A deadly illness once thought to be left behind in ancient history is making a comeback as it mutates to become more resistant to even the most powerful modern-day drugs.
Typhoid fever is caused by a type of Salmonella bacteria - Salmonella enterica serotype Typhi (S. Typhi) - and is more common in Africa, Asia and Latin America.
Globally, there are about 9.2 million cases reported each yeah, with just 5,700 in the US - most of which are contracted while traveling internationally.
In the US, typhoid fever leads to about 620 hospitalizations annually. Deaths are extremely rare in the US, with less than one reported a year. Without treatment, the fever is deadly in 10 to 20 percent of cases.
The standard of care is antibiotics, but resurfaced research has shown the bacterium is mutating to better evade go-to treatments and rarer antibiotic-resistant strains are now replacing strains that respond to oral medications.
In 2022, scientists from across the globe sequenced the genomes of 3,489 S. Typhi strains contracted from 2014 to 2019 in Nepal, Bangladesh, Pakistan and India. Results showed a rise in the resistant XDR Typhi strain.
Not only is this strain resistant to older medications, but more worryingly, it is resistant to newer, more powerful drugs as well.
Researchers raised concerns over the rise in the strain but also over the increased spread around the globe, including to North America and Europe.
Most XDR Typhi strains originate in South Asian countries, but the researchers identified 200 cases of international spread of the strain since 1990.
Spread has mainly been to East and Southern Africa , but now the strain has been found in places as far as Canada, the UK and the US.
Stanford University infectious disease researcher Jason Andrews, lead author on the study, said: 'The speed at which highly-resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk.
'At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem.'
Older medications it is resistant to include ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole, and the new drugs include fluoroquinolones and third-generation cephalosporins.
XDR typhi has been on scientists' radars since it was first identified in Pakistan in 2016. Just three years later, it became the dominant strain in the country.
Traditionally, it was treated with antimicrobials, but by the turn of the millennium, mutations that are resistant to those drugs accounted for more than 85 percent of all cases in Bangladesh, India, Pakistan, Nepal, and Singapore.
Now, just one medication can treat it, but researchers fear the strain will mutate soon and evade that drug as well.
The authors wrote in the study that the spread of drug-resistant strains is 'threatening the efficacy of all oral antimicrobials for typhoid treatment.'
The illness-causing bacteria is shed in people's stool and the fever spreads when someone comes into contact with the bacteria, either through food, drinks or water contaminated by stool or sewage.
Typhoid fever is caused by a type of Salmonella bacteria - Salmonella enterica serotype Typhi (S. Typhi) - and is more common in Africa, Asia and Latin America
The above map shows where in the world typhoid fever vaccines are recommended
It can also be contracted by touching something an infected person contaminated with their stool.
Symptoms include a high fever that typically lasts more than three days, weakness, stomach pain, constipation or diarrhea, cough, loss of appetite and, in some cases, a rash with rose-colored spots.
It is vital to seek treatment early as untreated typhoid fever can lead to lasting health impacts and death.
As antibiotic-resistance becomes more common, the bacteria can grow and multiple unchecked.
Drug-resistant illnesses are harder to treat, last longer and cause more severe illness.
To prevent typhoid fever, the CDC recommends getting a vaccine against the illness before traveling to countries where it is common.
An oral vaccine - four pills taken over four days - and an injectable vaccine - one shot - are both available for people six and older and two and older, respectively.
They both should be obtained two weeks before travel.
While traveling, the CDC urges people to follow safe eating and drinking habits, such as avoiding raw food and street vendors, thoroughly cooking food and drinking pasteurized milk, and to practice good hygiene, such as thorough hand washing.