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Clinical Microbiology Reviews, Ahead of Print.

It is known that pathogens can promote their propagation by hijacking their host’s cellular activities. This aggressive process usually causes severe damage to host cells, including RCD. RCD is a defensive strategy that the host employs to restrict pathogenic infections. On the contrary, pathogens could usurp various RCDs during infections to achieve propagation goals. Some pathogens induce cell death to release progeny and cause host injuries, while other species inhibit cell death to facilitate the proliferation stage or to evade the immune defense.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

Proceedings of the National Academy of Sciences, Volume 119, Issue 49, December 2022.

ABSTRACTBackgroundThis prospective study assesses symptoms three months after SARS-CoV-2-infection compared to test-negative and population controls, and the effect of vaccination prior to infection.MethodsParticipants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2-test, or after invitation from the general population (population controls). After three months, participants indicated presence of 41 symptoms, and severity of four symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection.Results9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At three months, 13 symptoms, and severity of fatigue, cognitive impairment and dyspnoea, were significantly elevated between cases and controls. Of cases, 48.5% reported ≥1 significantly elevated symptom, compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases <65yrs, and was significantly protective for loss of smell and taste but not for other symptoms.DiscussionThree months after SARS-CoV-2 infection, almost half of cases report symptoms, which is higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65.

ObjectivesWe aimed to evaluate the international variation in the use of evidence-based management (EBM) in bronchiolitis. We hypothesised that management consistent with full-EBM practices is associated with the research network of care, adjusted for patient-level characteristics. Secondary objectives were to determine the association between full-EBM and (1) hospitalisation and (2) emergency department (ED) revisits resulting in hospitalisation within 21 days.DesignA secondary analysis of a retrospective cohort study.Setting38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal.PatientsOtherwise healthy infants 2–11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013.Outcome measuresPrimary outcome was management consistent with full-EBM, that is, no bronchodilators/corticosteroids/antibiotics, no chest radiography or laboratory testing. Secondary outcomes included hospitalisations during the index and subsequent ED visits.Results1137/2356 (48.3%) infants received full-EBM (ranging from 13.2% in Spain/Portugal to 72.3% in UK/Ireland). Compared with the UK/Ireland, the adjusted ORs (aOR) of full-EBM receipt were lower in Spain/Portugal (aOR 0.08, 95% CI 0.02 to 0.29), Canada (aOR 0.13 (95% CI 0.06 to 0.31) and USA (aOR 0.16 (95% CI 0.07 to 0.35). EBM was less likely in infants with dehydration (aOR 0.49 (95% CI 0.33 to 0.71)), chest retractions (aOR 0.69 (95% CI 0.52 to 0.91)) and nasal flaring (aOR 0.69 (95% CI 0.52 to 0.92)). EBM was associated with reduced odds of hospitalisation at the index visit (aOR 0.77 (95% CI 0.60 to 0.98)) but not at revisits (aOR 1.17 (95% CI 0.74 to 1.85)).ConclusionsInfants with bronchiolitis frequently do not receive full-EBM ED management, particularly those outside of the UK/Ireland. Furthermore, there is marked variation in full-EBM between paediatric emergency networks, and full-EBM delivery is associated with lower likelihood of hospitalisation. Given the global bronchiolitis burden, international ED-focused deimplementation of non-indicated interventions to enhance EBM is needed.…

ObjectiveThe purpose of the systematic review was to assess the effectiveness of remote patient monitoring (RPM) follow-up compared with standard care, for patients with chronic kidney disease (CKD) who perform dialysis at home.MethodsWe conducted a systematic review in accordance with international guidelines. We performed systematic searches for publications from 2015 to 2021 in five databases (eg, Medline, Cinahl, Embase) and a search for grey literature in reference lists. Included effect measures were quality of life, hospitalisation, technical failure as the cause for transfer to a different dialysis modality, infections and time patients use for travel. Screening of literature, data extraction, risk-of-bias assessment and certainty of evidence assessment (using the Grading of Recommendations Assessment, Development and Evaluation approach) were done by two researchers. We conducted meta-analyses when possible.ResultsSeven studies met the inclusion criteria, of which two were randomised controlled trials and five were retrospective cohort studies with control groups. The studies included 9975 participants from 5 countries, who were a good representation of dialysis patients in high-income and upper-middle-income countries. The patients were on peritoneal dialysis (six studies) or home haemodialysis (one study). There was very low certainty of evidence for the outcomes, except for hospitalisations: there was low certainty evidence from three cohort studies for fewer hospitalisation days in the RPM group. No studies included data for time patients used for travel.ConclusionWe found low to very low certainty evidence that indicate there may be positive effects of RPM follow-up, in comparison to standard care only, for adult patients with CKD who perform dialysis at home. Offering RPM follow-up for home dialysis patients as an alternative or supplement to standard care appears to be safe and provide health benefits such as fewer hospitalisation days. Future implementation should be coupled with robust, high-quality evaluations.PROSPERO registration numberCRD42021281779.…

IntroductionPaediatric patients with chronic anterior uveitis are more prone to suffer from the chronic course of intraocular inflammation and adverse effects of long-term immunomodulatory therapy, either topical glucocorticosteroids or systemic immunomodulatory agents. The performance of adalimumab has been shown to be fairly favourable in treating refractory non-infectious uveitis, but the detailed indication is still under investigation. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious paediatric anterior uveitis with peripheral retinal vascular leakage, compared with methotrexate.Methods and analysisChildren weighed ≥30 kg and aged between 4 and 16 years old with active non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra-wildfield fluorescein fundus angiography will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either methotrexate 10 mg once a week or adalimumab once every 2 weeks and regularly followed up for 6 months. The primary endpoint is uveitis flare defined as defined as anterior chamber cell count grading increased from 0 to 1 within the observation period.Ethics and disseminationThe study was approved by the Institutional Review Board of Peking Union Medical College Hospital, Beijing, China (Approved protocol V3, dated 27 July 2021. Approval number 25-ZS-3062) and has been registered on ClinicalTrials.gov. Written informed consent will be collected from every patient and their guardians prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT05015335.…

ObjectiveThis study aimed to determine the prevalence of fluoroquinolone resistance-associated mutations (QRAMs) in Mycoplasma genitalium (MG) among clients of two sexual health centres (SHCs) in the Netherlands.DesignA cross-sectional study.Setting and participantsBetween 2018 and 2019, 669 clients with MG were included from two previous studies: 375 male clients with urethritis from the SHC in Amsterdam; and 294 clients (male and female) from the SHC in Amsterdam and The Hague. Urogenital and anal samples (705 in total) that tested positive for MG by nucleic acid amplification tests were selected.Outcome measuresThe presence of QRAM was detected by an MG-QRAM PCR targeting four mutations in the parC gene and investigated by sequence analysis of relevant regions of the gyrA and parC genes. Possible risk factors for the presence of QRAM were investigated.ResultsWe found QRAM in 58 of 669 (9%) clients with an MG infection: 36 of 375 (10%) in the study population of men with urethritis and 22 of 294 (7%) in the study population of other clients (including both men and women; p=0.334). Most prevalent mutations in the parC gene were S83I and D87N, occurring in 31 of 60 (52%) and 20 of 60 (33%) samples, respectively. Factors associated with the presence of QRAM were: men who have sex with men (adjusted OR (aOR) 3.4, 95% CI 1.7 to 6.9) and Asian origin (aOR 2.5, 95% CI 1.2 to 5.6). Multidrug resistance (QRAM plus macrolide resistance-associated mutations) was found in 46 of 669 (7%) clients.ConclusionsNine per cent of MG-positive clients from two Dutch SHCs had QRAM. New treatment strategies and antibiotics are needed to treat symptomatic patients with multidrug-resistant MG.…

ObjectivesThis study sought to conduct a systematic review of the literature on the impact of the COVID-19 pandemic on sleep health among Middle Eastern and North African (MENA) populations, understudied geographic regions including with regards to sleep health.SettingA systematic literature search of studies published from inception to 27 March 2022 was conducted on multiple databases using developed keywords.ParticipantsStudies were included if they (1) investigated one or more aspects/dimensions of sleep health as an outcome (eg, sleep duration, sleep quality, sleep problems); (2) measured the impact of a COVID-19 pandemic-related domain (eg, impact of quarantine, work from home, lifestyle changes); (3) focused on at least one MENA region population; (4) were peer-reviewed; (5) included ≥100 participants; (6) were written in English and (7) had full-text article publicly available.Primary and secondary outcomes measuredPrimary outcomes were sleep duration, sleep quality and sleep problems.ResultsIn line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 164 studies were included for data extraction. The Newcastle-Ottawa scale for cross-sectional studies was used to assess the quality of the studies. Overall, the COVID-19 pandemic significantly impacted sleep duration, sleep quality and presence and severity of sleep disorders in MENA populations, including adults, children, students, healthcare workers and people with chronic illnesses. The directionality and strength of associations, as well as the determinants of sleep health, varied by subpopulations.ConclusionsLongitudinal studies are needed to understand the longer-term impact of the COVID-19 pandemic on the sleep health of MENA populations. Sleep health interventions and policy measures should be tailored to the need of each subpopulation.PROSPERO registration numberCRD42022321128.…

PurposeTo better understand the household transmission of SARS-COV-2 in a low-resource community in Rio de Janeiro during the COVID-19 pandemic (2020–2022).ParticipantsThis is an open prospective cohort study of children ≤12 years old and their household contacts. During home visits over 24 months, we collected data on sociodemographic characteristics, behavioural data, clinical manifestations of SARS-CoV-2, vaccination status, SARS-CoV-2 (reverse transcription-polymerase chain reaction) RT-PCR and anti-S antibody tests. Among adults, the majority of participants were women (62%).Findings to dateWe enrolled 845 families from May 2020 to May 2022. The median number of residents per household was four. The median household density, defined as the number of persons per room, was 0.95. The risk of SARS-CoV-2 occurrence was higher in households with a high number of persons per room. Children were not the principal source of SARS-CoV-2 infections in their households during the first wave of the pandemic.Future plansFuture studies will investigate cellular and humoral immune responses to locally circulating SARS-CoV-2 variants, which is relevant for the design of vaccines, antivirals and monoclonal antibodies. We will also engage in outreach to encourage vaccination as a means of limiting the transmission of novel SARS-CoV-2 variants and other emerging pathogens.…

AbstractBackgroundThis phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic.MethodsPatients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events.ResultsA total of 341 patients (ensitrelvir 125 mg group, 114; ensitrelvir 250 mg group, 116; and placebo group, 111; male, 53.5%–64.9%; mean age, 35.3–37.3 years) were included in the efficacy analyses. The change from baseline in the SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL, P < 0.0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity.ConclusionsEnsitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile.

AbstractBackgroundMass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities.MethodsAs part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study.ResultsThe pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community).ConclusionsMass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Abstract Background Although the prevalence of hepatitis B in Guangzhou, China, is high, the epidemiological trends are not well-documented. We aimed to analyse newly reported hepatitis B cases in Guangzhou between 2009 and 2020 to explore the epidemiological trends and provide insights for the development of control measures. Methods Information on the population and new cases of hepatitis B in Guangzhou between 2009 and 2020 was obtained from the China Information System for Disease Control and Prevention, which was used to calculate the annual notification rates of hepatitis B by sex, age group (0–9; 10–19; 20–29; 30–39; 40–49; 50–59; ≥ 60 years), and location (urban or rural). Joinpoint regression analysis was used to analyse the temporal trends and calculate the average annual percentage change (AAPC) and annual percentage change (APC) for each identified trend line segment. Results Between 2009 and 2020, 287,034 new cases of hepatitis B were cumulatively reported. The average annual notification rate was 181.13/100,000, and the notification rate showed a long-term downward trend during the period 2009–2020, with an annual decrease of 6.30% (APC − 6.30%; 95% CI − 7.56 to − 5.02%). Men had a significantly higher notification rate than women; however, the sex ratio decreased from a maximum of 2.34 in 2010 to a minimum of 1.54 in 2020. A downward trend in the notification rate was observed in urban areas and an upward trend was observed in rural areas, with an increase in the rural/urban ratio from 0.46 in 2012 to 1.57 in 2020. The notification rate for all age groups showed a decreasing trend from 2009, with the exception of the 50–59 years and ≥ 60 years groups, whose notification rates began to decrease from 2014 and 2015, respectively. Conclusions Although the overall notification rate of hepatitis B in Guangzhou decreased annually, it remained high. Further, in rural areas, the notification rate has been increasing, and effective measures should be taken to control hepatitis B infection in Guangzhou. …

Abstract Background There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV. Methods We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X2 test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia. Results Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50–199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]). Conclusions Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV. …

Abstract Background Seasonal malaria chemoprevention (SMC) consists of the intermittent administration of a 3 day course of anti-malarial medications during the months of highest malaria risk in the Sahel region, where malaria transmission is highly seasonal. SMC is an effective intervention to reduce episodes of uncomplicated and severe malaria in children. However, morbidity cannot be lowered without adherence to medications. The objective of this study was to examine SMC medication adherence and to identify the attitudes and practices of caregivers during the 2020 SMC campaign in the Dosso region. Methods This study was conducted based on data from independent monitoring using random cluster sampling. Adherence levels and the attitudes and practices of caregivers were evaluated using data from caregivers’ self-reports and analysed according to Bernard Vrijens’ taxonomy. Results At the initiation of treatment phase, 99% of children (N = 2296) received their first administration of medication, with 90% of caregivers (N = 1436) knowing that the medications help prevent malaria. However, only 56% of caregivers (N = 1856) reported that treatment initiation took place under direct observation by the distributor. At the implementation of treatment phase, 90% of children (N = 2132) took their medication on the second day and 84% (N = 1068) took it the third day. “Forgetting,” “not having time,” and “the mother’s absence” were the main reasons caregivers gave to explain discontinuation of the 3 day course of medication. Conclusion This simple, low-cost survey demonstrated that coverage of SMC and adherence by caregivers to completing the full 3 day medication course was high. The survey also showed that knowledge, attitudes, and practices of some caregivers regarding adherence to medications during the SMC campaign could be improved. Expanding distributors’ training, developing and providing them with tools for interpersonal communication, and strengthening supervision could lead to even higher adherence. …

Abstract Background Malaria remains a major cause of morbidity and mortality in sub-Saharan Africa. Using insecticide-treated nets (ITNs) every night, year-round is critical to maximize protection against malaria. This study describes sociodemographic, psychosocial, and household factors associated with consistent ITN use in Cameroon, Côte d’Ivoire and Sierra Leone. Methods Cross-sectional household surveys employed similar sampling procedures, data collection tools, and methods in three countries. The survey sample was nationally representative in Côte d’Ivoire, representative of the North and Far North regions in Cameroon, and representative of Bo and Port Loko districts in Sierra Leone. Analysis used multilevel logistic regression and sociodemographic, ideational, and household independent variables among households with at least one ITN to identify correlates of consistent ITN use, defined as sleeping under an ITN every night the preceding week. Findings Consistent ITN use in Côte d’Ivoire was 65.4%, 72.6% in Cameroon, and 77.1% in Sierra Leone. While several sociodemographic and ideational variables were correlated with consistent ITN use, these varied across countries. Multilevel logistic regression results showed perceived self-efficacy to use ITNs and positive attitudes towards ITN use were variables associated with consistent use in all three countries. The perception of ITN use as a community norm was positively linked with consistent use in Cameroon and Côte d’Ivoire but was not significant in Sierra Leone. Perceived vulnerability to malaria was positively linked with consistent use in Cameroon and Sierra Leone but negatively correlated with the outcome in Côte d’Ivoire. Household net sufficiency was strongly and positively associated with consistent use in all three countries. Finally, the findings revealed strong clustering at the household and enumeration area (EA) levels, suggesting similarities in net use among respondents of the same EA and in the same household. Conclusions There are similarities and differences in the variables associated with consistent ITN use across the three countries and several ideational variables are significant. The findings suggest that a social and behaviour change strategy based on the ideation model is relevant for increasing consistent ITN use and can inform specific strategies for each context. Finally, ensuring household net sufficiency is essential. …

The COVID-19 pandemic, which emerged at the end of 2019, has caused millions of fatalities worldwide. The development and clinical introduction of anti-viral drugs directed against the SARS-CoV2 virus has to be considered as a milestone to combat this pandemic and to treat this infection. Antiviral therapy is most effective when given early in the course of COVID-19(1, 2). Accordingly, two orally applicable drugs, nirmatrelvir/ritonavir and molnupiravir have demonstrated in two double blinded randomized controlled trials that they significantly reduced the risk for hospitalization or death in unvaccinated ambulatory patients with risk factors for severe infection when given within the first days after onset of COVID-19 related symptoms(3, 4).

Science Advances, Volume 8, Issue 49, December 2022.

Antimicrobial Agents and Chemotherapy, Ahead of Print.