Typhoid fever

• 1. Introduction

  ›

  Typhoid fever has killed presidents, composers, and princes. It silenced Wilbur Wright in 1912, took Franz Schubert at 31, and may have helped launch the entire aviation age: when Orville Wright lay sick with typhoid in 1896, his brother read aloud to him from the writings of Otto Lilienthal, a German pioneer of human flight, and the two men never looked back.

  The disease is caused by a single bacterium, Salmonella enterica serotype Typhi, which spreads only through humans and enters the body through contaminated food or water. It travels through the intestines, the spleen, the liver, the bone marrow, and the blood. Without treatment, it can kill as many as one in five people it infects. With antibiotics, that figure drops below one in twenty-five.

  In 2015, there were 12.5 million new cases worldwide and roughly 149,000 deaths. India carries the heaviest burden. Children are the most commonly affected. And yet the disease is also a story of hard-won progress: a scientist named Almroth Edward Wright built the first effective vaccine in 1896, helping save what he later estimated as up to half a million soldiers in the First World War. How typhoid was understood, fought, and still not entirely defeated is a story that stretches from ancient Athens to a Pakistani city gripped by drug-resistant strains today.

• 2. How the Body Breaks Down

  ›

  Classically, untreated typhoid fever moves through three distinct stages, each lasting roughly a week. In the first week, the body temperature climbs slowly. A bloody nose appears in a quarter of cases. White blood cell counts drop. Blood cultures taken during this stage are positive for S. Typhi, yet the Widal test, which detects antibodies, usually returns negative.

  By the second week, the patient is often too exhausted to leave bed. Fever plateaus at a high level with a distinctive dicrotic pulse wave. The condition earned the nickname "nervous fever" because delirium sets in: patients are sometimes calm, sometimes agitated. Rose-colored spots appear on the lower chest and abdomen in around a third of patients. The spleen and liver enlarge and become tender. The abdomen is distended and painful.

  The third week brings the gravest dangers. Intestinal hemorrhage can occur as congested Peyer's patches in the gut begin to bleed. Intestinal perforation in the distal ileum is described in the source as "often fatal," and it may arrive without warning until sepsis or widespread infection of the abdominal cavity takes hold. Neuropsychiatric symptoms appear, described clinically as "muttering delirium" or "coma vigil," with patients picking at bedclothes or invisible objects. One study of patients who required surgery for intestinal perforation recorded a 30-day mortality rate of 9% and surgical site infections in 67% of cases, with that burden falling predominantly on low-resource countries.

• 3. Water, Milk, and Mary Mallon

  ›

  In 1847, physician William Budd investigated a typhoid epidemic in Clifton and found that all 13 of 34 people who had contracted the disease drew their drinking water from the same well. That observation came two years before John Snow published his early theory linking contaminated water to cholera. Budd later became health officer of Bristol, secured a clean water supply for the city, and spent his career documenting typhoid as a waterborne disease.

  Milk delivery created a separate avenue of infection in the early 20th century. Distributors sometimes diluted their milk with contaminated water, or washed the glass bottles with it. In Boston in 1899-24 cases of typhoid were traced to a single milkman whose wife had died of typhoid the week before. In 1908, a milkman named J.J. Fallon died of the disease, and subsequent investigation of his route turned up 348 cases across the city and 272 in the Jamaica Plain neighborhood alone. At least one death was recorded: Mrs. Sophia S. Engstrom, aged 46. The Boston Globe declared the outbreak over in a brief published statement. The Jamaica Plain neighborhood at that time was home largely to working-class and poor immigrants, mostly from Ireland.

  No carrier has become more famous than Mary Mallon. Working as a personal cook for upper-class families in New York City between 1907 and 1915, she was linked to 51 cases and 3 deaths. The concept of an asymptomatic carrier had been hypothesized but never proven before Mallon. Civil engineer George Soper, hired to investigate a household outbreak in the summer of 1906, eventually tracked her down. His published account bristles with self-congratulation; he complained that the media "robs me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America." New York City reported 3,000 to 4,500 cases of typhoid annually at the time Mallon was active. Her cases came almost exclusively from wealthy households that could afford a private cook.

• 4. From Athens to Aberdeen

  ›

  The plague of Athens, which struck during the Peloponnesian War around 430 B.C., is the oldest suspected outbreak. Athenians retreating from the Spartans crowded into a walled city and overwhelmed its water and waste infrastructure. In 2006, researchers examining a mass burial site from that period detected DNA fragments similar to modern S. Typhi in the remains. No Yersinia pestis, no Rickettsia prowazekii, no tuberculosis bacteria were found.

  Between 1607 and 1624, an outbreak killed 85% of the population at the James River in Virginia. The World Health Organization estimates more than 6,000 deaths during that period. In the Spanish-American War, government records show over 21,000 troops contracted typhoid, resulting in 2,200 deaths. In 1902, guests at mayoral banquets in Southampton and Winchester died after eating oysters sourced from Emsworth, where oyster beds had been contaminated with raw sewage; the dead included the Dean of Winchester.

  The Maidstone, Kent, outbreak of 1897-1898 holds a specific distinction: it was the first time a typhoid vaccine was used in a civilian outbreak. Almroth Edward Wright's vaccine was offered to 200 healthcare workers, and of the 84 who accepted it, none developed typhoid; 4 who declined became ill. In Aberdeen, Scotland, in the summer of 1964, more than 500 people were quarantined in hospital for a minimum of four weeks after eating contaminated canned beef from Argentina. The outbreak was contained without a single death.

• 5. Naming the Bacterium

  ›

  Polish scientist Tadeusz Browicz described a short bacillus in the organs and feces of typhoid victims in 1874. He could isolate and grow the bacteria but stopped short of claiming it caused the disease. In April 1880, Edwin Klebs found similar bacilli in Peyer's patches in typhoid victims and speculated on their role without proving it.

  The decisive work came from Karl Joseph Eberth, who in 1880 isolated the same bacterium from 18 of 40 typhoid victims while failing to find it in any control cases from other diseases. Pathologist Georg Theodor August Gaffky, born in 1850 and died in 1918, confirmed those findings in 1884 by isolating the bacterium from a typhoid victim's spleen and growing it on solid media. The organism acquired several names: Eberth's bacillus, Eberthella Typhi, the Gaffky-Eberth bacillus. It is now called Salmonella enterica serovar Typhi.

  The disease itself had been traveling under aliases for far longer. French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis distinguished typhoid from typhus through autopsies in Paris, noting that victims shared lesions in the Peyer's patches of the gut. British physicians were skeptical because both diseases circulated in Britain, but in France only typhoid was present, making the distinction clearer. It was Sir William Jenner who closed the argument, examining 66 autopsies and showing that the symptom cluster of headaches, diarrhea, rash spots, and abdominal pain appeared only in patients whose intestines carried those lesions. The word "typhoid" itself means "resembling typhus," a name that captured the confusion before Jenner's evidence settled it.

• 6. The Vaccine and the Wars

  ›

  Almroth Edward Wright built the first effective typhoid vaccine at the Army Medical School in Netley, Hampshire. Introduced in 1896, it was used by the British during the Second Boer War in South Africa, a conflict in which typhoid killed more soldiers than enemy fire. Wright grew the bacterium at body temperature in broth, then heated it to 60 degrees Celsius, killing the pathogen while keeping its surface structures intact. He then tested whether patients' blood could agglutinate, or clump, live typhoid bacteria after vaccination, using visible clumping as proof the body was producing what would later be called antibodies.

  Citing the Boer War, Wright persuaded the British Army to produce 10 million doses for the Western Front. It was the only army to enter the First World War with its troops fully vaccinated against typhoid, and for the first time in British military history, combat casualties exceeded those from disease.

  In the United States, Army physician Frederick F. Russell adopted Wright's vaccine in 1909, and two years later ran the first program in which an entire national army was vaccinated. Typhoid vaccination became mandatory for American military personnel in 1911. Before that, the rate of typhoid in the U.S. military ran at 14,000 or more cases per 100,000 soldiers. By the First World War, it had fallen to 37 per 100,000. In 1934, Arthur Felix and Margaret Pitt discovered the Vi capsular antigen, enabling the development of the safer Vi antigen vaccine used widely today. They also isolated the strain Ty2, which became the parent strain of Ty21a, the live-attenuated oral vaccine still given to travelers.

• 7. Resistance and the Road Ahead

  ›

  Chloramphenicol, isolated from Streptomyces bacteria by David Gotlieb in the 1940s, was the first antibiotic proven against typhoid fever. American army doctors tested it in Kuala Lumpur, Malaysia, in 1948. Patients who completed the full course cleared the infection; those who received a lower dose relapsed. Resistance to chloramphenicol spread through Southeast Asia by the 1950s. It is now used only as a last resort.

  Resistance to ampicillin, trimethoprim-sulfamethoxazole, and streptomycin is now so common that a specific category exists for typhoid that defeats all of them: multidrug-resistant typhoid. Ciprofloxacin, once a reliable alternative, faces increasing resistance particularly in the Indian subcontinent and Southeast Asia. Many treatment centers now shift to ceftriaxone as the first choice for suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. Azithromycin has been proposed as better still for resistant strains; it can be taken by mouth, unlike ceftriaxone, which requires injection, and it costs less.

  Since November 2016, Pakistan has been grappling with an outbreak of extensively drug-resistant typhoid, a strain that defeats even the newer options. The global picture in 2017 showed that across 22 European Union and European Economic Area countries, 90.9% of confirmed typhoid and paratyphoid cases were travel-related, mainly acquired during travel to South Asia. A phase 3 trial of the typhoid conjugate vaccine reported in December 2019 found 81% fewer cases among vaccinated children, a result that points toward the most plausible path forward: combining a newer, more robust vaccine with the public health infrastructure to deliver it.