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451. Diverse functional autoantibodies in patients with COVID-19

Author

Wang, Eric Y., Mao, Tianyang, Klein, Jon, Dai, Yile, Huck, John D., Jaycox, Jillian R., Liu, Feimei, Zhou, Ting, Israelow, Benjamin, Wong, Patrick, Coppi, Andreas, Lucas, Carolina, Silva, Julio, Oh, Ji Eun, Song, Eric, Perotti, Emily S., Zheng, Neil S., Fischer, Suzanne, Campbell, Melissa, Fournier, John B., Wyllie, Anne L., Vogels, Chantal B. F., Ott, Isabel M., Kalinich, Chaney C., Petrone, Mary E., Watkins, Anne E., Dela Cruz, Charles, Farhadian, Shelli F., Schulz, Wade L., Ma, Shuangge, Grubaugh, Nathan D., Ko, Albert I., Iwasaki, Akiko, and Ring, Aaron M.

Abstract

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Published
2021
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452. Detection of SARS-CoV-2 RNA by multiplex RT-qPCR.

Author

Kudo, Eriko, Israelow, Benjamin, Vogels, Chantal B. F., Lu, Peiwen, Wyllie, Anne L., Tokuyama, Maria, Venkataraman, Arvind, Brackney, Doug E., Ott, Isabel M., Petrone, Mary E., Earnest, Rebecca, Lapidus, Sarah, Muenker, M. Catherine, Moore, Adam J., Casanovas-Massana, Arnau, Omer, Saad B., Dela Cruz, Charles S., Farhadian, Shelli F., Ko, Albert I., and Grubaugh, Nathan D.

Subjects
SARS-CoV-2, RNA
Abstract

The current quantitative reverse transcription PCR (RT-qPCR) assay recommended for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in the United States requires analysis of 3 genomic targets per sample: 2 viral and 1 host. To simplify testing and reduce the volume of required reagents, we devised a multiplex RT-qPCR assay to detect SARS-CoV-2 in a single reaction. We used existing N1, N2, and RP primer and probe sets by the Centers for Disease Control and Prevention, but substituted fluorophores to allow multiplexing of the assay. The cycle threshold (Ct) values of our multiplex RT-qPCR were comparable to those obtained by the single assay adapted for research purposes. Low copy numbers (≥500 copies/reaction) of SARS-CoV-2 RNA were consistently detected by the multiplex RT-qPCR. Our novel multiplex RT-qPCR improves upon current single diagnostics by saving reagents, costs, time, and labor. The current RT-qPCR assay recommended for SARS-CoV-2 testing in the United States requires analysis of three genomic targets per sample: two viral and one host. This study describes a multiplex PCR that saves both reagents and labor while accurately detecting SARS-CoV-2 RNA. [ABSTRACT FROM AUTHOR]

Published
2020
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454. Fine-scale GPS tracking to quantify human movement patterns and exposure to leptospires in the urban slum environment

Author

Owers, Katharine A., primary, Odetunde, Juliana, additional, de Matos, Rosan Barbosa, additional, Sacramento, Gielson, additional, Carvalho, Mayara, additional, Nery, Nivison, additional, Costa, Federico, additional, Reis, Mitermayer G., additional, Childs, James E., additional, Hagan, José E., additional, Diggle, Peter J., additional, and Ko, Albert I., additional

Published
2018
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457. Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel

Author

Santos, Luciane A., primary, Adhikarla, Haritha, additional, Yan, Xiting, additional, Wang, Zheng, additional, Fouts, Derrick E., additional, Vinetz, Joseph M., additional, Alcantara, Luiz C. J., additional, Hartskeerl, Rudy A., additional, Goris, Marga G. A., additional, Picardeau, Mathieu, additional, Reis, Mitermayer G., additional, Townsend, Jeffrey P., additional, Zhao, Hongyu, additional, Ko, Albert I., additional, and Wunder, Elsio A., additional

Published
2018
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464. Spatial and temporal dynamics of pathogenic Leptospira in surface waters from the urban slum environment

Author

Casanovas-Massana, Arnau, primary, Costa, Federico, additional, Riediger, Irina N., additional, Cunha, Marcelo, additional, de Oliveira, Daiana, additional, Mota, Diogenes C., additional, Sousa, Erica, additional, Querino, Vladimir A., additional, Nery, Nivisson, additional, Reis, Mitermayer G., additional, Wunder, Elsio A., additional, Diggle, Peter J., additional, and Ko, Albert I., additional

Published
2018
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465. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

Author

Adhikarla, Haritha, primary, Wunder, Elsio A., additional, Mechaly, Ariel E., additional, Mehta, Sameet, additional, Wang, Zheng, additional, Santos, Luciane, additional, Bisht, Vimla, additional, Diggle, Peter, additional, Murray, Gerald, additional, Adler, Ben, additional, Lopez, Francesc, additional, Townsend, Jeffrey P., additional, Groisman, Eduardo, additional, Picardeau, Mathieu, additional, Buschiazzo, Alejandro, additional, and Ko, Albert I., additional

Published
2018
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466. Prospective evaluation of accuracy and clinical utility of the Dual Path Platform (DPP) assay for the point-of-care diagnosis of leptospirosis in hospitalized patients

Author

Nabity, Scott A., primary, Hagan, José E., additional, Araújo, Guilherme, additional, Damião, Alcinéia O., additional, Cruz, Jaqueline S., additional, Nery, Nivison, additional, Wunder, Elsio A., additional, Reis, Mitermayer G., additional, Ko, Albert I., additional, and Ribeiro, Guilherme S., additional

Published
2018
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467. Estudo multicêntrico da prevalência de tuberculose e HIV na população carcerária do Estado do Mato Grosso do Sul

Author

Carbone, Andrea da Silva Santos, primary, Sgarbi, Renata Viebrantz Enne, additional, Lemos, Everton Ferrreira, additional, Paião, Dayse Sanchez Guimarães, additional, Simionatto, Simone, additional, Castro, Ana Rita Coimbra Motta de, additional, Pompílio, Maurício Antonio, additional, Oliveira, Sandra Maria do Valle Leone de, additional, Ko, Albert I., additional, Andrews, Jason R., additional, and Croda, Julio, additional

Published
2018
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469. Does immunity after Zika virus infection cross-protect against dengue?

Author

Ribeiro, Guilherme Sousa, primary, Kikuti, Mariana, additional, Tauro, Laura B, additional, Nascimento, Leile Camila J, additional, Cardoso, Cristiane W, additional, Campos, Gúbio S, additional, Ko, Albert I, additional, Weaver, Scott C, additional, Reis, Mitermayer G, additional, Kitron, Uriel, additional, Paploski, Igor A D, additional, Silva, Monaise M O, additional, Kasper, Amelia M, additional, Tavares, Aline S, additional, Cruz, Jaqueline S, additional, Moreira, Patrícia S S, additional, Anjos, Rosângela O, additional, Araújo, Josélio M G, additional, Khouri, Ricardo, additional, and Sardi, Silvia I, additional

Published
2018
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474. The helminth community of a population ofRattus norvegicusfrom an urban Brazilian slum and the threat of zoonotic diseases

Author

Carvalho-Pereira, Ticiana, primary, Souza, Fábio N., additional, Santos, Luana R. N., additional, Walker, Ruth, additional, Pertile, Arsinoê C., additional, de Oliveira, Daiana S., additional, Pedra, Gabriel G., additional, Minter, Amanda, additional, Rodrigues, Maria Gorete, additional, Bahiense, Thiago C., additional, Reis, Mitermayer G., additional, Diggle, Peter J., additional, Ko, Albert I., additional, Childs, James E., additional, da Silva, Eduardo M., additional, Begon, Mike, additional, and Costa, Federico, additional

Published
2017
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476. Differences in the Prevalence of Non-Communicable Disease between Slum Dwellers and the General Population in a Large Urban Area in Brazil.

Author

Snyder, Robert E, Snyder, Robert E, Rajan, Jayant V, Costa, Federico, Lima, Helena CAV, Calcagno, Juan I, Couto, Ricardo D, Riley, Lee W, Reis, Mitermayer G, Ko, Albert I, Ribeiro, Guilherme S, Snyder, Robert E, Snyder, Robert E, Rajan, Jayant V, Costa, Federico, Lima, Helena CAV, Calcagno, Juan I, Couto, Ricardo D, Riley, Lee W, Reis, Mitermayer G, Ko, Albert I, and Ribeiro, Guilherme S

Abstract

Residents of urban slums are at greater risk for disease than their non-slum dwelling urban counterparts. We sought to contrast the prevalences of selected non-communicable diseases (NCDs) between Brazilian adults living in a slum and the general population of the same city, by comparing the age and sex-standardized prevalences of selected NCDs from a 2010 survey in Pau da Lima, Salvador Brazil, with a 2010 national population-based telephone survey. NCD prevalences in both populations were similar for hypertension (23.6% (95% CI 20.9⁻26.4) and 22.9% (21.2⁻24.6), respectively) and for dyslipidemia (22.7% (19.8⁻25.5) and 21.5% (19.7⁻23.4)). Slum residents had higher prevalences of diabetes mellitus (10.1% (7.9⁻12.3)) and of overweight/obesity (46.5% (43.1⁻49.9)), compared to 5.2% (4.2⁻6.1) and 40.6% (38.5⁻42.8) of the general population in Salvador. Fourteen percent (14.5% (12.1⁻17.0)) of slum residents smoked cigarettes compared to 8.3% (7.1⁻9.5) of the general population in Salvador. The national telephone survey underestimated the prevalence of diabetes mellitus, overweight/obesity, and smoking in the slum population, likely in part due to differential sampling inside and outside of slums. Further research and targeted policies are needed to mitigate these inequalities, which could have significant economic and social impacts on slum residents and their communities.

Published
2017

477. Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis.

Author

Lessa-Aquino, Carolina, Vinetz, Joseph M1, Lessa-Aquino, Carolina, Lindow, Janet C, Randall, Arlo, Wunder, Elsio, Pablo, Jozelyn, Nakajima, Rie, Jasinskas, Algis, Cruz, Jaqueline S, Damião, Alcineia O, Nery, Nívison, Ribeiro, Guilherme S, Costa, Federico, Hagan, José E, Reis, Mitermayer Galvão, Ko, Albert I, Medeiros, Marco Alberto, Felgner, Philip L, Lessa-Aquino, Carolina, Vinetz, Joseph M1, Lessa-Aquino, Carolina, Lindow, Janet C, Randall, Arlo, Wunder, Elsio, Pablo, Jozelyn, Nakajima, Rie, Jasinskas, Algis, Cruz, Jaqueline S, Damião, Alcineia O, Nery, Nívison, Ribeiro, Guilherme S, Costa, Federico, Hagan, José E, Reis, Mitermayer Galvão, Ko, Albert I, Medeiros, Marco Alberto, and Felgner, Philip L

Abstract

BackgroundLeptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection.Methods and principal findingsHere, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients' responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group.ConclusionsIn the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new target

Published
2017

478. Pathways to zoonotic spillover.

Author

Plowright, Raina, Plowright, Raina, Parrish, Colin, McCallum, Hamish, Hudson, Peter, Ko, Albert, Graham, Andrea, Lloyd-Smith, James, Plowright, Raina, Plowright, Raina, Parrish, Colin, McCallum, Hamish, Hudson, Peter, Ko, Albert, Graham, Andrea, and Lloyd-Smith, James

Abstract

Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.

Published
2017

479. Global population divergence and admixture of the brown rat (Rattus norvegicus)

Author

Puckett, Emily E., Park, Jane, Combs, Matthew, Blum, Michael J., Bryant, Juliet E., Caccone, Adalgisa, Costa, Federico, Deinum, Eva E., Esther, Alexandra, Himsworth, Chelsea G., Keightley, Peter D., Ko, Albert, McElhinney, Lorraine M., Morand, Serge, Robins, Judith, Russell, James, Strand, Tanja M., Suarez, Olga, Yon, Lisa, and Munshi-South, Jason

Subjects
commensal, invasive species, population genomics, cityscapes, phylogeography, RAD-Seq
Abstract

Native to China and Mongolia, the brown rat (Rattus norvegicus) now enjoys a worldwide distribution. While black rats and the house mouse tracked the regional development of human agricultural settlements, brown rats did not appear in Europe until the 1500s, suggesting their range expansion was a response to relatively recent increases in global trade. We inferred the global phylogeography of brown rats using 32 k SNPs, and detected 13 evolutionary clusters within five expansion routes. One cluster arose following a southward expansion into Southeast Asia. Three additional clusters arose from two independent eastward expansions: one expansion from Russia to the Aleutian Archipelago, and a second to western North America. Westward expansion resulted in the colonization of Europe from which subsequent rapid colonization of Africa, the Americas and Australasia occurred, and multiple evolutionary clusters were detected. An astonishing degree of fine-grained clustering between and within sampling sites underscored the extent to which urban heterogeneity shaped genetic structure of commensal rodents. Surprisingly, few individuals were recent migrants, suggesting that recruitment into established populations is limited. Understanding the global population structure of R. norvegicus offers novel perspectives on the forces driving the spread of zoonotic disease, and aids in development of rat eradication programmes.

Published
2016

480. Corrigendum: ALPK1 phosphorylates myosin IIA modulating TNF-α trafficking in gout flares

Author

Lee, Chi-Pin, Chiang, Shang-Lun, Ko, Albert Min-Shan, Liu, Yu-Fan, Ma, Che, Lu, Chi-Yu, Huang, Chung-Ming, Chang, Jan-Gowth, Kuo, Tzer-Min, Chen, Chia-Lin, Tsai, Eing-Mei, and Ko, Ying-Chin

Subjects
Gout, Tumor Necrosis Factor-alpha, Nonmuscle Myosin Type IIA, Genetic Vectors, Down-Regulation, Corrigenda, Models, Biological, Monocytes, Protein Structure, Secondary, Cell Line, Uric Acid, HEK293 Cells, Protein Domains, Gene Knockdown Techniques, Cytokines, Humans, Amino Acid Sequence, Phosphorylation, Colchicine, Protein Kinases, Protein Binding
Abstract

Gout is characterized by the monosodium urate monohydrate (MSU)-induced arthritis. Alpha kinase-1 (ALPK1) has shown to be associated with MSU-induced inflammation and gout. Here, we used bioinformatics, proteomics, cell models, and twenty in vitro human assays to clarify some of its role in the inflammatory response to MSU. We found myosin IIA to be a frequent interacting protein partner of ALPK1, binding to its N-terminal and forming a protein complex with calmodulin and F-actin, and that MSU-induced ALPK1 phosphorylated the myosin IIA. A knockdown of endogenous ALPK1 or myosin IIA significantly reduced the MSU-induced secretion of tumour necrosis factor (TNF)-α. Furthermore, all gouty patients expressed higher basal protein levels of ALPK1, myosin IIA, and plasma TNF-α, however those medicated with colchicine has shown reduced myosin IIA and TNF-α but not ALPK1. The findings suggest ALPK1 is a kinase that participates in the regulation of Golgi-derived TNF-α trafficking through myosin IIA phosphorylation in the inflammation of gout. This novel pathway could be blocked at the level of myosin by colchicine in gout treatment.

Published
2016

481. A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete

Author

Wunder, Elsio, Figueira, Cláudio, Benaroudj, Nadia, Hu, Bo, Tong, Brian, Trajtenberg, Felipe, Liu, Jun, Reis, Mitermayer, Charon, Nyles, Buschiazzo, Alejandro, Picardeau, Mathieu, Ko, Albert, Yale School of Public Health (YSPH), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris] (IP), The University of Texas Medical School at Houston, Molecular and structural microbiology / Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), West Virginia University [Morgantown], Département de Biologie structurale et Chimie - Department of Structural Biology and Chemistry, This work was supported by grants from the National Institutes of Health (U01 AI0038752, R01 AI052473, R01 TW009504, D43 TW000919, R01 DE0234431, R01 AI29743 and R01 AI087946), Brazilian National Research Council (CNPq), French Ministry of Research (ANR-08-MIE-018) and the Welch Foundation (AU-1714)., We thank Gisele R. Santos and Drs. Leyla Slamti, Kristel Lourdault and Vimla Bisht for their technical assistance. We also thank Dr. David Haake for providing polyclonal antibodies (α-FlaA1) and for his helpful discussions, Drs. Joe Vinetz and Derrick Fouts for their collaboration in sequencing the genomes of leptospiral strains, and Dr. Justin Radolf for his suggestions and advice throughout the study., ANR-08-MIEN-0018,LEPTOVIR,Les leptospires : de la génétique à la pathogénèse(2008), Fundação Oswaldo Cruz (FIOCRUZ), and Institut Pasteur [Paris]

Subjects
Leptospira, Male, Mesocricetus, Virulence, [SDV]Life Sciences [q-bio], Genetic Complementation Test, Article, Madin Darby Canine Kidney Cells, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Dogs, Bacterial Proteins, Flagella, Cricetinae, Mutation, Periplasm, Animals, Leptospirosis, Protein Structural Elements, Flagellin
Abstract

International audience; Leptospira are unique among bacteria based on their helical cell morphology with hook-shaped ends and the presence of periplasmic flagella (PF) with pronounced spontaneous supercoiling. The factors that provoke such supercoiling, as well as the role that PF coiling plays in generating the characteristic hook-end cell morphology and motility, have not been elucidated. We have now identified an abundant protein from the pathogen L. interrogans, exposed on the PF surface, and named it Flagellar-coiling protein A (FcpA). The gene encoding FcpA is highly conserved among Leptospira and was not found in other bacteria. fcpA(-) mutants, obtained from clinical isolates or by allelic exchange, had relatively straight, smaller-diameter PF, and were not able to produce translational motility. These mutants lost their ability to cause disease in the standard hamster model of leptospirosis. Complementation of fcpA restored the wild-type morphology, motility and virulence phenotypes. In summary, we identified a novel Leptospira 36-kDa protein, the main component of the spirochete's PF sheath, and a key determinant of the flagella's coiled structure. FcpA is essential for bacterial translational motility and to enable the spirochete to penetrate the host, traverse tissue barriers, disseminate to cause systemic infection and reach target organs.

Published
2016

482. Puckett_etal_RatPhylogeog_Supplemental from Global population divergence and admixture of the brown rat (Rattus norvegicus)

Author

Puckett, Emily E., Park, Jane, Combs, Matthew, Blum, Michael J., Bryant, Juliet E., Caccone, Adalgisa, Costa, Federico, Deinum, Eva E., Esther, Alexandra, Himsworth, Chelsea G., Keightley, Peter D., Ko, Albert, Lundkvist, Åke, McElhinney, Lorraine M., Morand, Serge, Robins, Judith, Russell, James, Strand, Tanja M., Suarez, Olga, Yon, Lisa, and Munshi-South, Jason

Abstract

Supplemental Methods, Supplemental Figures S1-S13

Published
2016
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483. S?ndrome de Guillain-Barr? ap?s Infec??o por v?rus Zika no Brasil: relato de caso

Author

Ros?rio, Mateus Santana do, Jesus, Pedro Antonio Pereira de, Vasilakis, Nikos, Farias, Daniel Santana, Novaes, Marco Ant?nio Caires, Rodrigues, Sueli Guerreiro, Martins, L?via Car?cio, Vasconcelos, Pedro Fernando da Costa, Ko, Albert Icksang, Alc?ntara, Luiz Carlos Junior, and Siqueira, Isadora Cristina de

Subjects
Infec??o pelo Zika virus / diagn?stico, S?ndrome de Guillain-Barr? / complica??es, Testes de Inibi??o da Hemaglutina??o / m?todos, Infec??o pelo Zika virus / complica??es, Rea??o em Cadeia da Polimerase Via Transcriptase Reversa / m?todos, Ensaio de Imunoadsor??o Enzim?tica / m?todos, Doen?as do Sistema Nervoso / complica??es, Brasil / epidemiologia
Abstract

Secretaria Estadual da Sa?de da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil. Secretaria Estadual da Sa?de da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil. University of Texas Medical Branch. Institute for Human Infections and Immunity. Department of Pathology. Center for Biodefense and Emerging Infectious Diseases. Galveston, TX, Texas / University of Texas Medical Branch. Center for Tropical Diseases. Galveston, TX, Texas. Secretaria Estadual da Sa?de da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brazil. Funda??o Monte Tabor. Hospital S?o Rafael. Salvador, BA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut. Minist?rio da Sa?de. Funda??o Oswaldo Cruz. Centro de Pesquisas Gon?alo Moniz. Salvador, BA, Brazil. Minist?rio da Sa?de. Funda??o Oswaldo Cruz. Centro de Pesquisas Gon?alo Moniz. Salvador, BA, Brazil. Zika virus (ZIKV) is an emerging flavivirus, which has caused a widespread outbreak in the Americas. Shortly after its introduction in 2015, a cluster of cases with Guillain-Barr? syndrome was detected in Brazil. Herein, we describe two cases from the city of Salvador, who developed ascending paresis after an acute exanthematous illness. The patients were admitted to the intensive care unit with tetraparesis and cranial nerve palsy, which resolved after intravenous administration of human immunoglobulin. Serological evaluation detected IgM-specific ZIKV antibodies. In regions of Zika virus transmission, health-care workers must be aware of the potential severe neurological complications associated with ZIKV infection and be prepared to provide prompt diagnosis, treatment, and supportive care.

Published
2016

484. Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge

Author

Vavinskaya, Vera, Baumgartner, Joel M., Ko, Albert, Saenz, Cheryl C., and Valasek, Mark A.

Subjects
Article Subject
Abstract

Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.

Published
2016
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485. Delayed production of neutralizing antibodies correlates with fatal COVID-19

Author

Lucas, Carolina, Klein, Jon, Sundaram, Maria E., Liu, Feimei, Wong, Patrick, Silva, Julio, Mao, Tianyang, Oh, Ji Eun, Mohanty, Subhasis, Huang, Jiefang, Tokuyama, Maria, Lu, Peiwen, Venkataraman, Arvind, Park, Annsea, Israelow, Benjamin, Vogels, Chantal B. F., Muenker, M. Catherine, Chang, C-Hong, Casanovas-Massana, Arnau, Moore, Adam J., Zell, Joseph, Fournier, John B., Wyllie, Anne L., Campbell, Melissa, Lee, Alfred I., Chun, Hyung J., Grubaugh, Nathan D., Schulz, Wade L., Farhadian, Shelli, Dela Cruz, Charles, Ring, Aaron M., Shaw, Albert C., Wisnewski, Adam V., Yildirim, Inci, Ko, Albert I., Omer, Saad B., and Iwasaki, Akiko

Abstract

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.

Published
2021
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486. High Prevalence of Treponema pallidum Infection in Brazilian Prisoners

Author

Correa, Maisa Estopa, primary, Ferreira de Sá Queiroz, Júlio Henrique, additional, Pompilio, Maurício Antonio, additional, Esther da Silva, Kesia, additional, Coimbra Motta de Castro, Ana Rita, additional, Omizolo de Souza, Ronaldo, additional, Simionatto, Simone, additional, Maria do Valle Leone de Oliveira, Sandra, additional, Ko, Albert I., additional, and Croda, Julio, additional

Published
2017
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487. Update on the Effect of Region-Wide Incorporation of an Algorithm Based on 2012 International Consensus Guideline on the Practice Pattern for the Management of Pancreatic Cystic Neoplasms in an Integrated Health System: 2017 Presidential Poster Award

Author

Lim, Brian, primary, Girgis, Agathon, additional, Alonso, Emilio, additional, Nguyen, Andrew, additional, Tekeste, Timnit, additional, Chang, Karen, additional, Adeyemo, Mopelola, additional, Eskandari, Armen, additional, Yaramada, Priya, additional, Chaya, Charles, additional, Burke, Edmund, additional, Ko, Albert, additional, Butler, Rebecca, additional, Kawatkar, Aniket, additional, and Roggow, Isaiah, additional

Published
2017
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488. Correction: Cathelicidin Insufficiency in Patients with Fatal Leptospirosis

Author

Lindow, Janet C., primary, Wunder, Elsio A., additional, Popper, Stephen J., additional, Min, Jin-na, additional, Mannam, Praveen, additional, Srivastava, Anup, additional, Yao, Yi, additional, Hacker, Kathryn P., additional, Raddassi, Khadir, additional, Lee, Patty J., additional, Montgomery, Ruth R., additional, Shaw, Albert C., additional, Hagan, Jose E., additional, Araújo, Guilherme C., additional, Nery, Nivison, additional, Relman, David A., additional, Kim, Charles C., additional, Reis, Mitermayer G., additional, and Ko, Albert I., additional

Published
2017
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490. Rapid, actionable diagnosis of urban epidemic leptospirosis using a pathogenic Leptospira lipL32-based real-time PCR assay

Author

Riediger, Irina N., primary, Stoddard, Robyn A., additional, Ribeiro, Guilherme S., additional, Nakatani, Sueli M., additional, Moreira, Suzana D. R., additional, Skraba, Irene, additional, Biondo, Alexander W., additional, Reis, Mitermayer G., additional, Hoffmaster, Alex R., additional, Vinetz, Joseph M., additional, Ko, Albert I., additional, and Wunder, Elsio A., additional

Published
2017
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492. Pathways to zoonotic spillover

Author

Plowright, Raina K., primary, Parrish, Colin R., additional, McCallum, Hamish, additional, Hudson, Peter J., additional, Ko, Albert I., additional, Graham, Andrea L., additional, and Lloyd-Smith, James O., additional

Published
2017
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493. Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico

Author

Robbiani, Davide F., primary, Bozzacco, Leonia, additional, Keeffe, Jennifer R., additional, Khouri, Ricardo, additional, Olsen, Priscilla C., additional, Gazumyan, Anna, additional, Schaefer-Babajew, Dennis, additional, Avila-Rios, Santiago, additional, Nogueira, Lilian, additional, Patel, Roshni, additional, Azzopardi, Stephanie A., additional, Uhl, Lion F.K., additional, Saeed, Mohsan, additional, Sevilla-Reyes, Edgar E., additional, Agudelo, Marianna, additional, Yao, Kai-Hui, additional, Golijanin, Jovana, additional, Gristick, Harry B., additional, Lee, Yu E., additional, Hurley, Arlene, additional, Caskey, Marina, additional, Pai, Joy, additional, Oliveira, Thiago, additional, Wunder, Elsio A., additional, Sacramento, Gielson, additional, Nery, Nivison, additional, Orge, Cibele, additional, Costa, Federico, additional, Reis, Mitermayer G., additional, Thomas, Neena M., additional, Eisenreich, Thomas, additional, Weinberger, Daniel M., additional, de Almeida, Antonio R.P., additional, West, Anthony P., additional, Rice, Charles M., additional, Bjorkman, Pamela J., additional, Reyes-Teran, Gustavo, additional, Ko, Albert I., additional, MacDonald, Margaret R., additional, and Nussenzweig, Michel C., additional

Published
2017
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494. Glaucoma and Congenital Zika Syndrome

Author

de Paula Freitas, Bruno, primary, Ko, Albert I., additional, Khouri, Ricardo, additional, Mayoral, Monica, additional, Henriques, Daniele Freitas, additional, Maia, Maurício, additional, and Belfort, Rubens, additional

Published
2017
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495. Using fine-scale spatial genetics of Norway rats to improve control efforts and reduce leptospirosis risk in urban slum environments

Author

Richardson, Jonathan L., primary, Burak, Mary K., additional, Hernandez, Christian, additional, Shirvell, James M., additional, Mariani, Carol, additional, Carvalho-Pereira, Ticiana S. A., additional, Pertile, Arsinoê C., additional, Panti-May, Jesus A., additional, Pedra, Gabriel G., additional, Serrano, Soledad, additional, Taylor, Josh, additional, Carvalho, Mayara, additional, Rodrigues, Gorete, additional, Costa, Federico, additional, Childs, James E., additional, Ko, Albert I., additional, and Caccone, Adalgisa, additional

Published
2017
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497. Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis

Author

Lessa-Aquino, Carolina, primary, Lindow, Janet C., additional, Randall, Arlo, additional, Wunder, Elsio, additional, Pablo, Jozelyn, additional, Nakajima, Rie, additional, Jasinskas, Algis, additional, Cruz, Jaqueline S., additional, Damião, Alcineia O., additional, Nery, Nívison, additional, Ribeiro, Guilherme S., additional, Costa, Federico, additional, Hagan, José E., additional, Reis, Mitermayer Galvão, additional, Ko, Albert I., additional, Medeiros, Marco Alberto, additional, and Felgner, Philip L., additional

Published
2017
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