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Volume 12, Number 2—February 2006

Volume 12, Number 2—February 2006   PDF Version [PDF - 6.66 MB - 191 pages]

Perspective

  • Antimicrobial Drug Resistance, Regulation, and Research PDF Version [PDF - 259 KB - 8 pages]
    J. P. Metlay et al.
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    Research models and regulatory measures could aid in developing antimicrobial drugs to address bacterial resistance.

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    Innovative regulatory and legislative measures to stimulate and facilitate the development of new antimicrobial drugs are needed. We discuss research approaches that can aid regulatory decision making on the treatment of resistant infections and minimization of resistance selection. We also outline current and future measures that regulatory agencies may employ to help control resistance and promote drug development. Pharmacokinetic/pharmacodynamic research models offer promising approaches to define the determinants of resistance selection and drug doses that optimize efficacy and reduce resistance selection. Internationally, variations exist in how regulators use drug scheduling, subsidy restrictions, central directives, educational guidelines, amendments to prescribing information, and indication review. Recent consultations and collaborations between regulators, academics, and industry are welcome. Efforts to coordinate regulatory measures would benefit from greater levels of international dialogue.

  • HIV Drug-resistant Strains as Epidemiologic Sentinels PDF Version [PDF - 201 KB - 7 pages]
    M. S. Sánchez et al.
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    The decrease in the proportion of drug resistance among newly infected HIV-1 patients may signal a worsening of the epidemic.

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    Observed declines in drug resistance to nucleoside reverse transcriptase inhibitors among persons recently infected with HIV-1 in monitored subpopulations can be interpreted as a positive sign and lead public health officials to decrease efforts towards HIV prevention. By means of a mathematical model, we identified 3 processes that can account for the observed decline: increase in high-risk behavior, decrease in proportion of acutely infected persons whose conditions are treated, and change in treatment efficacy. These processes, singly or in combination, can lead to increases or decreases in disease and drug-resistance prevalence in the general population. We discuss the most appropriate public health response under each scenario and emphasize how further data collection and analyses are required to more reliably evaluate the observed time trends and the relative importance of forces shaping the epidemic. Our study highlights how drug resistance markers can be used as epidemiologic sentinels to devise public health solutions.

  • Detecting Hepatitis B Surface Antigen Mutants PDF Version [PDF - 123 KB - 6 pages]
    P. F. Coleman
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    The emergence of HBsAg mutants presents a challenge to HBV screening programs.

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    Hepatitis B viral mutants can emerge in patients as a result of selection pressure from either immune response or treatment options. Mutations that occur within the immunodominant epitopes of hepatitis B surface antigen (HBsAg) allow mutant virus to propagate in the presence of a neutralizing immune response, while wild-type virus is reduced to undetectable levels. HBsAg mutants present as false-negative results in some immunoassays. An understanding of immunoassay reactivity with HBsAg mutants is key to establishing an appropriate testing algorithm for hepatitis B virus detection programs.

  • Detecting Emerging Diseases in Farm Animals through Clinical Observations PDF Version [PDF - 212 KB - 7 pages]
    G. Vourc'h et al.
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    Clinical observations will allow early detection of emerging diseases in animal to enhance response time and capabilities.

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    Predicting emerging diseases is among the most difficult challenges facing researchers and health managers. We present available approaches and tools to detect emerging diseases in animals based on clinical observations of farm animals by veterinarians. Three information systems are described and discussed: Veterinary Practitioner Aided Disease Surveillance in New Zealand, the Rapid Syndrome Validation Project—Animal in the United States, and "émergences" in France. These systems are based on syndromic surveillance with the notification of every case or of specific clinical syndromes or on the notification of atypical clinical cases. Data are entered by field veterinarians into forms available through Internet-accessible devices. Beyond challenges of implementing new information systems, minimizing economic and health effects from emerging diseases in animals requires strong synergies across a group of field partners, in research, and in international animal and public health customs and practices.

Synopses

  • Systematic Review of Antimicrobial Drug Prescribing in Hospitals PDF Version [PDF - 84 KB - 6 pages]
    P. Davey et al.
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    Standardizing methods and reporting could improve interventions that reduce Clostridium difficile–associated diarrhea and antimicrobial drug resistance.

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    Prudent prescribing of antimicrobial drugs to hospital inpatients may reduce incidences of antimicrobial drug resistance and healthcare-associated infection. We reviewed the literature from January 1980 to November 2003 to identify rigorous evaluations of interventions to improve hospital prescribing of antimicrobial drugs. We identified 66 studies with interpretable data, of which 16 reported 20 microbiologic outcomes: gram-negative resistant bacteria, 10 studies; Clostridium difficile–associated diarrhea, 5 studies; vancomycin-resistant enterococci, 3 studies; and methicillin-resistant Staphylococcus aureus, 2 studies. Four studies provided strong evidence that the intervention changed microbial outcomes with low risk for alternative explanations, 8 studies provided less convincing evidence, and 4 studies provided no evidence. The strongest and most consistent evidence was for C. difficile–associated diahrrea, but we were able to analyze only the immediate impact of interventions because of nonstandardized durations of follow-up. The ability to compare results of studies could be substantially improved by standardizing methods and reporting.

  • Bartonella quintana Characteristics and Clinical Management PDF Version [PDF - 294 KB - 7 pages]
    C. Foucault et al.
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    The pathogen is reemerging in the United States and Europe and is responsible for a number of clinical conditions.

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    Bartonella quintana, a pathogen that is restricted to human hosts and louse vectors, was first characterized as the agent of trench fever. The disease was described in 1915 on the basis of natural and experimental infections in soldiers. It is now recognized as a reemerging pathogen among homeless populations in cities in the United States and Europe and is responsible for a wide spectrum of conditions, including chronic bacteremia, endocarditis, and bacillary angiomatosis. Diagnosis is based on serologic analysis, culture, and molecular biology. Recent characterization of its genome allowed the development of modern diagnosis and typing methods. Guidelines for the treatment of B. quintana infections are presented.

  • Rickettsia africae in the West Indies PDF Version [PDF - 104 KB - 3 pages]
    P. J. Kelly
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    Amblyomma variegatum ticks should be eradicated to prevent R. africae and African tickborne fever from being established.

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    Rickettsia africae is the agent of African tick-bite fever, a mild but common disease of local persons and tourists in Africa. The major vector of this spotted fever group rickettsia is most likely Amblyomma variegatum, the tropical bont tick, which has become widely distributed through the West Indies in the last 30 years. This report reviews all available information on R. africae in the West Indies.

Research

  • Free-grazing Ducks and Highly Pathogenic Avian Influenza, Thailand PDF Version [PDF - 351 KB - 8 pages]
    M. Gilbert et al.
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    Free-grazing ducks in rice paddies are a critical factor in the spread and persistence of avian influenza.

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    Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI outbreaks in relation to poultry, land use, and other anthropogenic variables from the start of the second epidemic wave (July 2004–May 2005). Results demonstrate a strong association between H5N1 virus in Thailand and abundance of free-grazing ducks and, to a lesser extent, native chickens, cocks, wetlands, and humans. Wetlands used for double-crop rice production, where free-grazing duck feed year round in rice paddies, appear to be a critical factor in HPAI persistence and spread. This finding could be important for other duck-producing regions in eastern and southeastern Asian countries affected by HPAI.

  • Nipah Virus-associated Encephalitis Outbreak, Siliguri, India PDF Version [PDF - 289 KB - 6 pages]
    M. Chadha et al.
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    Nipah virus, not previously detected in India, caused an outbreak of febrile encephalitis in West Bengal.

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    During January and February 2001, an outbreak of febrile illness associated with altered sensorium was observed in Siliguri, West Bengal, India. Laboratory investigations at the time of the outbreak did not identify an infectious agent. Because Siliguri is in close proximity to Bangladesh, where outbreaks of Nipah virus (NiV) infection were recently described, clinical material obtained during the Siliguri outbreak was retrospectively analyzed for evidence of NiV infection. NiV-specific immunoglobulin M (IgM) and IgG antibodies were detected in 9 of 18 patients. Reverse transcription–polymerase chain reaction (RT-PCR) assays detected RNA from NiV in urine samples from 5 patients. Sequence analysis confirmed that the PCR products were derived from NiV RNA and suggested that the NiV from Siliguri was more closely related to NiV isolates from Bangladesh than to NiV isolates from Malaysia. NiV infection has not been previously detected in India.

  • Methicillin-resistant Staphylococcus aureus Clones, Western Australia PDF Version [PDF - 114 KB - 7 pages]
    G. W. Coombs et al.
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    The emergence of multiple multidrug-resistant Panton-Valentine leukocidin–positive MRSA clones in the community is a major public health concern.

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    Community-associated methicillin-resistant Staphylococcus aureus (MRSA) was first reported in Western Australia in the early 1990s from indigenous peoples living in remote areas. Although a statewide policy of screening all hospital patients and staff who have lived outside the state for MRSA has prevented the establishment of multidrug-resistant epidemic MRSA, the policy has not prevented SCCmec type IV and type V MRSA clones from becoming established. Of the 4,099 MRSA isolates analyzed (referred to the Gram-positive Bacteria Typing and Research Unit) from July 2003 to December 2004, 77.5% were community-associated MRSA (CA-MRSA). Using multilocus sequence/staphylococcal chromosome cassette mec typing, 22 CA-MRSA clones were characterized. Of these isolates, 55.5% were resistant to >1 non–β-lactam antimicrobial drug. Five Panton-Valentine leukocidin (PVL)–positive CA-MRSA clones were identified. The emergence of multidrug-resistant CA-MRSA clones and the detection of PVL toxin genes in clones previously reported as PVL negative is a major public health concern.

  • Ameba-associated Microorganisms and Diagnosis of Nosocomial Pneumonia PDF Version [PDF - 198 KB - 8 pages]
    P. Berger et al.
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    Ameba-associated microorganisms should be suspected when conventional microbiologic test results are negative.

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    To elucidate the role of ameba-associated microorganisms (AAMs) as etiologic agents of pneumonia, we screened for Legionella spp., Parachlamydia acanthamoeba, Afipia sp., Bosea spp., Bradyrhizobium spp., Mesorhizobium amorphae, Rasbo bacterium, Azorhizobium caulinodans, Acanthamoeba polyphaga mimivirus, and conventional microorganisms in 210 pneumonia patients in intensive-care units by using culture, polymerase chain reaction, and serologic testing. These resulted in 59 diagnoses in 40 patients. AAMs and non-AAMs were implicated in 10.5% of the patients. The infectious agents were identified in 15 patients: Acanthamoeba polyphaga mimivirus, 8; Legionella pneumophila, 3; L. anisa, 1; Parachlamydia sp., 1; Bosea massiliensis, L. worsleiensis, L. quinlivanii, and L. rubrilucens, 1; and M. amorphae and R. bacterium, 1. A. polyphaga mimivirus was the fourth most common etiologic agent, with a higher seroprevalence than noted in healthy controls. This finding suggested its clinical relevance. Therefore, AAM might cause nosocomial pneumonia and should be suspected when conventional microbiologic results are negative.

  • Rickettsial Infections and Fever, Vientiane, Laos PDF Version [PDF - 156 KB - 7 pages]
    S. Phongmany et al.
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    Rickettsia spp. are an underrecognized cause of undifferentiated febrile illness.

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    Rickettsial diseases have not been described previously from Laos, but in a prospective study, acute rickettsial infection was identified as the cause of fever in 115 (27%) of 427 adults with negative blood cultures admitted to Mahosot Hospital in Vientiane, Laos. The organisms identified by serologic analysis were Orientia tsutsugamushi (14.8%), Rickettsia typhi (9.6%), and spotted fever group rickettsia (2.6% [8 R. helvetica, 1 R. felis, 1 R. conorii subsp. indica, and 1 Rickettsia "AT1"]). Patients with murine typhus had a lower frequency of peripheral lymphadenopathy than those with scrub typhus (3% vs. 46%, p<0.001). Rickettsioses are an underrecognized cause of undifferentiated febrile illnesses among adults in Laos. This finding has implications for the local empiric treatment of fever.

  • Helicobacter pullorum in Chickens, Belgium PDF Version [PDF - 86 KB - 5 pages]
    L. M. Ceelen et al.
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    Helicobacter pullorum is present in approximately one third of the chickens in Belgium.

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    A total of 110 broilers from 11 flocks were tested for Helicobacter pullorum by polymerase chain reaction; positive samples were reexamined with a conventional isolation method. H. pullorum isolates were examined by amplified fragment length polymorphism (AFLP) fingerprinting for interstrain genetic diversity and relatedness. Sixteen isolates from cecal samples from 2 different flocks were obtained. AFLP analysis showed that these isolates and 4 additional isolates from a different flock clustered according to their origin, which indicates that H. pullorum colonization may occur with a single strain that disseminates throughout the flock. Strains isolated from different hosts or geographic sources displayed a distinctive pattern. H. pullorum is present in approximately one third of live chickens in Belgium and may represent a risk to human health.

  • Epizootiologic Parameters for Plague in Kazakhstan PDF Version [PDF - 90 KB - 6 pages]
    M. Begon et al.
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    Infection reduces survival of otherwise asymptomatic maintenance hosts in a natural reservoir population.

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    Reliable estimates are lacking of key epizootiologic parameters for plague caused by Yersinia pestis infection in its natural reservoirs. We report results of a 3-year longitudinal study of plague dynamics in populations of a maintenance host, the great gerbil (Rhombomys opimus), in 2 populations in Kazakhstan. Serologic results suggest a mid-summer peak in the abundance of infectious hosts and possible transmission from the reservoir to humans. Decrease in antibody titer to an undetectable level showed no seasonal pattern. Our findings did not support the use of the nitroblue-tetrazolium test characterization of plague-infected hosts. Y. pestis infection reduced survival of otherwise asymptomatic hosts.

  • Blastomycosis in Ontario, 1994–2003 PDF Version [PDF - 144 KB - 6 pages]
    S. K. Morris et al.
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    Clinicians in Ontario should be aware of symptoms and areas where disease is endemic.

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    We describe a case of blastomycosis in an 8-year-old boy with Blastomyces-associated osteomyelitis and possible pulmonary involvement. We also identify 309 cases of blastomycosis in Ontario that were seen during a 10-year period, 57% of which occurred from 2001 to 2003. The overall incidence during the study period was 0.30 cases per 100,000 population. Most patients were from north Ontario (n = 188), where the incidence was 2.44 cases per 100,000. The incidence in the Toronto region was 0.29 per 100,000. Thirteen percent of cases occurred in children <19 years of age. These findings substantially increase the number of known cases in Ontario and Canada. Clinicians may encounter persons infected with Blastomyces dermatitidis and must be familiar with its signs and symptoms and be aware of locations, such as northwestern Ontario, where disease is endemic or hyperendemic. We advocate resuming blastomycosis as a reportable disease in Ontario to facilitate tracking cases.

  • Fresh Chicken as Main Risk Factor for Campylobacteriosis, Denmark PDF Version [PDF - 175 KB - 5 pages]
    A. Wingstrand et al.
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    Increased consumption of fresh poultry in Denmark has contributed substantially to the increasing incidence of human campylobacteriosis.

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    We report the findings of a case-control study of risk factors for sporadic cases of human campylobacteriosis in Denmark. In 3 different analytical models, the main domestic risk factor identified was eating fresh, unfrozen chicken. Specifically, 28 of 74 domestically acquired case-patients were exposed to fresh chicken compared with 21 of 114 controls (multivariate matched odds ratio 5.8; 95% confidence interval 2.1–15.9). In contrast, a risk from eating other poultry, including previously frozen chicken, was only indicated from borderline significant 2-factor interactions. The marked increase in consumption of fresh, unfrozen poultry in Denmark during the 1990s likely contributed substantially to the increasing incidence of human campylobacteriosis in this period.

  • Ophthalmic Complications of Dengue PDF Version [PDF - 197 KB - 5 pages]
    D. Chan et al.
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    A case series suggests that the spectrum of complications in dengue infection is widening.

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    We report 13 cases of ophthalmic complications resulting from dengue infection in Singapore. We performed a retrospective analysis of a series of 13 patients with dengue fever who had visual impairment. Investigations included Humphrey automated visual field analyzer, Amsler charting, fundus fluorescein angiography, and optical coherence tomography. Twenty-two eyes of 13 patients were affected. The mean age of patients was 31.7 years. Visual acuity varied from 20/25 to counting fingers only. Twelve patients (92.3%) noted central vision impairment. Onset of visual impairment coincided with the nadir of serum thrombocytopenia. Ophthalmologic findings include macular edema and blot hemorrhages (10), cotton wool spots (1), retinal vasculitis (4), exudative retinal detachment (2), and anterior uveitis (1). All patients recovered visual acuity to 20/30 or better with residual central scotoma by 12 weeks. These new complications suggest a widening spectrum of ophthalmic complications in dengue infection.

  • Scrub Typhus, Republic of Palau PDF Version [PDF - 163 KB - 6 pages]
    L. J. Demma et al.
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    Scrub typhus is likely endemic in Palau.

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    Scrub typhus, caused by Orientia tsutsugamushi, is a severe febrile illness transmitted to humans by trombiculid mites, which normally feed on rodents. The first known outbreak of scrub typhus in Palau occurred in 2001 to 2003 among residents of the remote southwest islands. To determine the extent of scrub typhus distribution in Palau, we tested serum samples from humans and rodents for antibodies to O. tsutsugamushi. Of 212 Palau residents surveyed in 2003, 101 (47.6%) had immunoglobulin G (IgG) antibody titers >1:64, and 56 (26.4%) had concurrent IgG and IgM antibody titers >1:512 and 1:64, respectively. Of 635 banked serum samples collected from Palau residents in 1995, 34 (5.4%) had IgG antibody titers >1:64. Sera collected from rodents (Rattus norvegicus and R. rattus) in 2003 and 2005 were tested, and 18 (28.6%) of 63 had IgG antibody titers >1:64. These findings suggest that scrub typhus is endemic in Palau.

  • Global Socioeconomic Impact of Cystic Echinococcosis PDF Version [PDF - 300 KB - 8 pages]
    C. M. Budke et al.
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    Because the human and economic losses of cystic echinococcosis are substantial, global prevention and control measures should be increased.

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    Cystic echinococcosis (CE) is an emerging zoonotic parasitic disease throughout the world. Human incidence and livestock prevalence data of CE were gathered from published literature and the Office International des Epizooties databases. Disability-adjusted life years (DALYs) and monetary losses, resulting from human and livestock CE, were calculated from recorded human and livestock cases. Alternative values, assuming substantial underreporting, are also reported. When no underreporting is assumed, the estimated human burden of disease is 285,407 (95% confidence interval [CI], 218,515–366,133) DALYs or an annual loss of US $193,529,740 (95% CI, $171,567,331–$217,773,513). When underreporting is accounted for, this amount rises to 1,009,662 (95% CI, 862,119–1,175,654) DALYs or US $763,980,979 (95% CI, $676,048,731–$857,982,275). An annual livestock production loss of at least US $141,605,195 (95% CI, $101,011,553–$183,422,465) and possibly up to US $2,190,132,464 (95% CI, $1,572,373,055–$2,951,409,989) is also estimated. This initial valuation demonstrates the necessity for increased monitoring and global control of CE.

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