Interim Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza - California, October 2023-January 2024.

Surveillance data can provide rapid, within-season influenza vaccine effectiveness (VE) estimates to guide public health recommendations. Mandatory reporting of influenza vaccine administration to California's immunization information registry began January 1, 2023, and mandatory reporting of all influenza laboratory test results, including negative results, was instituted in California on June 15, 2023. These data, collected by the California Department of Public Health during October 1, 2023-January 31, 2024, were used to calculate interim influenza VE against laboratory-confirmed influenza by comparing the odds of vaccination among case-patients (persons who received a positive influenza laboratory test result) and control patients (those who received a negative influenza laboratory test result). VE was calculated as 1 - adjusted odds ratio using mixed-effects logistic regression, with age, race, and ethnicity as fixed effects and specimen collection week and county as random effects. Overall, during October 1, 2023-January 31, 2024, estimated VE was 45% among persons aged ≥6 months, 56% among children and adolescents aged 6 months-17 years, 48% among adults aged 18-49 years, 36% among those aged 50-64 years, and 30% among those aged ≥65 years. Consistent with some previous influenza seasons, influenza vaccination provided moderate protection against laboratory-confirmed influenza among infants, children, adolescents, and adults. All persons aged ≥6 months without a contraindication to vaccination should receive annual influenza vaccination to reduce influenza illness, severe influenza, and strain on health care resources. Influenza vaccination remains the best way to prevent influenza.

Linked surveillance and genetic data uncovers programmatically relevant geographic scale of Guinea worm transmission in Chad.

BACKGROUND: Guinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten-year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission. METHODOLOGY/PRINCIPAL FINDINGS: We coupled genomic and surveillance case data from 2012-2018 to investigate the modes of transmission between dog and human hosts and the geographic connectivity of worms. Eighty-six variants across four genes in the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling revealed worms with the same genotype ('genetically identical') were within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms varied in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm was surrounded by five to ten genetically distinct worms within a 50 kilometer radius. As expected, we observed a change in the genetic similarity distribution between pairs of worms using variants across the complete mitochondrial genome in an independent population. CONCLUSIONS/SIGNIFICANCE: In the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic identity and modeling can facilitate the understanding of local transmission. The co-occurrence of genetically non-identical worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between pairs of worms from variants identified across the complete mitochondrial genome suggests that expanding the number of genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination.

Methionine oxidized apolipoprotein A-I at the crossroads of HDL biogenesis and amyloid formation.

Apolipoprotein A-I (apoA-I) shares with other exchangeable apolipoproteins a high level of structural plasticity. In the lipid-free state, the apolipoprotein amphipathic α-helices interact intra- and intermolecularly, providing structural stabilization by self-association. We have reported that lipid-free apoA-I becomes amyloidogenic upon physiologically relevant (myeloperoxidase-mediated) Met oxidation. In this study, we established that Met oxidation promotes amyloidogenesis by reducing the stability of apoA-I monomers and irreversibly disrupting self-association. The oxidized apoA-I monomers also exhibited increased cellular cholesterol release capacity and stronger association with macrophages, compared to nonoxidized apoA-I. Of physiologic relevance, preformed oxidized apoA-I amyloid fibrils induced amyloid formation in nonoxidized apoA-I. This process was enhanced when self-association of nonoxidized apoA-I was disrupted by thermal treatment. Solid state NMR analysis revealed that aggregates formed by seeded nonoxidized apoA-I were structurally similar to those formed by the oxidized protein, featuring a ß-structure-rich amyloid fold alongside α-helices retained from the native state. In atherosclerotic lesions, the conditions that promote apoA-I amyloid formation are readily available: myeloperoxidase, active oxygen species, low pH, and high concentration of lipid-free apoA-I. Our results suggest that even partial Met oxidation of apoA-I can nucleate amyloidogenesis, thus sequestering and inactivating otherwise antiatherogenic and HDL-forming apoA-I.-Witkowski, A., Chan, G. K. L., Boatz, J. C., Li, N. J., Inoue, A. P., Wong, J. C., van der Wel, P. C. A., Cavigiolio, G. Methionine oxidized apolipoprotein A-I at the crossroads of HDL biogenesis and amyloid formation.