Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
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Query Trace: Bollweg B [original query] |
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A diagnostic algorithm for detection of leishmania spp. In human fresh and fixed tissue samples
Silva-Flannery LM , de Almeida ME , da Silva AJ , Bollweg BC , Fair PS , Ritter JM , Paddock CD , Martines RB , Zaki SR . Am J Trop Med Hyg 2024 Leishmaniasis is an important travel-related parasitic infection in the United States. Treatment regimens vary by Leishmania species and require an accurate diagnosis. The sensitivity and specificity of diagnostic methods depend on the type and condition of specimen analyzed. To identify the best algorithm for detection of parasites in fresh and fixed tissue samples, we evaluated parasite cultures, two PCR methods, and Leishmania immunohistochemistry (IHC) in samples received by the CDC from 2012 through 2019. The sensitivity and specificity of IHC assays were evaluated in fresh specimens tested. Diagnostic accuracy for formalin-fixed tissue was evaluated by using PCR-based methods and IHC. Of 100 suspected cases with fresh tissue available, Leishmania spp. infection was identified by PCR in 56% (56/100) of specimens; from these, 80% (45/56) were positive by parasite culture and 59% (33/56) by IHC. Of 420 possible cases where only fixed specimens were available, 58% (244/420) were positive by IHC and/or PCR. Of these, 96% (235/420) were positive by IHC and 84% (204/420) by PCR-based methods. Overall parasite detection using all methodologies was similar for fresh and formalin-fixed tissue specimens (56% versus 58%, respectively). Although PCR-based methods were superior for diagnosis of leishmaniasis and species identification in fresh samples, IHC in combination with PCR increased the accuracy for Leishmania spp. detection in fixed samples. In conclusion, PCR is the most effective method for detecting Leishmania infection in fresh tissue samples, whereas for formalin-fixed samples, IHC and PCR-based methods should be used in combination. |
Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies (preprint)
Chapman AP , Tang X , Lee JR , Chida A , Mercer K , Wharton RE , Kainulainen M , Harcourt JL , Martines RB , Schroeder M , Zhao L , Bryksin A , Zhou B , Bergeron E , Bollweg BC , Tamin A , Thornburg N , Wentworth DE , Petway D , Bagarozzi DA Jr , Finn MG , Goldstein JM . bioRxiv 2020 2020.10.13.338095 The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nanomolar-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.Competing Interest StatementThe authors have declared no competing interest. |
Probable vertical transmission of Alpha variant of concern (B.1.1.7) with evidence of SARS-CoV-2 infection in the syncytiotrophoblast, a case report.
Bullock HA , Fuchs E , Martines RB , Lush M , Bollweg B , Rutan A , Nelson A , Brisso M , Owusu-Ansah A , Sitzman C , Ketterl L , Timmons T , Lopez P , Mitchell E , McCutchen E , Figliomeni J , Iwen P , Uyeki TM , Reagan-Steiner S , Donahue M . Front Med (Lausanne) 2022 9 1099408 INTRODUCTION: Definitive vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been rarely reported. We present a case of a third trimester pregnancy with fetal distress necessitating cesarean section that demonstrated maternal, placental, and infant infection with the SARS-CoV-2 Alpha variant/B.1.1.7. METHODS: CDC's Influenza SARS-CoV-2 Multiplex RT-PCR Assay was used to test for SARS-CoV-2 in a maternal NP swab, maternal plasma, infant NP swab, and formalin-fixed paraffin-embedded (FFPE) placental tissue specimens. Whole genome sequencing (WGS) was performed on maternal plasma, infant, and placental specimens to determine the SARS-CoV-2 genotype. Histopathological evaluation, SARS-CoV-2 immunohistochemistry testing (IHC), and electron microscopy (EM) analysis were performed on placenta, umbilical cord, and membrane FFPE blocks. RESULTS: All specimens tested positive for SARS-CoV-2 by RT-PCR. WGS further revealed identical SARS-CoV-2 sequences from clade 20I/501Y.V1 (lineage Alpha/B.1.1.7) in maternal plasma, infant, and placental specimens. Histopathologic evaluation of the placenta showed histiocytic and neutrophilic intervillositis with fibrin deposition and trophoblast necrosis with positive SARS-CoV-2 immunostaining in the syncytiotrophoblast and electron microscopy evidence of coronavirus. DISCUSSION: These findings suggest vertical transmission of SARS-CoV-2, supported by clinical course timing, identical SARS-CoV-2 genotypes from maternal, placental, and infant samples, and IHC and EM evidence of placental infection. However, determination of the timing or distinction between prepartum and peripartum SARS-CoV-2 transmission remains unclear. |
BK virus associated with small cell carcinoma of bladder in a patient with renal transplant
Loria SJ , Siddiqui NN , Gary JM , Bhatnagar J , Bollweg BC , Ahmed B , Berenson CS . BMJ Case Rep 2022 15 (3) A man in his 70s with a complex medical history, including cadaveric renal transplant, presented with recurrent urinary tract infections. Investigation revealed recurrent urinary pathogens, including Enterobacter cloacae and persistent BK viruria. Cystoscopy revealed a pedunculated mass in the right posterior-lateral wall, inferior to the transplant urethral orifice, and biopsy of this mass showed invasive small cell carcinoma with a prominent adenocarcinoma component. The tumour was treated with complete transurethral resection followed by carboplatin, etoposide and radiation. Laboratory analysis of biopsied samples showed immunostaining and molecular evidence of BK virus DNA in the cancer cells. Follow-up cystoscopies have shown no recurrence of the cancer. |
Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison).
Ritter JM , Wilson TM , Gary JM , Seixas JN , Martines RB , Bhatnagar J , Bollweg BC , Lee E , Estetter L , Silva-Flannery L , Bullock HA , Towner JS , Cossaboom CM , Wendling NM , Amman BR , Harvey RR , Taylor D , Rettler H , Barton Behravesh C , Zaki SR . Vet Pathol 2022 59 (4) 3009858221079665 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans. |
Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies.
Chapman AP , Tang X , Lee JR , Chida A , Mercer K , Wharton RE , Kainulainen M , Harcourt JL , Martines RB , Schroeder M , Zhao L , Bryksin A , Zhou B , Bergeron E , Bollweg BC , Tamin A , Thornburg N , Wentworth DE , Petway D , Bagarozzi DA Jr , Finn MG , Goldstein JM . Sci Rep 2021 11 (1) 9682 The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence. |
Lassa virus antigen distribution and inflammation in the ear of infected strain 13/N guinea pigs
Huynh T , Gary JM , Welch SR , Coleman-McCray J , Harmon JR , Kainulainen MH , Bollweg BC , Ritter JM , Shieh WJ , Nichol ST , Zaki SR , Spiropoulou CF , Spengler JR . Antiviral Res 2020 183 104928 Sudden sensorineuronal hearing loss (SNHL) is reported in approximately one-third of survivors of Lassa fever (LF) and remains the most prominent cause of Lassa virus- (LASV) associated morbidity in convalescence. Using a guinea pig model of LF, and incorporating animals from LASV vaccine trials, we investigated viral antigen distribution and histopathology in the ear of infected animals to elucidate the pathogenesis of hearing loss associated with LASV infection. Antigen was detected only in animals that succumbed to disease and was found within structures of the inner ear that are intimately associated with neural detection and/or translation of auditory stimuli and in adjacent vasculature. No inflammation or viral cytopathic changes were observed in the inner ear or surrounding structures in these animals. In contrast, no viral antigen was detected in the ear of surviving animals. However, all survivors that exhibited clinical signs of disease during the course of infection developed perivascular mononuclear inflammation within and adjacent to the ear, indicating an ongoing inflammatory response in these animals that may contribute to hearing loss. These data contribute to the knowledge of LASV pathogenesis in the auditory system, support an immune-mediated process resulting in LASV-associated hearing loss, and demonstrate that vaccination protecting animals from clinical disease can also prevent infection-associated auditory pathology. |
Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series
Reagan-Steiner S , Gary J , Matkovic E , Ritter JM , Shieh WJ , Martines RB , Werner AK , Lynfield R , Holzbauer S , Bullock H , Denison AM , Bhatnagar J , Bollweg BC , Patel M , Evans ME , King BA , Rose DA , Baldwin GT , Jones CM , Krishnasamy V , Briss PA , Weissman DN , Meaney-Delman D , Zaki SR . Lancet Respir Med 2020 8 (12) 1219-1232 BACKGROUND: Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. METHODS: Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. FINDINGS: 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. INTERPRETATION: Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. FUNDING: US Centers for Disease Control and Prevention. |
Clinical characteristics, histopathology, and tissue immunolocalization of chikungunya virus antigen in fatal cases
Sharp TM , Keating MK , Shieh WJ , Bhatnagar J , Bollweg BC , Levine R , Blau DM , Torres JV , Rivera A , Perez-Padilla J , Munoz-Jordan J , Sanabria D , Fischer M , Garcia BR , Tomashek KM , Zaki SR . Clin Infect Dis 2020 73 (2) e345-e354 BACKGROUND: Death in patients with chikungunya is rare, and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection. METHODS: We identified individuals who died in Puerto Rico during 2014 following an acute illness, and had CHIKV RNA detected by RT-PCR in a pre- or post-mortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews. RESULTS: Thirty CHIKV-infected fatal cases were identified (0.8 per 100,000 population). Median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of four days (range: 1-29) after illness onset. Nearly all (93%) had at least one co-morbidity, most frequently hypertension, diabetes, or obesity. Nine had severe co-morbidities (e.g., chronic heart or kidney disease, sickle cell anemia) or co-infection (e.g., leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in two patients. CONCLUSIONS: Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations. |
Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.
Martines RB , Ritter JM , Matkovic E , Gary J , Bollweg BC , Bullock H , Goldsmith CS , Silva-Flannery L , Seixas JN , Reagan-Steiner S , Uyeki T , Denison A , Bhatnagar J , Shieh WJ , Zaki SR , Covid-Pathology Working Group . Emerg Infect Dis 2020 26 (9) 2005-2015 An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection. |
Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells.
Ayala-Nunez NV , Follain G , Delalande F , Hirschler A , Partiot E , Hale GL , Bollweg BC , Roels J , Chazal M , Bakoa F , Carocci M , Bourdoulous S , Faklaris O , Zaki SR , Eckly A , Uring-Lambert B , Doussau F , Cianferani S , Carapito C , Jacobs FMJ , Jouvenet N , Goetz JG , Gaudin R . Nat Commun 2019 10 (1) 4430 Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention. |
Anthrax epizootic in wildlife, Bwabwata National Park, Namibia, 2017
Cossaboom CM , Khaiseb S , Haufiku B , Katjiuanjo P , Kannyinga A , Mbai K , Shuro T , Hausiku J , Likando A , Shikesho R , Nyarko K , Miller LA , Agolory S , Vieira AR , Salzer JS , Bower WA , Campbell L , Kolton CB , Marston C , Gary J , Bollweg BC , Zaki SR , Hoffmaster A , Walke H . Emerg Infect Dis 2019 25 (5) 947-950 In late September 2017, Bwabwata National Park in Namibia experienced a sudden die-off of hippopotamuses and Cape buffalo. A multiorganizational response was initiated, involving several ministries within Namibia and the US Centers for Disease Control and Prevention. Rapid interventions resulted in zero human or livestock cases associated with this epizootic. |
Lassa virus targeting of anterior uvea and endothelium of cornea and conjunctiva in eye of guinea pig model
Gary JM , Welch SR , Ritter JM , Coleman-McCray J , Huynh T , Kainulainen MH , Bollweg BC , Parihar V , Nichol ST , Zaki SR , Spiropoulou CF , Spengler JR . Emerg Infect Dis 2019 25 (5) 865-874 Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors. |
Optimization of commercially available Zika virus antibodies for use in a laboratory-developed immunohistochemical assay
Bollweg BC , Silva-Flannery L , Spivey P , Hale GL . J Pathol Clin Res 2018 4 (1) 19-25 Zika virus (ZIKV) infection during pregnancy can cause adverse fetal outcomes and severe irreversible congenital birth defects including microcephaly. Immunohistochemistry (IHC) is a valuable diagnostic tool for detecting ZIKV antigens in tissues from cases of fetal loss in women infected with ZIKV, and for providing insights into disease pathogenesis. As a result, there is increasing demand for commercially available ZIKV antibodies for use in IHC assays. ZIKV antibodies were selected and obtained from commercial sources to include both mouse and rabbit hosts, and a variety of antigenic targets. Pretreatment conditions and antibody concentrations resulting in optimal immunohistochemical staining were determined using ZIKV cell control and polymerase chain reaction (PCR)-confirmed ZIKV case control material (fetal brain tissue). Cross-reactivity of the antibodies against other flaviviruses (dengue virus serogroups 1-4, yellow fever virus, Japanese encephalitis virus, West Nile virus) and chikungunya virus was also evaluated. Immunostaining using the commercially available antibodies was compared to a previously validated ZIKV IHC assay used for primary diagnosis. Four antibodies demonstrated optimal staining similar to the previously validated ZIKV IHC assay. Two of the four antibodies cross-reacted with dengue virus, while the other two antibodies showed no cross-reactivity with dengue, other flaviviruses, or chikungunya virus. Differences in the cross-reactivity profiles could not be entirely explained by the antigenic target. Commercially available ZIKV antibodies can be optimized for use in IHC testing to aid in ZIKV diagnostic testing and an evaluation of tissue tropism. |
Crimean-Congo hemorrhagic fever in humanized mice reveals glial cells as primary targets of neurological infection
Spengler JR , Keating MK , McElroy AK , Zivcec M , Coleman-McCray JD , Harmon JR , Bollweg BC , Goldsmith CS , Bergeron E , Keck JG , Zaki SR , Nichol ST , Spiropoulou CF . J Infect Dis 2017 216 (11) 1386-1397 Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. Here we inoculated NSGTM-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low passage CCHF virus strains isolated from human patients. Humanized mice develop lethal disease characterized by histopathological change in the liver and brain. To date, targets of neuroinfection and neuropathology have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggests a role for astrocyte dysfunction in neurologic disease, and distinguish key regions of infection in the CNS for future investigations of CCHF. |
Validity of self-reported concentration and memory problems: Relationship with neuropsychological assessment and depression
Bowler RM , Adams SW , Schwarzer R , Gocheva VV , Roels HA , Kim Y , Kircos CL , Wright CW , Colledge M , Bollweg G , Lobdell DT . J Clin Exp Neuropsychol 2017 39 (10) 1-11 BACKGROUND: This study investigated the validity of self-reported concentration and memory problems (CMP) in residents environmentally exposed to manganese (Mn). METHOD: Self-report of CMP from a health questionnaire (HQ) and the Symptom Checklist-90-Revised (SCL-90-R) was compared to neuropsychological assessment (Trails A&B; Digit Span; Digit Symbol; Similarities; Auditory Consonant Trigrams, ACT; NAB Memory; Rey-Osterrieth, Rey-O, Delayed). Participants included 146 residents from Ohio exposed to air-Mn, with a modeled average concentration of 0.55 microg m-3 (range = 0.01-4.58). RESULTS: Residents were primarily White (94.5%), aged 30-64 years (M = 51.24), with a minimum of 10 years of residence (range = 10-64). Ninety-four (65.3%) participants reported concentration problems, and 107 residents (73.3%) reported memory problems. More participants endorsed CMP on the SCL-90-R than on the HQ. The prevalence of self-reported CMP was higher for women than for men (88.4% vs. 68.3%). Point-biserial and Pearson's correlations between self-reported CMP and neuropsychological test scores were nonsignificant and weak for both the HQ (rpb = -.20 to rpb = .04) and the SCL-90-R (r = -.12 to r = .007). Greater levels of depression, anxiety, and female sex predicted having more self-reported CMP on both the HQ and the SCL-90-R. Air-Mn and blood-Mn were not associated with self-reported CMP. Residential distance from the Mn source accounted for a small proportion of variance (sr2 = .04), although depression remained the largest predictor (sr2 = .21). CONCLUSION: These results indicate that self-report of CMP in Mn-exposed residents appear to be invalid when compared to neuropsychological test scores. The participants' misperception of having CMP is associated with less education and higher levels of depression. Neuropsychological assessment is recommended to attain valid results. |
Facial nerve palsy including Bell's palsy: case definitions and guidelines for collection, analysis, and presentation of immunisation safety data
Rath B , Gidudu JF , Anyoti H , Bollweg B , Caubel P , Chen YH , Cornblath D , Fernandopulle R , Fries L , Galama J , Gibbs N , Grilli G , Grogan P , Hartmann K , Heininger U , Hudson MJ , Izurieta HS , Jevaji I , Johnson WM , Jones J , Keller-Stanislawski B , Klein J , Kohl K , Kokotis P , Li Y , Linder T , Oleske J , Richard G , Shafshak T , Vajdy M , Wong V , Sejvar J . Vaccine 2016 35 (15) 1972-1983 Facial nerve palsy is classified based on the location of its lesion. Central facial nerve palsy is the consequence of an upper motor neuron (UMN) lesion of the 7th cranial nerve, while peripheral palsy is due to a lesion of a lower motor neuron (LMN). Peripheral facial nerve palsy is the partial (i.e., paresis) or complete (i.e., paralysis) loss of function of some or all the structures innervated by the facial nerve (i.e. cranial nerve VII). Facial nerve palsy is also classified by the time course of its development depending on whether acute (minutes to days), subacute (days to weeks) or chronic (longer than weeks). Acute onset facial palsies are common. The most common cause of acute onset, central facial palsy is stroke. However, of the acute onset, peripheral facial palsies, the most common syndrome is that of idiopathic, acute onset, peripheral facial palsy, better known as Bell's palsy. Henceforth in this document, it will be understood that, when discussing Bell's palsy, we are referring to peripheral facial palsy that is ‘acute-onset’. | Clinical signs of peripheral facial nerve palsy include loss of facial tone with obliteration of the naso-labial fold, inability to raise the eyebrows and wrinkle the forehead, smile, open or draw the corner of the mouth, and completely close the eye on the affected side [1], [2], [3], [4]. They may further include hyperacusis, dryness of eye and decreased salivation. Peripheral facial nerve palsy most commonly presents on one side of the face, leading to facial asymmetry, or “facial droop” [1], [5]. Simultaneous bilateral acute-onset cases have also been described and are now recognised as an uncommon clinical feature [6], [7], [8], [9], [10], [11], [12], [13]. |
Ebola virus disease in pregnancy: clinical, histopathologic and immunohistochemical findings
Muehlenbachs A , de la Rosa Vazquez O , Bausch DG , Schafer IJ , Paddock CD , Nyakio JP , Lame P , Bergeron E , McCollum AM , Goldsmith CS , Bollweg BC , Prieto MA , Lushima RS , Ilunga BK , Nichol ST , Shieh WJ , Stroher U , Rollin PE , Zaki SR . J Infect Dis 2016 215 (1) 64-69 Here we describe clinicopathologic features of EVD in pregnancy. One woman infected with Sudan virus in Gulu, Uganda in 2000 had a stillbirth and survived, and another woman with Bundibugyo virus had a livebirth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemistry, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malaria pigment-laden macrophages. These data suggest trophoblast infection may be a mechanism of transplacental ebolavirus transmission. |
Cardiac tropism of Borrelia burgdorferi: an autopsy study of sudden cardiac death associated with Lyme carditis
Muehlenbachs A , Bollweg BC , Schulz TJ , Forrester JD , DeLeon Carnes M , Molins C , Ray GS , Cummings PM , Ritter JM , Blau DM , Andrew TA , Prial M , Ng DL , Prahlow JA , Sanders JH , Shieh WJ , Paddock CD , Schriefer ME , Mead P , Zaki SR . Am J Pathol 2016 186 (5) 1195-205 Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues. |
Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.
Igietseme JU , Omosun Y , Stuchlik O , Reed MS , Partin J , He Q , Joseph K , Ellerson D , Bollweg B , George Z , Eko FO , Bandea C , Liu H , Yang G , Shieh WJ , Pohl J , Karem K , Black CM . PLoS One 2015 10 (12) e0145198 Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV oncogene-transformed epithelial cells. These findings provide a novel understanding of the molecular pathogenesis of chlamydia-associated diseases, which may guide a rational prevention strategy. |
Environmental exposure to manganese in air: Associations with cognitive functions
Bowler RM , Kornblith ES , Gocheva VV , Colledge MA , Bollweg G , Kim Y , Beseler CL , Wright CW , Adams SW , Lobdell DT . Neurotoxicology 2015 49 139-48 Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.03 to 1.61 μg/m(3) in Marietta and 0.01-6.32 μg/m(3) in East Liverpool. A comprehensive screening test battery of cognitive function, including the domains of abstract thinking, attention/concentration, executive function and memory was administered. The mean age of the participants was 56 years (±10.8 years). Participants were mostly female (59.1) and primarily white (94.6%). Significant relationships (p<0.05) were found between Mn exposure and performance on working and visuospatial memory (e.g., Rey-O Immediate β=-0.19, Rey-O Delayed β=-0.16) and verbal skills (e.g., Similarities β=-0.19). Using extensive cognitive testing and computer modeling of 10-plus years of measured air monitoring data, this study suggests that long-term environmental exposure to high levels of air-Mn, the exposure metric of this paper, may result in mild deficits of cognitive function in adult populations. |
Environmental exposure to manganese in air: associations with tremor and motor function
Bowler RM , Beseler CL , Gocheva VV , Colledge M , Kornblith ES , Julian JR , Kim Y , Bollweg G , Lobdell DT . Sci Total Environ 2015 541 646-654 BACKGROUND: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products. METHODS: Chronic (≥10years) exposure to ambient air Mn in adult residents and effects on neuropsychological and neurological outcomes were investigated. Participants from Marietta (n=100) and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year period. Adult Mn-exposed residents' psychomotor ability was assessed using Finger Tapping, Hand Dynamometer, Grooved Pegboard, and the Computerized Adaptive Testing System (CATSYS) Tremor system. Bayesian structural equation modeling was used to assess associations between air-Mn and motor function and tremor. RESULTS: Air-Mn exposure was significantly correlated in bivariate analyses with the tremor test (CATSYS) for intensity, center frequency and harmonic index. The Bayesian path analysis model showed associations of air-Mn with the CATSYS non-dominant center frequency and harmonic index; while the Bayesian structural equation model revealed associations between air-Mn and lower Finger Tapping scores. Household income was significantly associated with motor dysfunction but not with tremor. CONCLUSION: Tremor and motor function were associated with higher exposure to airborne Mn. |
Phylogeography of Rickettsia rickettsii genotypes associated with fatal Rocky Mountain spotted fever.
Paddock CD , Denison AM , Lash RR , Liu L , Batten BC , Dahlgren FS , Kanamura CT , Angerami RN , Pereira Dos Santos FC , Brasil Martines R , Karpathy SE . Am J Trop Med Hyg 2014 91 (3) 589-97 Rocky Mountain spotted fever (RMSF), a tick-borne zoonosis caused by Rickettsia rickettsii, is among the deadliest of all infectious diseases. To identify the distribution of various genotypes of R. rickettsii associated with fatal RMSF, we applied molecular typing methods to samples of DNA extracted from formalin-fixed, paraffin-embedded tissue specimens obtained at autopsy from 103 case-patients from seven countries who died of RMSF. Complete sequences of one or more intergenic regions were amplified from tissues of 30 (29%) case-patients and revealed a distribution of genotypes consisting of four distinct clades, including the Hlp clade, regarded previously as a non-pathogenic strain of R. rickettsii. Distinct phylogeographic patterns were identified when composite case-patient and reference strain data were mapped to the state and country of origin. The phylogeography of R. rickettsii is likely determined by ecological and environmental factors that exist independently of the distribution of a particular tick vector. |
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