Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-21 (of 21 Records) |
Query Trace: Glaser K[original query] |
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Early effects of scaling up dolutegravir-based arv regimens among children living with HIV in Malawi
Makonokaya L , Maida A , Kalitera LU , Wang A , Kapanda L , Kayira D , Bottoman M , Nkhoma H , Dunga S , Joaki Z , Chamanga R , Nkanaunena K , Hrapcak S , Nyirenda R , Chiwandira B , Maulidi M , Woelk G , Machekano R , Maphosa T . AIDS Behav 2024 Viral suppression (VS) in children has remained suboptimal compared to that in adults. We evaluated the impact of transitioning children weighing < 20 kg to a pediatric formulation of dolutegravir (pDTG) on VS in Malawi. We analyzed routine retrospective program data from electronic medical record systems pooled across 169 healthcare facilities in Malawi supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). We included children who weighed < 20 kg and received antiretroviral therapy (ART) between July 2021-June 2022. Using descriptive statistics, we summarized demographic and clinical characteristics, ART regimens, ART adherence, and VS. We used logistic regression to identify factors associated with post-transition VS. A total of 2468 Children Living with HIV (CLHIV) were included, 55.3% of whom were < 60 months old. Most (83.8%) had initiated on non-DTG-based ART; 71.0% of these had a viral load (VL) test result before transitioning to pDTG, and 62.5% had VS. Nearly all (99.9%) CLHIV transitioned to pDTG-based regimens. Six months after the transition, 52.7% had good ART adherence, and 38.6% had routine VL testing results; 81.7% achieved VS. Post-transition VS was associated with good adherence and pre-transition VS: adjusted odds ratios of 2.79 (95% CI 1.65-4.71), p < 0.001 and 5.32 (95% CI 3.23-9.48), p < 0.001, respectively. After transitioning to pDTG, VS was achieved in most children tested within the first 6 months. However, adherence remained suboptimal post-transition and VL testing at 6 months was limited. Interventions to improve VL testing and enhance ART adherence are still needed in CLHIV on pDTG-based regimens. |
Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana
Mannathoko N , Lautenbach E , Mosepele M , Otukile D , Sewawa K , Glaser L , Cressman L , Cowden L , Alby K , Jaskowiak-Barr A , Gross R , Mokomane M , Paganotti GM , Styczynski A , Smith RM , Snitkin E , Wan T , Bilker WB , Richard-Greenblatt M . J Med Microbiol 2023 72 (11) Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), isolated from rectal swabs.Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate Escherichia coli and Klebsiella spp., Enterobacter spp. and Citrobacter spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4-93.3) and 86.8 % (95 % CI, 82.0-90.7) for E. coli and 88.1 % (95 % CI 83.2-92.1) and 87.6 % (95 % CI 84.7-90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country. |
Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Risk factors for community colonization with extended-spectrum cephalosporin-resistant enterobacterales (escre) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study
Lautenbach E , Mosepele M , Smith RM , Styczynski A , Gross R , Cressman L , Jaskowiak-Barr A , Alby K , Glaser L , Richard-Greenblatt M , Cowden L , Sewawa K , Otukile D , Paganotti GM , Mokomane M , Bilker WB , Mannathoko N . Clin Infect Dis 2023 77 S89-s96 BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs. |
Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) in healthcare and community settings in Botswana: an antibiotic resistance in communities and hospitals (ARCH) study.
Mannathoko N , Mospele M , Gross R , Smith RM , Alby K , Glaser L , Richard-Greenblatt M , Dumm R , Sharma A , Jaskowiak-Barr A , Cressman L , Sewawa K , Cowden L , Reesey E , Otukile D , Paganotti GM , Mokomane M , Lautenbach E . Int J Infect Dis 2022 122 313-320 OBJECTIVES: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. We sought to characterize colonization data critical for larger antibiotic resistance surveillance efforts. METHODS: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics as well as adults and children in the community. All participants had rectal swabs obtained for identification of ESCrE and CRE. RESULTS: Enrollment occurred from 1/15/20-9/4/20 but paused from 4/2/20-5/21/20 due to a countrywide COVID-19 lockdown. Of 5,088 individuals approached, 2,469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (p<0.001). 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (p<0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher pre-lockdown vs post-lockdown. CONCLUSIONS: ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased following a countrywide lockdown. |
Development and Evaluation of a Molecular Hepatitis A Virus Assay for Serum and Stool Specimens.
Kozak RA , Rutherford C , Richard-Greenblatt M , Chau NYE , Cabrera A , Biondi M , Borlang J , Day J , Osiowy C , Ramachandran S , Mayer N , Glaser L , Smieja M . Viruses 2022 14 (1) Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10-30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5'-untranslated region (5'-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention. |
Acute fulminant cerebral edema: A newly recognized phenotype in children with suspected encephalitis
Krishnan P , Glenn OA , Samuel MC , Sheriff H , Foster-Barber A , Sejvar JJ , Roy-Burman A , Wadford DA , Preas CP , Tureen JH , Glaser CA . J Pediatric Infect Dis Soc 2020 10 (3) 289-294 BACKGROUND: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. METHODS: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. RESULTS: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. CONCLUSIONS: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition. |
Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . Nat Med 2019 25 (11) 1748-1752 Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM. |
The epidemiology and clinical features of Balamuthia mandrillaris disease in the United States, 1974 - 2016
Cope JR , Landa J , Nethercut H , Collier SA , Glaser C , Moser M , Puttagunta R , Yoder JS , Ali IK , Roy SL . Clin Infect Dis 2018 68 (11) 1815-1822 Background: Balamuthia mandrillaris is a free-living ameba that causes rare, nearly always fatal disease in humans and animals worldwide. B. mandrillaris has been isolated from soil, dust, and water. Initial entry of Balamuthia into the body is likely via the skin or lungs. To date, only individual case reports and small case series have been published. Methods: The Centers for Disease Control and Prevention (CDC) maintains a free-living ameba (FLA) registry and laboratory. To be entered into the registry, a Balamuthia case must be laboratory-confirmed. Several sources were used to complete entries in the registry, including case report forms, CDC laboratory results, published case reports, and media information. SAS(c) version 9.3 software was used to calculate descriptive statistics and frequencies. Results: We identified 109 case reports of Balamuthia disease between 1974 and 2016. Most (99%) had encephalitis. The median age was 36 years (range 4 months to 91 years). Males accounted for 68% of the case patients. California had the highest number of case reports followed by Texas and Arizona. Hispanics constituted 55% for those with documented ethnicity. Exposure to soil was commonly reported. Among those with a known outcome, 90% of patients died. Conclusions: Balamuthia disease in the United States is characterized by a highly fatal encephalitis that affects patients of all ages. Hispanics were disproportionately affected. The southwest region of the U.S. reported the most cases. Clinician awareness of Balamuthia as a cause of encephalitis might lead to earlier diagnosis and initiation of treatment, resulting in better outcomes. |
Possible congenital Zika syndrome in older children due to earlier circulation of Zika virus
Chu V , Petersen LR , Moore CA , Meaney-Delman D , Nelson G , Christian Sonne D , Dodge NN , Glaser C , Rasmussen SA . Am J Med Genet A 2018 176 (9) 1882-1889 Congenital Zika syndrome (CZS) was identified following a large Zika virus (ZIKV) outbreak in Brazil in 2015. Two children with clinical presentations consistent with CZS, ages 7 and 8 years old, are described. Both mothers lived in Cambodia, a region with known ZIKV, during their pregnancies and reported fever and rash in the second trimester. The infants were born with severe microcephaly. Testing for congenital infection at birth and genetic testing were unremarkable. In 2017, serologic testing for both mothers were consistent with prior ZIKV infection. Review of infant neuroimaging demonstrated ventriculomegaly, severe cerebral atrophy, and subcortical calcifications consistent with CZS. Given the maternal symptoms suggesting ZIKV infection during pregnancy and the combination of clinical and radiological features unique to CZS, CZS is strongly suspected in these children, suggesting that CZS occurred before the 2013-2014 French Polynesia outbreak. As such, CZS should be considered in older children with congenital microcephaly of unknown etiology and a history consistent with possible ZIKV exposure. |
The eco-epidemiology of Pacific Coast tick fever in California
Padgett KA , Bonilla D , Eremeeva ME , Glaser C , Lane RS , Porse CC , Castro MB , Messenger S , Espinosa A , Hacker J , Kjemtrup A , Ryan B , Scott JJ , Hu R , Yoshimizu MH , Dasch GA , Kramer V . PLoS Negl Trop Dis 2016 10 (10) e0005020 Rickettsia philipii (type strain "Rickettsia 364D"), the etiologic agent of Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF in 2008, 13 additional human cases have been reported in California, more than half of which were pediatric cases. The most common features of PCTF are the presence of at least one necrotic lesion known as an eschar (100%), fever (85%), and headache (79%); four case-patients required hospitalization and four had multiple eschars. Findings presented here implicate the nymphal or larval stages of D. occidentalis as the primary vectors of R. philipii to people. Peak transmission risk from ticks to people occurs in late summer. Rickettsia philipii DNA was detected in D. occidentalis ticks from 15 of 37 California counties. Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D. occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R. philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum infection prevalence of 0.4% in larval pools. Although most human cases of PCTF have been reported from northern California, acarological surveillance suggests that R. philipii may occur throughout the distribution range of D. occidentalis. |
Hospital-based enhanced surveillance for West Nile virus neuroinvasive disease
Lindsey NP , Fischer M , Neitzel D , Schiffman E , Salas ML , Glaser CA , Sylvester T , Kretschmer M , Bunko A , Staples JE . Epidemiol Infect 2016 144 (15) 1-6 Accurate data on the incidence of West Nile virus (WNV) disease are important for directing public health education and control activities. The objective of this project was to assess the underdiagnosis of WNV neuroinvasive disease through laboratory testing of patients with suspected viral meningitis or encephalitis at selected hospitals serving WNV-endemic regions in three states. Of the 279 patients with cerebrospinal fluid (CSF) specimens tested for WNV immunoglobulin M (IgM) antibodies, 258 (92%) were negative, 19 (7%) were positive, and two (1%) had equivocal results. Overall, 63% (12/19) of patients with WNV IgM-positive CSF had WNV IgM testing ordered by their attending physician. Seven (37%) cases would not have been identified as probable WNV infections without the further testing conducted through this project. These findings indicate that over a third of WNV infections in patients with clinically compatible neurological illness might be undiagnosed due to either lack of testing or inappropriate testing, leading to substantial underestimates of WNV neuroinvasive disease burden. Efforts should be made to educate healthcare providers and laboratorians about the local epidemiology of arboviral diseases and the optimal tests to be used in different clinical situations. |
Acute flaccid myelitis in the United States-August - December 2014: Results of nation-wide surveillance
Sejvar JJ , Lopez AS , Cortese MM , Leshem E , Pastula DM , Miller L , Glaser C , Kambhampati A , Shioda K , Aliabadi N , Fischer M , Gregoricus N , Lanciotti R , Nix WA , Sakthivel SK , Schmid DS , Seward JF , Tong S , Oberste MS , Pallansch M , Feikin D . Clin Infect Dis 2016 63 (6) 737-745 BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the U.S., coincident with a national outbreak of enterovirus-D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported to Centers for Disease Control and Prevention (CDC) standardized clinical, epidemiologic, and radiologic information on AFM cases, and submitted biological samples for testing. Cases were≤21 years old, with acute onset of limb weakness 01 August-31 December 2014 and spinal MRI showing lesions predominantly restricted to gray matter. RESULTS: From August-December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but one case was hospitalized; none died. CSF pleocytosis (>5 white blood cells/mm3) was common (81%). At CDC, one CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time PCR, although the specimen had >3,000 red blood cells/mm3 The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 14 AFM cases reported from 11 states. CONCLUSIONS: Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology and etiology of AFM. |
Acute flaccid myelitis of unknown etiology in California, 2012-2015
Van Haren K , Ayscue P , Waubant E , Clayton A , Sheriff H , Yagi S , Glenn-Finer R , Padilla T , Strober JB , Aldrovandi G , Wadford DA , Chiu CY , Xia D , Harriman K , Watt JP , Glaser CA . JAMA 2015 314 (24) 2663-2671 IMPORTANCE: There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology. OBJECTIVE: To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury. DESIGN, SETTING, AND PARTICIPANTS: Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing. MAIN OUTCOMES AND MEASURES: Case incidence and infectious agent association. RESULTS: Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100000 person-years) compared with other monitoring periods (0.028 cases per 100000 person-years; P <.001). CONCLUSIONS AND RELEVANCE: In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged. |
Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014
Ayscue P , Haren KV , Sheriff H , Waubant E , Waldron P , Yagi S , Yen C , Clayton A , Padilla T , Pan C , Reichel J , Harriman K , Watt J , Sejvar J , Nix WA , Feikin D , Glaser C . MMWR Morb Mortal Wkly Rep 2014 63 (40) 903-6 In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines. |
Insights into pediatric herpes simplex encephalitis from a cohort of 21 children from the California Encephalitis Project, 1998-2011
To TM , Soldatos A , Sheriff H , Schmid DS , Espinosa N , Cosentino G , Preas CP , Glaser CA . Pediatr Infect Dis J 2014 33 (12) 1287-8 Twenty-one children with confirmed herpes simplex encephalitis were identified in the California Encephalitis Project. Noteworthy features included six (29%) patients with an initial negative herpes simplex virus CSF PCR test and 13 (59%) patients with extra-temporal lobe involvement identified by neuroimaging. Eleven cases were <4 years of age, but all four fatal cases occurred in adolescents. |
Influenza-associated intensive-care unit admissions and deaths - California, September 29, 2013-January 18, 2014
Ayscue P , Murray E , Uyeki T , Zipprich J , Harriman K , Salibay C , Kang M , Luu A , Glenn-Finer R , Watt J , Glaser C , Louie J . MMWR Morb Mortal Wkly Rep 2014 63 (7) 143-7 The California Department of Public Health (CDPH) conducts surveillance on severe influenza illness among California residents aged <65 years. Severe cases are defined as those resulting in admission to an intensive care unit (ICU) or death; reporting of ICU cases is voluntary, and reporting of fatal cases is mandatory. This report describes the epidemiologic, laboratory, and clinical characteristics of ICU and fatal influenza cases with symptom onset on or after September 29, 2013, and reported by January 18, 2014 of the 2013-14 influenza season. At the time of this report, local health jurisdictions (LHJs) in California had reported 94 deaths and 311 ICU admissions of patients with a positive influenza test result. The 405 reports of severe cases (i.e., fatal and ICU cases combined) were more than in any season since the 2009 pandemic caused by the influenza A (H1N1)pdm09 (pH1N1) virus. The pH1N1 virus is the predominant circulating influenza virus this season. Of 405 ICU and fatal influenza cases, 266 (66%) occurred among patients aged 41-64 years; 39 (10%) severe influenza illnesses occurred among children aged <18 years. Only six (21%) of 28 patients with fatal illness whose vaccination status was known had received 2013-14 seasonal influenza vaccine ≥2 weeks before symptom onset. Of 80 patients who died for whom sufficient information was available, 74 (93%) had underlying medical conditions known to increase the risk for severe influenza, as defined by the Advisory Committee on Immunization Practices (ACIP). Of 47 hospitalized patients with fatal illness and known symptom onset and antiviral therapy dates, only eight (17%) received neuraminidase inhibitors within 48 hours of symptom onset. This report supports previous recommendations that vaccination is important to prevent influenza virus infections that can result in ICU admission or death, particularly in high-risk populations, and that empiric antiviral treatment should be promptly initiated when influenza virus infection is suspected in hospitalized patients, despite negative results from rapid diagnostic tests. |
"Eczema coxsackium" and unusual cutaneous findings in an enterovirus outbreak
Mathes EF , Oza V , Frieden IJ , Cordoro KM , Yagi S , Howard R , Kristal L , Ginocchio CC , Schaffer J , Maguiness S , Bayliss S , Lara-Corrales I , Garcia-Romero MT , Kelly D , Salas M , Oberste MS , Nix WA , Glaser C , Antaya R . Pediatrics 2013 132 (1) e149-57 OBJECTIVE: To characterize the atypical cutaneous presentations in the coxsackievirus A6 (CVA6)-associated North American enterovirus outbreak of 2011-2012. METHODS: We performed a retrospective case series of pediatric patients who presented with atypical cases of hand, foot, and mouth disease (HFMD) from July 2011 to June 2012 at 7 academic pediatric dermatology centers. Patients were included if they tested positive for CVA6 or if they met clinical criteria for atypical HFMD (an enanthem or exanthem characteristic of HFMD with unusual morphology or extent of cutaneous findings). We collected demographic, epidemiologic, and clinical data including history of skin conditions, morphology and extent of exanthem, systemic symptoms, and diagnostic test results. RESULTS: Eighty patients were included in this study (median age 1.5 years, range 4 months-16 years). Seventeen patients were CVA6-positive, and 63 met clinical inclusion criteria. Ninety-nine percent of patients exhibited a vesiculobullous and erosive eruption; 61% of patients had rash involving >10% body surface area. The exanthem had a perioral, extremity, and truncal distribution in addition to involving classic HFMD areas such as palms, soles, and buttocks. In 55% of patients, the eruption was accentuated in areas of eczematous dermatitis, termed "eczema coxsackium." Other morphologies included Gianotti-Crosti-like (37%), petechial/purpuric (17%) eruptions, and delayed onychomadesis and palm and sole desquamation. There were no patients with serious systemic complications. CONCLUSIONS: The CVA6-associated enterovirus outbreak was responsible for an exanthem potentially more widespread, severe, and varied than classic HFMD that could be confused with bullous impetigo, eczema herpeticum, vasculitis, and primary immunobullous disease. |
Fatal transplant-associated West Nile virus encephalitis and public health investigation-California, 2010
Rabe IB , Schwartz BS , Farnon EC , Josephson SA , Webber AB , Roberts JP , de Mattos AM , Gallay BJ , van Slyck S , Messenger SL , Yen CJ , Bloch EM , Drew CP , Fischer M , Glaser CA . Transplantation 2013 96 (5) 463-8 BACKGROUND: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. METHODS: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. RESULTS: Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor's serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. CONCLUSIONS: Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients. |
A population-based study of neurologic manifestations of severe influenza A(H1N1)pdm09 in California
Glaser CA , Winter K , Dubray K , Harriman K , Uyeki TM , Sejvar J , Gilliam S , Louie JK . Clin Infect Dis 2012 55 (4) 514-20 BACKGROUND: Reported influenza-associated neurologic complications are generally limited to case series or case reports. We conducted a population-based study of neurologic manifestations associated with severe and fatal influenza A(H1N1)pdm09 (2009 H1N1) cases. METHODS: Medical records of patients with fatal or severe (hospitalized in intensive care unit) laboratory-confirmed 2009 H1N1 reported to the California Department of Public Health from 15 April 2009 through 31 December 2009 were reviewed to identify those with primary neurological manifestations. Cases with secondary neurologic manifestations (eg, hypoxia) were excluded. Primary influenza-associated neurologic complications (INCs) were classified into 4 groups: encephalopathy/encephalitis, seizures, meningitis, and other. Severe 2009 H1N1-associated neurologic incidence was calculated by using estimates of 2009 H1N1 illnesses in California. RESULTS: Of 2069 reported severe or fatal 2009 H1N1 cases, 419 (20%) had neurologic manifestations. Of these, 77 (18%) met our definition of INCs: encephalopathy/encephalitis (n = 29), seizures (n = 44), meningitis (n = 3), and other (Guillain-Barre Syndrome) (n = 1). The median age was 9 years (range, 4 months-92 years); the highest rate of disease was among pediatric Asian/Pacific Islanders (12.79 per 1,000,000) compared with pediatric white, non-Hispanics (3.09 per 1,000,000), Hispanics (4.58 per 1,000,000), and blacks (6.57 per 1,000,000). The median length of stay (LOS) was 4 days (range, 1-142), and there were 4 fatalities. The estimated incidence of INCs was 1.2 per 100,000 symptomatic 2009 H1N1 illnesses. CONCLUSIONS: Influenza-associated neurologic complications were observed in 4% of patients with fatal or severe 2009 H1N1. They were observed most often in pediatric patients, and Asian/Pacific Islanders appear to be overrepresented compared with the California population. Most patients with INCs had a relatively short LOS, and there were few fatalities. |
Pap testing and sexual activity among young women in the United States
Saraiya M , Martinez G , Glaser K , Kulasingam S . Obstet Gynecol 2009 114 (6) 1213-1219 OBJECTIVE: To understand whether and how recency of sexual activity is associated with Pap testing rates among young women. METHODS: We analyzed data on self-reported receipt of Pap testing and initiation of sexual activity among young women and girls aged 15 to 24 years using the 2002 National Survey of Family Growth, an in-person, population-based survey of reproductive-aged men and women in the United States. The primary outcome was receiving a Pap test and its relationship to initiation of sexual activity. A multivariable model was used to predict the probability of having had a Pap test in the previous 12 months. RESULTS: Thirty-three percent of the 2,513 women had never had sex. Of these, 13.9% had had a Pap test in the previous year. Sixty-seven percent of sexually-active women aged 15-24 reported receiving a Pap test (corresponding to 13.1 million tests). Approximately 59% women aged 15-20 years old who reported having initiated sexual activity in the previous 3 years also reported a Pap test in the previous year. CONCLUSION: The current guidelines recommend screening 3 years after initiation of vaginal intercourse or at age 21, whichever is earlier. Contrary to the current guidelines, many young women who have not had sex or who initiated sex within the previous 3 years reported having had a Pap test. Assuming that the patterns observed in this study persist, there is an urgent need for education regarding the need to adhere to guidelines to reduce the burden of potentially unnecessary Pap tests in young women. LEVEL OF EVIDENCE: III. |
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