Antibiotic-resistant typhoid pathogens continue to spread

/picture alliance, Armin Weigel

Stanford – An analysis of more than 7,500 bacterial genomes shows that typhoid pathogens are apparently becoming increasingly resistant to the most important antibiotics. In the The Lancet Microbe The largest genome analysis of Salmonella enterica serovar Typhi (S. Typhi) published to date also revealed that resistant strains have spread to other countries almost 200 times since 1990, mainly from South Asia (Lancet 2022; DOI: 10.1016/S2666-5247(22)00093-3).

Typhus has become very rare in this country. This year, a total of 13 cases of abdominal typhus were reported to the Robert Koch Institute (RKI) by week 19. Most of the cases reported in Germany are imported from predominantly Asian countries.

At around 70%, South Asia bears the brunt of the estimated 11 to 21 million typhoid cases and 128,000 to 161,000 typhoid-related deaths worldwide. But the disease is also of considerable significance in sub-Saharan Africa, Southeast Asia and Oceania.

Newer samples from South Asia and older samples from 70 countries

Although typhoid fever can be successfully treated with antibiotics, resistant strains of S. Typhi are becoming increasingly common. The authors, led by Kesia Esther da Silva from the Division of Infectious Diseases and Geographic Medicine at Stanford University, subjected 3489 S. Typhi isolates to whole-genome sequencing.

The isolates came from blood samples taken from typhoid patients in Bangladesh, India, Nepal and Pakistan between 2014 and 2019. In addition, a collection of 4169 S. Typhi samples collected between 1905 and 2018 in more than 70 countries was sequenced and analyzed.

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Checking for resistance to important antibiotics

The researchers identified the genes that mediate antibiotic resistance using gene databases. Strains were considered multi-resistant if they exhibited resistance genes to the classic frontline antibiotics ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole. In addition, however, the presence of resistance genes to macrolide and quinolone antibiotics was also examined.

Most of the countries of origin are in South Asia

The analysis found that resistant S. Typhi strains have spread from one country of origin to other countries at least 197 times since 1990. Most of these tribes emerged in South Asia and from there spread to Southeast Asia, East and South Africa. However, there have also been reports of cases in the UK, US and Canada.

Multidrug-resistant strains are declining but are being replaced by other resistant strains

Da Silva and her colleagues report that multidrug-resistant S. Typhi strains in Bangladesh and India have been steadily declining since 2000. In Nepal, they remained at a consistently low level, accounting for around 5% of all circulating S. Typhi strains. In Pakisten, the proportion of resistant strains has increased slightly. However, the multi-resistant S. Typhi would be replaced by strains that are resistant to other antibiotics.

South Asia: High proportion of S. Typhi strains resistant to quinolones

Gene mutations that confer resistance to quinolone antibiotics in bacteria have emerged and spread at least 94 times since 1990, with almost all of these strains (97%) originating in South Asia. Strains resistant to quinolone antibiotics accounted for more than 85% of S. Typhi strains circulating in Bangladesh in the early 2000s. In India, Pakistan and Nepal, the proportion rose to 95% by 2010.

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Rapid spread of S. Typhi with resistance to 3rd generation cephalosporins

Mutations that confer resistance to the macrolide antibiotic azithromycin have occurred at least 7 times in the last 20 years. Strains carrying these mutations emerged in Bangladesh around 2013. Since then, their population size has steadily increased. The results of the genomic analysis support recent evidence supporting the rapid emergence and spread of S. Typhi strains resistant to 3rd generation cephalosporins.

Sequenced genomes are not representative

The authors, working with da Silva, note that their results have some limitations: S. typhi sequences from several regions are underrepresented in the analysis, especially from countries in sub-Saharan Africa and Oceania, where typhoid is also endemic.

And even in countries with larger sample numbers, most isolates came from a small number of monitors and may not be representative of the distribution of circulating strains.

Spread of resistant typhoid pathogens probably underestimated

The sequenced S. Typhi genomes account for only a fraction of the world’s typhoid cases. Therefore, the Stanford scientists believe that their estimates of resistance-causing mutations and international distribution are likely to be underestimated. They stress that genomic surveillance urgently needs to be expanded to get a better picture of the emergence and spread of antibiotic-resistant strains.

Typhoid fever and antibiotic resistance are a global problem, not a local one

“The speed at which highly resistant strains of S. Typhi have emerged and spread in recent years is a real concern and underscores the urgent need to scale up prevention efforts, particularly in countries at highest risk,” says senior author Jason Andrews, also an infectious disease specialist at Stanford University.

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At the same time, the fact that resistant strains of S. Typhi have spread internationally so many times underscores the need to treat typhoid and antibiotic resistance control in general as a global rather than a local issue. © nec /



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