Academic literature on the topic 'Asymptomatic carriage'

Abstract Background Asymptomatic carriage of toxigenic Clostridioides difficile strains is common in healthcare settings. However, the natural history of C. difficile colonization and infection is not well understood, particularly for patients with new acquisition of carriage. Methods In 3 tertiary care hospitals and affiliated long-term care facilities (LTCFs), we conducted a 6-month cohort study to identify patients with new acquisition of rectal carriage of toxigenic C. difficile and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive with negative cultures before and after or persistent if 2 or more cultures were positive; clearance was defined as 2 consecutive negative rectal cultures. Results Of 4180 patients with negative initial cultures, 144 (3%) acquired asymptomatic carriage of toxigenic C. difficile, and 19 (13%) of these carriers subsequently were diagnosed with CDI. Of 50 asymptomatic carriers analyzed for duration of carriage, 33 (66%) had transient carriage of toxigenic C. difficile and 17 (34%) had persistent carriage. For persistent carriers, the estimated median time to clearance of colonization was 76 days (range, 41 to 95 days from acquisition). Ten of 17 (59%) persistent carriers had a high burden of carriage (defined as > 25 colonies recovered from 1 or more swabs) vs. only 1 of 33 (3%) transient carriers (P < 0.001). Conclusion Acquisition of asymptomatic carriage of toxigenic C. difficile carriage was common among patients in healthcare facilities, but most carriers had transient low-level carriage. Additional studies are needed to determine whether a higher burden of carriage predicts subsequent risk of transmission. Disclosures All authors: No reported disclosures.

SUMMARYAsymptomatic carriage of gastrointestinal zoonoses is more common in people whose profession involves them working directly with domesticated animals. Subclinical infections (defined as an infection in which symptoms are either asymptomatic or sufficiently mild to escape diagnosis) are important within a community as unknowing (asymptomatic) carriers of pathogens do not change their behaviour to prevent the spread of disease; therefore the public health significance of asymptomatic human excretion of zoonoses should not be underestimated. However, optimal strategies for managing diseases where asymptomatic carriage instigates further infection remain unresolved, and the impact on disease management is unclear. In this review we consider the environmental pathways associated with prolonged antigenic exposure and critically assess the significance of asymptomatic carriage in disease outbreaks Although screening high-risk groups for occupationally acquired diseases would be logistically problematical, there may be an economic case for identifying and treating asymptomatic carriage if the costs of screening and treatment are less than the costs of identifying and treating those individuals infected by asymptomatic hosts.

We previously reported trends in pneumococcal nasopharyngeal carriage in the post-PCV13 era as detected by conventional culture methods. Our current aim is to assess if there are fundamental differences in the clinical and demographic features of children who have pneumococcal carriage detected by qPCR compared with culture analysis. The CASPER team conducted point-prevalence surveys in 2016 in healthy children in Calgary to determine trends in overall and serotype-specific pneumococcal nasopharyngeal carriage. Being 18 months of age (p = 0.009), having at least one sibling under 2 years of age (p = 0.04), having only sibling(s) over 2 years of age (p = 0.001), and childcare attendance (p = 0.005) were associated with carriage by qPCR methods only. Having only sibling(s) older than 2 years of age was associated with carriage detected by both qPCR and culture methods (p = 0.001). No clinical factors were associated with carriage detected by both qPCR and culture compared to qPCR methods only. Both analyses are suitable methods to detect carriage; however, qPCR analysis is more sensitive and more cost-effective. As there are no fundamental differences in the children that have pneumococcal nasopharyngeal carriage detectable by qPCR methods compared to conventional culture methods, molecular analysis may be a preferable option for future carriage studies.

ABSTRACTDespite the high frequency of asymptomatic carriage of bacterial pathogens, we understand little about the bacterial molecular genetic underpinnings of this phenomenon. To obtain new information about the molecular genetic mechanisms underlying carriage of group AStreptococcus(GAS), we performed whole-genome sequencing of GAS strains recovered from a single individual during acute pharyngitis and subsequent asymptomatic carriage. We discovered that compared to the initial infection isolate, the strain recovered during asymptomatic carriage contained three single nucleotide polymorphisms, one of which was in a highly conserved region of a gene encoding a sensor kinase,liaS, resulting in an arginine-to-glycine amino acid replacement at position 135 of LiaS (LiaSR135G). Using gene replacement, we demonstrate that introduction of the carrier allele (liaSR135G) into a serotype-matched invasive strain increased mouse nasopharyngeal colonization and adherence to cultured human epithelial cells. The carrier mutation also resulted in a reduced ability to grow in human blood and reduced virulence in a mouse model of necrotizing fasciitis. Repair of the mutation in the GAS carrier strain restored virulence and decreased adherence to cultured human epithelial cells. We also provide evidence that the carrier mutation alters the GAS transcriptome, including altered transcription of GAS virulence genes, providing a potential mechanism for the pleiotropic phenotypic effects. Our data obtained using isogenic strains suggest that theliaSR135Gmutation in the carrier strain contributes to the transition from disease to asymptomatic carriage and provides new information about this poorly described regulatory system in GAS.

Bacterial respiratory tract infections (RTIs) are a major global health burden, and the role of antigen-presenting cells (APCs) in mounting an immune response to contain and clear invading pathogens is well-described. However, most encounters between a host and a bacterial pathogen do not result in symptomatic infection, but in asymptomatic carriage instead. The fact that a pathogen will cause infection in one individual, but not in another does not appear to be directly related to bacterial density, but rather depend on qualitative differences in the host response. Understanding the interactions between respiratory pathogens and airway APCs that result in asymptomatic carriage, will provide better insight into the factors that can skew this interaction towards infection. This review will discuss the currently available knowledge on airway APCs in the context of asymptomatic bacterial carriage along the entire respiratory tract. Furthermore, in order to interpret past and futures studies into this topic, we propose a standardized nomenclature of the different stages of carriage and infection, based on the pathogen’s position with regard to the epithelium and the amount of inflammation present.

This article reviews recent data on meningococcal disease and carriage in the Philippines. It aims to provide information on the epidemiology of meningococcal disease, its carriage, data on prevention, and the impact of vaccination on disease and carriage. The World Health Organization considers the Philippines as having low endemicity for meningococcal disease. However, current data underestimates the true burden in the country due to many factors. In recent years, data from the Philippines show a high case-fatality rate since only the septicemic form is being reported. Studies on asymptomatic meningococcal carriage rates are sparse, with one study by Gonzales, et al. investigating the prevalence of meningococcal nasopharyngeal carriage in Filipinos aged 5-24 years old living in an urban setting. The study showed that the overall prevalence of carriage was 3.7% and was highest (9%) among the 10-14 age group. Serogroup B was the most common isolate. Effective meningococcal vaccines are available. Although not included in the National Immunization Program, medical societies recommend giving vaccines to individuals at high risk of infection. Data on local epidemiology accounting for the disease and asymptomatic carriage are important to strengthen future programs on immunization and prevention of meningococcal disease.

Clostridium difficile was identified as an infective agent in the late 1970s and early 1980s and causes a spectrum of disease ranging from asymptomatic carriage, mild colitis, pseudomembranous colitis (PMC) to fulminant colitis and even death. Since its recognition as an infective pathogen, C. difficile has become the principal cause of nosocomial diarrhoea in adults. The main aims of this four-part thesis were to determine the extent of Clostridium difficile infection (CDI) within the local in-patient population and to establish the epidemiology of CDI within the specialty of colorectal surgery. The first study focused on the burden of CDI to the diagnostic laboratory and the relative incidence of disease in different clinical specialties over an 8-year period (2000 to 2007) in a region that had not been affected by the hypervirulent 027 strain. A 27-fold increase in the number of faecal samples analysed by the enteric laboratory occurred from 2000 to 2006 and the total number of potential CDI cases increased over the same period, with a decline finally seen in 2007. One-fifth of all toxinpositive samples were from age groups under 60 years of age providing further evidence that CDI was not just a disease of the elderly. Although Medicine of the Elderly provided the greatest faecal analysis workload; Renal Medicine/Transplant Surgery, Intensive Care, Infectious Disease and Gastrointestinal Medicine all had higher incidences of CDI than Medicine of the Elderly. Similarly the low risk group of Paediatrics was also starting to show a small but notable increase in potential incidence. Potential excess costs for CDI in this region rose from £3.5 million to £29 million over the study period. The second study aimed to assess the potential impact of CDI within all surgical services. In the absence of 027, a further aim of this study was to assess if the more severe and extreme forms of C. difficile disease were occurring from 2000 to 2006. Colorectal surgery had the greatest number of CDI episodes followed by Upper Gastrointestinal Surgery and Urology. Despite the total number of C. difficile toxinpositive in-patients increasing each year, a similar increase was not demonstrated in the number of patients diagnosed with more severe forms of CDI or in the number of CDI patients treated with surgical intervention. In the cases requiring surgical intervention up to 40% of patients did not present with diarrhoea and up to 50% of patients did not have a C. difficile toxin-positive faecal sample prior to surgery. Demonstrating the importance of clinical recognition of the entire spectrum of C. difficile related disease. The post-operative mortality rate for fulminant CDI was 26%. High mortality figures for fulminant CDI treated surgically have not changed significantly over the last two decades and may relate to surgical referral for CDI often occurring late when the patient is in extremis. The third and fourth studies examined the specific burden of C. difficile in the colorectal surgical patient population and the environmental surface contamination within colorectal wards. An asymptomatic carrier rate of 6.1% was identified in the out-patient colorectal surgical population. Asymptomatic carriers admitted from the community play an important role in sustaining the transmission of disease within the hospital environment with 42.8% of C. difficile strains only identified in the in-patients faecal samples but not on the surface environment of the wards. Standard enteric hospital laboratory CDI diagnosis using enzyme immuno-assay for toxin A+B detection was 52% less sensitive then toxigenic culture with a false positive rate of 2.5%. Toxigenic culture identified a further 58 colorectal surgical in-patients with CDI. Of all the C. difficile isolates identified from in-patients and the surface environment ribotype 001 was the commonest strain, consistent with other local studies where ribotype 001 has emerged as the dominant strain. A large proportion of the in-patient ribotype 001 isolates showed resistance to ceftriaxone and ciprofloxacin. The ribotype 001 isolates from the surface environment showed decreased resistance to ceftriaxone compared with the in-patient strains. Similarly 4.6% of all in-patient isolates showed intermediate resistance to vancomycin but no vancomycin resistance was demonstrated in the environmental surface isolates and may represent increased development of C. difficile resistance mechanisms in the host. The patient bed frames were the commonest contaminated environmental surface with C. difficile, followed by the patient's bedside lockers and tables. Therefore the risk of a patient ingesting a C. difficile spore from the surface environment is high. Following the introduction of a new cleaning protocol during the environmental sampling study a statistically significant reduction in environmental C. difficile surface contamination and in the number of CDI colorectal in-patients was demonstrated. Acquisition of CDI from the surface environment in hospitals is not to be under-estimated and judicious application of infection control measures remains an important factor in preventing CDI transmission.

Meningitis is an infection of the meninges, a layer of tissue surrounding the brain. In cases of pneumococcal meningitis (where the bacterium Streptococcus pneumoniae is the causat- ive agent) this causes severe inflammation, requiring intensive care and rapid antibiotic treatment. The contribution of variation in host and pathogen genetics to pneumococcal meningitis is unknown. In this thesis I develop and apply statistical genetics techniques to identify genomic variation associated with the various stages of pneumococcal meningitis, including colonisation, invasion and severity. I start by describing the development of a method to perform genome-wide association studies (GWAS) in bacteria, which can find variation in bacterial genomes associated with bacterial traits such as antibiotic resistance and virulence. I then applied this method to longitudinal samples from asymptomatic carriage, and found lineages and specific variants associated with altered duration of carriage. To assess meningitis versus carriage samples I applied similar analysis techniques, and found that the bacterial genome is crucial in determining invasive potential. As well as bacterial serotype, which I found to be the main effect, I discovered many independent sequence variants associated with disease. Separately, I analysed within host-diversity during the invasive phase of disease and found it to be of less relevance to disease progression. Finally, I analysed host genotype data from four independent studies using GWAS and heritability estimates to determine the contribution of human sequence variation to pneumococcal meningitis. Host sequence accounted for some variation in susceptibility to and severity of meningitis. The work concludes with a combined analysis of pairs of bacterial and human sequences from meningitis cases, and finds variation correlated between the two.

Clostridium difficile infections (CDIs) are some of the most common hospital-acquired infections and the most common cause of antibiotic-associated diarrhoea. CDIs lead to great loss of life, severe health outcomes, and incur very high financial costs through treatment, extended hospital stays, and readmissions. Despite extensive research and many resources committed to the prevention and treatment CDIs in hospitalised patients, hospitals continue to be hotspots for this disease. Meanwhile, there is an emerging awareness of the burden this disease places on the broader community including patients who have not recently been hospitalised. In the community approximately 5% of adults and a higher proportion of infants are asymptomatically colonised. Colonisation is also common in livestock and the pathogen has been isolated from meat and vegetables. However, the various sources of transmission in the community and the consequences for infections within and beyond hospitals are not well understood. This thesis develops and employs mathematical models of C. difficile transmission to explore three themes: improving models to capture the complex epidemiology of C. difficile, populations that sustain C. difficile transmission, and the classifi cation of CDIs as hospital or community-acquired. Addressing the fi rst theme, I argue that the essential epidemiology of C. difficile is captured by modelling the interactions of three key factors: pathogen, immunity, and gut flora. I argue that modelling transmission in an integrated model of adults and infants across hospitals and communities provides insights that hospital-only and adult-only models cannot. By incorporating seasonality into these models, I argue that seasonal variation of antibiotic prescription rates is more likely to be the main driver of CDI seasonality than seasonal transmission. In the second theme, I argue that most hospitals -- though hotspots for transmission -- are not disease sustaining populations. Instead, transmission outside hospitals maintains the disease in the hospital and community. I argue that reducing transmission in the hospital cannot eliminate the disease in the broader population, but that reducing transmission from adults or infants in the community could interrupt transmission in the human population. Similarly, I argue that C. difficile in the community may be driven by transmission from animal reservoirs if as few as 3.5-26.0% of human infections are acquired from animal or food sources. In the final theme, I argue that an illusion of hospital-driven disease is in part perpetuated by surveillance defi nitions that systematically misclassify many community-acquired cases as hospital-acquired. The incubation period for C. difficile infections often exceeds the two-day or three-day cut-offs commonly used to classify patients recently admitted to hospital. I argue that many patients who acquire the pathogen prior to admission develop symptoms after the cut-off and are therefore incorrectly classifi ed as having acquired the infection during their hospital stay. Furthermore, I argue that time since hospital discharge is a poor indicator of whether a CDI is hospital or community-acquired.

Protozoa are single-celled (unicellular) eukaryotic organisms. There are many protozoa causing parasitic infection in humans. This chapter will concentrate on the three that most commonly causes gastrointestinal disease worldwide and have the biggest impact in the UK: Giardia lamblia, Cryptosporidium spp., and Entamoeba histolytica. These three infections are of great significance worldwide, but are less common in Western settings. In the UK, they tend to be seen in more commonly in travellers returning from endemic countries, migrant populations, men who have sex with men, and the immunocompromised. The clinical features of all three infections vary from asymptomatic small- or large-bowel carriage with passage of cysts to infect others, to more serious manifestations.

Abstract Drug-resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug-resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of infections that may be difficult or impossible to treat with currently available antibiotics. Accumulating evidence suggests that such transmission occurs not only in hospital settings but also in the general community, although much more data are needed to assess the extent of this problem. Asymptomatic carriage of drug-resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens and costs on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug-resistant bacteria, noting important knowledge gaps and (ii) explore the implications of existing public health ethics frameworks for decision- and policy-making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission (and the effectiveness of available interventions) will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration.

AbstractApplications of bioluminescence for the in vivo study of pathogenic microorganisms are numerous, ranging from the quantification of virulence gene expression to measuring the effect of antimicrobial molecules on the colonization of tissues and organs by the pathogen. Most studies are performed in mice, but recent works demonstrate that this technique is applicable to larger animals like fish, guinea pigs, ferrets, and chickens. Here, we describe the construction and the utilization of a constitutively luminescent strain of Salmonella Typhimurium to monitor in vivo and ex vivo the colonization of mice in the gastroenteritis, typhoid fever, and asymptomatic carriage models of Salmonella infection.

Staphylococcus aureus is a common human pathogen that can cause mild superficial infections to deep-seated abscesses and sepsis. One of the characteristics of S. aureus is the ability to colonise healthy individuals while leaving them asymptomatic. These carriers’ risk harbouring an antibiotic-resistant strain that may be harmful to the individual and the community. S. aureus carriage in healthcare personnel is being studied extensively in many parts of the world. However, the relationship between colonisation and disease among those with no previous exposure to healthcare remains untouched. Colonisation of the nasal cavity and its surrounding by pathogenic organisms such as S. aureus leads to the increased risk of infection. Hospital-acquired infections associated with S. aureus infections are common and studies related to these types of infections among various study groups are largely documented. However, over the last decade, an increase in community-associated methicillin-resistant S. aureus has been noted, increasing the need to identify the prevalence of the organism among healthy individuals and assessing the antibiotic resistance patterns. Systemic surveillance of the community for colonisation of S. aureus and identifying the antibiotic-resistant pattern is critical to determine the appropriate empiric antibiotic treatment.