Social network analysis and whole-genome sequencing to evaluate disease transmission in a large, dynamic population: A study of avian mycobacteriosis in zoo birds.

This study combined a social network analysis and whole-genome sequencing (WGS) to test for general patterns of contagious spread of a mycobacterial infection for which pathways of disease acquisition are not well understood. Our population included 275 cases diagnosed with avian mycobacteriosis that were nested in a source population of 16,430 birds at San Diego Zoo Wildlife Alliance facilities from 1992 through mid-2014. Mycobacteria species were determined using conventional methods and whole genome sequencing (WGS). Mycobacterium avium avium (MAA) and Mycobacterium genavense were the most common species of mycobacteria identified and were present in different proportions across bird taxa. A social network for the birds was constructed from the source population to identify directly and indirectly connected cases during time periods relevant to disease transmission. Associations between network connectivity and genetic similarity of mycobacteria (as determined by clusters of genotypes separated by few single nucleotide polymorphisms, or SNPs) were then evaluated in observed and randomly generated network permutations. Findings showed that some genotypes clustered along pathways of bird connectivity, while others were dispersed throughout the network. The proportion of directly connected birds having a similar mycobacterial genotype was 0.36 and significant (p<0.05). This proportion was higher (0.58) and significant for MAA but not for M. genavense. Evaluations of SNP distributions also showed genotypes of MAA were more related in connected birds than expected by chance; however, no significant patterns of genetic relatedness were identified for M. genavense, although data were sparse. Integrating the WGS analysis of mycobacteria with a social network analysis of their host birds revealed significant genetic clustering along pathways of connectivity, namely for MAA. These findings are consistent with a contagious process occurring in some, but not all, case clusters.

Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway.

BACKGROUND: The aim of the current study was to improve our understanding of the origins and transmission of Mycobacterium africanum (MAF) in Norway. METHODS: Whole-genome sequences (WGS) were generated for all (n = 29) available clinical isolates received at the Norwegian National Reference Laboratory for Mycobacteria (NRL) and identified as MAF in Norway, in the period 2010-2020. Phylogenetic analyses were performed. RESULTS: The analyses indicated several imports of MAF lineage 6 from both East and West African countries, whereas MAF lineage 5 was restricted to patients with West African connections. We also find evidence for transmission of MAF in Norway. Finally, our analyses revealed that a group of isolates from patients originating in South Asia, identified as MAF by means of a commercial line-probe assay, in fact belonged to Mycobacterium orygis. CONCLUSIONS: Most MAF cases in Norway are the result of import, but transmission is occurring within Norway.

Risk Management in the New Frontier of Professional Liability for Nosocomial Infection: Review of the Literature on Mycobacterium Chimaera.

Background: Mycobacterium chimaera (MC) is of recent origin and belongs to the large family of non-tuberculous mycobacteria. In recent years, it has shown a high infectious capacity via the aerosol produced by operating room equipment, such as heater-cooler units (HCU). The infection has a long latent period and high mortality rate. Genetic and epidemiological studies have shown that there is a clear link between the infection and a specific HCU model manufactured by LivaNova/Sorin. There is, therefore, a strong possibility that contamination occurs during device construction. The objective of this article is to describe the characteristics of this particular infection in view of the medico-legal implications on professional liability, specifically focusing on current evidence regarding contamination prevention. Methods: we have analyzed the clinical characteristics and data from the autopsic investigations performed on a patient who died as a result of MC infection, in addition to analyzing all pertinent recommendation documents available internationally. We searched for all articles in the literature available on MEDLINE between 1995 and 30 July 2020, using the search words "Mycobacterium chimaera". We then analyzed those articles and reported only those that provide useful information regarding prevention techniques for containing dissemination and contamination. Results: the literature review produced 169 results that highlight the need to develop systems to mitigate and eliminate the risk of MC infection in operating rooms such as physical containment measures, e.g. device replacement, use of safe water, providing patients with information, and training healthcare professionals. Conclusions: from a medico-legal viewpoint, this particular situation represents a new frontier of professional liability, which includes manufacturers of electromedical equipment. In order to comprehend the true extent of this silent global epidemic, the development of an organic, preventative monitoring system is essential.

Spatiotemporal network structure among "friends of friends" reveals contagious disease process.

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown.

Source or Sink: Examining the Role of Biofilms in Transmission of Mycobacterium spp. in Laboratory Zebrafish.

Zebrafish health is a primary research concern because diseases can have unintended impacts on experimental endpoints. Ideally, research would be conducted using disease-free fish or fish with known disease status. Mycobacteriosis is a common bacterial disease in wild and captive fishes, including zebrafish. Despite its prevalence, the dynamics of transmission and potential sources of mycobacterial infections in zebrafish are only partially understood. One suspected natural infection source is surface biofilms on tanks and other system components. This study investigates the role that tank biofilms play in mycobacteriosis in laboratory zebrafish by evaluating the establishment of biofilms from bacteria shed from fish, and conversely, the acquisition of infections in fish from surface biofilms. We found that zebrafish infected with Mycobacterium chelonae shed bacteria through feces, and bacteria are transmitted to tank biofilms from one to 16 weeks postinfection. We also found that zebrafish acquire M. chelonae infections as soon as 2 weeks when introduced to tanks with established M. chelonae biofilms. The results from this study highlight the role that tank biofilms play as both a reservoir and source of mycobacterial infections in zebrafish. Results support the inclusion of biofilm surveillance and prevention as part of a disease control program in zebrafish research facilities.

Different Types of Heater-Cooler Units and Their Risk of Transmission of Mycobacterium chimaera During Open-Heart Surgery: Clues From Device Design.

OBJECTIVEWorldwide, Mycobacterium chimaera infections have been linked to contaminated aerosols from heater-cooler units (HCUs) during open-heart surgery. These infections have mainly been associated with the 3T HCU (LivaNova, formerly Sorin). The reasons for this and the risk of transmission from other HCUs have not been systematically assessed.DESIGNProspective observational study.SETTINGUniversity Hospital Basel, Switzerland.METHODSContinuous microbiological surveillance of 3 types of HCUs in use (3T from LivaNova/Sorin and HCU30 and HCU40 from Maquet) was initiated in June 2014, coupled with an epidemiologic workup. Monthly water and air samples were taken. Construction design was analyzed, and exhausted airflow was measured.RESULTS Mycobacterium chimaera grew in 8 of 12 water samples (66%) and 22 of 24 air samples (91%) of initial 3T HCUs in use, and in 2 of 83 water samples (2%) and 0 of 41 (0%) air samples of new replacement 3T HCUs. Moreover, 7 of 12 water samples (58%) and 0 of 4 (0%) air samples from the HCU30 were positive, and 0 of 64 (0%) water samples and 0 of 50 (0%) air samples from the HCU40 were positive. We identified 4 relevant differences in HCU design compared to the 3T: air flow direction, location of cooling ventilators, continuous cooling of the water tank at 4°C, and an electronic alarm in the HCU40 reminding the user of the next disinfection cycle.CONCLUSIONSAll infected patients were associated with a 3T HCU. The individual HCU design may explain the different risk of disseminating M. chimaera into the air of the operating room. These observations can help the construction of improved devices to ensure patient safety during cardiac surgery.Infect Control Hosp Epidemiol 2018;834-840.

Establishment of a Host-to-Host Transmission Model for Mycobacterium avium subsp. hominissuis Using Caenorhabditis elegans and Identification of Colonization-Associated Genes.

Mycobacterium avium subsp. hominissuis (M. avium) is a member of the non-tuberculous mycobacteria (NTM), and is a common cause of lung infection in patients with chronic NTM lung conditions. M. avium is an environmental bacterium believed to be transmitted from environmental sources. In this work we used a recently developed model in Caenorhabditis elegans to ask whether M. avium can be transmitted from host-to-host, and the bacterial genes associated with host colonization. Infection of C. elegans was carried out by placing the nematode in cultured with M. avium. Bacteria eliminated from the intestines of infected C. elegans were used to infect naïve nematodes. In parallel experiments, to identify colonization associated genes, a transposon library of M. avium was screened for the ability to bind to HEp-2 mucosal cells. Thirty clones were identified and five selected clones with impaired adherence to HEp-2 epithelial cells were used to infect C. elegans to determine the degree of colonization. It was determined that M. avium eliminated from infected C. elegans were able to colonize a naïve C. elegans with high efficiency. Thirty of the most adherence-deficient M. avium clones obtained from the HEp-2 cell screening were sequenced to identify the location of the transposon. Many of the genes associated with the bacterial cell wall synthesis were shown to be inactivated in the selected mutants. Five out of the 30 bacterial clones were then used to infect C. elegans. All five mutants had impaired ability to colonize C. elegans compared with the wild type bacteria (decrease of 1.5-2.0 logs, p < 0.05). The limitation of this work is that the model can be used for initial screening, but other more complex systems should be used to confirm the findings. C. elegans can be used as a model to test for M. avium adherence/colonization-associated virulence determinants. All the tested adherence-deficient clones that were examined had impaired ability to colonize the host C. elegans, and some can be potentially used to prevent colonization.

Global Health Estimate of Invasive Mycobacterium chimaera Infections Associated with Heater-Cooler Devices in Cardiac Surgery.

Investigations of a worldwide epidemic of invasive Mycobacterium chimaera associated with heater-cooler devices in cardiac surgery have been hampered by low clinical awareness and challenging diagnoses. Using data from Switzerland, we estimated the burden of invasive M. chimaera to be 156-282 cases/year in 10 major cardiac valve replacement market countries.

Mycobacterium tuberculosis Complex Members Adapted to Wild and Domestic Animals.

The Mycobacterium tuberculosis complex (MTBC) is composed of several highly genetically related species that can be broadly classified into those that are human-host adapted and those that possess the ability to propagate and transmit in a variety of wild and domesticated animals. Since the initial description of the bovine tubercle bacillus, now known as Mycobacterium bovis, by Theobald Smith in the late 1800's, isolates originating from a wide range of animal hosts have been identified and characterized as M. microti, M. pinnipedii, the Dassie bacillus, M. mungi, M. caprae, M. orygis and M. suricattae. This chapter outlines the events resulting in the identification of each of these animal-adapted species, their close genetic relationships, and how genome-based phylogenetic analyses of species-specific variation amongst MTBC members is beginning to unravel the events that resulted in the evolution of the MTBC and the observed host tropism between the human- and animal-adapted member species.

Mycobacterium chimaera infections associated with heater-cooler units in cardiac surgery.

PURPOSE OF REVIEW: Mycobacterium chimaera infections following cardiac surgery have been reported from an increasing number of countries. These infections are characterized by a poor prognosis with a case fatality rate around 50% despite treatment. Since the first description in 2013, our understanding has grown steadily. Several outbreak investigations, case series, and experiments with heater-cooler units (HCUs) have been published. This review summarizes the current knowledge. RECENT FINDINGS: M. chimaera transmission occurs during cardiopulmonary bypass via bioaerosols emitted from contaminated HCU water systems. Manifestations of M. chimaera infection comprise endocarditis, vascular graft infections, surgical site infections, and dissemination. So far, all cases were exposed to a single HCU brand. Samples from the manufacturing site as well as clonality of M. chimaera strains isolated from HCUs and patients suggest a contamination already at time of delivery representing the main source for the outbreak. Nevertheless, HCU contamination in hospitals cannot be excluded. SUMMARY: Improved awareness of physicians of M. chimaera infection is crucial to prompt adequate diagnostic workup in patients that have been exposed to HCU presenting with compatible symptoms. For risk mitigation, strict separation between the air volume in contact with HCUs and critical clinical areas such as operating rooms is essential.

Directriz para reducir el riesgo de transmisión de mycobacterium abscessus durante la práctica clínica odontológica / Guideline to reduce the risk of transmission of mycobacterium abscessusin clinical dental practice

Las medidas de bioseguridad están predestinadas a reducir el riesgo de transmisión de microorganismos a partir de fuentes de infección reconocidas o no reconocidas en clínicas dentales vinculadas con lacontaminación de los materiales, aparatos y/o instrumentos. Un microorganismo reemergente es el Mycobacterium abscessus, que es unabacteria ambiental que puede ocasionar problemas de salud muy serios, por lo que debe ser controlada y prevenida su transmisión.

Biosafety measures are designed to reduce the risk of transmission ofmicroorganisms from recognized or unrecognized sources of infectionin dental procedures associated with the contamination of materials,apparatus, and/or instruments. One reemerging microorganism isMycobacterium abscessus, which is an environmental bacterium thatcan cause serious health problems and therefore needs to be controlledand prevented.

A neonate born with Mycobacterium cosmeticum bacteraemia.

Mycobacterium cosmeticum is a rapidly growing mycobacterium that was recently identified. However, its role in human infection has not been well described. We present a case of an extremely premature neonate born with bacteraemia due to M. cosmeticum that resolved without sequelae. The infection likely occurred during a prolonged intrauterine transfusion procedure.

Infections and exposures: reported incidents associated with unsuccessful decontamination of reusable surgical instruments.

Reusable surgical instruments provide a potential route for the transmission of pathogenic agents between patients in healthcare facilities. As such, the decontamination process between uses is a vital component in the prevention of healthcare-associated infections. This article reviews reported outbreaks and incidents associated with inappropriate, inadequate, or unsuccessful decontamination of surgical instruments, indicating potential pitfalls of decontamination practices worldwide. To the author's knowledge, this is the first review of surgical instrument decontamination failures. Databases of medical literature, Medline and Embase, were searched systematically. Articles detailing incidents associated with unsuccessful decontamination of surgical instruments were identified. Twenty-one articles were identified reporting incidents associated with failures in decontamination. A large proportion of incidents involved the attempted disinfection, rather than sterilization, of surgical instruments (43% of articles), counter to a number of national guidelines. Instruments used in eye surgery were most frequently reported to be associated with decontamination failures (29% of articles). Of the few articles detailing potential or confirmed pathogenic transmission, Pseudomonas aeruginosa and Mycobacterium spp. were most represented. One incident of possible variant Creutzfeldt-Jakob disease transmission was also identified. Limitations of analysing only published incidents mean that the likelihood of under-reporting (including reluctance to publish failure) must be considered. Despite these limitations, the small number of articles identified suggests a relatively low risk of cross-infection through reusable surgical instruments when cleaning/sterilization procedures are adhered to. The diverse nature of reported incidents also suggests that failures are not systemic.

Paramecium caudatum enhances transmission and infectivity of Mycobacterium marinum and M. chelonae in zebrafish Danio rerio.

Mycobacterial infections in laboratory zebrafish Danio rerio are common and widespread in research colonies. Mycobacteria within free-living amoebae have been shown to be transmission vectors for mycobacteriosis. Paramecium caudatum are commonly used as a first food for zebrafish, and we investigated this ciliate's potential to serve as a vector of Mycobacterium marinum and M. chelonae. The ability of live P. caudatum to transmit these mycobacteria to larval, juvenile and adult zebrafish was evaluated. Infections were defined by histologic observation of granulomas containing acid-fast bacteria in extraintestinal locations. In both experiments, fish fed paramecia containing mycobacteria became infected at a higher incidence than controls. Larvae (exposed at 4 d post hatch) fed paramecia with M. marinum exhibited an incidence of 30% (24/80) and juveniles (exposed at 21 d post hatch) showed 31% incidence (14/45). Adult fish fed a gelatin food matrix containing mycobacteria within paramecia or mycobacteria alone for 2 wk resulted in infections when examined 8 wk after exposure as follows: M. marinum OSU 214 47% (21/45), M. marinum CH 47% (9/19), and M. chelonae 38% (5/13). In contrast, fish feed mycobacteria alone in this diet did not become infected, except for 2 fish (5%) in the M. marinum OSU 214 low-dose group. These results demonstrate that P. caudatum can act as a vector for mycobacteria. This provides a useful animal model for evaluation of natural mycobacterial infections and demonstrates the possibility of mycobacterial transmission in zebrafish facilities via contaminated paramecia cultures.

Direction of association between bite wounds and Mycobacterium bovis infection in badgers: implications for transmission.

BACKGROUND: Badgers are involved in the transmission to cattle of bovine tuberculosis (TB), a serious problem for the UK farming industry. Cross-sectional studies have shown an association between bite wounds and TB infection in badgers which may have implications for M. bovis transmission and control, although the sequence of these two events is unclear. Transmission during aggressive encounters could potentially reduce the effectiveness of policies which increase the average range of a badger and thus its opportunities for interaction with other social groups. METHODS: Data were obtained on badgers captured during a long term study at Woodchester Park, UK (1998-2006). Many badgers had multiple observations. At each observation, the badger was assigned a "state" depending on presence of bite wounds and/or TB infection. Hence each badger had a "transition" from the previous state to the current state. We calculated the numbers of each type of transition and the time spent in each state. Transition rates were calculated for each transition category, dividing the number of such transitions by the total time at risk. We compared the rate of bite wound acquisition in infected badgers with that for uninfected badgers and the rate of positive M.bovis test results in bitten badgers with that in unbitten badgers. RESULTS: The rate of bite wound acquisition in infected badgers (0.291 per year) was 2.09 (95% CI: 1.41, 3.08) times that in uninfected badgers (0.139 per year). The rate of positive M.bovis test results in bitten badgers (0.097 per year) was 2.45 (95% CI: 1.29, 4.65) times that in unbitten badgers (0.040 per year). CONCLUSIONS: We found strong evidence of both potential sequences of events consistent with transmission via bite wounds and distinctive behaviour in infected badgers. The complex relationship between behaviour and infection must be considered when planning TB control strategies.