Salmonella Typhi - historical perspective of discovery and forgotten contribution of Polish anatomopathology.

Outbreaks of typhoid fever for centuries decimated armies, cities and large hosts of people. Discovery of an agent causing such a grave disease became one of the most important achievements of bacteriology - science, which had experienced rapid development in the last quarter of the 19th century and changed the course of our civilization.The article deals with the discovery of Tadeusz Browicz, Polish anatomopathologist, who in 1874 reported about rod-shaped "parasites" in viscera of typhoid fever victim. His achievement became shaded by the later discoveries of Eberth, Klebs and Gaffky, but as authors stated below, Browicz should be recognized with mentioned scientists as a co-discoverer of the typhoid fever bacillus.

Typhoid-From Past to Future.

Making a Difference? brings together medical humanities and sciences experts to analyze how historical and new data on typhoid control can be brought to bear on the current context of typhoid conjugate vaccine rollouts and extensively drug-resistant typhoid.

A Biohistorical Perspective of Typhoid and Antimicrobial Resistance.

We combine methodology from history and genetics to reconstruct the biosocial history of antimicrobial resistance (AMR) in the bacterium Salmonella enterica serovar Typhi (S. Typhi). We show how evolutionary divergence in S. Typhi was driven by rising global antibiotic use and by the neglect of typhoid outside of high-income countries. Although high-income countries pioneered 1960s precautionary antibiotic regulations to prevent selection for multidrug resistance, new antibiotic classes, typhoid's cultural status as a supposedly ancient disease of "undeveloped" countries, limited international funding, and narrow biosecurity agendas helped fragment effective global collective action for typhoid control. Antibiotic-intensive compensation for weak water and healthcare systems subsequently fueled AMR selection in low- and middle-income countries but often remained invisible due to lacking surveillance capabilities. The recent rise of extensively drug-resistant typhoid bears the biosocial footprint of more than half a century of antibiotic-intensive international neglect.

Direct Medical Costs of 3 Reportable Travel-Related Infections in Ontario, Canada, 2012-2014.

Immigrants traveling to their birth countries to visit friends or relatives are disproportionately affected by travel-related infections, in part because most preventive travel health services are not publicly funded. To help identify cost-effective policies to reduce this disparity, we measured the medical costs (in 2015 Canadian dollars) of 3 reportable travel-related infectious diseases (hepatitis A, malaria, and enteric fever) that accrued during a 3-year period (2012-2014) in an ethnoculturally diverse region of Canada (Peel, Ontario) by linking reportable disease surveillance and health administrative data. In total, 318 case-patients were included, each matched with 2 controls. Most spending accrued in inpatient settings. Direct healthcare spending totaled $2,058,196; the mean attributable cost per case was $6,098 (95% CI $5,328-$6,868) but varied by disease (range $4,558-$7,852). Costs were greatest for enteric fever. Policies that address financial barriers to preventive health services for high-risk groups should be evaluated.

The Greater Good: Agency and Inoculation in the British Army, 1914-18.

As the First World War progressed, rates of typhoid diminished. This was heralded as a triumph of sanitary improvement and disease protection; yet as to how the British military achieved this remains a contentious issue. Objections arose around the danger of inoculation and the unpleasant and potentially deadly side effects. Between the unaffected and the sufferers of the vaccine's side effects are the unexplored stories of the refusers. Often bizarre, their accounts include stories of unsanctioned cajoling, arrests, suspension of privileges, and even physically forced inoculation. Soldiers could be encouraged, convinced, and, in rare cases, even forced to undergo inoculation. For others, the opportunity to refuse was often not made clear, as inoculation became part of routine military life. Despite the fact that soldiers were supposed to have complete autonomy over their own inoculation, the reality was often different. Penalties for noncompliance and a lack of clarification about soldiers' rights demonstrated that throughout the war a clash developed between individual autonomy and an authoritarian regime determined to ensure the health of its fighting force.

Edward Ballard and the Practice of Epidemiology in the 19th-Century United Kingdom.

This article recovers the history of Victorian epidemiology through the career of British physician Edward Ballard (1820-1897). Ballard's career provides a useful window into the practices of epidemiology in the 19th century because he held notable public health posts as medical officer of health for Islington and inspector at the Medical Department of the Local Government Board. By the time of his death, in 1897, he typified the transition toward professional epidemiology. In exploring some of the most important environmental and health-related problems in preventive medicine in the 19th century, Ballard was part of a group of influential epidemiologists who studied infectious disease. In particular, he was noted for his research into typhoid fever and industrial health. Yet Ballard's career has largely been forgotten. In this article, I explore Ballard's work as a window into the everyday practices of Victorian epidemiology and suggest that the process of professionalizing epidemiology in the 20th century was about forgetting epidemiology's Victorian past as much as it was about championing it.

Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola.

Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders.

William Boog Leishman: parasitologist and politician.

Famous for the discovery of the parasite, Leishmania, named after him, and the invention of Leishman's stain, William Boog Leishman should perhaps be better known for his work in military and public health, particularly the prevention of typhoid. Leishman was a Medical Officer in the British Army from 1887 until his death in 1926. His early research was on diseases affecting troops posted to stations within the British Empire. He saw cases of Leishmaniasis while stationed in India, and was able to identify the causative organism from his detailed records of his observations. Leishman's most important contribution to public health, however, was his work with typhoid, a major cause of morbidity and mortality in the army. Leishman planned experiments and the collection of data to demonstrate the efficacy of anti-typhoid inoculation and, using his considerable political skills, advocated the adoption of the vaccine. He planned for the inoculation of troops in an emergency so, when war broke out in 1914, the vaccine was available to save thousands of lives. Leishman's colleagues and mentors included Ronald Ross and Almroth Wright. Leishman was less outspoken than either Ross or Wright; this paper shows how the different contributions of the three men overlapped.

How World War 1 changed global attitudes to war and infectious diseases.

World War 1 was a key transition point towards scientific medicine. Medical officers incorporated Louis Pasteur's discoveries into their understanding of microorganisms as the cause of infectious diseases, which were therefore susceptible to rational control and treatment measures even in the pre-antibiotic era. Typhoid vaccination led to the successful evasion of the disastrous epidemics of previous wars. The incidence of tetanus was probably decreased by giving millions of doses of horse antitoxin to wounded soldiers. Quinine treated but could not control malaria; its use required mass compulsion. Tuberculosis was not a great military problem during World War 1, although mortality in civilian populations increased substantially. Treatment of sexually transmitted infections remained a matter of aversive conditioning, with invasive antiseptics used in the absence of antibiotics. Pandemic influenza in 1918-19 killed more people than died during the entire war, showing how much remained beyond the capability of the scientists and doctors who fought infectious diseases during World War 1.

Genomic signature of multidrug-resistant Salmonella enterica serovar typhi isolates related to a massive outbreak in Zambia between 2010 and 2012.

Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term "classical MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both.

What you don't know about vaccines can hurt you.

As physicians, we've all learned in detail about the science behind vaccinations, but I suspect few of us have been taught about the history of vaccinations. Sure, we all know that Dr. Jonas Salk developed the poliovirus vaccine, but I wasn't aware that he inoculated himself, his wife, and his three children with his then experimental vaccine. When our editorial committee decided to focus on vaccinations as our theme for this month's Greene County Medical Society's Journal, I perused the internet for interesting topics. I came across a fascinating website, historyofvaccines.org; this website is a project of the College of Physicians of Philadelphia, touted as being the oldest professional medical organization in the United States. I credit the majority of the information in this article to the above website and the rest to the National Institutes of Health (nih.gov) website; I trust that the information is valid and true, based on the agencies behind these websites. Below are some interesting tidbits about vaccine preventable diseases that I found noteworthy to pass on to our readers.

Death in the White House: President William Henry Harrison's Atypical Pneumonia.

Historians have long maintained that pneumonia killed William Henry Harrison (1773-1841) just 1 month after he became the ninth president of the United States. For more than a century and a half, it has been alleged that the aged Harrison caught a fatal chill the day he was sworn into office while delivering an overly long inaugural address in wet, freezing weather without a hat, overcoat, and gloves. However, a careful review of the detailed case summary written by his personal physician suggests that enteric fever, not pneumonia per se, was the disorder that carried off "Old Tippecanoe." Two other presidents of that era, James Knox Polk and Zachary Taylor, also developed severe gastroenteritis while in office. Taylor's illness, like Harrison's, proved fatal. In all 3 cases, the illnesses were likely a consequence of the unsanitary conditions that existed in the nation's capital during most of the nineteenth century.

Scientific strategy and ad hoc response: the problem of typhoid in America and England, C. 1910-50.

In the early twentieth century, death rates from typhoid in European cities reached an all time low. By contrast, death rates in America were six times as high, and the American public health community began a crusade against the disease in 1912. In the 1920s, hopes for greater control of the disease focused not just on sewers and drinking water supplies, but on the newly established scientific means of immunization, the supervision of food-related pathways of infection, and the management of healthy carriers. The management of carriers, which lay at the core of any typhoid control program, proved an intractable problem, and typhoid remained a public health concern. America and England both struggled with control of the disease during the interwar period. Coming from different starting points, however, their approaches to the problem differed. This paper compares and contrasts these different public health strategies, considers the variable quality of support provided by bacteriological laboratories, and demonstrates that "accidental" typhoid outbreaks continued to happen up to the outbreak of World War II.

CONTRIBUTION TO THE UNDERSTANDING OF THE HEALTH SITUATION WITHIN THE POPULATION IN SLAVONIA AND SRIJEM DURING THE SECOND WORLD WAR WITH AN EMPHASIS ON INFECTIOUS DISEASES / Prilog poznavanju zdravstvenih prilika stanovnistva u Slavoniji i Srijemu tijekom Drugoga svjetskog rata, s naglaskom na zarazne bolesti

During World War II, the population of agricultural areas of Slavonia and Srijem lived in privation, but there was no famine. A more serious threat was infectious diseases, such as malaria, typhoid fever, and dysentery, which were also present within the population in the post-war period. Major epidemics broke out mostly in areas under partisan control, especially in the areas of western and central Slavonia, where major epidemic typhus contagious broke out. Venereal diseases, less common in the Slavonian area before the war, were also on the rise. Two factors had an impact on the health situation within the population ­ state medical institutions and partisan medical corps. Health care and measures to combat infectious diseases were provided by state authorities, and that is still an insufficiently explored area in historiography. During the first years of the war, the partisan medical corps personnel, initially mostly semiskilled and lacking necessary medical equipment and medications, relied on the support from the population to a greater extent than they were able to provide medical care to them. With the arrival of professional staff and the acquisition of medicines and medical equipment, mainly sourced from medical institutions in areas under partisan control, they assumed a more active role in supporting civilian authorities under the "people's rule"­specifically, the people's liberation committees. Their focus shifted to healthcare for the civilian population, primarily aimed at suppressing and preventing infectious diseases. Further research on this topic will contribute to a more realistic perception of the civilian population's everyday life during the war, which was presented in memoir literature and historiography of the socialist period as a heroic act of resistance rather than a struggle for survival in the conditions of privation and diseases; it will also complete the picture of the human losses of the civilian population caused by infectious diseases.

[Pharmacologists in the camps In the Third Reich--part one]. / Farmakolodzy w obozach III Rzeszy--czesc pierwsza.

The outbreak of World War II is considered as the inception of the pharmacology of the III Reich. Hitler's soldiers are decimated on the front lines by malaria, typhoid, gas gangrene, they need efficient and easy accessible medicines. From now on German forces are engaged into pharmacology of war. Only augmentation of Fuehrer's army effectiveness is reckoned with. Research centers in the concentrations camps are being organized, prisoners are used as the human subject. In the investigations many noted and respected personages are involved. Dr. Helmut Vetter and Dr. Ding Erwing Schuler studied chemicals which may had potential use in the prevention and treatment of typhoid. Professor Eugen Haagen carried out experiments concerning the use of vaccines against typhoid. The latter, although sentenced to life imprisonment, he returned to research in 1952 as a result of the amnesty activities in the former West Germany, and then worked as a researcher. His studies were reflected in the book, and scientific publications. Professor. Eugen Haagen died of natural causes in 1972.

[The abdominal typhus outbreak in Civitella del Tronto (Teramo, Italy) during the first half of 1817]. / Notizie sull'epidemia di tifo addominale in Civitella del Tronto (Teramo) durante la prima metà dell'anno 1817.

The authors describe the characteristics of the large outbreak of typhoid fever in Civitella del Tronto (Italy) in the year 1817. As reported in the "Rapporti Periodici sulla Salute Pubblica" ("Public Health Reports") periodically written by general practitioners, from March to June 1817 the morbidity rate was over 1% and both genders were equally affected. The most affected age group was the 30 to 40 year-old. Only 13% of the cases involved children aged 0 to 10 years. Epidemiological data suggest that the disease was not very infectious: it affected a slight number of individuals and only marginally infected the inhabitants of the areas around the main town of Civitella del Tronto. Public Health authorities of the Kingdom of Naples were likely able to efficiently control the sanitary conditions of the territories bordering the state.

Brief communication: evidence of Bartonella quintana infections in skeletons of a historical mass grave in Kassel, Germany.

In 2008, a mass grave was found on the grounds of the University of Kassel, Germany. Historians hypothesized that the individuals died in a typhoid fever epidemic in winter 1813/14. To test this hypothesis, the bones were investigated on the presence of specific DNA of pathogens linked to the historical diagnosis oftyphoid fever. It was possible to prove the specific DNA of Bartonella quintana in three individuals, suggesting that their cause of death is linked to an epidemic background.

THE TERMINAL APHONIA OF ALEXANDER THE GREAT, A SILENT HERALD OF AN ORDINARY DEATH

Even though the absence of the body prevents sure conclusions, the death of Alexander the Great remains a hot topic of retrospective diagnosis. Due to the serious mishandling of ancient sources, the scientific literature had Alexander dying of every possible natural cause. In previous works, the hypothesis that typhoid fever killed Alexander was proposed, based on the presence of the remittent fever typical of this disease in the narrations of Plutarch and Arrian. Here we provide additional evidence for the presence of stupor, the second distinctive symptom of typhoid fever. In fact, based on the authority of Caelius Aurelianus and Galen, we demonstrate that the word ἄφωνος, used to describe the last moments of Alexander, is a technical word of the lexicon of the pathology of Hippocrates. Used by him, the word defines a group of diseases sharing a serious depression of consciousness and motility. The association of stupor with the remittent fever strengthens the typhoid fever hypothesis.

Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014-2019: a cross-sectional analytical study.

Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics.Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns.Aim. By characterising factors associated with antimicrobial resistance in cases of S. Typhi and S. Paratyphi imported to England, we aim to guide effective empirical treatment.Methodology. All English isolates of S. Typhi and S. Paratyphi 2014-2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005-2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance.Results. We identified 1088 cases of S. Typhi, 729 S. Paratyphi A, 93 S. Paratyphi B, and one S. Paratyphi C. In total, 93 % were imported. Overall, 90 % of S. Typhi and 97 % of S. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S. Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S. Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4-66.4), India (aOR=21.8, 95 % CI: 11.6-41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8-13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S. Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4-5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04-0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005-2012 London survey indicates substantial increases in the prevalence of resistance of S. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79-98 %) and Africa (from 12-60 %).Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.