Engagement with Traditional Healers for Early Detection of Plague in Uganda.

In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.

Regarding pandemics: Ibn Jatima from Almería anticipates the physiopathological concept of multi-organ failure in the 14th century.

In 1348, a pandemic known as Black Death devastated humanity and changed social, economic and geopolitical world order, as is the current case with SARS-CoV-2 coronavirus. The doctor of the Nasrid Kingdom of Granada, Ibn-Jatima from Almeria, wrote "Treatise on the Plague", in which it may be found epidemiological and clinical similarities between both plagues. In the context of Greco-Arab medicine, he discovered respiratory and contact contagion of Pestis and attributed its physiopathology to a lack of pulmonary cooling of the innate heat, generated in the heart and carried by the blood humor. The process described was equivalent to the oxygen transport system. Furthermore, it was supposed to generate toxic residues, such as free radicals, leading to an irreversible multiple organ failure (MOF), considered a mortality factor as in Covid-19. Due to its similitude, it would be the first antecedent of the MOF physiopathological concept, a finding that enriches the scientific and historical heritage of our clinical specialty.

Characterization of Yersinia pestis Phage Lytic Activity in Human Whole Blood for the Selection of Efficient Therapeutic Phages.

The global increase in multidrug-resistant (MDR) pathogenic bacteria has led to growing interest in bacteriophage ("phage") therapy. Therapeutic phages are usually selected based on their ability to infect and lyse target bacteria, using in vitro assays. In these assays, phage infection is determined using target bacteria grown in standard commercial rich media, while evaluation of the actual therapeutic activity requires the presence of human blood. In the present work, we characterized the ability of two different Yersinia pestis lytic phages (ϕA1122 and PST) to infect and kill a luminescent Y. pestis EV76 strain suspended in Brain Heart Infusion (BHI)-rich medium or in human whole blood, simulating the host environment. We found that the ability of the phages to infect and lyse blood-suspended Y. pestis was not correlated with their ability to infect and lyse BHI-suspended bacteria. While the two different phages exhibited efficient infective capacity in a BHI-suspended culture, only the PST phage showed efficient lysis ability against blood-suspended bacteria. Therefore, we recommend that for personalized phage therapy, selection of phage(s) for efficient treatment of patients suffering from MDR bacterial infections should include prior testing of the candidate phage(s) for their lysis ability in the presence of human blood.

The Plague Doctor of Venice.

There is a distinctive Venetian carnival mask with sinister overtones and historical significance to physicians because it belongs to the 'Doctor of the Plague'. The costume features a beaked white mask, black hat and waxed gown. This was worn by mediaeval Plague Doctors as protection according to the Miasma Theory of disease propagation. The plague (or Black Death), ravaged Europe over several centuries with each pandemic leaving millions of people dead. The cause of the contagion was not known, nor was there a cure, which added to the widespread desperation and fear. Venice was a major seaport, and each visitation of the plague (beginning in 1348) devastated the local population. In response, Venetians were among the first to establish the principles of quarantine and 'Lazarets' which we still use today. Plague outbreaks have occurred in Australia, notably in Sydney (1900-1925), and continue to flare up in poorer communities, most recently in Madagascar (2017). Antibiotics are the mainstay of treatment, but there are concerns regarding the emergence of resistant pathogenic strains of Yersinia pestis, and their potential use in bio-terrorism.

Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics.

Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs, Y. pestis emerged <6000 years ago from an enteric bacterial ancestor through events of gene gain and genome reduction. It is a highly remarkable model for the understanding of pathogenic bacteria evolution, and a major concern for public health as highlighted by recent human outbreaks. A complex set of virulence determinants, including the Yersinia outer-membrane proteins (Yops), the broad-range protease Pla, pathogen-associated molecular patterns (PAMPs), and iron capture systems play critical roles in the molecular strategies that Y. pestis employs to subvert the human immune system, allowing unrestricted bacterial replication in lymph nodes (bubonic plague) and in lungs (pneumonic plague). Some of these immunogenic proteins as well as the capsular antigen F1 are exploited for diagnostic purposes, which are critical in the context of the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague). Here, we review recent research advances on Y. pestis evolution, virulence factor function, bacterial strategies to subvert mammalian innate immune responses, vaccination, and problems associated with pneumonic plague diagnosis.

[The plague: An overview and hot topics]. / La peste : mise au point et actualités.

Plague is a bacterial zoonosis caused by Yersinia pestis, usually found in fleas and small rodents that constitute the reservoir of the disease. It is transmitted to humans by flea bite, contact with rodents or inhalation of infected droplets. There are three clinical forms: bubonic plague, pulmonary plague and septicemic plague. The usual presentation is a flu-like syndrome possibly accompanied by an inflammatory lymphadenopathy which appears after 1 to 7days of incubation. Bubonic plague has a case fatality rate of about 50% while other forms of plague are almost always fatal without treatment. Diagnosis can be confirmed by usual bacteriological techniques (Gram examination, culture) but also by serological examination, use of rapid diagnostic tests or PCR. Although aminoglycosides are traditionally regarded as the most effective treatment, fluoroquinolones or cyclins are currently recommended in France. Plague is one of the re-emerging diseases according to the WHO and Madagascar suffered in 2017 the most important plague epidemic of the 21st century with more than 2000 cases and 200 deaths. Peru and the Democratic Republic of Congo are also considered endemic areas. Public health measures and a relentless fight against poverty are the cornerstone of the control of the disease. Vaccine improvement in endemic areas may also play an important role.

A historical evaluation of Chinese tongue diagnosis in the treatment of septicemic plague in the pre-antibiotic era, and as a new direction for revolutionary clinical research applications.

Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities, may have discouraged doctors to come in direct contact with their patients and take the pulse. However, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world's earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research.

The Live Chicken Treatment for Buboes: Trying a Plague Cure in Medieval and Early Modern Europe.

This article traces a seven-hundred-year history of one puzzling treatment for plague buboes that used the rumps of chickens to draw out the bubo's poisons. It traces the origin of the recipe to Avicenna's Canon and explores how medieval and early modern physicians altered the treatment and explained its workings up to the early eighteenth century. Much of the analysis focuses on the variants of the recipe that German physicians created as they adapted or elaborated on older recipes. This article argues that most variations of the treatment likely resulted from physicians trying ideas on paper, rather than in practice, as they attempted to unlock the mysteries of the plague's underlying poisons. Starting in the sixteenth century, however, evidence suggests that practice began to play an important role in the adaptation and interpretation of the "live chicken" recipes.

Plague: Clinics, Diagnosis and Treatment.

Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.

Nathaniel Hodges (1629-1688): Plague doctor.

Nathaniel Hodges was the son of Thomas Hodges (1605-1672), an influential Anglican preacher and reformer with strong connections in the political life of Carolingian London. Educated at Westminster School, Trinity College Cambridge and Christ Church College, Oxford, Nathaniel established himself as a physician in Walbrook Ward in the City of London. Prominent as one of a handful of medical men who remained in London during the time of the Great Plague of 1665, he wrote the definitive work on the outbreak. His daily precautions against contracting the disease included fortifying himself with Théodore de Mayerne's antipestilential electuary and the liberal consumption of Sack. Hodges' approach to the treatment of plague victims was empathetic and based on the traditional Galenic method rather than Paracelsianism although he was pragmatic in the rejection of formulae and simples which he judged from experience to be ineffective. Besieged by financial problems in later life, his practice began to fail in the 1680s and he eventually died in a debtor's prison.

[PLAGUE:.CASES OF HUMAN INFECTION IN THE USA NATURAL FOCI AND THE DIFFICULTY OF THEIR DETECTION].

In this work we analyze the epidemic situations with plague in the United States of America, which are linked to internal migration - infection in a natural focus and movement of a diseased person within the boundaries of this focus to another district, state or non-endemic territory, as well as with international migration of infected person during incubation period.

Pneumonic Plague: The Darker Side of Yersinia pestis.

Inhalation of the bacterium Yersinia pestis results in primary pneumonic plague. Pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. Its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of Y. pestis as a biological weapon. Importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of Y. pestis infections. In this review we describe the characteristics of pneumonic plague, focusing on its disease progression and pathogenesis. The rapid time-course, severity, and difficulty of treating pneumonic plague highlight how differences in the route of disease transmission can enhance the lethality of an already deadly pathogen.

[Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy]. / Pest und Lungenpest : Pathogenität, Epidemiologie, Klinik und Therapie.

Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

[The "Black Death" : Crimean-Congo hemorrhagic fever]. / Der "schwarze Tod" : Krim-Kongo-Hämorrhagisches-Fieber.

The Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that has been known for centuries. In the last years more frequent cases reflect the effects of climate change, globalization and the increasing encroachment of humans into previously unexploited areas. Humans acquire the infection by tick bites or through the slaughtering and processing of infected animals. The course of the disease can be severe and the average mortality reaches up to 30 %. It is transmissible from human to human and there is no causal treatment. Thus, CCHF meets the criteria for a highly contagious life-threatening disease. In the following current data on the virus, its vector, the distribution and transmission will be presented, as well as information on the diagnosis, the disease, the underlying pathophysiology and consequences in dealing with patients and deceased.

Clinical management of potential bioterrorism-related conditions.

The agents most likely to be used in bioterrorism attacks are reviewed, along with the clinical syndromes they produce and their treatment.

Immunopotentiation for bacterial biodefense.

Activation of the innate immune system can enhance resistance to a variety of bacterial and viral infections. In situations where the etiological agent of disease is unknown, such as a bioterror attack, stimulation of innate immunity may be particularly useful as induced immune responses are often capable of providing protection against a broad range of pathogens. In particular, the threat of an intentional release of a highly virulent bacterial pathogen that is either intrinsically resistant to antibiotics, or has been weaponized via the introduction of antibiotic resistance, makes immunopotentiation an attractive complementary or alternative strategy to enhance resistance to bacterial biothreat agents. Francisella tularensis, Yersinia pestis, Bacillus anthracis, and Burkholderia mallei or pseudomallei can all be easily disseminated via the respiratory route and infections can result in high mortality rates. Therefore, there has been a marked increase in research on immunotherapeutics against these Tier 1 select agents over the last 10 years that will be covered in this review. In addition, immunopotentiation against non-Tier 1 select agents such as Brucella spp., and Coxiella burnetii has also been studied and will be reviewed here. In particular, we will focus on cellular targets, such as toll-like receptors (TLRs), carbohydrate receptors and cytokine receptors, which have been exploited by immunomodulatory regimens that confer broad-spectrum protection against virulent bacterial pathogens.

Biowarfare and bioterrorism.

Bioterrorism is not only a reality of the times in which we live but bioweapons have been used for centuries. Critical care physicians play a major role in the recognition of and response to a bioterrorism attack. Critical care clinicians must be familiar with the diagnosis and management of the most likely bioterrorism agents, and also be adequately prepared to manage a mass casualty situation. This article reviews the epidemiology, diagnosis, and treatment of the most likely agents of biowarfare and bioterrorism.

Is plague a problem in the Egyptians returning back from Libya?

Many employees return home with fever with or without other accompanying symptoms. Fever can be a manifestation of a minor, self-limited process or can herald a progressive, life-threatening illness. The assessment of this group is often hampered by the clinician's lack of familiarity with the types of infections that the patient may have encountered while traveling. The evaluation of such patients should focus on: What infections are possible given where the patient has lived or traveled and the time when exposures may have occurred? Which of these infections is more probable given the patient's clinical findings and potential exposures? Which of these infections is treatable or transmissible or both? On the other hand, the outbreak of plague at the Libyan-Egyptian borders and the high density rodents and their ecto-parasitic fleas in many Egyptian governorates should be embarked a control program to rodents and fleas and to raise the awareness of the concerned authorizes.