Chemical and Biological Threats to Public Safety
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Plague is an infectious disease of animals and humans caused by the bacterium Yersinia pestis. All yersinia infections are zoonotic, capable of spreading from rodents and their fleas (urban plague) as well as from squirrels, rabbits, field rats, and cats (sylvatic plague). Historically, pandemics resulting from yersinia infections have devastated human populations. The first of three urban plagues started in Egypt (541 AD) and spread through the Middle East, North Africa, Asia, and Europe, killing over 100 million persons. The Middle Ages (1340s) recorded a second pandemic that probably originated from Asia and spread through Europe, resulting in 25 million deaths in Europe. Recent history (1895) recorded a pandemic that began in Hong Kong and spread to Africa, India, Europe, and the Americas, leaving 10 million deaths in its wake over 20 years. The recognition of public health and maintenance of hygienic standards has essentially eradicated urban plague from most communities, although some cases are reported in the United States annually. Clinically, Y. pestis infections are manifested as bubonic plague and pneumonic plague.
A brief history of pandemics
Edward M. Rafalski, Ross M. Mullner in Healthcare Analytics, 2022
Prior to our understanding of the germ theory of disease, diseases such as the plague were thought to be caused by “miasmas” or pockets of unclean air, and the role of insect and rodent vectors was unappreciated. The Justinian Plague, named after the Byzantine Emperor Justinian I, began in Southeast Asia, spread to Constantinople, capital of the Byzantine Empire and the major trading port linking Asia and Europe, and spread in waves throughout Europe, North Africa, and the Middle East in 8–12 year intervals from 541 to 750 CE [5]. The plague is caused by a bacterium, Yersinia pestis, which is carried by fleas and lice. These vectors live on rodents including black rats but can pass the disease on to humans when the rats are in close proximity. The grain ships traveling to Constantinople were a rich environment for these rats and brought the plague with them.
The Black Death and Other Pandemics
Scott M. Jackson in Skin Disease and the History of Dermatology, 2023
A few thousand cases of bubonic plague occur each year in the world today; these cases provide us with a modern look at the medieval disease. A comparison of the medieval accounts to a summary of modern accounts of bubonic plague in Arizona and Madagascar supports the diagnosis of plague as the cause of the Black Death.43 Modern plague starts with fever, chills, weakness, and headache a few days after a flea bite. Then, the patient develops a bubo, which is a markedly enlarged, exquisitely tender infected lymph node in the region of the flea bite. Flea bites, which occur most commonly on the lower extremities, are most likely to cause buboes in the groin region. Children, who typically play low to the ground, are susceptible to flea bites on the upper extremities. In these cases, and in cases associated with a cat bite or scratch, the buboes are more common in the underarm or neck. Untreated bubonic plague can lead to sepsis with DIC, pneumonia, or meningitis. Septicemic and pneumonic forms of plague can both occur with or without a preceding bubo; pneumonic plague can result from inhalation of infected aerosolized respiratory secretions. Plague patients can uncommonly experience severe tonsillitis (pharyngeal plague) or prominent gastrointestinal symptoms, confusing the picture. The most atypical reported route of acquiring plague was a case of pharyngeal plague after the ingestion of camel meat from camels infected with plague by flea bites.44 Indeed, in modern plague, the flea appears to play a crucial role in the transmission of the infection.
Flagellin as a vaccine adjuvant
Published in Expert Review of Vaccines, 2018
Baofeng Cui, Xinsheng Liu, Yuzhen Fang, Peng Zhou, Yongguang Zhang, Yonglu Wang
Plague is an infectious disease of animals and humans caused by Yersinia pestis, a Gram-negative coccobacillus, that is acute and often fatal. Currently, there is no effective licensed vaccine that protects against pneumonic plague. However, a recombinant protein in which two protective antigens (F1 and V protein) of Y. pestis were fused to the hypervariable region of flagellin was designed to provide protection against respiratory exposure to Y. pestis [167]. Based on the results, the recombinant flagellin-F1-V protein was recognized by the TLR5 receptor and stimulated the production of proinflammatory cytokines, such as TNF-α, in vitro through the NK-κB pathway. Using a prime-boost immunization protocol, robust anti-F1 and anti-V humoral immunity in mice and two species of nonhuman primates was elicited by flagellin-F1-V. In immunized mice, the bacteria were completely cleared within 3 days of challenge. Based on outstanding preclinical results, the safety, immunogenicity, and tolerability of the flagellin-F1-V recombinant fusion protein were evaluated in humans. In phase I clinical trials (ClinicalTrials.gov Identifier: NCT01381744), increasing doses of the flagellin/F1/V vaccine in phosphate-buffered saline were administered via the i.m. route on days 0 and 28 to 18- to 45-year-old healthy volunteers. However, no further research results from phase I clinical trials have been formally posted to date.
COVID-19 and human reproduction: A pandemic that packs a serious punch
Published in Systems Biology in Reproductive Medicine, 2021
George Anifandis, Helen G. Tempest, Rafael Oliva, Grace M. Swanson, Mara Simopoulou, Charles A. Easley, Michael Primig, Christina I. Messini, Paul J. Turek, Peter Sutovsky, Steve J. Ory, Stephen A. Krawetz
The COVID-19 virus has been called the modern plague. This is in reference to the bubonic plague or Black Death, which holds the record for being the most lethal pandemic in human history (Alchon 2003). An estimated 75 million people died during the outbreak in mid 14th century Eurasia and North Africa. Almost half of Europe’s population was wiped out, as the plague was lethal to 30 to 90% of those infected. The plague caused flu symptoms, hemorrhage and pneumonia, as well as painful swollen lymph nodes that form pus-filled boils called buboes. Unlike COVID-19, and according to modern genetic analyses, the plague was due to the bacterium Yersinia pestis. It spread through flea bites and contact with animals (especially rats) but was not spread widely between humans. Notably, the plague still exists today, with about 651 cases reported worldwide annually (https://www.cdc.gov/plague/maps/index.html). It is curable with common antibiotics.
War on Rats: the architecture of the bubonic plague in Galveston
Published in Baylor University Medical Center Proceedings, 2023
Leonard Kuan-Pei Wang
The first case arrived in the summer of 1920. On June 8, a 17-year-old boy began experiencing plague symptoms: he was cold, dizzy, and his right femoral gland had a swelling, or “bubo.”1 Investigators found rats near the grain store where he worked as a collector as well as a dead rat and fleas at his home. Eight days later, the young man was unconscious. Four hours after he was admitted to John Sealy Hospital’s isolation ward, Emil Horridge became the first victim of Galveston’s bubonic plague. Figure 1 shows documentation of the first human case of bubonic plague in Galveston in a laboratory notebook.5 Two hours after Horridge died, Dr. Henry C. Hartman (1881–1963), chairman of the Department of Pathology at the University of Texas Medical Branch, began the autopsy.6 As reported by Hartman and his colleague, Dr. Anna M. Bowie (1890–1980), in the Journal of the American Medical Association, Horridge’s autopsy included pathologic findings of hemorrhagic necrosis of the right femoral gland, cloudy swelling and edema in the heart, marked hyperemia of the lungs, an enlarged spleen with hemorrhages, acute nephritis, fatty degeneration of the liver, and erosions in the gastric mucosa.7
Related Knowledge Centers
- Bubonic Plague
- Enterobacteriaceae
- Fever
- Lymph Node
- Necrosis
- Pneumonic Plague
- Yersinia Pestis
- Infection
- Headache
- Septicemic Plague