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1.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31530719

RESUMO

BACKGROUND: Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases. METHODS: Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed. RESULTS: In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months. CONCLUSIONS: Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.


Assuntos
Surtos de Doenças , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/genética , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Notificação de Doenças/estatística & dados numéricos , Feminino , Gastroenterite/imunologia , Gastroenterite/prevenção & controle , Genótipo , Humanos , Programas de Imunização , Imunogenicidade da Vacina , Lactente , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Resultado do Tratamento , Vacinas Atenuadas/uso terapêutico , Adulto Jovem
2.
World J Gastroenterol ; 25(15): 1899-1906, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057303

RESUMO

BACKGROUND: Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT). CASE SUMMARY: The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE. CONCLUSION: This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.


Assuntos
Doenças do Colo/diagnóstico , Infecções por Citomegalovirus/complicações , Gastroenterite/complicações , Perfuração Intestinal/diagnóstico , Transplante de Fígado/efeitos adversos , Antígenos Virais/sangue , Antígenos Virais/imunologia , Colo/diagnóstico por imagem , Colo/virologia , Doenças do Colo/etiologia , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Endoscopia Gastrointestinal , Feminino , Gastroenterite/sangue , Gastroenterite/imunologia , Gastroenterite/virologia , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Hepatite Autoimune/cirurgia , Humanos , Perfuração Intestinal/etiologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
3.
Arch Virol ; 164(8): 2107-2117, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144039

RESUMO

Species A rotavirus still remains a major cause of acute gastroenteritis in infants and young children. Globally, six genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]) account for >90% of circulating strains; however, genotype G12 in combination with P[6] or P[9] has been detected at increasing rates. We sought to broaden our knowledge about the rotavirus strains circulating during the early post-vaccine-introduction period. Stool samples were obtained from children hospitalised for acute gastroenteritis in Belém, Northern Brazil, from May 2008 to May 2011 and examined by reverse transcription polymerase chain reaction and nucleotide sequencing. A total of 122 out of the original 1076 rotavirus strains were judged to be non-typeable in the first analysis and were therefore re-examined. G2P[4] was the most prevalent genotype (58.0%), followed by G1P[8] (16.9%), and G12P[6] (7.5%). G12P[6] strains were identified at similar rates during the first (2.5%) and second (3.9%) years, and the rate jumped to 15.6% in the third year. Analysis of VP7 sequences of the G12P[6] strains showed that they belonged to lineage III. In addition, co-circulating G12P[6] strains displaying long and short RNA patterns were found to belong to the Wa-like and DS-1-like constellation, respectively. Additional unusual circulating strains G12P[9] and G3P[9] were also identified. This hospital-based study showed a high prevalence of G12P[6] strains in the third year of surveillance. Our results highlight the need for continuous longitudinal monitoring of circulating rotavirus strains after introduction of rotavirus vaccines in Brazil and elsewhere.


Assuntos
Gastroenterite/virologia , Rotavirus/genética , Antígenos Virais/imunologia , Brasil , Criança , Criança Hospitalizada , Gastroenterite/imunologia , Genótipo , Humanos , Epidemiologia Molecular/métodos , Filogenia , Prevalência , RNA Viral/genética , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Análise de Sequência de DNA/métodos
4.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126070

RESUMO

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1ß, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1.


Assuntos
Gastroenterite/imunologia , Glucose/imunologia , Insulina/imunologia , Transportador 1 de Glucose-Sódio/imunologia , Animais , Linhagem Celular , Células Cultivadas , Feminino , Polipeptídeo Inibidor Gástrico/imunologia , Gastroenterite/patologia , Peptídeo 1 Semelhante ao Glucagon/imunologia , Incretinas/imunologia , Inflamação/imunologia , Inflamação/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL
5.
PLoS Pathog ; 15(4): e1007745, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009517

RESUMO

The mechanisms by which the gut luminal environment is disturbed by the immune system to foster pathogenic bacterial growth and survival remain incompletely understood. Here, we show that STAT2 dependent type I IFN signaling contributes to the inflammatory environment by disrupting hypoxia enabling the pathogenic S. Typhimurium to outgrow the microbiota. Stat2-/- mice infected with S. Typhimurium exhibited impaired type I IFN induced transcriptional responses in cecal tissue and reduced bacterial burden in the intestinal lumen compared to infected wild-type mice. Although inflammatory pathology was similar between wild-type and Stat2-/- mice, we observed decreased hypoxia in the gut tissue of Stat2-/- mice. Neutrophil numbers were similar in wild-type and Stat2-/- mice, yet Stat2-/- mice showed reduced levels of myeloperoxidase activity. In vitro, the neutrophils from Stat2-/- mice produced lower levels of superoxide anion upon stimulation with the bacterial ligand N-formylmethionyl-leucyl-phenylalanine (fMLP) in the presence of IFNα compared to neutrophils from wild-type mice, indicating that the neutrophils were less functional in Stat2-/- mice. Cytochrome bd-II oxidase-mediated respiration enhances S. Typhimurium fitness in wild-type mice, while in Stat2-/- deficiency, this respiratory pathway did not provide a fitness advantage. Furthermore, luminal expansion of S. Typhimurium in wild-type mice was blunted in Stat2-/- mice. Compared to wild-type mice which exhibited a significant perturbation in Bacteroidetes abundance, Stat2-/- mice exhibited significantly less perturbation and higher levels of Bacteroidetes upon S. Typhimurium infection. Our results highlight STAT2 dependent type I IFN mediated inflammation in the gut as a novel mechanism promoting luminal expansion of S. Typhimurium.


Assuntos
Disbiose/imunologia , Gastroenterite/imunologia , Inflamação/imunologia , Interferon Tipo I/imunologia , Fator de Transcrição STAT2/fisiologia , Infecções por Salmonella/imunologia , Salmonella typhimurium/imunologia , Animais , Células Cultivadas , Disbiose/metabolismo , Disbiose/patologia , Feminino , Gastroenterite/metabolismo , Gastroenterite/microbiologia , Gastroenterite/patologia , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Interferon Tipo I/metabolismo , Intestinos/imunologia , Intestinos/microbiologia , Intestinos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Neutrófilos/patologia , Fator de Transcrição STAT1/fisiologia , Infecções por Salmonella/metabolismo , Infecções por Salmonella/microbiologia , Infecções por Salmonella/patologia
6.
Nat Microbiol ; 4(7): 1120-1128, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30936486

RESUMO

Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.


Assuntos
Infecções por Caliciviridae/prevenção & controle , Gastroenterite/prevenção & controle , Trato Gastrointestinal/virologia , Hospedeiro Imunocomprometido , Interferons/metabolismo , Norovirus/imunologia , Animais , Astroviridae/classificação , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/fisiologia , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Transplante de Microbiota Fecal , Fezes/virologia , Feminino , Gastroenterite/imunologia , Gastroenterite/virologia , Trato Gastrointestinal/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Transdução de Sinais , Eliminação de Partículas Virais
7.
Virus Genes ; 55(3): 280-289, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30725444

RESUMO

Noroviruses are leading cause of acute gastroenteritis worldwide. In our previous study, we established an in vitro histo-blood group antigens (HBGAs) binding blockade assay against GII.3 Norovirus virus like particles (VLPs) with trypsin digestion. In this study, we characterized the blocking antibody binding site and epitope type (linear or conformational) by using hyperimmune sera produced against different antigens. VP1 from Jingzhou402 (GII.3, JZ402) strain was expressed by using pGEX-6p-1 expression vector and the insoluble proteins were purified for immunization in rabbit. Previously characterized chimeric VP1-assembled VLPs (GII.4-VP1/GII.3-P2) were used to immunize guinea pig. Peptides reactive with hyperimmune serum against VLPs derived from the VP1 of JZ402 strain were conjugated with BSA and used to immunize rabbits. Hyperimmune sera against above antigens and JZ402 and JZ403 strain-derived VLPs were used to compare their HBGAs blocking effects. Rabbit anti-GST-VP1 and BSA-peptide conjugated hyperimmune sera demonstrated no blocking effects against the binding of GII.3 and GII.4 NoV VLPs to salivary HBGAs. Guinea pig anti-GII.4-VP1/GII.3-P2 hyperimmune serum blocked the binding of trypsin cleaved GII.3 VLPs to salivary HBGAs with no or very weak blocking effects against the binding of GII.4 VLPs to salivary HBGAs. Our data indicated that HBGAs blocking antibodies primarily bound the P2 domain of GII.3 NoV VP1 and their binding epitopes were most probably conformation-dependent.


Assuntos
Antígenos de Grupos Sanguíneos/genética , Epitopos/genética , Gastroenterite/genética , Norovirus/genética , Animais , Anticorpos/genética , Anticorpos/imunologia , Sítios de Ligação/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Epitopos/imunologia , Gastroenterite/imunologia , Gastroenterite/virologia , Genótipo , Cobaias , Humanos , Norovirus/imunologia , Ligação Proteica , Coelhos , Transdução de Sinais/genética
8.
Nat Commun ; 10(1): 250, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651557

RESUMO

T cell dependent secretory IgA (SIgA) generated in the Peyer's patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host's immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines. Ectopic expression of Shigella flexneri periplasmic ATP-diphosphohydrolase (apyrase) abolishes ATP release by bacteria and improves the specific IgA response against live oral vaccines. Antibody responses primed in the absence of intestinal extracellular ATP (eATP) also provide superior protection from enteropathogenic infection. Thus, modulation of eATP in the small intestine can affect high-affinity IgA response against gut colonizing bacteria.


Assuntos
Trifosfato de Adenosina/metabolismo , Gastroenterite/imunologia , Microbioma Gastrointestinal/fisiologia , Imunoglobulina A Secretora/metabolismo , Infecções por Salmonella/imunologia , Trifosfato de Adenosina/imunologia , Administração Oral , Animais , Apirase/imunologia , Apirase/metabolismo , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Modelos Animais de Doenças , Escherichia coli/imunologia , Escherichia coli/metabolismo , Feminino , Gastroenterite/microbiologia , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Humanos , Íleo/imunologia , Íleo/metabolismo , Íleo/microbiologia , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Receptores Purinérgicos P2X7/imunologia , Receptores Purinérgicos P2X7/metabolismo , Infecções por Salmonella/microbiologia , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Shigella flexneri/imunologia , Shigella flexneri/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
9.
J Immunol ; 202(3): 956-965, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30617224

RESUMO

The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic Salmonella gastroenteritis model, Ab-mediated neutralization of IL-22 impaired intestinal epithelial barrier integrity and, consequently, exaggerated expression of proinflammatory cytokines. As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum-a feature reminiscent of fibrotic strictures seen in Crohn disease patients. Corresponding to the exaggerated immunopathology caused by IL-22 suppression, Salmonella burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of Bacteroides acidifaciens Our findings thus indicate that IL-22 plays a protective role by limiting infection-induced gut immunopathology but can also lead to persistent pathogen colonization.


Assuntos
Gastroenterite/imunologia , Microbioma Gastrointestinal , Interleucinas/imunologia , Salmonelose Animal/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/imunologia , Bacteroides , Ceco/imunologia , Ceco/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Citocinas/imunologia , Gastroenterite/microbiologia , Inflamação , Interleucinas/antagonistas & inibidores , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Indução de Remissão , Salmonelose Animal/terapia , Salmonella typhimurium
10.
J Acquir Immune Defic Syndr ; 80(2): 242-245, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30422903

RESUMO

OBJECTIVE: To investigate the longitudinal changes of gut structural damage in chronically untreated HIV infection. DESIGN: This is a 96-week prospective, single-site, cohort study of antiretroviral therapy-naive HIV-infected participants. METHODS: Intestinal fatty acid-binding proteins (I-FABP) were used as a surrogate marker of gut structural damage. We assessed changes in I-FABP over 96 weeks and examined the associations between I-FABP, HIV variables, and inflammation. Spearman's correlations and linear mixed-effect models were used to study relationships among variables. RESULTS: A total of 63 HIV-infected, antiretroviral therapy-naive patients were included in this analysis. At baseline, 76% were male; 62% were African American, with median age and body mass index of 40 years and 27 kg/m, respectively. Median HIV-RNA and CD4 T-cell counts were 5520 copies per milliliter and 588 cells per mm, respectively. I-FABP significantly increased from baseline to week 96 (mean change +333.9 pg/mL; P = 0.03), and this increase was associated with viral replication (rho = +0.4; P = 0.03). I-FABP levels were found to be associated with markers of inflammation: sTNFR-II (rho = 0.4, P = 0.02) and sVCAM-1 (rho = 0.04; P < 0.01) at all study time points. Lower baseline CD4 T-cell counts was found to be independently associated with I-FABP progression after adjusting for baseline characteristic variables (P = 0.02). CONCLUSION: Gut structural damage is an ongoing process in the chronic phase of untreated HIV infection and is largely dependent on viral replication. I-FABP was found to be associated with worse immune function, increased inflammation, and viremia in chronically untreated HIV infection, supporting its role as a biomarker of intestinal barrier dysfunction.


Assuntos
Gastroenterite/fisiopatologia , Infecções por HIV/fisiopatologia , Mucosa Intestinal/patologia , Ativação Linfocitária/imunologia , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Progressão da Doença , Feminino , Gastroenterite/imunologia , Gastroenterite/virologia , Infecções por HIV/imunologia , Humanos , Mucosa Intestinal/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral
11.
Diagn Microbiol Infect Dis ; 93(1): 69-73, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30174143

RESUMO

OBJECTIVE: Predictive factors associated with clinical outcomes of chronic norovirus infection (CNI) in primary immunodeficiency diseases (PIDD) are lacking. METHOD: We sought to characterize CNI using a multi-institutional cohort of patients with PIDD and CNI using the Clinical Immunology Society's CIS-PIDD Listserv e-mail group. RESULTS: Thirty-four subjects (21 males and 13 females) were reported from centers across North America, Europe, and Asia. All subjects were receiving high doses (median IgG dose: 1200 mg/kg/month) of supplemental immunoglobulin therapy. Fifty-three percent had a complete absence of B cells (median B-cell count 0; range 0-139 cells/µL). Common Variable Immune Deficiency (CVID) subjects manifested a unique phenotype with B-cell lymphopenia, non O+ blood type, and villous atrophy (logistic regression model, P = 0.01). Five subjects died, all of whom had no evidence of villous atrophy. CONCLUSION: While Norovirus (NoV) is thought to replicate in B cells, in this PIDD cohort of CNI, B-cell lymphopenia was common, indicating that the presence of B lymphocytes is not essential for CNI.


Assuntos
Infecções por Caliciviridae/imunologia , Síndromes de Imunodeficiência/virologia , Norovirus/fisiologia , Adolescente , Adulto , Linfócitos B/patologia , Infecções por Caliciviridae/mortalidade , Infecções por Caliciviridae/patologia , Doença Crônica , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/terapia , Imunodeficiência de Variável Comum/virologia , Feminino , Gastroenterite/imunologia , Gastroenterite/mortalidade , Gastroenterite/patologia , Humanos , Imunização Passiva , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/patologia , Síndromes de Imunodeficiência/terapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Norovirus/genética , Estudos Retrospectivos , Adulto Jovem
12.
Cell Host Microbe ; 24(5): 665-676.e4, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30392829

RESUMO

Viral persistence can contribute to chronic disease and promote virus dissemination. Prior work demonstrated that timely clearance of systemic murine norovirus (MNV) infection depends on cell-intrinsic type I interferon responses and adaptive immunity. We now find that the capsid of the systemically replicating MNV strain CW3 promotes lytic cell death, release of interleukin-1α, and increased inflammatory cytokine release. Correspondingly, inflammatory monocytes and neutrophils are recruited to sites of infection in a CW3-capsid-dependent manner. Recruited monocytes and neutrophils are subsequently infected, representing a majority of infected cells in vivo. Systemic depletion of inflammatory monocytes or neutrophils from persistently infected Rag1-/- mice reduces viral titers in a tissue-specific manner. These data indicate that the CW3 capsid facilitates lytic cell death, inflammation, and recruitment of susceptible cells to promote persistence. Infection of continuously recruited inflammatory cells may be a mechanism of persistence broadly utilized by lytic viruses incapable of establishing latency.


Assuntos
Infecções por Caliciviridae/imunologia , Gastroenterite/imunologia , Células Mieloides/imunologia , Células Mieloides/virologia , Norovirus/imunologia , Norovirus/patogenicidade , Imunidade Adaptativa , Animais , Infecções por Caliciviridae/virologia , Capsídeo/imunologia , Morte Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Gastroenterite/virologia , Genes Virais/genética , Células HEK293 , Proteínas de Homeodomínio/genética , Interações Hospedeiro-Patógeno , Humanos , Inflamação/imunologia , Interferon Tipo I/imunologia , Interleucina-1alfa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Monócitos/virologia , Neutrófilos/imunologia , Neutrófilos/virologia , Norovirus/genética , Carga Viral
13.
Expert Rev Vaccines ; 17(11): 1037-1051, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30365904

RESUMO

INTRODUCTION: Latin American countries were among the first to adopt rotavirus vaccines into national immunization programs; we reviewed one decade of their experience with rotavirus vaccination. AREAS COVERED: We systematically reviewed manuscripts published January 1990-January 2018 to assess rotavirus vaccine effectiveness (VE) via meta-analysis; describe trends in rotavirus and acute gastroenteritis (AGE)-associated hospitalizations and mortality before and after vaccine introduction; and estimate annual hospitalizations and deaths averted by rotavirus vaccination in Latin American and Caribbean children <5 years. Rotavirus vaccines demonstrated VE against rotavirus hospitalization of 76% (95% CI: 58-87) in low-mortality countries and 67% (95% CI: 54-76) in high-mortality countries for children <1 year of age. Reductions of 64.0% (interquartile range (IQR): 49.9-69.2) were observed in rotavirus hospitalizations, 32.8% (IQR 29.0-40.3) in AGE hospitalizations, and 53.5% (IQR: 40.4-57.1) in AGE-related mortalities in children <5 years. In 2015, an estimated 125,000 rotavirus-associated hospitalizations and 800 rotavirus-related deaths were prevented in countries that implemented rotavirus vaccines. EXPERT COMMENTARY: Rotavirus vaccines remain an effective tool against diarrheal disease. The continued success of rotavirus vaccines provides evidence for adoption in Latin American and Caribbean countries that have not yet introduced it, and improvement within those with low coverage.


Assuntos
Gastroenterite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Região do Caribe , Pré-Escolar , Diarreia/imunologia , Diarreia/prevenção & controle , Diarreia/virologia , Gastroenterite/imunologia , Gastroenterite/virologia , Hospitalização/estatística & dados numéricos , Humanos , Programas de Imunização , Lactente , América Latina , Infecções por Rotavirus/imunologia , Vacinas contra Rotavirus/imunologia , Vacinação/métodos
15.
Expert Rev Vaccines ; 17(9): 773-784, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30092671

RESUMO

INTRODUCTION: Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis (AGE) cases globally, and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. AREAS COVERED: Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. EXPERT COMMENTARY: A norovirus vaccine should target high-risk populations, including the young and the elderly, and protect them against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development.


Assuntos
Infecções por Caliciviridae/prevenção & controle , Gastroenterite/prevenção & controle , Norovirus/imunologia , Vacinas Virais/administração & dosagem , Animais , Infecções por Caliciviridae/imunologia , Infecções por Caliciviridae/virologia , Efeitos Psicossociais da Doença , Gastroenterite/imunologia , Gastroenterite/virologia , Saúde Global , Humanos , Saúde Pública , Vacinas Virais/imunologia
16.
J Immunoassay Immunochem ; 39(3): 235-248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30044696

RESUMO

Immunoglobulin Y (IgY), an antibody present in birds, reptiles, and amphibians, is actively transported from the serum to egg yolks, where it is stored in large quantities. The use of chicken polyclonal IgY instead of mammalian IgG antibodies for biomedical applications has ethical and economic advantages, such as the lack of a need for animal bleeding because the antibodies are extracted from eggs after hen immunization and the low cost of the production and purification methods. This article reviews the latest IgY applications in diagnostic virology and the therapeutic use of IgY in viral gastroenteritis.


Assuntos
Galinhas/imunologia , Gastroenterite/tratamento farmacológico , Gastroenterite/virologia , Imunoglobulinas/imunologia , Virologia/métodos , Animais , Gastroenterite/imunologia , Imunoglobulinas/economia , Imunoglobulinas/isolamento & purificação , Imunoglobulinas/uso terapêutico
17.
Epidemiol Infect ; 146(15): 1996-2002, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30056817

RESUMO

Circulating 25-hydroxy vitamin D (25(OH)D) is related to decreased rates of gastrointestinal and ear infections in school-age children. Vitamin D-binding protein (DBP) transports 25(OH)D and exerts immunological functions; however, it is unknown whether DBP is associated with infectious morbidity in children. We quantified plasma DBP concentrations in 540 school-age children at the time of recruitment into a cohort study in Bogotá, Colombia and obtained daily information on infectious morbidity symptoms and doctor visits during the school year. We compared the incidence rates of gastrointestinal and respiratory symptoms across quartiles of DBP concentration by estimating adjusted incidence rate ratios (IRRs) with 95% confidence interval (CI). We also estimated the per cent of the associations between DBP and morbidity that were mediated through 25(OH)D using a counterfactual frame. Mean ± s.d. DBP concentration was 2650 ± 1145 nmol/l. DBP was inversely associated with the rates of diarrhoea with vomiting (IRR for quartiles 2-4 vs. 1 = 0.48; 95% CI 0.25-0.92; P = 0.03) and earache/ear discharge with fever (IRR for quartiles 2-4 vs. 1 = 0.29; 95% CI 0.12-0.71; P = 0.006). The DBP-morbidity associations were not mediated through 25(OH)D. We conclude that plasma DBP predicts lower incidence of gastrointestinal and ear infections in school-age children independent of 25(OH)D.


Assuntos
Gastroenterite/epidemiologia , Otite/epidemiologia , Instituições Acadêmicas , Estudantes , Proteína de Ligação a Vitamina D/sangue , Criança , Pré-Escolar , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Gastroenterite/imunologia , Humanos , Incidência , Masculino , Otite/imunologia , Plasma/química , Vitamina D/sangue
18.
Int J Med Microbiol ; 308(7): 796-802, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29970302

RESUMO

Salmonella enteric serovar infections result in high morbidity and mortality worldwide. Cross-protective vaccines are an effective strategy in controlling salmonellosis caused by multiple serotypes. In our previous study, outer membrane vesicles (OMVs) derived from flagellin-deficient Salmonella Typhimurium (S. Typhimurium) were proven effective in mediating cross-protection against infection by multiple Salmonella serotypes; OMVs also exhibit potent adjuvant effects. In this study, we further investigated the adjuvant capacities of flagellin-deficient S. Typhimurium OMVs. Our finding showed that outer membrane proteins (OMPs) in combination with flagellin-deficient S. Typhimurium OMVs could function as adjuvants and invoke stronger humoral, cellular, mucosal, and cross-protective immune responses compared to conventional aluminum (alum). Furthermore, as an adjuvant, OMVs could induce significantly higher cellular immune responses and display enhanced cross-protection for OMPs against wild-type virulent Salmonella Choleraesuis and Salmonella Enteritidis challenge. In summary, OMVs function as a potent adjuvant with the capability of conferring greater cross-protection against infection by multiple Salmonella serotypes, and may be of great value as an effective vaccine adjuvant in enteric diseases.


Assuntos
Adjuvantes Imunológicos , Proteínas da Membrana Bacteriana Externa/imunologia , Proteção Cruzada/imunologia , Flagelina/genética , Gastroenterite/imunologia , Salmonelose Animal/imunologia , Salmonella typhimurium/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Membrana Celular/genética , Feminino , Gastroenterite/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Salmonelose Animal/microbiologia , Vacinas contra Salmonella/imunologia
19.
J Infect Dis ; 218(5): 716-725, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29912471

RESUMO

Background: Human noroviruses (HuNoVs) are a prominent cause of gastroenteritis, yet fundamental questions remain regarding epidemiology, diversity, and immunity in sub-Saharan African children. We investigated HuNoV seroprevalence and genetic and sociodemographic risk factors in Ugandan children. Methods: We randomly screened 797 participants of a longitudinal birth cohort (Entebbe, EMaBS) and 378 from a cross-sectional survey (rural Lake Victoria, LaVIISWA), for antibodies against HuNoV genotypes by ELISA. We used linear regression modeling to test for associations between HuNoV antibody levels and sociodemographic factors, and with the human susceptibility rs601338 FUT2 secretor SNP and histo-blood group antigens (A/B/O). Results: Of EMaBS participants, 76.6% were seropositive by age 1, rising to 94.5% by age 2 years. Seroprevalence in 1 year olds of the rural LaVIISWA survey was even higher (95%). In the birth cohort, 99% of seropositive 2 year olds had responses to multiple HuNoV genotypes. We identified associations between secretor status and genogroup GII antibody levels (GII.4 P = 3.1 × 10-52), as well as ABO and GI (GI.2 P = 2.1 × 10-12). Conclusions: HuNoVs are highly prevalent in Ugandan children, indicating a substantial burden of diarrhea-associated morbidity with recurrent infections. Public health interventions, including vaccination, and increased surveillance are urgently needed.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Variação Genética , Genótipo , Norovirus/classificação , Norovirus/imunologia , Antígenos de Grupos Sanguíneos/análise , Infecções por Caliciviridae/genética , Infecções por Caliciviridae/imunologia , Pré-Escolar , Estudos Transversais , Demografia , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Fucosiltransferases/genética , Gastroenterite/epidemiologia , Gastroenterite/genética , Gastroenterite/imunologia , Gastroenterite/virologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Norovirus/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Socioeconômicos , Uganda/epidemiologia
20.
Clin Sci (Lond) ; 132(11): 1169-1177, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29925624

RESUMO

Oral vaccines (OVs), provide protection against pathogens that infect mucosal surfaces and their potency relies on their capacity to elicit T- and B-cell responses directed to these surfaces. Oral vaccination efficacy has been found to vary considerably with differences in geographical locations and socioeconomic status. Specifically, in children living in resource-poor countries, undernourishment and chronic gastrointestinal (GI) infection are associated with the failure of OVs, which is a tragic outcome for the children who would benefit most from mucosal-based protection from infection. Both undernutrition and GI infection have been shown to profoundly affect the microbiota, inducing 'dysbiosis' characterized by narrowed bacterial diversity and increased frequency of bacterial clades associated with the induction of inflammation. Recent studies have demonstrated that the microbiota exerts a profound effect on the development of mucosal immune responses. Therefore, it seems likely that OV failure in resource-poor regions is affected by alterations to the immune response driven by dysbiotic changes to the microbiota. Here, we review the contribution of the microbiota to OV efficacy in the context of diet and GI infection.


Assuntos
Fenômenos Fisiológicos da Nutrição Infantil/imunologia , Gastroenterite/imunologia , Microbioma Gastrointestinal/imunologia , Vacinas/administração & dosagem , Administração Oral , Criança , Pré-Escolar , Países em Desenvolvimento , Dieta , Disbiose/imunologia , Humanos , Imunidade nas Mucosas , Vacinas/imunologia
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