Jill Hacker - Academia.edu (original) (raw)

Papers by Jill Hacker

Research paper thumbnail of Severe Pneumonia in Young Patients in Northern California

Background: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in the... more Background: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in the US. Despite recent diagnostic advances, specific etiologies usually are found in <50% of cases. To better define infectious etiologies of severe pneumonia, enhanced diagnostic testing was performed on patients with CAP admitted to intensive care units (ICU). Methods: At 12 Northern California hospitals, ICU patients aged 6 months to 49 yrs with no known immunocompromising condition were enrolled. Clinical and epidemiological data and specimens were collected. Bacterial and viral PCR and serological testing were performed. Results: From April 2005-March 2006, 48 patients with severe CAP were enrolled. The median age was 8 years (range 0.5 - 49); 48% were <5 years. An infectious etiology was identified in 35 (73%) cases. Standard clinical testing found a pathogen in 22 (65%) cases. PCR testing confirmed 6 of these and found etiologies for 13 additional cases. PCR also detected a sec...

Research paper thumbnail of SARS and Common Viral Infections Janice K. Louie,*+

The Study From March 12, 2003, through July 30, 2003, cases of possible SARS reported to the CDHS... more The Study From March 12, 2003, through July 30, 2003, cases of possible SARS reported to the CDHS were classified as suspect, probable, or laboratory-confirmed, according to CDC criteria (3). Extensive diagnostic testing was performed at the CDHS Viral and Rickettsial Disease Laboratory on specimens from 165 patients, including those with conditions that did not meet strict CDC case criteria (Table 1). Submitted specimens were transported on cold pack and either frozen at --70C or processed immediately. A total of 281 respiratory specimens and 78 serum specimens were analyzed, including 210 nasopharyngeal swabs, 23 nasal swabs, 17 throat swabs, 15 nasal washes, 11 sputum specimens, 5 endotracheal aspirates, 39 single acute-phase serum specimens, and 39 acute- and convalescent-phase paired serum specimens. Convalescent-phase serum specimens were collected at least 28 days after symptom onset. Because of difficulties obtaining convalescent-phase sera, specimens from only 32 case-patie

Research paper thumbnail of Requirement for the G1 Protein of California Encephalitis Virus in Infection in Vitro and in Vivo

Research paper thumbnail of Adsorptive Endocytosis of California Encephalitis Virus into Mosquito and Mammalian Cells: A Role for G1

Virology, 1997

The G1 glycoprotein of California encephalitis (CE) virus plays a critical role in the infection ... more The G1 glycoprotein of California encephalitis (CE) virus plays a critical role in the infection of mosquito and mammalian cells. We found that CE virus enters baby hamster kidney (BHK-21) and Aedes albopictus (C6/36) cells by the endocytic pathway. Ammonium chloride, a lysosomotropic amine that prevents release of virus from endosomes, inhibited infection of both cell types when added within 10 min after viral adsorption. In addition, infected cells formed polykaryons when the extracellular pH was lowered to 6.3; optimal fusion occurred at pH 5.8 and 6.0 (C6/36 and BHK-21 cells, respectively). Two neutralizing G1 MAba, 6D5.5 and 7D4.5, inhibited low pH-induced syncytia formation without affecting viral attachment, suggesting a role for G1 in viral entry. Since viral fusion proteins have been demonstrated to undergo conformational changes at low pH, acid-induced changes in G1 and G2 were assessed. While both G1 and G2 demonstrated low pH-induced alterations in detergent binding, only G1 displayed an altered protease cleavage pattern at the fusion pH. These results indicate that the G1 protein of CE virus undergoes conformational changes necessary for low pH-mediated entry into both mosquito and mammalian cells.

Research paper thumbnail of Specific Single or Double Proline Substitutions in the "Spring-loaded" Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity

The Journal of Cell Biology, 1998

We tested the role of the "spring-loaded" conformational change in the fusion mechanism of the in... more We tested the role of the "spring-loaded" conformational change in the fusion mechanism of the influenza hemagglutinin (HA) by assessing the effects of 10 point mutants in the region of high coiled-coil propensity, HA2 54-81. The mutants included proline substitutions at HA2 55, 71, and 80, as well as a double proline substitution at residues 55 and 71. Mutants were expressed in COS or 293T cells and assayed for cell surface expression and structural features as well as for their ability to change conformation and induce fusion at low pH. We found the following: Specific mutations affected the precise carbohydrate structure and folding of the HA trimer. All of the mutants, however, formed trimers that could be expressed at the cell surface in a form that could be proteolytically cleaved from the precursor, HA0, to the fusion-permissive form, HA1-S-S-HA2. All mutants reacted with an antibody against the major antigenic site and bound red blood cells. Seven out of ten mutants displayed a wild-type (wt) or moderately elevated pH dependence for the conformational change. V55P displayed a substantial reduction ( ‫ف‬ 60-80%) in the initial rate of lipid mixing. The other single mutants displayed efficient fusion with the same pH dependence as wt-HA. The double proline mutant V55P/ S71P displayed no fusion activity despite being well expressed at the cell surface as a proteolytically cleaved trimer that could bind red blood cells and change conformation at low pH. The impairment in fusion for both V55P and V55P/S71P was at the level of outer leaflet lipid mixing. We interpret our results in support of the hypothesis that the spring-loaded conformational change is required for fusion. An alternate model is discussed.

Research paper thumbnail of PARAINFLUENZA VIRUS TYPE 4: CASE REPORT AND REVIEW OF THE LITERATURE

The Pediatric Infectious Disease Journal, 2000

Research paper thumbnail of Fatal Toxic Shock Syndrome Associated with Clostridium sordellii after Medical Abortion

New England Journal of Medicine, 2005

Research paper thumbnail of SARS and Common Viral Infections

Emerging Infectious Diseases, 2004

In California, molecular testing was useful in decreasing suspicion for severe acute respiratory ... more In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.

Research paper thumbnail of Predominant Kidney Involvement in a Fatal Case of Hantavirus Pulmonary Syndrome Caused by Sin Nombre Virus

Clinical Infectious Diseases, 2001

A 27-year-old woman presented to a hospital with symptoms resembling pyelonephritis; respiratory ... more A 27-year-old woman presented to a hospital with symptoms resembling pyelonephritis; respiratory distress did not develop until nearly a day after admission and she subsequently died. The Unexplained Deaths and Critical Illnesses Project of the Centers for Disease Control and Prevention confirmed Sin Nombre virus infection by the results of serological testing and sequencing of the viral genome; staining of Sin Nombre virus antigen in the pulmonary capillaries was relatively weak.

Research paper thumbnail of Adenovirus Type 3 Viremia in an Adult with Toxic Shock–Like Syndrome

Clinical Infectious Diseases, 2001

Surveillance by the Unexplained Deaths and Critical Illnesses Project (UNEX) uncovered a novel pr... more Surveillance by the Unexplained Deaths and Critical Illnesses Project (UNEX) uncovered a novel presentation of adenovirus type 3 infection that satisfied the criteria for toxic shock-like syndrome in a 28-year-old immunocompetent man. Adenovirus may be a cause of toxic shock syndrome; surveillance systems such as UNEX may uncover additional causes of this and other clinically defined infectious syndromes.

Research paper thumbnail of Invasive Group A Streptococcal Infection Concurrent with 2009 H1N1 Influenza

Clinical Infectious Diseases, 2010

Research paper thumbnail of Characterization of Viral Agents Causing Acute Respiratory Infection in a San Francisco University Medical Center Clinic during the Influenza Season

Clinical Infectious Diseases, 2005

With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, w... more With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, we characterized the viruses causing acute respiratory infection in adults during an influenza season. During January-March 2002, nasopharyngeal wash specimens from previously healthy adults presenting with respiratory symptoms were evaluated for viral pathogens with centrifugation-enhanced viral culture and PCR. The diagnoses in 266 cases included unspecified upper respiratory infection (in 142 [54%] of the cases), acute bronchitis (42 [16%]), sinusitis (23 [9%]), pharyngitis (22 [8%]), and pneumonia (17 [6%]). The use of a shell vial assay and PCR identified a pathogen in 103 (39%) of the patients, including influenza A or B in 54, picornavirus in 28 (including rhinovirus in 24), respiratory syncytial virus (RSV) in 12, human metapneumovirus in 4, human coronavirus OC43 in 2, adenovirus in 2, parainfluenza virus type 1 in 1, and coinfection with influenza and parainfluenza virus type 1 in 2. Our findings demonstrate that, even during the influenza season, rhinovirus and RSV are prevalent and must be considered in the differential diagnosis of adult acute respiratory infection before prescribing antiviral medication. Human coronavirus and human metapneumovirus did not play a substantial role. PCR was an especially useful tool in the identification of influenza and other viral pathogens not easily detected by traditional testing methods.

Research paper thumbnail of Severe Pneumonia Due to Adenovirus Serotype 14: A New Respiratory Threat?

Clinical Infectious Diseases, 2008

Adenoviruses are associated with sporadic infection and community and institutional outbreaks; th... more Adenoviruses are associated with sporadic infection and community and institutional outbreaks; they can cause especially severe disease in infants, young children, immunocompromised persons, and transplant recipients. Fifty-two adenovirus serotypes have been recognized and classified within 7 subgroups or species (A-G), with limited data available on associated clinical syndromes and disease severity in more than one-half of the known serotypes. We describe the clinical presentation and virologic characterization of 1 adult and 2 pediatric patients admitted to 2 separate hospitals during April-May 2006 with severe acute respiratory tract infection. All patients had underlying chronic pulmonary disease; none were severely immunocompromised. All 3 experienced serious chronic sequelae or died. Adenovirus was isolated from all 3 case patients. Adenovirus serotype 14, a subspecies B2 serotype not previously associated with severe clinical illness, was confirmed by neutralization assay and sequencing of the hexon gene. Restriction enzyme analysis with BamHI, BglII, HindIII, and SmaI showed all 3 viruses to be identical and to belong to a new genome type that we have designated &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Ad14a.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; Our identification of severe respiratory illness due to a previously rarely reported adenovirus serotype may signify the emergence in the United States of a new genomic variant that has the potential to spread globally and cause epidemics. These case reports highlight the need for rapid diagnosis and improved surveillance, with serotyping and molecular characterization, to identify emerging variants of adenovirus, which may assist with targeted development of antiviral agents or type-specific vaccines.

Research paper thumbnail of Performance Characteristics of Clinical Diagnosis, a Clinical Decision Rule, and a Rapid Influenza Test in the Detection of Influenza Infection in a Community Sample of Adults

Annals of Emergency Medicine, 2005

The accurate diagnosis of influenza remains a diagnostic dilemma. We examine the performance of v... more The accurate diagnosis of influenza remains a diagnostic dilemma. We examine the performance of various strategies for diagnosing influenza infection in an unselected sample of adults during influenza season. Consecutive adults presenting to a university emergency department or urgent care clinic between January and March 2002 with acute respiratory complaints were eligible for this prospective observational study. The performance of clinician judgment, a rapid influenza test, and a clinical prediction rule in predicting influenza infection was evaluated using referent standard of reverse transcriptase polymerase chain reaction. Statistical significance was assessed using McNemar&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s test of proportions. Fifty-three of 258 (21%) patients had a positive influenza reverse transcriptase polymerase chain reaction test. Overall, clinician judgment showed sensitivity of 29% (95% confidence interval [CI] 18% to 43%) and specificity of 92% (95% CI 87% to 95%). The rapid influenza test showed a sensitivity of 33% (95% CI 22% to 47%) and specificity of 98% (95% CI 96% to 99%). The clinical prediction rule showed a sensitivity of 40% (95% CI 27% to 54%) and specificity of 92% (95% CI 87% to 95%). Clinician judgment when patients presented within 48 hours showed a sensitivity of 67% (95% CI 39% to 86%) and specificity of 96% (95% CI 81% to 99%). Neither the rapid influenza test (P=.10) nor the clinical prediction rule (P=.42) was superior to clinician judgment alone in the diagnosis of influenza. The suggestion that a clinical decision rule or a rapid influenza test is better than clinical judgment alone for the diagnosis of influenza in an unselected patient population is not supported by this study.

Research paper thumbnail of Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age

American Journal of Obstetrics and Gynecology, 2009

In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Califor... more In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Californian women after medical abortions. The true incidence of this rare disease is unknown, and a population-based study has never been performed. Additional clostridiaassociated deaths were sought to describe associated clinical characteristics.

Research paper thumbnail of Surveillance for Unexplained Deaths and Critical Illnesses Due to Possibly Infectious Causes, United States, 1995-1998

Emerging Infectious Diseases, 2002

Research paper thumbnail of Severe Pneumonia in Young Patients in Northern California

Background: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in the... more Background: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in the US. Despite recent diagnostic advances, specific etiologies usually are found in <50% of cases. To better define infectious etiologies of severe pneumonia, enhanced diagnostic testing was performed on patients with CAP admitted to intensive care units (ICU). Methods: At 12 Northern California hospitals, ICU patients aged 6 months to 49 yrs with no known immunocompromising condition were enrolled. Clinical and epidemiological data and specimens were collected. Bacterial and viral PCR and serological testing were performed. Results: From April 2005-March 2006, 48 patients with severe CAP were enrolled. The median age was 8 years (range 0.5 - 49); 48% were <5 years. An infectious etiology was identified in 35 (73%) cases. Standard clinical testing found a pathogen in 22 (65%) cases. PCR testing confirmed 6 of these and found etiologies for 13 additional cases. PCR also detected a sec...

Research paper thumbnail of SARS and Common Viral Infections Janice K. Louie,*+

The Study From March 12, 2003, through July 30, 2003, cases of possible SARS reported to the CDHS... more The Study From March 12, 2003, through July 30, 2003, cases of possible SARS reported to the CDHS were classified as suspect, probable, or laboratory-confirmed, according to CDC criteria (3). Extensive diagnostic testing was performed at the CDHS Viral and Rickettsial Disease Laboratory on specimens from 165 patients, including those with conditions that did not meet strict CDC case criteria (Table 1). Submitted specimens were transported on cold pack and either frozen at --70C or processed immediately. A total of 281 respiratory specimens and 78 serum specimens were analyzed, including 210 nasopharyngeal swabs, 23 nasal swabs, 17 throat swabs, 15 nasal washes, 11 sputum specimens, 5 endotracheal aspirates, 39 single acute-phase serum specimens, and 39 acute- and convalescent-phase paired serum specimens. Convalescent-phase serum specimens were collected at least 28 days after symptom onset. Because of difficulties obtaining convalescent-phase sera, specimens from only 32 case-patie

Research paper thumbnail of Requirement for the G1 Protein of California Encephalitis Virus in Infection in Vitro and in Vivo

Research paper thumbnail of Adsorptive Endocytosis of California Encephalitis Virus into Mosquito and Mammalian Cells: A Role for G1

Virology, 1997

The G1 glycoprotein of California encephalitis (CE) virus plays a critical role in the infection ... more The G1 glycoprotein of California encephalitis (CE) virus plays a critical role in the infection of mosquito and mammalian cells. We found that CE virus enters baby hamster kidney (BHK-21) and Aedes albopictus (C6/36) cells by the endocytic pathway. Ammonium chloride, a lysosomotropic amine that prevents release of virus from endosomes, inhibited infection of both cell types when added within 10 min after viral adsorption. In addition, infected cells formed polykaryons when the extracellular pH was lowered to 6.3; optimal fusion occurred at pH 5.8 and 6.0 (C6/36 and BHK-21 cells, respectively). Two neutralizing G1 MAba, 6D5.5 and 7D4.5, inhibited low pH-induced syncytia formation without affecting viral attachment, suggesting a role for G1 in viral entry. Since viral fusion proteins have been demonstrated to undergo conformational changes at low pH, acid-induced changes in G1 and G2 were assessed. While both G1 and G2 demonstrated low pH-induced alterations in detergent binding, only G1 displayed an altered protease cleavage pattern at the fusion pH. These results indicate that the G1 protein of CE virus undergoes conformational changes necessary for low pH-mediated entry into both mosquito and mammalian cells.

Research paper thumbnail of Specific Single or Double Proline Substitutions in the "Spring-loaded" Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity

The Journal of Cell Biology, 1998

We tested the role of the "spring-loaded" conformational change in the fusion mechanism of the in... more We tested the role of the "spring-loaded" conformational change in the fusion mechanism of the influenza hemagglutinin (HA) by assessing the effects of 10 point mutants in the region of high coiled-coil propensity, HA2 54-81. The mutants included proline substitutions at HA2 55, 71, and 80, as well as a double proline substitution at residues 55 and 71. Mutants were expressed in COS or 293T cells and assayed for cell surface expression and structural features as well as for their ability to change conformation and induce fusion at low pH. We found the following: Specific mutations affected the precise carbohydrate structure and folding of the HA trimer. All of the mutants, however, formed trimers that could be expressed at the cell surface in a form that could be proteolytically cleaved from the precursor, HA0, to the fusion-permissive form, HA1-S-S-HA2. All mutants reacted with an antibody against the major antigenic site and bound red blood cells. Seven out of ten mutants displayed a wild-type (wt) or moderately elevated pH dependence for the conformational change. V55P displayed a substantial reduction ( ‫ف‬ 60-80%) in the initial rate of lipid mixing. The other single mutants displayed efficient fusion with the same pH dependence as wt-HA. The double proline mutant V55P/ S71P displayed no fusion activity despite being well expressed at the cell surface as a proteolytically cleaved trimer that could bind red blood cells and change conformation at low pH. The impairment in fusion for both V55P and V55P/S71P was at the level of outer leaflet lipid mixing. We interpret our results in support of the hypothesis that the spring-loaded conformational change is required for fusion. An alternate model is discussed.

Research paper thumbnail of PARAINFLUENZA VIRUS TYPE 4: CASE REPORT AND REVIEW OF THE LITERATURE

The Pediatric Infectious Disease Journal, 2000

Research paper thumbnail of Fatal Toxic Shock Syndrome Associated with Clostridium sordellii after Medical Abortion

New England Journal of Medicine, 2005

Research paper thumbnail of SARS and Common Viral Infections

Emerging Infectious Diseases, 2004

In California, molecular testing was useful in decreasing suspicion for severe acute respiratory ... more In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.

Research paper thumbnail of Predominant Kidney Involvement in a Fatal Case of Hantavirus Pulmonary Syndrome Caused by Sin Nombre Virus

Clinical Infectious Diseases, 2001

A 27-year-old woman presented to a hospital with symptoms resembling pyelonephritis; respiratory ... more A 27-year-old woman presented to a hospital with symptoms resembling pyelonephritis; respiratory distress did not develop until nearly a day after admission and she subsequently died. The Unexplained Deaths and Critical Illnesses Project of the Centers for Disease Control and Prevention confirmed Sin Nombre virus infection by the results of serological testing and sequencing of the viral genome; staining of Sin Nombre virus antigen in the pulmonary capillaries was relatively weak.

Research paper thumbnail of Adenovirus Type 3 Viremia in an Adult with Toxic Shock–Like Syndrome

Clinical Infectious Diseases, 2001

Surveillance by the Unexplained Deaths and Critical Illnesses Project (UNEX) uncovered a novel pr... more Surveillance by the Unexplained Deaths and Critical Illnesses Project (UNEX) uncovered a novel presentation of adenovirus type 3 infection that satisfied the criteria for toxic shock-like syndrome in a 28-year-old immunocompetent man. Adenovirus may be a cause of toxic shock syndrome; surveillance systems such as UNEX may uncover additional causes of this and other clinically defined infectious syndromes.

Research paper thumbnail of Invasive Group A Streptococcal Infection Concurrent with 2009 H1N1 Influenza

Clinical Infectious Diseases, 2010

Research paper thumbnail of Characterization of Viral Agents Causing Acute Respiratory Infection in a San Francisco University Medical Center Clinic during the Influenza Season

Clinical Infectious Diseases, 2005

With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, w... more With use of polymerase chain reaction (PCR) and a centrifugation-enhanced viral culture method, we characterized the viruses causing acute respiratory infection in adults during an influenza season. During January-March 2002, nasopharyngeal wash specimens from previously healthy adults presenting with respiratory symptoms were evaluated for viral pathogens with centrifugation-enhanced viral culture and PCR. The diagnoses in 266 cases included unspecified upper respiratory infection (in 142 [54%] of the cases), acute bronchitis (42 [16%]), sinusitis (23 [9%]), pharyngitis (22 [8%]), and pneumonia (17 [6%]). The use of a shell vial assay and PCR identified a pathogen in 103 (39%) of the patients, including influenza A or B in 54, picornavirus in 28 (including rhinovirus in 24), respiratory syncytial virus (RSV) in 12, human metapneumovirus in 4, human coronavirus OC43 in 2, adenovirus in 2, parainfluenza virus type 1 in 1, and coinfection with influenza and parainfluenza virus type 1 in 2. Our findings demonstrate that, even during the influenza season, rhinovirus and RSV are prevalent and must be considered in the differential diagnosis of adult acute respiratory infection before prescribing antiviral medication. Human coronavirus and human metapneumovirus did not play a substantial role. PCR was an especially useful tool in the identification of influenza and other viral pathogens not easily detected by traditional testing methods.

Research paper thumbnail of Severe Pneumonia Due to Adenovirus Serotype 14: A New Respiratory Threat?

Clinical Infectious Diseases, 2008

Adenoviruses are associated with sporadic infection and community and institutional outbreaks; th... more Adenoviruses are associated with sporadic infection and community and institutional outbreaks; they can cause especially severe disease in infants, young children, immunocompromised persons, and transplant recipients. Fifty-two adenovirus serotypes have been recognized and classified within 7 subgroups or species (A-G), with limited data available on associated clinical syndromes and disease severity in more than one-half of the known serotypes. We describe the clinical presentation and virologic characterization of 1 adult and 2 pediatric patients admitted to 2 separate hospitals during April-May 2006 with severe acute respiratory tract infection. All patients had underlying chronic pulmonary disease; none were severely immunocompromised. All 3 experienced serious chronic sequelae or died. Adenovirus was isolated from all 3 case patients. Adenovirus serotype 14, a subspecies B2 serotype not previously associated with severe clinical illness, was confirmed by neutralization assay and sequencing of the hexon gene. Restriction enzyme analysis with BamHI, BglII, HindIII, and SmaI showed all 3 viruses to be identical and to belong to a new genome type that we have designated &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Ad14a.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; Our identification of severe respiratory illness due to a previously rarely reported adenovirus serotype may signify the emergence in the United States of a new genomic variant that has the potential to spread globally and cause epidemics. These case reports highlight the need for rapid diagnosis and improved surveillance, with serotyping and molecular characterization, to identify emerging variants of adenovirus, which may assist with targeted development of antiviral agents or type-specific vaccines.

Research paper thumbnail of Performance Characteristics of Clinical Diagnosis, a Clinical Decision Rule, and a Rapid Influenza Test in the Detection of Influenza Infection in a Community Sample of Adults

Annals of Emergency Medicine, 2005

The accurate diagnosis of influenza remains a diagnostic dilemma. We examine the performance of v... more The accurate diagnosis of influenza remains a diagnostic dilemma. We examine the performance of various strategies for diagnosing influenza infection in an unselected sample of adults during influenza season. Consecutive adults presenting to a university emergency department or urgent care clinic between January and March 2002 with acute respiratory complaints were eligible for this prospective observational study. The performance of clinician judgment, a rapid influenza test, and a clinical prediction rule in predicting influenza infection was evaluated using referent standard of reverse transcriptase polymerase chain reaction. Statistical significance was assessed using McNemar&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s test of proportions. Fifty-three of 258 (21%) patients had a positive influenza reverse transcriptase polymerase chain reaction test. Overall, clinician judgment showed sensitivity of 29% (95% confidence interval [CI] 18% to 43%) and specificity of 92% (95% CI 87% to 95%). The rapid influenza test showed a sensitivity of 33% (95% CI 22% to 47%) and specificity of 98% (95% CI 96% to 99%). The clinical prediction rule showed a sensitivity of 40% (95% CI 27% to 54%) and specificity of 92% (95% CI 87% to 95%). Clinician judgment when patients presented within 48 hours showed a sensitivity of 67% (95% CI 39% to 86%) and specificity of 96% (95% CI 81% to 99%). Neither the rapid influenza test (P=.10) nor the clinical prediction rule (P=.42) was superior to clinician judgment alone in the diagnosis of influenza. The suggestion that a clinical decision rule or a rapid influenza test is better than clinical judgment alone for the diagnosis of influenza in an unselected patient population is not supported by this study.

Research paper thumbnail of Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age

American Journal of Obstetrics and Gynecology, 2009

In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Califor... more In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Californian women after medical abortions. The true incidence of this rare disease is unknown, and a population-based study has never been performed. Additional clostridiaassociated deaths were sought to describe associated clinical characteristics.

Research paper thumbnail of Surveillance for Unexplained Deaths and Critical Illnesses Due to Possibly Infectious Causes, United States, 1995-1998

Emerging Infectious Diseases, 2002