Greece played an important role in the early history of Salmonella and typhoid fever. The first recorded outbreak of typhoid fever may have been what is now known as the “plague of Athens” around 430 BC, with DNA from Salmonella enterica serovar Typhi identified from bodies in a burial pit housing presumed victims of this plague, potentially explaining how one-third of the city’s population, or nearly 300,000 people, may have died over just four years.1* Alexander the Great, the Greek military leader who built an empire stretching from modern day Egypt to Afghanistan, likely died of typhoid fever in 323 BC as well.2
It was around this time that Greek mythology described the 12 labors of the hero Heracles, undertaken at the behest of King Eurystheus. The second of these labors involved the slaying of the mythical Hydra, a multi-headed monster. Heracles found it easy enough to cleave off one of the monster’s heads, but soon learned that the creature simply grew two more heads, and that one of the original heads was immortal. Heracles enlisted the assistance of his nephew Iolaus, who cauterized every mortal head after it was severed from the body by Heracles (perhaps an early homage to sterilization?), who then finally removed and buried the remaining immortal head.
Like the mythical Greek Hydra’s heads, modern clinicians dealing with Salmonella over the last century may have felt like Heracles, faced with a constantly increasing number of Salmonella species and outbreaks emerging and wreaking havoc on the public health system. Prior to DNA analysis of Salmonella, each serotype was considered a separate species under the genus Salmonella.3 Salmonella slowly grew from 44 recognized species/serotypes in 1934 to over 2,500, with more described each year. Most species/serotypes arose from either a specific geographic location or a specific animal source. These species contributed to a devastating burden of human disease.
In 2005, the organism was reclassified under just two species: Salmonella enterica and Salmonella bongori.4 This greatly simplified the overwhelming task of keeping up to date with the ever-expanding list of Salmonella species and provided a helpful framework for clinicians to understand the disease. The majority of human infections are now attributed to just one species: S enterica (including typhoid fever and most non-typhoidal infections, such as Salmonella foodborne illnesses seen in the US).5
S enterica, however, like Hydra’s immortal head, single-handedly continues to plague humanity, despite our best efforts. Typhoid fever currently affects nearly 10 million people per year globally, with 110,000 deaths annually.6 Not to be outdone, invasive disease from non-typhoidal Salmonella may cause up to 535,000 infections per year and 77,500 deaths annually, with the highest incidence of disease in children under 5 years of age.7 Though we have vaccines and effective antimicrobial agents, ongoing and emerging barriers to control of the pathogen (eg, increasing antimicrobial resistance) and declining public health infrastructure (eg, lack of clean water and food sources) prevent effective control of the disease, particularly at a global level.
Muralidhar, Watts, and Kamath nicely summarize many of these issues for the practicing pediatrician in the January Pediatrics in Review article, Salmonella Infections. Unfortunately, Salmonella is likely here to stay for the immediate future, both in the US and globally. Heracles won’t come to our rescue to help us vanquish this ancient foe. However, just as he relied upon the help of others to destroy the Hydra, we will hopefully someday produce a concerted global effort toward more effective control of this devastating disease and be able to finally cleave the seemingly immortal head from Salmonella enterica, burying it once and for all.
*Some historians dispute this, claiming the historical record may be more supportive of alternative diagnoses, such as measles. See Cunha BA. The Cause of the Plague of Athens: Plague, Typhoid, Typhus, Smallpox, or Measles? Infect Dis Clin North Am. 2005;18(1):29-43.
References
- Papagrigorakis MJ, Yapijakis C, Synodinos PN, Baziotopoulou-Valavani E. DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the plague of Athens. Int J Infect Dis. 2006;19(3):206–214
- Cunha B. The death of Alexander the Great: malaria or typhoid fever? Infect Dis Clin North Am. 2004;18(1):53–63
- Gossner CM, Le Hello, S, de Jong B, et al. Around the world in 1,475 salmonella geo-serotypes. Emerg Infect Dis. 2016;22(7):1298–1302
- Judicial Commission of the International Committee on Systematics of Prokaryotes. Int J Syst Evol Microbiol. 2005;55:525–532
- Chattaway MA, Langridge GC, Wain J. Salmonella nomenclature in the genomic era: a time for a change. Nature. 2021;11:7494
- World Health Organization. Typhoid. Available at: https://www.who.int/news-room/fact-sheets/detail/typhoid. Accessed November 26, 2024. Last updated 30 March, 2023.
- GBD 2017 Non-Typhoidal Salmonella Invasive Disease Collaborators. The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the global burden of disease study 2017. Lancet. 2019;19:1312–1324