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Volume 10, Number 3—March 2004

Volume 10, Number 3—March 2004   PDF Version [PDF - 5.81 MB - 179 pages]


  • Clinical Trials and Novel Pathogens: Lessons Learned from SARS PDF Version [PDF - 223 KB - 6 pages]
    M. P. Muller et al.
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    During the recent global outbreak of severe acute respiratory syndrome (SARS), thousands of patients received treatments of uncertain efficacy and known toxicity such as ribavirin and corticosteroids. Despite this, no controlled clinical trials assessing the efficacy of these agents were conducted. If a second global SARS outbreak occurred, clinicians would not have controlled data on which to base therapeutic decisions. We discuss the unique methodologic and logistical challenges faced by researchers who attempt to conduct controlled trials of therapeutic agents during an outbreak of a novel or unknown infectious pathogen. We draw upon our own experience in attempting to conduct a randomized controlled trial (trial) of ribavirin therapy for SARS and discuss the lessons learned. Strategies to facilitate future clinical trials during outbreaks of unknown or novel pathogens are also presented.

  • SARS Transmission and Hospital Containment PDF Version [PDF - 103 KB - 6 pages]
    G. Gopalakrishna et al.
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    An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.

  • The RUsick2 Foodborne Disease Forum for Syndromic Surveillance PDF Version [PDF - 133 KB - 5 pages]
    H. Wethington and P. Bartlett
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    The RUsick2 Foodborne Disease Forum at the National Food Safety and Toxicology Center increased reporting of foodborne diseases to more than four times the rate seen in the previous 2 years. Since November 2002, the Forum has allowed pilot-area residents with sudden-onset vomiting or diarrhea to share and compare information regarding what they ate and did before becoming sick. The purpose is to identify a common food source, perhaps resulting in identifying a cluster of persons who ate the same contaminated food item. Such information can assist health departments in detecting foodborne outbreaks while the possibility for intervention remains.


  • Reemerging Leptospirosis, California PDF Version [PDF - 332 KB - 7 pages]
    E. Meites et al.
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    Leptospirosis is a reemerging infectious disease in California. Leptospirosis is the most widespread zoonosis throughout the world, though it is infrequently diagnosed in the continental United States. From 1982 to 2001, most reported California cases occurred in previously healthy young adult white men after recreational exposures to contaminated freshwater. We report five recent cases of human leptospirosis acquired in California, including the first documented common-source outbreak of human leptospirosis acquired in this state, and describe the subsequent environmental investigation. Salient features in the California cases include high fever with uniform renal impairment and mild hepatitis. Because leptospirosis can progress rapidly if untreated, this reemerging infection deserves consideration in febrile patients with a history of recreational freshwater exposure, even in states with a low reported incidence of infection.


  • Coronaviridae and SARS-associated Coronavirus Strain HSR1 PDF Version [PDF - 198 KB - 6 pages]
    E. Vicenzi et al.
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    During the recent severe acute respiratory (SARS) outbreak, the etiologic agent was identified as a new coronavirus (CoV). We have isolated a SARS-associated CoV (SARS-CoV) strain by injecting Vero cells with a sputum specimen from an Italian patient affected by a severe pneumonia; the patient traveled from Vietnam to Italy in March 2003. Ultrastructural analysis of infected Vero cells showed the virions within cell vesicles and around the cell membrane. The full-length viral genome sequence was similar to those derived from the Hong-Kong Hotel M isolate. By using both real-time reverse transcription–polymerase chain reaction TaqMan assay and an infectivity plaque assay, we determined that approximately 360 viral genomes were required to generate a PFU. In addition, heparin (100 μg/mL) inhibited infection of Vero cells by 50%. Overall, the molecular and biologic characteristics of the strain HSR1 provide evidence that SARS-CoV forms a fourth genetic coronavirus group with distinct genomic and biologic features.

  • Laboratory Analysis of Tularemia in Wild-Trapped, Commercially Traded Prairie Dogs, Texas, 2002 PDF Version [PDF - 88 KB - 7 pages]
    J. M. Petersen et al.
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    Oropharyngeal tularemia was identified as the cause of a die-off in captured wild prairie dogs at a commercial exotic animal facility in Texas. From this point source, Francisella tularensis–infected prairie dogs were traced to animals distributed to the Czech Republic and to a Texas pet shop. F. tularensis culture isolates were recovered tissue specimens from 63 prairie dogs, including one each from the secondary distribution sites. Molecular and biochemical subtyping indicated that all isolates were F. tularensis subsp. holarctica (Type B). Microagglutination assays detected antibodies against F. tularensis, with titers as great as 1:4,096 in some live animals. All seropositive animals remained culture positive, suggesting that prairie dogs may act as chronic carriers of F. tularensis. These findings demonstrate the need for additional studies of tularemia in prairie dogs, given the seriousness of the resulting disease, the fact that prairie dogs are sold commercially as pets, and the risk for pet-to-human transmission.

  • Monkeypox Transmission and Pathogenesis in Prairie Dogs PDF Version [PDF - 427 KB - 6 pages]
    J. Guarner et al.
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    During May and June 2003, the first cluster of human monkeypox cases in the United States was reported. Most patients with this febrile vesicular rash illness presumably acquired the infection from prairie dogs. Monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. Immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface epithelial cells of lesions in conjunctiva and tongue, with less amounts in adjacent macrophages, fibroblasts, and connective tissues. Viral antigens in the lung were abundant in bronchial epithelial cells, macrophages, and fibroblasts. Virus isolation and electron microscopy demonstrated active viral replication in lungs and tongue. These findings indicate that both respiratory and direct mucocutaneous exposures are potentially important routes of transmission of monkeypox virus between rodents and to humans. Prairie dogs offer insights into transmission, pathogenesis, and new vaccine and treatment trials because they are susceptible to severe monkeypox infection.

  • Acute Spotted Fever Rickettsiosis among Febrile Patients, Cameroon PDF Version [PDF - 256 KB - 6 pages]
    L. M. Ndip et al.
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    Although potential arthropod vectors are abundant in Cameroon, acute febrile illnesses are rarely evaluated for arboviral or rickettsial infections. Serum samples from 234 acutely febrile patients at clinics in Tiko and Buea, Cameroon, were examined for antibodies to Rickettsia africae and African alphaviruses and flaviviruses. These serum samples did not contain antibodies against typhoid, and blood malarial parasites were not detected. Serum samples of 32% contained immunoglobulin M antibodies reactive with R. africae by immunofluorescence assay and were reactive with outer membrane proteins A and B of R. africae by immunoblotting. These findings established a diagnosis of acute rickettsiosis, most likely African tick-bite fever. Hemagglutination inhibition testing of the serum samples also detected antibodies to Chikungunya virus (47%) and flaviviruses (47%). High prevalence of antibodies to arboviruses may represent a major, previously unrecognized public health problem in an area where endemic malaria and typhoid fever have been the principal diagnostic considerations.

  • Genomic Changes of Chagas Disease Vector, South America PDF Version [PDF - 142 KB - 9 pages]
    F. Panzera et al.
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    We analyzed the main karyologic changes that have occurred during the dispersion of Triatoma infestans, the main vector of Chagas disease. We identified two allopatric groups, named Andean and non-Andean. The Andean specimens present C-heterochromatic blocks in most of their 22 chromosomes, whereas non-Andean specimens have only 4–7 autosomes with C-banding. These heterochromatin differences are the likely cause of a striking DNA content variation (approximately 30%) between Andean and non-Andean insects. Our study, together with previous historical and genetic data, suggests that T. infestans was originally a sylvatic species, with large quantities of DNA and heterochromatin, inhabiting the Andean region of Bolivia. However, the spread of domestic T. infestans throughout the non-Andean regions only involved insects with an important reduction of heterochromatin and DNA amounts. We propose that heterochromatin and DNA variation mainly reflected adaptive genomic changes that contribute to the ability of T. infestans to survive, reproduce, and disperse in different environments.

  • Internet Use and Epidemiologic Investigation of Gastroenteritis Outbreak PDF Version [PDF - 46 KB - 4 pages]
    M. Kuusi et al.
  • Correlating Epidemiologic Trends with the Genotypes Causing Meningococcal Disease, Maryland PDF Version [PDF - 259 KB - 6 pages]
    M. C. McEllistrem et al.
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    Epidemic meningococcal infection is generally caused by single clones; whether nonepidemic increases in infection are clonal is unknown. We studied the molecular epidemiology of meningococcal infection during a period that the incidence increased in two age groups. Serogroup C and Y meningococcal isolates were analyzed by pulsed-field gel electrophoresis and multilocus sequence typing. From 1992 to 1999, 96.4% (27/28) of serogroup C isolates from persons 15–24 years of age were in clonal group 1, compared with 65.6% (21/32) of isolates from persons ≤14 years, and 64.3% (9/14) of isolates from adults ≥25 years (p ≤ 0.01). The proportion of clonal group 2 serogroup Y strains increased from 7.7% (1/13) in 1992 to 1993 to 52.0% (13/25) in 1998 to 1999 (p < 0.01). The nonepidemic age-specific increases in serogroup C meningococcal infection in Maryland were clonal in nature and the changes in serogroup Y incidence were associated with a shift in the genotypes of strains causing invasive disease.

  • Legionella Infection Risk from Domestic Hot Water PDF Version [PDF - 82 KB - 8 pages]
    P. Borella et al.
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    We investigated Legionella and Pseudomonas contamination of hot water in a cross-sectional multicentric survey in Italy. Chemical parameters (hardness, free chlorine, and trace elements) were determined. Legionella spp. were detected in 33 (22.6%) and Pseudomonas spp. in 56 (38.4%) of 146 samples. Some factors associated with Legionella contamination were heater type, tank distance and capacity, water plant age, and mineral content. Pseudomonas presence was influenced by water source, hardness, free chlorine, and temperature. Legionella contamination was associated with a centralized heater, distance from the heater point >10 m, and a water plant >10 years old. Furthermore, zinc levels of <20 μg/L and copper levels of >50 μg/L appeared to be protective against Legionella colonization. Legionella species and serogroups were differently distributed according to heater type, water temperature, and free chlorine, suggesting that Legionella strains may have a different sensibility and resistance to environmental factors and different ecologic niches.

  • Cysticercosis-related Deaths, California PDF Version [PDF - 59 KB - 5 pages]
    F. J. Sorvillo et al.
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    Cysticercosis is an increasingly important disease in the United States, but information on the occurrence of related deaths is limited. We examined data from California death certificates for the 12-year period 1989–2000. A total of 124 cysticercosis deaths were identified, representing a crude 12-year death rate of 3.9 per million population (95% confidence interval [CI] 3.2 to 4.6). Eighty-two (66%) of the case-patients were male; 42 (34%) were female. The median age at death was 34.5 years (range 7–81 years). Most patients (107, 86.3%) were foreign-born, and 90 (72.6%) had emigrated from Mexico. Seventeen (13.7%) deaths occurred in U.S.-born residents. Cysticercosis death rates were higher in Latino residents of California (13.0/106) than in other racial/ethnic groups (0.4/106), in males (5.2/106) than in females (2.7/106), and in persons >14 years of age (5.0/106). Cysticercosis is a preventable cause of premature death, particularly among young Latino persons in California and may be a more common cause of death in the United States than previously recognized.

  • Amoebae-resisting Bacteria Isolated from Human Nasal Swabs by Amoebal Coculture PDF Version [PDF - 250 KB - 8 pages]
    G. Greub et al.
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    Amoebae feed on bacteria, and few bacteria can resist their microbicidal ability. Amoebal coculture could therefore be used to selectively grow these amoebae-resisting bacteria (ARB), which may be human pathogens. To isolate new ARB, we performed amoebal coculture from 444 nasal samples. We recovered 7 (1.6%) ARB from 444 nasal swabs, including 4 new species provisionally named Candidatus Roseomonas massiliae, C. Rhizobium massiliae, C. Chryseobacterium massiliae, and C. Amoebinatus massiliae. The remaining isolates were closely related to Methylobacterium extorquens, Bosea vestrii, and Achromobacter xylosoxidans. Thus, amoebal coculture allows the recovery of new bacterial species from heavily contaminated samples and might be a valuable approach for the recovery of as-yet unrecognized emerging pathogens from clinical specimens.

  • Neutralizing Antibodies and Sin Nombre Virus RNA after Recovery from Hantavirus Cardiopulmonary Syndrome PDF Version [PDF - 162 KB - 5 pages]
    C. Ye et al.
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    Patients who later have a mild course of hantavirus cardiopulmonary syndrome (HCPS) are more likely to exhibit a high titer of neutralizing antibodies against Sin Nombre virus (SNV), the etiologic agent of HCPS, at the time of hospital admission. Because administering plasma from patients who have recovered from HCPS to those in the early stages of disease may be an advantageous form of passive immunotherapy, we examined the neutralizing antibody titers of 21 patients who had recovered from SNV infection. Even 1,000 days after admission to the hospital, 6 of 10 patients had titers of 800 or higher, with one sample retaining a titer of 3,200 after more than 1,400 days. None of the convalescent-phase serum samples contained detectable viral RNA. These results confirm that patients retain high titers of neutralizing antibodies long after recovery from SNV infection.




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