Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Blevins P[original query] |
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Successful collaborations that resulted in increased U.S. diagnostic testing during the 2022 Mpox outbreak
Hutson CL , Villanueva J , Stenzel T , Olson VA , Gerald N , McNall R , Courtney S , Aden T , Rager S , Egan C , Blevins P , Kuhnert W , Davidson W , Khan T , Baird N , Kling C , Van Meter S , Chaitram J , Salerno RM . J Public Health Manag Pract 2024 CONTEXT: The first case of mpox was detected in the United States in a Laboratory Response Network (LRN) laboratory at the Massachusetts Department of Public Health on May 17, 2022. Through previous years of smallpox preparedness efforts by the United States government, testing capacity in LRN laboratories across the United States utilizing the FDA-cleared Centers for Disease Control and Prevention (CDC) Non-variola orthopoxvirus (NVO) test was approximately 6000 tests weekly across the nation prior to the mpox outbreak. By early June 2022, the LRN laboratories had capacity to perform up to 8000 tests per week. As the outbreak expanded, cases were identified in every United States state, peaking at ~3000 cases per week nationally in August 2022. OBJECTIVE: Although NVO testing capacity in LRN laboratories exceeded national mpox testing demand overall, LRN testing access in some areas was challenged and test expansion was necessary. PARTICIPANTS: CDC engaged with partners and select commercial laboratories early to increase diagnostic testing access by allowing these commercial laboratories to utilize the NVO test. SETTING: The expansion of testing to commercial laboratories increased testing availability, capacity, and volume nationwide. This was the first time that CDC shared an FDA 510k-cleared molecular test with commercial laboratories to support a public health emergency. DESIGN: Extensive efforts were made to ensure the CDC NVO test was used appropriately in the private sector and that the transfer process met regulatory requirements. MAIN OUTCOME MEASURES, RESULTS, CONCLUSIONS: These novel methods to expand NVO testing to commercial laboratories increased national testing capacity to 80 000 mpox tests/week. Test volumes among these laboratories never exceeded this expanded capacity. The rapid increase in the nation's testing capacity, in conjunction and coordination with other public and private health efforts, helped to detect cases rapidly. These actions demonstrated the importance of highly functional and efficient public health and private sector partnerships for responding to public health emergencies. |
Health care-seeking behavior for childhood illnesses in western Kenya: Qualitative findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) Study
Ngere S , Maixenchs M , Khagayi S , Otieno P , Ochola K , Akoth K , Igunza A , Ochieng B , Onyango D , Akelo V , Blevins J , Barr BAT . Gates Open Res 2024 8 31 BACKGROUND: Child mortality in Kenya is 41 per 1,000 live births, despite extensive investment in maternal, newborn, and child health interventions. Caregivers' health-seeking for childhood illness is an important determinant of child survival, and delayed healthcare is associated with high child mortality. We explore determinants of health-seeking decisions for childhood illnesses among caregivers in western Kenya. METHODS: We conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County, and in rural Siaya County. Key informant interviews, semi-structured interviews and focus group discussions were performed. We adopted the Partners for Applied Social Sciences model focusing on factors that influence the decision-making process to seek healthcare for sick infants and children. The discussions were audio-recorded and transcribed. Data management was completed on Nvivo® software. Iterative analysis process was utilized and themes were identified and collated. RESULTS: Our findings reveal four thematic areas: Illness interpretation, the role of social relationship on illness recognition and response, medical pluralism and healthcare access. Participants reported some illnesses are caused by supernatural powers and some by biological factors, and that the illness etiology would determine the health-seeking pathway. It was common to seek consensus from respected community members on the diagnosis and therefore presumed cause and necessary treatment for a child's illness. Medical pluralism was commonly practiced and caregivers would alternate between biomedicine and traditional medicine. Accessibility of healthcare may determine the health seeking pathway. Caregivers unable to afford biomedical care may choose traditional medicine as a cheaper alternative. CONCLUSION: Health seeking behavior was driven by illness interpretation, financial cost associated with healthcare and advice from extended family and community. These findings enrich the perspectives of health education programs to develop health messages that address factors that hinder prompt health care seeking. |
Evaluation of the Laboratory Response Network and testing access during the first 10 weeks of the mpox response, United States, May 17-July 31, 2022
Thomas KL , Aden TA , Blevins PA , Raziano AJ , Wolford T , Honein MA , Villanueva JM . Public Health Rep 2024 333549241269497 OBJECTIVES: The Laboratory Response Network (LRN) consists of US and international laboratories that respond to public health emergencies, such as biothreats. We used a qualitative approach to assess the successes and challenges of the LRN during the initial 10 weeks of the 2022 mpox outbreak (May 17-July 31, 2022). METHODS: We conducted 9 unstructured interviews, which included 3 interviews with subject matter experts from the Centers for Disease Control and Prevention (CDC) and 6 interviews with state and local public health laboratories and epidemiologists and Association of Public Health Laboratories (APHL) staff. We asked guiding questions on investments in preparedness, successes, and challenges during the initial mpox response and asked for suggestions to improve future LRN responses to infectious disease outbreaks. We also reviewed data from 2 contemporaneous APHL surveys conducted in June and July 2022 in 84 LRN public health laboratories. RESULTS: Notable successes included availability of an assay that had received clearance from the US Food and Drug Administration (FDA) for testing orthopoxviruses (non-variola Orthopoxvirus [NVO] assay) and a trained workforce; strong relationships among FDA, CDC, and the LRN; and strong communications between LRN laboratories and CDC. Challenges included variability among LRN laboratories in self-reported testing capacity, barriers to accessing the NVO assay for health care providers, and gaps in LRN function during surges of testing needs. CONCLUSIONS: The LRN system plays an essential role in the response to emerging infectious disease outbreaks in the United States. Lessons learned from the LRN's initial response to the mpox outbreak can help guide improvements to better position the LRN for future responses, including continued engagement with health care providers, commercial laboratories, and laboratories in health care settings. |
Acceptability of minimally invasive autopsy by community members and healthcare workers in Siaya and Kisumu counties, western Kenya, 2017-2018
Otieno P , Akelo V , Khagayi S , Omore R , Akoth K , Nyanjom M , Ngere S , Ochola K , Maixenchs M , Kone A , Blevins J , Zielinski-Gutierrez E , Barr BAT . PLOS Glob Public Health 2023 3 (9) e0001319 Worldwide, nearly six million children under the age of five (<5s) die annually, a substantial proportion of which are due to preventable and treatable diseases. Efforts to reduce child mortality indicators in the most affected regions are often undermined by a lack of accurate cause of death data. To generate timely and more accurate causes of death data for <5s, the Child Health and Mortality Prevention Surveillance (CHAMPS) Network established mortality surveillance in multiple countries using Minimally Invasive Tissue Sampling (MITS) in <5 deaths. Here we present acceptability of MITS by community members and healthcare workers in Siaya and Kisumu counties, western Kenya. From April 2017 to February 2018, we conducted 40 in-depth interviews and five focus group discussions with healthcare workers and community members, before and during CHAMPS implementation. Participants were purposively selected. Field observations to understand traditional death-related practices were also performed. Interviews were transcribed into Nvivo 11.0 for data organization and management. Analysis was guided by the grounded theory approach. Facilitators of acceptability were desire to understand why death occurred, timely performance of MITS procedures, potential for MITS results in improving clinical practice and specific assistance provided to families by the CHAMPS program. However, cultural and religious beliefs highlighted important challenges to acceptability, including CHAMPS teams recruiting after a child's death, rumours and myths, unmet expectations from families, and fear by healthcare workers that some families could use MITS results to sue for negligence. Increasing MITS uptake requires sustained strategies to strengthen the identified facilitators of acceptability and simultaneously address the barriers. MITS acceptance will contribute to better characterization of causes of death and support the development of improved interventions aimed at reducing <5 mortality. |
Religion as a social force in health: complexities and contradictions
Idler E , Jalloh MF , Cochrane J , Blevins J . BMJ 2023 382 e076817 The relationship between religion and public health regularly makes headlines in the press, with both conflict and cooperation as themes. Recent examples include: “Battling covid when religion and public health collide,”1 “Churches and mosques educate on Ebola,”2 “Uganda: HIV-positive teens choose religion over ARV.”3 In some cases, religious institutions protect and support public health measures; in others, the opposite occurs. | | Religion is a set of spiritual beliefs and practices that manifest not only at individual level but at institutional levels through congregations of organised religions and faith based, charitable organisations. At the individual level religion may manifest as public participation in worship services of a congregation, as private practices such as prayer or meditation, or as private beliefs in the tenets of a faith or identifying as a religious person. Alongside education, income, ethnicity, and gender, religion has a quantifiable, demonstrable effect on population health.4 However, religion is different from other socioeconomic determinants of health; its unique complexities can produce both harmful and protective health effects. It therefore warrants a different conceptualisation as a social determinant of health, both to mitigate its harmful effects and to realise its protective and generative impact. |
Rapid diagnostic testing for response to the monkeypox outbreak - Laboratory Response Network, United States, May 17-June 30, 2022
Aden TA , Blevins P , York SW , Rager S , Balachandran D , Hutson CL , Lowe D , Mangal CN , Wolford T , Matheny A , Davidson W , Wilkins K , Cook R , Roulo RM , White MK , Berman L , Murray J , Laurance J , Francis D , Green NM , Berumen RA3rd , Gonzalez A , Evans S , Hudziec M , Noel D , Adjei M , Hovan G , Lee P , Tate L , Gose RB , Voermans R , Crew J , Adam PR , Haydel D , Lukula S , Matluk N , Shah S , Featherston J , Ware D , Pettit D , McCutchen E , Acheampong E , Buttery E , Gorzalski A , Perry M , Fowler R , Lee RB , Nickla R , Huard R , Moore A , Jones K , Johnson R , Swaney E , Jaramillo J , Reinoso Webb C , Guin B , Yost J , Atkinson A , Griffin-Thomas L , Chenette J , Gant J , Sterkel A , Ghuman HK , Lute J , Smole SC , Arora V , Demontigny CK , Bielby M , Geeter E , Newman KAM , Glazier M , Lutkemeier W , Nelson M , Martinez R , Chaitram J , Honein MA , Villanueva JM . MMWR Morb Mortal Wkly Rep 2022 71 (28) 904-907 As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders. |
Notes from the Field: SARS-CoV-2 Omicron Variant Infection in 10 Persons Within 90 Days of Previous SARS-CoV-2 Delta Variant Infection - Four States, October 2021-January 2022.
Roskosky M , Borah BF , DeJonge PM , Donovan CV , Blevins LZ , Lafferty AG , Pringle JC , Kelso P , Temte JL , Temte E , Barlow S , Goss M , Uzicanin A , Bateman A , Florek K , Kawakami V , Lewis J , Loughran J , Pogosjans S , Kay M , Duchin J , Lunn S , Schnitzler H , Arora S , Tate J , Ricaldi J , Kirking H . MMWR Morb Mortal Wkly Rep 2022 71 (14) 524-526 Vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19) and related hospitalizations (1,2), and surviving a previous infection protects against B.1.1.7 (Alpha) and B.1.617.2 (Delta) variant reinfections† (2). Since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States in late December 2021, reported reinfections have increased§ (3). Early reinfections (those occurring within 90 days of previous infection) are not well understood (4). Because some persons have prolonged detection of viral RNA after infection,¶ repeat positive nucleic acid amplification test (NAAT) results within 90 days could reflect prolonged shedding from earlier infection, presenting technical challenges to documenting and characterizing early reinfections. This report describes 10 patients from four states, with whole genome sequencing (WGS)–confirmed Omicron variant infections within 90 days of a previous Delta infection. This activity was reviewed by CDC, approved by respective institutional review boards, and was conducted consistent with applicable federal law and CDC policy.** |
Cluster of Oseltamivir-Resistant and Hemagglutinin Antigenically Drifted Influenza A(H1N1)pdm09 Viruses, Texas, USA, January 2020
Mohan T , Nguyen HT , Kniss K , Mishin VP , Merced-Morales AA , Laplante J , St George K , Blevins P , Chesnokov A , De La Cruz JA , Kondor R , Wentworth DE , Gubareva LV . Emerg Infect Dis 2021 27 (7) 1953-1957 Four cases of oseltamivir-resistant influenza A(H1N1)pdm09 virus infection were detected among inhabitants of a border detention center in Texas, USA. Hemagglutinin of these viruses belongs to 6B.1A5A-156K subclade, which may enable viral escape from preexisting immunity. Our finding highlights the necessity to monitor both drug resistance and antigenic drift of circulating viruses. |
Rumor surveillance in support of minimally invasive tissue sampling for diagnosing the cause of child death in low-income countries: A qualitative study
Islam MS , Al-Masud A , Maixenchs M , Cossa S , Guilaze R , Diarra K , Fofana I , Hussain F , Blevins J , Kone A , Arifeen SE , Mandomando I , Bassat Q , Sage EO , Gurley ES , Munguambe K . PLoS One 2021 16 (1) e0244552 In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure. Our surveillance activities included observations and interviews with stakeholders to understand how rumors are developed and spread and to anticipate rumors in the program areas. We also engaged young volunteers, local stakeholders, community leaders, and study staff to report rumors being spread in the community after MITS launch. Through community meetings, we also managed and responded to rumors. When a rumor was reported, the field team purposively conducted interviews and group discussions to track, verify and understand the rumor. From July 2016 through April 2018, the surveillance identified several rumors including suspicions of organs being harvested or transplanted; MITS having been performed on a living child, and concerns related to disrespecting the body and mistrust related to the study purpose. These rumors, concerns, and cues of mistrust were passed by word of mouth. We managed the rumors by modifying the consent protocol and giving additional information and support to the bereaved family and to the community members. Rumor surveillance was critical for anticipating and readily identifying rumors and managing them. Setting up rumor surveillance by engaging community residents, stakeholders, and volunteers could be an essential part of any public health program where there is a need to identify and react in real-time to public concern. |
Subtype diagnosis of sporadic Creutzfeldt-Jakob disease with diffusion MRI.
Bizzi A , Pascuzzo R , Blevins J , Moscatelli MEM , Grisoli M , Lodi R , Doniselli FM , Castelli G , Cohen ML , Stamm A , Schonberger LB , Appleby BS , Gambetti P . Ann Neurol 2020 89 (3) 560-572 OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion Magnetic Resonance Imaging (MRI). METHODS: MRI of 1458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile. We selected 487 patients with autopsy-confirmed diagnosis of "pure" sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure -"Prion Subtype Classification Algorithm with MRI" (PriSCA_MRI)- uses only MRI examinations; the second -"PriSCA_MRI+Gen"- includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on first and the last MRI follow-up. RESULTS: PriSCA_MRI classified the three most prevalent subtypes with 82% accuracy. PriSCA_MRI+Gen raised the accuracy to 89% and identified all subtypes. Individually, the two most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with both procedures with accuracies up to 95% and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. INTERPRETATION: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. This article is protected by copyright. All rights reserved. |
Human prion disease surveillance in Washington state, 2006-2017
Sánchez-González L , Maddox RA , Lewis LC , Blevins JE , Harker EJ , Appleby BS , Person MK , Schonberger LB , Belay ED , DeBolt C , Lofy KH . JAMA Netw Open 2020 3 (10) e2020690 IMPORTANCE: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. OBJECTIVE: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. EXPOSURE: Human prion disease diagnosis. MAIN OUTCOMES AND MEASURES: The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. RESULTS: A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases. |
Diagnosis of prion diseases by RT-QuIC results in improved surveillance
Rhoads DD , Wrona A , Foutz A , Blevins J , Glisic K , Person M , Maddox RA , Belay ED , Schonberger LB , Tatsuoka C , Cohen ML , Appleby BS . Neurology 2020 95 (8) e1017-e1026 OBJECTIVE: We present the National Prion Disease Pathology Surveillance Center's (NPDPSC) experience using cerebrospinal fluid (CSF) real time quaking induced conversion (RT-QuIC) as a diagnostic test, examine factors associated with false negative RT-QuIC results, and investigate RT-QuIC's impact on prion disease surveillance. METHODS: Between May 2015-April 2018, the NPDPSC received 10,498 CSF specimens that were included in the study. Sensitivity and specificity analyses were performed using 567 autopsy verified cases. Prion disease type, demographic characteristics, specimen color, and time variables were examined for association with RT-QuIC results. The effect of including positive RT-QuIC cases in prion disease surveillance was examined. RESULTS: The diagnostic sensitivity and specificity of RT-QuIC across all prion diseases was 90.3% and 98.5%, respectively. Diagnostic sensitivity was lower for fatal familial insomnia, Gerstmann-Straussler-Scheinker disease, sporadic fatal insomnia, variably protease sensitive prionopathy, and the VV1 and MM2 subtypes of sCJD. Individuals with prion disease and negative RT-QuIC results were younger, had elevated tau levels, and non-elevated 14-3-3 levels compared to RT-QuIC positive cases. Sensitivity was high throughout the disease course. Some cases that initially tested RT-QuIC negative had a subsequent specimen test positive. Including positive RT-QuIC cases in surveillance statistics increased laboratory-based case ascertainment of prion disease by 90% over autopsy alone. CONCLUSIONS: RT-QuIC has high sensitivity and specificity for diagnosing prion diseases. Sensitivity limitations are associated with prion disease type, age, and related CSF diagnostic results. RT-QuIC greatly improves laboratory-based prion disease ascertainment for surveillance purposes. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that 2(nd) generation real time quaking-induced conversion (RT-QuIC) identifies prion disease with sensitivity of 90.3% and specificity of 98.5%, among patients being screened for these diseases due to concerning symptoms. |
Prion propagation estimated from brain diffusion MRI is subtype dependent in sporadic Creutzfeldt-Jakob disease
Pascuzzo R , Oxtoby NP , Young AL , Blevins J , Castelli G , Garbarino S , Cohen ML , Schonberger LB , Gambetti P , Appleby BS , Alexander DC , Bizzi A . Acta Neuropathol 2020 140 (2) 169-181 Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible brain proteinopathy. Five main clinicopathological subtypes (sCJD-MM(V)1, -MM(V)2C, -MV2K, -VV1, and -VV2) are currently distinguished. Histopathological evidence suggests that the localisation of prion aggregates and spongiform lesions varies among subtypes. Establishing whether there is an initial site with detectable imaging abnormalities (epicentre) and an order of lesion propagation would be informative for disease early diagnosis, patient staging, management and recruitment in clinical trials. Diffusion magnetic resonance imaging (MRI) is the most-used and most-sensitive test to detect spongiform degeneration. This study was designed to identify, in vivo and for the first time, subtype-dependent epicentre and lesion propagation in the brain using diffusion-weighted images (DWI), in the largest known cross-sectional dataset of autopsy-proven subjects with sCJD. We estimate lesion propagation by cross-sectional DWI using event-based modelling, a well-established data-driven technique. DWI abnormalities of 594 autopsy-diagnosed subjects (448 patients with sCJD) were scored in 12 brain regions by 1 neuroradiologist blind to the diagnosis. We used the event-based model to reconstruct sequential orderings of lesion propagation in each of five pure subtypes. Follow-up data from 151 patients validated the estimated sequences. Results showed that epicentre and ordering of lesion propagation are subtype specific. The two most common subtypes (-MM1 and -VV2) showed opposite ordering of DWI abnormality appearance: from the neocortex to subcortical regions, and vice versa, respectively. The precuneus was the most likely epicentre also in -MM2 and -VV1 although at variance with -MM1, abnormal signal was also detected early in cingulate and insular cortices. The caudal-rostral sequence of lesion propagation that characterises -VV2 was replicated in -MV2K. Combined, these data-driven models provide unprecedented dynamic insights into subtype-specific epicentre at onset and propagation of the pathologic process, which may also enhance early diagnosis and enable disease staging in sCJD. |
Evaluation of a new criterion for detecting prion disease with diffusion magnetic resonance imaging
Bizzi A , Pascuzzo R , Blevins J , Grisoli M , Lodi R , Moscatelli MEM , Castelli G , Cohen ML , Schonberger LB , Foutz A , Safar JG , Appleby BS , Gambetti P . JAMA Neurol 2020 77 (9) 1141-1149 Importance: Early diagnosis is a requirement for future treatment of prion diseases. Magnetic resonance imaging (MRI) with diffusion-weighted images and improved real-time quaking-induced conversion (RT-QuIC) in cerebrospinal fluid (CSF) have emerged as reliable tests. Objectives: To assess the sensitivity and specificity of diffusion MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) with a new criterion (index test) of at least 1 positive brain region among the cortex of the frontal, parietal, temporal, and occipital lobes; the caudate; the putamen; and the thalamus. Design, Setting, and Participants: This diagnostic study with a prospective and a retrospective arm was performed from January 1, 2003, to October 31, 2018. MRIs were collected from 1387 patients with suspected sCJD consecutively referred to the National Prion Disease Pathology Surveillance Center as part of a consultation service. Intervention: Magnetic resonance imaging. Four neuroradiologists blinded to the diagnosis scored the MRIs of 200 randomly selected patients. One neuroradiologist scored the MRIs of all patients. Main Outcomes and Measures: Sensitivity and specificity of the index test compared with currently used criteria and CSF diagnostic (improved RT-QuIC, 14-3-3, and tau CSF tests). Results: A total of 872 patients matched the inclusion criteria (diffusion MRI and autopsy-confirmed diagnosis), with 619 having sCJD, 102 having other prion diseases, and 151 having nonprion disease. The primary analysis included 200 patients (mean [SD] age, 63.6 [12.9] years; 100 [50.0%] male). Sensitivity of the index test of 4 neuroradiologists was 90% to 95% and superior to sensitivity of current MRI criteria (69%-76%), whereas specificity was 90% to 100% and unchanged. Interrater reliability of the 4 neuroradiologists was high (kappa = 0.81), and individual intrarater reliability was excellent (kappa >/=0.87). The sensitivity of the index test of 1 neuroradiologist for 770 patients was 92.1% (95% CI, 89.7%-94.1%) and the specificity was 97.4% (95% CI, 93.4%-99.3%) compared with a sensitivity of 69.8% (95% CI, 66.0%-73.4%; P < .001) and a specificity of 98.0% (95% CI, 94.3%-99.6%; P > .99) according to the current criteria. For 88 patients, index test sensitivity (94.9%; 95% CI, 87.5%-98.6%) and specificity (100%; 95% CI, 66.4%-100%) were similar to those of improved RT-QuIC (86.1% [95% CI, 76.5%-92.8%] and 100% [95% CI, 66.4%-100%], respectively). Lower specificities were found for 14-3-3 and tau CSF tests in 452 patients. Conclusions and Relevance: In this study, the diagnostic performance of diffusion MRI with the new criterion was superior to that of current standard criteria and similar to that of improved RT-QuIC. These results may have important clinical implications because MRI is noninvasive and typically prescribed at disease presentation. |
Symptom level associations between attention-deficit hyperactivity disorder and school performance
Rigoni M , Blevins LZ , Rettew DC , Kasehagen L . Clin Pediatr (Phila) 2020 59 9922820924692 Attention-deficit hyperactivity disorder (ADHD) is associated with reduced school performance. To determine which ADHD symptoms and subtypes have the strongest association, we used type and frequency of symptoms on the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome (NS-DATA) to create symptom scores for inattention and hyperactivity-impulsivity and define subtypes (ADHD-Inattentive [ADHD-I], ADHD-Hyperactive-Impulsive, ADHD-Combined [ADHD-C]). Regression methods were used to examine associations between symptoms and subtype and a composite measure of school performance. Children with ADHD-C and ADHD-I had higher adjusted odds of having reduced overall school performance (ADHD-C = 5.8, 95% confidence interval [CI] = 3.1-10.9; ADHD-I = 5.5, 95% CI = 3.1-10.1) compared with children without ADHD. All inattentive symptoms were significantly related to reduced school performance in reading, writing, and handwriting, while 6 of 9 symptoms were significantly associated in mathematics. Children with ADHD-I were significantly more likely than children with other ADHD subtypes to receive a school-based Individualized Education Program or 504 Plan. ADHD-I symptoms may be broadly linked to reduced school performance. |
Prion disease incidence in the United States, 2003-2015
Maddox RA , Person MK , Blevins JE , Abrams JY , Appleby BS , Schonberger LB , Belay ED . Neurology 2019 94 (2) e153-e157 OBJECTIVE: To report the incidence of prion disease in the United States. METHODS: Prion disease decedents were retrospectively identified from the US national multiple cause-of-death data for 2003-2015 and matched with decedents in the National Prion Disease Pathology Surveillance Center (NPDPSC) database through comparison of demographic variables. NPDPSC decedents with neuropathologic or genetic test results positive for prion disease for whom no match was found in the multiple cause-of-death data were added as cases for incidence calculations; those with cause-of-death data indicating prion disease but with negative neuropathology results were removed. Age-specific and age-adjusted average annual incidence rates were then calculated. RESULTS: A total of 5,212 decedents were identified as having prion disease, for an age-adjusted average annual incidence of 1.2 cases per million population (range 1.0 per million [2004 and 2006] to 1.4 per million [2013]). The median age at death was 67 years. Ten decedents were <30 years of age (average annual incidence of 6.2 per billion); only 2 of these very young cases were sporadic forms of prion disease. Average annual incidence among those >/=65 years of age was 5.9 per million. CONCLUSIONS: Prion disease incidence can be estimated by augmenting mortality data with the results of neuropathologic and genetic testing. Cases <30 years of age were extremely rare, and most could be attributed to exogenous factors or the presence of a genetic mutation. Continued vigilance for prion diseases in all age groups remains prudent. |
Using participatory workshops to assess alignment or tension in the Community for Minimally Invasive Tissue Sampling Prior to Start of Child Mortality Surveillance: Lessons from 5 sites across the CHAMPS Network
Blevins J , O'Mara Sage E , Kone A , Maixenchs M , Raghunathan PL , Guilaze RA , Cossa S , Girma Z , Zegeye Y , Ackley C , Hussain F , Islam S , Myburgh N , Ngwenya N , Madhi SA , Otieno P , Ochola K , Munguambe K , Breiman RF . Clin Infect Dis 2019 69 S280-s290 The Child Health and Mortality Prevention Surveillance (CHAMPS) program is a 7-country network (as of December 2018) established by the Bill & Melinda Gates Foundation to identify the causes of death in children in communities with high rates of under-5 mortality. The program carries out both mortality and pregnancy surveillance, and mortality surveillance employs minimally invasive tissue sampling (MITS) to gather small samples of body fluids and tissue from the bodies of children who have died. While this method will lead to greater knowledge of the specific causes of childhood mortality, the procedure is in tension with cultural and religious norms in many of the countries where CHAMPS works-Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. Participatory Inquiry Into Community Knowledge of Child Health and Mortality Prevention (PICK-CHAMP) is a community entry activity designed to introduce CHAMPS to communities and gather initial perspectives on alignments and tensions between CHAMPS activities and community perceptions and priorities. Participants' responses revealed medium levels of overall alignment in all sites (with the exception of South Africa, where alignment was high) and medium levels of tension (with the exception of Ethiopia, where tension was high). Alignment was high and tension was low for pregnancy surveillance across all sites, whereas Ethiopia reflected low alignment and high tension for MITS. Participants across all sites indicated that support for MITS was possible only if the procedure did not interfere with burial practices and rituals. |
Investigating the feasibility of child mortality surveillance with postmortem tissue sampling: Generating constructs and variables to strengthen validity and reliability in qualitative research
O'Mara Sage E , Munguambe KR , Blevins J , Guilaze R , Kosia B , Maixenchs M , Bassat Q , Mandomando I , Kaiser R , Kone A , Jambai A , Myburgh ND , Ngwenya N , Madhi SA , Degefa K , Ackley C , Breiman RF , Raghunathan PL . Clin Infect Dis 2019 69 S291-s301 BACKGROUND: The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged <5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS. METHODS: Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting. RESULTS: Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability. CONCLUSIONS: These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS. |
An online program for caregivers of persons living with dementia: Lessons learned
Kovaleva M , Blevins L , Griffiths PC , Hepburn K . J Appl Gerontol 2017 38 (2) 733464817705958 The population of individuals living with dementia and their caregivers and the need to provide caregiver training will increase in the next several decades. In-person caregiver educational programs are delimited by logistical and resource boundaries that could be overcome with online programs. The purpose of this qualitative descriptive study was to explore the acceptability and ways to improve the content and delivery of an online 7-week psychoeducational pilot program-Tele-Savvy. Thirty-six caregivers who completed the pilot were interviewed about their experience with Tele-Savvy and their suggestions for its improvement. Conventional content analysis allowed for the identification of three themes: barriers and facilitators to establishing rapport with participants and instructors, content enrichment and diversification, and structural refinement. These lessons learned directly from the caregivers provide evidence to guide the refinement of analogous online interventions and highlight the need for their wider availability. |
Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.
Foutz A , Appleby BS , Hamlin C , Liu X , Yang S , Cohen Y , Chen W , Blevins J , Fausett C , Wang H , Gambetti P , Zhang S , Hughson A , Tatsuoka C , Schonberger LB , Cohen ML , Caughey B , Safar JG . Ann Neurol 2016 81 (1) 79-92 Objective-Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. Methods- We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance. Results-The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1-2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, while genetic prion diseases revealed distinct profiles for each PRNP gene mutation. Interpretation-The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and Tau proteins and together with PRNP gene sequencing, the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease-two important considerations for envisioned therapeutic interventions. |
Detection of Measles Virus RNA in Air and Surface Specimens in a Hospital Setting
Bischoff WE , McNall RJ , Blevins MW , Turner J , Lopareva EN , Rota PA , Stehle JR Jr . J Infect Dis 2015 213 (4) 600-3 Measles virus (MeV) is known to be highly contagious with an infectious period lasting from the four days preceding to the four days following rash onset. An unvaccinated, young, female patient with measles confirmed by direct epidemiologic link was hospitalized on day five after rash onset. Environmental samples were collected over the four day hospitalization period in a single room. MeV RNA was detectable in air, on surfaces, and respirators on days 5-8 after rash onset. This is the first report of environmental surveillance for MeV and the results suggest that measles infected fomites may be present in healthcare settings. |
Risk factors for delayed initiation of combination antiretroviral therapy in rural north central Nigeria
Aliyu MH , Blevins M , Parrish DD , Megazzini KM , Gebi UI , Muhammad MY , Ahmed ML , Shepherd BE , Hassan A , Vermund SH , Wester CW . J Acquir Immune Defic Syndr 2013 65 (2) e41-9 BACKGROUND: Timely initiation of combination antiretroviral therapy (ART) in eligible HIV-infected patients is associated with substantial reduction in mortality and morbidity. Nigeria has the second largest number of persons living with HIV/AIDS in the world. We examined patient characteristics, time to ART initiation, retention and mortality at five rural facilities in Kwara and Niger states of Nigeria. METHODS: We analyzed program-level cohort data for HIV-infected, ART-naive clients (≥15 years) enrolled from June 2009-February 2011. We modeled the probability of ART initiation among clients meeting national ART eligibility criteria using logistic regression with splines. RESULTS: We enrolled 1,948 ART-naive adults/adolescents into care, of whom 1174 were ART eligible (62% female). Only 74% of eligible patients (n=869) initiated ART within 90 days post-enrollment. The median CD4+ count for eligible clients was 156 cells/microL [IQR: 81-257], with 67% in WHO stage III/IV disease. Adjusting for CD4+ count, WHO stage, functional status, hemoglobin, body mass index, sex, age, education, marital status, employment, clinic of attendance, and month of enrollment, we found that immunosuppression (CD4 350 vs. 200, odds ratio (OR)=2.10 [95%CI: 1.31, 3.35], functional status (bedridden vs. working, OR=4.17 [95%CI: 1.63-10.67]), clinic of attendance (Kuta hospital vs. referent: OR=5.70 [95%CI:2.99-10.89]), and date of enrollment (December 2010 vs. June 2009: OR=2.13 [95%CI:1.19-3.81]) were associated with delayed ART initiation. CONCLUSION: Delayed initiation of ART was associated with higher CD4+ counts, lower functional status, clinic of attendance, and later dates of enrollment among ART-eligible clients. Our findings provide targets for quality improvement efforts that may help reduce attrition and improve ART uptake in similar settings. |
Seroprevalence of Powassan virus in New England deer, 1979-2010
Nofchissey RA , Deardorff ER , Blevins TM , Anishchenko M , Bosco-Lauth A , Berl E , Lubelczyk C , Mutebi JP , Brault AC , Ebel GD , Magnarelli LA . Am J Trop Med Hyg 2013 88 (6) 1159-62 Powassan virus and its subtype, deer tick virus, are closely related tick-borne flaviviruses that circulate in North America. The incidence of human infection by these agents appears to have increased in recent years. To define exposure patterns among white-tailed deer, potentially useful sentinels that are frequently parasitized by ticks, we screened serum samples collected during 1979-2010 in Connecticut, Maine, and Vermont for neutralizing antibody by using a novel recombinant deer tick virus-West Nile virus chimeric virus. Evidence of exposure was detected in all three states. Overall our results demonstrate that seroprevalence is variable in time and space, suggesting that risk of exposure to Powassan virus is similarly variable. |
Household transmission of pandemic (H1N1) 2009, San Antonio, Texas, USA, April-May 2009
Morgan OW , Parks S , Shim T , Blevins PA , Lucas PM , Sanchez R , Walea N , Loustalot F , Duffy MR , Shim MJ , Guerra S , Guerra F , Mills G , Verani J , Alsip B , Lindstrom S , Shu B , Emery S , Cohen AL , Menon M , Fry AM , Dawood F , Fonseca VP , Olsen SJ . Emerg Infect Dis 2010 16 (4) 631-7 To assess household transmission of pandemic (H1N1) 2009 in San Antonio, Texas, USA, during April 15-May 8, 2009, we investigated 77 households. The index case-patient was defined as the household member with the earliest onset date of symptoms of acute respiratory infection (ARI), influenza-like illness (ILI), or laboratory-confirmed pandemic (H1N1) 2009. Median interval between illness onset in index and secondary case-patients was 4 days (range 1-9 days); the index case-patient was likely to be < or =18 years of age (p = 0.034). The secondary attack rate was 4% for pandemic (H1N1) 2009, 9% for ILI, and 13% for ARI. The secondary attack rate was highest for children <5 years of age (8%-19%) and lowest for adults > or =50 years of age (4%-12%). Early in the outbreak, household transmission primarily occurred from children to other household members and was lower than the transmission rate for seasonal influenza. |
Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans
Garten RJ , Davis CT , Russell CA , Shu B , Lindstrom S , Balish A , Sessions WM , Xu X , Skepner E , Deyde V , Okomo-Adhiambo M , Gubareva L , Barnes J , Smith CB , Emery SL , Hillman MJ , Rivailler P , Smagala J , de Graaf M , Burke DF , Fouchier RA , Pappas C , Alpuche-Aranda CM , Lopez-Gatell H , Olivera H , Lopez I , Myers CA , Faix D , Blair PJ , Yu C , Keene KM , Dotson PD Jr , Boxrud D , Sambol AR , Abid SH , St George K , Bannerman T , Moore AL , Stringer DJ , Blevins P , Demmler-Harrison GJ , Ginsberg M , Kriner P , Waterman S , Smole S , Guevara HF , Belongia EA , Clark PA , Beatrice ST , Donis R , Katz J , Finelli L , Bridges CB , Shaw M , Jernigan DB , Uyeki TM , Smith DJ , Klimov AI , Cox NJ . Science 2009 325 (5937) 197-201 Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1). |
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