Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.

Longitudinal surveillance of Cryptosporidium spp. in broiler chickens in Xinjiang, northwest China: genetic diversity of Cryptosporidium meleagridis subtypes.

Cryptosporidium spp. are common enteric parasites in humans and animals. Herein, 175 faecal specimens were collected from a broiler farm in Xinjiang, China, including seven repeated samplings at 10-day intervals of broilers aged 10 to 70 days. Cryptosporidium was detected and identified by PCR-RFLP analysis. The overall infection rate of Cryptosporidium in broilers was 23.4% (41/175), with the highest infection rate of 48.0% (12/25) at 40 days of age, and no infection was detected at 10 days of age. Two Cryptosporidium species were confirmed, namely, C. baileyi (3.4%, 6/175) and C. meleagridis (20%, 35/175). In total, 21 of 35 C. meleagridis isolates were successfully subtyped based on the gp60 gene, and one known subtype, IIIgA22G3R1 (n = 1), and three novel subtypes, IIIbA25G1R1 (n = 10), IIIgA24G3R1 (n = 9) and IIIgA25G2R1 (n = 1), were identified. Our findings highlight the genetic diversity of C. meleagridis in Xinjiang and the potential endemic characteristics of the subtypes.

Distinct Characteristics of Escherichia coli Isolated from Patients with Urinary Tract Infections in a Medical Center at a Ten-Year Interval.

Escherichia coli causing urinary tract infections (UTIs) are one of the most common outpatient bacterial infections. This study aimed to compare the characteristics of E. coli isolated from UTI patients in a single medical center in 2009-2010 (n = 504) and 2020 (n = 340). The antimicrobial susceptibility of E. coli was determined by the disk diffusion method. PCRs were conducted to detect phylogenetic groups, ST131, K1 capsule antigen, and 15 virulence factors. Phylogenetic group B2 dominated in our 2009-2010 and 2020 isolates. Moreover, no phylogenetic group E strains were isolated in 2020. E. coli isolates in 2020 were more susceptible to amoxicillin, ampicillin/sulbactam, cefuroxime, cefmetazole, ceftazidime, cefoxitin, tetracycline, and sulfamethoxazole/trimethoprim, compared to the isolates in 2009-2010. Extensively drug-resistant (XDR)-E. coli in 2009-2010 were detected in groups B1 (5 isolates), B2 (12 isolates), F (8 isolates), and unknown (1 isolate). In 2020, XDR-E. coli were only detected in groups A (2 isolates), B2 (5 isolates), D (1 isolate), and F (4 isolates). The prevalence of virulence factor genes aer and fimH were higher in E. coli in 2009-2010 compared to those in 2020. In contrast, afa and sat showed higher frequencies in E. coli isolates in 2020 compared to E. coli in 2009-2010.

Campylobacter jejuni Strain Dynamics in a Raccoon (Procyon lotor) Population in Southern Ontario, Canada: High Prevalence and Rapid Subtype Turnover.

Free-ranging wildlife are increasingly recognized as potential reservoirs of disease-causing Campylobacter species such as C. jejuni and C. coli. Raccoons (Procyon lotor), which live at the interface of rural, urban, and more natural environments, are ideal subjects for exploring the potential role that wildlife play in the epidemiology of campylobacteriosis. We studied the prevalence and genetic diversity of Campylobacter from live-captured raccoons on five swine farms and five conservation areas in southwest Ontario. From 2011 to 2013, we collected fecal swabs (n = 1,096) from raccoons, and (n = 50) manure pit samples from the swine farm environment. We subtyped the resulting Campylobacter isolates (n = 581) using Comparative Genomic Fingerprinting (CGF) and 114 distinct subtypes were observed, including 96 and 18 subtypes among raccoon and manure pit isolates, respectively. Campylobacter prevalence in raccoons was 46.3%, with 98.7% of isolates recovered identified as C. jejuni. Novel raccoon-specific CGF subtypes (n = 40/96) accounted for 24.6% (n = 143/581) of Campylobacter isolates collected in this study. Our results also show that C. jejuni is readily acquired and lost in this wild raccoon population and that a high Campylobacter prevalence is observed despite transient carriage typically lasting 30 days or fewer. Moreover, although raccoons appeared to be colonized by species-adapted subtypes, they also harbored agriculture-associated genotypes that accounted for the majority of isolates observed (66.4%) and that are strongly associated with human infections. This suggests that raccoons may act as vectors in the transmission of clinically-relevant C. jejuni subtypes at the interface of rural, urban, and more natural environments.

Observational study: 27 years of severe malaria surveillance in Kilifi, Kenya.

BACKGROUND: Many parts of Africa have witnessed reductions in Plasmodium falciparum transmission over the last 15 years. Since immunity to malaria is acquired more rapidly at higher transmission, the slower acquisition of immunity at lower transmission may partially offset the benefits of reductions in transmission. We examined the clinical spectrum of disease and predictors of mortality after sustained changes in transmission intensity, using data collected from 1989 to 2016. METHODS: We conducted a temporal observational analysis of 18,000 children, aged 14 days to 14 years old, who were admitted to Kilifi County Hospital, Kenya, from 1989 to 2016 with malaria. We describe the trends over time of the clinical and laboratory criteria for severe malaria and associated risk of mortality. RESULTS: During the time periods 1989-2003, 2004-2008, and 2009-2016, Kilifi County Hospital admitted averages of 657, 310, and 174 cases of severe malaria per year including averages of 48, 14, and 12 malaria-associated deaths per year, respectively. The median ages in years of children admitted with cerebral malaria, severe anaemia, and malaria-associated mortality were 3.0 (95% confidence interval (CI) 2.2-3.9), 1.1 (95% CI 0.9-1.4), and 1.1 (95% CI 0.3-2.2) in the year 1989, rising to 4.9 (95% CI 3.9-5.9), 3.8 (95% CI 2.5-7.1), and 5 (95% CI 3.3-6.3) in the year 2016. The ratio of children with cerebral malaria to severe anaemia rose from 1:2 before 2004 to 3:2 after 2009. Hyperparasitaemia was a risk factor for death after 2009 but not in earlier time periods. CONCLUSION: Despite the evidence of slower acquisition of immunity, continued reductions in the numbers of cases of severe malaria resulted in lower overall mortality. Our temporal data are limited to a single site, albeit potentially applicable to a secular trend present in many parts of Africa.

A complete and multifaceted overview of antibiotic use and infection diagnosis in the intensive care unit: results from a prospective four-year registration.

BACKGROUND: Preparing an antibiotic stewardship program requires detailed information on overall antibiotic use, prescription indication and ecology. However, longitudinal data of this kind are scarce. Computerization of the patient chart has offered the potential to collect complete data of high resolution. To gain insight in our global antibiotic use, we aimed to explore antibiotic prescription in our intensive care unit (ICU) from various angles over a prolonged time period. METHODS: We studied all adult patients admitted to Ghent University Hospital ICU from 1 January 2013 until 31 December 2016. Antibiotic prescription data were prospectively merged with diagnostic (suspected focus, severity and probability of infection at the time of prescription, or prophylaxis) and microbiology data by ICU physicians during daily workflow through dedicated software. Definite focus of infection and probability of infection (classified as high/moderate/low) were reassessed by dedicated ICU physicians at patient discharge. RESULTS: During the study period, 8763 patients were admitted and overall antibiotic consumption amounted to 1232 days of therapy (DOT)/1000 patient days. Antibacterial DOT (84% of total DOT) were linked with infection in 80%; the predominant foci were the respiratory tract (49%) and the abdomen (19%). A microbial cause was identified in 56% (3169/5686). Moderate/low probability infections accounted for 42% of antibacterial DOT prescribed for respiratory tract infections; for abdominal infections, this figure was 15%. The median treatment duration of moderate/low probability respiratory infections was 4 days (IQR 3-7). Antifungal DOT (16% of total DOT) were linked with infection in 47% of total antifungal DOT. Antifungal prophylaxis was primarily administered in the surgical ICU (76%), with a median duration of 4 DOT (IQR 2-9). CONCLUSIONS: By prospectively combining antibiotic, microbiology and clinical data we were able to construct a longitudinal, multifaceted dataset on antibiotic use and infection diagnosis. A complete overview of this kind may allow the identification of antibiotic prescription patterns that require future antibiotic stewardship attention.

Impact of genotype-specific herd immunity on the circulatory dynamism of norovirus: a 10-year longitudinal study of viral acute gastroenteritis.

Human norovirus is a major cause of viral acute gastroenteritis worldwide. However, the transition of endemic norovirus genotypes remains poorly understood. The characteristics of natural immunity against norovirus are unclear because few studies have been performed in the natural infection setting. This prospective 10-year surveillance study of acute gastroenteritis in the province of Osaka, Japan, revealed that norovirus spread shows temporal, geographic, and age group-specific features in the humans. Genogroup II genotype 4 (GII.4) was detected in most sporadic pediatric cases, as well as in foodborne and nursing home outbreaks, respectively. The dominant genotypes in outbreaks at childcare facilities and schools shifted every season and involved GI, GII.2, GII.3, GII.4, and GII.6. Evidence at both the facility and individual levels indicated that genotype-specific herd immunity lasted long enough to influence the endemic norovirus genotype in the next season. Thus, norovirus circulates through human populations in a uniquely dynamic fashion.

Extending cluster lot quality assurance sampling designs for surveillance programs.

Lot quality assurance sampling (LQAS) has a long history of applications in industrial quality control. LQAS is frequently used for rapid surveillance in global health settings, with areas classified as poor or acceptable performance on the basis of the binary classification of an indicator. Historically, LQAS surveys have relied on simple random samples from the population; however, implementing two-stage cluster designs for surveillance sampling is often more cost-effective than simple random sampling. By applying survey sampling results to the binary classification procedure, we develop a simple and flexible nonparametric procedure to incorporate clustering effects into the LQAS sample design to appropriately inflate the sample size, accommodating finite numbers of clusters in the population when relevant. We use this framework to then discuss principled selection of survey design parameters in longitudinal surveillance programs. We apply this framework to design surveys to detect rises in malnutrition prevalence in nutrition surveillance programs in Kenya and South Sudan, accounting for clustering within villages. By combining historical information with data from previous surveys, we design surveys to detect spikes in the childhood malnutrition rate.