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The Bellagio Group for Accelerating AMR Action met in April 2024 to develop the ambitious but achievable 1-10-100 unifying goals to galvanize global policy change and investments for antimicrobial resistance mitigation: 1 Health; 10 million lives saved; and 100% sustainable access to effective antimicrobials. High profile political goals such as the Paris Agreement's objective to keep global warming well below 2° Celsius compared to pre-industrial levels, UNAIDS' 90-90-90 goal, and the Sustainable Development Goals challenge global norms, direct attention towards relevant activities, and serve an energizing function to motivate action over an extended period of time. The 1-10-100 unifying goals propose to unite the world through a One Health approach to safeguard human health, animal welfare, agrifood systems, and the environment from the emergence and spread of drug-resistant microbes and infections; save over 10 million lives by 2040 through concerted efforts to prevent and appropriately treat infections while preserving the vital systems and services that depend on sustained antimicrobial effectiveness; and commit to ensuring that antimicrobials are available and affordable for all, used prudently, and secured for the future through innovation. Compared to existing technical targets, these unifying goals offer advantages of focusing on prevention, encouraging multisectoral action and collaboration, promoting health equity, recognizing the need for innovation, and integrating with Sustainable Development Goals. By committing to 1 Health, 10 million lives saved, and 100% sustainable access to effective antimicrobials, we can protect lives and livelihoods today and safeguard options for tomorrow., (© 2024. The Author(s).)

Background: Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates., Methods: Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014-2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis., Results: Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1-5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7-3.7), history of preterm delivery < 34 weeks (43.4% vs 30.3%, OR 2.3, 95% CI 1.1-4.9), the mother's perception that the frequency of vaccine complications for babies is very low (54.6% vs 20.6%, OR 1.1, 95% CI 0.5-2.2), the mother's good knowledge of influenza and its vaccine (61.7% vs 24.4%, OR 3.1, 95% CI 2.2-4.4), hospital-based prenatal care in their first trimester of pregnancy (55.0% vs 30.2%, OR 2.1, 95% CI 1.2-3.7), vaccination recommendations during pregnancy by a healthcare worker (47.0% vs 2.7%, OR 18.8, 95% CI 10.0-35.8), receipt of a vaccine reimbursement form (52.4% vs 18.6%, OR 2.0, 95% CI 1.5-2.7), and information from at least one healthcare worker about the vaccine (43.8% vs 19.1%, OR 1.8, 95% CI 1.3-2.6)., Conclusions: Our findings suggest that in order to increase flu vaccination compliance among pregnant women, future public health programmes must ensure cost-free access to vaccination, and incorporate education about the risks of influenza and the efficacy/safety of vaccination and clear recommendations from healthcare professionals into routine antenatal care.

Background: Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host's immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury., Results: Ex vivo, Pa secretes clinically relevant kynurenine levels (μM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production., Conclusion: Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host's tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection.

The murine norovirus (MNV) is a recently discovered mouse pathogen, representing the most common contaminant in laboratory mouse colonies. Nevertheless, the effects of MNV infection on biomedical research are still unclear. We tested the hypothesis that MNV infection could alter immune response in mice with acute lung infection. Here we report that co-infection with MNV increases survival of mice with Pseudomonas aeruginosa acute lung injury and decreases in vivo production of pro-inflammatory cytokines. Our results suggest that MNV infection can deeply modify the parameters studied in conventional models of infection and lead to false conclusions in experimental models.

Background: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa., Methods: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed., Results: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa., Conclusions: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

BACKGROUND: The effects of the murine monoclonal anti-PcrV antibody Mab166 on acute lung injury induced by Pseudomonas aeruginosa were analyzed in a rat model. METHODS: Lung injury was induced by the instillation of P. aeruginosa strain PA103 directly into the left lungs of anesthetized rats. One hour after the bacterial instillation, rabbit polyclonal anti-PcrV IgG, murine monoclonal anti-PcrV IgG Mab166 or Mab166 Fab-fragments were administered intratracheally directly into the lungs. The degree of alveolar epithelial injury, amount of lung edema, decrease in oxygenation and extent of lung inflammation by histology were evaluated as independent parameters of acute lung injury. RESULTS: These parameters improved in rats that had received intratracheal instillation of either rabbit polyclonal anti-PcrV IgG, murine monoclonal anti-PcrV IgG Mab166 or Mab166 Fab-fragments in comparison with the control group. CONCLUSION: Mab166 and its Fab fragments have potential as adjuvant therapy for acute lung injury due to P. aeruginosa pneumonia.