Targeting specific checkpoints in the management of SARS-CoV-2 induced cytokine storm

COVID-19-infected patients require an intact immune system to suppress viral replication and prevent complications. However, the complications of SARS-CoV-2 infection that led to death were linked to the overproduction of proinflammatory cytokines known as cytokine storm syndrome. This article reported the various checkpoints targeted to manage the SARS-CoV-2-induced cytokine storm. The literature search was carried out using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Journal articles that discussed SARS-CoV-2 infection and cytokine storm were retrieved and appraised. Specific checkpoints identified in managing SARS-CoV-2 induced cytokine storm include a decrease in the level of Nod-Like Receptor 3 (NLRP3) inflammasome where drugs such as quercetin and anakinra were effective. Janus kinase-2 and signal transducer and activator of transcription-1 (JAK2/STAT1) signaling pathways were blocked by medicines such as tocilizumab, baricitinib, and quercetin. In addition, inhibition of interleukin (IL)-6 with dexamethasone, tocilizumab, and sarilumab effectively treats cytokine storm and significantly reduces mortality caused by COVID-19. Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial. These agents' overall mechanisms of action involve a decrease in circulating proinflammatory chemokines and cytokines and or blockade of their receptors. Consequently, the actions of these drugs significantly improve respiration and raise lymphocyte count and PaO2/FiO2 ratio. Targeting cytokine storms' pathogenesis genetic and molecular apparatus will substantially enhance lung function and reduce mortality due to the COVID-19 pandemic.https://www.mdpi.com/journal/lifeam2023Pharmacolog

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Cervical cancer risk factors and screening preferences among Muslim women in Monrovia, Liberia

Cervical cancer is the most common cancer in reproductive aged women in Liberia. Lack of awareness and screening capacity are both major contributors to the prevalence of this disease. The minority Muslim population in this country is largely unscreened. The objective of the study was to assess cervical cancer risk factors and screening preferences among Muslim women living in Monrovia, Liberia and to offer self-screening with HPV testing. A multiple step implementation strategy was devised in order to outreach to the Muslim population with the engagement of community and religious leaders, about an upcoming screening program and informational session at a local clinic. Over 150 Muslim women attended the session, 120 completed the HPV screening, and 55 women completed the questionnaires. Questionnaire data revealed overall low risk factors for cervical cancer, but also low use of family planning as well as low knowledge about cervical cancer and HPV. Participants showed an interest in screening and a majority preferred self-collected tests. These preferences should be incorporated in future programming. To engage minority populations in screening programs, there may be success with targeted messages, involvement of community religious leaders, and eliciting feedback to incorporate preferred strategies and improve participation and programming. Keywords: HPV screening, Muslim, cervical cancer &nbsp; Le cancer du col de l'utérus est le cancer le plus courant chez les femmes en âge de procréer au Libéria. Le manque de sensibilisation et de capacité de dépistage sont tous deux des facteurs majeurs de la prévalence de cette maladie. La population musulmane minoritaire de ce pays est largement non filtrée. L'objectif de l'étude était d'évaluer les facteurs de risque de cancer du col de l'utérus et les préférences en matière de dépistage chez les femmes musulmanes vivant à Monrovia, au Libéria, et de proposer un auto-dépistage avec des tests HPV. Une stratégie de mise en oeuvre en plusieurs étapes a été élaborée afin de sensibiliser la population musulmane avec l'engagement des chefs communautaires et religieux, sur un programme de dépistage à venir et une séance d'information dans une clinique locale. Plus de 150 femmes musulmanes ont assisté à la session, 120 ont terminé le dépistage du VPH et 55 femmes ont rempli les questionnaires. Les données du questionnaire ont révélé des facteurs de risque globalement faibles pour le cancer du col de l'utérus, mais aussi une faible utilisation de la planification familiale ainsi qu'une faible connaissance du cancer du col de l'utérus et du VPH. Les participants ont montré un intérêt pour le dépistage et une majorité préféraient les tests auto-collectés. Ces préférences devraient être incorporées dans la programmation future. Pour impliquer les populations minoritaires dans les programmes de dépistage, il peut y avoir du succès avec des messages ciblés, la participation des chefs religieux de la communauté et l'obtention de commentaires pour intégrer les stratégies préférées et améliorer la participation et la programmation. Mots-clés: Dépistage du VPH chez les femmes musulmanes Libéri

Implementation status of national tuberculosis infection control guidelines in Bangladeshi hospitals.

In response to the World Health Organization (WHO) recommendation to reduce healthcare workers' (HCWs') exposure to tuberculosis (TB) in health settings, congregate settings, and households, the national TB control program of Bangladesh developed guidelines for TB infection prevention and control (IPC) in 2011. This study aimed to assess the implementation of the TB IPC healthcare measures in health settings in Bangladesh. Between February and June 2018, we conducted a mixed-method study at 11 health settings. The team conducted 59 key-informant interviews with HCWs to understand the status of and barriers impeding the implementation of the TB IPC guidelines. The team also performed a facility assessment survey and examined TB IPC practices. Most HCWs were unaware of the national TB IPC guidelines. There were no TB IPC plans or committees at the health settings. Further, a presumptive pulmonary TB patient triage checklist was absent in all health settings. However, during facility assessment, we observed patient triaging and separation in the TB specialty hospitals. Routine cough-etiquette advice was provided to the TB patients mentioned during the key-informant interviews, which was consistent with findings from the survey. This study identified poor implementation of TB IPC measures in health settings. Limited knowledge of the guidelines resulted in poor implementation of the recommendations. Interventions focusing on the dissemination of the TB IPC guidelines to HCWs along with regular training may improve compliance. Such initiatives should be taken by hospital senior leadership as well as national policy makers

A tuberculin skin test survey among healthcare workers in two public tertiary care hospitals in Bangladesh.

In Bangladesh, there is currently no data on the burden of latent TB infection (LTBI) amongst hospital healthcare workers (HCWs). This study aimed to determine the prevalence of LTBI and compare the prevalence among HCWs in two public tertiary care hospitals. Between September 2018 and August 2019, we conducted a cross-sectional study in two public tertiary care general hospitals. Using a survey and tuberculin skin test (TST), we assessed risk factors for LTBI, adjusting for known and plausible confounders. In addition, a facility assessment was undertaken to understand the implementation of relevant IPC measures. The prevalence of LTBI among HCWs was 42%. HCWs spent a median of 6 hours (SD = 1.76, IQR 2.00) per day and attended an average of 1.87 pulmonary TB patients per week. HCWs did not receive any TB IPC training, the wards lacked a symptom checklist to screen patients for TB, and no masks were available for coughing patients. Seventy-seven percent reportedly did not use any facial protection (masks or respirators) while caring for patients. In the multivariable model adjusting for hospital level clustering effect, TST positivity was significantly higher among HCWs aged 35-45 years (aOR1.36, 95% CI: 1.06-1.73) and with >3 years of service (aOR 1.67, 95% CI: 1.62-1.72). HCWs working in the medicine ward had 3.65 (95% CI: 2.20-6.05) times, and HCWs in the gynecology and obstetrics ward had 2.46 (95% CI: 1.42-4.27) times higher odds of TST positivity compared to HCWs working in administrative areas. This study identified high prevalence of LTBI among HCWs. This may be due to the level of exposure to pulmonary TB patients, and/or limited use of personal protective equipment along with poor implementation of TB IPC in the hospitals. Considering the high prevalence of LTBI, we recommend the national TB program consider providing preventative therapy to the HCWs as the high-risk group, and implement TB IPC in the hospitals

Invasive Fungal Infections in Under-Five Diarrheal Children: Experience from an Urban Diarrheal Disease Hospital

Invasive fungal infections (IFIs) are opportunistic, especially in immunocompromised and hospitalized patients. Children with IFIs are more vulnerable to a fatal outcome. For early diagnosis and treatment, knowledge of the spectrum and frequency of IFIs among children is prerequisite. In this prospective observational study, we enrolled 168 children of 2–59 months old of either sex from March 2018 to December 2019 admitted to the Dhaka hospital, icddr,b. Study participants with suspected IFIs were with or without severe acute malnutrition (SAM) along with sepsis/pneumonia and fulfilled any of the following criteria: (i) failure to respond to injectable antibiotics, (ii) development of a late-onset hospital-acquired infection, (iii) needed ICU care for >7 days, (iv) took steroids/antibiotics for >2 weeks before hospitalization, and (v) developed thrush after taking injectable antibiotics. The comparison group included non-SAM (weight-for-length Z score ≥ −2) children with diarrhea and fever p = 0.013) and had a higher death rate (46.7% vs. 8.9%; p p = 0.042) after adjusting for potential confounders. Our findings thus implicate that, malnourished children with septic shock require targeted screening for the early diagnosis and prompt management of IFIs that may help to reduce IFIs related deaths

Examining pulmonary TB patient management and healthcare workers exposures in two public tertiary care hospitals, Bangladesh.

Implementation of tuberculosis (TB) infection prevention and control (IPC) guidelines in public tertiary care general hospitals remain challenging due to limited evidence of pulmonary TB (PTB) patients' duration of hospital stay and management. To fill this evidence gap, this study examined adult PTB patient management, healthcare workers' (HCWs) exposures and IPC practices in two public tertiary care hospitals in Bangladesh.Between December 2017 and September 2019, a multidisciplinary team conducted structured observations, a hospital record review, and in-depth interviews with hospital staff from four adult medicine wards.Over 20 months, we identified 1,200 presumptive TB patients through the hospital record review, of whom 263 were confirmed PTB patients who stayed in the hospital, a median of 4.7 days without TB treatment and possibly contaminated the inpatients wards. Over 141 observation hours, we found a median of 3.35 occupants present per 10 m2 of floor space and recorded a total of 17,085 coughs and 316 sneezes: a median of 3.9 coughs or sneezes per 10 m2 per hour per ward. Only 8.4% of coughs and 21% of sneezes were covered by cloths, paper, tissues, or by hand. The HCWs reportedly could not isolate the TB patients due to limited resources and space and could not provide them with a mask. Further, patients and HCWs did not wear any respirators.The study identified that most TB patients stayed in the hospitals untreated for some duration of time. These PTB patients frequently coughed and sneezed without any facial protection that potentially contaminated the ward environment and put everyone, including the HCWs, at risk of TB infection. Interventions that target TB patients screening on admission, isolation of presumptive TB patients, respiratory hygiene, and HCWs' use of personal protective equipment need to be enhanced and evaluated for acceptability, practicality and scale-up