recent transmission
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2022 ◽  
Vol 9 ◽  
Author(s):  
Kristin N. Nelson ◽  
Sarah Talarico ◽  
Shameer Poonja ◽  
Clinton J. McDaniel ◽  
Martin Cilnis ◽  
...  

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.


Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Joseph Yamweka Chizimu ◽  
Eddie Samuneti Solo ◽  
Precious Bwalya ◽  
Wimonrat Tanomsridachchai ◽  
Herman Chambaro ◽  
...  

Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.


2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Muhammad Bilal Sarwar ◽  
Muhammad Yasir ◽  
Nabil-Fareed Alikhan ◽  
Nadeem Afzal ◽  
Leonardo de Oliveira Martins ◽  
...  

The SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world’s largest populations, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that began in March 2021. In Pakistan, during the third wave until now only 12 SARS-CoV-2 genomes have been collected and among these nine are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact, more genomes are available among travellers with a travel history from Pakistan, than from within the country itself. We thus aimed to provide a snapshot assessment of circulating lineages in Lahore and surrounding areas with a combined population of 11.1 million. Within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from two hospitals with a diagnostic PCR cutoff value of less than 25 cycles. Analysis of the lineages shows that the Alpha variant of concern (first identified in the UK) dominates, accounting for 97.9 % (97/99) of cases, with the Beta variant of concern (first identified in South Africa) accounting for 2.0 % (2/99) of cases. No other lineages were observed. In depth analysis of the Alpha lineages indicated multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (seven UK, one Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low-density genome sequencing. Vaccines remain effective against Alpha, however, the low level of Beta against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jean Baptiste Ndahetuye ◽  
Mikael Leijon ◽  
Renée Båge ◽  
Karin Artursson ◽  
Ylva Persson

Whole-genome sequencing was carried out on 30 Staphylococcus (S.) aureus isolates from dairy cows with subclinical mastitis from all five provinces of Rwanda. Twenty-five of the isolates produced enough sequence to be analyzed using core genome multilocus sequence typing (cg-MLST). The isolates group into three main clusters. The largest cluster contain isolates of sequence type (ST) 152 (n = 6) and the closely related ST1633 (n = 2). These sequence types have previously mainly been encountered in humans. The isolates of the second-largest cluster belong to ST5477 (n = 5),so far exclusively isolated from cows in Rwanda. The third cluster consists of isolates of ST97 (n = 4), which is a well-known bovine-adapted sequence type. These three clusters were all widespread over the country. Isolates of the usually human-adapted sequence types 1 (n = 2) and 5 (n= 1) were found and a single isolate of ST2430, previously found among humans in Africa. Finally, four isolates of novel sequence types were found: ST7108 (n = 2), ST7109 (n = 1), and ST7110 (n = 1). The blaZ penicillin resistance gene was found in 84% of the isolates and was in all cases corroborated by phenotypic resistance determination. Five (20%) of the isolates carried a tetracycline resistance gene, tet(K) or tetM, and three of these five also displayed phenotypic resistance while two isolates carried a tetM-gene but were yet tetracycline susceptible. Seven (28%) isolates carried the dfrG gene conferring resistance to trimethoprim. Four of these isolates indeed were resistant to trimethoprim while three isolates were sensitive. The str gene conferring resistance to aminoglycosides was found in three isolates; however, none of these displayed resistance to gentamycin. Our data revealed a high diversity of the sequence types of S. aureus isolates from cows with subclinical mastitis in Rwanda. Two major clusters of ST97 and ST5477 are likely to be bovine adapted and cause mastitis while the third cluster of ST152 usually have been found in humans and may signify a recent transmission of these types from human to cows, for example from hand milking. The high prevalence of this sequence type among dairy cows may pose zoonotic threat. The sequence types were widely distributed without any geographic correlation. Penicillin resistance, the most common type of resistance with a prevalence over 80%, but also tetracycline and trimethoprim resistance were displayed by several isolates.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiying Han ◽  
Jing Li ◽  
Guomei Sun ◽  
Kaikan Gu ◽  
Yangyi Zhang ◽  
...  

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015. Methods We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation. Results The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases. Conclusions The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.


Author(s):  
Christopher Ruis ◽  
Josephine M. Bryant ◽  
Scott C. Bell ◽  
Rachel Thomson ◽  
Rebecca M. Davidson ◽  
...  

AbstractMycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.


2021 ◽  
Vol 17 (9) ◽  
pp. e1009436
Author(s):  
Siyu Chen ◽  
Jennifer A. Flegg ◽  
Lisa J. White ◽  
Ricardo Aguas

Accurate knowledge of prior population exposure has critical ramifications for preparedness plans for future SARS-CoV-2 epidemic waves and vaccine prioritization strategies. Serological studies can be used to estimate levels of past exposure and thus position populations in their epidemic timeline. To circumvent biases introduced by the decay in antibody titers over time, methods for estimating population exposure should account for seroreversion, to reflect that changes in seroprevalence measures over time are the net effect of increases due to recent transmission and decreases due to antibody waning. Here, we present a new method that combines multiple datasets (serology, mortality, and virus positivity ratios) to estimate seroreversion time and infection fatality ratios (IFR) and simultaneously infer population exposure levels. The results indicate that the average time to seroreversion is around six months, IFR is 0.54% to 1.3%, and true exposure may be more than double the current seroprevalence levels reported for several regions of England.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthias Merker ◽  
Nkongho F. Egbe ◽  
Yannick R. Ngangue ◽  
Comfort Vuchas ◽  
Thomas A. Kohl ◽  
...  

Abstract Background Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance. Methods We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission. Results Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%). Conclusion Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.


2021 ◽  
Author(s):  
Bing Zhao ◽  
Chunfa Liu ◽  
Jiale Fan ◽  
Aijing Ma ◽  
Wencong He ◽  
...  

Abstract Background: Multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrel for ‘Stop TB plan’. China has the second highest MDR/RR-TB burden in whole world wide. Understanding the transmission dynamic is facilitated for disease control. Methods: Whole genome sequencing (WGS) data from patients of Chongqing tuberculosis control institute were used for phylogenetic classifications, resistance predictions, and cluster analysis as indicator for recent transmission (RT). Factors associated with MDR/RR-TB were defined by a logistic regression model. Results: A total of 223 cases of MDR/RR-TB were recorded between Jan 1, 2018 and Dec 31, 2020, and 200 cases obtained relevant treatment information. The patients who are older than 55 year old were more likely to suffering from death. 178 MDR/RR strains were obtained WGS data, 152 were classified as lineage 2 strains. 80 (44.9%, 80 of 178) strains were in 20 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating RT. Patients who were infected with lineage 2 strains is a significant factor driving the epidemic towards MDR/RR-TB. Resistance mutations of first-line tuberculosis drugs analysis found that 79 (98.8%) of all 80 strains defined as RT have same mutations among each clusters totally. 55% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially fluoroquinolones (FQs) (63.6%, 28 of 44). Conclusions: The age is the most significant factor that causes death of MDR/RR-TB patients. RT of MDR/RR strains is not only drove the MDR/RR-TB epidemic, but also accumulated more serious resistance along the transmission chains.


2021 ◽  
Author(s):  
Chunfa Liu ◽  
Ping He ◽  
Jiale Fan ◽  
Aijing Ma ◽  
Wencong He ◽  
...  

Abstract Background: Whole genome based Mycobacterium tuberculosis (Mtb) surveillance is facilitated to tuberculosis control. The proportion of genotypic clusters in a population represents the recent transmission rate of Mtb.Methods: We did a population based study of culture-positive Mtb in Golmud, Qinghai, China. Whole-genome sequencing (WGS) was used to discriminate the apparent genetic clusters and resistant associated genes of Mtb, and the risk of genomically clustered Mtb was analyzed combined with epidemiological data. Results: A total of 133 cases of culture-positive tuberculosis were recorded between Jan 1, 2013 and Dec 31, 2018, 17 (13%, 17/133) cases of which were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB). Patients who were previous treatment or were younger than 35 years had high risk of MDR/RR-TB. 62 (47%, 62/132) strains were in 23 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission. Patients who were Tibetan nationality, or those 35-44 years old were more likely to have recent transmission. 15 (65%, 15/23) patients with genotypic rifampin resistant tuberculosis have epidemiological link. Mutation of rifampicin resistance associated genes in rpoB Ser450Leu was showed lower cluster rate (42%, 5/12) compared with other mutations.Conclusions: Recent transmissions of Mtb strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, Qinghai, China.


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