Transmission Clusters Research Articles

Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020.

Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

Investigating Local Patterns of Mumps Virus Circulation, Using a Combination of Molecular Tools.

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.

Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022.

Molecular epidemiology of HIV-1 infection is challenging due to the highly diverse HIV-genome. We investigated the genetic diversity and prevalence of transmitted drug resistance (TDR) followed by phylogenetic analysis in 270 HIV-1 infected, treatment-naïve individuals from Croatia in the period 2019-2022. The results of this research confirmed a high overall prevalence of TDR of 16.7%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PIs) was found in 9.6%, 7.4%, and 1.5% of persons, respectively. No resistance to integrase strand-transfer inhibitors (INSTIs) was found. Phylogenetic analysis revealed that 173/229 sequences (75.5%) were part of transmission clusters, and the largest identified was T215S, consisting of 45 sequences. Forward transmission was confirmed in several clusters. We compared deep sequencing (DS) with Sanger sequencing (SS) on 60 randomly selected samples and identified additional surveillance drug resistance mutations (SDRMs) in 49 of them. Our data highlight the need for baseline resistance testing in treatment-naïve persons. Although no major INSTIs were found, monitoring of SDRMs to INSTIs should be continued due to the extensive use of first- and second-generation INSTIs.

Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.

The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.

A cluster of autochthonous dengue transmission in the Paris region - detection, epidemiology and control measures, France, October 2023.

A cluster of three confirmed autochthonous dengue cases was detected in October 2023 in the Val-de-Marne department neighbouring Paris, France. This marks the northernmost transmission of dengue in Europe reported to date. The epidemiological and microbiological investigations and the vector control measures are described. This event confirms the need for early case detection and response to contain dengue in Europe, especially given the 2024 Summer Olympic and Paralympic Games, when millions of visitors will visit the Greater Paris area.

2285. Using Genomic Sequencing to Describe SARS-CoV-2 Transmission Dynamics in U.S. Major League Soccer Clubs

Abstract Background In 2020–2022, U.S. Major League Soccer (MLS) used SARS-CoV-2 mitigation protocols that included masking, social distancing, avoiding contact with others outside of training and games, testing, quarantine, and isolation. In addition to isolation for those who tested positive, a SARS-CoV-2 genomic sequencing strategy was developed to identify whether infections were associated with intra-league transmission. Methods Nasopharyngeal swabs were collected by MLS club medical staff from players and staff from February 2021 through September 2022. During this time, surveillance testing changed from daily to weekly to testing only symptomatic players and staff. SARS-CoV-2 positive samples were analyzed using amplicon-based whole genome sequencing. A phylogenetic tree was constructed using Nextstrain to visualize genomes from infected players and staff in the context of genomes available on GISAID circulating in the United States during corresponding time periods. To identify transmission links, all genomes were compared in a pairwise fashion. Genomes that were 0–2 nucleotides different were considered part of direct transmission clusters. Results Of 250 samples that were rtPCR positive for SARS-CoV-2, 215 (86%) were sequenced. Phylogenetic analysis showed a broad diversity of lineages, including some predominant overseas (e.g., AY.98.1). Pairwise comparison revealed SARS-CoV-2 sequences from 7 individuals appeared to be linked. These individuals were on 2 different MLS teams; there was an off-field exposure (dinner). Five (71%) had identical SARS-CoV-2 sequences; 2 had sequences that were 1 nucleotide different at the consensus level. Subconsensus genome analysis revealed that differences of 1 nucleotide were due to subconsensus mutations fluctuating below and above 50%, suggesting all 7 individuals were part of a transmission cluster. Phylogenetic analysis revealed that the sequences from the cluster were distinct from reference sequences and were likely a unique transmission chain. Conclusion SARS-CoV-2 transmission may occur within, and even between, professional sports teams. Pairwise comparison of individual genomes can provide improved granularity to identify clusters and understand SARS-CoV-2 transmission. Disclosures Davidson H. Hamer, MD, Kephera Diagnostics: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Trinity Biotech, LLC: Advisor/Consultant|Valneva: Advisor/Consultant|Valneva: Grant/Research Support Daniel Bourque, MD, Kephera Diagnostics: Grant/Research Support

Barriers and Facilitators to HIV Service Access among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in Metropolitan Atlanta-a Qualitative Analysis.

Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.

Genomic transmission clusters and circulating lineages of Mycobacterium tuberculosis among refugees residing in refugee camps in Ethiopia

BackgroundUnderstanding the transmission dynamics of Mycobacterium tuberculosis (Mtb) could benefit the design of tuberculosis (TB) prevention and control strategies for refugee populations. Whole Genome Sequencing (WGS) has not yet been used to document the Mtb transmission dynamics among refugees in Ethiopia. We applied WGS to accurately identify transmission clusters and Mtb lineages among TB cases in refugee camps in Ethiopia. Method and designWe conducted a cross-sectional study of 610 refugees in refugee camps in Ethiopia presenting with symptoms of TB. WGS data of 67 isolates was analyzed using the Maximum Accessible Genome for Mtb Analysis (MAGMA) pipeline; iTol and FigTree were used to visualize phylogenetic trees, lineages, and the presence of transmission clusters. ResultsMtb culture-positive refugees originated from South Sudan (52/67, 77.6%), Somalia (9/67, 13.4%). Eritrea (4/67, 6%), and Sudan (2/67, 3%). The majority (52, 77.6%) of the isolates belonged to Mtb lineage (L) 3, and one L9 was identified from a Somalian refugee. The vast majority (82%) of the isolates were pan-susceptible Mtb, and none were multi-drug-resistant (MDR)-TB. Based on the 5-single nucleotide polymorphisms cutoff, we identified eight potential transmission clusters containing 23.9% of the isolates. Contact investigation confirmed epidemiological links with either family or social interaction within the refugee camps or with neighboring refugee camps. ConclusionFour lineages (L1, L3, L4, and L9) were identified, with the majority of strains being L3, reflecting the Mtb L3 dominance in South Sudan, where the majority of refugees originated from. Recent transmission among refugees was relatively low (24%), likely due to the short study period. The improved understanding of the Mtb transmission dynamics using WGS in refugee camps could assist in designing effective TB control programs for refugees.

Utility of Mycobacterium tuberculosis Genome Sequencing Snapshots to Assess Transmission Dynamics Over Time.

We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) "snapshots" at a sentinel site within Lima, Peru, for evaluating local transmission dynamics over time. Within a 17-km2 area, 15 of 70 (21%) isolates with WGS collected during 2011-2012 and 22 of 81 (27%) collected during 2020-2021 were clustered (P = .414), and additional isolates clustered with those from outside the area. Isolates from the later period were disproportionately related to large historic clusters in Lima from the earlier period. WGS snapshots at a sentinel site may not be useful for monitoring transmission, but monitoring the persistence of large transmission clusters might be.

Transmitted Drug Resistance and HIV Diversity Among Adolescents Newly Diagnosed With HIV in Spain.

Virological characterization of newly HIV-diagnosed adolescents could help to improve their specific needs. The objective was to describe the transmitted drug resistance mutations (TDR) and its transmission by clusters in this population in Spain. TDR to retrotranscriptase and protease inhibitors included in the WHO TDR list 2009 implemented in the Calibrated Population Resistance tool v8.0 (Stanford) were studied in HIV pol sequences from all HIV-diagnosed adolescents (12-19-year-old) enrolled during 2004-2019 period in the Spanish pediatric and adult (CoRISpe-CoRIS) cohorts. The found TDR were compared with the provided by the Stanford algorithm v9.0 2021. HIV-1 variants and transmission clusters were also studied. Among 410 HIV-1 adolescents diagnosed, 141 (34.4%) had available ART-naive sequences. They were mostly male (81.6%), Spanish (55.3%) and with behavioral risk (92.2%), mainly male-to-male sexual contact (63.1%). TDR prevalence was significantly higher by Stanford versus WHO list (18.4% vs. 7.1%; P = 0.004). The most prevalent TDR by the WHO list was K103N (3.6%) and by Stanford E138A (6.6%), both at retrotranscriptase. E138A, related to rilpivirine/etravirine resistance, was absent in the WHO list. One in 4 adolescents carried HIV-1 non-B variants. We described 5 transmission clusters, and 2 carried TDR mutations. Our data suggest a high TDR prevalence in adolescents with a new HIV diagnosis in Spain, similar to adults, 2 active TDR transmission clusters, and the need for the WHO TDR list update. These findings could have implications for the options of the recently available rilpivirine-related long-acting treatment and in first-line regimen election.

Population genomic analysis of clinical ST15 Klebsiella pneumoniae strains in China.

ST15 Klebsiella pneumoniae (Kpn) is a growing public health concern in China and worldwide, yet its genomic and evolutionary dynamics in this region remain poorly understood. This study comprehensively elucidates the population genomics of ST15 Kpn in China by analyzing 287 publicly available genomes. The proportion of the genomes increased sharply from 2012 to 2021, and 92.3% of them were collected from the Yangtze River Delta (YRD) region of eastern China. Carbapenemase genes, including OXA-232, KPC-2, and NDM, were detected in 91.6% of the studied genomes, and 69.2% of which were multidrug resistant (MDR) and hypervirulent (hv). Phylogenetic analysis revealed four clades, C1 (KL112, 59.2%), C2 (mainly KL19, 30.7%), C3 (KL48, 0.7%) and C4 (KL24, 9.4%). C1 appeared in 2007 and was OXA-232-producing and hv; C2 and C4 appeared between 2005 and 2007, and both were KPC-2-producing but with different levels of virulence. Transmission clustering detected 86.1% (n = 247) of the enrolled strains were grouped into 55 clusters (2-159 strains) and C1 was more transmissible than others. Plasmid profiling revealed 88 plasmid clusters (PCs) that were highly heterogeneous both between and within clades. 60.2% (n = 53) of the PCs carrying AMR genes and 7 of which also harbored VFs. KPC-2, NDM and OXA-232 were distributed across 14, 4 and 1 PCs, respectively. The MDR-hv strains all carried one of two homologous PCs encoding iucABCD and rmpA2 genes. Pangenome analysis revealed two major coinciding accessory components predominantly located on plasmids. One component, associated with KPC-2, encompassed 15 additional AMR genes, while the other, linked to OXA-232, involved seven more AMR genes. This study provides essential insights into the genomic evolution of the high-risk ST15 CP-Kpn strains in China and warrants rigorous monitoring.

Epidemiological characteristics of HIV transmission in southeastern China from 2015 to 2020 based on HIV molecular network.

HIV/AIDS remains a global public health problem, and understanding the structure of social networks of people living with HIV/AIDS is of great importance to unravel HIV transmission, propose precision control and reduce new infections. This study aimed to investigate the epidemiological characteristics of HIV transmission in Fujian province, southeastern China from 2015 to 2020 based on HIV molecular network. Newly diagnosed, treatment-naive HIV/AIDS patients were randomly sampled from Fujian province in 2015 and 2020. Plasma was sampled for in-house genotyping resistance test, and HIV molecular network was created using the HIV-TRACE tool. Factors affecting the inclusion of variables in the HIV molecular network were identified using univariate and multivariate logistic regression analyses. A total of 1,714 eligible cases were finally recruited, including 806 cases in 2015 and 908 cases in 2020. The dominant HIV subtypes were CRF01_AE (41.7%) and CRF07_BC (38.3%) in 2015 and CRF07_BC (53. 3%) and CRF01_AE (29.1%) in 2020, and the prevalence of HIV drug resistance was 4.2% in 2015 and 5.3% in 2020. Sequences of CRF07_BC formed the largest HIV-1 transmission cluster at a genetic distance threshold of both 1.5 and 0.5%. Univariate and multivariate logistic regression analyses showed that ages of under 20 years and over 60 years, CRF07_BC subtype, Han ethnicity, sampling in 2015, absence of HIV drug resistance, married with spouse, sampling from three cities of Jinjiang, Nanping and Quanzhou resulted in higher proportions of sequences included in the HIV transmission molecular network at a genetic distance threshold of 1.5% (p < 0.05). Our findings unravel the HIV molecular transmission network of newly diagnosed HIV/AIDS patients in Fujian province, southeastern China, which facilitates the understanding of HIV transmission patterns in the province.

HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021

BackgroundAs the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions.MethodsConsecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013.ResultsA total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021.ConclusionsThis study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan.

Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine drug resistance, compensatory mutations, population structure, and transmission patterns in a sample of 24 clinical isolates of L2/Beijing Mtb collected in Astana, Kazakhstan between 2021 and 2022. The genotypic prediction of Mtb susceptibility to anti-TB agents was consistent with the phenotypic susceptibility, except for bedaquiline. An analysis of resistance-associated genes characterized most of the isolates as pre-extensively drug-resistant tuberculosis (pre-XDR-TB) (n = 15; 62.5%). The phylogenetic analysis grouped the isolates into four transmission clusters; the dominant cluster was assigned to the "aggressive" Central Asia outbreak (CAO) clade of L2/Beijing (n = 15; 62.5%). Thirteen mutations with putative compensatory effects were observed exclusively in Mtb isolates containing the rpoB S450L mutation. The putative compensatory mutations had a stabilizing effect on RpoABC protein stability and dynamics. The high prevalence of the CAO clade in the population structure of Mtb may explain the rapid spread of MDR-TB in Kazakhstan.

Prevention and Control Are Not a Regional Matter: A Spatial Correlation and Molecular Linkage Analysis Based on Newly Reported HIV/AIDS Patients in 2021 in Jiangsu, China.

HIV-related spatial analysis studies in China are relatively few, and Jiangsu Province has not reported the relevant data in recent years. To describe the spatial distribution and molecular linkage characteristics of HIV-infected patients, this article combined descriptive epidemiology, spatial analysis, and molecular epidemiology methods to analyze patient reporting, patient mobility information, and HIV sequence information simultaneously. The results showed that HIV reporting profiles differed among Jiangsu cities, with the reporting rate in southern Jiangsu being above average. There was a spatial autocorrelation (Global Moran I = 0.5426, p < 0.05), with Chang Zhou showing a High-High aggregation pattern. Chang Zhou and Wu Xi were identified as hotspots for HIV reporting and access to molecular transmission networks. Some infected individuals still showed cross-city or even cross-province mobility after diagnosis, and three were linked with individuals in the destination cities within the largest molecular transmission cluster, involving 196 patients. The cross-city or cross-province mobility of patients may result in a potential HIV transmission risk, suggesting that combining timely social network surveys, building an extensive transmission network across cities and provinces, and taking critical regions and key populations as entry points could contribute to improved prevention and control efficiency and promote achievement of the 95-95-95 target and cascade.

JOCP: A jointly optimized clustering protocol for industrial wireless sensor networks using double‐layer selection evolutionary algorithm

SummaryIndustrial Wireless Sensor Networks (IWSNs) have gained significant popularity for their ability to improve plant productivity and production efficiency through self‐organization and rapid deployment. However, the challenge of achieving reliable and sustainable data transmission remains due to the large amount of heterogeneous data generated by large‐scale IWSNs. In this paper, we present a systematic approach that addresses this challenge by focusing on data transmission clustering strategies, optimal cluster head selection, and routing design. We propose a novel Jointly Optimized Clustering Protocol (JOCP), which enhances cluster head selection by considering multiple critical factors that impact the IWSN life cycle. JOCP incorporates two key modules: the many‐objective clustering model and the double‐layer selection evolutionary algorithm. Specifically, the many‐objective clustering model considers cluster head selection from different perspectives, including maximum node survival cycle, minimum node distance, minimum network overall energy consumption, and balanced cluster energy consumption, with the aim of extending the network life cycle. Additionally, the double‐layer selection evolutionary algorithm optimizes the many‐objective clustering model to select appropriate cluster heads. Through performance verification, we demonstrate that the JOCP protocol effectively enhances the network life cycle and increases the number of surviving nodes compared to baseline clustering algorithms. Our research provides a comprehensive solution to the challenges associated with reliable and sustainable data transmission in large‐scale IWSNs, highlighting the potential for improved performance in industrial applications.

Identifying spatial heterogeneity of COVID-19 transmission clusters and their built-environment features at the neighbourhood scale

The identification of high-risk areas for infectious disease transmission and its built-environment features are crucial for targeted surveillance and early prevention efforts. While previous research has explored the association between infectious disease incidence and urban built environment, the investigation of spatial heterogeneity of built-environment features in high-risk areas has been insufficient. This paper aims to address this gap by analysing the spatial heterogeneity of COVID-19 clusters in Shanghai at the neighbourhood scale and examining associated built-environment features. Using a spatiotemporal clustering algorithm, the study analysed 1395 reported cases in Shanghai from March 6 to March 17, 2022. Both global Poisson regression (GPR) and geographically weighted Poisson regression (GWPR) models were applied to examine the association between built-environment variables and the size of COVID-19 clusters. Our findings suggest that larger COVID-19 clusters emerging in the suburbs compared with the downtown and multiple built-environment features are significantly associated with this pattern. Specifically, neighbourhoods with a higher proportion of commercial, public service and industrial land, higher centrality of metro stations, and proximity to hospitals are positively associated with larger COVID-19 clusters, while neighbourhoods with higher land use mix and green/open spaces density are associated with smaller COVID-19 clusters. Moreover, we identified that metro stations with high centrality present the highest risk in the downtown, while commercial and public service places exhibit the highest risk in the suburbs. By highlighting the overlooked spatial heterogeneity of built-environment features for high-risk areas, this study aims to provide valuable guidance for public health departments in implementing place-based interventions to effectively prevent the spread of potential epidemics.

Exploring programmatic indicators of tuberculosis control that incorporate routine Mycobacterium tuberculosis sequencing in low incidence settings: a comprehensive (2017–2021) patient cohort analysis

Routine whole genome sequencing of Mycobacterium tuberculosis has been implemented with increasing frequency. However, its value for tuberculosis (TB) control programs beyond individual case management and enhanced drug resistance detection has not yet been explored. We analysed routine sequencing data of culture-confirmed TB cases notified between 1st January 2017 and 31st December 2021 in New South Wales (NSW), Australia. Genomic surveillance included evidence of local TB transmission, defined by single nucleotide polymorphism (SNP) clustering over a variable (0-25) SNP threshold, and drug resistance conferring mutations. M.tuberculosis sequences from 1831 patients were examined, representing 64.8% of all notified TB cases and 96.2% of culture-confirmed cases. Applying a traditional 5-SNP cluster threshold identified 62 transmission clusters with 183 clustered cases; 101/183 (55.2%) had 0 SNP differences. Cluster assessment over a 5-year period, using a 5-SNP threshold, provided a comprehensive overview of likely recent transmission within NSW, Australia, as an indicator of local TB control. Genotypic drug susceptibility testing (DST) was highly concordant with phenotypic DST and provided a 6.8% increase in antimycobacterial resistance detection. Importantly, it detected mutations missed by routine molecular tests. Lineage 2 strains were more likely to be drug resistant (p<0.0001) and locally transmitted if drug resistant (p<0.0001). Performing routine prospective WGS in a low incidence country like Australia, provides genomically informed programmatic indicators of local TB control. A rolling 5-year cluster assessment reflects epidemic containment and progress towards 'zero TB transmission'. Genomic DST also provides valuable information for clinical care and drug resistance surveillance. NHMRC Centre for Research Excellence in Tuberculosis (www.tbcre.org.au) and NSW Health Prevention Research Support Program.

Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh.

The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44 % of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8 %) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.

Monocentric observational cohort study to investigate the transmission of third-generation cephalosporin-resistant Enterobacterales in a neonatal intensive care unit in Heidelberg, Germany.

Third-generation cephalosporin-resistant Enterobacterales is a major threat for newborns in neonatal intensive care units (NICUs). The route of acquisition in a non-outbreak setting should be investigated to implement adequate infection prevention measures. To identify risk factors for colonization with and to investigate the transmission pattern of third-generation cephalosporin-resistant Enterobacterales in a NICU setting. This monocentric observational cohort study in a tertiary NICU in Heidelberg, Germany, enrolled all hospitalized neonates screened for cephalosporin-resistant Enterobacterales. Data were collected from 1 January 2018 to 31 December 2021. Weekly screening by rectal swabs for colonization with third-generation cephalosporin-resistant Enterobacterales was performed for all newborns until discharge. Whole-genome sequencing was performed for molecular characterization and transmission analysis. In total, 1,287 newborns were enrolled. The median length of stay was 20 (range 1-250) days. Eighy-eight infants (6.8%) were colonized with third-generation cephalosporin-resistant Enterobacterales. Low birth weight [<1500 g (adjusted odds ratio, 5.1; 95% CI 2.2-11.5; P < 0.001)] and longer hospitalization [per 30 days (adjusted odds ratio, 1.7; 95% CI 1.5-2.0; P < 0.001)] were associated with colonization or infection with drug-resistant Enterobacterales in a multivariate analysis. Enterobacter cloacae complex was the most prevalent third-generation cephalosporin-resistant Enterobacterales detected, 64.8% (59 of 91). Whole-genome sequencing, performed for the available 85 of 91 isolates, indicated 12 transmission clusters involving 37 patients. This cohort study suggests that transmissions of third-generation cephalosporin-resistant Enterobacterales in newborns occur frequently in a non-outbreak NICU setting, highlighting the importance of surveillance and preventive measures in this vulnerable patient group. IMPORTANCE Preterm newborns are prone to infections. Therefore, infection prevention should be prioritized in this vulnerable patient group. However, outbreaks involving drug-resistant bacteria, such as third-generation resistant Enterobacterales, are often reported. Our study aims to investigate transmission and risk factors for acquiring third-generation cephalosporin-resistant Enterobacterales in a non-outbreak NICU setting. Our data indicated that premature birth and low birth weight are significant risk factors for colonization/infection with third-generation cephalosporin-resistant Enterobacterales. Furthermore, we could identify putative transmission clusters by whole-genome sequencing, highlighting the importance of preemptive measures to prevent infections in this patient collective.