligotyping resulted in the modification of ongoing antimycobacterial treatment in 40 cases and appropriate therapy in the absence of cultures in 11 cases. The rapidity of this method in detection and typing could make it useful in the management of tuberculosis in a clinical setting.

Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immunization interventions. We used contact network epidemiology to predict the effect of various control policies for a mildly contagious disease, such as severe acute respiratory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends on the transmissibility of the disease and the contact pattern between persons within a community. The model predicts that use of face masks and general vaccination will only moderately affect the spread of mildly contagious diseases. In contrast, quarantine and ring vaccination can prevent the spread of a wide spectrum of diseases. Contact network epidemiology can provide valuable quantitative input to public health decisionmaking, even before a pathogen is well characterized.

We estimated for Australia the number of cases, hospitalizations, and deaths due to foodborne gastroenteritis in a typical year, circa 2000. The total amount of infectious gastroenteritis was measured by using a national telephone survey. The foodborne proportion was estimated from Australian data on each of 16 pathogens. To account for uncertainty, we used simulation techniques to calculate 95% credibility intervals (CrI). The estimate of incidence of gastroenteritis in Australia is 17.2 million (95% confidence interval 14.5–19.9 million) cases per year. We estimate that 32% (95% CrI 24%–40%) are foodborne, which equals 0.3 (95% CrI 0.2–0.4) episodes per person, or 5.4 million (95% CrI 4.0–6.9 million) cases annually in Australia. Norovirus, enteropathogenic Escherichia coli, Campylobacter spp., and Salmonella spp. cause the most illnesses. In addition, foodborne gastroenteritis causes ≈15,000 (95% CrI 11,000–18,000) hospitalizations and 80 (95% CrI 40–120) deaths annually. This study highlights global public health concerns about foodborne diseases and the need for standardized methods, including assessment of uncertainty, for international comparison.

The increasing prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae has required replacing inexpensive oral ciprofloxacin treatment with more expensive injectable ceftriaxone. Further, monitoring antimicrobial resistance requires culture testing, but nonculture gonorrhea tests are rapidly replacing culture. Since the strategies were similar in effectiveness (>99%), we evaluated, from the healthcare system perspective, cost-minimizing strategies for both diagnosis (culture followed by antimicrobial susceptibility tests versus nonculture-based tests) and treatment (ciprofloxacin versus ceftriaxone) of gonorrhea in women. Our results indicate that switching from ciprofloxacin to ceftriaxone is cost-minimizing (i.e., optimal) when the prevalence of gonorrhea is >3% and prevalence of ciprofloxacin resistance is >5%. Similarly, culture-based testing and susceptibility surveillance are optimal when the prevalence of gonorrhea is <13%; nonculture-based testing is optimal (cost-minimizing) when gonorrhea prevalence is ≥13%.

Scrapie is a small ruminant, transmissible spongiform encephalopathy (TSE). Although in the past scrapie has not been considered a zoonosis, the emergence of bovine spongiform encephalopathy, transmissible to humans and experimentally to sheep, indicates that risk exists for small ruminant TSEs in humans. To identify the risk factors for introducing scrapie into sheep flocks, a case-control study was conducted in France from 1999 to 2000. Ninety-four case and 350 control flocks were matched by location and main breed. Three main hypotheses were tested: direct contact between flocks, indirect environmental contact, and foodborne risk. Statistical analysis was performed by using adjusted generalized linear models with the complementary log-log link function, considering flock size as an offset. A notable effect of using proprietary concentrates and milk replacers was observed. The risk was heterogeneous among feed factories. Contacts between flocks were not shown to be a risk factor.

We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.

We report the first known case of a device-related bloodstream infection involving Staphylococcus lugdunensis small-colony variants. Recurrent pacemaker-related bloodstream infection within a period of 10 months illustrates the poor clinical and microbiologic response even to prolonged antimicrobial drug therapy in a patient infected with this staphylococcal subpopulation.

We recovered Bartonella quintana DNA from dental pulp of a domestic cat. This study, the first to detect B. quintana in a nonhuman mammal, changes our understanding of the epidemiology of this infection and proposes that cats may be an emerging source of human infection.

We investigated the prevalence of malaria and associated risk factors in children living in urban Ghana. Malaria prevalence was associated with low hemoglobin concentration, low socioeconomic status, and higher age. Our findings indicate that African urban poor are seriously affected by malaria and that irrigated agriculture may increase this risk.

We report West Nile virus (WNV) RNA in urine collected from a patient with encephalitis 8 days after symptom onset. Viral RNA was detected by reverse transcriptase–polymerase chain reaction (RT-PCR). Sequence and phylogenetic analysis confirmed the PCR product to have ≥99% similarity to the WNV strain NY 2000-crow3356.

Posttraumatic stress disorder (PTSD) can arise in patients with medical illness. We used 2 Chinese self-report measures to examine features of PTSD, anxiety, and depression in 131 survivors of severe acute respiratory syndrome at 1 month and 3 months after discharge from the hospital. Risk factors associated with psychological distress were identified.

We used hospital antibiograms to assess predominant pathogens and their patterns of in vitro antimicrobial resistance in central Illinois, USA. We found a lack of information about national guidelines for in vitro antimicrobial susceptibility testing and differences in interpretation among laboratories in the region.

We developed a sensitive and rapid real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to detect influenza A H5N1 virus in clinical samples. This assay was evaluated with samples from H5N1-infected patients and demonstrated greater sensitivity and faster turnaround time than nested RT-PCR.

Diarrheogenic Escherichia coli isolates from 45 (73%) of 62 hospitalized patients were resistant to common antimicrobial drugs. Sixty-two percent were multidrug resistant, and >70% were resistant to trimethoprim-sulfamethoxazole and ampicillin. Ciprofloxacin and cefotaxime were uniformly active. Effective and safe oral agents are needed to treat children with bacterial diarrhea.