David Metzgar
Research interests
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InterestsMolecular Evolution, Antibiotic Resistance, Diagnostics
Publications
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5.15Impact points
Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.
Journal of virology. 01/2012; 86(1):635-6.
Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, ... [more] Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment.
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4.16Impact points
Adaptive evolution of diagnostic resistance.
Journal of clinical microbiology. 05/2011; 49(7):2774-5.
Theodosius Dobzhansky said "Nothing in biology makes sense except in the light of evolution" (3).…
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2.22Impact points
Antimicrobial resistance surveillance in the AFHSC-GEIS network.
BMC public health. 01/2011; 11 Suppl 2:S8.
International infectious disease surveillance has been conducted by the United States (U.S.) Department of Defense (DoD) for many years and has been consolidated within the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) s... [more] International infectious disease surveillance has been conducted by the United States (U.S.) Department of Defense (DoD) for many years and has been consolidated within the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) since 1998. This includes activities that monitor the presence of antimicrobial resistance among pathogens. AFHSC-GEIS partners work within DoD military treatment facilities and collaborate with host-nation civilian and military clinics, hospitals and university systems. The goals of these activities are to foster military force health protection and medical diplomacy. Surveillance activities include both community-acquired and health care-associated infections and have promoted the development of surveillance networks, centers of excellence and referral laboratories. Information technology applications have been utilized increasingly to aid in DoD-wide global surveillance for diseases significant to force health protection and global public health. This section documents the accomplishments and activities of the network through AFHSC-GEIS partners in 2009.
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2.22Impact points
A growing global network's role in outbreak response: AFHSC-GEIS 2008-2009.
BMC public health. 01/2011; 11 Suppl 2:S3.
A cornerstone of effective disease surveillance programs comprises the early identification of infectious threats and the subsequent rapid response to prevent further spread. Effectively identifying, tracking and responding to these threats is often difficult and requires international cooperation d... [more] A cornerstone of effective disease surveillance programs comprises the early identification of infectious threats and the subsequent rapid response to prevent further spread. Effectively identifying, tracking and responding to these threats is often difficult and requires international cooperation due to the rapidity with which diseases cross national borders and spread throughout the global community as a result of travel and migration by humans and animals. From Oct.1, 2008 to Sept. 30, 2009, the United States Department of Defense's (DoD) Armed Forces Health Surveillance Center Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) identified 76 outbreaks in 53 countries. Emerging infectious disease outbreaks were identified by the global network and included a wide spectrum of support activities in collaboration with host country partners, several of which were in direct support of the World Health Organization's (WHO) International Health Regulations (IHR) (2005). The network also supported military forces around the world affected by the novel influenza A/H1N1 pandemic of 2009. With IHR (2005) as the guiding framework for action, the AFHSC-GEIS network of international partners and overseas research laboratories continues to develop into a far-reaching system for identifying, analyzing and responding to emerging disease threats.
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4.16Impact points
Initial identification and characterization of an emerging zoonotic influenza virus prior to pandemic spread.
Journal of clinical microbiology. 11/2010; 48(11):4228-34.
Two cases of febrile respiratory illness associated with untypeable influenza A virus were identified in Southern California in March 2009. One was initially detected as influenza virus using an experimental diagnostic device in a clinical trial, while the other was detected at a local reference lab... [more] Two cases of febrile respiratory illness associated with untypeable influenza A virus were identified in Southern California in March 2009. One was initially detected as influenza virus using an experimental diagnostic device in a clinical trial, while the other was detected at a local reference lab using a diagnostic PCR assay. In both cases, analyses yielded negative results for strain-specific tests targeting circulating strains of influenza A virus (seasonal H1 and H3). These two samples became the first reported cases of the pandemic 2009/H1N1 influenza virus. The first reportable characterization was made from the second collected specimen on 15 April 2009 at the Centers for Disease Control and Prevention central lab using traditional culture and sequencing methods. The novel nature of the strain and its apparent zoonotic origins were initially characterized using the first collected specimen at the Naval Health Research Center in San Diego, CA, on 13 April using an experimental molecular analysis tool, PCR electro-spray ionization-mass spectrometry (PCR/ESI-MS), designed to amplify PCR products from any strain of influenza virus and to generate informative (phylogenetic) strain identifications through mass spectrometry of PCR amplicons. The ability of this high-throughput tool to correctly identify both well-characterized and novel influenza strains offers the possibility to integrate surveillance for emerging strains with on-site rapid diagnosis used for patient management, shortening the times between the emergence of new strains, their detection and identification, and appropriate public health response activities. Here we describe the initial characterization of the pandemic 2009/H1N1 influenza strain and discuss the possible roles of diagnostic tools with discovery potential.
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3.04Impact points
Computational analysis of adenovirus serotype 5 (HAdV-C5) from an HAdV coinfection shows genome stability after 45 years of circulation.
Virology. 09/2010; 404(2):180-6.
Adenovirus coinfections present opportunities for genome recombination. Computational analysis of an HAdV-C5 field strain genome, recovered from a patient with acute respiratory disease and coinfected with HAdV-B21, shows that there was no exchange of genomic material into HAdV-C5. Comparison of thi... [more] Adenovirus coinfections present opportunities for genome recombination. Computational analysis of an HAdV-C5 field strain genome, recovered from a patient with acute respiratory disease and coinfected with HAdV-B21, shows that there was no exchange of genomic material into HAdV-C5. Comparison of this genome to the sparsely amplified prototype demonstrates a high level of sequence conservation and stability of this genome across 45 years. Further, comparison to a version of the prototype that had been passaged in laboratory settings shows stability as well. HAdV genome stability and evolution are considerations for applications as vaccines and as vectors for gene delivery. In the annotation analysis, a single sequencing error in the HAdV-C5_ARM (Adenovirus Reference Material) genome is noted and may lead to erroneous annotation and biological interpretations.
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5.87Impact points
Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States.
The Journal of infectious diseases. 07/2010; 202(1):93-103.
First isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With no precedent of circulation in North America, HAdV-14 has been isolated from military and civilian cases ... [more] First isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With no precedent of circulation in North America, HAdV-14 has been isolated from military and civilian cases of ARD of variable severity since 2003 in the United States. Ninety-nine isolates from military and civilian cases from different geographic locations and circulation periods were characterized by restriction enzyme analysis of viral DNA and select gene sequencing. All examined viruses were found to be identical and to belong to a new genome type designated "HAdV-14p1" (formerly known as "14a"). Comparative alignments of E1A, hexon, and fiber gene sequences with other subspecies B2 HAdVs suggest that HAdV-14p1, like the closely related HAdV-11a, arose from recombination among similar HAdV-11 and HAdV-14 ancestral strains. A deletion of 2 amino acids in the knob region of the fiber protein is the only identified unique characteristic of HAdV-14p1. The current geographic distribution of HAdV-14p1 involves at least 15 states in the Unites States. The role of the fiber mutations in the recent emergence of HAdV-14p1 ARD in North America warrants further study.
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4.16Impact points
Multiplexed Luminex xMAP assay for detection and identification of five adenovirus serotypes associated with epidemics of respiratory disease in adults.
Journal of clinical microbiology. 06/2010; 48(6):2217-22.
Several serotypes of human adenovirus (HAdV) cause acute respiratory disease (ARD) among healthy adults, sometimes generating broad outbreaks with high attack rates and occasional fatalities. Timely serotype identification provides valuable epidemiological information and significantly contributes t... [more] Several serotypes of human adenovirus (HAdV) cause acute respiratory disease (ARD) among healthy adults, sometimes generating broad outbreaks with high attack rates and occasional fatalities. Timely serotype identification provides valuable epidemiological information and significantly contributes to prevention (vaccination) strategies. The prevalence of specific serotypes causing ARD varies geographically. HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 are the serotypes most commonly found in adult populations in the Western Hemisphere. Unfortunately, conventional serotype identification is a tedious process which can take a week or longer. For this reason, new molecular methods for serotype identification are needed. Commercially available rapid antigen and PCR assays for the detection of HAdV are universal but do not distinguish between the different serotypes. We describe the development of a sensitive and specific multiplex assay capable of identifying serotypes 3, 4, 7, 14, and 21. Two sets of primers were used for nonspecific (universal) PCR amplification, and serotype-specific probes coupled to Luminex tags were used for target-specific extension (TSE). PCR and TSE primers were designed using known hexon gene sequences of HAdV. The TSE products of HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 were correctly identified using the Luminex xMAP fluid microsphere-based array system. No cross-reactivity with other respiratory pathogens or other HAdV serotypes was observed. This multiplexed assay can be expanded to include more serotypes and will allow broad and rapid detection and identification of adenoviral serotypes in a high-throughput environment.
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2.56Impact points
Genomic characterization of human adenovirus 36, a putative obesity agent.
Virus research. 05/2010; 149(2):152-61.
Increased levels of serum antibody titers against human adenovirus 36 (HAdV-D36) are associated with human obesity and experimental obesity in laboratory animals. While HAdV-D36 has been studied as an infectious agent implicated in obesity for over a decade, the complete genome sequence and its anal... [more] Increased levels of serum antibody titers against human adenovirus 36 (HAdV-D36) are associated with human obesity and experimental obesity in laboratory animals. While HAdV-D36 has been studied as an infectious agent implicated in obesity for over a decade, the complete genome sequence and its analysis have yet to be reported. A detailed analysis of the genome sequence of HAdV-D36 may be important to understand its role in obesity. Genomic and bioinformatic comparisons with other HAdVs identified differences that suggested unique functions. Global pairwise genome alignment with all sequenced human adenovirus D (HAdV-D) genomes revealed areas of nonconserved sequences in the hexon, E3 CR1 beta, E3 CR1 gamma, and fiber genes. Phylogenetic analysis of all HAdV-D36 proteins confirmed that this virus belongs to species Human adenovirus D. This genomic analysis of HAdV-D36 provides an important tool for comprehending the role that this unique adenovirus may play in human obesity. Low amino acid sequence identity in the E3 CR1 beta and CR1 gamma genes may suggest distinctive roles for these proteins. Furthermore, the predicted molecular models of the HAdV-D36 fiber protein seem to implicate a unique tissue tropism for HAdV-D36.
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4.16Impact points
Outbreak of febrile respiratory illness associated with adenovirus 11a infection in a Singapore military training cAMP.
Journal of clinical microbiology. 04/2010; 48(4):1438-41.
Outbreak cases of acute respiratory disease (ARD) associated with subspecies B2 human adenovirus 11a (HAdV-11a) infection were detected during 2005 in a military basic training camp in Singapore. The Singapore HAdV-11a strain is highly similar to other Asian strains of HAdV-11, including strain QS-D... [more] Outbreak cases of acute respiratory disease (ARD) associated with subspecies B2 human adenovirus 11a (HAdV-11a) infection were detected during 2005 in a military basic training camp in Singapore. The Singapore HAdV-11a strain is highly similar to other Asian strains of HAdV-11, including strain QS-DLL, which is responsible for the recently described 2006 outbreak of ARD in China.
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4.16Impact points
Evaluation of multiplex type-specific real-time PCR assays using the LightCycler and joint biological agent identification and diagnostic system platforms for detection and quantitation of adult human respiratory adenoviruses.
Journal of clinical microbiology. 04/2010; 48(4):1397-403.
Every year, thousands of basic military trainees in each service of the U.S. Armed Forces experience acute respiratory disease. The majority of this disease burden results from infection with human adenoviruses. We designed single- and multiplex assays that detect and discriminate adenovirus types B... [more] Every year, thousands of basic military trainees in each service of the U.S. Armed Forces experience acute respiratory disease. The majority of this disease burden results from infection with human adenoviruses. We designed single- and multiplex assays that detect and discriminate adenovirus types B3, E4, B7, B11, B14, and B21. A total of 116 oropharyngeal swab specimens obtained from patients at the Naval Health Research Center were used to validate the new assays. Type-specific singleplex assays were designed and used independently to successfully identify 94 representative patient specimens. The lower limits of detection for our singleplex real-time PCR assays were calculated to be 50, 500, 500, 50, 50, and 50 genomic copies per reaction for human adenovirus type B3 (HAdV-B3), HAdV-E4, HAdV-B7, HAdV-B11, HAdV-B14, and HAdV-B21, respectively. These were then multiplexed to increase efficiency and tested against singleplex assays using titrated controls. The HAdV-B3/B11 and HAdV-E4/B7 multiplex assays were as sensitive and specific as they were individually. The HAdV-B14/B21 multiplex assay was not as efficient at detecting HAdV-B14 as the singleplex assay. Interestingly, a statistically significant difference was found between the viral loads of HAdV-B14 and those of HAdV-B3, -E4, -B7, and -B21 (P < 0.001). The assays did not cross-react with other adenoviruses, influenza virus, respiratory syncytial virus, or respiratory disease-causing bacteria. These assays have the potential to be useful as clinical diagnostic tools for the detection of HAdV infection in adult populations.
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3.25Impact points
Broad spectrum respiratory pathogen analysis of throat swabs from military recruits reveals interference between rhinoviruses and adenoviruses.
Microbial ecology. 03/2010; 59(4):623-34.
Military recruits experience a high incidence of febrile respiratory illness (FRI), leading to significant morbidity and lost training time. Adenoviruses, group A Streptococcus pyogenes, and influenza virus are implicated in over half of the FRI cases reported at recruit training center clinics, whi... [more] Military recruits experience a high incidence of febrile respiratory illness (FRI), leading to significant morbidity and lost training time. Adenoviruses, group A Streptococcus pyogenes, and influenza virus are implicated in over half of the FRI cases reported at recruit training center clinics, while the etiology of the remaining cases is unclear. In this study, we explore the carriage rates and disease associations of adenovirus, enterovirus, rhinovirus, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in military recruits using high-density resequencing microarrays. The results showed that rhinoviruses, adenoviruses, S. pneumoniae, H. influenzae, and N. meningitidis were widely distributed in recruits. Of these five agents, only adenovirus showed significant correlation with illness. Among the samples tested, only pathogens associated with FRI, such as adenovirus 4 and enterovirus 68, revealed strong temporal and spatial clustering of specific strains, indicating that they are transmitted primarily within sites. The results showed a strong negative association between adenoviral FRI and the presence of rhinoviruses in recruits, suggesting some form of viral interference.
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3.12Impact points
Viral agents responsible for febrile respiratory illnesses among military recruits training in tropical Singapore.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 03/2010; 47(3):289-92.
Military personnel are highly susceptible to febrile respiratory illnesses (FRI), likely due to crowding, stress and other risk factors present in the military environment. Our objective was to investigate the viral etiological agents responsible for FRI among military recruits training in a tropica... [more] Military personnel are highly susceptible to febrile respiratory illnesses (FRI), likely due to crowding, stress and other risk factors present in the military environment. Our objective was to investigate the viral etiological agents responsible for FRI among military recruits training in a tropical climate in Singapore. From March 2006 through April 2007, a total of 1354 oropharyngeal (throat) swabs were collected from military recruits who reported sick with an oral temperature of > or =38 degrees C and a cough and/or sore throat. Real-time polymerase chain reaction (PCR) was used to assay for the presence of influenza A and B viruses and adenoviruses (H-AdV), and conventional PCR used for the remaining respiratory viruses in all specimens. Influenza A virus was the dominant infection with a laboratory-confirmed incidence of 24% (326/1354) and a predominance of the H3N2 subtype. The temporal pattern for influenza A virus infections coincided with the nation-wide pattern in the civilian community. Detection rates of 12% (159/1354) and 2.7% (5/1354) were obtained for influenza B virus and other respiratory viruses, respectively. The laboratory findings identified influenza A virus as the primary causative viral agent for FRI in the Singapore military, in strong contrast to findings from temperate countries and countries where recruits are often vaccinated for influenza. Our results suggest that influenza vaccination should be considered as a requirement to reduce the incidence of influenza infections. This is the first report describing respiratory infections in a tropical military setting, in a developed country in Asia.
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4.41Impact points
Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.
PloS one. 01/2010; 5(2):e8995.
For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least... [more] For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.
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3.13Impact points
Genome sequences of human adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America.
Respiratory research. 01/2010; 11:116.
Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotyp... [more] Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotype in surveillance methods. In 2006 and 2007, this virus suddenly emerged in North America, causing high attack rate epidemics of FRI and, in some cases, severe pneumonias and occasional fatalities. Some outbreaks have been relatively mild, with low rates of progression beyond uncomplicated FRI, while other outbreaks have involved high rates of more serious outcomes. In this paper we present the complete genomic sequence of this emerging pathogen, and compare genomic sequences of isolates from both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the closely related sequence of HAdV-11a, which has been circulating in southeast Asia. The data suggest that the currently circulating strain of HAdV-14 is closely related to the historically recognized prototype throughout its genome, though it does display a couple of potentially functional mutations in the fiber knob and E1A genes. There are no polymorphisms that suggest an obvious explanation for the divergence in severity between outbreak events, suggesting that differences in outcome are more likely environmental or host determined rather than viral genetics.
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4.34Impact points
Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personnel.
International journal of obesity (2005). 11/2009;
Background:Although several studies have shown a positive association between evidence of anti-adenovirus 36 (Ad-36) antibodies (Ad-36 exposure) and (1) obesity and (2) serum cholesterol in animals, there is limited research demonstrating this association in humans. There is also limited research on... [more] Background:Although several studies have shown a positive association between evidence of anti-adenovirus 36 (Ad-36) antibodies (Ad-36 exposure) and (1) obesity and (2) serum cholesterol in animals, there is limited research demonstrating this association in humans. There is also limited research on transmission, presentation and demographics of Ad-36 infection.Design:(1) Body mass (body mass index (BMI)), (2) fasting serum cholesterol and triglyceride levels and (3) demographic characteristics were compared between Ad-36 seropositive and seronegative groups. The majority of subjects were matched as cases versus controls on a number of demographic variables.Subjects:A total of 150 obese and 150 lean active-duty military personnel were studied.Measurements:Subjects completed a questionnaire regarding demographic and behavioral characteristics. Subject serum samples were tested by serum neutralization assay for the presence of anti-Ad-36 antibodies.Results:In all, 34% of obese and 39% of lean subjects had Ad-36 exposure, an insignificant difference. Serum cholesterol and triglyceride levels were significantly higher among the obese subjects than among the lean, but there were no associations between serum cholesterol and triglyceride levels and Ad-36 exposure. Positive associations were found between Ad-36 exposure and age, race and gender.Conclusion:The study stands in contrast to previous work that has shown a positive relationship between Ad-36 exposure and (1) obesity, and (2) levels of serum cholesterol and triglycerides. In this study there was no association in either case. Unanticipated relationships between Ad-36 exposure and age, race and gender were found, and this is the first time that such a link between Ad-36 exposure and demographics has been found.International Journal of Obesity advance online publication, 10 November 2009; doi:10.1038/ijo.2009.224.
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4.16Impact points
An Outbreak of Acute Respiratory Disease Caused by Mycoplasma pneumoniae Onboard a Deployed US Navy Ship.
Journal of clinical microbiology. 10/2009;
We identified 179 cases of acute respiratory illness including 50 cases of radiographically-confirmed pneumonia over the course of four months on a deployed US Navy vessel. Laboratory tests showed Mycoplasma pneumoniae to be the etiological agent. This report represents the first published descripti... [more] We identified 179 cases of acute respiratory illness including 50 cases of radiographically-confirmed pneumonia over the course of four months on a deployed US Navy vessel. Laboratory tests showed Mycoplasma pneumoniae to be the etiological agent. This report represents the first published description of a shipboard outbreak of this pathogen.
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4.16Impact points
Adenovirus Microsatellite Reveals Dynamics of Transmission During a Recent HAdV-14 Epidemic.
Journal of clinical microbiology. 05/2009;
This study reveals diverse length polymorphisms in long mononucleotide repeats (microsatellites) in several serotypes of epidemic human respiratory adenovirus. The length of one of these microsatellites, a homopolymeric thymidine (poly T) repeat, is measured in 68 isolates of adenovirus serotype 14.... [more] This study reveals diverse length polymorphisms in long mononucleotide repeats (microsatellites) in several serotypes of epidemic human respiratory adenovirus. The length of one of these microsatellites, a homopolymeric thymidine (poly T) repeat, is measured in 68 isolates of adenovirus serotype 14. These isolates were collected during a series of sudden and sometimes fatal outbreaks among both military recruits and civilians as the virus emerged for the first time in the United States in 2006 and 2007. The results demonstrate the usefulness of adenoviral microsatellites as high-resolution molecular strain markers. The described homopolymer is hypervariable in length, varying from 12 to 17 base pairs in the analyzed sample set. All intermediate lengths were identified in at least one isolate. Furthermore, the specific length of the marker is stable over significant periods of time (up to 7 months) at individual sites where the virus is in consistent circulation. The microsatellite can also maintain specific length identity through site-to-site transmission events, determined by analysis of isolates from three advanced training sites that appeared to be subject to pathogen transfer from one of the affected recruit training installations. Public database searches revealed that the polymorphic nature of the microsatellite extends to other species B serotypes, and that other polymorphic microsatellites can be readily identified in a variety of epidemic respiratory adenovirus clades. This study shows that microsatellites are a ubiquitous source of polymorphic markers for human adenoviruses, and demonstrates their use through an epidemiological analysis of isolates from a recent North American epidemic.
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4.16Impact points
Universal detection and identification of avian influenza virus by use of resequencing microarrays.
Journal of clinical microbiology. 05/2009; 47(4):988-93.
Zoonotic microbes have historically been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the appearance of some human infections have increased the concern of a possible new influenza pandemic, which highlig... [more] Zoonotic microbes have historically been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the appearance of some human infections have increased the concern of a possible new influenza pandemic, which highlights the need for broad-spectrum detection methods for rapidly identifying the spread or outbreak of all variants of avian influenza virus. In this study, we demonstrate that high-density resequencing pathogen microarrays (RPM) can be such a tool. The results from 37 influenza virus isolates show that the RPM platform is an effective means for detecting and subtyping influenza virus, while simultaneously providing sequence information for strain resolution, pathogenicity, and drug resistance without additional analysis. This study establishes that the RPM platform is a broad-spectrum pathogen detection and surveillance tool for monitoring the circulation of prevalent influenza viruses in the poultry industry and in wild birds or incidental exposures and infections in humans.
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5.87Impact points
Outbreak of Severe Respiratory Disease Associated with Emergent Human Adenovirus Serotype 14 at a US Air Force Training Facility in 2007.
The Journal of infectious diseases. 05/2009;
Background. In 2007, a US Air Force training facility reported a cluster of severe respiratory illnesses associated with a rare human adenovirus (Ad) serotype, Ad14. We investigated this outbreak to better understand its epidemiology, clinical spectrum, and associated risk factors. Methods. Data wer... [more] Background. In 2007, a US Air Force training facility reported a cluster of severe respiratory illnesses associated with a rare human adenovirus (Ad) serotype, Ad14. We investigated this outbreak to better understand its epidemiology, clinical spectrum, and associated risk factors. Methods. Data were collected from ongoing febrile respiratory illness (FRI) surveillance and from a retrospective cohort investigation. Because an Ad7 vaccine is in development, Ad7 antibody titers in pretraining serum samples from trainees with mild and those with severe Ad14 illness were compared. Results. During 2007, an estimated 551 (48%) of 1147 trainees with FRI were infected with Ad14; 23 were hospitalized with pneumonia, 4 required admission to an intensive care unit, and 1 died. Among cohort members ([Formula: see text]), the Ad14 infection rate was high (50%). Of those infected, 40% experienced FRI. No cohort members were hospitalized. Male sex (risk ratio [RR], 4.7 [95% confidence interval {CI}, 2.2-10.1]) and an ill close contact (RR, 1.6 [95% CI, 1.2-2.2]) were associated with infection. Preexisting Ad7 neutralizing antibodies were found in 7 (37%) of 19 Ad14-positive trainees with mild illness but in 0 of 16 trainees with Ad14 pneumonia ([Formula: see text]). Conclusions. Emergence of Ad14, a rare Ad serotype, caused a protracted outbreak of respiratory illness among military recruits. Most infected recruits experienced FRI or milder illnesses. Some required hospitalization, and 1 died. Natural Ad7 infection may protect against severe Ad14 illness.
Following (9)
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Morris Jones
United States Department of Agriculture -
Valiolah Mahdizadeh
Tarbiat Modares University -
Don Seto
George Mason University -
Balazs Harrach
Veterinary Medical Research Institute, Hungarian Academy of Sciences -
Om Parkash
Universiti Sains Malaysia
