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1.
Vaccines (Basel) ; 12(3)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38543859

RESUMEN

The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26-35) to 9.6% (3-5) in Nha Trang (2017) and from 7.2% (age 26-35) to 11.4% (6-15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.

2.
PLoS One ; 19(2): e0298147, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38359004

RESUMEN

The emergence of macrolide-resistant Bordetella pertussis (MRBP) is a significant problem because it reduces treatment options for pertussis and exacerbates the severity and spread of the disease. MRBP has been widely prevalent in mainland China since the 2010s and has been sporadically detected in other Asian countries. In Japan, two MRBP clinical strains were first isolated in Tokyo and Osaka between June and July 2018. The isolates BP616 in Osaka and BP625 in Tokyo harbored the same virulence-associated allelic genes (including ptxP1, ptxA1, prn1, fim3A, and fhaB3) and MT195 genotype and exhibited similar antimicrobial susceptibility profiles. However, despite their simultaneous occurrence, a distinguishable epidemiological link between these isolates could not be established. To gain further insight into the genetic relationship between these isolates in this study, we performed whole-genome analyses. Phylogenetic analysis based on genome-wide single-nucleotide polymorphisms revealed that the isolates belonged to one of the three clades of Chinese MRBP isolates, but there were 11 single-nucleotide polymorphism differences between BP616 and BP625. Genome structure analysis revealed two large inversions (202 and 523 kbp) and one small transposition (3.8 kbp) between the genomes. These findings indicate that the two Japanese MRBP isolates are closely related to Chinese MRBP isolates but are genomically distinct, suggesting that they were introduced into Japan from mainland China through different transmission routes.


Asunto(s)
Bordetella pertussis , Tos Ferina , Humanos , Bordetella pertussis/genética , Macrólidos/farmacología , Japón/epidemiología , Filogenia , Tos Ferina/epidemiología , Antibacterianos/farmacología , Genotipo
3.
Microbiol Immunol ; 68(3): 111-114, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38224024

RESUMEN

We evaluated the genetic diversity of Bordetella pertussis, the causative agent of pertussis, within households by whole-genome sequencing. In pairwise comparisons of 23 isolates collected from 11 households, single-nucleotide polymorphism (SNP) analysis revealed extremely low SNP diversity (≤1 SNP) between isolate pairs: no SNPs were detected in 10 households and one SNP was obtained in the remaining household. This SNP was uncommon for B. pertussis and resulted in a nonsynonymous substitution (Ala303Thr) in nicotinate phosphoribosyltransferase. We demonstrated that the same strain is transmitted between household members and that B. pertussis is genomically stable during household transmission.


Asunto(s)
Bordetella pertussis , Tos Ferina , Humanos , Bordetella pertussis/genética , Secuenciación Completa del Genoma , Vacuna contra la Tos Ferina
4.
Front Physiol ; 14: 1243983, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37664430

RESUMEN

Objective: This study clarified the risk factors and pathophysiology of pancreatic cancer by examining the factors associated with fatty pancreas. Methods: The degree of fatty pancreas, background factors, and incidence of pancreatic cancer were examined among nonalcoholic fatty liver disease (NAFLD) patients (n = 281) and intraductal papillary mucinous neoplasm (IPMN) patients with a family history of pancreatic cancer (n = 38). The presence of fatty pancreas was confirmed by the pancreatic CT value/splenic CT value ratio (P/S ratio). Immunohistochemical staining was performed on 10 cases with fatty pancreas, confirmed via postoperative pathology. Results: Fatty pancreas occurred in 126 patients (44.8%) in the NAFLD group who were older (p = 0.0002) and more likely to have hypertension (p < 0.0001). The IPMN group had 18 patients (47.4%) with fatty pancreas, included more men than women (p = 0.0056), and was more likely to have patients with hypertension (p = 0.0010). On histological examination, a significant infiltration of adipocytes into the acini from the pancreatic interstitium induced atrophy of the pancreatic parenchyma, and both M1 and M2 macrophages were detected in the area where adipocytes invaded the pancreatic parenchyma. Accumulation of p62 and increased positive staining of NQO1 molecules related to autophagy dysfunction were detected in pancreatic acinar cells in the fatty area, acinar-ductal metaplasia, and pancreatic cancer cells. The rate of p62-positive cell area and that of NQO1-positive cell area were significantly higher in the fatty pancreatic region than those in the control lesion (pancreatic region with few adipocyte infiltration). Furthermore, the rate of p62-positive cell area or that of NQO1-positive cell area showed strong positive correlations with the rate of fatty pancreatic lesion. These results suggest that adipocyte invasion into the pancreatic parenthyme induced macrophage infiltration and autophagy substrate p62 accumulation. High levels of NQO1 expression in the fatty area may be dependent on p62 accumulation. Conclusion: Hypertension was a significant risk factor for fatty pancreas in patients with NAFLD and IPMN. In fatty pancreas, fatty infiltration into the pancreatic parenchyme might induce autophagy dysfunction, resulting in activation of antioxidant proteins NQO1. Thus, patients with fatty pancreas require careful follow-up.

5.
Microbiol Spectr ; 11(3): e0406522, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37191540

RESUMEN

Bordetella pertussis, the causative agent of whooping cough, can cause pertussis outbreaks in humans, especially in school-aged children. Here, we performed whole-genome sequencing of 51 B. pertussis isolates (epidemic strain MT27) collected from patients infected during 6 school-associated outbreaks lasting less than 4 months. We compared their genetic diversity with that of 28 sporadic isolates (non-outbreak MT27 isolates) based on single-nucleotide polymorphisms (SNPs). Our temporal SNP diversity analysis revealed a mean SNP accumulation rate (time-weighted average) of 0.21 SNPs/genome/year during the outbreaks. The outbreak isolates showed a mean of 0.74 SNP differences (median, 0; range, 0 to 5) between 238 isolate pairs, whereas the sporadic isolates had a mean of 16.12 SNP differences (median, 17; range 0 to 36) between 378 isolate pairs. A low SNP diversity was observed in the outbreak isolates. Receiver operating characteristic analysis demonstrated that the optimal cutoff value to distinguish between the outbreak and sporadic isolates was 3 SNPs (Youden's index of 0.90 with a true-positive rate of 0.97 and a false-positive rate of 0.07). Based on these results, we propose an epidemiological threshold of ≤3 SNPs per genome as a reliable marker of B. pertussis strain identity during pertussis outbreaks that span less than 4 months. IMPORTANCE Bordetella pertussis is a highly infectious bacterium that easily causes pertussis outbreaks in humans, especially in school-aged children. In detection and investigation of outbreaks, excluding non-outbreak isolates is important for understanding the bacterial transmission routes. Currently, whole-genome sequencing is widely used for outbreak investigations, and the genetic relatedness of outbreak isolates is assessed based on differences in the number of single-nucleotide polymorphisms (SNPs) in the genomes of different isolates. The optimal SNP threshold defining strain identity has been proposed for many bacterial pathogens, but not for B. pertussis. In this study, we performed whole-genome sequencing of 51 B. pertussis outbreak isolates and identified a genetic threshold of ≤3 SNPs per genome as a marker defining the strain identity during pertussis outbreaks. This study provides a useful marker for identifying and analyzing pertussis outbreaks and can serve as a basis for future epidemiological studies on pertussis.


Asunto(s)
Bordetella pertussis , Tos Ferina , Niño , Humanos , Bordetella pertussis/genética , Tos Ferina/epidemiología , Tos Ferina/microbiología , Polimorfismo de Nucleótido Simple , Brotes de Enfermedades , Secuenciación Completa del Genoma/métodos , Genoma Bacteriano
6.
Sci Rep ; 13(1): 7629, 2023 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-37165008

RESUMEN

Autoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown. Repeated single colony isolation enabled us to detect an Agg- mutant in the supernatant of an Agg+ strain of B. pertussis. Whole-genome sequencing and immunoblot analysis disclosed that the Agg- mutant had a single C-deletion in its fim3 promoter region (Pfim3) which abolished Fim3 fimbriae production. A B. pertussis fim3-knock out mutant also lacked the Agg+ phenotype. Agg+ clinical isolates were detected a higher production of Fim3 than Fim3-producing Agg- isolates. B. pertussis is known to harbor multiple Pfim3 poly(C) lengths within a single strain culture and our newly developed PCR/LDR assay revealed that Agg+ isolates harbor the highest Pfim3 poly-14C abundance. We evaluated the frequency of autoagglutination in clinical B. pertussis isolates collected in Japan between 1994 and 2018 (n = 203). Fim3 production was confirmed for 190 isolates and 74.7% of them displayed the Agg+ phenotype. The Agg+ phenotype was strongly associated with Pfim3 poly-14C abundance. Taken together, our findings demonstrated that B. pertussis autoagglutination occurs in response to high Fim3 levels and the Agg+ strain has predominated in Japan over the past two decades.


Asunto(s)
Bordetella pertussis , Tos Ferina , Humanos , Fimbrias Bacterianas/genética , Fenotipo , Vacuna contra la Tos Ferina
7.
J Glob Antimicrob Resist ; 31: 263-269, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36270447

RESUMEN

OBJECTIVES: Macrolide-resistant Bordetella pertussis (MRBP) has been emerging and prevailing in mainland China since 2011. In this study, we aimed to investigate the genotype and macrolide resistance of circulating B. pertussis in East and Southeast Asia using genetic analyses. METHODS: A total of 302 DNA extracts from clinical specimens and isolates from 2010 to 2020 were analyzed: 145 from Vietnam, 76 from Cambodia, 48 from Taiwan, and 33 from Japan. Genotypes were determined by multilocus variable-number tandem-repeat analysis (MLVA). Macrolide-resistant A2047G mutation in B. pertussis 23S rRNA was investigated using the duplex Cycleave real-time polymerase chain reaction (PCR) assay. Whole-genome sequencing was performed on two MRBP isolates that were identified for the first time in Taiwan. RESULTS: Overall, 286 DNA extracts (95%) generated a complete MLVA genotype and 283 DNA extracts (94%) yielded a complete result for the A2047G mutation analysis. The A2047G mutation was detected in 18 DNA extracts: fourteen from Vietnam, one from Cambodia, two from Taiwan, and one from Japan. Most of them (78%) showed the genotypes MT104 and MT195, which have previously been reported in Chinese MRBP isolates. Further, the Taiwanese MRBP isolates were classified into the MT104 clade of Chinese MRBP isolates. CONCLUSION: After MRBP emerged and spread in mainland China, it may have spread to East and Southeast Asia in the 2010s. Continued surveillance targeting the A2047G mutation of MRBP is needed to prevent further spread of this emerging pathogen.


Asunto(s)
Bordetella pertussis , Tos Ferina , Humanos , Bordetella pertussis/genética , Macrólidos/farmacología , Tos Ferina/epidemiología , Antibacterianos/farmacología , Genotipo , Farmacorresistencia Bacteriana , Mutación , Asia Sudoriental , Asia Oriental
8.
Microbiol Resour Announc ; 11(10): e0071822, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36129277

RESUMEN

We report the complete genome sequence of macrolide-resistant Bordetella pertussis BP616, which was first isolated in 2018 in Japan. The BP616 genome can serve as a valuable specific reference for genomic and epidemiological studies of this resistant bacterium.

9.
Open Forum Infect Dis ; 9(3): ofac020, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35146052

RESUMEN

We describe a case of bacteremia in a human immunodeficiency virus-infected patient caused by a Bordetella pertussis strain lacking 2 major virulence factors, filamentous hemagglutinin and fimbriae. Although B pertussis bacteremia is uncommon, physicians should be aware that even attenuated B pertussis strains can cause invasive infection in immunocompromised patients. Bordetella pertussis is a gram-negative coccobacillus that causes a severe paroxysmal coughing disease known as whooping cough or pertussis. Bordetella pertussis colonizes the epithelial cells of the human respiratory tract, and the organisms are typically isolated from nasopharynx. We describe a case of B pertussis bacteremia in a patient with human immunodeficiency virus (HIV) infection. Interestingly, the isolate recovered from blood culture did not produce the major virulence factors, filamentous hemagglutinin (FHA) and fimbriae (FIM). Previously, 3 cases of B pertussis bacteremia were reported in the literature. We discuss the features of B pertussis bacteremia.

10.
Sci Rep ; 11(1): 4823, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649512

RESUMEN

Multilocus variable-number tandem repeat analysis (MLVA) is widely used for genotyping of Bordetella pertussis, the causative bacteria for pertussis. However, MLVA genotyping is losing its discriminate power because prevalence of the epidemic MT27 strain (MLVA-27) is increasing worldwide. To address this, we developed a single nucleotide polymorphism (SNP) genotyping method for MT27 based on multiplexed single-base extension (SBE) assay. A total of 237 MT27 isolates collected in Japan during 1999-2018 were genotyped and classified into ten SNP genotypes (SG1 to SG10) with a Simpson's diversity index (DI) of 0.79 (95% CI 0.76-0.82). Temporal trends showed a marked increase in the genotypic diversity in the 2010s: Simpson's DI was zero in 1999-2004, 0.16 in 2005-2009, 0.83 in 2010-2014, and 0.76 in 2015-2018. This indicates that the SNP genotyping is applicable to the recently circulating MT27 strain. Additionally, almost all outbreak-associated MT27 isolates were classified into the same SNP genotypes for each outbreak. Multiplexed SBE assay allows for rapid and simple genotyping, indicating that the SNP genotyping can potentially be a useful tool for subtyping the B. pertussis MT27 strain in routine surveillance and outbreak investigations.


Asunto(s)
Bordetella pertussis/genética , ADN Bacteriano/genética , Técnicas de Genotipaje , Tipificación de Secuencias Multilocus , Polimorfismo de Nucleótido Simple , Humanos , Japón/epidemiología , Tos Ferina/epidemiología , Tos Ferina/genética
11.
Emerg Infect Dis ; 26(10): 2511-2513, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32946738

RESUMEN

Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a macrolide-resistant mutation, A2047G, in the 23S rRNA. We identified the MT104 genotype of macrolide-resistant B. pertussis (which is prevalent in mainland China) and its variants in these patients.


Asunto(s)
Bordetella pertussis , Macrólidos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bordetella pertussis/genética , China , Farmacorresistencia Bacteriana , Eritromicina , Humanos , Macrólidos/farmacología , ARN Ribosómico 23S/genética , Vietnam/epidemiología
12.
J Med Microbiol ; 68(11): 1671-1676, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31613204

RESUMEN

Purpose. Human-adapted Bordetella parapertussis is one of the causative agents of whooping cough; however, there are currently no genotyping systems with high discriminatory power for this bacterial pathogen. We therefore aimed to develop a multilocus variable-number tandem repeat analysis (MLVA) for human-adapted B. parapertussis.Methodology. Four highly polymorphic variable number tandem repeat (VNTR) loci in the B. parapertussis genome were selected and amplified by multiplex PCR. MLVA was performed based on the number of tandem repeats at VNTR loci. The discriminatory power of MLVA was evaluated with three laboratory reference strains and 50 human isolates of B. parapertussis.Results. Multiplex PCR-based MLVA characterized 53 B. parapertussis reference strains and isolates into 25 MLVA types and the Simpson diversity index was 0.91 (95 % confidence interval, 0.86-0.97). The three reference strains exhibited different MLVA types. Thirty-one Japanese isolates, ten French isolates and three Taiwanese isolates belonged to fourteen, nine and three MLVA types, respectively. In contrast, all five Australian isolates belonged to the same type. Two Japanese isolates collected from patients with known epidemiological links had the same type.Conclusion. Our novel MLVA method has high discriminatory power for genotyping human B. parapertussis. Regarding this organism, this genotyping system is a promising tool for epidemiological surveillance and investigating outbreaks.


Asunto(s)
Bordetella parapertussis/genética , Bordetella parapertussis/aislamiento & purificación , Tipificación de Secuencias Multilocus/métodos , Tos Ferina/microbiología , Bordetella parapertussis/clasificación , Humanos , Repeticiones de Minisatélite , Tos Ferina/diagnóstico
13.
PLoS One ; 14(7): e0219255, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31260500

RESUMEN

Pertussis is a human respiratory infection caused by the gram-negative bacterium, Bordetella pertussis. To evaluate the pertussis burden and vaccine efficacy, diagnosis and epidemiological surveillance should be based on accurate and valid diagnostic methods. Recently, the serodiagnostic tests Novagnost Bordetella pertussis IgA and IgM were approved in Japan for pertussis diagnostics. Although the anti-pertussis toxin (PT) IgG assay has been used for pertussis diagnosis worldwide, little is known about the anti-B. pertussis IgA and IgM assays. In this study, serum samples from 460 healthy donors were examined to determine the seroprevalence of anti-B. pertussis IgA and IgM in a Japanese population, and its correlation with donor age. Our data demonstrated that anti-B. pertussis IgA and IgM are positively and negatively correlated with age (r = 0.27, r = -0.37; P < 0.001, respectively). Age-specific analysis revealed high titers of anti-B. pertussis IgA in adults (46-50 years), while anti-B. pertussis IgM titers were high in schoolchildren (6-10, 11-15 years). When applying the arbitrary cut-off values for these ages, 17.6% and 39.5% of healthy donors were interpreted as pertussis-positive or indeterminate with anti-B. pertussis IgA (46-50 years) and IgM (11-15 years) titers, respectively. Overall, our findings indicated that the Novagnost Bordetella pertussis IgA and IgM testing could be greatly affected by subject age, limiting its value for pertussis diagnosis.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Bordetella pertussis/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina M/sangre , Tos Ferina/epidemiología , Adolescente , Adulto , Anticuerpos Antibacterianos/inmunología , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina M/inmunología , Lactante , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Tos Ferina/sangre , Tos Ferina/microbiología , Adulto Joven
14.
Vaccine ; 37(18): 2463-2469, 2019 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-30930008

RESUMEN

To gain insights into the current Japanese pertussis immunization schedule, we examined the distributions of antibody titers and avidities to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 460 Japanese healthy subjects (aged 1-60 years) based on age category. Our avidity enzyme-linked immunosorbent assays revealed that young children aged 1-2 years, which corresponded to ages after receiving primary and/or booster pertussis vaccinations, had relatively high-avidity anti-PT IgG (mean avidity index [AI], 40.5%) compared with other age groups (AI, 26.5-31.9%); however, they had relatively low-avidity anti-FHA IgG (AI, 41.8%). In contrast, children aged 3-6 years had both low-avidity anti-PT IgG (AI, 26.5%) and low-avidity anti-FHA IgG (AI, 40.4%). A significant age-related difference in anti-PT IgG avidity was observed between children aged 1-2 years and 3-6 years (P < 0.05); however, the difference in anti-FHA IgG avidity was not significant. The anti-PT IgG avidity was positively correlated with the antibody titer, especially among children aged 1-15 years (rs = 0.508-0.685; P < 0.01), indicating that the avidity of vaccine-induced anti-PT IgG decreases with decreasing IgG antibody titer to PT. Our findings strongly suggest that vaccine-induced anti-PT IgG avidity rapidly wanes after vaccination, but this is not observed for anti-FHA IgG avidity. Because children aged 3-6 years have both low-quantity and low-quality antibodies against PT, an additional booster vaccination with acellular pertussis vaccines is required for such children in Japan.


Asunto(s)
Factores de Edad , Anticuerpos Antibacterianos/sangre , Afinidad de Anticuerpos , Hemaglutininas/inmunología , Toxina del Pertussis/inmunología , Vacuna contra la Tos Ferina/inmunología , Adolescente , Adulto , Anticuerpos Antibacterianos/inmunología , Niño , Preescolar , Femenino , Voluntarios Sanos , Humanos , Inmunización Secundaria , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lactante , Japón , Masculino , Persona de Mediana Edad , Vacunación , Tos Ferina/prevención & control , Adulto Joven
15.
Microb Genom ; 4(5)2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29771235

RESUMEN

Bordetella pertussis, the causative agent of whooping cough, has experienced a resurgence in the past 15 years, despite the existence of both whole-cell and acellular vaccines. Here, we performed whole genome sequencing analysis of 149 clinical strains, provided by the National Institute of Infectious Diseases (NIID), Japan, isolated in 1982-2014, after Japan became the first country to adopt acellular vaccines against B. pertussis. Additionally, we sequenced 39 strains provided by the Konan Kosei Hospital in Aichi prefecture, Japan, isolated in 2008-2013. The genome sequences afforded insight into B. pertussis genome variability and population dynamics in Japan, and revealed that the B. pertussis population in Japan was characterized by two major clades that divided more than 40 years ago. The pertactin gene was disrupted in about 20 % of the 149 NIID isolates, by either a deletion within the signal sequence (ΔSS) or the insertion of IS element IS481 (prn :: IS481). Phylogeny suggests that the parent clones for these isolates originated in Japan. Divergence dating traced the first generation of the pertactin-deficient mutants in Japan to around 1990, and indicated that strains containing the alternative pertactin allele prn2 may have appeared in Japan around 1974. Molecular clock data suggested that observed fluctuations in B. pertussis population size may have coincided with changes in vaccine usage in the country. The continuing failure to eradicate the disease warrants an exploration of novel vaccine compositions.


Asunto(s)
Bordetella pertussis/clasificación , Bordetella pertussis/genética , Bordetella pertussis/aislamiento & purificación , Vacuna contra la Tos Ferina/uso terapéutico , Filogenia , Alelos , Proteínas de la Membrana Bacteriana Externa/genética , Biodiversidad , Elementos Transponibles de ADN/genética , Genes Bacterianos/genética , Variación Genética , Humanos , Japón/epidemiología , Polimorfismo de Nucleótido Simple , Dinámica Poblacional , Eliminación de Secuencia , Vacunas Acelulares/uso terapéutico , Factores de Virulencia de Bordetella/genética , Secuenciación Completa del Genoma
16.
Cancer Chemother Pharmacol ; 82(2): 245-250, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29846765

RESUMEN

PURPOSE: New chemotherapies have become available for the treatment of advanced pancreatic cancer and have led to changes in its standard treatments. Since pancreatic cancer is becoming more common as a result of population aging, there is a need for diversification of chemotherapy. METHODS: Between March 2014 and April 2017, FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (G-nab) was used as first-line therapy to treat 27 patients with locally advanced and metastatic pancreatic cancer at our hospital. In this study, we retrospectively evaluated their clinical characteristics, survival outcomes and adverse events. RESULTS: Twelve of the 27 patients were treated with FFX, and the other 15 patients were treated with G-nab. The disease control rate was 86.7% in the G-nab group and 75% in the FFX group. Median OS time was 8.9 months in the FFX group and 11.8 months in the G-nab group. The 1-year survival rate was 46.6% in the G-nab group and 16.6% in the FFX group. The second-line treatment rate was 40% in the G-nab group and 66.7% in the FFX group. The grade 3-4 neutropenia rate was 20% in the G-nab group and 25% in the FFX group. No patients developed febrile neutropenia, or severe nausea, diarrhea, or anorexia. The peripheral sensory neuropathy rate was 73.3% in the G-nab group and 75% in the FFX group. CONCLUSIONS: Although G-nab and FFX are effective treatments for advanced pancreatic cancer, the G-nab group had a higher 1-year survival rate, and G-nab can be more safely administered to older patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Albúminas/administración & dosificación , Albúminas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Tasa de Supervivencia , Gemcitabina
17.
Microbiology (Reading) ; 163(9): 1364-1368, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28809156

RESUMEN

Bordetella pertussis, a human pathogenic bacterium, produces either one or two types of serologically distinct fimbriae, Fim2 and Fim3, as virulence factors. The expression of fim2 and fim3 is regulated by the BvgAS two-component system and the length of poly(C) stretches in Pfim promoters. In the Bvg+ phase, B. pertussis virulence-activated genes (vags) are up-regulated and virulence-repressed genes (vrgs) are down-regulated. Previous studies have shown that fim2 is a vag, but there is no consensus on fim3 regulation. We examined the regulation of fimbrial expression in B. pertussis clinical isolates. Our findings indicate that fim2 is a vag, while fim3 is a vag when Pfim3 poly(C)>13C, and a vrg when poly(C)≤13C. Although increased fim3 expression was observed in the Bvg- phase in isolates with Pfim3 poly(C)≤13C, Fim3 production was not detected, suggesting post-transcriptional regulation of fim3 expression. These findings provide an insight into the regulation of fimbrial expression in B. pertussis.


Asunto(s)
Bordetella pertussis/genética , Bordetella pertussis/metabolismo , Proteínas Fimbrias/genética , Fimbrias Bacterianas/genética , Regiones Promotoras Genéticas , Factores de Virulencia de Bordetella/genética , Factores de Virulencia de Bordetella/metabolismo , Composición de Base , Regulación Bacteriana de la Expresión Génica , Humanos , Modelos Biológicos
18.
Int J Infect Dis ; 62: 56-58, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28751008

RESUMEN

OBJECTIVES: This study sought to determine the genotypes of circulating Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct molecular typing of clinical specimens. METHODS: DNA extracts from nasopharyngeal swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter ptxP were also investigated by DNA sequence-based typing. RESULTS: Forty-four DNA extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which are common in developed countries, were the predominant strain types (total 73%). The predominant profile of virulence-associated allelic genes was the combination of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire study period, whereas MT29 strains were only found in 2014-2016. CONCLUSIONS: The B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV) has been continuously used, resembled those observed previously in developed countries where acellular pertussis vaccines are used. Circulating B. pertussis strains in Cambodia were distinct from those in other countries using WCVs.


Asunto(s)
Bordetella pertussis/genética , Tos Ferina/microbiología , Alelos , Bordetella pertussis/patogenicidad , Cambodia/epidemiología , ADN Bacteriano , Genotipo , Humanos , Repeticiones de Minisatélite , Epidemiología Molecular , Tipificación Molecular , Toxina del Pertussis/genética , Vacuna contra la Tos Ferina/inmunología , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Tos Ferina/epidemiología
19.
PLoS One ; 12(7): e0181181, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28700751

RESUMEN

In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT) from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s) of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA) among adults (35-44 years old), young children (4-7 years old), and older children (10-14 years old). Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children. Positive correlations were observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all age groups (rs values of 0.326-0.522), although the correlation tended to decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was significantly different when we compared the serum and purified IgG fractions among adults (p = 0.016), although this result was not observed among young and older children. Thus, it appears that some adults had non-IgG immunoglobulins to PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity index: 63.5%, similar results were observed among the children); however, the adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05). It is possible that low-avidity anti-FHA IgG is related to infection with other respiratory pathogens (e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma pneumoniae), which produces antibodies to FHA-like proteins. Our observations suggest that these adults had been infected with B. pertussis and other pathogen(s) during their adulthood.


Asunto(s)
Adhesinas Bacterianas/inmunología , Anticuerpos Antibacterianos/inmunología , Toxina del Pertussis/inmunología , Adolescente , Adulto , Bordetella parapertussis/inmunología , Niño , Preescolar , Femenino , Haemophilus influenzae/inmunología , Humanos , Inmunoglobulinas/inmunología , Masculino , Mycoplasma pneumoniae/inmunología , Estudios Seroepidemiológicos
20.
Emerg Infect Dis ; 23(4): 699-701, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28322702

RESUMEN

Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014-2016 (8%) was significantly lower than the frequency in 2005-2007 (41%), 2008-2010 (35%), and 2011-2013 (25%). This reduction was closely associated with changes in genotypes.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/metabolismo , Bordetella pertussis/genética , Regulación Bacteriana de la Expresión Génica/fisiología , Factores de Virulencia de Bordetella/metabolismo , Proteínas de la Membrana Bacteriana Externa/genética , Evolución Molecular , Genotipo , Japón , Mutación , Factores de Virulencia de Bordetella/genética
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