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1.
Antimicrob Agents Chemother ; 68(9): e0157623, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39136465

RESUMEN

The emergence of drug-resistant Plasmodium falciparum parasites in sub-Saharan Africa will substantially challenge malaria control. Here, we evaluated the frequency of common drug resistance markers among adolescents from Northern Uganda with asymptomatic infections. We used an established amplicon deep sequencing strategy to screen dried blood spot samples collected from 2016 to 2017 during a reported malaria epidemic within the districts of Kitgum and Pader in Northern Uganda. We screened single-nucleotide polymorphisms within: kelch13 (Pfk13), dihydropteroate synthase (Pfdhps), multidrug resistance-1 (Pfmdr1), dihydrofolate reductase (Pfdhfr), and apical membrane antigen (Pfama1) genes. Within the study population, the median age was 15 years (14.3-15.0, 95% CI), and 54.9% (78/142) were Plasmodium positive by 18S rRNA qPCR, which were subsequently targeted for sequencing analysis. We observed a high frequency of resistance markers particularly for sulfadoxine-pyrimethamine (SP), with no wild-type-only parasites observed for Pfdhfr (N51I, C59R, and S108N) and Pfdhps (A437G and K540E) mutations. Within Pfmdr1, mixed infections were common for NF/NY (98.5%). While for artemisinin resistance, in kelch13, there was a high frequency of C469Y (34%). Using the pattern for Pfama1, we found a high level of polygenomic infections with all individuals presenting with complexity of infection greater than 2 with a median of 6.9. The high frequency of the quintuple SP drug-resistant parasites and the C469Y artemisinin resistance-associated mutation in asymptomatic individuals suggests an earlier high prevalence than previously reported from symptomatic malaria surveillance studies (in 2016/2017). Our data demonstrate the urgency for routine genomic surveillance programs throughout Africa and the value of deep sequencing.


Asunto(s)
Antimaláricos , Infecciones Asintomáticas , Resistencia a Medicamentos , Malaria Falciparum , Plasmodium falciparum , Pirimetamina , Sulfadoxina , Plasmodium falciparum/genética , Plasmodium falciparum/efectos de los fármacos , Humanos , Uganda/epidemiología , Adolescente , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Malaria Falciparum/tratamiento farmacológico , Pirimetamina/farmacología , Pirimetamina/uso terapéutico , Estudios Retrospectivos , Sulfadoxina/farmacología , Sulfadoxina/uso terapéutico , Resistencia a Medicamentos/genética , Femenino , Infecciones Asintomáticas/epidemiología , Masculino , Mutación , Proteínas Protozoarias/genética , Combinación de Medicamentos , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Artemisininas/farmacología , Artemisininas/uso terapéutico , Tetrahidrofolato Deshidrogenasa/genética
2.
Int J Infect Dis ; 148: 107218, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39181438

RESUMEN

OBJECTIVES: This study investigated the genotype-specific dynamics of molecular HIV clusters (MHCs) in Guangzhou, China, aiming to enhance HIV control. METHODS: HIV pol sequences from people with HIV (PWH) in Guangzhou (2008-2020) were obtained for genotyping and molecular network creation. MHCs were identified and categorized into three types: emerging, growing, or stable. Clustering rates, proportions of cluster types, and members within each type were calculated and their trends were assessed using joinpoint regression. RESULTS: Among 8395 PWH, the most prevalent HIV-1 genotypes were CRF07_BC (39.7%) and CRF01_AE (32.6%). The genotype composition has been stable since 2012 (Ps > 0.05). The overall clustering rate was 43.3%, with significant variations across genotypes (P < 0.001), indicating genotype-specific transmission fitness. Significant declines in overall and genotype-specific clustering rates toward the end of 2020 (Ps < 0.05), potentially offer support for HIV control efforts in reducing local infections. The continuously increasing proportions of stable clusters and the gradually decreasing proportions of emerging and growing clusters (either Ps < 0.05 or Ps > 0.05) suggest a trend toward stable molecular network structure. However, growing clusters exhibited CRF55_01B, CRF07_BC, and CRF59_01B dominance that indicate their priority for interventions. CONCLUSION: The evolving MHCs highlight the genotype-specific cluster dynamics, providing fresh insights for enhanced prevention and control strategies.

3.
J Clin Microbiol ; 62(9): e0062824, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39158309

RESUMEN

Nanopore sequencing has shown the potential to democratize genomic pathogen surveillance due to its ease of use and low entry cost. However, recent genotyping studies showed discrepant results compared to gold-standard short-read sequencing. Furthermore, although essential for widespread application, the reproducibility of nanopore-only genotyping remains largely unresolved. In our multicenter performance study involving five laboratories, four public health-relevant bacterial species were sequenced with the latest R10.4.1 flow cells and V14 chemistry. Core genome MLST analysis of over 500 data sets revealed highly strain-specific typing errors in all species in each laboratory. Investigation of the methylation-related errors revealed consistent DNA motifs at error-prone sites across participants at read level. Depending on the frequency of incorrect target reads, this either leads to correct or incorrect typing, whereby only minimal frequency deviations can randomly determine the final result. PCR preamplification, recent basecalling model updates and an optimized polishing strategy notably diminished the non-reproducible typing. Our study highlights the potential for new errors to appear with each newly sequenced strain and lays the foundation for computational approaches to reduce such typing errors. In conclusion, our multicenter study shows the necessity for a new validation concept for nanopore sequencing-based, standardized bacterial typing, where single nucleotide accuracy is critical.


Asunto(s)
Bacterias , Técnicas de Genotipaje , Secuenciación de Nanoporos , Secuenciación de Nanoporos/métodos , Reproducibilidad de los Resultados , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Humanos , Técnicas de Genotipaje/métodos , Genotipo , Tipificación de Secuencias Multilocus/métodos , ADN Bacteriano/genética , Genoma Bacteriano/genética , Análisis de Secuencia de ADN/métodos
4.
BMC Infect Dis ; 24(1): 718, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039455

RESUMEN

Mumps is a vaccine-preventable disease with high contagious capability. Its incidence declined rapidly since one dose of mumps vaccine was introduced into Expanded Program of Immunization (EPI) in 2008 in China. Nonetheless, the outbreaks of mumps remain frequent in China. Here we aim to assess herd immunity level followed by one-dose mumps ingredient vaccine and to elucidate the genetic characteristics of mumps viruses circulating in the post vaccine era in Jiangsu province of China. The complete sequences of mumps virus small hydrophobic(SH) gene were amplified and sequenced; coalescent-based Bayesian method was used to perform phylogenetic analysis with BEAST 1.84 software. Commercially available indirect enzyme-linked immune-sorbent IgG assay was used for the quantitative detection of IgG antibody against mumps virus. Our results show that genotype F was the predominant mumps viruses and belonged to indigenous spread, and most of Jiangsu sequences clustered together and formed a monophyly. The prevalence of mumps reached a peak in 2012 and subsequently declined, which presented an obvious different trajectory with virus circulating in other regions of China. The gene diversity of viruses circulating in Jiangsu province was far less than those in China. The antibody prevalence reached 70.42% in the general population during 2018 to 2020. The rising trend of antibody level was also observed. Although mumps antibody prevalence does not reach expected level, mumps virus faces higher pressure in Jiangsu province than the whole of China. To reduce further the prevalence of mumps viruses, two doses of mumps vaccine should be involved into EPI.


Asunto(s)
Anticuerpos Antivirales , Vacuna contra la Parotiditis , Virus de la Parotiditis , Paperas , Filogenia , Virus de la Parotiditis/genética , Virus de la Parotiditis/inmunología , Virus de la Parotiditis/clasificación , Humanos , China/epidemiología , Paperas/epidemiología , Paperas/virología , Paperas/inmunología , Paperas/prevención & control , Anticuerpos Antivirales/sangre , Vacuna contra la Parotiditis/administración & dosificación , Vacuna contra la Parotiditis/inmunología , Adulto , Adulto Joven , Femenino , Masculino , Genotipo , Adolescente , Niño , Inmunoglobulina G/sangre , Persona de Mediana Edad , Preescolar , Inmunidad Colectiva , Variación Genética , Proteínas Virales
6.
Vaccines (Basel) ; 12(7)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39066448

RESUMEN

Molecular surveillance of circulating measles variants serves as a line of evidence for the absence of endemic circulation and provides a means to track chains of transmission. Molecular surveillance for measles (genotyping) is based on the sequence of 450 nucleotides at the end of the nucleoprotein coding region (N450) of the measles genome. Genotyping was established in 1998 and, with over 50,000 sequence submissions to the Measles Nucleotide Surveillance database, has proven to be an effective resource for countries attempting to trace pathways of transmission. This review summarizes the tools used for the molecular surveillance of measles and describes the challenge posed by the decreased number of circulating measles genotypes. The Global Measles and Rubella Laboratory Network addressed this challenge through the development of new tools such as named strains and distinct sequence identifiers that analyze the diversity within the currently circulating genotypes. The advantages and limitations of these approaches are discussed, together with the need to generate additional sequence data including whole genome sequences to ensure the continued utility of strain surveillance for measles.

7.
Antibiotics (Basel) ; 13(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39061338

RESUMEN

Resistance to last-resort antibiotics is a global threat to public health. Therefore, surveillance and monitoring systems for antimicrobial resistance should be established on a national and international scale. For the development of a One Health surveillance system, we collected exemplary data on carbapenem and colistin-resistant bacterial isolates from human, animal, food, and environmental sources. We pooled secondary data from routine screenings, hospital outbreak investigations, and studies on antimicrobial resistance. For a joint One Health evaluation, this study incorporates epidemiological metadata with phenotypic resistance information and molecular data on the isolate level. To harmonise the heterogeneous original information for the intended use, we developed a generic strategy. By defining and categorising variables, followed by plausibility checks, we created a catalogue for prospective data collections and applied it to our dataset, enabling us to perform preliminary descriptive statistical analyses. This study shows the complexity of data management using heterogeneous secondary data pools and gives an insight into the early stages of the development of an AMR surveillance programme using secondary data.

8.
Front Health Serv ; 4: 1289394, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957804

RESUMEN

The rapid detection and continuous surveillance of infectious diseases are important components of an effective public health response. However, establishing advanced molecular surveillance systems, crucial for monitoring and mitigating pandemics, poses significant challenges in resource-limited developing countries. In a collaborative effort, research institutions from Benin joined forces with Mali's National Institute of Public Health to implement a state-of-the-art molecular surveillance system in Mali. This approach was characterized by collaboration, multidisciplinarity, and tutoring. Key activities included a comprehensive assessment of infrastructure and human resources through document reviews, interviews, and laboratory visits; the development and validation of Standard Operating Procedures (SOPs) for advanced molecular surveillance following an inclusive approach; capacity-building initiatives for 25 biologists in Mali on sequencing techniques; and international tutoring sessions for eight Malian professionals held in Benin. These collective efforts enabled Mali to establish an advanced molecular surveillance system aligned with the WHO's global strategy for genomic surveillance. This manuscript aims to share experiences, insights, and outcomes from this initiative, with the hope of contributing to the broader discussion on strengthening global health security through collaborative approaches and capacity-building efforts, particularly in developing countries.

9.
Viruses ; 16(6)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38932144

RESUMEN

Monitoring the genetic variability of human respiratory syncytial virus (hRSV) is of paramount importance, especially for the potential implication of key antigenic mutations on the emergence of immune escape variants. Thus, to describe the genetic diversity and evolutionary dynamics of hRSV circulating in Sicily (Italy), a total of 153 hRSV whole-genome sequences collected from 770 hRSV-positive subjects between 2017 and 2023, before the introduction of expanded immunization programs into the population, were investigated. The phylogenetic analyses indicated that the genotypes GA.2.3.5 (ON1) for hRSV-A and GB.5.0.5a (BA9) for hRSV-B co-circulated in our region. Amino acid (AA) substitutions in the surface and internal proteins were evaluated, including the F protein antigenic sites, as the major targets of immunoprophylactic monoclonal antibodies and vaccines. Overall, the proportion of AA changes ranged between 1.5% and 22.6% among hRSV-A, whereas hRSV-B varied in the range 0.8-16.9%; the latter was more polymorphic than hRSV-A within the key antigenic sites. No AA substitutions were found at site III of both subgroups. Although several non-synonymous mutations were found, none of the polymorphisms known to potentially affect the efficacy of current preventive measures were documented. These findings provide new insights into the global hRSV molecular epidemiology and highlight the importance of defining a baseline genomic picture to monitor for future changes that might be induced by the selective pressures of immunological preventive measures, which will soon become widely available.


Asunto(s)
Variación Genética , Genotipo , Filogenia , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Secuenciación Completa del Genoma , Humanos , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Sicilia/epidemiología , Preescolar , Lactante , Femenino , Masculino , Niño , Adulto , Adolescente , Genoma Viral , Persona de Mediana Edad , Adulto Joven , Anciano , Gripe Humana/virología , Gripe Humana/epidemiología , Sustitución de Aminoácidos , Recién Nacido
10.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38833323

RESUMEN

The emergence and rapid spread of SARS-CoV-2 prompted the global community to identify innovative approaches to diagnose infection and sequence the viral genome because at several points in the pandemic positive case numbers exceeded the laboratory capacity to characterize sufficient samples to adequately respond to the spread of emerging variants. From week 10, 2020, to week 13, 2023, Slovenian routine complete genome sequencing (CGS) surveillance network yielded 41 537 complete genomes and revealed a typical molecular epidemiology with early lineages gradually being replaced by Alpha, Delta, and finally Omicron. We developed a targeted next-generation sequencing based variant surveillance strategy dubbed Spike Screen through sample pooling and selective SARS-CoV-2 spike gene amplification in conjunction with CGS of individual cases to increase throughput and cost-effectiveness. Spike Screen identifies variant of concern (VOC) and variant of interest (VOI) signature mutations, analyses their frequencies in sample pools, and calculates the number of VOCs/VOIs at the population level. The strategy was successfully applied for detection of specific VOC/VOI mutations prior to their confirmation by CGS. Spike Screen complemented CGS efforts with an additional 22 897 samples sequenced in two time periods: between week 42, 2020, and week 24, 2021, and between week 37, 2021, and week 2, 2022. The results showed that Spike Screen can be applied to monitor VOC/VOI mutations among large volumes of samples in settings with limited sequencing capacity through reliable and rapid detection of novel variants at the population level and can serve as a basis for public health policy planning.


Asunto(s)
COVID-19 , Secuenciación de Nucleótidos de Alto Rendimiento , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , COVID-19/virología , COVID-19/diagnóstico , COVID-19/epidemiología , Glicoproteína de la Espiga del Coronavirus/genética , Mutación , Genoma Viral , Eslovenia/epidemiología
11.
Epidemiol Mikrobiol Imunol ; 73(1): 30-36, 2024.
Artículo en Checo | MEDLINE | ID: mdl-38697838

RESUMEN

Streptococcus pneumoniae (pneumococcus) is a Gram-positive coccus causing both non-invasive and invasive infectious diseases. Pneumococcal diseases are vaccine preventable. Invasive pneumococcal diseases (IPD) meeting the international case definition are reported nationally and internationally and are subject to surveillance programmes in many countries, including the Czech Republic. An important part of IPD surveillance is the monitoring of causative serotypes and their frequency over time and in relation to ongoing vaccination programmes. In the world and in the Czech Republic, whole genome sequencing (WGS) is increasingly used for pneumococci, which allows for serotyping from sequencing data, precise analysis of their genetic relationships, and the study of genes present in their genome. Whole-genome sequencing enables the generation of reliable and internationally comparable data that can be easily shared. Sequencing data are analysed using bioinformatics tools that require knowledge in the field of natural sciences with an emphasis on genetics and expertise in bioinformatics. This publication presents some options for pneumococcal analysis, i.e., serotyping, multilocus sequence typing (MLST), ribosomal MLST (rMLST), core genome MLST (cgMLST), whole genome MLST (wgMLST), single nucleotide polymorphism (SNP) analysis, assignment to Global Pneumococcal Sequence Cluster (GPSC), and identification of virulence genes and antibiotic resistance genes. The WGS strategies and applications for Europe and WGS implementation in practice are presented. WGS analysis of pneumococci allows for improved IPD surveillance, thanks to molecular serotyping, more detailed typing, generation of internationally comparable data, and improved evaluation of the effectiveness of vaccination programmes.


Asunto(s)
Infecciones Neumocócicas , Streptococcus pneumoniae , Secuenciación Completa del Genoma , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/clasificación , Humanos , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , República Checa , Genoma Bacteriano , Tipificación de Secuencias Multilocus , Serotipificación
12.
J Clin Microbiol ; 62(6): e0172523, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38780286

RESUMEN

The environmental bacterium Klebsiella oxytoca displays an alarming increase of antibiotic-resistant strains that frequently cause outbreaks in intensive care units. Due to its prevalence in the environment and opportunistic presence in humans, molecular surveillance (including resistance marker screening) and high-resolution cluster analysis are of high relevance. Furthermore, K. oxytoca previously described in studies is rather a species complex (KoSC) than a single species comprising at least six closely related species that are not easily differentiated by standard typing methods. To reach a discriminatory power high enough to identify and resolve clusters within these species, whole genome sequencing is necessary. The resolution is achievable with core genome multilocus sequence typing (cgMLST) extending typing of a few housekeeping genes to thousands of core genome genes. CgMLST is highly standardized and provides a nomenclature enabling cross laboratory reproducibility and data exchange for routine diagnostics. Here, we established a cgMLST scheme not only capable of resolving the KoSC species but also producing reliable and consistent results for published outbreaks. Our cgMLST scheme consists of 2,536 core genome and 2,693 accessory genome targets, with a percentage of good cgMLST targets of 98.31% in 880 KoSC genomes downloaded from the National Center for Biotechnology Information (NCBI). We also validated resistance markers against known resistance gene patterns and successfully linked genetic results to phenotypically confirmed toxic strains carrying the til gene cluster. In conclusion, our novel cgMLST enables highly reproducible typing of four different clinically relevant species of the KoSC and thus facilitates molecular surveillance and cluster investigations.


Asunto(s)
Genoma Bacteriano , Klebsiella oxytoca , Tipificación de Secuencias Multilocus , Tipificación de Secuencias Multilocus/métodos , Klebsiella oxytoca/genética , Klebsiella oxytoca/clasificación , Klebsiella oxytoca/aislamiento & purificación , Humanos , Genoma Bacteriano/genética , Filogenia , Infecciones por Klebsiella/microbiología , Secuenciación Completa del Genoma , Técnicas de Tipificación Bacteriana/métodos , Genes Esenciales/genética , Reproducibilidad de los Resultados
13.
Zoonoses Public Health ; 71(5): 584-590, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38693773

RESUMEN

OBJECTIVE: We contribute to the understanding of the transmission dynamics of Leishmania infantum suggesting the involvement of rabbits as wild reservoirs. RESULTS: The prevalence of infection was 86.0% (270/314 wild rabbits) ranging from 18.2% to 100% in natural geographical regions. The estimated average parasite load was 324.8 [CI 95% 95.3-554.3] parasites per mg of ear lobe ranging from 0 to 91,597 parasites/mg per tissue section. CONCLUSIONS: A positive correlation was found between skin parasite load in wild rabbits and human incidence with evidence of the presence of the same L. infantum genotypes in rabbits and humans, providing new epidemiological and biological basis for the consideration of wild rabbits as a relevant L. infantum wild reservoir. Molecular parasite surveillance reflects the great genotypic variability of the parasite population in wild rabbits. Most of these genotypes have also been found to infect humans, dogs and sandflies in the region. Our findings also highlight that direct genotyping of the parasite in host tissues should be used for molecular surveillance of the parasite instead of cultured isolates.


Asunto(s)
Reservorios de Enfermedades , Leishmania infantum , Leishmaniasis Visceral , Animales , Leishmania infantum/genética , Leishmania infantum/aislamiento & purificación , Conejos/parasitología , España/epidemiología , Reservorios de Enfermedades/veterinaria , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/veterinaria , Leishmaniasis Visceral/transmisión , Leishmaniasis Visceral/parasitología , Humanos , Animales Salvajes/parasitología , Prevalencia , Genotipo
15.
J Infect Dis ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38547503

RESUMEN

BACKGROUND: Chlamydia trachomatis is the causative agent of most prevalent bacterial sexually transmitted infection globally. Whole-genome sequencing is essential for molecular Chlamydia surveillance; however, its application is hampered by the pathogen's low abundance in clinical specimens and the expensive, labor-intensive nature of existing enrichment methodologies for Chlamydia. METHODS: We developed a targeted whole-genome amplification tool termed SWTICH, by integrating phi29 DNA polymerase-mediated amplification with meticulously designed primer sets to enrich Chlamydia trachomatis genome, followed by whole-genome sequencing. This method underwent evaluation through testing synthetic and clinical specimens. RESULTS: SWITCH demonstrated robust ability to achieve up to 98.3% genomic coverage of Chlamydia trachomatis from as few as 26.4 genomic copies present in synthetic specimens and exhibited excellent performance across diverse Chlamydia trachomatis serovars. Utilizing SWITCH, we directly generated 21 Chlamydia genomes from 26 clinical samples, enabling us to gain insights into the genetic relationships and phylogeny of current Chlamydia strains circulating in the country. Remarkably, this study marked the first instance of generating Chinese Chlamydia genomes directly from clinical samples. CONCLUSIONS: SWITCH represents a practical, cost-efficient approach to enrich Chlamydia genome directly from clinical specimens, offering an efficient avenue for molecular surveillance of Chlamydia.

16.
Int J Med Microbiol ; 314: 151610, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38310676

RESUMEN

Shiga toxin-producing E. coli (STEC), including the subgroup of enterohemorrhagic E. coli (EHEC), are important bacterial pathogens which cause diarrhea and the severe clinical manifestation hemolytic uremic syndrome (HUS). Genomic surveillance of STEC/EHEC is a state-of-the-art tool to identify infection clusters and to extract markers of circulating clinical strains, such as their virulence and resistance profile for risk assessment and implementation of infection prevention measures. The aim of the study was characterization of the clinical STEC population in Germany for establishment of a reference data set. To that end, from 2020 to 2022 1257 STEC isolates, including 39 of known HUS association, were analyzed and lead to a classification of 30.4 % into 129 infection clusters. Major serogroups in all clinical STEC analyzed were O26, O146, O91, O157, O103, and O145; and in HUS-associated strains were O26, O145, O157, O111, and O80. stx1 was less frequently and stx2 or a combination of stx, eaeA and ehxA were more frequently found in HUS-associated strains. Predominant stx gene subtypes in all STEC strains were stx1a (24 %) and stx2a (21 %) and in HUS-associated strains were mainly stx2a (69 %) and the combination of stx1a and stx2a (12.8 %). Furthermore, two novel O-antigen gene clusters (RKI6 and RKI7) and strains of serovars O45:H2 and O80:H2 showing multidrug resistance were detected. In conclusion, the implemented surveillance tools now allow to comprehensively define the population of clinical STEC strains including those associated with the severe disease manifestation HUS reaching a new surveillance level in Germany.


Asunto(s)
Escherichia coli Enterohemorrágica , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Humanos , Virulencia/genética , Antígenos O/genética , Proteínas de Escherichia coli/genética , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Genómica , Alemania/epidemiología , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/microbiología , Familia de Multigenes
17.
J Travel Med ; 31(3)2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38127641

RESUMEN

BACKGROUND: Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers returning to non-endemic areas can provide valuable data to inform endemic country programmes. To evaluate the potential for novel global insights into malaria, we examined epidemiological and molecular data from imported malaria cases to Australia. METHODS: We analysed malaria cases reported in Australia from 2012 to 2022 using National Notifiable Disease Surveillance System data. Molecular data on imported malaria cases were obtained from literature searches. RESULTS: Between 2012 and 2022, 3204 malaria cases were reported in Australia. Most cases (69%) were male and 44% occurred in young adults aged 20-39 years. Incidence rates initially declined between 2012 and 2015, then increased until 2019. During 2012-2019, the incidence in travellers ranged from 1.34 to 7.71 per 100 000 trips. Cases were primarily acquired in Sub-Saharan Africa (n = 1433; 45%), Oceania (n = 569; 18%) and Southern and Central Asia (n = 367; 12%). The most common countries of acquisition were Papua New Guinea (n = 474) and India (n = 277). Plasmodium falciparum accounted for 58% (1871/3204) of cases and was predominantly acquired in Sub-Saharan Africa, and Plasmodium vivax accounted for 32% (1016/3204), predominantly from Oceania and Asia. Molecular studies of imported malaria cases to Australia identified genetic mutations and deletions associated with drug resistance and false-negative rapid diagnostic test results, and led to the establishment of reference genomes for P. vivax and Plasmodium malariae. CONCLUSIONS: Our analysis highlights the continuing burden of imported malaria into Australia. Molecular studies have offered valuable insights into drug resistance and diagnostic limitations, and established reference genomes. Integrating molecular data into national surveillance systems could provide important infectious disease intelligence to optimize treatment guidelines for returning travellers and support endemic country surveillance programmes.


Asunto(s)
Malaria Vivax , Malaria , Adulto Joven , Masculino , Humanos , Femenino , Viaje , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/epidemiología , Plasmodium falciparum , Australia/epidemiología
18.
Trends Parasitol ; 40(2): 147-163, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38129280

RESUMEN

Over recent years, progress in molecular markers for genotyping malaria parasites has enabled informative studies of epidemiology and transmission dynamics. Results have highlighted the value of these tools for surveillance to support malaria control and elimination strategies. There are many different types and panels of markers available for malaria parasite genotyping, and for end users, the nuances of these markers with respect to 'use case', resolution, and accuracy, are not well defined. This review clarifies issues surrounding different molecular markers and their application to malaria control and elimination. We describe available marker panels, use cases, implications for different transmission settings, limitations, access, cost, and data accuracy. The information provided can be used as a guide for molecular epidemiology and surveillance of malaria.


Asunto(s)
Malaria Falciparum , Malaria , Humanos , Malaria/epidemiología , Epidemiología Molecular , Biomarcadores , Malaria Falciparum/parasitología
19.
Hum Genomics ; 17(1): 114, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38105239

RESUMEN

BACKGROUND: Despite a clear appreciation of the impact of human pathogens on community health, efforts to understand pathogen dynamics within populations often follow a narrow-targeted approach and rely on the deployment of specific molecular probes for quantitative detection or rely on clinical detection and reporting. MAIN TEXT: Genomic analysis of wastewater samples for the broad detection of viruses, bacteria, fungi, and antibiotic resistance genes of interest/concern is inherently difficult, and while deep sequencing of wastewater provides a wealth of information, a robust and cooperative foundation is needed to support healthier communities. In addition to furthering the capacity of high-throughput sequencing wastewater-based epidemiology to detect human pathogens in an unbiased and agnostic manner, it is critical that collaborative networks among public health agencies, researchers, and community stakeholders be fostered to prepare communities for future public health emergencies or for the next pandemic. A more inclusive public health infrastructure must be built for better data reporting where there is a global human health risk burden. CONCLUSIONS: As wastewater platforms continue to be developed and refined, high-throughput sequencing of human pathogens in wastewater samples will emerge as a gold standard for understanding community health.


Asunto(s)
Virus , Aguas Residuales , Humanos , Monitoreo Epidemiológico Basado en Aguas Residuales , Virus/genética , Bacterias/genética , Farmacorresistencia Microbiana/genética
20.
BMC Infect Dis ; 23(1): 673, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37817087

RESUMEN

BACKGROUND: The transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory. METHOD: From 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports. RESULTS: Among all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse-transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (pTrend=0.024) during 2017-2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (pTrend=0.049) while the frequency of minority subtypes (each < 1%) increased (pTrend=0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%). CONCLUSION: The percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Minorías Sexuales y de Género , Virus , Masculino , Humanos , Homosexualidad Masculina , Farmacorresistencia Viral/genética , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Mutación , ARN Polimerasas Dirigidas por ADN/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Genotipo
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