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Grantham, M.

Publications and source records attributed to Grantham, M..

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Nasal and aerosol shedding of infectious influenza virus - a community based study

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5 m and fine <5 m fractions) on days 1 to 3 post symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8x104/30-min fine, 1.2x104/30-min coarse aerosol sample, and 8.2x108 per NP swab. Fine and coarse aerosol viral RNA was positively associated with body mass index (fine p<0.05, coarse p<0.10) and number of coughs (fine p<0.001, coarse p<0.01) and negatively associated with increasing days since symptom onset (fine p<0.05 to p<0.01, coarse p<0.10) in adjusted models. Fine aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season (p<0.01). NP swab viral RNA was positively associated with upper respiratory symptoms (p<0.01) and negatively associated with age (p<0.01) but was not significantly associated with fine or coarse aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.\n\nSignificanceLack of human data on influenza virus aerosol shedding fuels debate over the importance of airborne transmission. We provide overwhelming evidence that humans generate infectious aerosols and quantitative data to improve mathematical models of transmission and public health interventions. We show that sneezing is rare and not important for, and that coughing is not required for influenza virus aerosolization. Our findings, that upper and lower airway infection are independent and that fine particle exhaled aerosols reflect infection in the lung, open a new pathway for understanding the human biology of influenza infection and transmission. Our observation of an association between repeated vaccination and increased viral aerosol generation demonstrated the power of our method, but needs confirmation.

epidemiology

Unravelling the genomic basis and evolution of the pea aphid male wing dimorphism

Wing dimorphisms have long served as models for examining the ecological and evolutionary tradeoffs associated with alternative morphologies [1], yet the mechanistic basis of morph determination remains largely unknown. Here we investigate the genetic basis of the pea aphid (Acyrthosiphon pisum) wing dimorphism, wherein males exhibit one of two alternative morphologies that differ dramatically in a set of correlated traits that inclused the presence or absence of wings [2-4]. Unlike the environmentally-induced asexual female aphid wing polyphenism [5], the male wing polymorphism is genetically determined by a single uncharacterized locus on the X chromosome called aphicarus (\"aphid\" plus \"Icarus\", api) [6, 7]. Using recombination and association mapping, we localized api to a 130kb region of the pea aphid genome. No nonsynonymous variation in coding sequences strongly associated with the winged and wingless phenotypes, indicating that api is likely a regulatory change. Gene expression level profiling revealed an aphid-specific gene from the region expressed at higher levels in winged male embryos, coinciding with the expected stage of api action. Comparison of the api region across biotypes (pea aphid populations specialized to different host plants that began diverging ~16,000 years ago [8, 9]) revealed that the two alleles were likely present prior to biotype diversification. Moreover, we find evidence for a recent selective sweep of a wingless allele since the biotypes diversified. In sum, this study provides insight into how adaptive, complex traits evolve within and across natural populations.

evolutionary biology