Estudio observacional de las características clínicas, epidemiológicas y de laboratorio en pacientes pediátricos con dengue de la ciudad de Córdoba / Observational study of clinical, epidemiological, and laboratory characteristics of pediatric patients with dengue in the city of Córdoba

Introducción. El dengue es la enfermedad transmitida por mosquitos con mayor propagación mundial en los últimos años. Presenta un amplio espectro de manifestaciones clínicas y, en ocasiones, evoluciona a un estado crítico llamado dengue grave. Su tratamiento es de sostén. La información disponible acerca de las características clínicas, epidemiológicas y de laboratorio de la enfermedad en la población pediátrica es limitada. Objetivo. Describir la epidemiología y las manifestaciones clínicas y de laboratorio de la enfermedad. Población y métodos. Estudio descriptivo, observacional y retrospectivo. Incluyó pacientes entre 1 y 180 meses asistidos por dengue probable o confirmado en un hospital de niños, desde el 01 de enero de 2020 hasta el 31 de mayo de 2020. Resultados. Se incluyeron 85 pacientes por criterios microbiológicos de positividad o clínicoepidemiológicos. Veinticinco (29 %) confirmados por RT-PCR, todos serotipos DENV-1. La mediana de  edad fue de 108 meses (rango intercuartílico: 84-144). Las principales manifestaciones clínicas fueron fiebre, cefalea y mialgias. Los hallazgos de laboratorio más importantes fueron leucopenia, trombocitopenia y elevación de transaminasas. Conclusión. El reconocimiento y la comprensión de las alteraciones clínicas y de laboratorio que se presentan durante la enfermedad pueden permitir un abordaje eficaz y contribuir a la reducción de cuadros clínicos más graves en los niños.

Introduction. Dengue has been the most widespread mosquito-borne disease worldwide in recent years. It develops with a broad spectrum of clinical manifestations and sometimes progresses to a critical condition known as severe dengue. It is managed with supportive treatment. Available information about its clinical, epidemiological, and laboratory characteristics in the pediatric population is limited. Objective. To describe the clinical, epidemiological, and laboratory characteristics of dengue. Population and methods. Descriptive, observational, and retrospective study. It included patients aged 1 to 180 months seen due to probable or confirmed dengue at a children's hospital between 1/1/2020 and 5/31/2020. Results. A total of 85 patients with positive microbiological or clinical-epidemiological criteria were included. Of these, 25 (29%) were confirmed by RT-PCR; all corresponded to DENV-1 serotype. Patients' median age was 108 months (interquartile range: 84­144). The main clinical manifestations were fever, headache, and myalgia. The most important laboratory findings were leukopenia, thrombocytopenia, and high transaminase levels. Conclusion. The recognition and understanding of clinical and laboratory alterations that occur during dengue disease may allow an effective approach and help to reduce the more severe clinical form in children.

Serotipos prevalentes de Streptococcus mutans en América Latina / Prevalent serotypes of Streptococcus mutans in Latin America

La microbiota oral está conformada por diversas especies bacterianas que en condiciones normales desempeñan una función protectora del huésped; sin embargo, cuando existe un desequilibrio en el ecosistema, estos microorganismos son capaces de producir diversas manifestaciones como lo es el caso de la caries dental, enfermedad infecciosa producida principalmente por Streptococcus mutans, patógeno capaz de desmineralizar los tejidos duros del diente mediante la fermentación de hidratos de carbono obtenidos de la dieta. Se ha identificado en la pared celular de este microorganismo ocho serotipos que intervienen en la adhesión, agregación y coagregación bacteriana. En los seres humanos S. mutans presenta los serotipos c, e y f, siendo el serotipo c el más prevalente a nivel mundial, el cual se conoce que está asociado a pacientes sanos, a diferencia del e y f que son capaces de invadir las células endoteliales de las arterias coronarias. No obstante, en los últimos años se ha logrado identificar el serotipo k que de igual manera presenta alta capacidad de invadir el endotelio humano, actuando en la patogénesis de las enfermedades cardiovasculares. El objetivo de la presente revisión bibliográfica es lograr cuantificar los serotipos prevalentes de S. mutans en América Latina (AU)

The oral microbiota is made up of various bacterial species that under normal conditions perform a protective function of the host, however, when there is an imbalance in the ecosystem, these microorganisms are capable of producing various manifestations such as caries, an infectious disease. produced mainly by Streptococcus mutans, a pathogen capable of demineralizing the hard tissues of the tooth through the fermentation of carbohydrates obtained from the diet. Eight serotypes involved in bacterial adhesion, aggregation and coaggregation have been identified in the cell wall of this microorganism. In humans, S. mutans presents serotypes c, e, and f, serotype c being the most prevalent worldwide, which is known to be associated with healthy patients, unlike e and f, which are capable of invading the endothelial cells of the coronary arteries. However, in recent years it has been possible to identify serotype k, which also has a high capacity to invade the human endothelium, acting in the pathogenesis of cardiovascular diseases. The objective of this literature review is to quantify the prevalent serotypes of S. mutans in Latin America (AU)

Establishment and Modification of Ninety-seven Pneumococcal Serotyping Assays Based on Quantitative Real-time Polymerase Chain Reaction / 生物医学与环境科学（英文）

OBJECTIVE@#To establish and modify quantitative real-time polymerase chain reaction (qPCR)-based serotyping assays to distinguish 97 pneumococcal serotypes.@*METHODS@#A database of capsular polysaccharide ( cps) loci sequences was generated, covering 97 pneumococcal serotypes. Bioinformatics analyses were performed to identify the cps loci structure and target genes related to different pneumococcal serotypes with specific SNPs. A total of 27 novel qPCR serotyping assay primers and probes were established based on qPCR, while 27 recombinant plasmids containing serotype-specific DNA sequence fragments were constructed as reference target sequences to examine the specificity and sensitivity of the qPCR assay. A panel of pneumococcal reference strains was employed to evaluate the capability of pneumococcal serotyping.@*RESULTS@#A total of 97 pneumococcal serotyping assays based on qPCR were established and modified, which included 64 serotypes previously reported as well as an additional 33 serotypes. Twenty-seven novel qPCR serotyping target sequences were implemented in the pneumococcal qPCR serotyping system. A total of 97 pneumococcal serotypes, which included 52 individual serotypes and 45 serotypes belonging to 20 serogroups, could not be identified as individual serotypes. The sensitivity of qPCR assays based on 27 target sequences was 1-100 copies/µL. The specificity of the qPCR assays was 100%, which were tested by a panel of 90 serotypes of the pneumococcal reference strains.@*CONCLUSION@#A total of 27 novel qPCR assays were established and modified to analyze 97 pneumococcal serotypes.

Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo / 中西医结合学报

OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

Drug resistance and genomic characteristics of Salmonella enterica serovar London from clinical and food sources in Hangzhou City from 2017 to 2021 / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.

Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children / 中国当代儿科杂志

OBJECTIVES@#To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines.@*METHODS@#The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage.@*RESULTS@#The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates.@*CONCLUSIONS@#There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Ocorrência de sorogrupos/sorovares de Leptospira spp. em cães com suspeita clínica de leptospirose em Santa Maria ­ RS / Occurrence of serogroups/serovars of Leptospira spp. in dogs with clinical suspicion of leptospirosis in Santa Maria ­ RS

A leptospirose é uma zoonose de distribuição mundial que pode acometer cães e ser altamente letal para a espécie. No Brasil, tal enfermidade tem caráter endêmico na espécie canina e configura-se como um sério problema de saúde pública. Objetivou-se verificar a ocorrência dos sorogrupos/sorovares de Leptospira spp. que mais acometem cães com suspeita clínica de leptospirose na cidade de Santa Maria ­ RS, Brasil, analisando sua titulação de anticorpos. No estudo, utilizou-se os laudos dos exames de soroaglutinação microscópica (SAM) para leptospirose de 218 cães provenientes da cidade de Santa Maria ­ RS durante o período de janeiro de 2015 a dezembro de 2019. Todos os laudos foram emitidos pelo Laboratório de Leptospirose (LabLepto - UFSM). Das 218 amostras de soro processadas nos cinco anos, 101 (46,33%) resultaram positivas para, pelo menos, um sorogrupo/sorovar testado. Este estudo demonstrou maior ocorrência do sorogrupo Icterohaemorrhagiae (53,37%) contemplado pelas sorovares Copenhageni e Icterohaemorrhagiae, com 49 (30,06%) e 38 (23,31%) soros reagentes, respectivamente. As titulações variaram de 100 a 6400, sendo que a mais recorrente encontrada nas amostras deste estudo foi 100, representando 47,85% dos títulos de anticorpos. Os dados obtidos neste estudo são de grande valia para o conhecimento dos sorogrupos/sorovares circulantes na região e sua epidemiologia podendo, inclusive, auxiliar para futuras formulações vacinais considerando sorogrupos/sorovares mais frequentemente detectados, contribuindo, assim, com a saúde pública.

Leptospirosis is a worldwide distribution zoonosis that can affect dogs and be highly lethal for the species. In Brazil, this disease is endemic in the canine species and represents a serious public health problem. The aim of this study was to verify the occurrence of Leptospira spp. that most affect dogs with clinical suspicion of leptospirosis in the city of Santa Maria ­ RS, Brazil, analyzing their antibody titers. In the study, we used the reports of microscopic agglutination tests (MAS) for leptospirosis in 218 dogs from the city of Santa Maria - RS during the period from January 2015 to December 2019. All reports were issued by the Leptospirosis Laboratory (LabLepto - UFSM). Of the 218 serum samples processed over the five years, 101 (46.33%) were positive for at least one serogroup/serovar tested. This study showed a higher occurrence of serogroup Icterohaemorrhagiae (53.37%) covered by serovars Copenhageni and Icterohaemorrhagiae, with 49 (30.06%) and 38 (23.31%) reagent sera, respectively. The titers ranged from 100 to 6400, and the most recurrent found in the samples in this study was 100, representing 47.85% of the antibody titers. The data obtained in this study are of great value for understanding the serogroups/serovars circulating in the region and their epidemiology, and may even contribute to future vaccine formulations considering the most frequently detected serogroups/serovars, thus contributing to public health.

Clinical and molecular characteristics of Streptococcus pneumoniae-associated hemophagocytic lymphohistiocytosis in children / 中华儿科杂志

Objective: To summarize the clinical features of Streptococcus pneumoniae-associated hemophagocytic syndrome (SP-HLH), and the serotypes and drug-resistant characteristics of the isolated strains. Methods: There were 15 children with SP-HLH admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital, Capital Medical University from January 2013 to December 2020 were included in this study. Clinical data including children's general characteristics, clinical features, laboratory examinations, treatments, prognosis and the outcomes of follow-up by May 2021 were analyzed retrospectively. The serotypes and drug resistance of the isolated strains were identified. All children were divided into the clinical improvement group and the death group. Mann-Whitney U test, Fisher's exact test were used to compare the data of the two groups. Results: Among the 15 children with SP-HLH, 8 were males and 7 were females. The age of these children was 1.0 (1.0, 2.5) years. Regarding the primary infection, there were 9 cases of severe pneumonia, 3 cases of meningitis and 3 cases of blood stream infection. None of these children had received pneumoniae conjugate vaccine (PCV) and all of them were admitted to the PICU. Respiratory failure was observed in 10 patients, acute renal injury in 5, and hemolytic uremic syndrome in 3 patients. All children received glucocorticoids and high-dose intravenous immunogloblin (IVIG) in addition to anti-infective treatment. Eight of the children were cured while the other 7 died. The neutrophil count in the death group was lower than that in the clinical improvement group ((5.0 (1.7, 9.3) × 109 vs. 5.2 (3.4, 10.5) ×109/L, Z =-2.43, P<0.015), and the length of hospital stay and days of PICU stay in the death group were both shorter than those in the improvement group statistically (3 (1, 11) vs. 39 (34, 48) d, 2 (1, 4) vs. 19 (12, 31) d, Z=-3.25, -3.24, both P=0.001). Ten serotypes of Streptococcus pneumoniae were identified, including 4 strains of 19F, 3 of 19A, 1 of 23F, 1 of 15A and 1 of 14, among which 9 strains (9/10) were covered by PCV13. All strains were resistant to erythromycin yet sensitive to vancomycin and linezolid. Conclusions: SP-HLH is more common in children under the age of 3, with a high mortality rate. The death cases have lower neutrophil count and rapid disease progression. The comprehensive treatment is anti-infective combined with glucocorticoids and high-dose IVIG. The predominant serotypes are 19F and 19A and all isolated strains were susceptible to vancomycin and linezolid.

Incidence of leptospirosis in Fujian province, 2015-2020 / 中华流行病学杂志

Objective: To analyze the incidence of leptospirosis in Fujian province from 2015 to 2020 and provide the scientific evidences for the risk assessment, prevention and control of leptospirosis. Methods: The incidence data of leptospirosis in Fujian during 2015-2020 were collected from China Information System for Disease Control and Prevention for a descriptive analysis, and software ArcGIS 10.3.1 was used for spatial autocorrelation analysis, and rats were captured in 17 surveillance areas during the same period, and the rat organs were collected for pathogen culture, the level of Leptospira antibody was detected in serum samples of rats, healthy population and the serum samples of patients sent by the hospitals. The infection status of Leptospira in human and rats were analyzed. Results: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020. A total of 176 cases of leptospirosis were reported. There were obvious seasonality and bimodal distribution. The majority of cases were farmers, accounting for 49.43% (87/176). Most cases were aged 30-69 years (85.80%, 151/176). The male to female ratio of the cases was 3.51∶1 (137∶39). Spatial autocorrelation analysis showed that leptospirosis had high or low clustering areas. From 2015 to 2020, the average capture rate of rats in 17 surveillance areas was 6.96% (1 519/21 838), Rattus losea, Rattus flavipectus and Niviventer fulvescens were the main species. The average positive rate of Leptospira antibody in rats was 28.64% (252/880). Java and Autumnalis were the predominant serogroups, accounting for 56.75% (143/252) and 17.46% (44/252), respectively. The average positive rate of Leptospira antibody in healthy population was 16.13% (254/1 575), and Autumnalis and Australis were the predominant serogroups, accounting for 71.65% (182/254). The confirmation rate of leptospirosis in patient serum samples sent by the hospitals was 2.23% (188/8 431), Autumnalis (56.38%, 106/188) and Hebdomadis (19.68%, 37/188) were the major serogroups. Conclusions: The incidence of leptospirosis in Fujian showed a downward trend from 2015 to 2020, there were obvious area clustering and seasonality. The high clustering areas were mainly distributed in northern, western and central Fujian. Java and Autumnalis were the predominant serogroups in rats. The infection rate in healthy population decreased year by year. Autumnalis and Hebdomadis were the main serogroups in population in Fujian.

Epidemiological and etiological analysis of two infantile cases of serogroup B epidemic cerebrospinal meningitis epidemics in Shandong Province, 2021 / 中华预防医学杂志

Two cases of epidemic situation of serogroup B meningitis in infants in Shandong Province in 2021 were investigated. Samples of cases and their close contacts were collected for isolation, culture and identification of Neisseria meningitides (Nm). The isolates were subjected to multi-locus sequence typing, outer membrane protein porA and fetA genotyping and drug sensitivity test. Two laboratory-confirmed outbreaks of serogroup B meningitis were reported from Yantai city and Linyi city. The indicated cases were infants aged 5 months and 2 months old respectively. They were not vaccinated with meningitis vaccine. Their epidemiological characteristics and clinical manifestations were similar and the prognosis was good. The same sequence type (ST) of serogroup B Nm strains as the indicated cases was detected in the samples of close family contacts, but without subsequent cases. Among them, Yantai strain was were identified as the type ST-8920, belonging to CC4821 clonal complex, and the genotypes of porA and fetA were p1.21-2, 23 and F3-1. Linyi strain was a new type, belonging to CC4821 clonal complex and the genotypes of porA and fetA were p1.20, 23 and F1-91. The above strains were resistant to penicillin, ciprofloxacin, levofloxacin and Chemitrim, and their sensitivity to cephalosporin decreased. Two cases of infant serogroup B epidemic were relatively rare in China, which were different from the epidemiological and pathogenic characteristics of other Nm serogroups in the past.

Research progress on immunogenicity evaluation of serogroup B meningococcal vaccine / 中华预防医学杂志

Epidemic cerebrospinal meningitis (meningococcal meningitis) is an acute respiratory infectious disease with high mortality and serious sequelae. Meningococcal vaccine is an effective measure to prevent and control meningococcal meningitis. At present, group B meningococcal meningitis has become the main prevalent serum group in the world, including China. Meningococcal ACYW and other vaccines are mainly composed of capsular polysaccharides, while the main component of group B meningococcal vaccine is protein, including outer membrane vesicles (OMV) and recombinant protein vaccine. The methods for evaluating the immunogenicity of group B meningococcal vaccine include hSBA and alternative methods such as meningococcal antigen typing system (MATS), flow cytometric meningococcal antigen surface expression assay (MEASURE), genetic meningococcal antigen typing system (gMATS) and bexsero antigen sequence type (BAST). The evaluation of vaccine immunogenicity is the basis of vaccine development and clinical trial research, However, at present, there is no group B meningococcal vaccine in China. Therefore, in this paper, the research progress of immunogenicity evaluation of group B meningococcal vaccine has been reviewed, in order to provide technical guidance for the research and development of group B meningococcal vaccine, immunogenicity evaluation and clinical trial research in China.

Construction of recombinant adenovirus expressing capsid protein of serotype O foot-and-mouth disease virus and analysis of its immunogenicity / 生物工程学报

In order to construct a recombinant replication deficient human type 5 adenovirus (Ad5) expressing a foot-and-mouth disease virus (FMDV) capsid protein, specific primers for P12A and 3B3C genes of FMDV-OZK93 were synthesized. The P12A and 3B3C genes were then amplified and connected by fusion PCR, and a recombinant shuttle plasmid pDC316-mCMV-EGFP-P12A3B3C expressing the FMDV-OZK93 capsid protein precursor P12A and 3B3C protease were obtained by inserting the P12A3B3C gene into the pDC316-mCMV-EGFP plasmid. The recombinant adenovirus rAdv-P12A3B3C-OZK93 was subsequently packaged, characterized and amplified using AdMaxTM adenovirus packaging system, and the expression was verified by infecting human embryonic kidney cell HEK-293. The humoral and cellular immunity levels of well-expressed and purified recombinant adenovirus immunized mice were evaluated. The results showed that rAdv-P12A3B3C-OZK93 could be stably passaged and the maximum virus titer reached 1×109.1 TCID50/mL. Western blotting and indirect immunofluorescence showed that rAdv-P12A3B3C-OZK93 expressed the FMDV-specific proteins P12A and VP1 in HEK-293 cells. In addition, the PK cell infection experiment confirmed that rAdv-P12A3B3C-OZK93 could infect porcine cells, which is essential for vaccination in pigs. Comparing with the inactivated vaccine group, the recombinant adenovirus could induce higher FMDV-specific IgG antibodies, γ-IFN and IL-10. This indicates that the recombinant adenovirus has good immunity for animal, which is very important for the subsequent development of foot-and-mouth disease vaccine.

Presença de Salmonella spp. na produção animal e o uso de fermentados bacterianos para mitigação dos riscos ­ revisão de literatura / Presence of Salmonella spp. in animal production and the use of bacterial fermentations to mitigate risks ­ a literature review / Presencia de Salmonella spp. en la producción animal y uso de fermentaciones bacterianas para mitigar riesgos - revisión de la literatura

As bactérias do gênero Salmonella são um dos principais problemas na produção animal e, consequentemente, na produção de alimentos. Elas são causadoras principalmente de gastroenterites, com alguns serovares podendo resultar na morte do animal ou indivíduo afetado. Órgãos governamentais em todo o mundo determinam condições mínimas de segurança alimentar, exigindo a ausência de Salmonella nos alimentos, sendo exigida análise de no mínimo 25 gramas de amostragem a cada lote. Dessa forma, seu controle na produção animal também é necessário, devido à grande prevalência existente. Dentre as várias estratégias de controle apresentadas, destaca-se o uso de sobrenadantes livres de células (SLC) produzidos por bactérias lácticas, com grande número de pesquisas in vitro. Nesse contexto, o objetivo deste artigo é revisar os avanços recentes no uso de SLC contra Salmonella. Ao final do trabalho, pode-se observar que os SLC têm grande potencial para utilização na produção animal, embora ainda seja necessária uma completa caracterização da sua ação in vivo.(AU)

Bacteria of the Salmonella genus are one of the main problems in animal production and, consequently, in food production. They mainly cause gastroenteritis, with some serovars that can result in the death of the affected animal or individual. Government agencies around the world determine minimum conditions for food safety, requiring the absence of Salmonella in foods, requiring analysis of at least 25 grams of sampling for each batch. Thus, its control in animal production is also necessary, due to the high prevalence that exists. Among the various control strategies presented, the use of cell-free supernatants (CFS) produced by lactic acid bacteria stands out, with a large number of in vitro research. In this context, the purpose of this article is to review recent advances in the use of CFS against Salmonella. At the end of the research, it can be seen that CFS have great potential for use in animal production, although a complete characterization of their in vivo action is still needed.(AU)

Las bacterias del género Salmonella son uno de los principales problemas en la producción animal y, en consecuencia, en la producción de alimentos. Son principalmente la causa de gastroenteritis, con algunos serovares que pueden resultar en la muerte del animal o individuo afectado. Las agencias gubernamentales de todo el mundo determinan las condiciones mínimas para la seguridad alimentaria, lo que requiere la ausencia de Salmonella en los alimentos, lo que requiere el análisis de al menos 25 gramos de muestreo para cada lote. Por tanto, su control en la producción animal también es necesario, debido a la alta prevalencia que existe. Entre las diversas estrategias de control presentadas, destaca el uso de sobrenadantes libres de células (SLC) producidos por bacterias del ácido láctico, con un gran número de investigaciones in vitro. En este contexto, el propósito de este artículo es revisar los avances recientes en el uso de SLC contra Salmonella. Al final del trabajo, se puede ver que los SLC tienen un gran potencial para su uso en la producción animal, aunque aún se necesita una caracterización completa de su acción in vivo.(AU)

Resistencia a múltiples antibióticos en serovariedades de Salmonella aisladas de muestras clínicas y alimentos / Resistance to multiple antibiotics in serovarities of Salmonella isolated from clinical samples and foods

Salmonella enterica es un patógeno transmitido por alimentos y agente etiológico de brotes alimentarios de gran impacto en la salud humana. El aumento de la resistencia bacteriana constituye una amenaza a la salud pública, la aparición de cepas de Salmonella con resistencia a múltiples antimicrobianos (MDR) fue descrita en humanos, alimentos y animales para consumo; por ello se considera muy importante conocer la situación epidemiológica local. El objetivo de este trabajo fue generar información sobre los serotipos circulantes, resistencia a los antibióticos y presencia de resistencia simultánea a múltiples fármacos en Salmonella provenientes de muestras clínicas humanas y muestras de alimentos en el periodo desde 2017 a 2019. Fueron analizadas un total de 668 cepas de Salmonella aisladas en los años 2017, 2018 y 2019 a partir de muestras clínicas humanas y de alimentos, en el Laboratorio Central de Salud Pública y/o remitidas por Laboratorios de la Red de Enteropatógenos. Se observaron serotipos muy diversos con prevalencia del serovar Heidelberg en alimentos y Typhimurium en muestras de humanos. Se encontró que el 45,4% de las cepas fueron sensibles a todos los antibióticos (ATB), el 35,6% fueron resistentes de 1 a 6 ATB y el 19% con sensibilidad intermedia; observándose mayor resistencia a Tetraciclina, Ác. Nalidíxico, Ampicilina y Nitrofurantoína, en menor grado se evidenció resistencia a cefalosporinas (C3ªG) y a ciprofloxacina. El 16.9% de las cepas presentaron resistencia múltiple (3 o más antibióticos) con 37 fenotipos distintos. Las serovariedades que presentaron mayor resistencia a los antimicrobianos fueron Heidelberg, Schwarzengrund y Typhimurium

Salmonella enterica is a foodborne pathogen and etiological agent of food outbreaks with a great impact on human health. The increase in bacterial resistance constitutes a threat to public health. The appearance of Salmonella strains with resistance to multiple antimicrobials (MDR) has already been described in humans, food and animals for consumption; for this reason, it is considered very important to know the local epidemiological situation. The target of this work was to generate information on circulating serotypes, antibiotic resistance and the presence of simultaneous resistance to multiple drugs in Salmonella from human clinical samples and food samples in the period from 2017 to 2019. A total of 668 Salmonella strains isolated in the years 2017, 2018 and 2019 were analyzed from human and food clinical samples, at the Central Public Health Laboratory and / or sent by Laboratories of the Enteropathogens Network. Very diverse serotypes were observed with prevalence of Heidelberg serovar in food and Typhimurium in human samples .It was found that 45,4% of the strains were sensitive to all antibiotics (ATB), 35,6% were resistant from 1 to 6 ATB and 19% with intermediate sensitivity; observing greater resistance to Tetracycline, Ác. Nalidixic, Ampicillin and Nitrofurantoin, to a lesser degree resistance to cephalosporins (C3ªG) and ciprofloxacin was evidenced. The 16.9% the strains presented multiple resistance (3 or more antibiotics) with 37 different phenotypes. The serovars with the highest antimicrobial resistance were Heidelberg, Schwarzengrund and Typhimurium

Entry of dengue virus serotypes and their geographic distribution in Brazilian federative units: a systematic review / Entrada e distribuição geográfica dos sorotipos do vírus da dengue nas unidades federativas brasileiras: uma revisão sistemática

Objective: To describe the entry of Dengue virus (DENV) serotypes in Brazil and its federative units. Methods: A systematic review of studies published between 1980 and 2018 in databases and in the gray literature was performed using descriptors related to the years of entry of the DENV serotypes. Additionally, experts and official sources of information (Brazilian Ministry of Health) were consulted. Results: From 100 publications selected for the systematic review, 26 addressed the entry of DENV serotypes in the North region of the country, 33 in the Northeast, 24 in the Southeast, 14 in the Central-West, and five in the South. DENV-1 and DENV-4 were introduced in the North region in 1981. DENV-2 was introduced in the Southeast in 1990. DENV-3 was introduced in the North in 1999. Conclusion: The rapid expansion of dengue throughout the Brazilian territory was verified from the second half of the 1980s, with the gradual entry of the four serotypes, which resulted in the emergence of epidemics of arbovirus, which are currently verified in the country. Considering the epidemiology of the disease, more information should be disseminated and published in the wide-ranging scientific literature for a better understanding of the spread and circulation of DENV serotypes.

RESUMO: Objetivo: Descreveu-se a entrada de sorotipos do vírus da Dengue (DENV) no Brasil e em suas unidades federativas. Métodos: Realizou-se uma revisão sistemática de estudos publicados entre 1980 e 2018 em bancos de dados e na literatura cinzenta, utilizando-se descritores relacionados aos anos de entrada dos sorotipos do DENV. Além disso, consultou-se especialistas e fontes oficiais de informação (Ministério da Saúde do Brasil). Resultados: Das 100 publicações selecionadas para a revisão sistemática, 26 abordaram a entrada de sorotipos de DENV na região Norte do país, 33 no Nordeste, 24 no Sudeste, 14 no Centro-Oeste e cinco no Sul. O DENV-1 e o DENV-4 foram introduzidos na região Norte em 1981. O DENV-2 foi introduzido no Sudeste em 1990. O DENV-3 foi introduzido no Norte em 1999. Conclusão: A rápida expansão da dengue por todo o território brasileiro foi verificada a partir da segunda metade dos anos de 1980, com a entrada gradativa dos quatro sorotipos, o que resultou no surgimento de epidemias da arbovirose, que são atualmente verificadas no país. Considerando a epidemiologia da doença, mais informações devem ser divulgadas e publicadas na literatura científica de amplo alcance, para melhor entendimento da propagação e circulação dos sorotipos de DENV.

Invasive pneumococcal disease in children with cancer: Incidence density, risk factors and isolated serotypes

ABSTRACT Background: Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil. Methods: This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year. Results: A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis. Conclusion: Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

Primer aislamiento de Leptospira borgpetersenii serovar Hardjo tipo Hardjo Bovis a partir de un caso clínico en Argentina / First isolation of Leptospira borgpetersenii serovar Hardjo type Hardjo Bovis from aclinical case in cattle in Argentina

Resumen Se describe el primer aislamiento y la tipificación molecular de Leptospira borgpetersenii serovar Hardjo Bovis en Argentina, obtenido a partir de orina de vacas abortadas de unrodeo de cría ubicado en Saladillo, provincia de Buenos Aires. Los abortos coincidieron con unperíodo de importantes inundaciones, en el que varios animales presentaron títulos serológicossospechosos y posterior seroconversión. El porcentaje de abortos alcanzó el 3,5% del total delrodeo, compuesto por 1700 vacas, y se aisló el microorganismo en 7 de 20 muestras de orinaobtenidas.

Abstract We here describe the first isolation and molecular typing of Leptospira borgpe-tersenii serovar Hardjo Bovis in Argentina, obtained from urine of aborted cows from abreeding herd located in Saladillo, Buenos Aires Province. The abortions occurred in coincidence with important floods with many cows presenting suspicious serological titers and subsequentseroconversion. The percentage of abortions was 3.5% of a herd of 1700 cows and the microor-ganism was isolated from 7 of the 20 urine samples obtained.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013-2017 / Distribución de los serotipos PCV13 y PPSV23 de Streptococcus pneumoniae en adultos argentinos con enfermedad invasiva, 2013-2017

Abstract Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18-64 and >65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sep-sis/bacteremia the most prevalent was serotype 8. In this work, for the 18-64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the >65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Resumen Streptococcus pneumoniae es una causa importante de enfermedad invasiva grave asociada con una alta mortalidad y morbilidad en todo el mundo. Para identificar los serotipos principales asociados con la infección en adultos en Argentina, 791 aislamientos de neumococo de 56 hospitales pertenecientes a 16 provincias y la ciudad de Buenos Aires fueron serotipificados. Los aislamientos fueron remitidos como parte del Programa Nacional de Vigilancia para la enfermedad neumocócica invasiva en adultos, que comenzó en 2013. Los serotipos 3, 8, 12F, 7F y 1 fueron los más prevalentes. Durante el período de estudio no hubo diferencias significativas en la distribución de serotipos entre los dos grupos de adultos estudiados (18-64 y >65 años), excepto para los serotipos 1, 3 y 23A. Los serotipos más prevalentes en casos de neumonía fueron 7F, 1, 12F, 8 y 3. Cuando el diagnóstico clínico fue meningitis, los serotipos 3 y 12F fueron los más prevalentes. Y el serotipo 8 fue el más prevalente en la sepsis/bacteriemia. En el grupo de 18-64 años, los serotipos PPSV23 y PCV13 representaron, respectivamente, el 74,56 y el 44,54% de los casos de enfermedad invasiva en el período estudiado. En el grupo de >65 años, estos serotipos representaron el 72,30 y 41,42%, respectivamente. Es importante conocer los serotipos causantes de infecciones neumocócicas invasivas en la población adulta en Argentina y detectar eventuales cambios en su distribución a lo largo del tiempo, para explorar la potencial cobertura de las vacunas utilizadas.

Trajectory of serogroups causing Invasive Meningococcal Disease in Santa Catarina state, Brazil (2007-2019)

Abstract The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.