Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 247
Filtrar
1.
Genome Biol Evol ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439297

RESUMO

The isolation of Streptococcus pneumoniae serotypes in systemic tissues of patients with invasive disease versus the nasopharynx of healthy individuals with asymptomatic carriage varies widely. Some serotypes are hyper-invasive, particularly serotype 1, but the underlying genetics remain poorly understood due to the rarity of carriage isolates, reducing the power of comparison with invasive isolates. Here, we use a well-controlled genome-wide association study to search for genetic variation associated with invasiveness of serotype 1 pneumococci from a serotype 1 endemic setting in Africa. We found no consensus evidence that certain genomic variation is overrepresented among isolates from patients with invasive disease than asymptomatic carriage. Overall, the genomic variation explained negligible phenotypic variability, suggesting a minimal effect on the disease status. Furthermore, changes in lineage distribution were seen with lineages replacing each other over time, highlighting the importance of continued pathogen surveillance. Our findings suggest that the hyper-invasiveness is an intrinsic property of the serotype 1 strains, not specific for a "disease-associated" subpopulation disproportionately harbouring unique genomic variation.

2.
Microb Genom ; 8(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35384831

RESUMO

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , África do Sul/epidemiologia , Streptococcus pneumoniae/genética , Vacinas Conjugadas
4.
Microb Genom ; 8(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35302932

RESUMO

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern, and in 2006-2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby-Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Salmonella in Silico Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. Salmonella serovars Typhimurium (26/64; 30.6 %) and Enteritidis (13/64; 20.3 %) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9 %). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8 %) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted.


Assuntos
Gastroenterite , Infecções por Salmonella , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Gâmbia/epidemiologia , Gastroenterite/epidemiologia , Genômica , Humanos , Filogenia , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/epidemiologia , Salmonella typhimurium/genética
6.
Microb Genom ; 8(2)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35119356

RESUMO

The transmission dynamics of Streptococcus pneumoniae in sub-Saharan Africa are poorly understood due to a lack of adequate epidemiological and genomic data. Here we leverage a longitudinal cohort from 21 neighbouring villages in rural Africa to study how closely related strains of S. pneumoniae are shared among infants. We analysed 1074 pneumococcal genomes isolated from 102 infants from 21 villages. Strains were designated for unique serotype and sequence-type combinations, and we arbitrarily defined strain sharing where the pairwise genetic distance between strains could be accounted for by the mean within host intra-strain diversity. We used non-parametric statistical tests to assess the role of spatial distance and prolonged carriage on strain sharing using a logistic regression model. We recorded 458 carriage episodes including 318 (69.4 %) where the carried strain was shared with at least one other infant. The odds of strain sharing varied significantly across villages (χ2=47.5, df=21, P-value <0.001). Infants in close proximity to each other were more likely to be involved in strain sharing, but we also show a considerable amount of strain sharing across longer distances. Close geographic proximity (<5 km) between shared strains was associated with a significantly lower pairwise SNP distance compared to strains shared over longer distances (P-value <0.005). Sustained carriage of a shared strain among the infants was significantly more likely to occur if they resided in villages within a 5 km radius of each other (P-value <0.005, OR 3.7). Conversely, where both infants were transiently colonized by the shared strain, they were more likely to reside in villages separated by over 15 km (P-value <0.05, OR 1.5). PCV7 serotypes were rare (13.5 %) and were significantly less likely to be shared (P-value <0.001, OR -1.07). Strain sharing was more likely to occur over short geographical distances, especially where accompanied by sustained colonization. Our results show that strain sharing is a useful proxy for studying transmission dynamics in an under-sampled population with limited genomic data. This article contains data hosted by Microreact.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/transmissão , População Rural , Streptococcus pneumoniae/genética , África/epidemiologia , Humanos , Lactente , Microbiota , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Sequenciamento Completo do Genoma
7.
Transplant Cell Ther ; 28(4): 187.e1-187.e10, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35081472

RESUMO

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Prolinfocítica de Células T , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Prolinfocítica de Células T/terapia , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos
8.
EBioMedicine ; 73: 103644, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34695658

RESUMO

BACKGROUND: The specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored. METHODS: We applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent. FINDINGS: Children with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors. INTERPRETATION: Our findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones.  Further exploration of these systems will help inform innovative preventive and therapeutic interventions. FUNDING: The work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD].


Assuntos
Metabolismo Energético , Microbioma Gastrointestinal , Hormônios/metabolismo , Interações Hospedeiro-Patógeno , Desnutrição Aguda Grave/etiologia , Desnutrição Aguda Grave/metabolismo , Biodiversidade , Estudos Transversais , Suscetibilidade a Doenças , Enterobacteriaceae/patogenicidade , Fezes/microbiologia , Gâmbia/epidemiologia , Humanos , Metagenoma , Metagenômica/métodos , Fenótipo , População Rural , Desnutrição Aguda Grave/diagnóstico , Desnutrição Aguda Grave/epidemiologia , Fatores de Virulência
9.
Microb Genom ; 7(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34550067

RESUMO

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus, the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis, Streptococcus oralis and S. pneumoniae. With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis. Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced ß-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis.


Assuntos
Farmacorresistência Bacteriana/genética , Nasofaringe/microbiologia , Proteínas de Ligação às Penicilinas/genética , Sorogrupo , Streptococcus mitis/genética , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Proteínas de Bactérias/genética , Transferência Genética Horizontal , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Penicilinas , Filogenia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Streptococcus/classificação , Streptococcus/genética , Streptococcus oralis , Sequenciamento Completo do Genoma , Resistência beta-Lactâmica
10.
J Infect Dis ; 224(12 Suppl 2): S848-S855, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34528677

RESUMO

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.


Assuntos
Antibacterianos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Cryptosporidium/patogenicidade , Diarreia/tratamento farmacológico , Escherichia coli/patogenicidade , Transtornos do Crescimento/etiologia , Shigella/patogenicidade , Estudos de Casos e Controles , Criança , Cryptosporidium/isolamento & purificação , Diarreia/epidemiologia , Diarreia/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Shigella/isolamento & purificação
11.
J Infect Dis ; 224(12 Suppl 2): S161-S173, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469555

RESUMO

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.


Assuntos
Saúde Global/estatística & dados numéricos , Meningites Bacterianas/prevenção & controle , Meningite Pneumocócica/prevenção & controle , Vigilância de Evento Sentinela , Doenças Preveníveis por Vacina/epidemiologia , Vacinas Conjugadas/administração & dosagem , Criança , Pré-Escolar , Haemophilus influenzae , Humanos , Lactente , Meningites Bacterianas/epidemiologia , Meningite Pneumocócica/epidemiologia , Neisseria meningitidis , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae , Vacinação/estatística & dados numéricos , Doenças Preveníveis por Vacina/microbiologia , Organização Mundial da Saúde
12.
J Infect Dis ; 224(12 Suppl 2): S299-S306, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469559

RESUMO

Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.


Assuntos
Meningites Bacterianas/prevenção & controle , Meningite Meningocócica/prevenção & controle , Neisseria meningitidis , Vigilância de Evento Sentinela , Vacinação , África ao Sul do Saara/epidemiologia , Humanos , Meningite Meningocócica/epidemiologia
13.
J Infect Dis ; 224(12 Suppl 2): S174-S183, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469561

RESUMO

BACKGROUND: The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. METHODS: Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. RESULTS: A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. CONCLUSIONS: Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.


Assuntos
Meningite Meningocócica/epidemiologia , Meningite Pneumocócica/epidemiologia , Streptococcus pneumoniae , África ao Sul do Saara/epidemiologia , Surtos de Doenças , Humanos , Vigilância em Saúde Pública
14.
Nefrologia (Engl Ed) ; 2021 Aug 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34391607

RESUMO

OBJECTIVE: To analyze the results of endovascular treatment of venous anastomotic stenosis (VAS) in humero-axillary arteriovenous grafts (HAG), comparing outcomes between patent and thrombosed HAG. MATERIAL AND METHODS: A retrospective cohort study was made of endovascular treated patients because of a VAS in a HAG between January 2009 and December 2019. Group A: Thrombosed HAG secondary to a VAS. Group B: Patent HAG with a VAS detected during follow-up. Technical success was defined as residual stenosis after treatment <30%, and clinical success as satisfactory immediate dialysis after surgery. After ET a biannual clinical and ultrasound follow-up was performed. STATISTICAL ANALYSIS: Survival analysis was performed for time-to-event data to assess patency. RESULTS: Group A: 55 patients. Group B: 22. There were no significative differences in demographic and anatomical factors between groups. Technical and clinical success were 100% in Group B and 94.5% and 91% respectively in Group A. Primary patency at 1, 6 and 12 months was: Group A: 81.8%, 22.4% and 15.7% respectively. Group B: 100%, 85.9%, 76.4% (p<0.001). Secondary patency at 1, 6 and 12 months was: Group A: 85.2%, 45.8% and 31.3% respectively. Group B 100%, 95.3%, 95.2% (p<0.001). Use of non-covered stents was associated with an increased risk of occlusion (HR 2.669 95% CI 1.146-6.216, p=0.010). CONCLUSION: A higher patency of EV performed on a patent HAG is expected. It is therefore advisable to develop surveillance programs that are capable to detect VAS before its occlusion.

15.
Pediatr Infect Dis J ; 40(9S): S7-S17, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448740

RESUMO

BACKGROUND: Pneumonia remains the leading cause of death in young children globally. The changing epidemiology of pneumonia requires up-to-date data to guide both case management and prevention programs. The Gambia study site contributed a high child mortality, high pneumonia incidence, low HIV prevalence, Haemophilus influenzae type b and pneumococcal conjugate vaccines-vaccinated rural West African setting to the Pneumonia Etiology Research for Child Health (PERCH) Study. METHODS: The PERCH study was a 7-country case-control study of the etiology of hospitalized severe pneumonia in children 1-59 months of age in low and middle-income countries. Culture and nucleic acid detection methods were used to test nasopharyngeal/oropharyngeal swabs, blood, induced sputum and, in selected cases, lung or pleural fluid aspirates. Etiology was determined by integrating case and control data from multiple specimens using the PERCH integrated analysis based on Bayesian probabilistic methods. RESULTS: At The Gambia study site, 638 cases of World Health Organization-defined severe and very severe pneumonia (286 of which were chest radiograph [CXR]-positive and HIV-negative) and 654 age-frequency matched controls were enrolled. Viral causes predominated overall (viral 58% vs. bacterial 28%), and of CXR-positive cases respiratory syncytial virus (RSV) accounted for 37%, Streptococcus pneumoniae 13% and parainfluenza was responsible for 9%. Nevertheless, among very severe cases bacterial causes dominated (77% bacterial vs. 11% viral), led by S. pneumoniae (41%); Mycobacterium tuberculosis, not included in "bacterial", accounted for 9%. 93% and 80% of controls ≥1 year of age were, respectively, fully vaccinated for age against Haemophilus influenzae and S. pneumoniae. CONCLUSIONS: Viral causes, notably RSV, predominated in The Gambia overall, but bacterial causes dominated the severest cases. Efforts must continue to prevent disease by optimizing access to existing vaccines, and to develop new vaccines, notably against RSV. A continued emphasis on appropriate case management of severe pneumonia remains important.


Assuntos
Pneumonia/etiologia , Teorema de Bayes , Estudos de Casos e Controles , Saúde da Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Gâmbia/epidemiologia , Vacinas Anti-Haemophilus , Hospitalização , Humanos , Incidência , Lactente , Modelos Logísticos , Masculino , Gravidade do Paciente , Vacinas Pneumocócicas , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Fatores de Risco
16.
PLoS One ; 16(8): e0241942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34464385

RESUMO

The SARS-CoV-2 disease, first detected in Wuhan, China, in December 2019 has become a global pandemic and is causing an unprecedented burden on health care systems and the economy globally. While the travel history of index cases may suggest the origin of infection, phylogenetic analysis of isolated strains from these cases and contacts will increase the understanding and link between local transmission and other global populations. The objective of this analysis was to provide genomic data on the first six cases of SARS-CoV-2 in The Gambia and to determine the source of infection. This ultimately provide baseline data for subsequent local transmission and contribute genomic diversity information towards local and global data. Our analysis has shown that the SARS-CoV-2 virus identified in The Gambia are of European and Asian origin and sequenced data matched patients' travel history. In addition, we were able to show that two COVID-19 positive cases travelling in the same flight had different strains of SARS-CoV-2. Although whole genome sequencing (WGS) data is still limited in sub-Saharan Africa, this approach has proven to be a highly sensitive, specific and confirmatory tool for SARS-CoV-2 detection.


Assuntos
COVID-19/patologia , Genoma Viral , SARS-CoV-2/genética , COVID-19/virologia , Gâmbia , Variação Genética , Humanos , Funções Verossimilhança , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Sequenciamento Completo do Genoma
17.
Microb Genom ; 7(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34241588

RESUMO

Pathogens of the Mycobacterium tuberculosis complex (MTBC) are considered to be monomorphic, with little gene content variation between strains. Nevertheless, several genotypic and phenotypic factors separate strains of the different MTBC lineages (L), especially L5 and L6 (traditionally termed Mycobacterium africanum) strains, from each other. However, this genome variability and gene content, especially of L5 strains, has not been fully explored and may be important for pathobiology and current approaches for genomic analysis of MTBC strains, including transmission studies. By comparing the genomes of 355 L5 clinical strains (including 3 complete genomes and 352 Illumina whole-genome sequenced isolates) to each other and to H37Rv, we identified multiple genes that were differentially present or absent between H37Rv and L5 strains. Additionally, considerable gene content variability was found across L5 strains, including a split in the L5.3 sub-lineage into L5.3.1 and L5.3.2. These gene content differences had a small knock-on effect on transmission cluster estimation, with clustering rates influenced by the selected reference genome, and with potential overestimation of recent transmission when using H37Rv as the reference genome. We conclude that full capture of the gene diversity, especially high-resolution outbreak analysis, requires a variation of the single H37Rv-centric reference genome mapping approach currently used in most whole-genome sequencing data analysis pipelines. Moreover, the high within-lineage gene content variability suggests that the pan-genome of M. tuberculosis is at least several kilobases larger than previously thought, implying that a concatenated or reference-free genome assembly (de novo) approach may be needed for particular questions.


Assuntos
Variação Genética/genética , Genoma Bacteriano/genética , Mycobacterium tuberculosis/genética , Mapeamento Cromossômico , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mycobacterium tuberculosis/classificação , Análise de Sequência de DNA , Especificidade da Espécie , Tuberculose/microbiologia , Tuberculose/transmissão , Sequenciamento Completo do Genoma
18.
Microb Genom ; 7(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34328412

RESUMO

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Meningite Pneumocócica/epidemiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Adolescente , África Ocidental/epidemiologia , Antituberculosos/farmacologia , Criança , Pré-Escolar , Genoma Bacteriano/genética , Humanos , Lactente , Recém-Nascido , Meningite Pneumocócica/imunologia , Meningite Pneumocócica/prevenção & controle , Testes de Sensibilidade Microbiana , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Sequenciamento Completo do Genoma
19.
Viruses ; 13(7)2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198998

RESUMO

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing.


Assuntos
Nasofaringe/virologia , Infecções por Picornaviridae/epidemiologia , Pneumonia Viral/epidemiologia , Rhinovirus/patogenicidade , África/epidemiologia , Ásia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções por Picornaviridae/etnologia , Pneumonia Viral/etiologia , Sons Respiratórios/etiologia
20.
Lancet Infect Dis ; 21(9): 1293-1302, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280357

RESUMO

BACKGROUND: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. METHODS: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. FINDINGS: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49). INTERPRETATION: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. FUNDING: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.


Assuntos
Infecções Pneumocócicas/psicologia , Vacinas Pneumocócicas/imunologia , Pneumonia/prevenção & controle , Streptococcus pneumoniae/imunologia , Vacinação , Vacinas Conjugadas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Gâmbia , Humanos , Imunização , Incidência , Lactente , Masculino , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vigilância da População
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...