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Volume 10, Number 9—September 2004

Volume 10, Number 9—September 2004   PDF Version [PDF - 5.68 MB - 195 pages]


  • New Measurable Indicator for Tuberculosis Case Detection PDF Version [PDF - 285 KB - 6 pages]
    M. W. Borgdorff
       View Abstract

    The World Health Organization’s goal for tuberculosis (TB) control is to detect 70% of cases with a new, smear-positive TB test and cure 85% of these cases. The case detection rate is the number of reported cases per 100,000 persons per year divided by the estimated incidence rate per 100,000 per year. TB incidence is uncertain and not measured but estimated; therefore, the case detection rate is uncertain. This article proposes a new indicator to assess case detection: the patient diagnostic rate. The patient diagnostic rate is the rate at which prevalent cases are detected by control programs and can be measured as the number of reported cases per 100,000 persons per year divided by the prevalence per 100,000. Prevalence can be measured directly through national prevalence surveys. Conducting prevalence surveys at 5- to 10-year intervals would allow countries with high rates of disease to determine their case detection performance by using the patient diagnostic rate and determine the effect of control measures.

  • Potential Public Health Impact of New Tuberculosis Vaccines PDF Version [PDF - 358 KB - 7 pages]
    E. Ziv et al.
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    Developing effective tuberculosis (TB) vaccines is a high priority. We use mathematical models to predict the potential public health impact of new TB vaccines in high-incidence countries. We show that preexposure vaccines would be almost twice as effective as postexposure vaccines in reducing the number of new infections. Postexposure vaccines would initially have a substantially greater impact, compared to preexposure vaccines, on reducing the number of new cases of disease. However, the effectiveness of postexposure vaccines would diminish over time, whereas the effectiveness of preexposure vaccines would increase. Thus, after 20 to 30 years, post- or preexposure vaccination campaigns would be almost equally effective in terms of cumulative TB cases prevented. Even widely deployed and highly effective (50%–90% efficacy) pre- or postexposure vaccines would only be able to reduce the number of TB cases by one third. We discuss the health policy implications of our analyses.

  • Deaths due to Unknown Foodborne Agents PDF Version [PDF - 119 KB - 8 pages]
    P. D. Frenzen
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    This study reviews the available evidence on unknown pathogenic agents transmitted in food and examines the methods that have been used to estimate that such agents cause 3,400 annual U.S. deaths per year in the United States. The estimate of deaths was derived from hospital discharge and death certificate data on deaths attributed to gastroenteritis of unknown cause. Fatal illnesses due to unknown foodborne agents do not always involve gastroenteritis, and gastroenteritis may not be accurately diagnosed or reported on hospital charts or death certificates. The death estimate consequently omitted deaths from unknown foodborne agents that do not cause gastroenteritis and likely overstated the number of deaths from agents that cause gastroenteritis. Although the number of deaths from unknown foodborne agents is uncertain, the possible economic cost of these deaths is so large that increased efforts to identify the causal agents are warranted.


  • Laboratory Exposures to Staphylococcal Enterotoxin B PDF Version [PDF - 175 KB - 6 pages]
    J. M. Rusnak et al.
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    Staphylococcal enterotoxins are 23- to 29-kDa polypeptides in the bacterial superantigen protein family. Clinical symptoms from intoxication with staphylococcal enterotoxins vary by exposure route. Ingestion results in gastrointestinal symptoms, and inhalation results in fever as well as pulmonary and gastrointestinal symptoms. Review of occupational exposures at the U.S. Army Medical Research Institute of Infectious Diseases from 1989 to 2002 showed that three laboratory workers had symptoms after ocular exposure to staphylococcal enterotoxin B (SEB). Conjunctivitis with localized cutaneous swelling occurred in three persons within 1 to 6 hours after exposure to SEB; two of these persons also had gastrointestinal symptoms, which suggests that such symptoms occurred as a result of exposure by an indirect cutaneous or ocular route. Ocular exposures from SEB resulting in conjunctivitis and localized swelling have not previously been reported. Symptoms from these patients and review of clinical symptoms of 16 laboratory-acquired inhalational SEB intoxications may help healthcare workers evaluate and identify SEB exposures in laboratory personnel at risk.


  • Viral Loads in Clinical Specimens and SARS Manifestations PDF Version [PDF - 195 KB - 8 pages]
    I. Hung et al.
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    A retrospective viral load study was performed on clinical specimens from154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS), prospectively collected during patients’ illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.

  • SARS Antibody Test for Serosurveillance PDF Version [PDF - 100 KB - 5 pages]
    P. Hsueh et al.
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    A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. The assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-associated coronavirus. The new peptide ELISA consistently detected seroconversion by week 2 of onset of fever, and seropositivity remained through day 100. Specificity was 100% on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. The peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for SARS. The assay was used for a retrospective survey of healthy healthcare workers in Taiwan who treated SARS patients. Asymptomatic seroconversions were detected in two hospitals that had nosocomial disease.

  • Experimental Infection of Ground Squirrels (Spermophilus tridecemlineatus) with Monkeypox Virus PDF Version [PDF - 294 KB - 5 pages]
    R. B. Tesh et al.
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    A proposed new small-animal (rodent) model for studying the pathogenesis and treatment of severe orthopoxvirus infections is described. Thirteen-lined ground squirrels (Spermophilus tridecemlineatus) were infected intraperitoneally and intranasally with monkeypox virus (MPXV). A fulminant illness developed in all animals, and they died 6–9 days after infection. Virus was cultured from the blood and oropharynx several days before death; at necropsy, all of the organs tested contained relatively high titers of MPXV. The major pathologic findings were in the liver, which showed centrilobular necrosis, steatosis, and basophilic inclusion bodies in hepatocytes. Splenic necrosis was also observed, as well as interstitial inflammation in the lungs. The pathologic features of MPXV in ground squirrels is similar to that described with MPXV in macaques and severe variola (smallpox) virus infection in humans.

  • Silent Nucleotide Polymorphisms and a Phylogeny for Mycobacterium tuberculosis PDF Version [PDF - 309 KB - 10 pages]
    L. Baker et al.
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    Much remains unknown of the phylogeny and evolution of Mycobacterium tuberculosis, an organism that kills 2 million people annually. Using a population-based approach that analyzes multiple loci around the chromosome, we demonstrate that neutral genetic variation in genes associated with antimicrobial drug resistance has sufficient variation to construct a robust phylogenetic tree for M. tuberculosis. The data describe a clonal population with a minimum of four distinct M. tuberculosis lineages, closely related to M. bovis. The lineages are strongly geographically associated. Nucleotide substitutions proven to cause drug resistance are distributed throughout the tree, whereas nonsynonymous base substitutions unrelated to drug resistance have a restricted distribution. The phylogenetic structure is concordant with all the previously described genotypic and phenotypic groupings of M. tuberculosis strains and provides a unifying framework for both epidemiologic and evolutionary analysis of M. tuberculosis populations.

  • Genetic Divergence and Dispersal of Yellow Fever Virus, Brazil PDF Version [PDF - 349 KB - 7 pages]
    P. Vasconcelos et al.
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    Examining viral isolates collected over 66 years shows divergence into clades and potential dispersal by human migration.

       View Abstract

    An analysis of 79 yellow fever virus (YFV) isolates collected from 1935 to 2001 in Brazil showed a single genotype (South America I) circulating in the country, with the exception of a single strain from Rondônia, which represented South America genotype II. Brazilian YFV strains have diverged into two clades; an older clade appears to have become extinct and another has become the dominant lineage in recent years. Pairwise nucleotide diversity between strains ranged from 0% to 7.4%, while amino acid divergence ranged from 0% to 4.6%. Phylogenetic analysis indicated traffic of virus variants through large geographic areas and suggested that migration of infected people may be an important mechanism of virus dispersal. Isolation of vaccine virus from a patient with a fatal case suggests that vaccine-related illness may have been misdiagnosed in the past.

  • Rotavirus Serotype G9P[8] and Acute Gastroenteritis Outbreak in Children, Northern Australia PDF Version [PDF - 168 KB - 8 pages]
    C. D. Kirkwood et al.
       View Abstract

    During 2001, an outbreak of severe acute gastroenteritis swept through Central and northern Australia and caused serious disruption to health services. We tracked and characterized the rotavirus strain implicated in the outbreak. Comparison of the electropherotypes of outbreak samples suggested that one G9P[8] strain was likely responsible for the outbreak. Samples were obtained from geographically distinct regions of Australia where the epidemic had occurred. The outbreak strains showed identical nucleotide sequences in genes encoding three rotavirus proteins, VP7, VP8, and NSP4, but they were distinct from G9P[8] strains isolated in previous years. Several of the amino acid substitutions on the VP7 and NSP4 proteins were identified in regions known to influence function and may have contributed to the emergence and increased dominance of the outbreak strains. Rotavirus serotype surveillance should continue with methods capable of identifying new and emerging types.

  • Foodborne Botulism in the Republic of Georgia PDF Version [PDF - 182 KB - 5 pages]
    J. K. Varma et al.
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    Foodborne botulism is a potentially fatal, paralytic illness that can cause large outbreaks. A possible increase in botulism incidence during 2001 in Georgia prompted this study. We reviewed surveillance data and abstracted records of patients with botulism who were hospitalized from 1980 to 2002. During this period, 879 botulism cases were detected. The median annual incidence increased from 0.3 per 100,000 during 1980 to 1990 to 0.9 per 100,000 during 1991 to 2002. For 706 botulism patients hospitalized from 1980 to 2002, 80% of their cases were attributed to home-preserved vegetables. Surveillance evaluation verified that botulism incidence varied greatly by region. Georgia has the highest nationally reported rate of foodborne botulism in the world. A strategy addressing individual behaviors in the home is needed to improve food safety; developing this strategy requires a deeper understanding of why botulism has increased and varies by region.

  • Foodborne Botulism in the United States, 1990–2000 PDF Version [PDF - 67 KB - 6 pages]
    J. Sobel et al.
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    Foodborne botulism, a potentially lethal neuroparalytic disease, is caused by ingesting preformed Clostridium botulinum neurotoxin. We reviewed surveillance data and reports from 1990 to 2000. Of 263 cases from 160 foodborne botulism events (episode of one or more related cases) in the United States, 103 (39%) cases and 58 events occurred in Alaska. Patients’ median age was 48 years; 154 (59%) were female; the case-fatality rate was 4%. The median number of cases per event was 1 (range 1–17). Toxin type A caused 51% of all cases; toxin type E caused 90% of Alaska cases. A particular food was implicated in 126 (79%) events. In the lower 49 states, a noncommercial food item was implicated in 70 (91%) events, most commonly, home-canned vegetables (44%). Two restaurant-associated outbreaks affected 25 persons. All Alaska cases were attributable to traditional Alaska Native foods. Botulism prevention efforts should be focused on those who preserve food at home, Alaska Natives, and restaurant workers.

  • Computer Algorithms To Detect Bloodstream Infections PDF Version [PDF - 285 KB - 9 pages]
    W. E. Trick et al.
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    We compared manual and computer-assisted bloodstream infection surveillance for adult inpatients at two hospitals. We identified hospital-acquired, primary, central-venous catheter (CVC)-associated bloodstream infections by using five methods: retrospective, manual record review by investigators; prospective, manual review by infection control professionals; positive blood culture plus manual CVC determination; computer algorithms; and computer algorithms and manual CVC determination. We calculated sensitivity, specificity, predictive values, plus the kappa statistic (κ) between investigator review and other methods, and we correlated infection rates for seven units. The κ value was 0.37 for infection control review, 0.48 for positive blood culture plus manual CVC determination, 0.49 for computer algorithm, and 0.73 for computer algorithm plus manual CVC determination. Unit-specific infection rates, per 1,000 patient days, were 1.0–12.5 by investigator review and 1.4–10.2 by computer algorithm (correlation r = 0.91, p = 0.004). Automated bloodstream infection surveillance with electronic data is an accurate alternative to surveillance with manually collected data.

  • Space-Time Cluster Analysis of Invasive Meningococcal Disease PDF Version [PDF - 98 KB - 6 pages]
    C. J. Hoebe et al.
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    Clusters are recognized when meningococcal cases of the same phenotypic strain (markers: serogroup, serotype, and subtype) occur in spatial and temporal proximity. The incidence of such clusters was compared to the incidence that would be expected by chance by using space-time nearest-neighbor analysis of 4,887 confirmed invasive meningococcal cases identified in the 9-year surveillance period 1993–2001 in the Netherlands. Clustering beyond chance only occurred among the closest neighboring cases (comparable to secondary cases) and was small (3.1%, 95% confidence interval 2.1%–4.1%).

  • Methicillin-resistant Staphylococcus aureus in Europe, 1999–2002 PDF Version [PDF - 158 KB - 8 pages]
    E. W. Tiemersma et al.
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    We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from <1% in northern Europe to >40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be most effective at regional and hospital levels.

  • Outbreak of Hantavirus Pulmonary Syndrome, Los Santos, Panama, 1999–2000 PDF Version [PDF - 118 KB - 8 pages]
    V. Bayard et al.
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    An outbreak of hantavirus pulmonary syndrome occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic surveys resulted in an overall hantavirus antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections in Central America.

  • Detection of Anaplasma phagocytophilum DNA in Ixodes Ticks (Acari: Ixodidae) from Madeira Island and Setúbal District, Mainland Portugal PDF Version [PDF - 203 KB - 6 pages]
    A. S. Santos et al.
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    A total of 278 Ixodes ticks, collected from Madeira Island and Setúbal District, mainland Portugal, were examined by polymerase chain reaction (PCR) for the presence of Anaplasma phagocytophilum. Six (4%) of 142 Ixodes ricinus nymphs collected in Madeira Island, and 1 nymph and 1 male (2%) of 93 I. ventalloi collected in Setúbal District tested positive for A. phagocytophilum msp2 genes or rrs. Infection was not detected among 43 I. ricinus on mainland Portugal. All PCR products were confirmed by nucleotide sequencing to be identical or to be most closely related to A. phagocytophilum. To our knowledge, this is the first evidence of A. phagocytophilum in ticks from Setúbal District, mainland Portugal, and the first documentation of Anaplasma infection in I. ventalloi. Moreover, these findings confirm the persistence of A. phagocytophilum in Madeira Island’s I. ricinus.

  • Genotyping, Orientalis-like Yersinia pestis, and Plague Pandemics PDF Version [PDF - 176 KB - 8 pages]
    M. Drancourt et al.
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    Two historical plague pandemics were likely caused by Orientalis-like strains of Yersinia pestis.

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    Three pandemics have been attributed to plague in the last 1,500 years. Yersinia pestis caused the third, and its DNA was found in human remains from the second. The Antiqua biovar of Y. pestis may have caused the first pandemic; the other two biovars, Medievalis and Orientalis, may have caused the second and third pandemics, respectively. To test this hypothesis, we designed an original genotyping system based on intergenic spacer sequencing called multiple spacer typing (MST). We found that MST differentiated every biovar in a collection of 36 Y. pestis isolates representative of the three biovars. When MST was applied to dental pulp collected from remains of eight persons who likely died in the first and second pandemics, this system identified original sequences that matched those of Y. pestis Orientalis. These data indicate that Y. pestis caused cases of Justinian plague. The two historical plague pandemics were likely caused by Orientalis-like strains.



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