Typhoid-Causing Bacteria Becoming Increasingly Resistant To Antibiotics: Study In Lancet

Typhoid fever is a global public health concern which causes 11 million infections and more than 100,000 deaths per year, and has significant impacts in sub-Saharan Africa, Southeast Asia, and Oceania

Typhoid-causing bacteria are becoming increasingly resistant to some of the most important antibiotics for human health, and the resistant strains have spread to other countries nearly 200 times since 1990. The image shows a child infected with Typhoid fever

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Typhoid-causing bacteria are becoming increasingly resistant to some of the most important antibiotics for human health, and the resistant strains have spread to other countries nearly 200 times since 1990, according to a study published in The Lancet Microbe journal. This is the largest genome analysis of Salmonella enterica serovar Typhi (S. Typhi). Most of the resistant strains originated in South Asia. Typhoid fever is most prevalent in South Asia. 

Typhoid fever is a global public health concern which 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, affecting many organs, and without prompt treatment, can cause serious complications and can even be fatal.

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

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

What Threatens The Effectiveness Of Antibiotics?

Though antibiotics can be used to successfully treat typhoid fever infections, their effectiveness is threatened by the emergence of resistant S. Typhi strains. There has been a limited analysis of the rise and spread of resistant S. Typhi so far, and most of the studies were based on small samples.

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 analysed as part of the study. The authors on the paper performed whole-genome sequencing of these samples. As many as 4,169 S. Typhi samples isolated from more than 70 countries between 1905 and 2018 were also sequenced and included in the analysis.

What Are Multidrug-Resistant Strains?

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

Where Have Resistant S. Typhi Strains Spread?

Resistant S. Typhi strains were found to have spread between countries at least 197 times since 1990. The strains most often occurred within South Asia and from South Asia to Southeast Asia, East and Southern Africa. However, the strains have also been reported in the UK, USA, and Canada, the study said.

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 five per cent of Typhoid strains are prevalent. However, MDR S. Typhi are being replaced by strains resistant to other antibiotics. 

Gene Mutations Giving Resistance To Quinolones Have Arisen

For instance, gene mutations giving resistance to quinolones have arisen and spread at least 94 times since 1990, the study said. Around 97 per cent of these strains originated in South Asia. By the early 2000s, quinolone-resistant strains accounted for more than 85 per cent of S. Typhi in Bangladesh. The strains increased to more than 95 per cent in India, Pakistan, and Nepal by 2010. 

Pattern Of Emergence Of Mutations Causing Resistance To Azithromycin

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

Rise In Strains Resistant To Cephalosporins

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

In a statement released by The Lancet, Dr Jason Andrews, the lead author on the paper, 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 in countries at greatest risk. He added that 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.

Limitations To The Study

The authors stated some limitations to the study, including the fact that there remains of 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 timing and patterns of spread, more sequences from 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 resistance-causing mutations and international spread are likely underestimated because S. Typhi genomes only cover a fraction of all typhoid fever cases. The authors believe that there is a need to expand genomic surveillance to provide a more comprehensive window into the emergence, expansion, and spread of antibiotic-resistant organisms.