Monkeypox outbreak diagnostics and implications for vaccine protective effect.
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Animals↗
Biomedical subjects
Kevin L Karem
Publications and source records attributed to Kevin L Karem.
Seroprevalence of human papillomavirus type 16 in children.
We evaluated the prevalence of antibodies to human papillomavirus (HPV) type 16 in a representative sample of children 6-11 years of age in the United States. Serum samples and questionnaire data were collected between 1991 and 1994, for the National Health and Nutrition Examination Survey III. HPV-16-specific immunoglobulin G antibodies were detected by an HPV-16 L1 virus-like particle-based enzyme-linked immunosorbant assay. Overall, 2.4% of 1316 children 6-11 years of age were seropositive. Seroprevalence was higher in boys than in girls (3.5% vs. 1.2%; P=.08) and in children >7 years of age than in children < or =7 years of age (3.3% vs. 0.4%; P<.05). None of the variables tested for, including race/ethnicity, socioeconomic status, and urban or rural residence, were significantly associated with HPV-16 seropositivity. To explain HPV-16 seropositivity in this population, further study is required.
Age Factors↗
Evaluation of human-to-human transmission of monkeypox from infected patients to health care workers.
BACKGROUND: In 2003, human monkeypox was first identified in the United States. The outbreak was associated with exposure to infected prairie dogs, but the potential for person-to-person transmission was a concern. This study examines health care worker (HCW) exposure to 3 patients with confirmed monkeypox. METHODS: Exposed HCWs, defined as HCWs who entered a 2-m radius surrounding case patients with confirmed monkeypox, were identified by infection-control practitioners. A self-administered questionnaire and analysis of paired serum specimens determined exposure status, immune response, and postexposure signs and symptoms of monkeypox. RESULTS: Of 81 exposed HCWs, 57 (70%) participated in the study. Among 57 participants, 40 (70%) had > or =1 unprotected exposure; none reported signs or symptoms consistent with monkeypox illness. One exposed HCW (2%), who had been vaccinated for smallpox within the past year, had serological evidence of recent orthopoxvirus infection; acute- and convalescent-phase serum specimens tested positive for anti-orthopoxvirus IgM. No exposed HCWs had signs and symptoms consistent with monkeypox. CONCLUSION: More than three-quarters of exposed HCWs reported at least 1 unprotected encounter with a patient who had monkeypox. One asymptomatic HCW showed laboratory evidence of recent orthopoxvirus infection, which was possibly attributable to either recent infection or smallpox vaccination. Transmission of monkeypox likely is a rare event in the health care setting.
Adult↗
Transmission of monkeypox among persons exposed to infected prairie dogs in Indiana in 2003.
OBJECTIVE: To describe a cluster of human monkeypox cases associated with exposure to ill prairie dogs in a home child care. DESIGN, SETTING, PARTICIPANTS: We identified all persons exposed to 2 pet prairie dogs in County A, Indiana; performed active surveillance for symptomatic monkeypox infection; and evaluated the types of exposure that may have resulted in infection. For children who attended the child care where the animals were housed, we also measured the rate of seroconversion to monkeypox virus. MAIN OUTCOME MEASURES: Nine (13%) of 70 persons exposed to the prairie dogs reported signs and symptoms of monkeypox. Two (40%) of 5 symptomatic child care attendees reported direct contact with the prairie dogs. Two (13%) of 15 child care attendees evaluated tested positive for IgM antibodies against orthopoxvirus; both reported symptoms consistent with monkeypox. RESULTS: The risk of symptomatic infection correlated with the time and intensity of animal exposure, which was 100% (4/4) among family members with extensive direct contact, 19% (5/26) among the veterinarian and nonfamily child care attendees with moderate exposure, and 0% (0/40) among school children with limited exposure (P<.01). CONCLUSIONS: Monkeypox virus was transmitted from ill prairie dogs in a child care and veterinary facilities. The risk of symptomatic infection correlated with the amount of exposure to the prairie dogs. Although most cases of human monkeypox were associated with direct animal contact, other routes of transmission cannot be excluded.
Adult↗
characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak.
A monkeypox outbreak occurred in the United States in 2003. Patient's sera were sent to the Centers for Disease Control and Prevention as a part of outbreak response measures. Clinical and epidemiologic information was abstracted from the case investigation forms. Serum samples from patients were tested by using an immunoglobulin M (IgM)-capture and an IgG enzyme-linked immunosorbent assay ELISA against Orthopoxvirus antigen. The detection of antiviral IgG and IgM antibodies and the kinetics of the antiviral IgG and IgM antibody responses were evaluated. Patients were classified as confirmed, probable, or suspect cases or were excluded as cases based on laboratory test results and epidemiologic and clinical criteria. A total of 37 confirmed case patients with monkeypox were identified, and 116 patients were excluded as case patients based on molecular testing or insufficient epidemiology and clinical data to warrant classification as a suspect or probable case. Of 37 confirmed case patients, 36 had a known history (presence or absence) of smallpox vaccination. Of those, 29 of the 36 either had or developed an IgG response, while 34 of the 36 developed an IgM response, regardless of vaccination status. Serum collected > or =5 days for IgM detection or serum collected > or =8 days after rash onset for IgG detection was most efficient for the detection of monkeypox virus infection. IgM ELISA detects recent infection with orthopoxviruses and, in this case, recent infection with monkeypox virus. In addition, analysis of paired sera for IgG and IgM detected seroconversion, another indicator of recent infection. The ELISA results correlated with the virologic PCR and viral culture results, indicating its diagnostic capabilities for monkeypox and potentially other orthopoxvirus infections due to zoonotic transmission or bioterrorism events.
Antibodies, Viral↗
Quantitative, multiplexed detection of bacterial pathogens: DNA and protein applications of the Luminex LabMAP system.
Escherichia coli, Salmonella, Listeria monocytogenes and Campylobacter jejuni are bacterial pathogens commonly implicated in foodborne illnesses. Generally used detection methods (i.e., culture, biochemical testing, ELISA and nucleic acid amplification) can be laborious, time-consuming and require multiple tests to detect all of the pathogens. Our objective was to develop rapid assays to simultaneously detect these four organisms through the presence of antigen or DNA using the Luminex LabMAP system. For nucleic acid detection, organism-specific capture probes corresponding to the 23S ribosomal RNA gene (rrl) were coupled covalently to LabMAP microspheres. Target molecules included synthetic complementary oligonucleotides and genomic DNA isolated from ATCC type strains or other well-characterized strains of each organism. Universal PCR primers were designed to amplify variable regions of bacterial 23S ribosomal DNA, yielding biotinylated amplicons of 86 to 109 bp in length. Varying quantities of targets were hybridized to the combined microsphere sets, labeled with streptavidin-R-phycoerythrin and analyzed on the Luminex(100) system. Results of nucleic acid detection assays, obtained in 30 to 40 min following amplification, correctly and specifically identified each bacterial species with a detection sensitivity of 10(3) to 10(5) genome copies. Capture-sandwich immunoassays were developed with organism-specific antibodies coupled to different microsphere sets. Microspheres were incubated with organism-specific standards and reactivity was assessed with biotinylated detection antibodies and streptavidin-R-phycoerythrin. In the immunoassays, microsphere-associated fluorescence was organism concentration dependent with detectable response at < or = 1000 organisms/ml and with no apparent cross-reactivity. We have demonstrated that the Luminex LabMAP system is a rapid, flexible platform capable of simultaneous, sensitive and specific detection of pathogens. The practical significance of this multiplexing approach would be to provide more timely, economical and comprehensive information than is available with conventional isolation and identification methodologies.
Antigens, Bacterial↗
Seroprevalence of human papillomavirus type 16 infection in the United States.
Infection with human papillomavirus (HPV) type 16 accounts for about half of cervical cancers worldwide. This study investigated the seroepidemiology of HPV-16 infection in the United States by using a population-based survey. Serum samples and questionnaire data were collected from 1991 to 1994 for the National Health and Nutrition Examination Surveys. HPV-16-specific IgG antibody was detected by use of an HPV-16 virus-like particle ELISA. HPV-16 seropositivity in the US population aged 12-59 years was 13.0% (95% confidence interval, 11.5%-14.7%). Seroprevalence was higher in women (17.9%) than in men (7.9%). Age, race/ethnicity, and number of lifetime sex partners were associated with HPV seropositivity in women. Race/ethnicity, age at first intercourse, urban/nonurban residence, years of sexual activity, and having had sex with a man were associated with HPV seropositivity in men. Information on HPV-16 seroepidemiology will be important for designing prevention efforts including vaccine programs.
Adolescent↗
Optimization of a human papillomavirus-specific enzyme-linked immunosorbent assay.
A strategy was developed for the control, standardization, and critical evaluation of an enzyme-linked immunosorbent assay (ELISA) for the detection of human papillomavirus-specific immunoglobulin G in human sera. Control human sera, polyclonal animal sera, and monoclonal antibodies were used to establish optimal assay parameters, including antigen coating, serum dilutions, and criteria for daily reproducibility, monitoring, and rejection of assays. Three evaluation techniques were used in parallel to define an optimal cutoff absorbance value that yields greater than 93% sensitivity and 98.5% specificity in the assay's ability to discriminate positive and negative control sera. This strategy provides an optimal method by which to determine cutoff absorbance values for ELISA.
Animals↗
Assessment of normal variability in peripheral blood gene expression.
Peripheral blood is representative of many systemic processes and is an ideal sample for expression profiling of diseases that have no known or accessible lesion. Peripheral blood is a complex mixture of cell types and some differences in peripheral blood gene expression may reflect the timing of sample collection rather than an underlying disease process. For this reason, it is important to assess study design factors that may cause variability in gene expression not related to what is being analyzed. Variation in the gene expression of circulating peripheral blood mononuclear cells (PBMCs) from three healthy volunteers sampled three times one day each week for one month was examined for 1,176 genes printed on filter arrays. Less than 1% of the genes showed any variation in expression that was related to the time of collection, and none of the changes were noted in more than one individual. These results suggest that observed variation was due to experimental variability.
Adult↗