Novel intervention to promote COVID-19 protective behaviours among Black and South Asian communities in the UK: protocol for a mixed-methods pilot evaluation.

INTRODUCTION: Culturally appropriate interventions to promote COVID-19 health protective measures among Black and South Asian communities in the UK are needed. We aim to carry out a preliminary evaluation of an intervention to reduce risk of COVID-19 comprising a short film and electronic leaflet. METHODS AND ANALYSIS: This mixed methods study comprises (1) a focus group to understand how people from the relevant communities interpret and understand the intervention's messages, (2) a before-and-after questionnaire study examining the extent to which the intervention changes intentions and confidence to carry out COVID-19 protective behaviours and (3) a further qualitative study exploring the views of Black and South Asian people of the intervention and the experiences of health professionals offering the intervention. Participants will be recruited through general practices. Data collection will be carried out in the community. ETHICS AND DISSEMINATION: The study received Health Research Authority approval in June 2021 (Research Ethics Committee Reference 21/LO/0452). All participants provided informed consent. As well as publishing the findings in peer-reviewed journals, we will disseminate the findings through the UK Health Security Agency, NHS England and the Office for Health Improvement and Disparities and ensure culturally appropriate messaging for participants and other members of the target groups.

A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings.

BACKGROUND: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19. METHODS: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences. RESULTS: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more ß-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001). CONCLUSIONS: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.

Host-directed therapies for COVID-19.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus-2-induced hyperinflammation is a major cause of death or end-organ dysfunction in COVID-19 patients. We review adjunct host-directed therapies (HDTs) for COVID-19 management. RECENT FINDINGS: The use of umbilical cord-derived mesenchymal stem cells as HDT for COVID-19 has been shown to be safe in phase 1 and 2 trials. Trials of anti-interleukin-6 receptor antibodies show promising mortality benefit in hospitalized COVID-19 patients. Repurposed drugs and monoclonal antibodies targeting specific cytokines acting on different aspects of the pro- and anti-inflammatory cascades are under evaluation. SUMMARY: A range of HDTs shows promise for reducing mortality and improving long term disability in patients with severe COVID-19, and require evaluation in randomized, controlled trials.

Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

Mass gathering events and transmission of respiratory tract infections: updates pre and post COVID-19 lockdown.

PURPOSE OF REVIEW: This article reviews the epidemiology and transmission of respiratory tract infections (RTIs) during mass gathering events (MGEs) before and during the COVID-19 pandemic. RECENT FINDINGS: RTIs of viral cause such as influenza, rhinovirus and coronaviruses (229E, HKU1, OC43) are common in MGEs. No cases of MERS-CoV have yet been identified in pilgrims during Hajj, despite the fact that MERS-CoV continues to circulate in the Middle East. Due to the COVID-19 pandemic, organizers of mass gathering religious and sporting events have implemented risk-based infection control measures and lockdowns that limited transmission of RTIs. SUMMARY: Large-scale RTI outbreaks at MGEs are uncommon due to more robust public health planning, prevention, risk assessment and improved health infrastructures in host countries during the COVID-19 pandemic.

The disproportionate case-fatality ratio of COVID-19 between countries with the highest vaccination rates and the rest of the world.

Objectives: The global reported cumulative case-fatality ratios (rCFRs) and excess mortality rates of the 20 countries with the highest coronavirus disease 2019 (COVID-19) vaccination rates, the rest of the world and Sub-Saharan Africa (SSA) were compared before and after the commencement of vaccination programmes. Methods: A time series model was used to understand the trend of rCFR over time, and a generalized linear mixed model was used to understand the effect of vaccination on rCFR. Results: By 31 December 2022, an average of 260.3 doses of COVID-19 vaccine per 100 population had been administered in the top 20 vaccinated countries, compared with 152.1 doses in the rest of the world and 51.2 doses in SSA. The mean rCFR of COVID-19 had decreased by 69.0% in the top 20 vaccinated countries, 26.5% in the rest of the world and 7.6% in SSA. Excess mortality had decreased by 48.7% in the top 20 vaccinated countries, compared with 62.5% in the rest of the world and 60.7% in SSA. In a generalized linear mixed model, the reported number of vaccine doses administered (/100 population) (odds ratio 0.64) was associated with a steeper reduction in COVID-19 rCFR. Conclusions: Vaccine equity and faster roll-out across the world is critically important in reducing COVID-19 transmission and CFR.

Middle East respiratory syndrome coronavirus-a 10-year (2012-2022) global analysis of human and camel infections, genomic sequences, lineages, and geographical origins.

OBJECTIVES: The World Health Organization priority zoonotic pathogen Middle East respiratory syndrome (MERS) coronavirus (CoV) has a high case fatality rate in humans and circulates in camels worldwide. METHODS: We performed a global analysis of human and camel MERS-CoV infections, epidemiology, genomic sequences, clades, lineages, and geographical origins for the period January 1, 2012 to August 3, 2022. MERS-CoV Surface gene sequences (4061 bp) were extracted from GenBank, and a phylogenetic maximum likelihood tree was constructed. RESULTS: As of August 2022, 2591 human MERS cases from 26 countries were reported to the World Health Organization (Saudi Arabia, 2184 cases, including 813 deaths [case fatality rate: 37.2%]) Although declining in numbers, MERS cases continue to be reported from the Middle East. A total of 728 MERS-CoV genomes were identified (the largest numbers were from Saudi Arabia [222: human = 146, camels = 76] and the United Arab Emirates [176: human = 21, camels = 155]). A total of 501 'S'-gene sequences were used for phylogenetic tree construction (camels [n = 264], humans [n = 226], bats [n = 8], other [n=3]). Three MERS-CoV clades were identified: clade B, which is the largest, followed by clade A and clade C. Of the 462 clade B lineages, lineage 5 was predominant (n = 177). CONCLUSION: MERS-CoV remains a threat to global health security. MERS-CoV variants continue circulating in humans and camels. The recombination rates indicate co-infections with different MERS-CoV lineages. Proactive surveillance of MERS-CoV infections and variants of concern in camels and humans worldwide, and development of a MERS vaccine, are essential for epidemic preparedness.

The association between acid-base status and clinical outcome in critically ill COVID-19 patients admitted to intensive care unit with an emphasis on high anion gap metabolic acidosis.

OBJECTIVE: The aim of this study was to identify arterial blood gas (ABG) abnormalities, with a focus on a high anion gap (AG) metabolic acidosis and evaluate outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU. METHODS: A retrospective, observational study was conducted in a tertiary hospital in Cape Town during the first and second COVID-19 waves. Age, gender, sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3std), pH, partial pressure of carbon dioxide (pCO2), creatinine, estimated glomerular filtration rate (eGFR), lactate levels and ABG results were obtained. The Pearson χ2 test or Fisher exact test and the Wilcoxon rank-sum test were used to compare mortality and survival. To identify factors associated with non-survival, a multivariable model was developed. RESULTS: This study included 465 patients, 226 (48%) of whom were female. The sample population's median (IQR) age was 54.2 (46.1-61.3) years, and 63% of the patients died. ABG analyses found that 283 (61%) of the 465 patients had alkalosis (pH ≥ 7.45), 65 (14%) had acidosis (pH ≤ 7.35) and 117 (25%) had normal pH (7.35-7.45). In the group with alkalosis, 199 (70.3%) had a metabolic alkalosis and in the group with acidosis, 42 (64%) had a metabolic acidosis with an increased AG of more than 17. Non-survivors were older than survivors (56.4 years versus 50.3 years, p < .001). CONCLUSION: Most of the COVID-19 patients admitted to the ICU had an alkalosis, and those with acidosis had a much worse prognosis. Higher AG metabolic acidosis was not associated with patients' characteristics.

Monkeypox: another test for PCR.

Monkeypox was declared a public health emergency of international concern by the World Health Organization (WHO) on 23 July 2022. Between 1 January and 23 July 2022, 16,016 laboratory confirmed cases of monkeypox and five deaths were reported to WHO from 75 countries on all continents. Public health authorities are proactively identifying cases and tracing their contacts to contain its spread. As with COVID-19, PCR is the only method capable of being deployed at sufficient speed to provide timely feedback on any public health interventions. However, at this point, there is little information on how those PCR assays are being standardised between laboratories. A likely reason is that testing is still limited on a global scale and that detection, not quantification, of monkeypox virus DNA is the main clinical requirement. Yet we should not be complacent about PCR performance. As testing requirements increase rapidly and specimens become more diverse, it would be prudent to ensure PCR accuracy from the outset to support harmonisation and ease regulatory conformance. Lessons from COVID-19 should aid implementation with appropriate material, documentary and methodological standards offering dynamic mechanisms to ensure testing that most accurately guides public health decisions.

Global and regional governance of One Health and implications for global health security.

The apparent failure of global health security to prevent or prepare for the COVID-19 pandemic has highlighted the need for closer cooperation between human, animal (domestic and wildlife), and environmental health sectors. However, the many institutions, processes, regulatory frameworks, and legal instruments with direct and indirect roles in the global governance of One Health have led to a fragmented, global, multilateral health security architecture. We explore four challenges: first, the sectoral, professional, and institutional silos and tensions existing between human, animal, and environmental health; second, the challenge that the international legal system, state sovereignty, and existing legal instruments pose for the governance of One Health; third, the power dynamics and asymmetry in power between countries represented in multilateral institutions and their impact on priority setting; and finally, the current financing mechanisms that predominantly focus on response to crises, and the chronic underinvestment for epidemic and emergency prevention, mitigation, and preparedness activities. We illustrate the global and regional dimensions to these four challenges and how they relate to national needs and priorities through three case studies on compulsory licensing, the governance of water resources in the Lake Chad Basin, and the desert locust infestation in east Africa. Finally, we propose 12 recommendations for the global community to address these challenges. Despite its broad and holistic agenda, One Health continues to be dominated by human and domestic animal health experts. Substantial efforts should be made to address the social-ecological drivers of health emergencies including outbreaks of emerging, re-emerging, and endemic infectious diseases. These drivers include climate change, biodiversity loss, and land-use change, and therefore require effective and enforceable legislation, investment, capacity building, and integration of other sectors and professionals beyond health.

A global analysis of One Health Networks and the proliferation of One Health collaborations.

There has been a renewed focus on threats to the human-animal-environment interface as a result of the COVID-19 pandemic, and investments in One Health collaborations are expected to increase. Efforts to monitor the development of One Health Networks (OHNs) are essential to avoid duplication or misalignment of investments. This Series paper shows the global distribution of existing OHNs and assesses their collective characteristics to identify potential deficits in the ways OHNs have formed and to help increase the effectiveness of investments. We searched PubMed, Google, Google Scholar, and relevant conference websites for potential OHNs and identified 184 worldwide for further analysis. We developed four case studies to show important findings from our research and exemplify best practices in One Health operationalisation. Our findings show that, although more OHNs were formed in the past 10 years than in the preceding decade, investment in OHNs has not been equitably distributed; more OHNs are formed and headquartered in Europe than in any other region, and emerging infections and novel pathogens were the priority focus area for most OHNs, with fewer OHNs focusing on other important hazards and pressing threats to health security. We found substantial deficits in the OHNs collaboration model regarding the diversity of stakeholder and sector representation, which we argue impedes effective and equitable OHN formation and contributes to other imbalances in OHN distribution and priorities. These findings are supported by previous evidence that shows the skewed investment in One Health thus far. The increased attention to One Health after the COVID-19 pandemic is an opportunity to focus efforts and resources to areas that need them most. Analyses, such as this Series paper, should be used to establish databases and repositories of OHNs worldwide. Increased attention should then be given to understanding existing resource allocation and distribution patterns, establish more egalitarian networks that encompass the breadth of One Health issues, and serve communities most affected by emerging, re-emerging, or endemic threats at the human-animal-environment interface.

How prepared is the world? Identifying weaknesses in existing assessment frameworks for global health security through a One Health approach.

The COVID-19 pandemic has exposed faults in the way we assess preparedness and response capacities for public health emergencies. Existing frameworks are limited in scope, and do not sufficiently consider complex social, economic, political, regulatory, and ecological factors. One Health, through its focus on the links among humans, animals, and ecosystems, is a valuable approach through which existing assessment frameworks can be analysed and new ways forward proposed. Although in the past few years advances have been made in assessment tools such as the International Health Regulations Joint External Evaluation, a rapid and radical increase in ambition is required. To sufficiently account for the range of complex systems in which health emergencies occur, assessments should consider how problems are defined across stakeholders and the wider sociopolitical environments in which structures and institutions operate. Current frameworks do little to consider anthropogenic factors in disease emergence or address the full array of health security hazards across the social-ecological system. A complex and interdependent set of challenges threaten human, animal, and ecosystem health, and we cannot afford to overlook important contextual factors, or the determinants of these shared threats. Health security assessment frameworks should therefore ensure that the process undertaken to prioritise and build capacity adheres to core One Health principles and that interventions and outcomes are assessed in terms of added value, trade-offs, and cobenefits across human, animal, and environmental health systems.

Incidental Tuberculosis in sudden, unexpected, and violent deaths in the community Lusaka, Zambia - A descriptive forensic post-mortem examination study.

OBJECTIVES: Tuberculosis remains a global emergency. In Zambia only 55% of tuberculosis cases are diagnosed. We performed a study to determine incidental cases of tuberculosis seen at forensic autopsy of individuals who died suddenly and unexpectedly in the community in Lusaka, Zambia. METHODS: Whole-body autopsies were performed according to Standard Operating Procedures. Representative samples obtained from relevant organs were subjected to pathological examination. Information on circumstances surrounding the death was obtained. Data on patient demographics, gross and microscopic pathological findings, and cause(s) of death were analysed. RESULTS: Incidental tuberculosis was found in 52 cases (45 male, 7 female, age range 14-66) out of 4286 whole-body autopsies. 41/52 (80%) were aged 21-50 years. One was a 14-year old boy who died during a football match. 39/52 (75%) deaths were attributable specifically to tuberculosis only. Other deaths were due to acute alcohol intoxication(4), violence(7), ruptured ectopic pregnancy(1), bacterial meningitis (1). All the cases were from poor socio-economic backgrounds and lived in high-density areas of Lusaka. CONCLUSIONS: Incidental cases of active tuberculosis undiagnosed antemortem seen at forensic autopsy reflects major gaps in the national TB control programs. More investments into proactive screening, testing, treatment activities, and accurate data collection are required.

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa.

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.