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Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 629-631, September 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 692-702, September 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 713-722, September 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 725-728, September 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 728-730, September 15, 2021.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Objectives The HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID (≤30 years of age), who are hard to engage in services. We assessed perspectives of young PWID to guide development of youth-specific services. Setting We conducted focus group discussions (FGDs) with PWID and staff at venues offering services to PWID in three Indian cities representing historical and emerging drug use epidemics. Participants PWID were eligible to participate if they were between 18 and 35 years, had initiated injection as adolescents or young adults and knew adolescent PWID in their networks. 43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. A semistructured interview guide was used to elicit participants’ narratives on injection initiation experiences, barriers to seeking harm reduction services, service delivery gaps and recommendations to promote engagement. Thematic analysis was used to develop an explanatory model for service engagement in each temporal stage across the injection continuum. Results Injection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the preinjection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low-risk perception resulted in low motivation to seek services. Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID. Conclusions Development of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm reduction services.

Background Overuse and misuse of antibiotics is a public health problem in low-income and middle-income countries. Although the association of antibiotics with atopic and allergic diseases has been established, most studies focused on prenatal exposure and the occurrence of disease in infants or young children. Objective To investigate the association of preschool use of antibiotics with atopic and allergic skin diseases in young adulthood. Design Population-based retrospective cohort. Setting and participants The first-year college students (n=20 123) from five universities were investigated. The sampled universities are located in Changsha, Wuhan, Xiamen, Urumqi and Hohhot, respectively. Methods We conducted a dermatological field examination and a questionnaire survey inquiring the participants about the frequency of upper respiratory tract infection (URTI) and the preschool antibiotics use (prior to 7 years old). The two-level probit model was used to estimate the associations, and adjusted risk ratio (aRR) and 95% CI were presented as the effect size. Results A total of 20 123 participants with complete information was included in the final analysis. The frequent antibiotics use intravenously (aRR 1.36, 95% CI 1.14 to 1.62) and orally (aRR 1.18, 95% CI 1.01 to 1.38) prior to 7 years old was significantly associated with atopic dermatitis in young adulthood. Similar trends could be observed in allergic skin diseases among those who use antibiotics orally and intravenously, with RRs of 1.16 (95% CI 1.01 to 1.34) and 1.33 (95% CI 1.13 to 1.57), respectively. Conclusions Preschool URTI and antibiotics use significantly increases the risk of atopic and allergic skin diseases in young adulthood.

Introduction Postoperative infection (PI) is one of the main severe complications after cardiovascular surgery. Therefore, antibiotics are routinely used during the first 48 hours after cardiovascular surgery. However, there is no effective method for early diagnosis of infection after cardiovascular surgery, particularly, to determine whether postoperative patients need to prolong the use of antibiotics after the first 48 hours. In this study, we aim to develop and validate a diagnostic model to help identify whether a patient has been infected after surgery and guide the appropriate use of antibiotics. Methods and analysis In this prospective study, we will develop and validate a diagnostic model to determine whether the patient has a bacterial infection within 48 hours after cardiovascular surgery. Baseline data will be collected through the electronic medical record system. A total of 2700 participants will be recruited (n=2000 for development, n=700 for validation). The primary outcome of the study is the newly PI during the first 48 hours after cardiovascular surgery. Logistic regression penalised with elastic net regularisation will be used for model development and bootstrap and k-fold cross-validation aggregation will be performed for internal validation. The derived model will be also externally validated in patients who are continuously included in another time period (N=700). We will evaluate the calibration and differentiation performance of the model by Hosmer-Lemeshow good of fit test and the area under the curve, respectively. We will report sensitivity, specificity, positive predictive value and negative predictive value in the validation data-set, with a target of 80% sensitivity. Ethics and dissemination Ethical approval was obtained from Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (2020-249-01). Trial registration number Chinese Clinical Trial Register (www.chictr.org.cn, ChiCTR2000038762); Pre-results.

Purpose The Communities, Households and SARS-CoV-2 Epidemiology (CHASING) COVID Cohort Study is a community-based prospective cohort study launched during the upswing of the USA COVID-19 epidemic. The objectives of the cohort study are to: (1) estimate and evaluate determinants of the incidence of SARS-CoV-2 infection, disease and deaths; (2) assess the impact of the pandemic on psychosocial and economic outcomes and (3) assess the uptake of pandemic mitigation strategies. Participants We began enrolling participants from 28 March 2020 using internet-based strategies. Adults≥18 years residing anywhere in the USA or US territories were eligible. 6740 people are enrolled in the cohort, including participants from all 50 US states, the District of Columbia, Puerto Rico and Guam. Participants are contacted regularly to complete study assessments, including interviews and dried blood spot specimen collection for serologic testing. Findings to date Participants are geographically and sociodemographically diverse and include essential workers (19%). 84.2% remain engaged in cohort follow-up activities after enrolment. Data have been used to assess SARS-CoV-2 cumulative incidence, seroincidence and related risk factors at different phases of the US pandemic; the role of household crowding and the presence of children in the household as potential risk factors for severe COVID-19 early in the US pandemic; to describe the prevalence of anxiety symptoms and its relationship to COVID-19 outcomes and other potential stressors; to identify preferences for SARS-CoV-2 diagnostic testing when community transmission is on the rise via a discrete choice experiment and to assess vaccine hesitancy over time and its relationship to vaccine uptake. Future plans The CHASING COVID Cohort Study has outlined a research agenda that involves ongoing monitoring of the incidence and determinants of SARS-CoV-2 outcomes, mental health outcomes and economic outcomes. Additional priorities include assessing the incidence, prevalence and correlates of long-haul COVID-19.

Objectives This study was aimed to assess the willingness of elderly people to seek medical care for tuberculosis (TB) and the associated influencing factors. Design A cross-sectional study. Setting A multistage random survey was conducted in Bao’an District of Shenzhen in China. Participants A total of 1200 elderly people aged 65 or above were recruited for the study and completed a structured questionnaire between September and October 2019. Main outcome measures Descriptive and binary logistic stepwise regression analyses were conducted to analyse the characteristics of elderly individuals, their willingness to seek medical care for TB and associated factors. Results Among the final 1123 respondents, 943 (84.0%) were willing to seek medical care if they discovered suspicious TB symptoms. Binary logistic stepwise regression analysis indicated that respondents whose family annual income per capita was 50 000–100 000¥ (OR=2.56, 95% CI: 1.44 to 4.54, p<0.01) and who had positive attitudes (≥3 scores: OR=3.10, 95% CI: 1.90 to 5.05, p<0.01) or practices (≥4 scores: OR=3.13, 95% CI: 1.82 to 5.39, p<0.01) towards TB were more willing to seek medical care for TB. Conclusions Willingness to seek medical care for TB in the elderly population can be improved according to the determinants.

Objective This study aimed to capture key epidemiological data on SARS-CoV-2 infection in Nicaraguan children (≤18 years) seeking medical care, between 6 October and 16 November 2020. Design In this cross-sectional study, 418 children were recruited: 319 with symptoms characteristic of COVID-19 and 99 with no symptoms of illness. Children were tested for SARS-CoV-2 RNA using loop-mediated isothermal amplification. A questionnaire was employed to identify symptoms, risk factors, comorbidities and COVID-19 prevention measures. Setting Research was carried out in four hospitals and two clinics in Managua, Nicaragua, where schools and businesses remained open throughout the COVID-19 pandemic. Participants Children were enrolled into a possible COVID-19 group if presenting with clinical symptoms. A comparison group included children lacking any COVID-19 symptoms attending routine check-ups or seeking care for issues unrelated to COVID-19. Results A high prevalence (43%) of SARS-CoV-2 infection was found, which was relatively equivalent in symptomatic and non-symptomatic children. Age distribution was similar between symptomatic and non-symptomatic children testing positive for SARS-CoV-2. Symptomatic children who tested positive for SARS-CoV-2 were 2.7 times more likely to have diarrhoea (26.7% in positive vs 12.0% in negative; OR=2.7 (95% CI 1.5 to 4.8), p=0.001) and were 2.0 times more likely to have myalgia (17.8% in positive vs 9.8% in negative; OR=2.0 (95% CI 1.0 to 3.8), p=0.04). Children with COVID-19 symptoms, who tested positive for SARS-CoV-2, were more likely to be under age 5 years and to have a pre-existing comorbid condition than children who tested positive but did not have symptoms. Conclusions This is the first paediatric study to provide laboratory-confirmed data on SARS-CoV-2 infection in Nicaragua, crucial for paediatric health services planning and a successful COVID-19 response. The high prevalence of the virus suggests widespread and sustained community transmission, underscoring the urgent need for robust data on the true extent of SARS-CoV-2 infection throughout Nicaragua.

Objective Until effective treatments and vaccines are made readily and widely available, preventative behavioural health measures will be central to the SARS-CoV-2 public health response. While current recommendations are grounded in general infectious disease prevention practices, it is still not entirely understood which particular behaviours or exposures meaningfully affect one’s own risk of incident SARS-CoV-2 infection. Our objective is to identify individual-level factors associated with one’s personal risk of contracting SARS-CoV-2. Design Prospective cohort study of adult participants from 26 March 2020 to 8 October 2020. Setting The COVID-19 Citizen Science Study, an international, community and mobile-based study collecting daily, weekly and monthly surveys in a prospective and time-updated manner. Participants All adult participants over the age of 18 years were eligible for enrolment. Primary outcome measure The primary outcome was incident SARS-CoV-2 infection confirmed via PCR or antigen testing. Results 28 575 unique participants contributed 2 479 149 participant-days of data across 99 different countries. Of these participants without a history of SARS-CoV-2 infection at the time of enrolment, 112 developed an incident infection. Pooled logistic regression models showed that increased age was associated with lower risk (OR 0.98 per year, 95% CI 0.97 to 1.00, p=0.019), whereas increased number of non-household contacts (OR 1.10 per 10 contacts, 95% CI 1.01 to 1.20, p=0.024), attending events of at least 10 people (OR 1.26 per 10 events, 95% CI 1.07 to 1.50, p=0.007) and restaurant visits (OR 1.95 per 10 visits, 95% CI 1.42 to 2.68, p<0.001) were associated with significantly higher risk of incident SARS-CoV-2 infection. Conclusions Our study identified three modifiable health behaviours, namely the number of non-household contacts, attending large gatherings and restaurant visits, which may meaningfully influence individual-level risk of contracting SARS-CoV-2.

Objectives Knowledge on the impact of heated tobacco product (HTP) use in pregnant women with associated maternal and neonatal risks for hypertensive disorders of pregnancy (HDP) and low birth weight (LBW) is limited. We aimed to assess the status of HTP use among pregnant women in Japan and explore the association of HTP use with HDP and LBW. Design Cross-sectional study. Setting Data from the Japan ‘COVID-19 and Society’ Internet Survey study, a web-based nationwide survey. Participants We investigated 558 postdelivery and 365 currently pregnant women in October 2020. Primary and secondary outcome measures Information on HDP and LBW was collected from the postdelivery women’s Maternal and Child Health Handbooks (maternal and newborn records). We estimated the age-adjusted ORs and 95% CIs of ever HTP smokers for HDP and LBW and compared them with those of never HTP smokers in a logistic regression analysis. Results The prevalence of ever and current HTP use were 11.7% and 2.7% in postdelivery women and 12.6% and 1.1% in currently pregnant women, respectively. Among currently pregnant women who were former combustible cigarette smokers, 4.4% (4/91) were current HTP smokers. Among postdelivery women, ever HTP smokers had a higher HDP incidence (13.8% vs 6.5%, p=0.03; age-adjusted OR=2.48, 95% CI 1.11 to 5.53) and higher LBW incidence (18.5% vs 8.9%, p=0.02; age-adjusted OR=2.36, 95% CI 1.16 to 4.87). Conclusions In Japan, the incidence of ever HTP use exceeded 10% among pregnant women, and HTP smoking may be associated with maternal and neonatal risks.

Introduction The COVID-19 pandemic has emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, very few treatment strategy has been established for patients with mild COVID-19 who do not require oxygen administration. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza. In this study, we aim to evaluate the efficacy of clarithromycin in patients with mild COVID-19. Methods and analysis This is an exploratory, multicentre, open-label, randomised controlled trial. This study was initiated in May 2021 and will end in July 2022. Patients with mild COVID-19 pneumonia who do not require oxygen administration will be enrolled and randomly assigned in a 1:1:1 ratio to group A (administration of clarithromycin 800 mg/day), group B (administration of clarithromycin 400 mg/day) or group C (standard treatment without clarithromycin). The planned number of enrolled patients is 60 (20 patients x three groups). The primary endpoint is the number of days required to improve the clinical symptoms as measured by the severity score. Secondary endpoints include days for recovery of the body temperature, proportion of patients with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers and pneumonia infiltrations. Ethics and dissemination The study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported as journal publications. Trial registration number jRCTs071210011.

Introduction The COVID-19 pandemic is likely to have a prolonged impact on mental health (MH); however, the long-term MH effects of the COVID-19 pandemic remain unknown. The Serbian national survey—CoV2Soul.RS—was launched to document the MH status of the Serbian population following the COVID-19 pandemic and to contribute to an international evidence base about MH prevalence rates during different phases of the pandemic. Methods and analysis This cross-sectional study was designed to collect a nationally representative sample (N=1200; age 18–65 years; estimated start/end—June/November 2021) using multistage probabilistic household sampling. Trained staff will conduct in-person diagnostic interviews. A battery of self-report instruments will be administered to assess the quality of life (QoL), general distress and associated protective and harmful psychological and societal factors. Analyses will be conducted to delineate the prevalence rates of MH disorders, how MH conditions and QoL vary with respect to sociodemographic variables, personality, health status and traumatic events during the COVID-19 pandemic, and to test how these relations depend on geographical region. Moreover, this study was designed to explore mechanisms linking personality and the perception of pandemic consequences and associated distress. Prevalence rates of MH disorders will be calculated using descriptive statistics. For additional analyses, we will use correlations, analysis of variance and regression analyses. The hierarchical structure of the data will be explored using multilevel random coefficient modelling. Structural equation modelling will be used to investigate the indirect effects of personality on distress through relevant variables. Ethics and dissemination Ethical Committees of the Faculty of Medicine (1322-VII/31) and Faculty of Philosophy in Belgrade (02-33/273) and Faculty of Philosophy in Novi Sad (05-27, br.893/1) approved the protocol. Only respondents able to provide informed consent will participate in the study. Research reports will be submitted to peer-reviewed journals and the results will be placed on the website www.cov2soul.rs to be available to funders, researchers, policy-makers and interested laypeople, and will be advertised through social media. Trial registration number NCT04896983.

Objectives To summarise the evidence relating to the prevalence of anxiety and depression among healthcare workers (HCWs) during the COVID-19 pandemic. Design An umbrella review of systematic reviews was undertaken using the Joanna Briggs Institute (JBI) methods. Data sources The Cochrane database of systematic reviews, JBI Evidence Synthesis, MEDLINE, Web of Science, PsycINFO, Embase and CINAHL were searched in March 2021 for reviews published in English. Eligibility criteria Systematic reviews reporting the prevalence of anxiety and depression among HCWs during the COVID-19 pandemic. Two researchers screened each abstract and independently reviewed full text articles. Study quality was assessed using the JBI critical appraisal tool for systematic reviews, and the degree of overlap in primary studies was calculated. Results Ten systematic reviews (100 unique studies), including 169 157 HCWs from 35 countries were included. The prevalence of anxiety among all HCWs ranged from 22.2% (95% CI 21.3% to 23.1%) to 33.0% (95% CI 31.9% to 34.1%). The prevalence of anxiety among physicians (n=5820) was reported to be between 17% and 19.8% and for nurses (n=14 938) between 22.8% and 27%. The prevalence of depression among all HCWs ranged from 17.9% (95% CI 17.1% to 18.8%) to 36% (95% CI 34.9% to 37.1%). The prevalence of depression among physicians (n=643) and nurses (n=8063) was reported to be 40.4% and 28%, respectively. Conclusions There is wide variation evident in the presence of anxiety and depression among HCWs. In particular, the prevalence of depression among physicians was high. Strategies to reduce the incidence of anxiety and depression are urgently required. PROSPERO registration number CRD42021238960.

Introduction Surgical site infection (SSI) is a potential complication of surgical procedure. SSI after implant surgery is a disaster both for patients and surgeons. Although predictive tools for SSI are available, none of them estimate early infection based on inflammatory blood parameters. The inflammatory process can be measured using several parameters including interleukin-6, C reactive protein, neutrophil to lymphocyte ratio, white cell count, erythrocyte sedimentation rate or procalcitonin. This systematic review aims to determine whether inflammatory blood parameters could be used as significant predictive factors for SSI after primary hip or knee arthroplasty. Methods and analysis A systematic review of randomised controlled trials, cross-sectional studies, case–control studies and cohort studies, published in English, will be searched in the following electronic bibliographic databases: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials and Web of Science. Studies performed in adult patients of all ages who underwent knee or hip arthroplasty, studies containing data on the risk/prognostic factors for preknee or postknee or hip arthroplasty SSI and studies with a minimum follow-up of 30 days after surgery will be included. A standardised form will be used to extract data from the included studies comprising study characteristics, participant characteristics, details of the intervention, study methodology and outcomes. Quality Assessment of Diagnostic Accuracy tool, second version, and Standards for Reporting of Diagnostic Accuracy Studies checklist will be used to assess risk of bias. Heterogeneity will be assessed using Cochran ² statistic and I2 statistics where applicable. Grading of Recommendations Assessment, Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be used to report findings. Ethics and dissemination No ethics approval is required. The findings will be disseminated at national and international scientific sessions, also to be published in a peer-reviewed journal. PROSPERO registration number CRD42020147925.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

CD4+ T cell subpopulations have been difficult to genetically interrogate because of shared pathways with CD8+ T cells during T cell development. Using an allele-conditioning strategy, Andrews et al. generate murine lines that temporally restrict Cre activity and gene deletion to CD4+ T conventional cells, while sparing CD4+ T regulatory cells.

Science Translational Medicine, Ahead of Print.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract Background The inappropriate use of antimicrobials for acute infectious diarrhea is widespread and leads to the problem of antimicrobial resistance. To improve the use of antimicrobials, it is first necessary to understand the actual situation of diarrheal disease and to identify potential targets for intervention. This study aimed to investigate the recent epidemiological characteristics of and antimicrobial prescriptions for acute infectious diarrhea in Japan. Methods This was a retrospective observational study of outpatients aged 0–65 years, separated into children (age 0–17 years) and adults (age 18–65 years), diagnosed with acute infectious diarrhea, using the administrative claims database of the Japan Medical Data Center from 2013 to 2018. We evaluated the number of eligible visits/number of database registrants (defined as the visit rate). The analysis of the antimicrobial prescription rate was restricted to otherwise healthy individuals diagnosed with acute infectious diarrhea alone by excluding patients with multiple disease diagnoses and with medical backgrounds of chronic bowel diseases or immunocompromised conditions. We further classified them by diagnosis of bacterial or nonbacterial acute infectious diarrhea. Results The total number of eligible visits for acute infectious diarrhea was 2,600,065. The visit rate, calculated based on the number of eligible visits by database registrants, was higher in children (boys, 0.264; girls, 0.229) than in adults (men, 0.070; women, 0.079), with peaks in early summer and winter. The peaks for visits in adults lagged those of children. In total, 482,484 visits were analyzed to determine the antimicrobial prescription rate; 456,655 (94.6%) were diagnosed with nonbacterial acute infectious diarrhea. Compared with children (boys, 0.305; girls, 0.304), the antimicrobial prescription rate was higher in adults, and there were differences between sexes in adults (men, 0.465; women, 0.408). Fosfomycin and fluoroquinolone were most frequently used for nonbacterial acute infectious diarrhea in children (44.1%) and adults (50.3%), respectively. Conclusions These results revealed overprescription of antimicrobials for acute infectious diarrhea in this administrative claims database in Japan and contribute to the development of antimicrobial stewardship strategies and the identification of targets for efficiently reducing inappropriate antimicrobial use.

Abstract Background The diagnosis of tuberculosis (TB) using smear microscopy has been based on testing two specimens: one spot and one early morning sputa. Recently, the World Health Organization (WHO) has recommended to replace, whenever possible, microscopy with GeneXpert® MTB/RIF performed on a single specimen. However, as the bacterial load is higher in early morning specimens than in spot specimens, one could expect lower sensitivity of GeneXpert® MTB/RIF performed only on spot specimens. In this study, we compared results of GeneXpert® MTB/RIF on spot specimens versus early morning specimens, under programmatic conditions in Cotonou, Benin. Methods From June to September 2018, all sputa received from presumptive TB patients at the Supranational Reference Laboratory for Tuberculosis of Cotonou were included in the study. From each patient, two specimens were collected (one spot and one early morning) and GeneXpert® MTB/RIF was performed on both specimens. Results In total, 886 participants were included in the study, of whom 737 provided both sputa and 149 (16.8%) gave only the spot specimen. For the 737 participants who provided both sputa, GeneXpert® MTB/RIF was positive for both specimens in 152 participants; for three participants GeneXpert® MTB/RIF was positive on spot specimen but negative on morning specimen while for another three, the test was positive on morning specimen but negative on spot specimen. The overall percentage of agreement was excellent (99.2%) with a positive and negative percent agreement greater than 98%. Conclusion For TB diagnosis under programmatic conditions in Cotonou, GeneXpert® MTB/RIF in spot specimens gave similar results with the test in morning specimens. Performing GeneXpert® MTB/RIF in both specimens did not significantly increase the number of cases detected. To avoid losing patients from the diagnostic cascade, it is preferable to test sputa produced at the time of the first visit at the health center.

Abstract Background Studies show men who have sex with men (MSM) practising receptive anal sex are more likely to present with secondary syphilis, suggesting anorectal primary lesions are being missed. Regular anal self-examination might be able to detect anorectal syphilis lesions, hence potentially reducing transmission. This study aimed to explore the attitudes of MSM on performing anal self-examination to detect primary syphilis. Methods In this qualitative study, 20 MSM over 18 years of age were purposively sampled from a sexual health clinic to participate in semi-structured interviews. Interviews were recorded, transcribed verbatim and data analysed thematically. Results Four major themes and 12 sub-themes were generated from the study: (1) reasons for performing anal self-examination, (2) preferred educational resources for anal self-examination, (3) attitudes towards partner anal examination, and (4) acceptability of anal self-examination. Most participants had performed some form of anal self-examination in the past, and, just over half performed regularly for mostly health-related concerns. Most participants who infrequently or never performed anal self-examination were agreeable to perform regularly if it was recommended by health professionals with appropriate guidance. Participants preferred education on anal self-examination from health professionals and trusted online learning resources. Conclusion Our study showed MSM were agreeable to anal self-examination however would like to receive education and training to gain more confidence in conducting anal self-examination as a screening tool. Further studies are required to explore the adherence and acceptability of anal self-examination for syphilis prior to studies examining efficacy. The study provides foundation for any future policy aiming at utilising anal self-examination as a screening tool for syphilis among MSM.

Abstract Background Dengue fever is a common mosquito borne viral infection. Severe dengue fever associated severe hepatitis carries high mortality. Based on the beneficial effect of N-acetylcysteine (NAC) in paracetamol poisoning and non-acetaminophen induced liver failure, it is used in dengue fever associated hepatitis in clinical practice. We aim to study the reversal of liver enzymes with NAC in the setting of severe hepatitis due to severe dengue infection. Methods A retrospective analysis was conducted on hospitalized 30 adults with severe dengue fever with severe hepatitis. These 30 patients had aspartate transaminase (AST) and alanine transaminases (ALT) more than 500 U/L and/or PT INR (prothrombin time and international normalized ratio) more than 1.5. They were treated with NAC infusion of 100 mg/h for 3 to 5 days. Results The mean age of the group was 49.9 ± 11.46 years and 18 (60%) patients were males. Nineteen patients (63%) developed dengue shock. Of them 12 patients (40%) developed hepatic encephalopathy. Median AST on the day of administration of NAC was 1125 U/L interquartile range (IQR) 1653.25 while median ALT was 752 (IQR 459.25). There was a statistically significant reduction of both ALT (p = 0.034) and AST (p = 0.049) from day 1 to 4 after NAC infusion. Rise of platelet count between day 1 and day 4 also showed statistically significant difference (p = 0.011) but the reduction of prothrombin time and international normalized ratio (PT/INR) from 1 to day 4 did not show statistical significance difference. Mean duration of treatment with NAC was 3.61 ± 0.75 days while mean length of hospital stay was 6.2 ± 1.27 days. Only one patient died (3.3%). None of the patients reported adverse drug reaction due to NAC. Conclusion Majority of patients demonstrated marked clinical and biochemical improvements and they recovered fully. We observed faster and significant recovery of liver enzymes following administration of NAC. Based on the above findings, this study provides preliminary evidence for the beneficial effect of NAC in severe hepatitis in dengue infection with greater survival benefits.

Abstract Background South Africa has not achieved the 90–90–90 goals, in part due to low rates of antiretroviral therapy (ART) initiation among those aware of their HIV status. Perceived risk of HIV at the time of testing may affect likelihood of rapid ART initiation. The purpose of this study was to evaluate factors associated with perceived risk of HIV and the relationship between perceived HIV risk and rapid ART initiation during the universal test and treat era which was adapted in October 2016. Methods We conducted a prospective study of adults undergoing HIV testing from October 2016–February 2019 at Ithembalabantu Clinic in Durban. Eligible participants reported not previously being diagnosed with HIV. Before HIV testing, participants were asked to assess their perceived HIV risk on a four-level scale. We categorized “definitely not” and “probably not going to acquire HIV” as a low perceived risk, and “probably will” and “definitely will become HIV-infected” as a high perceived risk of HIV infection. Participants were followed for up to 14 months following HIV testing to assess ART initiation. Results Among 1519 people newly diagnosed with HIV, 55% were female and mean age was 33 years. Among those, 1382 (90.9%) had a high HIV risk perception and 137 (9.1%) reported low HIV risk perception. In the low risk group individuals were more likely to be female (58% vs 55%), unemployed (62% vs 59%), have a partner with unknown HIV status (61% vs 55%) compared to the high risk group. 83.2% of those with low HIV risk perception reported previously HIV testing compared 91.5% of those with high HIV risk perception. In the multivariate model, males were associated with a higher chances of initiating ART compared to females (adjusted hazard ratio (aHR): 1.187, CI 1.187 (1.060–1.329) and being unemployed (aHR 0.767 CI (0.650–0.905). Those with a low HIV risk perception were less likely to initiate ART 125 (91%) vs 1310 (95%) p = 0.022), and took longer to initiate on ART after HIV diagnosis (11 days’ vs 4 days, p = 0.042). Conclusion Factors associated with high HIV risk perception included being unemployed, single, and having a partner of unknown HIV status. People living with HIV (PLHIV) in South Africa who had a low self-perceived risk to HIV infection were less likely to initiate ART. Assessing self-perceived risk of HIV infection may help direct counselling and improve ART initiation to achieve universal 90–90–90 goal.

Abstract Background Retention of pregnant and breastfeeding women and their infants in HIV care still remains low in Uganda. Recent literature has shown that the effects of COVID-19 mitigation measures may increase disease burden of common illnesses including HIV, Tuberculosis, Malaria and other key public health outcomes such as maternal mortality. A research program was undertaken to locate disengaged HIV positive women on option B+ and supported them to reengage in care. A 1 year follow up done following the tracing revealed that some women still disengaged from care. We aimed to establish the barriers to and facilitators for reengagement in care among previously traced women on option B+, and how these could have been impacted by the COVID-19 pandemic. Methods This was a cross sectional qualitative study using individual interviews conducted in June and July, 2020, a period when the COVID-19 response measures such as lockdown and restrictions on transport were being observed in Uganda. Study participants were drawn from nine peri-urban and rural public healthcare facilities. Purposive sampling was used to select women still engaged in and those who disengaged from care approximately after 1 year since they were last contacted. Seventeen participants were included. Data was analysed using the content analysis approach. Results Women reported various barriers that affected their reengagement and retention in care during the COVID-19 pandemic. These included structural barriers such as transport difficulties and financial constraints; clinical barriers which included unsupportive healthcare workers, short supply of drugs, clinic delays, lack of privacy and medicine side effects; and psychosocial barriers such as perceived or experienced stigma and non-disclosure of HIV sero-status. Supportive structures such as family, community-based medicine distribution models, and a friendly healthcare environment were key facilitators to retention in care among this group. The COVID-19 pandemic was reported to exacerbate the barriers to retention in care. Conclusions COVID-19 may exacerbate barriers to retention in HIV care among those who have experienced previous disengagement. We recommend community-based models such as drop out centres, peer facilitated distribution and community outreaches as alternative measures for access to ART during the COVID-19 pandemic.

Abstract Background The World Health Organization (WHO) has ranked dengue as one of the top ten threats to Global health in 2019. Sri Lanka faced a massive dengue epidemic in 2017, the largest outbreak in the country during the last three decades, consisting of 186,101 reported cases, and over 320 deaths. The epidemic was controlled by intense measures taken by the health sector. However, the reported dengue cases and dengue deaths in 2019 were significantly higher than that of 2018. Deaths were mostly due to delay in hospitalization of severe dengue patients. The mortality of dengue hemorrhagic fever is 2–5% if detected early and treated promptly, but is high as 20% if left untreated. Methods A descriptive cross-sectional study was done among patients with dengue fever presenting to the Sri Jayawardenepura General Hospital during October 2019. Data was collected using a questionnaire comprising 20 questions based on knowledge, attitudes and practices on dengue, which were categorized into questions on awareness of mortality and severity of dengue burden, prevention of dengue vector mosquito breeding and acquiring the infection, patient’s role in dengue management, and warning signs requiring prompt hospitalization. Results The mean KAP score on all questions was 55%, while a majority of 65.2% patients scored moderate KAP scores (50–75%) on all questions, and only 7.6% had high KAP scores (> 75%). The highest categorical mean score of 62% was on awareness of dengue prevention, followed by 54% on awareness of dengue burden, and only 51% on dengue management. Only 5.3% patients scored high scores on awareness of dengue management, followed by 28.5%, and 40.9% patients scoring high scores on awareness of dengue burden, and awareness of prevention of dengue respectively. The mean KAP scores on all questions increased with increasing age category. Conclusion The population relatively has a better awareness of dengue prevention, as compared to awareness of dengue mortality and dengue management. The identified weak point is patient awareness of the patients’ role in dengue management, and identifying warning signs requiring prompt hospitalization. This results in delay in treatment, which is a major cause for increased mortality. There was a correlation between those who had good knowledge on dengue burden and those who were aware of patients’ role in dengue management. An action plan should be implemented to improve public awareness through education programs on the role of the public and patients in dengue management to drive a better outcome.

Abstract Background Multidrug-resistant (MDR) Klebsiella pneumoniae infections, from pancreatic infections to bloodstream infections, influence the mortality of patients with acute pancreatitis (AP) on the condition of limited antibiotic choices. The aim of this study was to investigate the predictor of mortality among AP patients complicated with MDR-K. pneumoniae infections. Methods Seventy-one AP patients who occurred MDR-K. pneumoniae infections from August 1st, 2016 to August 1st, 2020 were enrolled. MDR-K. pneumoniae was defined as the K. pneumoniae strain non-susceptible to at least one agent in three or more antimicrobial categories. MDR-K. pneumoniae isolates were confirmed by Vitek-2 system. Antibiotic susceptibility test was carried out using a micro broth dilution method. Clinical characteristics and drug-resistance rates were retrospectively reviewed, and the predictors of mortality were evaluated by univariate and multivariate analyses. Results The mortality rate of AP patients complicated with MDR-K. pneumoniae infections reached 46.5% (33 of 71), and pancreas (n = 53) was the most common site of MDR-K pneumoniae strains. The drug resistance rates of MDR-K. pneumoniae were high to 11 of 12 common antibiotics (more than 50.0%) except of tigecycline (23.9%). The predictor independently associated with mortality was septic shock (hazard ratio 2.959, 95% confidence intervals 1.396 – 6.272, P = 0.005). Conclusions More attention should be paid for pancreatic MDR-K. pneumoniae infections among AP patients The predictor for mortality of AP patients complicated with MDR-K. pneumoniae infection is septic shock. Therefore, further clinical investigations should focus on areas against septic shock.

Smallpox is one of the most devastating diseases known to mankind. Its deadly hold, now vanished from the face of the earth thanks to a large-scale eradication campaign launched by the World Health Organization (WHO) in 1967, has since become a subject of medical, epidemiological and historical interest for the scientific community [1]. Ancient biological remains have been investigated for variola virus (VARV) DNA, broadening our knowledge on its evolutionary history in medieval/modern Northern Europe and modern Siberia [2-4]; however, we are still unable to estimate efficiently its presence in ancient urban or rural populations from Western Europe.

The recent discovery of pangenotypic oral direct-acting antivirals (DAAs) has resulted in significantly improved treatment for hepatitis C virus (HCV) infection, with sustained virologic response rates reaching above 90%-95% after 8-12 weeks of treatment (Asselah, Marcellin, & Schinazi, 2018; Liang & Ghany, 2013). The availability of pangenotypic DAAs with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. However, HCV still has high prevalence worldwide and is one of the major causes of chronic liver diseases (Polaris Observatory, 2017).

To better understand B cell responses to SARS-CoV-2 mRNA vaccination, Sokal et al. analyzed memory B cells from COVID-19-recovered and -naive individuals. In recovered patients, vaccination amplifies a broad repertoire of matured MBCs and generates variant-neutralizing plasma cells. In naïve individuals, vaccination induces an MBC pool containing potent neutralizing clones against all current variants of concern, including beta and delta.