Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 51 Records) |
Query Trace: Gibbons A[original query] |
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Surveillance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis During the COVID-19 Pandemic - United States, 2019-2021
Williams SL , Smith DJ , Benedict K , Ahlers JR , Austin C , Birn R , Carter AM , Christophe NN , Cibulskas K , Cieslak PR , Gibbons-Burgener SN , Gosciminski M , Ireland MJ , Lazenby KV , Loftus T , Lunquest K , Mathewson AA , Nguyen AD , Oltean HN , Osborn B , Petro EM , Power DJ , Reik RR , Schlosser L , Sedivy J , Smelser CB , Chiller T , Toda M . MMWR Morb Mortal Wkly Rep 2024 73 (11) 239-244 Coccidioidomycosis, histoplasmosis, and blastomycosis are lower respiratory tract fungal infections whose signs and symptoms can resemble those of other respiratory illnesses, including pneumonia caused by bacterial or viral etiologies; this overlap in clinical presentation might lead to missed or delayed diagnoses. The causative fungi live in the environment, often in soil or plant matter. To describe the epidemiologic characteristics of cases of coccidioidomycosis, histoplasmosis, and blastomycosis during the COVID-19 pandemic, CDC analyzed case surveillance data for 2019-2021. During this period, a total of 59,655 coccidioidomycosis cases, 3,595 histoplasmosis cases, and 719 blastomycosis cases were reported to CDC. In 2020, fewer cases of each disease occurred in spring compared with other seasons, and most cases occurred in fall; national seasonality is not typically observed, and cases were seasonally distributed more evenly in 2019 and 2021. Fewer cases coinciding with the start of the COVID-19 pandemic, along with an unusually high blastomycosis case fatality rate in 2021 (17% compared with more typical rates of 8%-10%), suggest that the pandemic might have affected patients' health care-seeking behavior, public health reporting practices, or clinical management of these diseases. Increased awareness and education are needed to encourage health care providers to consider fungal diseases and to identify pneumonia of fungal etiology. Standardized diagnostic guidance and informational resources for fungal testing could be incorporated into broader respiratory disease awareness and preparedness efforts to improve early diagnosis of coccidioidomycosis, histoplasmosis, and blastomycosis. |
A phylogeographic description of histoplasma capsulatum in the United States
Bagal UR , Gade L , Benedict K , Howell V , Christophe N , Gibbons-Burgener S , Hallyburton S , Ireland M , McCracken S , Metobo AK , Signs K , Warren KA , Litvintseva AP , Chow NA . J Fungi (Basel) 2023 9 (9) Histoplasmosis is one of the most under-diagnosed and under-reported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases were predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied to the surveillance and outbreak investigation of histoplasmosis. |
Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020 (preprint)
Havers FP , Reed C , Lim T , Montgomery JM , Klena JD , Hall AJ , Fry AM , Cannon DL , Chiang CF , Gibbons A , Krapiunaya I , Morales-Betoulle M , Roguski K , Rasheed MAU , Freeman B , Lester S , Mills L , Carroll DS , Owen SM , Johnson JA , Semenova V , Schiffer J , Thornburg NJ , Blackmore C , Blog D , Dunn A , Lindquist S , Pritchard S , Sosa L , Turabelidze G , Wiesman J , Williams RW . medRxiv 2020 2020.06.25.20140384 Importance Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States.Design Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies.Setting Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State’s (WA) Puget Sound region.Participants Persons of all ages with serum collected during intervals from March 23 through May 3, 2020.Exposure SARS-CoV-2 virus infection.Main outcomes and measures We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date.Results We tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site.Conclusions and relevance Our seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures.Question What proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020?Findings We tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data.Meaning For most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This protocol underwent review by CDC human subjects research officials, who determined that the testing represented non-research activity in the setting of a public health response to the COVID-19 pandemic.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any su h study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesA limited dataset will be made publicly available at a later time. |
Notes from the field: Cluster of blastomycosis among neighborhood residents - St. Croix County, Wisconsin, 2022
Segaloff HE , Wu K , Shaw S , Klasen EM , Peterson L , Lindberg S , Williams SL , Wiese A , Bellay YM , Smith M , Engen K , Toda M , Gibbons-Burgener S . MMWR Morb Mortal Wkly Rep 2023 72 (13) 348-349 Blastomycosis, caused by the fungus Blastomyces, is a rare but potentially serious infection in humans and animals. Blastomyces is endemic in Wisconsin, which reports the highest incidence of Blastomyces infection in the country, with an estimated annual statewide incidence of 2.1 cases per 100,000 residents. Some high-incidence counties report 20–40 cases per 100,000 population (1,2). Blastomyces is also found in other midwestern, south-central, and southeastern states, and lives in moist, organic soils and decaying wood and leaves. Infections typically occur when Blastomyces spores are inhaled. Blastomyces infections do not spread between humans and animals through the air. Blastomycosis usually begins with mild respiratory symptoms, which often self-resolve, but can progress to a severe, and occasionally fatal, disease without antifungal treatment. In February 2022, a veterinarian in St. Croix County, Wisconsin, alerted the Wisconsin Department of Agriculture, Trade and Consumer Protection (DATCP) and the Wisconsin Department of Health Services (DHS) of four dogs with diagnoses of blastomycosis, all living within a 1-mile area. Review of surveillance data identified two human cases reported in the same area within 3 weeks of the canine cases. With 1–5 human cases reported annually, St. Croix County is not considered an area with hyperendemic transmission. |
Adaptation to a multiplex bead assay and seroprevalence to Rift Valley Fever N protein: Nampula Province, Mozambique, 2013-2014
Rogier E , Plucinski M , Candrinho B , Moss DM , Gibbons A , Colborn J , Higgins J , Chambe G , Muchanga J , Muguande O , Matsinhe G , Mathe G , Doyle T , Zulliger R , Saifodine A , Montgomery JM , Klena JD , Priest JW . J Virol 2022 96 (16) e0067222 Rift Valley fever virus (RVFV) is endemic in sub-Saharan Africa (SSA), with outbreaks reported in the Arabian Peninsula and throughout SSA. The natural reservoir for RVFV are ruminants, with livestock populations exceeding 50% exposure rates in some areas of SSA. Transmission to humans can occur through exposure to infected livestock products or multiple species of mosquito vectors. In 2013 and 2014, cross-sectional surveys occurred in two districts of Nacala-a-Velha and Mecubri in northern Mozambique, and participants provided blood samples for later serological assays. IgG against the N protein of RVFV was detected through multiplex bead assay (MBA). Of the 2,278 persons enrolled between the two surveys and study sites, 181 (7.9%, 95% confidence interval (CI): 6.9%-9.1%) were found to be IgG seropositive with increasing seroprevalence with older age and significantly higher seroprevalence in Nacala-a-Velha (10.5%, 8.8%-12.5%) versus Mecubri (5.7%, 4.5%-7.1%). Seroprevalence estimates were not significantly different between the 2013 and 2014 surveys. Significant spatial clustering of IgG positive persons were consistent among surveys and within the two districts, pointing toward the consistency of serology data for making population-level assumptions regarding RVFV seroprevalence. A subset of persons (n=539) provided samples for both the 2013 and 2014 surveys, and a low percentage (0.81%) of these were found to seroconvert between these two surveys. Including the RVFV N protein in an MBA antigen panel could assist elucidate RVFV exposure in SSA. IMPORTANCE Due to sporadic transmission, human contact with Rift Valley Fever Virus (RVFV) is difficult to ascertain at a population level. Detection of antibodies against RVFV antigens assist in estimating exposure as antibodies remain in the host long after the virus has been cleared. In this study, we show that antibodies against RVFV N protein can be detected from dried blood spot (DBS) samples being assayed by multiplex bead assay. DBS from two districts in northern Mozambique were tested for IgG against the N protein, and 7.9% of all enrolled persons were seropositive. Older persons, males, and persons residing closer to the coast had higher RVFV N protein seroprevalence. Spatial clustering of IgG positive persons was noted in both districts. These results show low exposure rates to RVFV in these two northern districts in Mozambique, and the ability to perform serology for the RVFV N protein from dried blood samples. |
Blastomycosis Surveillance in 5 States, United States, 1987-2018
Benedict K , Gibbons-Burgener S , Kocharian A , Ireland M , Rothfeldt L , Christophe N , Signs K , Jackson BR . Emerg Infect Dis 2021 27 (4) 999-1006 Blastomycosis is caused by inhalation of Blastomyces spp. fungi. Limited data are available on the incidence and geographic range of blastomycosis in the United States. To better characterize its epidemiologic features, we analyzed combined surveillance data from the 5 states in which blastomycosis is reportable: Arkansas, Louisiana, Michigan, Minnesota, and Wisconsin. Surveillance identified 4,441 cases during 1987–2018, a mean of 192 cases per year. The mean annual incidence was <1 case/100,000 population in most areas but >20 cases/100,000 population in some northern counties of Wisconsin. Median patient age was 46 years, 2,892 (65%) patients were male, 1,662 (57%) were hospitalized, and 278 (8%) died. The median time from symptom onset to diagnosis was 33 days. The severity of illness and diagnostic delays suggest that surveillance underestimates the true number of cases. More in-depth surveillance in additional states could elucidate blastomycosis incidence and inform efforts to increase awareness. | The median time from symptom onset to diagnosis and the severity of illness suggest that surveillance underestimates the true number of cases. | eng |
Microcephaly Outcomes among Zika Virus-Infected Pregnant Women in Honduras
Alger J , Buekens P , Cafferata ML , Alvarez Z , Berrueta M , Bock H , Bustillo C , Calderón A , Callejas A , Castillo M , Ciganda A , Fúnes J , García J , García K , Gibbons L , Gilboa SM , Harville EW , Hernández G , López R , López W , Lorenzana I , Tulio Luque M , Maldonado C , Moore CA , Ochoa C , Parham L , Pastrana K , Rico F , Rodríguez H , Stella C , Valencia D , Varela D , Wesson DM , Zúniga C , Tong VT . Am J Trop Med Hyg 2021 104 (5) 1737-1740 The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase-PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3-77.7%) risk of HC more than three SDs below the mean. |
Measurement of head circumference: Implications for microcephaly surveillance in Zika-affected areas
Harville EW , Tong VT , Gilboa SM , Moore CA , Cafferata ML , Alger J , Gibbons L , Bustillo C , Callejas A , Castillo M , Fúnes J , García J , Hernández G , López W , Ochoa C , Rico F , Rodríguez H , Zúniga C , Ciganda A , Stella C , Tomasso G , Buekens P . Trop Med Infect Dis 2020 6 (1) Worldwide recognition of the Zika virus outbreak in the Americas was triggered by an unexplained increase in the frequency of microcephaly. While severe microcephaly is readily identifiable at birth, diagnosing less severe cases requires comparison of head circumference (HC) measurement to a growth chart. We examine measured values of HC and digit preference in those values, and, by extension, the prevalence of microcephaly at birth in two data sources: a research study in Honduras and routine surveillance data in Uruguay. The Zika in Pregnancy in Honduras study enrolled pregnant women prenatally and followed them until delivery. Head circumference was measured with insertion tapes (SECA 212), and instructions including consistent placement of the tape and a request to record HC to the millimeter were posted where newborns were examined. Three indicators of microcephaly were calculated: (1) HC more than 2 standard deviations (SD) below the mean, (2) HC more than 3 SD below the mean (referred to as "severe microcephaly") and (3) HC less than the 3rd percentile for sex and gestational age, using the INTERGROWTH-21st growth standards. We compared these results from those from a previous analysis of surveillance HC data from the Uruguay Perinatal Information System (Sistema Informático Perinatal (SIP). Valid data on HC were available on 579 infants, 578 with gestational age data. Nine babies (1.56%, 95% CI 0.71-2.93) had HC < 2SD, including two (0.35%, 95% CI 0.04-1.24) with HC < 3SD, and 11 (1.9%, 95% CI, 0.79-3.02) were below the 3rd percentile. The distribution of HC showed strong digit preference: 72% of measures were to the whole centimeter (cm) and 19% to the half-cm. Training and use of insertion tapes had little effect on digit preference, nor were overall HC curves sufficient to detect an increase in microcephaly during the Zika epidemic in Honduras. When microcephaly prevalence needs to be carefully analyzed, such as during the Zika epidemic, researchers may need to interpret HC data with caution. |
COVID-19 Outbreak at an Overnight Summer School Retreat - Wisconsin, July-August 2020.
Pray IW , Gibbons-Burgener SN , Rosenberg AZ , Cole D , Borenstein S , Bateman A , Pevzner E , Westergaard RP . MMWR Morb Mortal Wkly Rep 2020 69 (43) 1600-1604 During July 2-August 11, 2020, an outbreak of coronavirus disease 2019 (COVID-19) occurred at a boys' overnight summer school retreat in Wisconsin. The retreat included 152 high school-aged boys, counselors, and staff members from 21 states and territories and two foreign countries. All attendees were required to provide documentation of either a positive serologic test result* within the past 3 months or a negative reverse transcription-polymerase chain reaction (RT-PCR) tests result for SARS-CoV-2 (the virus that causes COVID-19) ≤7 days before travel, to self-quarantine within their households for 7 days before travel, and to wear masks during travel. On July 15, the Wisconsin Department of Health Services (WDHS) began an investigation after being notified that two students at the retreat had received positive SARS-CoV-2 RT-PCR test results. WDHS offered RT-PCR testing to attendees on July 28 and serologic testing on August 5 and 6. Seventy-eight (51%) attendees received positive RT-PCR results (confirmed cases), and 38 (25%) met clinical criteria for COVID-19 without a positive RT-PCR result (probable cases). By the end of the retreat, 118 (78%) persons had received a positive serologic test result. Among 24 attendees with a documented positive serologic test result before the retreat, all received negative RT-PCR results. After RT-PCR testing on July 28, WDHS recommended that remaining susceptible persons (asymptomatic and with negative RT-PCR test results) quarantine from other students and staff members at the retreat. Recommended end dates for isolation or quarantine were based on established guidance (1,2) and determined in coordination with CDC. All attendees were cleared for interstate and commercial air travel to return home on August 11. This outbreak investigation documented rapid spread of SARS-CoV-2, likely from a single student, among adolescents and young adults in a congregate setting. Mitigation plans that include prearrival quarantine and testing, cohorting, symptom monitoring, early identification and isolation of cases, mask use, enhanced hygiene and disinfection practices, and maximal outdoor programming are necessary to prevent COVID-19 outbreaks in these settings (3,4). |
Enhanced surveillance for histoplasmosis - 9 states, 2018-2019
Benedict K , McCracken S , Signs K , Ireland M , Amburgey V , Serrano JA , Christophe N , Gibbons-Burgener S , Hallyburton S , Warren KA , Keyser Metobo A , Odom R , Groenewold MR , Jackson BR . Open Forum Infect Dis 2020 7 (9) ofaa343 BACKGROUND: Histoplasmosis is often described as the most common endemic mycosis in the United States, but much remains unknown about its epidemiology among the general population. METHODS: We conducted enhanced surveillance in 9 states during 2018-2019 by identifying cases through routine surveillance and interviewing 301 patients about their clinical features and exposures. RESULTS: Before being tested for histoplasmosis, 60% saw a health care provider ≥3 times, and 53% received antibacterial medication. The median time from seeking health care to diagnosis (range) was 23 (0-269) days. Forty-nine percent were hospitalized, and 69% said that histoplasmosis interfered with their daily activities (median [range], 56 [2-3960] days). Possible exposures included handling plants (48%) and bird or bat droppings (24%); 22% reported no specific exposures. Only 15% had heard of histoplasmosis before their illness. CONCLUSIONS: Histoplasmosis can be severe and prolonged. Additional educational efforts to increase public and provider awareness and reduce delays in diagnosis are needed. |
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020.
Havers FP , Reed C , Lim T , Montgomery JM , Klena JD , Hall AJ , Fry AM , Cannon DL , Chiang CF , Gibbons A , Krapiunaya I , Morales-Betoulle M , Roguski K , Rasheed MAU , Freeman B , Lester S , Mills L , Carroll DS , Owen SM , Johnson JA , Semenova V , Blackmore C , Blog D , Chai SJ , Dunn A , Hand J , Jain S , Lindquist S , Lynfield R , Pritchard S , Sokol T , Sosa L , Turabelidze G , Watkins SM , Wiesman J , Williams RW , Yendell S , Schiffer J , Thornburg NJ . JAMA Intern Med 2020 IMPORTANCE: Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. OBJECTIVE: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. EXPOSURES: Infection with SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. RESULTS: Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. CONCLUSIONS AND RELEVANCE: During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population. |
Validation of a SARS-CoV-2 spike protein ELISA for use in contact investigations and serosurveillance.
Freeman B , Lester S , Mills L , Rasheed MAU , Moye S , Abiona O , Hutchinson GB , Morales-Betoulle M , Krapinunaya I , Gibbons A , Chiang CF , Cannon D , Klena J , Johnson JA , Owen SM , Graham BS , Corbett KS , Thornburg NJ . bioRxiv 2020 Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed tohave had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population. |
Seoul virus infection and spread in US home-based ratteries-rat and human testing results from a multistate outbreak investigation.
Knust B , Brown S , de St Maurice A , Whitmer S , Koske SE , Ervin E , Patel K , Graziano J , Morales-Betoulle ME , House J , Cannon D , Kerins J , Holzbauer S , Austin C , Gibbons-Burgener S , Colton L , Dunn J , Zufan S , Choi MJ , Davis WR , Chiang CF , Manning CR , Roesch L , Shoemaker T , Purpura L , McQuiston J , Peterson D , Radcliffe R , Garvey A , Christel E , Morgan L , Scheftel J , Kazmierczak J , Klena JD , Nichol ST , Rollin PE . J Infect Dis 2020 222 (8) 1311-1319 BACKGROUND: During 2017, a multi-state outbreak investigation occurred following the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested. METHODS: In addition to IgG and IgM serology and traditional RT-PCR, novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed. RESULTS: Seventeen people had SEOV IgM, indicating recent infection; seven reported symptoms and three were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with >/=10 rats tested, rat IgG prevalence ranged 2-70% and SEOV RT-PCR positivity ranged 0-70%. Human lab-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (p=0.03 and p=0.006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities. CONCLUSIONS: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections. |
Acute human orthopneumovirus infection in a captive white-handed gibbon.
Sojka PA , Ploog CL , Garner MM , Kiupel M , Kuypers J , Huynh T . J Vet Diagn Invest 2020 32 (3) 450-453 We report herein a fatal case of acute human orthopneumovirus (formerly respiratory syncytial virus) infection in a captive white-handed gibbon (Hylobates lar). Other members of the housing group had mild respiratory signs. Gross examination revealed bilateral pulmonary congestion and froth in the bronchi. Microscopically, the lungs had lymphocytic, neutrophilic infiltration of the interstitium and alveolar walls. There was necrosis of terminal bronchiolar epithelium and terminal bronchioles, and surrounding alveoli contained necrotic and exfoliated epithelial cells admixed with histiocytes and syncytial cells. Additional lesions included nonsuppurative meningoencephalitis, and epidermal hyperkeratosis and hyperplasia with syncytial cell formation. PCR screening for 12 human respiratory viruses was positive for orthopneumovirus in multiple tissues, including lung, and immunohistochemical staining for human orthopneumovirus detected viral antigen within bronchial epithelial cells. IHC and PCR for measles virus on preserved sections were negative. White-handed gibbons have not been previously reported as hosts for human orthopneumovirus, an important respiratory pathogen of both primates and humans. |
Clonal spread of Yersinia enterocolitica 1B/O:8 in multiple zoo species
Hicks CL , Napier JE , Armstrong DL , Gladney LM , Tarr CL , Freeman MM , Iwen PC . J Zoo Wildl Med 2020 51 (1) 170-176 Yersinia enterocolitica (YE) bioserotype 1B/O:8 (YE 1B/O:8) was identified in routine culture of a variety of zoo species housed at Omaha's Henry Doorly Zoo and Aquarium (OHDZA) from April to July 2011. Animal cases representing 12 species had YE detected from 34 cases during routine fecal monitoring and/or during postmortem examination: Coquerel's sifakas (Propithecus coquereli, two cases), black & white (BW) ruffed lemurs (Varecia variegata variegata, six cases), red ruffed lemurs (Varecia rubra, seven cases), white handed gibbon (Hylobates lar albimana, one case), black lemurs (Eulemur macaco, three cases), mongoose lemurs (Eulemur mongoz, two cases), African hunting dogs (Lycaon pictus, five cases), agile gibbons (Hylobates agilis, three cases), siamangs (Hylobates syndactylus, two cases), colobus monkey (Colobus angolensis palliates, one case), argus pheasant (Argusianus argus, one case), and orangutan (Pongo pygmaeus, one case). Most species were not symptomatic; however, three symptomatic cases in Coquerel's sifakas (two) and a white handed gibbon (one) showed clinical signs of diarrhea and lethargy that resulted in death for the Coquerel's sifakas. One unexpected death also occurred in a BW ruffed lemur. To the authors' knowledge, this is the first report of YE 1B/O:8 in such a large variety of zoo species. The source of the YE could not be identified, prompting the initiation of a diseases surveillance program to prevent further cases for the species that are sensitive to YE. To date, no additional cases have been identified, thus suggesting a single introduction of the YE 1B/O:8 strain into the zoo environment. |
Proposed key characteristics of male reproductive toxicants as an approach for organizing and evaluating mechanistic evidence in human health hazard assessments
Arzuaga X , Smith MT , Gibbons CF , Skakkebaek NE , Yost EE , Beverly BEJ , Hotchkiss AK , Hauser R , Pagani RL , Schrader SM , Zeise L , Prins GS . Environ Health Perspect 2019 127 (6) 65001 BACKGROUND: Assessing chemicals for their potential to cause male reproductive toxicity involves the evaluation of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in hazard identification and evidence integration, the process of identifying, screening and analyzing mechanistic studies and outcomes is a challenging exercise due to the diversity of research models and methods and the variety of known and proposed pathways for chemical-induced toxicity. Ten key characteristics of carcinogens provide a valuable tool for organizing and assessing chemical-specific data by potential mechanisms for cancer-causing agents. However, such an approach has not yet been developed for noncancer adverse outcomes. OBJECTIVES: The objective in this study was to identify a set of key characteristics that are frequently exhibited by exogenous agents that cause male reproductive toxicity and that could be applied for identifying, organizing, and summarizing mechanistic evidence related to this outcome. DISCUSSION: The identification of eight key characteristics of male reproductive toxicants was based on a survey of known male reproductive toxicants and established mechanisms and pathways of toxicity. The eight key characteristics can provide a basis for the systematic, transparent, and objective organization of mechanistic evidence relevant to chemical-induced effects on the male reproductive system. https://doi.org/10.1289/EHP5045. |
Molecular Analysis of the Complete Genome of a Simian Foamy Virus Infecting Hylobates pileatus (pileated gibbon) Reveals Ancient Co-Evolution with Lesser Apes.
Shankar A , Sibley SD , Goldberg TL , Switzer WM . Viruses 2019 11 (7) Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser apes widespread across Southeast Asia that can be infected with SFV, but only two partial SFV sequences are currently available. We used a metagenomics approach with next-generation sequencing of nucleic acid extracted from the cell culture of a blood specimen from a lesser ape, the pileated gibbon (Hylobates pileatus), to obtain the complete SFVhpi_SAM106 genome. We used Bayesian analysis to co-infer phylogenetic relationships and divergence dates. SFVhpi_SAM106 is ancestral to other ape SFVs with a divergence date of ~20.6 million years ago, reflecting ancient co-evolution of the host and SFVhpi_SAM106. Analysis of the complete SFVhpi_SAM106 genome shows that it has the same genetic architecture as other SFVs but has the longest recorded genome (13,885-nt) due to a longer long terminal repeat region (2,071 bp). The complete sequence of the SFVhpi_SAM106 genome fills an important knowledge gap in SFV genetics and will facilitate future studies of FV infection, transmission, and evolutionary history. |
Enhanced surveillance for coccidioidomycosis, 14 US states, 2016
Benedict K , Ireland M , Weinberg MP , Gruninger RJ , Weigand J , Chen L , Perez-Lockett K , Bledsoe C , Denny L , Cibulskas K , Gibbons-Burgener S , Kocharian A , DeBess E , Miller TK , Lepp A , Cronquist L , Warren K , Serrano JA , Loveland C , Turabelidze G , McCotter O , Jackson BR . Emerg Infect Dis 2018 24 (8) 1444-1452 Although coccidioidomycosis in Arizona and California has been well-characterized, much remains unknown about its epidemiology in states where it is not highly endemic. We conducted enhanced surveillance in 14 such states in 2016 by identifying cases according to the Council of State and Territorial Epidemiologists case definition and interviewing patients about their demographic characteristics, clinical features, and exposures. Among 186 patients, median time from seeking healthcare to diagnosis was 38 days (range 1-1,654 days); 70% had another condition diagnosed before coccidioidomycosis testing occurred (of whom 83% were prescribed antibacterial medications); 43% were hospitalized; and 29% had culture-positive coccidioidomycosis. Most (83%) patients from nonendemic states had traveled to a coccidioidomycosis-endemic area. Coccidioidomycosis can cause severe disease in residents of non-highly endemic states, a finding consistent with previous studies in Arizona, and less severe cases likely go undiagnosed or unreported. Improved coccidioidomycosis awareness in non-highly endemic areas is needed. |
Multistate epidemiology of histoplasmosis, United States, 2011-2014
Armstrong PA , Jackson BR , Haselow D , Fields V , Ireland M , Austin C , Signs K , Fialkowski V , Patel R , Ellis P , Iwen PC , Pedati C , Gibbons-Burgener S , Anderson J , Dobbs T , Davidson S , McIntyre M , Warren K , Midla J , Luong N , Benedict K . Emerg Infect Dis 2018 24 (3) 425-431 Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States. |
Amblyomma americanum (Acari: Ixodidae) ticks are not vectors of the Lyme disease agent, Borrelia burgdorferi (Spirocheatales: Spirochaetaceae): A review of the evidence
Stromdahl EY , Nadolny RM , Hickling GJ , Hamer SA , Ogden NH , Casal C , Heck GA , Gibbons JA , Cremeans TF , Pilgard MA . J Med Entomol 2018 55 (3) 501-514 In the early 1980s, Ixodes spp. ticks were implicated as the key North American vectors of Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt and Brenner) (Spirocheatales: Spirochaetaceae), the etiological agent of Lyme disease. Concurrently, other human-biting tick species were investigated as potential B. burgdorferi vectors. Rashes thought to be erythema migrans were observed in patients bitten by Amblyomma americanum (L.) (Acari: Ixodidae) ticks, and spirochetes were visualized in a small percentage of A. americanum using fluorescent antibody staining methods, sparking interest in this species as a candidate vector of B. burgdorferi. Using molecular methods, the spirochetes were subsequently described as Borrelia lonestari sp. nov. (Spirocheatales: Spirochaetaceae), a transovarially transmitted relapsing fever Borrelia of uncertain clinical significance. In total, 54 surveys from more than 35 research groups, involving more than 52,000 ticks, have revealed a low prevalence of B. lonestari, and scarce B. burgdorferi, in A. americanum. In Lyme disease-endemic areas, A. americanum commonly feeds on B. burgdorferi-infected hosts; the extremely low prevalence of B. burgdorferi in this tick results from a saliva barrier to acquiring infection from infected hosts. At least nine transmission experiments involving B. burgdorferi in A. americanum have failed to demonstrate vector competency. Advancements in molecular analysis strongly suggest that initial reports of B. burgdorferi in A. americanum across many states were misidentified B. lonestari, or DNA contamination, yet the early reports continue to be cited without regard to the later clarifying studies. In this article, the surveillance and vector competency studies of B. burgdorferi in A. americanum are reviewed, and we conclude that A. americanum is not a vector of B. burgdorferi. |
High clinical suspicion of donor-derived disease leads to timely recognition and early intervention to treat solid organ transplant-transmitted lymphocytic choriomeningitis virus
Mathur G , Yadav K , Ford B , Schafer IJ , Basavaraju SV , Knust B , Shieh WJ , Hill S , Locke GD , Quinlisk P , Brown S , Gibbons A , Cannon D , Kuehnert M , Nichol ST , Rollin PE , Stroher U , Miller R . Transpl Infect Dis 2017 19 (4) Despite careful donor screening, unexpected donor-derived infections continue to occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus (LCMV) is one such transplant-transmitted infection that in previous reports has resulted in a high mortality among the affected OTRs. We report a LCMV case cluster that occurred 3 weeks post-transplant in three OTRs who received allografts from a common organ donor in March 2013. Following confirmation of LCMV infection at Centers for Disease Control and Prevention, immunosuppression was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were initiated in OTRs. The liver recipient died, but right kidney recipients survived without significant sequelae and left kidney recipient survived acute LCMV infection with residual mental status deficit. Our series highlights how early recognition led to prompt therapeutic intervention, which may have contributed to more favorable outcome in the kidney transplant recipients. This article is protected by copyright. All rights reserved. |
Ebola Virus Disease Diagnostics, Sierra Leone: Analysis of Real-time Reverse Transcription-Polymerase Chain Reaction Values for Clinical Blood and Oral Swab Specimens.
Erickson BR , Sealy TK , Flietstra T , Morgan L , Kargbo B , Matt-Lebby VE , Gibbons A , Chakrabarti AK , Graziano J , Presser L , Flint M , Bird BH , Brown S , Klena JD , Blau DM , Brault AC , Belser JA , Salzer JS , Schuh AJ , Lo M , Zivcec M , Priestley RA , Pyle M , Goodman C , Bearden S , Amman BR , Basile A , Bergeron E , Bowen MD , Dodd KA , Freeman MM , McMullan LK , Paddock CD , Russell BJ , Sanchez AJ , Towner JS , Wang D , Zemtsova GE , Stoddard RA , Turnsek M , Guerrero LW , Emery SL , Stovall J , Kainulainen MH , Perniciaro JL , Mijatovic-Rustempasic S , Shakirova G , Winter J , Sexton C , Liu F , Slater K , Anderson R , Andersen L , Chiang CF , Tzeng WP , Crowe SJ , Maenner MJ , Spiropoulou CF , Nichol ST , Stroher U . J Infect Dis 2016 214 S258-S262 During the Ebola virus outbreak of 2013-2016, the Viral Special Pathogens Branch field laboratory in Sierra Leone tested approximately 26 000 specimens between August 2014 and October 2015. Analysis of the B2M endogenous control Ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. For live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. However, swabs are highly sensitive for diagnostic testing of corpses. |
Preliminary Evaluation of the Effect of Investigational Ebola Virus Disease Treatments on Viral Genome Sequences.
Whitmer SL , Albarino C , Shepard SS , Dudas G , Sheth M , Brown SC , Cannon D , Erickson BR , Gibbons A , Schuh A , Sealy T , Ervin E , Frace M , Uyeki TM , Nichol ST , Stroher U . J Infect Dis 2016 214 S333-S341 BACKGROUND: Several patients with Ebola virus disease (EVD) managed in the United States have received ZMapp monoclonal antibodies, TKM-Ebola small interfering RNA, brincidofovir, and/or convalescent plasma as investigational therapeutics. METHODS: To investigate whether treatment selected for Ebola virus (EBOV) mutations conferring resistance, viral sequencing was performed on RNA extracted from clinical blood specimens from patients with EVD following treatment, and putative viral targets were analyzed. RESULTS: We observed no major or minor EBOV mutations within regions targeted by therapeutics. CONCLUSIONS: This small subset of patients and clinical specimens suggests that evolution of resistance is not a direct consequence of antiviral treatment. As EVD antiviral treatments are introduced into wider use, it is essential that continuous viral full-genome surveillance is performed, to monitor for the emergence of escape mutations. |
Detailed phylogenetic analysis of primate T-lymphotropic virus type 1 (PTLV-1) sequences from orangutans (Pongo pygmaeus) reveals new insights into the evolutionary history of PTLV-1 in Asia.
Reid MJ , Switzer WM , Schillaci MA , Ragonnet M , Joanisse I , Caminiti K , Lowenberger CA , Galdikas BM , Sandstrom PA , Brooks JI . Infect Genet Evol 2016 43 434-50 While human T-lymphotropic virus type 1 (HTLV-1) originates from ancient cross-species transmission of simian T-lymphotropic virus type 1 (STLV-1) from infected nonhuman primates, much debate exists on whether the first HTLV-1 occurred in Africa, or in Asia during early human evolution and migration. This topic is complicated by a lack of representative Asian STLV-1 to infer PTLV-1 evolutionary histories. In this study we obtained new STLV-1 LTR and tax sequences from a wild-born Bornean orangutan (Pongo pygmaeus) and performed detailed phylogenetic analyses using both maximum likelihood and Bayesian inference of available Asian PTLV-1 and African STLV-1 sequences. Phylogenies, divergence dates and nucleotide substitution rates were co-inferred and compared using six different molecular clock calibrations in a Bayesian framework, including both archaeological and/or nucleotide substitution rate calibrations. We then combined our molecular results with paleobiogeographical and ecological data to infer the most likely evolutionary history of PTLV-1. Our analyses robustly inferred an Asian source for PTLV-1 with cross-species transmission of STLV-1 likely from a macaque (Macaca sp.) to an orangutan about 207.5-17.2 kya, and to humans between 125.9-10.4 kya. An orangutan diversification of STLV-1 commenced approximately 3.2 - 37.5 kya. Our analyses also inferred that HTLV-1 was first introduced into Australia ~3.1-3.7 kya, corresponding to both genetic and archaeological changes occurring in Australia at that time. Finally, HTLV-1 appears in Melanesia at ~2.3-2.7 kya corresponding to the migration of the Lapita peoples into the region. Our results also provide an important future reference for calibrating information essential for PTLV evolutionary timescale inference. Longer sequence data, or full genomes from a greater representation of Asian primates, including gibbons, leaf monkeys, and Sumatran orangutans are needed to fully elucidate these evolutionary dates and relationships using the model criteria suggested herein. |
Ebola virus persistence in semen of male survivors
Uyeki TM , Erickson BR , Brown S , McElroy AK , Cannon D , Gibbons A , Sealy T , Kainulainen MH , Schuh AJ , Kraft CS , Mehta AK , Lyon GM , Varkey JB , Ribner BS , Ellison RT 3rd , Carmody E , Nau GJ , Spiropoulou C , Nichol ST , Stroher U . Clin Infect Dis 2016 62 (12) 1552-1555 We investigated the duration of Ebola virus (EBOV) ribonucleic acid (RNA) and infectious EBOV in semen specimens of five Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively after EVD onset. |
Prognostic indicators for Ebola patient survival
Crowe SJ , Maenner MJ , Kuah S , Erickson BR , Coffee M , Knust B , Klena J , Foday J , Hertz D , Hermans V , Achar J , Caleo GM , Van Herp M , Albarino CG , Amman B , Basile AJ , Bearden S , Belser JA , Bergeron E , Blau D , Brault AC , Campbell S , Flint M , Gibbons A , Goodman C , McMullan L , Paddock C , Russell B , Salzer JS , Sanchez A , Sealy T , Wang D , Saffa G , Turay A , Nichol ST , Towner JS . Emerg Infect Dis 2016 22 (2) 217-23 To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations. |
A multifaceted strategy to implement brief smoking cessation counselling during antenatal care in Argentina and Uruguay: a cluster randomized trial
Althabe F , Aleman A , Berrueta M , Morello P , Gibbons L , Colomar M , Tong VT , Dietz PM , Farr SL , Ciganda A , Mazzoni A , Llambi L , Becu A , Smith RA , Johnson C , Belizan JM , Buekens PM . Nicotine Tob Res 2015 18 (5) 1083-1092 INTRODUCTION: We evaluated a multifaceted intervention to increase the frequency of pregnant women who received brief smoking cessation counselling based on the 5As. METHODS: We randomly assigned (1:1) 20 antenatal care clusters in Buenos Aires, Argentina and Montevideo, Uruguay to receive a multifaceted intervention to implement brief smoking cessation counselling into routine antenatal care, or no intervention. Outcomes included receipt of 5As, smoking until the end of pregnancy, and attitudes and readiness of providers towards providing counseling. Women's outcomes were surveyed at baseline and at the end of the 14 to 18-month intervention at the postpartum hospital stay. Cessation was verified with saliva cotinine. The trial took place between October 03, 2011 and November 29, 2013. RESULTS: The rate of women who recalled receiving the 5As increased from 14.0% to 33.6% in the intervention group (median rate change, 22.1%), and 10.8% to 17.0% in the control group (median rate change, 4.6%) (P=0.001 for the difference in change between groups). The proportion of women who continued smoking during pregnancy was unchanged at follow-up in both groups; the relative difference between groups was not significant (ratio of odds ratios 1.16, 95% CI, 0.98 -1.37; P=0.086). No effect observed in attitudes and readiness of providers. CONCLUSION: The intervention showed a moderate effect in increasing the proportion of women who recalled receiving the 5As, with a third receiving counselling in more than one visit. The frequency of women who smoked until the end of the pregnancy was not significantly reduced by the intervention. IMPLICATION: No implementation trials of smoking cessation interventions for pregnant women have been carried out in Latin American or in middle-income countries where health care systems or capacities may differ. We evaluated a multifaceted strategy designed to increase the frequency of pregnant women who receive brief smoking cessation counseling based on the 5As in Argentina and Uruguay. We found that the intervention showed a moderate effect in increasing the proportion of women receiving the 5As, with a third of women receiving counselling in more than one visit. However, the frequency of women who smoked until the end of the pregnancy was not significantly reduced by the intervention. |
Randomized controlled trial to compare immunogenicity of standard dose intramuscular versus intradermal trivalent inactivated influenza vaccine in HIV-infected men who have sex with men in Bangkok, Thailand
Garg S , Thongcharoen P , Prapasiri P , Chitwarakorn A , Sathirapanya P , Fernandez S , Rungrojcharoenkit K , Chonwattana W , Mock PA , Sukwicha W , Katz JM , Widdowson MA , Curlin ME , Gibbons RV , Holtz T , Dawood FS , Olsen SJ . Clin Infect Dis 2015 62 (3) 383-391 BACKGROUND: HIV-infected persons are at increased risk for severe influenza, yet immune responses to standard dose intramuscular influenza vaccine are suboptimal in this population. Intradermal delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. METHODS: We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard dose (15mcg) intradermal (ID) versus standard dose (15mcg) intramuscular (IM) inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4 fold rise in antibody titer) at 1 month post vaccination based on serum hemagglutination inhibition (HI) antibody titers against each vaccine strain. Adverse events in the 7 days following vaccination were also assessed. RESULTS: We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV viral load and antiretroviral treatment. Percent seroconversion to all (ID 14% vs. IM 15%; p=0.8) or at least one (ID 69% vs. IM 68%; p=0.7) of the three vaccine strains did not differ significantly between ID versus IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection site adverse events compared to participants who received IM vaccine (77% versus 27%). CONCLUSIONS: There were no significant differences in the immunogenicity of standard dose ID versus IM influenza vaccine in this HIV-infected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed. |
Dengue viruses cluster antigenically but not as discrete serotypes
Katzelnick LC , Fonville JM , Gromowski GD , Arriaga JB , Green A , James SL , Lau L , Montoya M , Wang C , VanBlargan LA , Russell CA , Thu HM , Pierson TC , Buchy P , Aaskov JG , Munoz-Jordan JL , Vasilakis N , Gibbons RV , Tesh RB , Osterhaus AD , Fouchier RA , Durbin A , Simmons CP , Holmes EC , Harris E , Whitehead SS , Smith DJ . Science 2015 349 (6254) 1338-43 The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV. |
Multidistrict outbreak of Marburg virus disease - Uganda, 2012
Knust B , Schafer IJ , Wamala J , Nyakarahuka L , Okot C , Shoemaker T , Dodd K , Gibbons A , Balinandi S , Tumusiime A , Campbell S , Newman E , Lasry E , DeClerck H , Boum Y , Makumbi I , Bosa HK , Mbonye A , Aceng JR , Nichol ST , Stroher U , Rollin PE . J Infect Dis 2015 212 Suppl 2 S119-28 In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection. |
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