Antibiotic-resistant typhus pathogens continue to spread

/ Photographic alliance, Armin Weigel

Stanford – An analysis of over 7,500 bacterial genomes shows that typhus pathogens are becoming increasingly resistant to major antibiotics. In the The Microbe Lancet The largest genome analysis of Salmonella enterica serovar Typhi (S. Typhi) published to date has also revealed that resistant strains have spread to other countries nearly 200 times since 1990, mainly from South Asia (Hand 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 11-21 million cases of typhus and 128,000-161,000 typhus-related deaths worldwide. But the disease is also of considerable importance 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 more and more common. The authors, led by Kesia Esther da Silva of Stanford University’s Division of Infectious Diseases and Geographic Medicine, subjected 3,489 isolates of S. Typhi to whole genome sequencing.

The isolates were from blood samples taken from typhus patients in Bangladesh, India, Nepal and Pakistan between 2014 and 2019. In addition, a collection of 4169 S. Typhi samples collected between 1905 and 19 was sequenced and analyzed. 2018 in more than 70 countries.

Verification of resistance to important antibiotics

Researchers identified genes that mediate antibiotic resistance using databases of genes. Strains were considered multidrug-resistant if they showed resistance genes to classic first-line antibiotics ampicillin, chloramphenicol and trimethoprim / sulfamethoxazole. In addition, however, the presence of macrolide and quinolone antibiotic resistance genes was also examined.

Most of the countries of origin are located 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. Asia, East and South Africa. However, there have also been case reports in the UK, US and Canada.

Multi-resistant strains are dwindling, but are being replaced by other resistant strains

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

South Asia: high percentage 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 nearly all of these strains (97%) originating in South Asia. Strains resistant to quinolone antibiotics accounted for over 85% of S. Typhi strains circulating in Bangladesh in the early 2000s. In India, Pakistan and Nepal, the percentage had risen to 95% by 2010.

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

Mutations conferring resistance to the macrolide antibiotic azithromycin have occurred at least 7 times in the past 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 strains of S. Typhi resistant to 3rd generation cephalosporins.

The sequenced genomes are not representative

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

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

Spread of typhus-resistant pathogens probably underestimated

Sequenced S. Typhi genomes represent only a fraction of typhus cases worldwide. Therefore, Stanford scientists believe their estimates of resistance-causing mutations and international distribution may 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 with which highly resistant strains of S. Typhi have emerged and spread in recent years is a real concern and underscores the urgent need to step up prevention efforts, particularly in higher-risk countries,” says the senior author Jason Andrews, also an infectious disease specialist at Stanford University.

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

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