Rabbit Spleen and Medicinal Herbs: Animal Infectious Diseases, Grassroots Communes, and the State in Maoist China.

This article explores how Mao-era China responded to major epizootic and zoonotic diseases. It foregrounds a series of patterns in fighting contagious animal diseases-lockdowns, quarantines, disinfection, mass animal vaccination, mass education, and prioritizing the treatment of infected animals over mass culling-which were together called the Comprehensive Prevention and Treatment (CPT). Shedding light on this understudied topic in the fields of the history of medicine and of the People's Republic of China (PRC), the author argues that it was not the central or provincial governments but rather local communes that led the effort to protect livestock from animal infectious diseases. This article critically demonstrates how the story of the CPT highlights the resilience of communal actors as well as the possibilities and limitations of the Maoist ideal of self-reliance.

Dating first cases of COVID-19.

Questions persist as to the origin of the COVID-19 pandemic. Evidence is building that its origin as a zoonotic spillover occurred prior to the officially accepted timing of early December, 2019. Here we provide novel methods to date the origin of COVID-19 cases. We show that six countries had exceptionally early cases, unlikely to represent part of their main case series. The model suggests a likely timing of the first case of COVID-19 in China as November 17 (95% CI October 4). Origination dates are discussed for the first five countries outside China and each continent. Results infer that SARS-CoV-2 emerged in China in early October to mid-November, and by January, had spread globally. This suggests an earlier and more rapid timeline of spread. Our study provides new approaches for estimating dates of the arrival of infectious diseases based on small samples that can be applied to many epidemiological situations.

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis.

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.

MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017.

We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.

Hepatitis E Virus Infection in European Brown Hares, Germany, 2007-2014.

Rabbit-associated hepatitis E viruses (HEVs) cause zoonotic infections. We investigated 2,389 hares in Germany during 2007-2014. Complete genome characterization of a hare-associated HEV strain revealed close genomic relatedness to rabbit-associated HEV strains. Although hare-specific HEV seroprevalence was low, at 2.6%, hares represent a potential source of sporadic HEV infections.

Origins of the 1918 Pandemic: Revisiting the Swine "Mixing Vessel" Hypothesis.

How influenza A viruses host-jump from animal reservoir species to humans, which can initiate global pandemics, is a central question in pathogen evolution. The zoonotic and spatial origins of the influenza virus associated with the "Spanish flu" pandemic of 1918 have been debated for decades. Outbreaks of respiratory disease in US swine occurred concurrently with disease in humans, raising the possibility that the 1918 virus originated in pigs. Swine also were proposed as "mixing vessel" intermediary hosts between birds and humans during the 1957 Asian and 1968 Hong Kong pandemics. Swine have presented an attractive explanation for how avian viruses overcome the substantial evolutionary barriers presented by different cellular environments in humans and birds. However, key assumptions underpinning the swine mixing-vessel model of pandemic emergence have been challenged in light of new evidence. Increased surveillance in swine has revealed that human-to-swine transmission actually occurs far more frequently than the reverse, and there is no empirical evidence that swine played a role in the emergence of human influenza in 1918, 1957, or 1968. Swine-to-human transmission occurs periodically and can trigger pandemics, as in 2009. But swine are not necessary to mediate the establishment of avian viruses in humans, which invites new perspectives on the evolutionary processes underlying pandemic emergence.

Plague: A Disease Which Changed the Path of Human Civilization.

Plague caused by Yersinia pestis is a zoonotic infection, i.e., it is maintained in wildlife by animal reservoirs and on occasion spills over into human populations, causing outbreaks of different entities. Large epidemics of plague, which have had significant demographic, social, and economic consequences, have been recorded in Western European historical documents since the sixth century. Plague has remained in Europe for over 1400 years, intermittently disappearing, yet it is not clear if there were reservoirs for Y. pestis in Western Europe or if the pathogen was rather reimported on different occasions from Asian reservoirs by human agency. The latter hypothesis thus far seems to be the most plausible one, as it is sustained by both ecological and climatological evidence, helping to interpret the phylogeny of this bacterium.

Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought "Monkeys and Man" Closer Together in the 1960s.

In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to "monkey malaria." The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney's team of parasitologists and their subjects: from the human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch's postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney's experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding "that monkeys and man are more closely related than some of us wish to admit." In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge.

'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology.

The Swiss-born medical researcher Karl Friedrich Meyer (1884-1974) is best known as a 'microbe hunter' who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer's 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a 'reservoir of disease' as a forerunner of 'one medicine' approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer's other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer-like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet-can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet's and Smith's contributions to this scientific field have been widely acknowledged, Meyer's have been largely ignored. Drawing on Meyer's published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer's intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague-exchanges that not only showed how environmental and ecological conditions could 'tip the balance' in favor of parasites but which transformed Meyer thinking about resistance to infection and disease.

[Not Available]. / Les recherches d'Étienne Burnet (1920-1928) sur la brucellose.

Mediterranean fever or brucellosis was an endemic disease at the beginning of the 20th century in the Mediterranean area. Étienne Burnet, a pastorian researcher, studied this zoonosis in the Pasteur Institute of Tunis between 1920 and 1928 and enhanced our knowledge with various experiences on the genius Brucella, particularly melitensis variety. He developed the so-called Burnet's test or melitine IDR diagnose test. The thermo-agglutination of paramelitensis group, now known as the S forms colonies, led him question the variability of this non-specific character. He showed that thermo-agglutination is associated with specific antigenic properties and is common with other bacteria's species and could be acquired cross over colonies culture... The authors attempt to reconstitute the context of these experiences and to show the actuality of evolutionary Burnet's conception of living micro-organisms.

Molecular investigation of tularemia outbreaks, Spain, 1997-2008.

Tularemia outbreaks occurred in northwestern Spain in 1997-1998 and 2007-2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002-00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection.

Transmission of brucellosis from elk to cattle and bison, Greater Yellowstone area, U.S.A., 2002-2012.

Bovine brucellosis has been nearly eliminated from livestock in the United States. Bison and elk in the Greater Yellowstone Area remain reservoirs for the disease. During 1990-2002, no known cases occurred in Greater Yellowstone Area livestock. Since then, 17 transmission events from wildlife to livestock have been investigated.

Zoonotic Onchocerca lupi infection in dogs, Greece and Portugal, 2011-2012.

Onchocerca lupi infection is reported primarily in symptomatic dogs. We aimed to determine the infection in dogs from areas of Greece and Portugal with reported cases. Of 107 dogs, 9 (8%) were skin snip-positive for the parasite. DNA sequences of parasites in specimens from distinct dog populations differed genetically from those in GenBank.

The roots of evil: the amazing history of trichinellosis and Trichinella parasites.

This review aims to investigate, from a historical point of view, the roots of the Trichinella pathogens and the disease they produce, beginning from the times first recorded in the Bible and continuing until the scientific mysteries of the pathogen were finally unveiled. Our journey sheds light on "strange" epidemics developing before the discovery of the parasite and bearing a clinical similitude to trichinellosis; it follows the controversies that erupted after the nineteenth century discovery of the parasite and the subsequent official outbreaks, and then examines the pioneering methods used for its visualization. Finally, it tries to reveal the possible relationship of trichinellosis with the arts. Furthermore, it seems that the saga of the helminth, "destined to remain with us, both in nature and in the laboratory," will continue to haunt and fascinate scientists from both developing and developed countries, as they try to answer new questions about the parasite's "evil" nature.

Structure, receptor binding, and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic.

The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 A resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

[COVID-19 and Its Environment: From a History of Human Medicine Towards an Ecological History of Medicine?] / COVID-19 und seine Umwelt: Von einer Geschichte der Humanmedizin zu einer ökologischen Medizingeschichte?

This paper is part of the Forum COVID-19: Perspectives in the Humanities and Social Sciences. The history of medicine is mostly written as a history of human medicine. COVID-19 and other zoonotic infectious diseases, however, demand a reconsideration of medical history in terms of ecology and the inclusion of non-human actors and diverse environments. This contribution discusses possible approaches for an ecological history of medicine which satisfies the needs of several current and overlapping crises.

On the Use of Phylogeographic Inference to Infer the Dispersal History of Rabies Virus: A Review Study.

Rabies is a neglected zoonotic disease which is caused by negative strand RNA-viruses belonging to the genus Lyssavirus. Within this genus, rabies viruses circulate in a diverse set of mammalian reservoir hosts, is present worldwide, and is almost always fatal in non-vaccinated humans. Approximately 59,000 people are still estimated to die from rabies each year, leading to a global initiative to work towards the goal of zero human deaths from dog-mediated rabies by 2030, requiring scientific efforts from different research fields. The past decade has seen a much increased use of phylogeographic and phylodynamic analyses to study the evolution and spread of rabies virus. We here review published studies in these research areas, making a distinction between the geographic resolution associated with the available sequence data. We pay special attention to environmental factors that these studies found to be relevant to the spread of rabies virus. Importantly, we highlight a knowledge gap in terms of applying these methods when all required data were available but not fully exploited. We conclude with an overview of recent methodological developments that have yet to be applied in phylogeographic and phylodynamic analyses of rabies virus.