Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-28 (of 28 Records) |
Query Trace: Winkler AS[original query] |
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Neuroinvasive bacillus cereus infection in immunocompromised hosts: Epidemiologic investigation of 5 patients with acute myeloid leukemia
Little JS , Coughlin C , Hsieh C , Lanza M , Huang WY , Kumar A , Dandawate T , Tucker R , Gable P , Vazquez Deida AA , Moulton-Meissner H , Stevens V , McAllister G , Ewing T , Diaz M , Glowicz J , Winkler ML , Pecora N , Kubiak DW , Pearson JC , Luskin MR , Sherman AC , Woolley AE , Brandeburg C , Bolstorff B , McHale E , Fortes E , Doucette M , Smole S , Bunnell C , Gross A , Platt D , Desai S , Fiumara K , Issa NC , Baden LR , Rhee C , Klompas M , Baker MA . Open Forum Infect Dis 2024 11 (3) ofae048 BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. |
Evaluation of a point-of-care test for the diagnosis of Taenia solium neurocysticercosis in rural southern Tanzania: a diagnostic accuracy study
Stelzle D , Makasi CE , Schmidt V , Van Damme I , Trevisan C , Ruether C , Fleury A , Noh J , Handali S , Dorny P , Magnussen P , Zulu G , Mwape KE , Bottieau E , Gabriël S , Ngowi BJ , Winkler AS . Lancet Infect Dis 2023 24 (1) 98-106 BACKGROUND: Neurocysticercosis is a common cause of epilepsy in Taenia solium-endemic areas in sub-Saharan Africa but is often undiagnosed because of an absence of affordable diagnostic tools. This study evaluated the diagnostic accuracy of a T solium cysticercosis antibody-detecting lateral-flow point-of-care assay (TS POC test) for the neuroimaging-based diagnosis of neurocysticercosis. METHODS: Patients with epileptic seizures or severe progressive headache were recruited consecutively from three hospitals in southern Tanzania. All patients were tested with the TS POC test. All patients positive for cysticercosis on the TS POC test and every tenth patient who was negative for cysticercosis received a brain CT examination and underwent reference testing for T solium cysticercosis (ie, rT24H-EITB, LLGP-EITB, and antigen ELISA). The primary outcome of the study was the sensitivity of the TS POC test for the diagnosis of neurocysticercosis. FINDINGS: Of the 601 recruited participants, 102 (17%) tested positive for cysticercosis with the TS POC test. Overall, 48 (62%) of the 77 patients positive for cysticercosis and five (17%) of the 29 patients negative for cysticercosis on the TS POC test had CT-confirmed neurocysticercosis. The TS POC test yielded a sensitivity of 49% (uncertainty interval [UI] 41-58) for neurocysticercosis. Sensitivity was similar to that of the rT24H-EITB (44%, UI 37-51) and the antigen ELISA (50%, 43-56). For the subset of neurocysticercosis cases with at least one active (ie, vesicular) lesion, sensitivity was above 98% for the TS POC test, the rT24H-ETIB, and the antigen ELISA. INTERPRETATION: The TS POC test showed promising results for the diagnosis of neurocysticercosis in patients with vesicular lesions, which need to be confirmed in a larger study. This test could be considered to support policies on screening patients with suspected neurocysticercosis in clinical settings, which would allow appropriate referral for neuroimaging and early treatment. FUNDING: German Federal Ministry of Education and Research and the European & Developing Countries Clinical Trials Partnership. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section. |
Investigating employment quality for population health and health equity: A perspective of power
Fujishiro K , Ahonen EQ , Winkler M . Int J Environ Res Public Health 2022 19 (16) Employment quality (EQ) has gained increasing attention as a determinant of health, but the debate among occupational health researchers over the measurement of EQ poses a challenge to advancing the literature. This is especially problematic when the concept is used across social, cultural, and national borders, as EQ is shaped by power dynamics within sociopolitical and economic contexts that are specific to each society. Investigating EQ in context could help develop a clearer understanding as to why EQ is configured in certain ways, how best EQ could be measured, how EQ impacts health, and ultimately how EQ could be improved. In this paper, we propose that attention to social context-and in particular power-may help advance the research on EQ and health. We present an allegory, or a visual description, that articulates the power balance in the employer-worker relation as well as in the sociopolitical context in which the employer-worker relation takes place. We end by proposing specific approaches for occupational health researchers to incorporate a perspective of power in EQ research that may clarify the concept and measurement of EQ. A clearer recognition of EQ as a product of power in social context aligns with the research approach of addressing work as a social structural determinant of health. |
Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.
Singh B , Lant S , Cividini S , Cattrall JWS , Goodwin LC , Benjamin L , Michael BD , Khawaja A , Matos AMB , Alkeridy W , Pilotto A , Lahiri D , Rawlinson R , Mhlanga S , Lopez EC , Sargent BF , Somasundaran A , Tamborska A , Webb G , Younas K , Al Sami Y , Babu H , Banks T , Cavallieri F , Cohen M , Davies E , Dhar S , Fajardo Modol A , Farooq H , Harte J , Hey S , Joseph A , Karthikappallil D , Kassahun D , Lipunga G , Mason R , Minton T , Mond G , Poxon J , Rabas S , Soothill G , Zedde M , Yenkoyan K , Brew B , Contini E , Cysique L , Zhang X , Maggi P , van Pesch V , Lechien J , Saussez S , Heyse A , Brito Ferreira ML , Soares CN , Elicer I , Eugenín-von Bernhardi L , Ñancupil Reyes W , Yin R , Azab MA , Abd-Allah F , Elkady A , Escalard S , Corvol JC , Delorme C , Tattevin P , Bigaut K , Lorenz N , Hornuss D , Hosp J , Rieg S , Wagner D , Knier B , Lingor P , Winkler AS , Sharifi-Razavi A , Moein ST , SeyedAlinaghi S , JamaliMoghadamSiahkali S , Morassi M , Padovani A , Giunta M , Libri I , Beretta S , Ravaglia S , Foschi M , Calabresi P , Primiano G , Servidei S , Biagio Mercuri N , Liguori C , Pierantozzi M , Sarmati L , Boso F , Garazzino S , Mariotto S , Patrick KN , Costache O , Pincherle A , Klok FA , Meza R , Cabreira V , Valdoleiros SR , Oliveira V , Kaimovsky I , Guekht A , Koh J , Fernández Díaz E , Barrios-López JM , Guijarro-Castro C , Beltrán-Corbellini Á , Martínez-Poles J , Diezma-Martín AM , Morales-Casado MI , García García S , Breville G , Coen M , Uginet M , Bernard-Valnet R , Du Pasquier R , Kaya Y , Abdelnour LH , Rice C , Morrison H , Defres S , Huda S , Enright N , Hassell J , D'Anna L , Benger M , Sztriha L , Raith E , Chinthapalli K , Nortley R , Paterson R , Chandratheva A , Werring DJ , Dervisevic S , Harkness K , Pinto A , Jillella D , Beach S , Gunasekaran K , Rocha Ferreira Da Silva I , Nalleballe K , Santoro J , Scullen T , Kahn L , Kim CY , Thakur KT , Jain R , Umapathi T , Nicholson TR , Sejvar JJ , Hodel EM , Tudur Smith C , Solomon T . PLoS One 2022 17 (6) e0263595 BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. |
Timing of headache after COVID-19 vaccines and its association with cerebrovascular events: An analysis of 41,700 VAERS reports.
Garcia-Azorin D , Baykan B , Beghi E , Doheim MF , Fernandez-de-Las-Penas C , Gezegen H , Guekht A , Hoo FK , Santacatterina M , Sejvar J , Tamborska AA , Thakur KT , Westenberg E , Winkler AS , Frontera JA . Cephalalgia 2022 42 3331024221099231 BACKGROUND: Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. METHODS: All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. RESULTS: There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75-0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63-76) for ischemic stroke and 0.76 (95% CI: 0.67-84) for intracranial hemorrhage, and >99% negative predictive value. CONCLUSION: Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events. |
Ictal electroencephalographic characteristics of nodding syndrome: A comparative case-series from South Sudan, Tanzania, and Uganda
Mazumder R , Lagoro DK , Nariai H , Danieli A , Eliashiv D , Engel JJr , Dalla Bernardina B , Kegele J , Lerche H , Sejvar J , Matuja W , Schmutzhard E , Bonanni P , De Polo G , Wagner T , Winkler AS . Ann Neurol 2022 92 (1) 75-80 Nodding syndrome (NS) is a poorly understood form of childhood-onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp-and-slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30- 70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub-Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. This article is protected by copyright. All rights reserved. |
Diesel aerosols in an underground coal mine
Bugarski AD , Vanderslice S , Hummer JA , Barone T , Mischler SE , Peters S , Cochrane S , Winkler J . Min Metall Explor 2022 39 (3) 937-945 The case study was conducted in an underground coal mine to characterize submicron aerosols at a continuous miner (CM) section, assess the concentrations of diesel aerosols at the longwall (LW) section, and assess the exposures of selected occupations to elemental carbon (EC) and total carbon (TC). The results show that aerosols at the CM sections were a mixture of aerosols freshly generated at the outby portion of the CM section and those generated in the main drifts that supply fresh air to the section. The relatively low ambient concentrations and personal exposures of selected occupations suggest that currently applied control strategies and technologies are relatively effective in curtailing exposures to diesel aerosols. Further reductions in EC and TC concentrations and personal exposures to those would be possible by more effective curtailment of emissions from high-emitting light duty (LD) vehicles. 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. |
Neurological Events Reported after COVID-19 Vaccines: An Analysis of VAERS.
Frontera JA , Tamborska AA , Doheim MF , Garcia-Azorin D , Gezegen H , Guekht A , Yusof Khan AHK , Santacatterina M , Sejvar J , Thakur KT , Westenberg E , Winkler AS , Beghi E . Ann Neurol 2022 91 (6) 756-71 OBJECTIVE: To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S.. METHODS: We utilized publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021-June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. RESULTS: Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1273; 0.15% versus 0.03% versus 0.03% of doses, respectively,P<0.0001). The observed-to-expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. INTERPRETATION: Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. This article is protected by copyright. All rights reserved. |
Evaluation of an Antibody Detecting Point of Care Test for Diagnosis of Taenia solium Cysticercosis in a Zambian Rural Community: A Prospective Diagnostic Accuracy Study
Mubanga C , Van Damme I , Trevisan C , Schmidt V , Phiri IK , Zulu G , Noh J , Handali S , Mambo R , Chembensofu M , Masuku M , Reynders D , Jansen F , Bottieau E , Magnussen P , Winkler AS , Dorny P , Mwape KE , Gabriël S . Diagnostics (Basel) 2021 11 (11) The lack of cheap, easy-to-use, rapid diagnostic tests has led to the development of several rapid diagnostic tests for cysticercosis. The new prototype two-strip, Taenia solium point of care test (TS POC) detects antibodies against taeniosis (TS POC T) and cysticercosis (TS POC CC). This study evaluated the diagnostic performance of the TS POC CC in the Sinda district in eastern Zambia. A sample of 1254 participants was recruited and tested with the TS POC. Out of the 1249 participants with a valid TS POC result, 177 (14%) tested positive while 1072 (86%) tested negative. All individuals with a positive TS POC and a subset of negative TS POC participants were selected for serum sampling, and were subjected to the recombinant glycoprotein T24H enzyme-linked immunoelectrotransfer blot (rT24H EITB) and the serum B60/158 (serum Ag) enzyme-linked immunosorbent assay (Ag ELISA). Performance characteristics were estimated using a Bayesian approach with probabilistic constraints. Based on 255 complete cases, the estimated sensitivity and specificity of the TS POC CC test were 35% (95% CI: 14-63%) and 87% (95% CI: 83-90%), respectively. The diagnostic performance needs to be improved, possibly by titrating antigen and other reagents' concentration in the strip to produce a performance similar to existing cysticercosis tests such as the rT24H EITB. |
Challenges encountered when evaluating an antibody-detecting point-of-care test for taeniosis in an endemic community in Zambia: A prospective diagnostic accuracy study
Mubanga C , Trevisan C , Van Damme I , Schmidt V , Phiri IK , Zulu G , Noh J , Handali S , Mambo R , Chembensofu M , Masuku M , Reynders D , Jansen F , Bottieau E , Magnussen P , Winkler AS , Dorny P , Mwape KE , Gabriel S . Diagnostics (Basel) 2021 11 (11) Taenia solium taeniosis diagnosis is challenging because current tests perform sub-optimally and/or are expensive, require sophisticated equipment, infrastructure and trained manpower, and therefore are not community deployable. A recently-developed, multi-strip, T. solium point-of-care test (TS POC) for simultaneous detection of tapeworm (TS POC T) and cysticercus (TS POC CC) human antibodies was evaluated for diagnostic accuracy on consecutively recruited community participants in Sinda district, Zambia. All participants were tested using the TS POC test. All test-positives and 20% of the test-negative participants were invited to give a blood and stool sample for reference testing. Three different reference tests were used for taeniosis diagnosis: recombinant rES33 enzyme-linked immunoelectrotransfer blot (rES33 EITB), copro PCR and copro Ag ELISA. Bayesian analysis with probabilistic constraints was used to estimate sensitivity and specificity. In total, 1254 participants were tested with the TS POC test, of whom 13 tested positive using the TS POC T. Based on 161 participants with complete data, the estimated sensitivity and specificity for the TS POC T test were 38% (95% CI: 5–93%) and 99% (95% CI: 98–100%), respectively. The challenge of highly variable inter-assay performance is highlighted. We recommend either increasing the sensitivity or redesigning the test. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
Poor-quality employment and health: How a welfare regime typology with a gender lens Illuminates a different work-health relationship for men and women
Fujishiro K , Ahonen EQ , Winkler M . Soc Sci Med 2021 291 114484 In the growing literature on employment quality and health, poor quality of employment is generally associated with poor health. However, this association may not be uniform for men and women if unpaid caregiving labor is taken into consideration. How paid and unpaid labor is performed varies across societies because of differences in both state support for families and labor market penalties for women. Applying a gender lens to a welfare regime typology, we investigated the relationship between poor-quality employment and poor health for men and women. For each of five welfare regime types, we hypothesized if men or women would be more strongly affected by poor-quality employment based on the regime's family support policies and labor practices. Our analysis of 18 countries using the 2015 European and American Working Conditions Surveys data largely supported our hypotheses. In countries that support traditional gender roles with high state expenditure and have labor markets that penalize women, the association between poor-quality employment and health was stronger for men. The association was stronger for women in countries that rely on women to provide unpaid caregiving without substantial state support. In countries with apparently gender-neutral expectations for both paid work and unpaid caregiving work, no difference was found between men and women in the association of poor-quality employment with poor health. We discuss the importance of institutional perspectives to understand work as a gendered experience that impacts health. We suggest more comprehensive welfare regime typologies that recognize women both as caregivers and workers. Expanding the scope of research on work and health to include this integrated view of life could make a stride toward gender health equity. |
A call for a global COVID-19 Neuro Research Coalition.
Winkler AS , Knauss S , Schmutzhard E , Leonardi M , Padovani A , Abd-Allah F , Charway-Felli A , Emmerich JV , Umapathi T , Satishchandra P , Hoo FK , Dalmau J , Oreja-Guevara C , Ferreira LB , Pfausler B , Michael B , Tagliavini F , Hoglinger G , Endres M , Klein C , Hemmer B , Correll W , Sejvar J , Solomon T . Lancet Neurol 2020 19 (6) 482-484 Reports are emerging at a rapid pace that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the nervous system in various ways. Preliminary data from Wuhan, China, suggest that neurological manifestations are present in more than 30% of patients presenting with coronavirus disease 2019 (COVID-19).1 Neurological features range from quite diffuse neurological signs and symptoms like headache, dizziness, reduced level of consciousness, confusion, diffuse corticospinal tract signs, and paraesthesia, to more specific manifestations, such as seizures, stroke, encephalitis, or meningoencephalitis, and myopathy.1, 2 To date, SARS-CoV-2 has not been detected in the neural tissue directly, although it has been isolated from the CSF of some patients.3 The hypothesis of neurotropism with subsequent neuronal injury, either directly or indirectly (through immune mechanisms), is supported by previous findings from other infections with severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV.3 |
Taenia solium cysticercosis and taeniasis in urban settings: Epidemiological evidence from a health-center based study among people with epilepsy in Dar es Salaam, Tanzania
Schmidt V , O'Hara MC , Ngowi B , Herbinger KH , Noh J , Wilkins PP , Richter V , Kositz C , Matuja W , Winkler AS . PLoS Negl Trop Dis 2019 13 (12) e0007751 In Africa, urbanization is happening faster than ever before which results in new implications for transmission of infectious diseases. For the zoonotic parasite Taenia solium, a major cause of acquired epilepsy in endemic countries, the prevalence in urban settings is unknown. The present study investigated epidemiological, neurological, and radiological characteristics of T. solium cysticercosis and taeniasis (TSCT) in people with epilepsy (PWE) living in Dar es Salaam, Tanzania, one of the fastest growing cities worldwide. A total of 302 PWE were recruited from six health centers in the Kinondoni district of Dar es Salaam. Serological testing for T. solium cysticercosis-antigen (Ag) and -antibodies (Abs) and for T. solium taeniasis-Abs was performed in all PWE. In addition, clinical and radiological examinations that included cranial computed tomography (CT) were performed. With questionnaires, demographic data from study populations were collected, and factors associated with TSCT were assessed. Follow-up examinations were conducted in PWE with TSCT. T. solium cysticercosis-Ag was detected in three (0.99%; 95% CI: 0-2.11%), -Abs in eight (2.65%; 95% CI: 0.84-4.46%), and taeniasis-Abs in five (1.66%; 95% CI: 0.22-3.09%) of 302 PWE. Six PWE (1.99%; 95% CI: 0.41-3.56%) were diagnosed with neurocysticercosis (NCC). This study demonstrates the presence of TSCT in Dar es Salaam, however, NCC was only associated with a few cases of epilepsy. The small fraction of PWE with cysticercosis- and taeniasis-Abs may suggest that active transmission of T. solium plays only a minor role in Dar es Salaam. A sufficiently powered risk analysis was hampered by the small number of PWE with TSCT; therefore, further studies are required to determine the exact routes of infection and risk behavior of affected individuals. |
The use of next generation sequencing for improving food safety: Translation into practice.
Jagadeesan B , Gerner-Smidt P , Allard MW , Leuillet S , Winkler A , Xiao Y , Chaffron S , Van Der Vossen J , Tang S , Katase M , McClure P , Kimura B , Ching Chai L , Chapman J , Grant K . Food Microbiol 2019 79 96-115 Next Generation Sequencing (NGS) combined with powerful bioinformatic approaches are revolutionising food microbiology. Whole genome sequencing (WGS) of single isolates allows the most detailed comparison possible hitherto of individual strains. The two principle approaches for strain discrimination, single nucleotide polymorphism (SNP) analysis and genomic multi-locus sequence typing (MLST) are showing concordant results for phylogenetic clustering and are complementary to each other. Metabarcoding and metagenomics, applied to total DNA isolated from either food materials or the production environment, allows the identification of complete microbial populations. Metagenomics identifies the entire gene content and when coupled to transcriptomics or proteomics, allows the identification of functional capacity and biochemical activity of microbial populations. The focus of this review is on the recent use and future potential of NGS in food microbiology and on current challenges. Guidance is provided for new users, such as public health departments and the food industry, on the implementation of NGS and how to critically interpret results and place them in a broader context. The review aims to promote the broader application of NGS technologies within the food industry as well as highlight knowledge gaps and novel applications of NGS with the aim of driving future research and increasing food safety outputs from its wider use. |
Where No Universal Health Care Identifier Exists: Comparison and Determination of the Utility of Score-Based Persons Matching Algorithms Using Demographic Data
Waruru A , Natukunda A , Nyagah LM , Kellogg TA , Zielinski-Gutierrez E , Waruiru W , Masamaro K , Harklerode R , Odhiambo J , Manders EJ , Young PW . JMIR Public Health Surveill 2018 4 (4) e10436 BACKGROUND: A universal health care identifier (UHID) facilitates the development of longitudinal medical records in health care settings where follow up and tracking of persons across health care sectors are needed. HIV case-based surveillance (CBS) entails longitudinal follow up of HIV cases from diagnosis, linkage to care and treatment, and is recommended for second generation HIV surveillance. In the absence of a UHID, records matching, linking, and deduplication may be done using score-based persons matching algorithms. We present a stepwise process of score-based persons matching algorithms based on demographic data to improve HIV CBS and other longitudinal data systems. OBJECTIVE: The aim of this study is to compare deterministic and score-based persons matching algorithms in records linkage and matching using demographic data in settings without a UHID. METHODS: We used HIV CBS pilot data from 124 facilities in 2 high HIV-burden counties (Siaya and Kisumu) in western Kenya. For efficient processing, data were grouped into 3 scenarios within (1) HIV testing services (HTS), (2) HTS-care, and (3) within care. In deterministic matching, we directly compared identifiers and pseudo-identifiers from medical records to determine matches. We used R stringdist package for Jaro, Jaro-Winkler score-based matching and Levenshtein, and Damerau-Levenshtein string edit distance calculation methods. For the Jaro-Winkler method, we used a penalty (Ñ€)=0.1 and applied 4 weights (ω) to Levenshtein and Damerau-Levenshtein: deletion ω=0.8, insertion ω=0.8, substitutions ω=1, and transposition ω=0.5. RESULTS: We abstracted 12,157 cases of which 4073/12,157 (33.5%) were from HTS, 1091/12,157 (9.0%) from HTS-care, and 6993/12,157 (57.5%) within care. Using the deterministic process 435/12,157 (3.6%) duplicate records were identified, yielding 96.4% (11,722/12,157) unique cases. Overall, of the score-based methods, Jaro-Winkler yielded the most duplicate records (686/12,157, 5.6%) while Jaro yielded the least duplicates (546/12,157, 4.5%), and Levenshtein and Damerau-Levenshtein yielded 4.6% (563/12,157) duplicates. Specifically, duplicate records yielded by method were: (1) Jaro 5.7% (234/4073) within HTS, 0.4% (4/1091) in HTS-care, and 4.4% (308/6993) within care, (2) Jaro-Winkler 7.4% (302/4073) within HTS, 0.5% (6/1091) in HTS-care, and 5.4% (378/6993) within care, (3) Levenshtein 6.4% (262/4073) within HTS, 0.4% (4/1091) in HTS-care, and 4.2% (297/6993) within care, and (4) Damerau-Levenshtein 6.4% (262/4073) within HTS, 0.4% (4/1091) in HTS-care, and 4.2% (297/6993) within care. CONCLUSIONS: Without deduplication, over reporting occurs across the care and treatment cascade. Jaro-Winkler score-based matching performed the best in identifying matches. A pragmatic estimate of duplicates in health care settings can provide a corrective factor for modeled estimates, for targeting and program planning. We propose that even without a UHID, standard national deduplication and persons-matching algorithm that utilizes demographic data would improve accuracy in monitoring HIV care clinical cascades. |
Evaluating the recombinant T24H enzyme-linked immunoelectrotransfer blot assay for the diagnosis of neurocysticercosis in a panel of samples from a large community-based randomized control trial in 60 villages in Burkina Faso
Dermauw V , Carabin H , Cisse A , Millogo A , Tarnagda Z , Ganaba R , Noh J , Handali S , Breen K , Richter V , Cisse R , Preux PM , Boncoeur-Martel MP , Winkler AS , Van Hul A , Dorny P , Gabriel S . Am J Trop Med Hyg 2018 98 (2) 565-569 Current guidelines for the diagnosis of neurocysticercosis (NCC) recommend the use of the lentil lectin-bound glycoprotein enzyme-linked immunoelectrotransfer blot assay (LLGP-EITB) as the reference standard for serological testing. In response to the drawbacks involved with the use of the LLGP-EITB, a recombinant T24H antigen (rT24H) EITB assay was developed, with promising results. However, the test has yet to be evaluated among individuals from sub-Saharan Africa (SSA). The aim of the present study was to investigate the performance of the rT24H EITB assay for the detection of NCC cases in a panel of serum samples (N = 366, of which 173 patients presented with epileptic seizures and/or severe chronic headaches, and 193 matched manifestation-free participants) collected as part of a large community-based trial in Burkina Faso. A perfect agreement between the rT24H EITB and the native gp24 (and its homodimer, gp42) LLGP-EITB was found (kappa value of 1.0). Furthermore, among patients with the neurological manifestations of interest who underwent a computed tomography scan, the rT24H EITB and native antigen LLGP-EITB had a comparable ability to correctly identify NCC cases with multiple viable (rT24H: sensitivity: 80.0%), single viable (66.7%), and calcified/degenerating cysts only (25.0%), albeit for multiple viable and calcified cysts, the rT24H estimated sensitivity seemed lower, but more uncertain, than previously reported. The rT24H EITB specificity was high (98.2%) and in line with previous studies. This study confirms the value of the recombinant rT24H EITB as an alternative to the native antigen LLGP-EITB for the diagnosis of NCC in a SSA community setting. |
Implementing STEADI in Academic Primary Care to Address Older Adult Fall Risk
Eckstrom E , Parker EM , Lambert GH , Winkler G , Dowler D , Casey CM . Innov Aging 2017 1 (2) igx028 BACKGROUND AND OBJECTIVES: Falls are the leading cause of injury-related deaths in older adults. Objectives include describing implementation of the Centers for Disease Control and Prevention's Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative to help primary care providers (PCPs) identify and manage fall risk, and comparing a 12-item and a 3-item fall screening questionnaire. DESIGN AND METHODS: We systematically incorporated STEADI into routine patient care via team training, electronic health record tools, and tailored clinic workflow. A retrospective chart review of patients aged 65 and older who received STEADI measured fall screening rates, provider compliance with STEADI (high-risk patients), results from the 12-item questionnaire (Stay Independent), and comparison with a 3-item subset of this questionnaire (three key questions). RESULTS: Eighteen of 24 providers (75%) participated, screening 773 (64%) patients over 6 months; 170 (22%) were high-risk. Of these, 109 (64%) received STEADI interventions (gait, vision, and feet assessment, orthostatic blood pressure measurement, vitamin D, and medication review). Providers intervened on 85% with gait impairment, 97% with orthostatic hypotension, 82% with vision impairment, 90% taking inadequate vitamin D, 75% with foot issues, and 22% on high-risk medications. Using three key questions compared to the full Stay Independent questionnaire decreased screening burden, but increased the number of high-risk patients. DISCUSSION AND IMPLICATIONS: We successfully implemented STEADI, screening two-thirds of eligible patients. Most high-risk patients received recommended assessments and interventions, except medication reduction. Falls remain a substantial public health challenge. Systematic implementation of STEADI could help clinical teams reduce older patient fall risks. |
Coxiella burnetii antibody seropositivity is not a risk factor for AIDS-related non-Hodgkin lymphoma
Miller HK , Santo L , Camargo MC , Winkler CA , Goedert JJ , Kersh GJ , Rabkin CS . Blood 2017 129 (24) 3262-3264 Coxiella burnetii is an important human pathogen and the causative agent of Q fever, a disease that can lead to life-threatening endocarditis and other serious conditions. About 3% of the US population has antibody evidence of exposure to this agent, which can persist for months to years after infection. Recently, chronic C burnetii infection has been linked to the development of non-Hodgkin B-cell lymphoma (NHL).1 This study of 1468 patients from the French National Referral Center for Q Fever database found a 25-fold increase in the risk of NHL development among Q fever patients relative to the general population. The link between Q fever and NHL development is believed to be related to plasmacytoid dendritic cell infection within lymphoid tumors and interleukin-10 (IL-10) overproduction. | HIV is also linked to NHL as progression to AIDS puts patients at increased risk for development of NHL subtypes.2,3 A link between HIV and increased C burnetii seroprevalence has been suggested. Two independent studies in France and Brazil found increased C burnetii seroprevalence in HIV-positive individuals relative to the general population.4-6 Conversely, a study in Spain found seroprevalence among HIV-infected IV drug users similar to that of HIV-negative IV drug users.7 This same study and work in Tanzania found the percentage of HIV-positive individuals within cohorts of acute Q fever patients to be comparable to the general population.7,8 Whether HIV infection alters antibody responses to C burnetii infection or plays a role in increased susceptibility or disease severity is not known. |
Nakalanga Syndrome: Clinical characteristics, potential causes, and its relationship with recently described Nodding Syndrome
Foger K , Gora-Stahlberg G , Sejvar J , Ovuga E , Jilek-Aall L , Schmutzhard E , Kaiser C , Winkler AS . PLoS Negl Trop Dis 2017 11 (2) e0005201 Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder. |
Association between Taenia solium infection and HIV/AIDS in northern Tanzania: A matched cross sectional-study
Schmidt V , Kositz C , Herbinger KH , Carabin H , Ngowi B , Naman E , Wilkins PP , Noh J , Matuja W , Winkler AS . Infect Dis Poverty 2016 5 (1) 111 BACKGROUND: The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). METHODS: In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4+ cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. RESULTS: No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4+ cell counts, HAART duration or HIV stage. CONCLUSIONS: This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself. |
Lessons learned from implementing CDC's STEADI falls prevention algorithm in primary care
Casey CM , Parker EM , Winkler G , Liu X , Lambert GH , Eckstrom E . Gerontologist 2016 57 (4) 787-796 BACKGROUND: Falls lead to a disproportionate burden of death and disability among older adults despite evidence-based recommendations to screen regularly for fall risk and clinical trials demonstrating the effectiveness of multifactorial interventions to reduce falls. The Centers for Disease Control and Prevention developed STEADI (Stopping Elderly Accidents, Deaths, and Injuries) to assist primary care teams to screen for fall risk and reduce risk of falling in older adults. PURPOSE OF THE STUDY: This paper describes a practical application of STEADI in a large academic internal medicine clinic utilizing the Kotter framework, a tool used to guide clinical practice change. DESIGN AND METHODS: We describe key steps and decision points in the implementation of STEADI as they relate to the recommended strategies of the Kotter framework. Strategies include: creating a sense of urgency, building a guiding coalition, forming a strategic vision and initiative, enlisting volunteers, enabling success by removing barriers, generating short-term wins, sustaining change, and instituting change. RESULTS: Fifty-six patients were screened during pilot testing; 360 patients were screened during the first 3 months of implementation. Key to successful implementation was (a) the development of electronic health record (EHR) tools and workflow to guide clinical practice and (b) the proactive leadership of clinical champions within the practice to identify and respond to barriers. IMPLICATIONS: Implementing falls prevention in a clinical setting required support and effort across multiple stakeholders. We highlight challenges, successes, and lessons learned that offer guidance for other clinical practices in their falls prevention efforts. |
Screening for post-traumatic stress disorder in a civilian emergency department population with traumatic brain injury
Haarbauer-Krupa J , Taylor CA , Yue JK , Winkler EA , Pirracchio R , Cooper SR , Burke JF , Stein MB , Manley GTMDPh D . J Neurotrauma 2016 34 (1) 50-58 Post-traumatic stress disorder (PTSD) is a condition associated with traumatic brain injury (TBI). While the importance of PTSD and TBI among military personnel is widely recognized, there is less awareness of PTSD associated with civilian TBI. We examined the incidence and factors associated with PTSD six months post-injury in a civilian emergency department population using measures from the (NINDS) TBI Common Data Elements (TBI-CDE) Outcome Battery. Participants with mild TBI (mTBI) from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study with complete six-month outcome batteries (N=280) were analyzed. Screening for PTSD symptoms was conducted using the PTSD Checklist-Civilian Version (PCL-C). Descriptive measures are summarized and predictors for PTSD were examined using logistic regression. Incidence of screening positive for PTSD was 26.8% at six months following mTBI. Screening positive for PTSD was significantly associated with concurrent functional disability, postconcussive and psychiatric symptomatology, decreased satisfaction with life, and decreased performance in visual processing and mental flexibility. Multivariable regression showed injury mechanism of assault (odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.63, p=0.001) and prior psychiatric history (OR 2.56, 95% CI 1.42-4.61, p=0.002) remained significant predictors of screening positive for PTSD, while education (per-year OR 0.88, 95% CI 0.79-0.98, p=0.021) was associated with decreased odds of PTSD. Standardized data collection and review of pre-injury education, psychiatric history, and injury mechanism during initial hospital presentation can aid in identifying patients with mTBI at risk for developing PTSD symptoms, who may benefit from closer follow-up after initial injury care. |
An unusual presentation of neurocysticercosis: a space-occupying lesion in the fourth ventricle associated with progressive cognitive decline
Kurz C , Schmidt V , Poppert H , Wilkins P , Noh J , Poppert S , Schlegel J , Ertelt-Delbridge C , da Costa CP , Winkler AS . Am J Trop Med Hyg 2015 94 (1) 172-5 We communicate a case of a middle-aged Brazilian patient with an unusual presentation of fourth ventricular neurocysticercosis: occurrence of two intraventricular cysts at different locations in the brain within 2 years and cognitive decline as the only neurological symptom. Neurocysticercosis was confirmed by magnetic resonance imaging, serology, histology, and genetic analysis. Neurocysticercosis should be considered as a differential diagnosis in cases with atypical neurologic or psychiatric symptoms, atypical neuroimaging, and travel history. Especially, fourth ventricular cysts carry the risk of obstructive hydrocephalus and brainstem compression and therefore should be extirpated completely. If complete removal of the cystic structures cannot be proven in cases with surgically treated neurocysticercosis, anthelminthic therapy and thorough follow-up examinations should be conducted. |
Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis
Lai YS , Biedermann P , Ekpo UF , Garba A , Mathieu E , Midzi N , Mwinzi P , N'Goran EK , Raso G , Assare RK , Sacko M , Schur N , Talla I , Tchuente LA , Toure S , Winkler MS , Utzinger J , Vounatsou P . Lancet Infect Dis 2015 15 (8) 927-40 BACKGROUND: Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries. METHODS: We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 x 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity. FINDINGS: The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18.5%, 17.6-19.5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52.8%, 95% CrI 48.7-57.8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population. INTERPRETATION: Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions. FUNDING: European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation. |
The use of TKM-100802 and convalescent plasma in 2 patients with Ebola virus disease in the United States
Kraft CS , Hewlett AL , Koepsell S , Winkler AM , Kratochvil CJ , Larson L , Varkey JB , Mehta AK , Lyon GM 3rd , Friedman-Moraco RJ , Marconi VC , Hill CE , Sullivan JN , Johnson DW , Lisco SJ , Mulligan MJ , Uyeki TM , McElroy AK , Sealy T , Campbell S , Spiropoulou C , Stroher U , Crozier I , Sacra R , Connor MJ Jr , Sueblivong V , Franch HA , Smith PW , Ribner BS . Clin Infect Dis 2015 61 (4) 496-502 The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD. |
Spatial and temporal distribution of soil-transmitted helminth infection in sub-Saharan Africa: a systematic review and geostatistical meta-analysis
Karagiannis-Voules DA , Biedermann P , Ekpo UF , Garba A , Langer E , Mathieu E , Midzi N , Mwinzi P , Polderman AM , Raso G , Sacko M , Talla I , Tchuente LA , Toure S , Winkler MS , Utzinger J , Vounatsou P . Lancet Infect Dis 2014 15 (1) 74-84 BACKGROUND: Interest is growing in predictive risk mapping for neglected tropical diseases (NTDs), particularly to scale up preventive chemotherapy, surveillance, and elimination efforts. Soil-transmitted helminths (hookworm, Ascaris lumbricoides, and Trichuris trichiura) are the most widespread NTDs, but broad geographical analyses are scarce. We aimed to predict the spatial and temporal distribution of soil-transmitted helminth infections, including the number of infected people and treatment needs, across sub-Saharan Africa. METHODS: We systematically searched PubMed, Web of Knowledge, and African Journal Online from inception to Dec 31, 2013, without language restrictions, to identify georeferenced surveys. We extracted data from household surveys on sources of drinking water, sanitation, and women's level of education. Bayesian geostatistical models were used to align the data in space and estimate risk of with hookworm, A lumbricoides, and T trichiura over a grid of roughly 1 million pixels at a spatial resolution of 5 x 5 km. We calculated anthelmintic treatment needs on the basis of WHO guidelines (treatment of all school-aged children once per year where prevalence in this population is 20-50% or twice per year if prevalence is greater than 50%). FINDINGS: We identified 459 relevant survey reports that referenced 6040 unique locations. We estimate that the prevalence of hookworm, A lumbricoides, and T trichiura among school-aged children from 2000 onwards was 16.5%, 6.6%, and 4.4%. These estimates are between 52% and 74% lower than those in surveys done before 2000, and have become similar to values for the entire communities. We estimated that 126 million doses of anthelmintic treatments are required per year. INTERPRETATION: Patterns of soil-transmitted helminth infection in sub-Saharan Africa have changed and the prevalence of infection has declined substantially in this millennium, probably due to socioeconomic development and large-scale deworming programmes. The global control strategy should be reassessed, with emphasis given also to adults to progress towards local elimination. FUNDING: Swiss National Science Foundation and European Research Council. |
Clinical, neurological, and electrophysiological features of nodding syndrome in Kitgum, Uganda: an observational case series
Sejvar JJ , Kakooza AM , Foltz JL , Makumbi I , Atai-Omoruto AD , Malimbo M , Ndyomugyenyi R , Alexander LN , Abang B , Downing RG , Ehrenberg A , Guilliams K , Helmers S , Melstrom P , Olara D , Perlman S , Ratto J , Trevathan E , Winkler AS , Dowell SF , Lwamafa D . Lancet Neurol 2013 12 (2) 166-74 BACKGROUND: Nodding syndrome is an unexplained illness characterised by head-bobbing spells. The clinical and epidemiological features are incompletely described, and the explanation for the nodding and the underlying cause of nodding syndrome are unknown. We aimed to describe the clinical and neurological diagnostic features of this illness. METHODS: In December, 2009, we did a multifaceted investigation to assess epidemiological and clinical illness features in 13 parishes in Kitgum District, Uganda. We defined a case as a previously healthy child aged 5-15 years with reported nodding and at least one other neurological deficit. Children from a systematic sample of a case-control investigation were enrolled in a clinical case series which included history, physical assessment, and neurological examinations; a subset had electroencephalography (EEG), electromyography, brain MRI, CSF analysis, or a combination of these analyses. We reassessed the available children 8 months later. FINDINGS: We enrolled 23 children (median age 12 years, range 7-15 years) in the case-series investigation, all of whom reported at least daily head nodding. 14 children had reported seizures. Seven (30%) children had gross cognitive impairment, and children with nodding did worse on cognitive tasks than did age-matched controls, with significantly lower scores on tests of short-term recall and attention, semantic fluency and fund of knowledge, and motor praxis. We obtained CSF samples from 16 children, all of which had normal glucose and protein concentrations. EEG of 12 children with nodding syndrome showed disorganised, slow background (n=10), and interictal generalised 2.5-3.0 Hz spike and slow waves (n=10). Two children had nodding episodes during EEG, which showed generalised electrodecrement and paraspinal electromyography dropout consistent with atonic seizures. MRI in four of five children showed generalised cerebral and cerebellar atrophy. Reassessment of 12 children found that six worsened in their clinical condition between the first evaluation and the follow-up evaluation interval, as indicated by more frequent head nodding or seizure episodes, and none had cessation or decrease in frequency of these episodes. INTERPRETATION: Nodding syndrome is an epidemic epilepsy associated with encephalopathy, with head nodding caused by atonic seizures. The natural history, cause, and management of the disorder remain to be determined. FUNDING: Division of Global Disease Detection and Emergency Response, US Centers for Disease Control and Prevention. |
Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru
Penny M , Bartolini R , Mosqueira NR , Lamontagne DS , Mendoza MA , Ramos I , Winkler JL , Villafana J , Janmohamed A , Jumaan AO . Vaccine 2011 29 (31) 5022-30 Operational research using a mixed method, cross-sectional, case-study approach assessed the feasibility and health system impact of large-scale implementation of human papillomavirus (HPV) vaccination into routine vaccine delivery by the Ministry of Health in Peru. The strategy was school-based vaccination of fifth grade girls in 527 primary schools in Piura region. Our evaluation showed that school-based HPV vaccination is feasible without major changes in existing health systems. This was reflected in the opinions of health personnel, the lack of impact on other vaccine coverage, and the high HPV vaccine coverage documented in routine records and by an independent community-based survey. |
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