Current status of plague and plague control in the United States

During the first quarter of the 20th century, massive rat-borne plague epidemics occurred in port cities of the United States in conjunction with the last world-wide pandemic which originated in China in 1893. By 1950, plague was found to be firmly established in wild rodent populations in states west of the 100th meridian. Presumably because of improved sanitation coupled with retreat of the world-wide pandemic, there have been no human cases in this country associated with urban rats since 1924. However, sporadic cases, fewer than 10 per year, are reported as due to contact with wild rodents, lagomorphs, rural rats, and/or their fleas. Recent observations suggest that: a) in the current decade there has been an increase in human plague cases; b) there continues to be a serious potential of a single undiagnosed and untreated case, which possibility is intensified by the very paucity of human cases decreasing the likelihood of a correct diagnosis and by changing patterns of life exhibited by members of our society (e.g., hippie communes and a generally increased mobility); and c) the apparent distribution of plague only in the area west of the 100th meridian might be found to represent an unrealistic generalization if adequate surveillance were carried out. At the present time human plague cases from wild animal sources tend to be isolated events both spatially and temporally and often cannot be attributed to confined and definable epizootic sources amenable to effective control programs. Improved means for epizootic control and long-term management of enzootic plague sources must be sought aggressively. These measures should include development of: a) a surveillance network to detect plague activity in rodent and lagomorph populations throughout the western United States; b) effective, yet ecologically sound, means of ectoparasite control, including suitable materials and methods of application; c) methods for management of plague-susceptible wild animal populations, particularly where they exist in contact with high use recreation and residential areas; and d) more extensive knowledge of enzootic plague and the factors that bring about epizootic plague and potential human contact

CURRENT STATUS OF PLAGUE AND PLAGUE CONTROL IN THE UNITED STATES

During the first quarter of the 20th century massive rat-borne plague epidemics occurred in port cities of the United States in conjunction with the last world-wide pandemic which originated in China in 1893. By 1950, plague was found to be firmly established in wild rodent populations in states west of the 100th meridian. Presumably because of improved sanitation coupled with retreat of the world-wide pandemic there have been no human cases in this country associated with urban rats since 1924. However, sporadic cases, fewer than 10 per year, are reported as due to contact with wild rodents, lagomorphs, rural rats, and/or their fleas. Recent observations suggest that: a) in the current decade there has been an increase in human plague cases; b) there continues to be a serious potential of a single undiagnosed and untreated case, which possibility is intensified by the very paucity of human cases decreasing the likelihood of a correct diagnosis and by changing patterns of life exhibited by members of our society (e.g., hippie communes and a generally increased mobility); and c) the apparent distribution of plague only in the area west of the 100th meridian might be found to represent an unrealistic generalization if adequate surveillance were carried out. At the present time human plague cases from wild animal sources tend to be isolated events both spatially and temporally and often cannot be attributed to confined and definable epizootic sources amenable to effective control programs. Improved means for epizootic control and long term management of enzootic plague sources must be sought aggressively. These measures should include development of: a) a surveillance network to detect plague activity in rodent and lagomorph populations throughout the western United States; b) effective, yet ecologically sound, means of ectoparasite control, including suitable materials and methods of application; c) methods for management of plague-susceptible wild animal populations, particularly where they exist in contact with high use recreation and residential areas; and d) more extensive knowledge of enzootic plague and the factors that bring about epizootic plague and potential human contact

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m−3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Graphene oxide nanomaterials have been developed for wide-ranging applications, but has potential safety concerns for human health. Controlled inhalation exposures in human volunteers have been a vital means to determine the effects and mechanisms of ultrafine particles in air pollution, however, few studies have used this approach to explore the effects of nanomaterials. We conducted a double-blind randomised controlled study to determine whether inhalation of graphene oxide affects pulmonary or cardiovascular function. A high purity graphene oxide was synthesised with a thickness of 1-2 layers in two sizes: ‘small’ (lateral dimensions: 100-1700 nm) and ‘ultrasmall’ (30-500 nm). Graphene oxide particles at 200 µg/m3, or filtered air, were inhaled for 2 hours by 14 young healthy volunteers on repeated visits, with measurement of cardiorespiratory parameters before and across 4 hours after exposure. Graphene oxide exposure was well-tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected by graphene oxide irrespective of particle size. GO did not change blood biomarkers of coagulation, however, there was a mild increase in thrombus formation in an ex vivo model of arterial injury. Proteomics revealed very few differential plasma proteins. Overall, acute inhalation of graphene oxide was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures for risk assessment of graphene nanomaterials

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Datasets for manuscript published in Nature Nanotechnology. Graphene oxide nanomaterials are being developed for wide-ranging applications, but have potential safety concerns for human health. We conducted a double-blind randomised controlled study to determine how inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at µg/m3 or filtered air were inhaled for 2 hours by 14 young healthy volunteers on repeated visits. Overall, graphene oxide nanosheet exposure was well-tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of such highly purified and thin graphene oxide nanosheets of nanometre dimensions was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two dimensional nanomaterials in humans