August 7, 2022

Typhoid-causing bacteria are becoming increasingly resistant to antibiotics Lancet Study

According to a study published in The lancet microbe log. This is the largest genome analysis of Salmonella enterica serovar Typhi (S. Typhi). Most resistant strains originate from South Asia. Typhoid fever is most prevalent in South Asia.

Typhoid fever is a global public health problem that causes 11 million infections and more than 100,000 deaths per year, and has significant impacts in sub-Saharan Africa, Southeast Asia and Oceania, highlighting the need for a global response.

What is typhoid fever?

Typhoid fever is a bacterial infection that can spread throughout the body, affect many organs and, without prompt treatment, can lead to serious complications and even be fatal.

The disease is rare in developed countries, but remains a serious health threat in developing countries, especially for children.

Typhoid fever is a contagious disease transmitted through contaminated food and water or through close contact with an infected person. Signs and symptoms of typhoid fever include high fever, headache, stomach pain, and constipation or diarrhea.

What threatens the effectiveness of antibiotics?

Although antibiotics can be used to successfully treat typhoid fever infections, their effectiveness is threatened by the emergence of resistant strains of S. Typhi. There has been limited analysis of the increase and spread of resistant S. Typhi so far, and most studies have been based on small sample sizes.

Whole genome sequencing of S. Typhi samples performed

As many as 3,489 S. Typhi isolates obtained from blood samples collected between 2014 and 2019 from people in Bangladesh, India, Nepal and Pakistan with confirmed cases of typhoid fever were analyzed as part of of the study. The authors of the article performed whole genome sequencing of these samples. No less than 4,169 samples of S. Typhi isolated in more than 70 countries between 1905 and 2018 were also sequenced and included in the analysis.

What are multi-resistant strains?

According to the study, genetic databases were used to identify genes conferring resistance in the 7,658 sequenced genomes. Strains containing genes for resistance to the classic first-line antibiotics ampicillin, chloramphenicol and trimethoprim or sulfamethoxazole were classified as multidrug-resistant (MDR). Macrolides and quinolones are among the most important antibiotics for human health, and therefore the authors traced the presence of genes conferring resistance to these antibiotics.

Where have resistant strains of S. Typhi spread?

Resistant strains of S. Typhi have spread between countries at least 197 times since 1990. Strains have occurred most often in South Asia and from South Asia to Southeast Asia, the Eastern and Southern Africa. However, the strains have also been reported in the UK, US and Canada, according to the study.

Prevalence of MDR S. Typhi

MDR S. Typhi has declined steadily in Bangladesh and India since 2000. It has also remained low in Nepal, where less than 5% of typhoid strains are prevalent. However, S. Typhi MDR are being replaced by strains resistant to other antibiotics.

Genetic mutations giving resistance to quinolones have appeared

For example, genetic mutations giving resistance to quinolones have emerged and spread at least 94 times since 1990, according to the study. About 97% of these strains originate from South Asia. In the early 2000s, quinolone resistant strains accounted for more than 85% of S. Typhi in Bangladesh. Strains increased to over 95% in India, Pakistan and Nepal in 2010.

Pattern of emergence of mutations causing resistance to azithromycin

Over the past 20 years, mutations causing resistance to azithromycin have appeared at least seven times over the past 20 years. It is a widely used macrolide antibiotic. Around the year 2013, strains containing these mutations appeared in Bangladesh. Since then, the population size of these strains has steadily increased.

Increase in strains resistant to cephalosporins

There was recent evidence of the rapid increase and spread of strains of S. Typhi resistant to third-generation cephalosporins, another class of antibiotics critically important to human health, and the findings add to these proofs.

In a statement published by The Lancet, Dr. Jason Andrews, the paper’s lead author, said the speed at which highly resistant strains of S. Typhi have emerged and spread in recent years is a real source. of concern and stresses the urgent need to extend preventive measures in the countries most at risk. He added that at the same time, the fact that resistant strains of S. Typhi have spread internationally so often also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than a local problem.

Study limitations

The authors indicated some limitations to the study, including the fact that there remains an underrepresentation of S. Typhi sequences from several regions, particularly many countries in sub-Saharan Africa and Oceania, where typhoid is endemic.

In order to improve understanding of the timing and patterns of propagation, more sequences of these regions are needed. Most isolates come from a small number of surveillance sites and may not be representative of the distribution of circulating strains, even in countries with better sampling.

According to the authors, estimates of mutations causing resistance and international spread are likely underestimated because S. Typhi genomes cover only a fraction of all cases of typhoid fever. The authors believe there is a need to expand genomic surveillance to provide a more comprehensive window into the emergence, expansion, and spread of antibiotic-resistant organisms.

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