Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Publication date: Available online 31 May 2023 Source: Infectious Disease Modelling Author(s): Zenebe Shiferaw Kifle, Legesse Lemecha Obsu …

Publication date: Available online 30 May 2023 Source: International Journal for Parasitology Author(s): Mélanie Duc, Tanja Himmel, Mikas Ilgūnas, Vytautas Eigirdas, Herbert Weissenböck, Gediminas Valkiūnas …

AbstractBackgroundRifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons initiate treatment and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, six-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200 mg linezolid. After U.S. FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial linezolid 600 mg dose adjusted by serum drug concentrations and clinical monitoring.MethodsData from U.S. patients treated with BPaL between 10/14/2019 and 4/30/2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider-driven, and most had linezolid adjusted by therapeutic drug monitoring (TDM).ResultsOf 70 patients starting BPaL, two changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and two of these 68 (2.9%) patients relapsed after completion. Using an initial 600 mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three (4.4%) patients with hematologic toxicity and four (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months.ConclusionsBPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in ATS/CDC/ERS/IDSA 2019 guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the U.S. is feasible.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

Proceedings of the National Academy of Sciences, Volume 120, Issue 22, May 2023.

AbstractIntroductionPrevious studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV seasonal epidemics, possibly due to not accounting for confounders such as meteorological factors. We aimed to improve the understanding of the association through a global-level systematic analysis that accounted for these potential confounders.MethodsWe compiled published data on RSV seasonality through a systematic literature review, and supplemented with unpublished data shared by international collaborators. RSV seasonal characteristics were defined for each study-year based on the annual cumulative proportion (ACP) of RSV-positive cases, with ACP of 10% and 90% being defined as season onset and offset, respectively. Linear regression models with study-level clustered standard errors were conducted to analyse the association of proportion of RSV-A with the corresponding RSV season onset and offset separately, while accounting for meteorological factors.ResultsWe included a total of 36 studies from 36 sites in 20 countries, which cumulatively provided data for 179 study-years in 1995–2019. Overall, year-on-year variations in RSV season onset, offset, and duration were generally comparable among tropical, sub-tropical, and temperate regions. Regression analysis by latitude groups showed that RSV subgroup distribution was not significantly associated with RSV season onset or offset globally; the only exception was for RSV season offset in the tropics in one model, possibly by chance. Models that included both RSV subgroup distribution and meteorological factors only jointly explained 2–4% of the variations in RSV season onset and offset.ConclusionGlobally, RSV subgroup distribution had negligible impact on the RSV seasonal characteristics. RSV subgroup distribution and meteorological factors jointly could only explain limited year-on-year variations in RSV season onset and offset. The role of population susceptibility, mobility, and viral interference should be examined in future studies.

AbstractBackgroundRespiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalisations. Estimating RSV-associated hospitalisation is critical for planning RSV-related healthcare across Europe.MethodsWe gathered RSV-associated hospitalisation estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006-2017. We extrapolated these estimates to 28 EU countries using nearest-neighbour matching, multiple imputations, and two sets of 10 indicators.ResultsOn average, 158229 (95%CI:140865-175592) RSV-associated hospitalisations occur annually among adults in the EU (≥18years); 92% of these hospitalisations occur in adults ≥65years. Among 75-84years, the annual average is estimated at 74519 (69923-79115) at a rate of 2.24 (2.10-2.38) per 1000. Among ≥85years, the annual average is estimated at 37904 (32444-43363) at a rate of 2.99 (2.56-3.42).ConclusionOur estimates of RSV-associated hospitalisations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalisation estimate in adults was lower but of a similar magnitude to the estimate in young children(0-4years): 158229 (140865–175592) versus 245244 (224688–265799).

AbstractBackgroundNo overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). We aimed to estimate the RSV hospitalisation burden in children under 5 years in EU countries and Norway, by age group.MethodsWe collated national RSV-associated hospitalisation estimates calculated using linear regression models via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. Additional estimates were obtained from a systematic review. Using the multiple imputation and nearest neighbour matching methods, we estimated overall RSV-associated hospitalisations and rates in the EU.ResultsAdditional estimates for only two countries (France and Spain) were found in the literature. In the EU, an average of 245,244 (95%CI 224,688-265,799) yearly hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 66.6-76.6).ConclusionOur findings will help support decisions regarding prevention efforts and represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe.

AbstractBackgroundPulmonary tuberculosis (TB) and lung cancer (LC) have similar clinical symptoms and atypical imaging findings which are easily misdiagnosed. There is an urgent need for a noninvasive and accurate biomarker to distinguish LC from TB.MethodsA total of 694 subjects were enrolled and divided into discovery set (n = 122), identification set (n = 214), and validation set (n = 358). Metabolites were identified by multivariate and univariate analyses. Receiver operating characteristic curve were used to evaluate the diagnostic efficacy of biomarkers.ResultsSeven metabolites were identified and validated. Phenylalanylphenylalanine for distinguish LC from TB yielded an area under the curve of 0.89, sensitivity of 71%, and specificity of 92%. It also showed good diagnostic abilities in discovery set and identification set. Compared with that in healthy volunteers (1.57 (1.01, 2.34) μg·mL-1), it was elevated in LC (4.76 (2.74-7.08) μg·mL-1; ratio of median, ROM = 3.03, p 

Dogma is defined as “a belief or set of beliefs that is accepted by the members of a group without being questioned or doubted” (https://www.britannica.com/dictionary/dogma; accessed May 2, 2023). Everyone who has worked in different healthcare institutions, maybe even in different countries, knows that there are local ‘dogmas’ that are not evidence-based.(1) Indeed, one may identify dogmas as such only once one has been confronted with other, possibly opposing ‘dogmas’ elsewhere. The question of whether, for which patients, at what interval(s), and how often to repeat blood cultures in the case of Gram-negative bacteremia may be an example.

Abstract Background Although tuberculosis (TB) patients coinfected with HIV are at risk of poor treatment outcomes, there is paucity of data on changing trends of TB/HIV co-infection and their treatment outcomes. This study aims to estimate the burden of TB/HIV co-infection over time, describe the treatment available to TB/HIV patients and estimate the effect of TB/HIV co-infection on TB treatment outcomes. Methods This was a retrospective data analyses from TB surveillance in two counties in Kenya (Nyeri and Kilifi): 2012‒2020. All TB patients aged ≥ 18 years were included. The main exposure was HIV status categorised as infected, negative or unknown status. World Health Organization TB treatment outcomes were explored; cured, treatment complete, failed treatment, defaulted/lost-to-follow-up, died and transferred out. Time at risk was from date of starting TB treatment to six months later/date of the event and Cox proportion with shared frailties models were used to estimate effects of TB/HIV co-infection on TB treatment outcomes. Results The study includes 27,285 patients, median (IQR) 37 (29‒49) years old and 64% male. 23,986 (88%) were new TB cases and 91% were started on 2RHZE/4RH anti-TB regimen. Overall, 7879 (29%, 95% 28‒30%) were HIV infected. The proportion of HIV infected patient was 32% in 2012 and declined to 24% in 2020 (trend P-value = 0.01). Uptake of ARTs (95%) and cotrimoxazole prophylaxis (99%) was high. Overall, 84% patients completed six months TB treatment, 2084 (7.6%) died, 4.3% LTFU, 0.9% treatment failure and 2.8% transferred out. HIV status was associated with lower odds of completing TB treatment: infected Vs negative (aOR 0.56 (95%CI 0.52‒0.61) and unknown vs negative (aOR 0.57 (95%CI 0.44‒0.73). Both HIV infected and unknown status were associated with higher hazard of death: (aHR 2.40 (95%CI 2.18‒2.63) and 1.93 (95%CI 1.44‒2.56)) respectively and defaulting treatment/LTFU: aHR 1.16 (95%CI 1.01‒1.32) and 1.55 (95%CI 1.02‒2.35)) respectively. HIV status had no effect on hazard of transferring out and treatment failure. Conclusion The overall burden of TB/HIV coinfection was within previous pooled estimate. Our findings support the need for systematic HIV testing as those with unknown status had similar TB treatment outcomes as the HIV infected. …

Abstract Background Liver failure is severe hepatic cellular damage caused by multiple factors that leads to clinical manifestations. Hepatic infiltration by malignancy is rarely reported as a cause of liver failure. Case presentation A 51-year-old male patient was admitted to the Wuhan Union Hospital complaining of bloating and jaundice. He had been diagnosed with polymyositis ten prior and was taking oral glucocorticoids. Physical examination revealed seroperitoneum and icteric sclera; laboratory tests revealed liver dysfunction, a coagulopathy, and negative results for the common causes of liver failure. Moreover, an ascitic tap and bone marrow aspirate and trephine confirmed a metastatic, poorly differentiated adenocarcinoma. These findings indicate that malignant infiltration is the most likely cause of liver failure. Regrettably, the patient refused complete liver and lymph node biopsies and was discharged on day 31. Conclusion Clinicians should consider the possibility of malignant infiltration when approaching a case of liver failure with prodromal symptoms or imaging abnormalities, especially in patients with autoimmune diseases, such as polymyositis. …

Abstract Aim Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. Methods Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. Results A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. Conclusions In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM. …

Once integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an ...

Some people do not believe long COVID (also known as post-COVID-19 condition) is real. In fact, patients have reported that there are even doctors who sit in this camp, who might dismiss their symptoms as psychosomatic, or do not know how to recognise or treat long COVID. It is complicated, even for researchers. People might not have had severe symptoms when infected with SARS-CoV-2 virus, they might be young, without a significant medical history or risk factors. Although studies suggest around 10–20% of individuals who did not have severe acute disease might develop long COVID symptoms, the number of people who are facing long-term effects is hard to quantify.

In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation.

by Ye Ji Lee, Min A. Yuh, In Soo Kim, Byul Nym Hee Cho, Seon Hee Woo, Sungyoup Hong Background People experienced various stress and psychological responses to the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to examine the changes in emergency medical services (EMSs) utilization by self-harm patients in early pandemic and the impacts of physical distancing measures on the EMSs utilization by self-harm patients. Methods Data for all patients presenting to emergency departments (EDs) after self-harm injuries including self-poisoning were collected from the National ED Information System (NEDIS). Characteristics of patients in two study regions (urban versus rural) were compared. Weekly and annual ED visit rates after self-harm (VRSH) per 100,000 population were calculated. Mobile phone mobility index (MPMI) was calculated by dividing a region’s aggregated mobile phone mobility by mid-year population. Joinpoint regression analysis was conducted to assess changes in 2020 over pre-pandemic years. Test for presence of joinpoint at the end of 2019 was performed. A cross-correlation function was used to estimate the maximal morphological similarity and lag time between changes in MPMI and VRSH. Results In 2020, in early phases of the pandemic, there was a moderate decline in self-harm-related ED visits to 30,797 from a continuously increasing trend seen in previous years. However, proportions of young people (50.1%) and females (62.3%) increased over previous years. VRSHs among women and young people aged 15–34 years showed higher levels in 2020 than in previous five years. There was a significant decrease in the proportion of patients transported directly from the scene. In addition, there was a polarization of mental state upon ED arrival from alert and unresponsive. The median correlation coefficient between MPMI values and VRSH values was 0.601 (interquartile range [IQR]: 0.539–0.619) in urban regions and 0.531 (IQR: 0.454–0.595) in rural regions, showing no statistically significant difference between the two. Conclusion Physical distancing measures adopted to prevent the spread of transmittable diseases following the pandemic had the effect of decreasing ED visits due to self-harm. When the pandemic has ended, and daily life has been restored, it will be particularly important to pay attention to the increased numbers of self-harm patients expected to visit EDs compared to during the pandemic. …

by Kathleen Subramoney, Nkhensani Mtileni, Ashlyn Davis, Jennifer Giandhari, Houriiyah Tegally, Eduan Wilkinson, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Andiswa Simane, Bhaveshan Reddy, Bonolo Mashishi, Nonhlanhla Mbenenge, Tulio de Oliveira, Burtram C. Fielding, Florette K. Treurnicht Intra-host diversity studies are used to characterise the mutational heterogeneity of SARS-CoV-2 infections in order to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. The study included SARS-CoV-2 respiratory samples, from individuals of all ages, received at the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic hospital, Gauteng, South Africa, from June 2020 to May 2022. Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on a random selection of SARS-CoV-2 positive samples. The allele frequency (AF) was determined using TaqMan Genotyper software for SNP PCR analysis and galaxy.eu for analysis of FASTQ reads from sequencing. The SNP assays identified 5.3% (50/948) of Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50), however only heterogeneity for E484Q and delY144 were confirmed by sequencing. From sequencing we identified 9% (210/2381) of cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages that had heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2–0.7), 371 (92.3%) with S371FP (AF 0.1–1.0), and 484 (1.9%) with E484AK (0.2–0.7), E484AQ (AF 0.4–0.5) and E484KQ (AF 0.1–0.4). Mutations at heterozygous amino acid positions 19, 371 and 484 are known antibody escape mutations, however the impact of the combination of multiple substitutions identified at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host’s natural and vaccine-induced immune responses.

by Yingjun Nie, Yuanyan Ma, Xiaozhi Yao, Yijia Gao, Xiangping Zheng Background COVID-19 caused severe effects on the psychological well-being of Chinese students overseas (COS). Physical activity (PA) is critical to strengthen immunity, prevent infection, and reduce the psychological burden caused by COVID-19. However, there is a severe lack of effective PA intervention for mental health in most countries, and COS have limited access to mental healthcare during the pandemic. Objective We aim to examine the effects of PA on COS’ mental health during the pandemic abroad and to better understand that certain types of PA might be associated with a greater reduction in psychological burdens during the pandemic. Methods and results In a multi-country cross-sectional analysis, a questionnaire was distributed to COS living in 37 foreign countries via WeChat Subscription using a snowball sampling strategy. A total of 10,846 participants were included. Descriptive statistics and Binary logistic regression analysis were used for statistical analysis. We found that COS had negative psychology during the pandemic, especially with fear (2.90, 95% CI 2.88−2.92), anxiety (2.84, 95% CI 2.82−2.85), and stress (2.71, 95% CI 2.69−2.73). PA had meaningful effects on reducing COS self-reported mental health burdens (3.42, 95% CI 3.41–3.44) during the pandemic. The largest associations were seen for recreational and home-based PA (i.e., family games, home aerobic exercise), individual outdoor PA (i.e., walking or running, rope skipping), and PA with a duration of 30 to 70 min per session at frequencies of 4 to 6 times and a total of 150 to 330 min of moderate and vigorous intensity per week tends to be an optimal choice during social distancing times. Conclusions COS had several poor mental health conditions during the pandemic. The improvement of PA on COS’ psychology was positively effective during the pandemic. Specific types, intensities, durations, and frequencies of PA might have advantages over others for improving COS’ mental health during periods of public health emergencies, and the topic may merit interventional study to reveal multiple factors causing COS’ psychological burdens and enrich the PA forms for all COS’ mental health improvement (i.e., infected, recovered, and asymptomatic COS). …

by Tomomitsu Tahara, Kazuya Takahama, Sayumi Tahara, Noriyuki Horiguchi, Kohei Funasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Tetsuya Tsukamoto, Hiro-o Ieda, Toshiro Fukui, Makoto Naganuma, Naoki Ohmiya Background/Aim Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. Patients/Methods 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. Results Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27–0.86) and adenoma (OR = 0.47, 95%CI = 0.26–0.86). Conclusion LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma. …

by Amir Hossein Khoshakhlagh, Saeid Yazdanirad, Hamid Reza Saberi, Masoud Motalebi Kashani, Fatemeh Ghanaei Khaledabadi, Fazel Mohammadi-Moghadam, Muhammet Gul The need for a biological disease risk assessment method to prevent the contagion of these diseases, particularly among healthcare personnel, is crucial. Therefore, this study aimed to develop and validate a biological risk assessment tool for biological agents among hospital personnel under COVID-19 conditions. This cross-sectional study was performed on 301 employees in two hospitals. Firstly, we identified the items affecting the contagion of biological agents. Then, we computed the weight of the items using the Fuzzy Analytical Hierarchy Process (FAHP) method. We used the identified items and the estimated weights in the next step to develop a predictive equation. The outcome of this tool was the risk score of biological disease contagion. After that, we used the developed method to evaluate the biological risk of the participants. The ROC curve was also used to reveal accuracy of developed method. In this study, 29 items were identified and categorized into five dimensions, including environmental items, ventilation items, job items, equipment-related items, and organizational items. The weights of these dimensions were estimated at 0.172, 0.196, 0.255, 0.233, and 0.144, respectively. The final weight of items was used to develop a predictive equation. The area under ROC curves (AUC) was also calculated as 0.762 (95% CI: 0.704, 0.820) (p…

by Francis Hassard, Milan Vu, Shadi Rahimzadeh, Victor Castro-Gutierrez, Isobel Stanton, Beata Burczynska, Dirk Wildeboer, Gianluca Baio, Mathew R. Brown, Hemda Garelick, Jan Hofman, Barbara Kasprzyk-Hordern, Azeem Majeed, Sally Priest, Hubert Denise, Mohammad Khalifa, Irene Bassano, Matthew J. Wade, Jasmine Grimsley, Lian Lundy, Andrew C. Singer, Mariachiara Di Cesare Background Schools are high-risk settings for infectious disease transmission. Wastewater monitoring for infectious diseases has been used to identify and mitigate outbreaks in many near-source settings during the COVID-19 pandemic, including universities and hospitals but less is known about the technology when applied for school health protection. This study aimed to implement a wastewater surveillance system to detect SARS-CoV-2 and other public health markers from wastewater in schools in England. Methods A total of 855 wastewater samples were collected from 16 schools (10 primary, 5 secondary and 1 post-16 and further education) over 10 months of school term time. Wastewater was analysed for SARS-CoV-2 genomic copies of N1 and E genes by RT-qPCR. A subset of wastewater samples was sent for genomic sequencing, enabling determination of the presence of SARS-CoV-2 and emergence of variant(s) contributing to COVID-19 infections within schools. In total, >280 microbial pathogens and >1200 AMR genes were screened using RT-qPCR and metagenomics to consider the utility of these additional targets to further inform on health threats within the schools. Results We report on wastewater-based surveillance for COVID-19 within English primary, secondary and further education schools over a full academic year (October 2020 to July 2021). The highest positivity rate (80.4%) was observed in the week commencing 30th November 2020 during the emergence of the Alpha variant, indicating most schools contained people who were shedding the virus. There was high SARS-CoV-2 amplicon concentration (up to 9.2x106 GC/L) detected over the summer term (8th June - 6th July 2021) during Delta variant prevalence. The summer increase of SARS-CoV-2 in school wastewater was reflected in age-specific clinical COVID-19 cases. Alpha variant and Delta variant were identified in the wastewater by sequencing of samples collected from December to March and June to July, respectively. Lead/lag analysis between SARS-CoV-2 concentrations in school and WWTP data sets show a maximum correlation between the two-time series when school data are lagged by two weeks. Furthermore, wastewater sample enrichment coupled with metagenomic sequencing and rapid informatics enabled the detection of other clinically relevant viral and bacterial pathogens and AMR. Conclusions Passive wastewater monitoring surveillance in schools can identify cases of COVID-19. Samples can be sequenced to monitor for emerging and current variants of concern at the resolution of school catchments. Wastewater based monitoring for SARS-CoV-2 is a useful tool for SARS-CoV-2 passive surveillance and could be applied for case identification and containment, and mitigation in schools and other congregate settings with high risks of transmission. Wastewater monitoring enables public health authorities to develop targeted prevention and education programmes for hygiene measures within undertested communities across a broad range of use cases. …

by Günter Schneckenreither, Lukas Herrmann, Rafael Reisenhofer, Niki Popper, Philipp Grohs Structural features and the heterogeneity of disease transmissions play an essential role in the dynamics of epidemic spread. But these aspects can not completely be assessed from aggregate data or macroscopic indicators such as the effective reproduction number. We propose in this paper an index of effective aggregate dispersion (EffDI) that indicates the significance of infection clusters and superspreading events in the progression of outbreaks by carefully measuring the level of relative stochasticity in time series of reported case numbers using a specially crafted statistical model for reproduction. This allows to detect potential transitions from predominantly clustered spreading to a diffusive regime with diminishing significance of singular clusters, which can be a decisive turning point in the progression of outbreaks and relevant in the planning of containment measures. We evaluate EffDI for SARS-CoV-2 case data in different countries and compare the results with a quantifier for the socio-demographic heterogeneity in disease transmissions in a case study to substantiate that EffDI qualifies as a measure for the heterogeneity in transmission dynamics.