Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), reemerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world’s most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Disease (NIAID) have contributed substantially to this effort. This review highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed.

An outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) occurred in a college football team from August to September 2003. Eleven case-players were identified, and boils were the most common sign. Linemen had the highest attack rate (18%). Among 99 (93% of team) players with cultured specimens, 8 (8%) had positive MRSA nasal cultures. All available case-players’ MRSA isolates characterized had the community-associated pulsed-field type USA300. A case-control study found that sharing bars of soap and having preexisting cuts or abrasions were associated with infection. A carrier-control study found that having a locker near a teammate with an SSTI, sharing towels, and living on campus were associated with nasal carriage. Successful outbreak control measures included daily hexachlorophene showers and hygiene education.

Until recently, bed bugs have been considered uncommon in the industrialized world. This study determined the extent of reemerging bed bug infestations in homeless shelters and other locations in Toronto, Canada. Toronto Public Health documented complaints of bed bug infestations from 46 locations in 2003, most commonly apartments (63%), shelters (15%), and rooming houses (11%). Pest control operators in Toronto (N = 34) reported treating bed bug infestations at 847 locations in 2003, most commonly single-family dwellings (70%), apartments (18%), and shelters (8%). Bed bug infestations were reported at 20 (31%) of 65 homeless shelters. At 1 affected shelter, 4% of residents reported having bed bug bites. Bed bug infestations can have an adverse effect on health and quality of life in the general population, particularly among homeless persons living in shelters.

Studies of experimental infection of prairie dogs (Cynomys ludovicianus) with monkeypox virus are described. After intraperitoneal infection, all of the animals died within 11 days. Virus was cultured from their blood and oropharynx several days before death; at necropsy, most of the organs tested contained monkeypox virus. Marked hepatic and splenic necrosis were observed, along with mild inflammatory changes in the lungs. After intranasal infection, the primary pathologic changes were in the lungs and pleural cavity. Some of the intranasally infected animals (40%) survived, and monkeypox virus could be cultured from their nasal discharge and oropharynx for <22 days. Ulcerative lesions also developed on the lips, tongue, and buccal mucosa of the surviving animals. Our findings support an earlier report, which suggested that infected prairie dogs can transmit monkeypox virus by respiratory and mucocutaneous contact with susceptible animals and persons.

To address the public health problem of antimicrobial resistance, the European Union founded the European Antimicrobial Resistance Surveillance System. A network of 32 Spanish hospitals, serving ≈9.6 million persons, submitted antimicrobial-susceptibility data on 7,098 invasive Escherichia coli species (2001–2003). Resistance to ampicillin, cotrimoxazole, ciprofloxacin, gentamicin, and tobramycin was found at rates of 59.9%, 32.6%, 19.3%, 6.8%, and 5.3%, respectively. Resistance to multiple drugs increased from 13.8% in 2001 to 20.6% in 2003 (p < 0.0001). Antimicrobial consumption data were obtained from the Spanish National Health System. In spite of decreased cephalosporin and β-lactam use, overall extended-spectrum β-lactamase production increased from 1.6% (2001) to 4.1% (2003) (p < 0.0001), mainly due to the rising prevalence of cefotaximases. Resistance to ciprofloxacin significantly increased, mostly in community-onset infections, which coincided with a rise in community quinolone use. Cotrimoxazole resistance remained stable at ≈30%, even though its use was dramatically reduced.

Staphylococcus aureus bacteremia (SAB) is common and increasing worldwide. A retrospective review was undertaken to quantify the number of cases, their place of acquisition, and the proportions caused by methicillin-resistant S. aureus (MRSA) in 17 hospitals in Australia. Of 3,192 episodes, 1,571 (49%) were community onset. MRSA caused 40% of hospital-onset episodes and 12% of community-onset episodes. The median rate of SAB was 1.48/1,000 admissions (range 0.61–3.24; median rate for hospital-onset SAB was 0.7/1,000 and for community onset 0.8/1,000 admissions). Using these rates, we estimate that ≈6,900 episodes of SAB occur annually in Australia (35/100,000 population). SAB is common, and a substantial proportion of cases may be preventable. The epidemiology is evolving, with >10% of community-onset SAB now caused by MRSA. This is an emerging infectious disease concern and is likely to impact on empiric antimicrobial drug prescribing in suspected cases of SAB.

An outbreak of aseptic meningitis occurred in the northern area of Jiangsu Province in China from January to July in 2003. A total of 1,681 cases were involved in this outbreak, and 99% of patients were <15 years of age. To identify the etiologic agent, 66 cerebrospinal fluid specimens were tested by cell culture. Eighteen showed an enteroviruslike cytopathic effect on MRC-5 human fetal diploid lung cells. An enterovirus primer-mediated reverse transcriptase–polymerase chain reaction, a standard neutralization assay, and sequencing of the complete capsid-encoding (VP1) gene identified the 18 isolates (FDJS03) as echovirus 30. At least a 10% difference was seen in nucleotide sequences of VP1 between FDJS03 isolates and other global strains of echovirus 30. Phylogenetic analysis based on complete sequences of VP1 was performed to further characterize the FDJS03 isolates. This report is the first to identify a distinct lineage of echovirus 30 as a probable cause of this outbreak.

As a consequence of large-scale outdoor slaughter of sheep during the 2001 foot and mouth disease (FMD) outbreak in the United Kingdom and the possibility of increased risk for transmission of Echinococcus granulosus between sheep and dogs, a large survey of canine echinococcosis was undertaken in mid-Wales in 2002. An Echinococcus coproantigen-positive rate of 8.0% (94/1,164) was recorded on 22% of farms surveyed, which compares to a rate of 3.4% obtained in the same region in 1993. Positivity rates between FMD-affected properties and unaffected ones did not differ significantly. Significant risk factors for positive results in farm dogs were allowing dogs to roam free and the infrequent dosing (>4-month intervals) of dogs with praziquantel. When these data are compared to those of a previous pilot hydatid control program in the area (1983–1989), an increase in transmission to humans appears probable.

We report the first seroprevalence study of the occurrence of specific antibodies to European bat lyssavirus type 2 (EBLV-2) in Daubenton bats. Bats were captured from 19 sites across eastern and southern Scotland. Samples from 198 Daubenton bats, 20 Natterer bats, and 6 Pipistrelle bats were investigated for the presence of EBLV-2. Blood samples (N = 94) were subjected to a modified fluorescent antibody virus neutralization test to determine antibody titer. From 0.05% to 3.8% (95% confidence interval) of Daubenton bats were seropositive. Antibodies to EBLV-2 were not detected in the 2 other species tested. Mouth swabs (N = 218) were obtained, and RNA was extracted for a reverse transcription–polymerase chain reaction (RT-PCR). The RT-PCR included pan lyssavirus-primers (N gene) and internal PCR control primers for ribosomal RNA. EBLV-2 RNA was not detected in any of the saliva samples tested, and live virus was not detected in virus isolation tests.

Influenza may rapidly disseminate within populations living in confined settings, causing considerable morbidity and disrupting daily activities. We describe an influenza A outbreak on a military base where 3,000young adults, most of whom were unvaccinated, lived in close daily contact. The presentation to the base clinic of 48 cases of acute respiratory illness within 2 days allowed early identification of this outbreak and prompted immediate epidemiologic investigation. Overall, 85 personnel (2.83% of base population) met the case definition for influenzalike illness. On-site laboratory confirmation with field detection kits, rapid implementation of respiratory illness control protocols, and a mass vaccination campaign were applied to limit disease dissemination. The outbreak was halted 14 days after the mass vaccination campaign was completed. We review the control measures available for controlling influenza outbreaks in confined settings and discuss the role of rapid mass vaccination within this context

Buruli ulcer is a recognized public health problem in West Africa. In Benin, from 1989 to 2001, the Centre Sanitaire et Nutritionnel Gbemoten (CSNG) treated >2,500 Buruli ulcer patients. From March 2000 to February 2001, field trips were conducted in the Zou and Atlantique regions. The choice of the 2 regions was based on the distance from CSNG and on villages with the highest number of patients treated at CSNG. A total of 66 (44.0%) of 150 former patients treated at CSNG were located in the visited villages. The recurrence rate of CSNG-treated patients after a follow-up period of up to 7 years was low (6.1%, 95% confidence interval [CI] 2.0–15.6). We attribute this low rate to the high quality of Buruli ulcer treatment at an accessible regional center (CSNG). The World Health Organization definition of a Buruli ulcer recurrent case should be revised to include a follow-up period >1 year.

We conducted prospective surveillance of childhood hemolytic uremic syndrome (HUS) from 1997 to 2001 to describe disease incidence and clinical, epidemiologic and microbiologic characteristics. We compared our findings, where possible, with those of a previous study conducted from 1985 to 1988. The average annual incidence of HUS for the United Kingdom and Ireland (0.71/100,000) was unchanged from 1985 to 1988. The overall early mortality had halved, but the reduction in mortality was almost entirely accounted for by improved outcome in patients with diarrhea-associated HUS. The principal infective cause of diarrhea-associated HUS was Shiga toxin–producing Escherichia coli O157 (STEC O157), although in the 1997–2001 survey STEC O157 phage type (PT) 21/28 had replaced STEC O157 PT2 as the predominant PT. The risk of developing diarrhea-associated HUS was significantly higher in children infected with STEC O157 PT 2 and PT 21/28 compared with other PTs. Hypertension as a complication of HUS was greatly reduced in patients with diarrhea-associated HUS.

This study assessed progress towards tuberculosis (TB) elimination in the Netherlands by using DNA fingerprinting. Mycobacterium tuberculosis strains were defined as new if the IS6110 restriction fragment length polymorphism pattern had not been observed in any other patient during the previous 2 years. Other cases were defined as clustered and attributed to recent transmission. In the period 1995–2002, the incidence of TB with new strains was stable among non-Dutch residents and declined among the Dutch. However, the decline among the Dutch was restricted to those >65 years of age. Moreover, the average number of secondary cases per new strain did not change significantly over time. We conclude that the decline of TB in the Netherlands over the past decade was mainly the result of a cohort effect: older birth cohorts with high infection prevalence were replaced by those with lower infection prevalence. Under current epidemiologic conditions and control efforts, TB may not be eliminated.

Escherichia coli O157:H7 causes 73,000 illnesses in the United States annually. We reviewed E. coli O157 outbreaks reported to Centers for Disease Control and Prevention (CDC) to better understand the epidemiology of E. coli O157. E. coli O157 outbreaks (>2 cases of E. coli O157 infection with a common epidemiologic exposure) reported to CDC from 1982 to 2002 were reviewed. In that period, 49 states reported 350 outbreaks, representing 8,598 cases, 1,493 (17%) hospitalizations, 354 (4%) hemolytic uremic syndrome cases, and 40 (0.5%) deaths. Transmission route for 183 (52%) was foodborne, 74 (21%) unknown, 50 (14%) person-to-person, 31 (9%) waterborne, 11 (3%) animal contact, and 1 (0.3%) laboratory-related. The food vehicle for 75 (41%) foodborne outbreaks was ground beef, and for 38 (21%) outbreaks, produce.

We investigated a large outbreak of Salmonella enterica serotype Javiana among attendees of the 2002 U.S. Transplant Games, including 1,500 organ transplant recipients. Web-based survey methods identified pre-diced tomatoes as the source of this outbreak, which highlights the utility of such investigative tools to cope with the changing epidemiology of foodborne diseases.

We report 2 clinically characteristic and serologically positive cases of Ross River virus infection in Canadian tourists who visited Fiji in late 2003 and early 2004. This report suggests that Ross River virus is once again circulating in Fiji, where it apparently disappeared after causing an epidemic in 1979 to 1980.

In 2000, an outbreak of Mycobacterium fortuitum furunculosis affected customers using whirlpool footbaths at a nail salon. We swabbed 30 footbaths in 18 nail salons from 5 California counties and found mycobacteria in 29 (97%); M. fortuitum was the most common. Mycobacteria may pose an infectious risk for pedicure customers.

Dairy cattle are a primary reservoir of Coxiella burnetii, which causes Q fever. However, no recent nationwide studies have assessed the prevalence and risks of Q fever in dairy cattle. We report >94% prevalence in samples of bulk tank milk from US dairy herds tested during the past 3 years.

Serum specimens from patients at 4 sites in Peru were tested for evidence of spotted fever group rickettsial infection. Results showed that 30 (18%) of 170 patients had spotted fever group rickettsial infections, which likely caused their illnesses. These findings document laboratory-confirmed spotted fever from diverse areas of Peru.

We reinterviewed healthcare workers who had been exposed to a patient with severe acute respiratory syndrome (SARS) in an intensive care unit to evaluate the effect of time on recall reliability and willingness to report contact activities and infection control precautions. Healthcare workers reliably recalled events 6 months after exposure.

We analyzed the response of human glioma cells to West Nile virus infection by investigating host transcriptional changes. Changes in expression of 23 genes showed similarities to those in other neurodegenerative diseases. These changes may be useful as potential biomarkers and elucidate novel mechanisms behind the neuropathology of infection with this virus.