Prevalence and Genetic Diversity of Adenovirus 40/41, Astrovirus, and Sapovirus in Children with Acute Gastroenteritis in Kansas City 2011-2016.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

Does vaping affect the taste and smell perception? An exploratory study with New Zealand young adults.

OBJECTIVE: The study aimed to assess potential effects of vaping on individual taste and smell perception in a sample of young adult New Zealanders. DESIGN: This cross-sectional study measured taste and smell perception using intensity and hedonic ratings to two olfactory (i.e., vanillin, methional) and two gustatory stimuli (i.e., sucrose, monosodium glutamate), representing sweet and savoury flavours. Detection sensitivities to sucrose and vanillin were also assessed using a forced choice detection paradigm aligned with the signal detection framework. MANCOVAs were employed to compare sensory perception between groups based on vaping use frequency. Additional regression analyses were conducted to identify potential predictors of intensity and hedonic sensory ratings. SETTING: Participants were recruited from the University of Otago student population and surrounding neighbourhoods of Dunedin, New Zealand in 2023. PARTICIPANTS: The study included 213 university students (98 vapers and 115 non-vapers) RESULTS: We found a significant difference in hedonic ratings for vanillin, indicating a stronger preference among non-vapers. However, no other differences between the two groups were significant. Notably, the use of tobacco and mint flavours were emerged as significant predictors for hedonic responses to the savoury smell and sweet taste stimulus, respectively. No significant differences were observed between groups in the ability to detect weak stimuli. CONCLUSIONS: Our findings suggest that vape use, particularly with specific flavours, may be associated with alterations in hedonic responses to smells. This finding may have potential implications for how vaping affects on food preferences and dietary choices.

Gain-of-function factor H-related 5 protein impairs glomerular complement regulation resulting in kidney damage.

Genetic variation within the factor H-related (FHR) genes is associated with the complement-mediated kidney disease, C3 glomerulopathy (C3G). There is no definitive treatment for C3G, and a significant proportion of patients develop end-stage renal disease. The prototypical example is CFHR5 nephropathy, through which an internal duplication within a single CFHR5 gene generates a mutant FHR5 protein (FHR5mut) that leads to accumulation of complement C3 within glomeruli. To elucidate how abnormal FHR proteins cause C3G, we modeled CFHR5 nephropathy in mice. Animals lacking the murine factor H (FH) and FHR proteins, but coexpressing human FH and FHR5mut (hFH-FHR5mut), developed glomerular C3 deposition, whereas mice coexpressing human FH with the normal FHR5 protein (hFH-FHR5) did not. Like in patients, the FHR5mut had a dominant gain-of-function effect, and when administered in hFH-FHR5 mice, it triggered C3 deposition. Importantly, adeno-associated virus vector-delivered homodimeric mini-FH, a molecule with superior surface C3 binding compared to FH, reduced glomerular C3 deposition in the presence of the FHR5mut. Our data demonstrate that FHR5mut causes C3G by disrupting the homeostatic regulation of complement within the kidney and is directly pathogenic in C3G. These results support the use of FH-derived molecules with enhanced C3 binding for treating C3G associated with abnormal FHR proteins. They also suggest that targeting FHR5 represents a way to treat complement-mediated kidney injury.

O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular Function.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN. METHODS: To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls. RESULTS: Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA. CONCLUSIONS: Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function.

Homotypic and Heterotypic Protection and Risk of Reinfection Following Natural Norovirus Infection in a Highly Endemic Setting.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide, yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time reverse-transcription polymerase chain reaction followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HRs) of infection among children with vs without prior exposure. RESULTS: Norovirus was detected in 1288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR, 0.35; P = .015), GI.7 (HR, 0.19; P = .022), GII.4 (HR, 0.39; P < .001), and GII.6 (HR, 0.52; P = .006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR, 0.52; P = .005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to reinfection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.

Incidence, Etiology, and Severity of Acute Gastroenteritis Among Prospectively Enrolled Patients in 4 Veterans Affairs Hospitals and Outpatient Centers, 2016-2018.

BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California), collectively serving >320 000 patients annually. METHODS: From 1 July 2016 to 30 June 2018, we actively identified inpatient AGE case patients and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatients with AGE through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens by means of multiplex gastrointestinal polymerase chain reaction panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatients with AGE, 394 non-AGE inpatient controls, and 506 outpatients with AGE. Clostridioides difficile and norovirus were most frequently detected among inpatients (for AGE case patients vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; P < .01 for both) and outpatients (norovirus, 10.7%; C. difficile, 10.5%). The incidence per 100 000 population was highest among outpatients (AGE, 2715; C. difficile, 285; norovirus, 291) and inpatients ≥65 years old (AGE, 459; C. difficile, 91; norovirus, 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/enteroinvasive Escherichia coli cases. Overall, 12% of inpatients with AGE had intensive care unit stays, and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

Clinical and Laboratory Findings in Patients With Potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection, May-July 2020.

BACKGROUND: We investigated patients with potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including reverse transcription polymerase chain reaction (RT-PCR), viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent coronavirus disease 2019 (COVID-19) symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47-76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional 3 patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current Centers for Disease Control and Prevention (CDC) guidance around quarantine and testing for patients who have recovered from COVID-19.

Epidemiologic Characteristics Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen-Based Test Results, Real-Time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) Cycle Threshold Values, Subgenomic RNA, and Viral Culture Results From University Testing.

BACKGROUND: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. METHODS: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. RESULTS: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03-.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4-.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values < 29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). CONCLUSIONS: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.

Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis.

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

Sexually transmitted infection (STI) research priority-setting: a two-stage study including the perspectives of patients, the public, clinicians and stakeholders.

OBJECTIVES: Patient and public involvement (PPI) in research priority-setting remains limited, especially for non-HIV STI. We identify and compare the top 10 patient and public STI research priorities with those of clinicians and STI stakeholders. METHODS: This two-stage study was conducted in May-August 2019. First, STI research priorities were canvassed through qualitative questionnaires issued to all patients attending a large sexual health clinic, all clinicians in region-wide mailing lists, all stakeholders identified through existing networks and the Charity Commission database, and to the Liverpool public. Raw responses were organised by theme into a shortlist of 25. In stage 2, these were ranked through priority-setting activities by telephone with patients and the public (n=8) and some clinicians (n=3), and in two workshops with clinicians (n=26) and stakeholders (n=5), respectively. The top 10 priorities were compared. RESULTS: Of 373 surveys submitted, 106 were analysed (83 patient and public; 23 clinician and stakeholder). Exclusions included lack of completion and responses out of scope. Among patient and public respondents, 55% (n=46) were aged 18-24 years, 51% (n=42) identified as heterosexual women and 23% (n=19) as men who have sex with men. Clinicians included all cadres; stakeholders were academics, commissioners and third sector representatives. In stage 2, 4 of 10 themes (STI education, targeted services for high-risk groups, antibiotic resistance and counselling for those with STI) were prioritised by all. Remote STI services and rapid diagnostics also ranked highly but the rationale differed between groups. CONCLUSION: This is the first non-HIV STI research priority-setting exercise to be reported in the UK. It identifies overlaps and differences between public and provider concerns, highlights gaps in the public understanding of STI research, and shows how PPI can promote research responsive to the concerns of both those who use and deliver services.

Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison - Texas, July-August 2021.

Incarcerated populations have experienced disproportionately higher rates of COVID-19-related illness and death compared with the general U.S. population, due in part to congregate living environments that can facilitate rapid transmission of SARS-CoV-2, the virus that causes COVID-19, and the high prevalence of underlying medical conditions associated with severe COVID-19 (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant has caused outbreaks among vaccinated and unvaccinated persons in congregate settings and large public gatherings (3,4). During July 2021, a COVID-19 outbreak involving the Delta variant was identified in a federal prison in Texas, infecting 172 of 233 (74%) incarcerated persons in two housing units. The Federal Bureau of Prisons (BOP) partnered with CDC to investigate. CDC analyzed data on infection status, symptom onset date, hospitalizations, and deaths among incarcerated persons. The attack rate was higher among unvaccinated versus fully vaccinated persons (39 of 42, 93% versus 129 of 185, 70%; p = 0.002).† Four persons were hospitalized, three of whom were unvaccinated, and one person died, who was unvaccinated. Among a subset of 70 persons consenting to an embedded serial swabbing protocol, the median interval between symptom onset and last positive reverse transcription-polymerase chain reaction (RT-PCR) test result in fully vaccinated versus unvaccinated persons was similar (9 versus 11 days, p = 0.37). One or more specimens were culture-positive from five of 12 (42%) unvaccinated and 14 of 37 (38%) fully vaccinated persons for whom viral culture was attempted. In settings where physical distancing is challenging, including correctional and detention facilities, vaccination and implementation of multicomponent prevention strategies (e.g., testing, medical isolation, quarantine, and masking) are critical to limiting SARS-CoV-2 transmission (5).

Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020.

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).

Predicting food choices based on eye-tracking data: Comparisons between real-life and virtual tasks.

As eye-trackers become increasingly important in studies on consumer food choice, it is crucial to test the ecological validity of virtual eye-tracking tests. The present study aims to cross-examine eye-tracking data obtained from real-life versus virtual food choice tasks. Sixty-two healthy females participated in this study by attending two sessions, with virtual and real-life settings, respectively. Both sessions were constructed identically - with participants required to view eight common snack food items with different arrangements, while wearing mobile eye-trackers. To complete each task, the participants were asked to select three types of food for consumption. Analyses of summed dwell time (i.e., total visit duration - the summed latency of gaze visit on an 'area of interest' from entry to exit) were performed to assess food attention biases across test conditions, and between the selected and unselected food items. While the results revealed only minor differences in visual preferences between real-life and virtual settings, data from these two settings showed differential relationships to food choices. Eye-tracking data obtained in the virtual setting supported the notion that the selected food items were looked at longer (p < 0.05). However, the dwell time is shown inadequate to fully capture the more complex cognitive processes underpinning real-life food choices, with non-significant differences being reflected in dwell time for selected versus unselect foods. Overall, our study demonstrates inconsistent outcomes of eye-tracking food research in virtual versus real-life settings, highlighting the importance of accounting for environmental variation when interpreting eye-tracking data for food cues.

Trends in Incidence of Norovirus-associated Acute Gastroenteritis in 4 Veterans Affairs Medical Center Populations in the United States, 2011-2015.

BACKGROUND: Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years. METHODS: From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served. RESULTS: Of 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively). CONCLUSIONS: This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

CrAssphage as a Novel Tool to Detect Human Fecal Contamination on Environmental Surfaces and Hands.

CrAssphage is a recently discovered human gut-associated bacteriophage. To validate the potential use of crAssphage for detecting human fecal contamination on environmental surfaces and hands, we tested stool samples (n = 60), hand samples (n = 30), and environmental swab samples (n = 201) from 17 norovirus outbreaks for crAssphage by real-time PCR. In addition, we tested stool samples from healthy persons (n = 173), respiratory samples (n = 113), and animal fecal specimens (n = 68) and further sequenced positive samples. Overall, we detected crAssphage in 71.4% of outbreak stool samples, 48%-68.5% of stool samples from healthy persons, 56.2% of environmental swabs, and 60% of hand rinse samples, but not in human respiratory samples or animal fecal samples. CrAssphage sequences could be grouped into 2 major genetic clusters. Our data suggest that crAssphage could be used to detect human fecal contamination on environmental surfaces and hands.

Molecular epidemiology of noroviruses in children under 5 years of age with acute gastroenteritis in Yaoundé, Cameroon.

Norovirus is a common cause of acute gastroenteritis (AGE) among children in developing countries. Limited data on the prevalence and genetic variability of norovirus are available in Cameroon, where early childhood mortality due to AGE is common. We tested 902 fecal specimens from children younger than 5 years of age hospitalized with AGE between January 2010 and December 2013. Overall, 76 (8.4%) samples tested positive for norovirus, of which 83% (63/76) were among children below 12 months old. Most of the noroviruses detected were in children infected between July and December of each year. All norovirus-positive specimens were genotyped, with 80% (61/76) being GII.4 (three variants detected). Genotypes GI.2, GI.6, GII.1, GII.2, GII.3, GII.6, GII.16, GII.17, and GII.21 were also detected. Interestingly, GII.4 Sydney and GII.17 Kawasaki viruses were found as early as 2010, years before their emergence globally. This study suggests norovirus is a significant cause of moderate to severe gastroenteritis among young children in Cameroon. The results are important to highlight appropriate prevention and control strategies for reducing the burden of norovirus disease.

Human Norovirus Replication in Human Intestinal Enteroids as Model to Evaluate Virus Inactivation.

Human noroviruses are a leading cause of epidemic and endemic acute gastroenteritis worldwide and a leading cause of foodborne illness in the United States. Recently, human intestinal enteroids (HIEs) derived from human small intestinal tissue have been shown to support human norovirus replication. We implemented the HIE system in our laboratory and tested the effect of chlorine and alcohols on human norovirus infectivity. Successful replication was observed for 6 norovirus GII genotypes and was dependent on viral load and genotype of the inoculum. GII.4 viruses had higher replication levels than other genotypes. Regardless of concentration or exposure time, alcohols slightly reduced, but did not completely inactivate, human norovirus. In contrast, complete inactivation of the 3 GII.4 viruses occurred at concentrations as low as 50 ppm of chlorine. Taken together, our data confirm the successful replication of human noroviruses in HIEs and their utility as tools to study norovirus inactivation strategies.

Circulating complement factor H-related protein 5 levels contribute to development and progression of IgA nephropathy.

IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility. Here we compared circulating levels of FHR-5 in 1126 patients with IgAN and regular follow-up with those of 153 unrelated healthy individuals to explore the relationship of FHR-5 levels with IgAN development and progression. Circulating FHR-5 levels were significantly elevated in patients with IgAN compared to healthy individuals (median 4.55 [interquartile range 3.58 to 5.85] µg/ml vs 3.19 [interquartile range 2.55 to 3.92] µg/ml). Higher circulating FHR-5 levels were associated with a lower estimated glomerular filtration rate, hypertension, and severe Oxford-T and Oxford-C scores. High FHR-5 levels were independently and significantly associated with a risk of developing either a 30% decline in the estimated glomerular filtration rate or end-stage renal disease (hazard ratio, per standard deviation increment of natural square root transformed FHR-5 of 1.226; 95% confidence interval: 1.106-1.359). Thus, the circulating FHR-5 level is an independent risk factor for IgAN progression.

IgA1 Glycosylation Is Heritable in Healthy Twins.

IgA nephropathy (IgAN) is the most common form of primary GN and an important cause of kidney failure. Characteristically, patients with IgAN have increased serum levels of undergalactosylated IgA1 (gd-IgA1). To assess the degree to which serum gd-IgA1 levels are genetically determined in healthy individuals, we determined serum IgA and gd-IgA1 levels by ELISA in a sample of 148 healthy female twins, including 27 monozygotic and 47 dizygotic pairs. Using the classic twin model, we found the heritability of serum gd-IgA1 and IgA levels to be 80% (95% confidence interval, 66% to 89%) and 46% (95% confidence interval, 15% to 69%), respectively. These data indicate that serum gd-IgA1 levels are highly heritable. Elucidating the genetic basis of this heritability will be important in understanding the pathogenesis of IgAN.