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1.
N Engl J Med ; 382(4): 318-327, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31971677

RESUMEN

BACKGROUND: The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. METHODS: We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline. RESULTS: A total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P = 0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified. CONCLUSIONS: Among Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT03089086.).


Asunto(s)
Portador Sano/prevención & control , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo B/aislamiento & purificación , Neisseria meningitidis/aislamiento & purificación , Adolescente , Australia/epidemiología , Portador Sano/epidemiología , Femenino , Humanos , Masculino , Neisseria meningitidis/genética , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Serogrupo , Método Simple Ciego
2.
Chem Commun (Camb) ; 56(3): 344-347, 2020 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-31808481

RESUMEN

Exploiting synergistic remote participation effects of acyl groups at the O3 and O6 positions was key to the complete α-selectivity during the total synthesis of the unique (1 → 2)- and (1 → 3)-linked α-oligoglucosides from the Helicobacter pylori O2 O-antigen. Acyl remote participation and solvent effects were found to counteract during α-stereoselective glucosylations for the first time. The resulting antigen is a lead for the development of a carbohydrate-conjugate vaccine.


Asunto(s)
Helicobacter pylori/metabolismo , Antígenos O/química , Oligosacáridos/síntesis química , Oligosacáridos/química , Serogrupo , Solventes/química , Estereoisomerismo , Vacunas Conjugadas/química
3.
Food Microbiol ; 85: 103280, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31500706

RESUMEN

Listeria monocytogenes causes severe diseases in humans, including febrile gastroenteritis and systemic infections that has a high mortality despite antibiotic treatment. This pathogen may cause massive outbreaks associated to the consumption of contaminated food products, which highlight its importance in public health. In the last decade, L. monocytogenes has emerged as a foodborne pathogen of major importance in Chile. A previous work showed that in Chile during 2008 and 2009, L. monocytogenes serotypes 1/2a, 1/2b and 4b were the most frequently identified in food and clinical strains. Here we report the molecular characterization of L. monocytogenes strains isolated from 2008 to 2017 in the country. Our results indicate that serotypes 1/2a, 1/2b and 4b continue to be the most commonly found in food products. In addition, we identify persistent and widespread PFGE subtypes. This study reports ten years of epidemiological surveillance ofL. monocytogenes in Chile.


Asunto(s)
Monitoreo Epidemiológico , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Listeria monocytogenes/genética , Listeriosis/epidemiología , Chile/epidemiología , Recuento de Colonia Microbiana , ADN Bacteriano/genética , Brotes de Enfermedades , Enfermedades Transmitidas por los Alimentos/microbiología , Gastroenteritis/epidemiología , Gastroenteritis/microbiología , Variación Genética , Humanos , Listeria monocytogenes/patogenicidad , Productos de la Carne/microbiología , Epidemiología Molecular , Salud Pública , Serogrupo , Serotipificación , Factores de Virulencia/genética
4.
Acta Virol ; 63(4): 403-414, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31802683

RESUMEN

The use of live attenuated vaccine (LAV) is the main method for controlling infectious bronchitis (IB). It is advisable to develop a LAV using a dominant serotype in the region in the case of vaccine failure. Since 793/B serotype is one of the most predominant circulating IB viruses in Iran, attenuation of three Iranian 793/B isolates (IR/773/2001, IR/794/2002 and IR/520/2002) was done by serial passaging in specific pathogen free (SPF) embryonated chicken eggs up to 90 passages to assess the degree of their attenuation to achieve a native LAV in the future. Virulence and pathogenicity of passage levels 15 and 90 of isolates 773 and 794 were compared using histopathology, ciliostasis and potency tests. The results showed a decrease in the virulence and pathogenicity of the isolates at passage 90 compared to passage 15, although this decrease in pathogenicity was very mild and viruses after passage 90 were not adequately attenuated. Each isolate underwent some amino acid changes at passage 90. In case of isolate 773 it was 5 aa changes, while in isolate 794 it was 19 aa changes. Some amino acid changes resulted in change into amino acid with different hydrophobicity characteristics. No amino acid change was found at passage level 15 compared to wild type viruses. Interestingly, we did not find previously reported change in amino acid 95 in passage levels 15 and 90. Keywords: infectious bronchitis; live attenuated vaccine; 793/B serotype; pathogenicity; attenuation; nucleotide sequencing.


Asunto(s)
Aminoácidos , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral , Aminoácidos/genética , Animales , Embrión de Pollo , Pollos , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Virus de la Bronquitis Infecciosa/clasificación , Virus de la Bronquitis Infecciosa/genética , Irán , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Serogrupo , Vacunas Atenuadas
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1403-1408, 2019 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-31838812

RESUMEN

Objective: To investigate the molecular characterization of adult diarrhea cases caused by enterotoxic Escherichia coli (ETEC) and explore the practical model of epidemiology for laboratory technique and data needs based on the surveillance network. Methods: Epidemiological design and sampling targeted adult cases ETEC caused diarrhea in epidemic season. The enterotoxin type, serogroup, resistance, colonization factor and molecular type of ETEC were identified. Multiple dynamic phenotypic characteristics of ETEC were indicated by multidimensional and multivariable data. Results: From 2016 to 2018, 84 eligible ETEC strains were detected. The dominant serums/toxins were O∶6 (STh), O∶25 (LT), O∶159 (STh), O∶153 (STh). O∶6 (STh+CS21), which replaced O∶25 and O∶159 as the popular clones in 2018. Six cases of O∶153 (STh+CFA/I+CS8+PT34) in outbreak in 2017 were imported ones. The resistance rates of ETEC strains detected in adults to sulfasoxazole, naproxinic acid, ampicillin and azithromycin were more than 30%, multidrug resistance (MDR) reached 58.3%. Serum/toxin types suggested that attenuated strains were more likely to become MDR. Molecular typing confirmed that the genetic similarity of the dominant clone of O∶6 serogroup (PT20-24) was higher than O∶25 and O∶159. There was a high correlation between the minimal inhibitory concentration (MIC) of azithromycin and the resistant gene mphA (87.5%, 28/32). O∶6 (STh+CS21+mphA) resistant clone was first detected in 2016. Conclusion: A new epidemic clone in adult ETEC diarrhea cases in Shanghai was O∶6 (STh+CS21+mphA). For the first time the association between azithromycin resistance gene mphA and a serum group of ETEC was observed. Multidimensional and multivariate analysis techniques based on epidemiology can help reveal the potential transmission pattern of ETEC for the accurate surveillance and early warning of outbreaks.


Asunto(s)
Antibacterianos/farmacología , Azitromicina/uso terapéutico , Diarrea/tratamiento farmacológico , Escherichia coli Enterotoxigénica/genética , Escherichia coli Enterotoxigénica/aislamiento & purificación , Enterotoxinas/análisis , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Adulto , China , Diarrea/microbiología , Farmacorresistencia Microbiana , Escherichia coli Enterotoxigénica/clasificación , Escherichia coli Enterotoxigénica/efectos de los fármacos , Enterotoxinas/genética , Proteínas de Escherichia coli/genética , Humanos , Pruebas de Sensibilidad Microbiana , Serogrupo , Serotipificación
6.
Pol J Microbiol ; 68(3): 295-302, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31880874

RESUMEN

The article presents data on serological studies of 573 sera samples of cattle that were collected from the farms affected by leptospirosis in different regions of Ukraine in the period of 2014-2015. Samples were investigated by the microscopic agglutination test (MAT), which was conducted within eight serological groups of Leptospira and nine serovars: Sejroe (serovars polonica and hardjo), Hebdomadis (serovar kabura), Tarassovi (serovar tarassovi), Pomona (serovar pomona), Grippotyphosa (serovar grippotyphosa), Canicola (serovar canicola), Icterohaemorrhagiae (serovar copenhageni), and Australis (serovar bratislava). The circulation of L. interrogans serovar hardjo among cattle has been observed in all 11 regions of Ukraine investigated within 25.8-60.0% of the leptospirosis-positive serum samples in these regions. Antibodies in the cattle sera against serovar hardjo (serogroup Sejroe) were detected in 139 of the 370 cows reacting positively in MAT. Overall, they were detected in 24.3% animals out of the total of 573 cows investigated. These are the preliminary results, however, in our opinion, they should allow to include the serovar hardjo in a standard panel of strains for MAT in Ukraine.The article presents data on serological studies of 573 sera samples of cattle that were collected from the farms affected by leptospirosis in different regions of Ukraine in the period of 2014­2015. Samples were investigated by the microscopic agglutination test (MAT), which was conducted within eight serological groups of Leptospira and nine serovars: Sejroe (serovars polonica and hardjo), Hebdomadis (serovar kabura), Tarassovi (serovar tarassovi), Pomona (serovar pomona), Grippotyphosa (serovar grippotyphosa), Canicola (serovar canicola), Icterohaemorrhagiae (serovar copenhageni), and Australis (serovar bratislava). The circulation of L. interrogans serovar hardjo among cattle has been observed in all 11 regions of Ukraine investigated within 25.8­60.0% of the leptospirosis-positive serum samples in these regions. Antibodies in the cattle sera against serovar hardjo (serogroup Sejroe) were detected in 139 of the 370 cows reacting positively in MAT. Overall, they were detected in 24.3% animals out of the total of 573 cows investigated. These are the preliminary results, however, in our opinion, they should allow to include the serovar hardjo in a standard panel of strains for MAT in Ukraine.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Enfermedades de los Bovinos/sangre , Leptospira interrogans/inmunología , Leptospirosis/veterinaria , Pruebas de Aglutinación , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Femenino , Leptospira interrogans/clasificación , Leptospira interrogans/genética , Leptospira interrogans/aislamiento & purificación , Leptospirosis/sangre , Leptospirosis/microbiología , Masculino , Serogrupo , Ucrania
7.
Pol J Microbiol ; 68(4): 439-447, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31880888

RESUMEN

Salmonella infection is most common in patients with infected aortic aneurysm, especially in Asia. When the aortic wall is heavily atherosclerotic, the intima is vulnerable to invasion by Salmonella, leading to the development of infected aortic aneurysm. By using THP-1 macrophage-derived foam cells to mimic atherosclerosis, we investigated the role of three Salmonella enterica serotypes - Typhimurium, Enteritidis, and Choleraesuis - in foam cell autophagy and inflammasome formation. Herein, we provide possible pathogenesis of Salmonella-associated infected aortic aneurysms. Three S. enterica serotypes with or without virulence plasmid were studied. Through Western blotting, we investigated cell autophagy induction and inflammasome formation in Salmonella-infected THP-1 macrophage-derived foam cells, detected CD36 expression after Salmonella infection through flow cytometry, and measured interleukin (IL)-1ß, IL-12, and interferon (IFN)-α levels through enzyme-linked immunosorbent assay. At 0.5 h after infection, plasmid-bearing S. Enteritidis OU7130 induced the highest foam cell autophagy - significantly higher than that induced by plasmid-less OU7067. However, plasmid-bearing S. Choleraesuis induced less foam cell autophagy than did its plasmid-less strain. In foam cells, plasmid-less Salmonella infection (particularly S. Choleraesuis OU7266 infection) led to higher CD36 expression than did plasmid-bearing strains infection. OU7130 and OU7266 infection induced the highest IL-1ß secretion. OU7067-infected foam cells secreted the highest IL-12p35 level. Plasmid-bearing S. Typhimurium OU5045 induced a higher IFN-α level than did other Salmonella serotypes. Salmonella serotypes are correlated with foam cell autophagy and IL-1ß secretion. Salmonella may affect the course of foam cells formation, or even aortic aneurysm, through autophagy.Salmonella infection is most common in patients with infected aortic aneurysm, especially in Asia. When the aortic wall is heavily atherosclerotic, the intima is vulnerable to invasion by Salmonella, leading to the development of infected aortic aneurysm. By using THP-1 macrophage-derived foam cells to mimic atherosclerosis, we investigated the role of three Salmonella enterica serotypes ­ Typhimurium, Enteritidis, and Choleraesuis ­ in foam cell autophagy and inflammasome formation. Herein, we provide possible pathogenesis of Salmonella-associated infected aortic aneurysms. Three S. enterica serotypes with or without virulence plasmid were studied. Through Western blotting, we investigated cell autophagy induction and inflammasome formation in Salmonella-infected THP-1 macrophage-derived foam cells, detected CD36 expression after Salmonella infection through flow cytometry, and measured interleukin (IL)-1ß, IL-12, and interferon (IFN)-α levels through enzyme-linked immunosorbent assay. At 0.5 h after infection, plasmid-bearing S. Enteritidis OU7130 induced the highest foam cell autophagy ­ significantly higher than that induced by plasmid-less OU7067. However, plasmid-bearing S. Choleraesuis induced less foam cell autophagy than did its plasmid-less strain. In foam cells, plasmid-less Salmonella infection (particularly S. Choleraesuis OU7266 infection) led to higher CD36 expression than did plasmid-bearing strains infection. OU7130 and OU7266 infection induced the highest IL-1ß secretion. OU7067-infected foam cells secreted the highest IL-12p35 level. Plasmid-bearing S. Typhimurium OU5045 induced a higher IFN-α level than did other Salmonella serotypes. Salmonella serotypes are correlated with foam cell autophagy and IL-1ß secretion. Salmonella may affect the course of foam cells formation, or even aortic aneurysm, through autophagy.


Asunto(s)
Aneurisma de la Aorta/microbiología , Infecciones por Salmonella/microbiología , Salmonella typhimurium/patogenicidad , Animales , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/inmunología , Línea Celular , Humanos , Interferón-alfa/genética , Interferón-alfa/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Antígeno Ki-1/genética , Antígeno Ki-1/inmunología , Macrófagos/inmunología , Macrófagos/microbiología , Monocitos/inmunología , Monocitos/microbiología , Plásmidos/genética , Plásmidos/metabolismo , Infecciones por Salmonella/genética , Infecciones por Salmonella/inmunología , Salmonella typhimurium/genética , Salmonella typhimurium/fisiología , Serogrupo , Virulencia
8.
BMC Infect Dis ; 19(1): 1009, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31779587

RESUMEN

BACKGROUND: Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed. METHODS: Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR. RESULTS: The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene. 21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele. CONCLUSIONS: The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections. This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.


Asunto(s)
Infecciones Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética , Adulto , Antibacterianos/farmacología , Proteínas Bacterianas/genética , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Humanos , Hungría/epidemiología , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Fenotipo , Prevalencia , Serogrupo , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/aislamiento & purificación , Streptococcus agalactiae/patogenicidad , Virulencia/genética
9.
BMC Infect Dis ; 19(1): 933, 2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31690269

RESUMEN

BACKGROUND: Hand, foot and mouth disease (HFMD) has emerged as a major public health issue in Vietnam since 2003. We aimed to investigate the household transmission of HFMD and its causative viruses from 150 households in a high incidence province in Vietnam. METHODS: A longitudinal study was conducted in patients presenting to the provincial hospital with a HFMD-like syndrome, along with their household members between April and August 2014 in Dong Thap Province. Each participant was followed up for 2 weeks. We enrolled 150 patients aged under 15 who were clinically diagnosed with HFMD in Dong Thap Hospital, 600 household members, and 581/600 household members completed the study. All participants were interviewed using a standard questionnaire. Throat swabs and blood samples were taken for molecular detection of viruses and assessment of neutralizing antibodies, respectively. Index cases were defined using a clinical case definition, household contact cases were defined using a similar definition applied to the 2 weeks before admission and 2 weeks after discharge of the index case. Characteristics of index cases, household contacts, the attack rate, serotype features and related factors of HFMD were reported. RESULT: Among 150 index cases, 113 were laboratory confirmed: 90/150 were RT-PCR-positive, 101/142 had a ≥ 4-fold increase of neutralizing antibody against Enterovirus A71 (EV-A71), Coxsackievirus (CV) A6 or CV-A16 across the two samples collected. 80/150 (53%) were males, and 45/150 (30%) were under the age of 1. The predominant serotype was CV-A6, identified in 57/87 (65.5%) of the specimens. No deaths were reported. Among 581 household contacts, 148 were laboratory confirmed: 12/581 were RT-PCR-positive, 142/545 had a ≥ 4-fold increase of neutralizing antibodies against EV-A71, CV-A6 or CV-A16; 4 cases experienced HFMD in the past 4 weeks. Attack rate among household contacts was 148/581 (25.5%). In 7/12 (58%) instances, the index and secondary cases were infected with the same serotype. Having a relationship to index case was significantly associated with EV infection. CONCLUSION: The attack rate among household contacts was relatively high (25.5%) in this study and it seems justified to also consider the household setting as an additional target for intervention programs.


Asunto(s)
Enterovirus/aislamiento & purificación , Enfermedad de Boca, Mano y Pie/diagnóstico , Adolescente , Anticuerpos Neutralizantes/sangre , Niño , Preescolar , Enterovirus/genética , Enterovirus/inmunología , Femenino , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/transmisión , Enfermedad de Boca, Mano y Pie/virología , Humanos , Incidencia , Lactante , Estudios Longitudinales , Masculino , ARN Viral/genética , ARN Viral/metabolismo , Serogrupo , Vietnam/epidemiología
10.
N Engl J Med ; 381(21): 2009-2019, 2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31693803

RESUMEN

BACKGROUND: Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019. METHODS: We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype. RESULTS: Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively). CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).


Asunto(s)
Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/prevención & control , Enfermedades Endémicas/prevención & control , Adolescente , Américas/epidemiología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Asia/epidemiología , Niño , Preescolar , Dengue/epidemiología , Dengue/inmunología , Vacunas contra el Dengue/efectos adversos , Virus del Dengue/aislamiento & purificación , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Serogrupo , Resultado del Tratamiento
14.
Mikrobiyol Bul ; 53(4): 451-456, 2019 Oct.
Artículo en Turco | MEDLINE | ID: mdl-31709942

RESUMEN

Streptococcus pneumoniae is a major cause of bacterial meningitis in children. It can progress and carries a serious risk of mortality and morbidity despite effective treatment. Cochlear implantation is a fairly successful procedure for restoring hearing in cases of sensorineural hearing loss. Moreover, patients with cochlear implants are at increased risk of contracting pneumococcal meningitis compared to the general population. The development of meningitis is associated with pathogens in the middle ear that contaminate the cerebrospinal fluid (CSF), as a result of congenital anomalies in the cochlea, and the cochlear implant. A 4-year-old girl presented to our clinic with fever, vomiting, and weakness. A physical examination showed an axillary temperature of 38.3°C, heart rate of 134/min, respiration rate of 50 breaths/minute, and arterial blood pressure of 120/88 mmHg. The patient also had a neck stiffness and her Kernig and Brudzinski signs were positive. It was discovered that the patient had undergone cochlear implantation approximately five months prior due to bilateral congenital sensorineural hearing loss. She had also received the Haemophilus influenzae type b and PCV-13 vaccines in line with the national immunization calendar. Her laboratory findings showed a leukocyte count of 21.900/mm3 (neutrophils 90% and lymphocytes 10%) and her procalcitonin level was 1.22 ng/ml. An uncountable number of neutrophils was identified in her cerebrospinal fluid, which led to the initial diagnosis of meningitis. There was also 1 mg/dl of glucose (blood glucose, 102 mg/dl) and 706 mg/dl of protein in her cerebrospinal fluid. Empirically, vancomycin (60 mg/kg/day) and ceftriaxone (100 mg/kg/day) were started. Following 5 days of antibiotic treatment, penicillin-susceptible S.pneumoniae was yielded in her CSF culture and identified as serotype 24B. S.pneumoniae with the same antibiotic sensitivity was also identified in her blood culture. Since rhinorrhea was observed on day 16 of hospitalization, she underwent an operation to repair the fistula tract. A computerized tomography cranial scan was performed after the development of acute mental fog at postoperative day 3 and showed brain edema and a thrombus in the right middle cerebral artery. The patient died on day 42 of hospitalization due to multiple organ failure. To our knowledge, this is the first case of meningitis reported in our country associated with S.pneumoniae serotype 24B in a patient with a cochlear implant. While there has been a decrease in the prevalence of invasive pneumococcal disease with routine administration of the pneumococcal conjugate vaccine, a relative increase has been observed in its non-vaccine serotypes. This is relevant not only to patients with more risk factors, such as a cochlear implant, but also those who are at lower risk for pneumococcal infection.


Asunto(s)
Implantación Coclear , Meningitis Neumocócica , Vacunas Neumococicas , Streptococcus pneumoniae , Preescolar , Implantación Coclear/efectos adversos , Resultado Fatal , Femenino , Humanos , Meningitis Neumocócica/etiología , Serogrupo , Streptococcus pneumoniae/fisiología
15.
BMC Vet Res ; 15(1): 340, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31615533

RESUMEN

BACKGROUND: Foot and mouth disease (FMD) is endemic in Afghanistan with serotypes O, A and Asia 1 being prevalent. A retrospective study of data collected through passive surveillance of outbreaks of FMD in Afghanistan from 1995 to 2016 was undertaken to determine the temporal and spatial distribution of FMD in the country. RESULTS: A total of 4171 outbreaks were reported between 1995 and 2008 with a strong correlation between the number of outbreaks and the number of provinces (r = 0.85, s = 68.2, p < 0.001); and between the number of outbreaks and the number of districts containing infected animals (r = 0.68, s = 147.8, p = 0.008). Of 7558 samples collected from livestock originating from 34 provinces in 2009, 2011 and 2013-2015, 54.1% were test positive (FMDV 3ABC-trapping ELISA) and the prevalence varied significantly between years (χ2 = 263.98, df = 4, P < 0.001). Clinically suspected cases were reported in 2016 with a substantial positive correlation (r = 0.70, P < 0.001) between the number of districts with cases and the number of reported cases. Serotype O was the predominant serotype detected during the study period, although serotypes A and Asia1 were also detected. Cattle were involved in all outbreaks in the study period and infections were detected in all years of the study in Hirat province in the north-west (bordering Iran), Nangarhar province in the east (bordering Pakistan) and Kabul province in the centre of the country. CONCLUSIONS: The current paper was the first analysis of existing data focusing on the spatiotemporal distribution of FMD in Afghanistan. The findings from this study provide valuable direction for further research to understand the epidemiology of FMD and its control in Afghanistan.


Asunto(s)
Brotes de Enfermedades/veterinaria , Fiebre Aftosa/epidemiología , Afganistán/epidemiología , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Brotes de Enfermedades/estadística & datos numéricos , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/aislamiento & purificación , Estudios Retrospectivos , Rumiantes/virología , Serogrupo
16.
Infect Immun ; 88(1)2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31636138

RESUMEN

Salmonella is an intracellular bacterium found in the gastrointestinal tract of mammalian, avian, and reptilian hosts. Mouse models have been extensively used to model in vivo distinct aspects of human Salmonella infections and have led to the identification of several host susceptibility genes. We have investigated the susceptibility of Collaborative Cross strains to intravenous infection with Salmonella enterica serovar Typhimurium as a model of human systemic invasive infection. In this model, strain CC042/GeniUnc (CC042) mice displayed extreme susceptibility with very high bacterial loads and mortality. CC042 mice showed lower spleen weights and decreased splenocyte numbers before and after infection, affecting mostly CD8+ T cells, B cells, and all myeloid cell populations, compared with control C57BL/6J mice. CC042 mice also had lower thymus weights with a reduced total number of thymocytes and double-negative and double-positive (CD4+, CD8+) thymocytes compared to C57BL/6J mice. Analysis of bone marrow-resident hematopoietic progenitors showed a strong bias against lymphoid-primed multipotent progenitors. An F2 cross between CC042 and C57BL/6N mice identified two loci on chromosome 7 (Stsl6 and Stsl7) associated with differences in bacterial loads. In the Stsl7 region, CC042 carried a loss-of-function variant, unique to this strain, in the integrin alpha L (Itgal) gene, the causative role of which was confirmed by a quantitative complementation test. Notably, Itgal loss of function increased the susceptibility to S. Typhimurium in a (C57BL/6J × CC042)F1 mouse background but not in a C57BL/6J mouse inbred background. These results further emphasize the utility of the Collaborative Cross to identify new host genetic variants controlling susceptibility to infections and improve our understanding of the function of the Itgal gene.


Asunto(s)
Bacteriemia/genética , Antígeno CD11a/deficiencia , Predisposición Genética a la Enfermedad , Mutación con Pérdida de Función , Infecciones por Salmonella/genética , Salmonella typhimurium/crecimiento & desarrollo , Animales , Bacteriemia/inmunología , Bacteriemia/patología , Carga Bacteriana , Médula Ósea/patología , Modelos Animales de Enfermedad , Genes , Subgrupos Linfocitarios/inmunología , Ratones , Ratones Endogámicos C57BL , Infecciones por Salmonella/inmunología , Infecciones por Salmonella/patología , Serogrupo , Bazo/patología , Análisis de Supervivencia , Timo/patología
17.
Yonsei Med J ; 60(11): 1103-1107, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31637893

RESUMEN

The incidence of vaccine-type Streptococcus pneumoniae carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) S. pneumoniae are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) S. pneumoniae transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by S. pneumoniae. Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of S. pneumoniae identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored S. pneumoniae of NVT. The spread of NVT S. pneumoniae in the post-vaccine era has increased in the community, and resistance pattern for S. pneumoniae of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/transmisión , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/fisiología , Adulto , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Pruebas de Sensibilidad Microbiana , Filogenia , Infecciones Neumocócicas/diagnóstico por imagen , Infecciones Neumocócicas/inmunología , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología
18.
Vet Microbiol ; 238: 108427, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31648724

RESUMEN

Outbreaks of fowl adenovirus (FAdV) has resulted in huge economic losses in poultry industry in China since 2015. This study detected the pathogens from diseased chickens and determined that fowl adenovirus serotype 4 (FAdV-4) and co-infection of immunosuppressive pathogens were the causes of the outbreaks. Phylogenetic analysis results indicated that these pandemic strains originated from previously FAdV-4 predecessor in China and had obtain gene mutations that might contribute to enhanced pathogenicity of these strains. Compared with early strains, the pathogenicity of novel FAdV-4 strains significantly increased, which led to systemic infections and injuries to multiple organs in the infected chickens. Our study could provide useful information for understanding of the FAdV-4 and favorable theory basis for clinical prevention and control of the disease.


Asunto(s)
Infecciones por Adenoviridae/veterinaria , Aviadenovirus/clasificación , Enfermedades de las Aves de Corral/virología , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/virología , Animales , Aviadenovirus/genética , Aviadenovirus/patogenicidad , Pollos , China , Mutación , Filogenia , Enfermedades de las Aves de Corral/prevención & control , Serogrupo , Virulencia/genética
19.
BMC Infect Dis ; 19(1): 860, 2019 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-31623567

RESUMEN

BACKGROUND: Enhanced surveillance for confirmed cases of invasive meningococcal disease (IMD) was introduced in the Netherlands in 2003, in which reference laboratory data (NRLBM) are linked with notification data (OSIRIS). The quality of surveillance information is important for public health decision making. Our objective was to describe the system and evaluate it for data completeness and timeliness. METHODS: Cases reported in the surveillance system from 2004 to 2016 were included. For the notification data, we used information on serogroup, vaccination status, mortality, and country of infection as indicators for record completeness. Notification times to regional and national level were calculated using the reported dates available in the notification database. RESULTS: A total of 2123 cases were reported in the years 2004-2016, of which 1.968 (93%) were reported by the reference laboratory and 1.995 (94%) in the notification system. Of all cases, 1.840 cases (87%) were reported in both systems and could be linked. The serogroup was known in 86% of the notified cases, and was significantly higher (94%) in the years 2013-2016. Information on vaccination status, mortality and country of infection was available in 88, 99 and 97% of notified cases, respectively. Regional notification of cases occurred within one working day for 86% of cases and 98% were notified nationally within three days. CONCLUSIONS: A well performing IMD surveillance system was demonstrated and serogroup completeness has improved over the years. Underlining the need for reporting to both the clinical and laboratory surveillance system remains important to further improve the overall performance in supporting public health response and vaccination policy.


Asunto(s)
Infecciones Meningocócicas/diagnóstico , Vigilancia de la Población/métodos , Bases de Datos Factuales , Humanos , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/microbiología , Neisseria meningitidis/inmunología , Neisseria meningitidis/aislamiento & purificación , Neisseria meningitidis/metabolismo , Países Bajos/epidemiología , Serogrupo , Vacunación/estadística & datos numéricos
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