A hot topic at the environment–health nexus: investigating the impact of climate change on infectious diseases

Climate change — the ultimate challenge of our time: COVID-19 pandemic aside, climate change is the ultimate challenge of our time. However, to date, there has been insufficient political thrust to make that much-needed climate action a reality. Climate change and infectious diseases: Infectious diseases represent only one facet of the threats arising from climate change. Direct impacts from climate change include the more frequent occurrence and increased magnitude of extreme weather events, as well as changing temperatures and precipitation patterns. For climate-sensitive infectious diseases, these changes implicate a shift in geographical and temporal distribution, seasonality, and transmission intensity. Sizing up the problem: Susceptibility to the deleterious effects of climate change is a net result of the interplay of not only environmental factors, but also human, societal, and economic factors, with social inequalities being a major determinant of vulnerability. The global South is already disproportionately affected by the climate crisis. The financial capacity to pursue adaptation options is also limited and unevenly distributed. Conclusions: Climate change-induced mortality and morbidity from both infectious and non-infectious diseases, among other adverse scenarios, are expected to rise globally in the future. The coming decade will be crucial for using all remaining opportunities to develop and implement adequate mitigation and adaptation strategies

Using telemedicine for a lower carbon footprint in healthcare: A twofold tale of healing

The carbon footprint associated with healthcare has recently raised concerns about how medical practice can be made more sustainable. At the same time, Telemedicine has grown enough to enable medical practitioners to provide reliable healthcare services remotely. The propagation of telehealth amid the COVID-19 pandemic serves as an opportunity to work more consistently towards lowering healthcare’s carbon footprint by decreasing transportation and other carbon-emitting activities. Efforts in research methodology, medical education and policy are necessary to further investigate how it can contribute to lowering the footprint of the healthcare sector

Principles for co-producing climate services: Practical insights from FRACTAL

Co-production is increasingly acknowledged as the preferred mode for producing climate services, especially in complex and information-limited decision contexts. This paper contributes knowledge on practices and processes that can enable effective climate services in such contexts, through sharing experiences from the Future Resilience for African CiTies And Lands (FRACTAL) project.FRACTAL focused on informing actions to tackle climate-related issues in nine cities in six southern African countries over a six-year period and, in parallel, developing research findings and insights. Principles for effectively co-producing climate services were collaboratively identified by the project team, after which practical insights were detailed by analysing the body of evidence produced during FRACTAL using qualitative methods. This analysis helped to understand how principles were engendered, as well as associated challenges.While many principles identified resonate with the growing body of relevant knowledge, practical insights from this study contribute to understanding ‘how’ principles can be engendered. Experiences emphasise the importance of engaging participants’ emotions, avoiding centring on climate information, using a “third space” to facilitate equitable engagements, directing resources towards having fun and learning actively, process-driven iteration, focusing on contemporary issues with which stakeholders can connect, introducing a pathways framing, and embedding researchers in decision-making contexts. This constitutes a more comprehensive set of principles than was previously available in the literature. Application of these principles and the transdisciplinary framing, which was core to FRACTAL, supports a shift away from a focus on ‘products’ to knowledge co-production ‘processes’ where collaborative learning is the defining characteristic of climate services

Management of superficial and deep-seated Staphylococcus aureus skin and soft tissue infections in sub-Saharan Africa: a post hoc analysis of the StaphNet cohort

Purpose: The incidence of Staphylococcus aureus skin and soft tissue infection (SSTI) is high in sub-Saharan Africa. This is fueled by a high prevalence of Panton-Valentine leukocidin (PVL), which can be associated with necrotizing disease. The aim was to describe the clinical presentation and the treatment of SSTI in the African setting and to identify challenges in the management. Methods: Patients (n = 319) were recruited in DR Congo (n = 56, 17.6%), Gabon (n = 89, 27.9%), Mozambique (n = 79, 24.8%) and Tanzania (n = 95, 29.8%) during the prospective observational StaphNet cohort study (2010–2015). A physician recorded the clinical management in standardized questionnaires and stratified the entity of SSTI into superficial (sSSTI) or deep-seated (dSSTI). Selected virulence factors (PVL, β hemolysin) and multilocus sequence types (MLST) were extracted from whole genome sequencing data. Results: There were 220/319 (69%) sSSTI and 99/319 (31%) dSSTI. Compared to sSSTI, patients with dSSTI were more often hospitalized (13.2 vs. 23.5%, p = 0.03), HIV-positive (7.6 vs. 15.9%, p = 0.11), and required more often incision and drainage (I&D, 45.5 vs. 76.5%, p = 0.04). The proportion of an adequate antimicrobial therapy increased marginally from day 1 (empirical therapy) to day 3 (definite therapy), for sSSTI (70.7 to 72.4%) and dSSTI (55.4 to 58.9%). PVL was a risk factor for I&D (OR = 1.7, p = 0.02) and associated with MLST clonal complex CC121 (OR = 2.7, p < 0.001). Conclusion: Appropriate antimicrobial agents and surgical services to perform I&D were available for the majority of patients. Results from susceptibility testing should be considered more efficiently in the selection of antimicrobial therapy

Supporting Climate-Resilient Urban Planning: 10 Lessons from Cities in Southern Africa

This brief presents key insights on integrating climate information into climate change-related adaptation planning in African cities. The projects – FRACTAL (Future Resilience for African CiTies And Lands) and its successor, FRACTAL-Plus – took place over a seven-year period (2015-2022) in nine cities in sub-Saharan Africa.1 Here we present 10 lessons learned through the projects, providing examples of key elements that can support long-term, transformational action to build climate resilience (McClure et al., in review)

Community-associated Staphylococcus aureus from sub-saharan Africa and Germany : a cross-sectional geographic correlation study

Clonal clusters and gene repertoires of Staphylococcus aureus are essential to understand disease and are well characterized in industrialized countries but poorly analysed in developing regions. The objective of this study was to compare the molecular-epidemiologic profiles of S. aureus isolates from Sub-Saharan Africa and Germany. S. aureus isolates from 600 staphylococcal carriers and 600 patients with community-associated staphylococcal disease were characterized by DNA hybridization, clonal complex (CC) attribution, and principal component (PCA)-based gene repertoire analysis. 73% of all CCs identified representing 77% of the isolates contained in these CCs were predominant in either African or German region. Significant differences between African versus German isolates were found for alleles encoding the accessory gene regulator type, enterotoxins, the Panton-Valentine leukocidin, immune evasion gene cluster, and adhesins. PCA in conjunction with silhouette analysis distinguished nine separable PCA clusters, with five clusters primarily comprising of African and two clusters of German isolates. Significant differences between S. aureus lineages in Africa and Germany may be a clue to explain the apparent difference in disease between tropical/(so-called) developing and temperate/industrialized regions. In low-resource countries further clinical-epidemiologic research is warranted not only for neglected tropical diseases but also for major bacterial infections

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry such TLR7 variants (P = 3.5 × 10 −5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is <6.5 × 10 −4. We show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old