A Brief History of Shigella.

The history of Shigella, the causative agent of bacillary dysentery, is a long and fascinating one. This brief historical account starts with descriptions of the disease and its impact on human health from ancient time to the present. Our story of the bacterium starts just before the identification of the dysentery bacillus by Kiyoshi Shiga in 1898 and follows the scientific discoveries and principal scientists who contributed to the elucidation of Shigella pathogenesis in the first 100 years. Over the past century, Shigella has proved to be an outstanding model of an invasive bacterial pathogen and has served as a paradigm for the study of other bacterial pathogens. In addition to invasion of epithelial cells, some of those shared virulence traits include toxin production, multiple-antibiotic resistance, virulence genes encoded on plasmids and bacteriophages, global regulation of virulence genes, pathogenicity islands, intracellular motility, remodeling of host cytoskeleton, inflammation/polymorphonuclear leukocyte signaling, apoptosis induction/inhibition, and "black holes" and antivirulence genes. While there is still much to learn from studying Shigella pathogenesis, what we have learned so far has also contributed greatly to our broader understanding of bacterial pathogenesis.

Wartime infections and tragedies at the beginning of the 20th century in the Eastern part of Turkey.

In the early 20th century, Europe and the Ottoman Empire as a whole experienced a large number of epidemic diseases, and several wars. During World War I (WW1) a general mobilization of the medical services under Ottoman Empire rule was enacted. However, shortages of food and water, unfavourable weather and poor sanitary conditions resulted in numerous diseases at the battle fronts. Indeed, during the Ottoman-Russian war on the Eastern Front, the Turks suffered massive loss of life. This article therefore emphasises that during WW1, such loss of life in the Ottoman Army on the Eastern Front, which was one of the key fronts of the war, was mainly due to epidemic diseases rather than battles.

Multiple- locus variable-number tandem-repeat analysis (MLVA) of Shigella sonnei isolates of 2012 outbreak I. R. Iran.

Shigella sonnei is a major cause of diarrhea especially in children. Molecular study can help to determine the outbreak of this bacterium. Multiple-Locus Variable number tandem repeat Analysis (MLVA) will largely influence the public health field by introducing newer, faster, safer, and effective procedure for typing of microorganisms. A total of fifty shigella isolates were collected between November 2012 to October 2013 in Tehran, Iran. The strains were identified base on biochemical and molecular tests. Subsequently, all shigella species were confirmed by species-specific polymerase chain reaction (PCR). Virulence factors were detected using PCR for ial, set1A, and set1B genes. The strains were genotyped by MLVA typing method. All of the isolates were identified as S. sonnei by biochemical and molecular (PCR) methods. Virulence genes identified among all isolates included ial, and set1A genes in 20% and 5% of all isolates, respectively. On the other hand, none of isolates were positive for set1B gene. Using MLVA method 22 MLVA types were identified. MLVA type 11 accounted for 32% of isolates. Moreover, all virulence factors were only detected in MLVA type 11, 9, 5, 4. The results of this study indicate that the Iranian 2012-2013 S. sonnei outbreak isolates were virulent and clonaly related. Furthermore, this study showed that MLVA can be used as useful method for S. sonnei genotyping in epidemiological investigations.

ESBL-Producing and Macrolide-Resistant Shigella sonnei Infections among Men Who Have Sex with Men, England, 2015.

In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum ß-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.

Elevated Risk for Antimicrobial Drug-Resistant Shigella Infection among Men Who Have Sex with Men, United States, 2011-2015.

Shigella spp. cause ≈500,000 illnesses in the United States annually, and resistance to ciprofloxacin, ceftriaxone, and azithromycin is emerging. We investigated associations between transmission route and antimicrobial resistance among US shigellosis clusters reported during 2011-2015. Of 32 clusters, 9 were caused by shigellae resistant to ciprofloxacin (3 clusters), ceftriaxone (2 clusters), or azithromycin (7 clusters); 3 clusters were resistant to >1 of these drugs. We observed resistance to any of these drugs in all 7 clusters among men who have sex with men (MSM) but in only 2 of the other 25 clusters (p<0.001). Azithromycin resistance was more common among MSM-associated clusters than other clusters (86% vs. 4% of clusters; p<0.001). For adults with suspected shigellosis, clinicians should culture feces; obtain sex histories; discuss shigellosis prevention; and choose treatment, when needed, according to antimicrobial drug susceptibility. Public health interviews for enteric illnesses should encompass sex practices; health messaging for MSM must include shigellosis prevention.

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities.

Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug-resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.

Multidrug-Resistant Shigella Infections in Patients with Diarrhea, Cambodia, 2014-2015.

We observed multidrug resistance in 10 (91%) of 11 Shigella isolates from a diarrheal surveillance study in Cambodia. One isolate was resistant to fluoroquinolones and cephalosporins and showed decreased susceptibility to azithromycin. We found mutations in gyrA, parC, ß-lactamase, and mphA genes. Multidrug resistance increases concern about shigellosis treatment options.

Global phylogeography and evolutionary history of Shigella dysenteriae type 1.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

Lethality of First Contact Dysentery Epidemics on Pacific Islands.

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history.

Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014.

To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004-2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis.

Shift in serotype distribution of Shigella species in China, 2003-2013.

We identified 2912 Shigella isolates from diarrhoeal patients in China during 2003-2013. The most common species was Shigella flexneri (55.3%), followed by Shigella sonnei (44.1%); however, S. sonnei is becoming increasingly prevalent. Among the S. flexneri isolates, serotypes 2a and X variant (-:7,8, E1037) were the two most prevalent serotypes, and serologically atypical isolates were also commonly identified. Overall, S. sonnei, S. flexneri 2a and S. flexneri X variant (-:7,8, E1037) accounted for 76.1% of all Shigella isolates, and their prevalence increased from 54.0% during 2003-2004 to 84.1% during 2011-2013. A change was observed in the serotype distribution of Shigella in China during this period, and we propose an ideal strategy to inform the development of a broadly effective Shigella vaccine candidate.

Spatiotemporal pattern of bacillary dysentery in China from 1990 to 2009: what is the driver behind?

BACKGROUND: Little is known about the spatiotemporal pattern of bacillary dysentery (BD) in China. This study assessed the geographic distribution and seasonality of BD in China over the past two decades. METHODS: Data on monthly BD cases in 31 provinces of China from January 1990 to December 2009 obtained from Chinese Center for Disease Control and Prevention, and data on demographic and geographic factors, as well as climatic factors, were compiled. The spatial distributions of BD in the four periods across different provinces were mapped, and heat maps were created to present the seasonality of BD by geography. A cosinor function combined with Poisson regression was used to quantify the seasonal parameters of BD, and a regression analysis was conducted to identify the potential drivers of morbidity and seasonality of BD. RESULTS: Although most regions of China have experienced considerable declines in BD morbidity over the past two decades, Beijing and Ningxia still had high BD morbidity in 2009. BD morbidity decreased more slowly in North-west China than other regions. BD in China mainly peaked from July to September, with heterogeneity in peak time between regions. Relative humidity was associated with BD morbidity and peak time, and latitude was the major predictor of BD amplitude. CONCLUSIONS: The transmission of BD was heterogeneous in China. Improved sanitation and hygiene in North-west China, and better access to clean water and food in the big floating population in some metropolises could be the focus of future preventive interventions against BD. BD control efforts should put more emphasis on those dry areas in summer.

Genomic analysis of the emergence of 20th century epidemic dysentery.

BACKGROUND: Shigella dysenteriae type 1 (Sd1) causes recurrent epidemics of dysentery associated with high mortality in many regions of the world. Sd1 infects humans at very low infectious doses (10 CFU), and treatment is complicated by the rapid emergence of antibiotic resistant Sd1 strains. Sd1 is only detected in the context of human infections, and the circumstances under which epidemics emerge and regress remain unknown. RESULTS: Phylogenomic analyses of 56 isolates collected worldwide over the past 60 years indicate that the Sd1 clone responsible for the recent pandemics emerged at the turn of the 20th century, and that the two world wars likely played a pivotal role for its dissemination. Several lineages remain ubiquitous and their phylogeny indicates several recent intercontinental transfers. Our comparative genomics analysis reveals that isolates responsible for separate outbreaks, though closely related to one another, have independently accumulated antibiotic resistance genes, suggesting that there is little or no selection to retain these genes in-between outbreaks. The genomes appear to be subjected to genetic drift that affects a number of functions currently used by diagnostic tools to identify Sd1, which could lead to the potential failure of such tools. CONCLUSIONS: Taken together, the Sd1 population structure and pattern of evolution suggest a recent emergence and a possible human carrier state that could play an important role in the epidemic pattern of infections of this human-specific pathogen. This analysis highlights the important role of whole-genome sequencing in studying pathogens for which epidemiological or laboratory investigations are particularly challenging.

Neil Hamilton Fairley KBE FRCP FRS (1891-1966): an outstanding tropical physician in the twentieth century.

In the late nineteenth and early twentieth centuries, British physicians led the way in tropical medicine research. Several years later scientific advances had slowed, and Fairley's numerous contributions were thus most welcome. Neil Hamilton Fairley was born of Scottish parents at Victoria, Australia. After qualification at Melbourne, he joined the Australian Army Medical Service (AAMS) and after several minor research projects, made valuable contributions to the understanding of tropical sprue at Bombay (now Mumbai), India. However, Fairley's major researches were carried out during World War II (1939-45). Together with J S K Boyd he demonstrated the great value of sulphaguanidine in bacillary dysentery. Working in northern Australia and the south-Pacific region, he both contributed to elucidation of the Plasmodium vivax life-cycle, and more importantly demonstrated the value of alternative anti-malarial compounds to quinine (which was not readily available). Back in London after the war, Fairley briefly occupied the Wellcome Chair of Tropical Medicine, strongly supported London's clinical tropical medicine, and was subsequently knighted in 1950.

The plague of the Philistines and other pestilences in the Ancient World: exploring relations between the religious-literary tradition, artistic evidence and scientific proof.

In ancient times the term pestilence referred not only to infectious disease caused by Yersinia pestis, but also to several different epidemics. We explore the relations between references in the Bible and recent scientific evidence concerning some infectious diseases, especially the so-called Plague of the Philistines and leprosy. In addition, some considerations regarding possible connections among likely infectious epidemic diseases and the Ten Plagues of Egypt are reported. Evidence suggesting the presence of the rat in the Nile Valley in the II millennium BC is shown; a possible role of the rat in the plague spreading already in this historical period should be confirmed by these data. While the biblical tale in the Book of Samuel may well report an epidemic event resembling the plague, as to date this infectious disease remains unknown, it is not conceivable to confirm the presence of leprosy in the same age, because the little palaeopathologic evidence of the latter disease, in the geographic area corresponding to Egypt and Palestine, is late, dating back only to the II century AD.