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Volume 10, Number 4—April 2004

Volume 10, Number 4—April 2004   PDF Version [PDF - 16.26 MB - 215 pages]


  • Economics of Preventing Hospital Infection PDF Version [PDF - 133 KB - 6 pages]
    N. Graves
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    The economics of preventing hospital-acquired infections is most often described in general terms. The underlying concepts and mechanisms are rarely made explicit but should be understood for research and policy-making. We define the key economic concepts and specify an illustrative model that uses hypothetical data to identify how two related questions might be addressed: 1) how much should be invested for infection control, and 2) what are the most appropriate infection-control programs? We aim to make explicit the economics of preventing hospital-acquired infections.

  • Reanalyzing the 1900–1920 Sleeping Sickness Epidemic in Uganda PDF Version [PDF - 155 KB - 7 pages]
    E. Fèvre et al.
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    Sleeping sickness has long been a major public health problem in Uganda. From 1900 to 1920, more than 250,000 people died in an epidemic that affected the southern part of the country, particularly the Busoga region. The epidemic has traditionally been ascribed to T. b. gambiense, a parasite now confined to central and western Africa. The Busoga region still reports sleeping sickness, although it is caused by Trypanosoma brucei rhodesiense, commonly believed to have spread to Uganda from Zambia in the 1940s. Our analysis of clinical data recorded in the early 1900s shows that the clinical course of sleeping sickness cases during the 1900–1920 epidemic in Uganda was markedly different from T.b. gambiense cases, but similar to T.b. rhodesiense. These findings suggest that T.b. rhodesiense was present in Uganda and contributed to the epidemic. The historic context is reassessed in the light of these data.


  • Pediatric Influenza Prevention and Control PDF Version [PDF - 206 KB - 7 pages]
    N. Principi and S. Esposito
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    Global evaluation of influenza vaccination in children indicates that current recommendations are not followed. Most children at high risk for influenza-related complications do not receive the vaccine, and increased efforts are needed to protect them. Furthermore, immunizing healthy infants 6–23 months of age and their close contacts should be strongly encouraged. Vaccinations are recommended for children with recurrent acute otitis media or recurrent respiratory tract infections and possibly for healthy daycare and school-age children because of the potential socioeconomic implications of influenza. Issues that need to be addressed include educating physicians and parents concerning influenza-related illness and complications, cost-effectiveness and safety of licensed vaccines, adequate vaccine supply, and availability of intranasal products.


  • Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs PDF Version [PDF - 132 KB - 6 pages]
    E. L. Tan et al.
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    Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti–SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon α. These findings support clinical testing of approved interferons for the treatment of SARS.

  • SARS Transmission, Risk Factors, and Prevention in Hong Kong PDF Version [PDF - 68 KB - 6 pages]
    J. Lau et al.
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    We analyzed information obtained from 1,192 patients with probable severe acute respiratory syndrome (SARS) reported in Hong Kong. Among them, 26.6% were hospital workers, 16.1% were household members of SARS patients and had probable secondary infections, 14.3% were Amoy Garden residents, 4.9% were inpatients, and 20.1% were contacts of SARS patients who were not family members. The remaining 347 case-patients (29.1%) did not have “known” sources of infection. Excluding those <16 years of age, 330 patients with cases from “undefined” sources were used in a 1:2 matched case-control study. Multivariate analysis of this case-control study showed that having visited mainland China, hospitals, or the Amoy Gardens were risk factors (odds ratio [OR] 1.95 to 7.63). In addition, frequent mask use in public venues, frequent hand washing, and disinfecting the living quarters were significant protective factors (OR 0.36 to 0.58). In Hong Kong, therefore, community-acquired infection did not make up most transmissions, and public health measures have contributed substantially to the control of the SARS epidemic.

  • Myanmar Dengue Outbreak Associated with Displacement of Serotypes 2, 3, and 4 by Dengue 1 PDF Version [PDF - 168 KB - 5 pages]
    H. M. Thu et al.
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    In 2001, Myanmar (Burma) had its largest outbreak of dengue—15,361 reported cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), including 192 deaths. That year, 95% of dengue viruses isolated from patients were serotype 1 viruses belonging to two lineages that had diverged from an earlier, now extinct, lineage sometime before 1998. The ratio of DHF to DSS cases in 2001 was not significantly different from that in 2000, when 1,816 cases of DHF/DSS were reported and dengue 1 also was the most frequently isolated serotype. However, the 2001 ratio was significantly higher than that in 1998 (also an outbreak year) and in 1999, when all four serotypes were detected and serotypes 1, 2, and 3 were recovered in similar numbers. The large number of clinical cases in 2001 may have been due, in part, to a preponderance of infections with dengue 1 viruses.

  • Predicting Geographic Variation in Cutaneous Leishmaniasis, Colombia PDF Version [PDF - 520 KB - 10 pages]
    R. J. King et al.
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    Approximately 6,000 cases of cutaneous leishmaniasis are reported annually in Colombia, a greater than twofold increase since the 1980s. Such reports certainly underestimate true incidence, and their geographic distribution is likely biased by local health service effectiveness. We investigated how well freely available environmental data explain the distribution of cases among 1,079 municipalities. For each municipality, a unique predictive logistic regression model was derived from the association among remaining municipalities between elevation, land cover (preclassified maps derived from satellite images), or both, and the odds of at least one case being reported. Land cover had greater predictive power than elevation; using both datasets improved accuracy. Fitting separate models to different ecologic zones, reflecting transmission cycle diversity, enhanced the accuracy of predictions. We derived measures that can be directly related to disease control decisions and show how results can vary, depending on the threshold selected for predicting a disease-positive municipality. The results identify areas where disease is most likely to be underreported.

  • Epidemiologic Determinants for Modeling Pneumonic Plague Outbreaks PDF Version [PDF - 494 KB - 7 pages]
    R. Gani and S. Leach
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    Pneumonic plague poses a potentially increasing risk to humans in plague nonendemic regions either as a consequence of an aerosolized release or through importation of the disease. Pneumonic plague is person-to-person transmissible. We provide a quantitative assessment of transmissibility based on past outbreaks that shows that the average number of secondary cases per primary case (R0) was 1.3 (variance = 3.1), assuming a geometric probability distribution, prior to outbreak control measures. We also show that the latent and infectious periods can be approximated by using lognormal distributions with means (SD) of 4.3 (1.8) and 2.5 (1.2) days. Based on this parameter estimation, we construct a Markov-chain epidemic model to demonstrate the potential impact of delays in implementing outbreak control measures and increasing numbers of index cases on the incidence of cases in simulated outbreaks.

  • Dengue Spatial and Temporal Patterns, French Guiana, 2001 PDF Version [PDF - 538 KB - 7 pages]
    A. Tran et al.
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    To study a 2001 dengue fever outbreak in Iracoubo, French Guiana, we recorded the location of all patients’ homes and the date when symptoms were first observed. A geographic information system was used to integrate the patient-related information. The Knox test, a classic space-time analysis technique, was used to detect spatiotemporal clustering. Analysis of the relative-risk (RR) variations when space and time distances vary, highlighted the maximum space and time extent of a dengue transmission focus. The results show that heterogeneity in the RR variations in space and time corresponds to known entomologic and epidemiologic factors, such as the mosquito feeding cycle and host-seeking behavior. This finding demonstrates the relevance and potential of the use of GIS and spatial statistics for elaborating a dengue fever surveillance strategy.

  • Babesia divergens–like Infection, Washington State PDF Version [PDF - 266 KB - 8 pages]
    B. L. Herwaldt et al.
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    Most reported U.S. zoonotic cases of babesiosis have occurred in the Northeast and been caused by Babesia microti. In Washington State, three cases of babesiosis have been reported previously, which were caused by WA1 (for “Washington 1”)-type parasites. We investigated a case of babesiosis in Washington in an 82–year-old man whose spleen had been removed and whose parasitemia level was 41.4%. The complete 18S ribosomal RNA gene of the parasite was amplified from specimens of his whole blood by polymerase chain reaction. Phylogenetic analysis showed the parasite is most closely related, but not identical, to B. divergens (similarity score, 99.5%), a bovine parasite in Europe. By indirect fluorescent-antibody testing, his serum reacted to B. divergens but not to B. microti or WA1 antigens. This case demonstrates that babesiosis can be caused by novel parasites detectable by manual examination of blood smears but not by serologic or molecular testing for B. microti or WA1-type parasites.

  • Influenza A Virus PB1-F2 Gene in Recent Taiwanese Isolates PDF Version [PDF - 748 KB - 7 pages]
    G. Chen et al.
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    Influenza A virus contains eight RNA segments and encodes 10 viral proteins. However, an 11th protein, called PB1-F2, was found in A/Puerto Rico/8/34 (H1N1). This novel protein is translated from an alternative open reading frame (ORF) in the PB1 gene. We analyzed the PB1 gene of 42 recent influenza A isolates in Taiwan, including 24 H1N1 and 18 H3N2 strains. One H1N1 isolate and 17 H3N2 isolates contained the entire PB1-F2 ORF of 90 residues, three amino acids (aa) longer than the PB1-F2 of A/Puerto Rico/8/34 at the C terminal. The one remaining H3N2 isolate encoded a truncated PB1-F2 with 79 residues. The other 23 H1N1 isolates contained a truncated PB1-F2 of 57 aa. Phylogenetic analysis of both the HA and the PB1 genes showed that they shared similar clustering of these Taiwanese isolates, suggesting that no obvious reassortment occurred between the two genomic segments.

  • Coccidioidomycosis among Workers at an Archeological Site, Northeastern Utah PDF Version [PDF - 340 KB - 6 pages]
    L. R. Petersen et al.
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    In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9–12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, extending northward its known geographic distribution in Utah by approximately 200 miles.

  • Maternal Malaria and Perinatal HIV Transmission, Western Kenya PDF Version [PDF - 132 KB - 10 pages]
    J. G. Ayisi et al.
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    To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had malaria, and 102 (19.9%) infants acquired HIV perinatally. Log10 HIV viral load and episiotomy or perineal tear were associated with increased perinatal HIV transmission, whereas low-density malaria (<10,000 parasites/μL) was associated with reduced risk (adjusted relative risk [ARR] 0.4). Among women dually infected with malaria and HIV, high-density malaria (>10,000 parasites/μL) was associated with increased risk for perinatal MTCT (ARR 2.0), compared to low-density malaria. The interaction between placental malaria and MTCT appears to be variable and complex: placental malaria that is controlled at low density may cause an increase in broad-based immune responses that protect against MTCT; uncontrolled, high-density malaria may simultaneously disrupt placental architecture and generate substantial antigen stimulus to HIV replication and increase risk for MTCT.

  • Ixodid and Argasid Tick Species and West Nile Virus PDF Version [PDF - 50 KB - 5 pages]
    C. H. Lawrie et al.
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    Control of West Nile virus (WNV) can only be effective if the vectors and reservoirs of the virus are identified and controlled. Although mosquitoes are the primary vectors, WNV has repeatedly been isolated from ticks. Therefore tick-borne transmission studies were performed with an ixodid (Ixodes ricinus) and an argasid tick species (Ornithodoros moubata). Both species became infected after feeding upon viremic hosts, but I. ricinus ticks were unable to maintain the virus. In contrast, O. moubata ticks were infected for at least 132 days, and the infection was maintained through molting and a second bloodmeal. Infected O. moubata ticks transmitted the virus to rodent hosts, albeit at a low level. Moreover, the virus was nonsystemically transmitted between infected and uninfected O. moubata ticks co-fed upon uninfected hosts. Although ticks are unlikely to play a major role in WNV transmission, our findings suggest that some species have the potential to act as reservoirs for the virus.

  • Antigenic and Genetic Variability of Human Metapneumoviruses PDF Version [PDF - 533 KB - 9 pages]
    B. G. van den Hoogen et al.
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    Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxoviridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups based on genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences.

  • Pneumocystis jiroveci Dihydropteroate Synthase Genotypes in Immunocompetent Infants and Immunosuppressed Adults, Amiens, France PDF Version [PDF - 246 KB - 7 pages]
    A. Totet et al.
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    To date, investigations of Pneumocystis jiroveci circulation in the human reservoir through the dihydropteroate synthase (DHPS) locus analysis have only been conducted by examining P. jirovecii isolates from immunosuppressed patients with Pneumocystis pneumonia (PCP). Our study identifies P. jirovecii genotypes at this locus in 33 immunocompetent infants colonized with P. jirovecii contemporaneously with a bronchiolitis episode and in 13 adults with PCP; both groups of patients were monitored in Amiens, France. The results have pointed out identical features of P. jirovecii DHPS genotypes in the two groups, suggesting that in these two groups, transmission cycles of P. jirovecii infections are linked. If these two groups represent sentinel populations for P. jirovecii infections, our results suggest that all persons parasitized by P. jirovecii, whatever their risk factor for infection and the form of parasitism they have, act as interwoven circulation networks of P. jirovecii.

  • PorA Variable Regions of Neisseria meningitidis PDF Version [PDF - 350 KB - 5 pages]
    J. E. Russell et al.
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    Subtypes, defined by variation in the outer membrane protein PorA, are an integral part of the characterization scheme for Neisseria meningitidis. Identification of these variants remains important as the PorA protein is a major immunogenic component of several meningococcal vaccines under development, and characteristics of PorA are used to provide detailed epidemiologic information. Historically, serosubtypes have been defined by reactivity with a set of monoclonal antibodies. However, nucleotide sequence analyses of porA genes have established that the panel of serosubtyping monoclonal antibodies is not exhaustive and many porA variants cannot be detected. In addition, the nomenclature system used to define subtypes is inadequate. We examined all available nucleotide sequences of the porA VR1 and VR2 regions to identify and define subtype families. A revised nomenclature scheme, compatible with the previous serologic nomenclature scheme, was devised. A Web-accessible database describing this nomenclature and its relationship to previous schemes was established (available from:

  • Antimicrobial Resistance Gene Delivery in Animal Feeds PDF Version [PDF - 164 KB - 5 pages]
    K. Lu et al.
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    Avoparcin, a glycopeptide antimicrobial agent related to vancomycin, has been used extensively as a growth promoter in animal feeds for more than 2 decades, and evidence has shown that such use contributed to the development of vancomycin-resistant enterococci. A cluster that includes three genes, vanH, vanA, and vanX, is required for high-level resistance to glycopeptides. In the vancomycin producer Amycolatopsis orientalis C329.2, homologs of these genes are present, suggesting an origin for the cluster. We found substantial bacterial DNA contamination in animal-feed-grade avoparcin. Furthermore, nucleotide sequences related to the cluster vanHAX are present in this DNA, suggesting that the prolonged use of avoparcin in agriculture led to the uptake of glycopeptide resistance genes by animal commensal bacteria, which were subsequently transferred to humans.

  • Flea-borne Bartonella grahamii and Bartonella taylorii in Bank Voles PDF Version [PDF - 75 KB - 4 pages]
    K. J. Bown et al.
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    Bartonella species are increasingly associated with a range of human and animal diseases. Despite this, we have a poor understanding of the ecology and epidemiology of many species, especially those circulating in wild populations. Previous studies have demonstrated that a diverse range of Bartonella species are abundant in wild rodent populations; little is known regarding their modes of transmission, although both direct and indirect routes have been suggested. In this study, with bank voles (Clethrionomys glareolus) as the host species, we demonstrate that the rodent flea Ctenophthalmus nobilis is a competent vector of at least two Bartonella species, B. grahamii, which has previously been associated with human infection, and B. taylorii. In contrast, no evidence of either horizontal or vertical transmission was seen in bank voles inoculated with B. taylorii maintained in an arthropod-free environment; this finding suggests that fleas may be essential for transmitting some Bartonella species.

  • Restaurant Inspection Scores and Foodborne Disease PDF Version [PDF - 92 KB - 5 pages]
    T. F. Jones et al.
        View Abstract

    Restaurants in the United States are regularly inspected by health departments, but few data exist regarding the effect of restaurant inspections on food safety. We examined statewide inspection records from January 1993 through April 2000. Data were available from 167,574 restaurant inspections. From 1993 to 2000, mean scores rose steadily from 80.2 to 83.8. Mean inspection scores of individual inspectors were 69–92. None of the 12 most commonly cited violations were critical food safety hazards. Establishments scoring <60 had a mean improvement of 16 points on subsequent inspections. Mean scores of restaurants experiencing foodborne disease outbreaks did not differ from restaurants with no reported outbreaks. A variety of factors influence the uniformity of restaurant inspections. The restaurant inspection system should be examined to identify ways to ensure food safety.

  • Recombination Resulting in Virulence Shift in Avian Influenza Outbreak, Chile PDF Version [PDF - 172 KB - 7 pages]
    D. L. Suarez et al.
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    Influenza A viruses occur worldwide in wild birds and are occasionally associated with outbreaks in commercial chickens and turkeys. However, avian influenza viruses have not been isolated from wild birds or poultry in South America. A recent outbreak in chickens of H7N3 low pathogenic avian influenza (LPAI) occurred in Chile. One month later, after a sudden increase in deaths, H7N3 highly pathogenic avian influenza (HPAI) virus was isolated. Sequence analysis of all eight genes of the LPAI virus and the HPAI viruses showed minor differences between the viruses except at the hemagglutinin (HA) cleavage site. The LPAI virus had a cleavage site similar to other low pathogenic H7 viruses, but the HPAI isolates had a 30 nucleotide insert. The insertion likely occurred by recombination between the HA and nucleoprotein genes of the LPAI virus, resulting in a virulence shift. Sequence comparison of all eight gene segments showed the Chilean viruses were also distinct from all other avian influenza viruses and represent a distinct South American clade.

  • Human Metapneumovirus Infection among Children Hospitalized with Acute Respiratory Illness PDF Version [PDF - 235 KB - 6 pages]
    J. A. Mullins et al.
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    Recent studies have associated human Metapneumovirus (HMPV) infection in children with respiratory disease of similar severity as respiratory syncytial virus (RSV) infection. We studied 668 banked swab specimens (one per admission) collected from a population-based, prospective study of acute respiratory illness among inpatient children from two U.S. cities. Specimens were tested for HMPV, RSV, influenza, and parainfluenza viruses by reverse transcription–polymerase chain reaction assays. Twenty-six (3.9%) were positive for HMPV; 125 (18.7%) for RSV; 45 (6.7%) for parainfluenza 1, 2, or 3; and 23 (3.4%) for influenza. HMPV-positive children were significantly older than RSV-positive children. HMPV-positive children required medical intensive care and received supplemental oxygen in similar frequencies to RSV-positive children. Among children hospitalized with respiratory illness, the incidence of HMPV infection was less than RSV, but clinical disease severity mirrored that of RSV infection. Further investigations to better characterize HMPV infection and its clinical effect are needed.


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