Although typhoid fever has been present in mankind for thousands of years, it is rarely seen as a threat in developed countries today. However, this historic disease remains a significant health problem in many countries.
Research published in 2022 identified a worrying trend: the bacteria responsible for typhoid are becoming increasingly resistant to drugs, leaving only strains still sensitive to therapy.
Typhoid is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi), and antibiotic therapy is currently the only effective therapeutic option. However, over the last few decades, resistance to antibiotics in this bacterium has increased, significantly complicating the treatment and control of the disease.
As part of the aforementioned research, a team of scientists analyzed genetic material from 3.489 S. Typhi samples collected between 2014 and 2019 in Nepal, Bangladesh, Pakistan, and India. The results showed an increasingly frequent occurrence of strains with extensive drug resistance (XDR Typhi), which indicates the spread of highly resistant variants of this bacterium.
XDR Typhi strains show extremely high levels of antibiotic resistance. They are becoming less responsive to standard drugs that were previously used as first-line therapy, such as ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. In addition, they are increasingly developing resistance to newer antibiotics, including fluoroquinolones and third-generation cephalosporins, which makes treatment difficult.
Even more worrying is that these highly resistant strains are spreading rapidly outside the regions where they were originally found. Although most cases originate in South Asia, since 1990, scientists have registered close to 200 cases in which these strains have spread to other countries.
The highest number of transmission cases was recorded in Southeast Asia and in East and Southern Africa. However, the presence of these resistant typhus variants has also been confirmed in developed countries, including the United Kingdom, the United States of America, and Canada.
According to Stanford University infectious disease scientist Jason Andrews, the speed with which resistant strains of S. Typhi have emerged and spread in recent years is cause for concern. He emphasizes that these findings indicate an urgent need to strengthen preventive strategies, especially in regions most at risk of disease spread.
Experts have been warning for years about the increasing frequency of antibiotic-resistant typhoid, which shows resistance to antibiotics. The first case of an extensively resistant (XDR) strain of typhus was registered in Pakistan in 2016, and by 2019, the strain had become the most widespread form of the bacteria in that country.
Previously, infections caused by these bacteria were most often treated with modern antibiotics, such as quinolones, cephalosporins, and macrolides. However, at the beginning of the 21st century, genetic changes emerged that enabled bacteria to develop resistance to quinolones.
As a result, more than 85% of thyroid cases in Bangladesh, India, Pakistan, Nepal, and Singapore began to involve drug-resistant strains. At the same time, an increasing number of bacteria resistant to cephalosporins has been recorded.
In modern typhoid therapy, there is practically only one oral antibiotic left – azithromycin, a macrolide. However, there are growing doubts about the program’s effectiveness. Research results from 2022 showed that mutations conferring resistance to azithromycin are already emerging and spreading.
This fact poses a serious challenge, as it may compromise the effectiveness of all currently used oral antibiotics as therapeutic options for treating typhus. Although these mutations have not yet been reported in XDR strains of S. Typhi, their eventual appearance in combination with existing multiple resistance could significantly complicate the treatment of this infection.
If typhoid fever is not diagnosed and treated promptly, the disease can be fatal in 1in 5 cases. Data from 2024 indicate that more than 13 million cases have been recorded worldwide, which confirms that typhus remains a significant public health challenge.
One way to reduce the risk of an epidemic of this disease is the use of conjugate vaccines against typhus, which can help better control its spread. However, experts stress that the first priority is to expand access to these vaccines. Without widespread access to immunization, the world could face a major new health problem.
Scientists especially emphasize that the recent emergence of extensively drug-resistant (XDR) strains of S. Typhi and azithromycin-resistant variants underscores the need to implement and disseminate preventive measures. Among these measures, vaccination is primary in countries where typhus is endemic.
However, experts emphasize that prevention strategies should not be limited to countries where bacterial resistance is currently the most pronounced. Today, pathogens easily spread across borders, so control measures must have a broader, international character.
Although South Asia remains the region with the highest number of cases, where about 70% of all infections occur, the COVID-19 pandemic has shown that, in the modern world, infectious diseases and their variants can spread rapidly to other parts of the planet.
To prevent further typhoid outbreaks and the spread of drug resistance, scientists emphasize that countries must facilitate access to typhoid vaccines and invest in the development of new antibiotics. A 2021 study in India found that vaccinating children could prevent as many as 36% of thyroid cases and deaths related to the disease.
In this field, Pakistan leads by example – it was the first country in the world to introduce routine vaccination against typhoid. Today, several other countries either already implement or are considering introducing vaccination in the near future.
According to the CDC, by April 2025, the World Health Organization (WHO) will have requalified four typhoid conjugate vaccines. These vaccines are now being gradually introduced into childhood immunization programs in countries where typhus is endemic, a crucial step in preventing new epidemics.
