How many human pathogens are there in Laos? An estimate of national human pathogen diversity and analysis of historical trends.

OBJECTIVE: The emergence of infectious diseases pose major global health threats. Estimates of total in-country human pathogen diversity, and insights as to how and when species were described through history, could be used to estimate the probability of new pathogen discoveries. Data from the Lao People's Democratic Republic (Laos) were used in this proof-of-concept study to estimate national human pathogen diversity and to examine historical discovery rate drivers. METHODS: A systematic survey of the French and English scientific and grey literature of pathogen description in Laos between 1874 and 2017 was conducted. The first descriptions of each known human pathogen in Laos were coded according to the diagnostic evidence available. Cumulative frequency of discovery across time informed the rate of discovery. Four distinct periods of health systems development in Laos were identified prospectively and juxtaposed to the unmodelled rate of discovery. A model with a time-varying rate of discovery was fitted to these data using a Markov-Chain- Monte-Carlo technique. RESULTS: From 6456 pathogen descriptions, 245 discoveries of known human pathogens in Laos, including repeat discoveries using different grades of evidence, were identified. The models estimate that the Laos human pathogen species diversity in 2017 is between 169 and 206. During the last decade, there has been a 33-fold increase in the discovery rate coinciding with the strengthening of medical research and microbiology. CONCLUSION: Discovery curves can be used to model and estimate country-level human pathogen diversity present in a territory. Combining this with historical assessment improves the understanding of the factors affecting local pathogen discovery. PROSPERO REGISTRATION NUMBER: A protocol of this work was registered on PROSPERO (ID:CRD42016046728).

Stomatal heterogeneity in responses to humidity and temperature: Testing a mechanistic model.

The role of stomatal heterogeneity in the response of stomatal conductance (gs ) to the mole fraction difference in water vapour between the inside of the leaf and the ambient air (Δw) was determined using thermography and gas exchange for 3 species. The value of Δw for the leaf was varied in 2 different ways: first by varying air humidity while holding leaf temperature constant and second by varying leaf temperature while holding air humidity constant. Stomatal heterogeneity was explored by examining the response of gs in small areas of the leaf (as determined by thermography) and comparing them to each other and to the average value of gs (as determined by gas exchange). These analyses show that despite substantial heterogeneity in gs values, the response of gs to Δw was qualitatively similar in all areas of the leaf, and all responses of gs to Δw were well predicted by a recently proposed, vapour-phase mechanism for stomatal responses to temperature and humidity. Remarkably, the 2 model parameters, Θ and Z, that depend on leaf anatomy were constant for a given species, and only the maximum conductance varied in different regions of the leaf.

Proinflammatory adjuvants enhance the cognate helper activity of aged CD4 T cells.

Age-related declines in humoral responses contribute to the reduced efficacy of vaccines in older populations. Using an adoptive transfer model, we have shown that age-related intrinsic declines in CD4 T cell function contribute significantly to the reduced humoral responses observed with aging, resulting in reduced B cell expansion and differentiation as well as reduced IgG production. In this current study, we show that the helper function of aged CD4 T cells can be enhanced using a TLR-binding adjuvant or an adjuvant containing proinflammatory (PI) cytokines. The helper function of aged CD4 T cells was also enhanced when PI cytokines were added during in vitro CD4 effector generation. Enhanced helper activity resulted in improved expansion and differentiation of B cells and affinity maturation of IgG. PI cytokines also induced significant production of effector cytokines, including IL-4, IFN-gamma, IL-17, and IL-21, by both young and aged CD4 T cells. Importantly, we also show that proinflammatory adjuvants can significantly enhance the humoral response in intact aged animals. We propose that one of the mechanisms involved in the ability of adjuvants to enhance both young and aged T cell responses includes driving multifaceted T cell differentiation and production of multiple cytokines by responding CD4 T cells.