Super-resistant Salmonella Typhi causes concern

Salmonella Typhi causes typhoid fever which is one of the major health threats in low-income countries. Researchers of the Institut National de Recherche Biomédicale (INRB) in Kinshasa and the Institute of Tropical Medicine Antwerp (ITM) isolated a super-resistant Salmonella Typhi strain from a six-years old boy at a rural health centre in southwestern DRC, as part of an ongoing investigation of a suspected typhoid fever epidemic in the area. If this strain would spread around, it could have a deadly impact, they say. The researchers reported their findings in the leading journal Clinical Infectious Diseases.

Typhoid fever – caused by Salmonella Typhi – affects more than 10 million people yearly with an estimated 100,000 deaths, mainly in low- and middle-income countries, including in Sub-Saharan Africa. Antibiotics are key for treatment and over the past decades, rising antibiotic resistance has limited the available antibiotics to ciprofloxacin and ceftriaxone. Although rare, typhoid fever is also seen among travelers returning from endemic areas in Africa and Asia. Physicians in ITM’s travel clinical see each year around five cases of typhoid fever among Belgian travelers.  

Discovery of unusual resistance

The discovery started with sound investigational work by Prof. Octavie Lunguya and Dr. Marie-France Phoba at INRB in Kinshasa, who observed the resistant strain in the child’s blood and identified it as Salmonella Typhi. They  sent the strain to ITM for confirmation and further investigation. At ITM’s Tropical Laboratory Medicine Unit, antibiotic susceptibility testing of the strain showed unusual resistance to several key antibiotics, including ciprofloxacin. To the surprise of the researchers, the strain also produced an extended spectrum beta-lactamase (ESBL), an enzyme that causes resistance to a variety of important antibiotics (including ceftriaxone), which the World Health Organization identifies as one of the three most critical antibiotic resistance threats.

“The combination of resistance to these different antibiotics virtually rules out options for appropriate treatment of typhoid fever in Central Africa and is of huge concern. This is the first time we observe ESBL production in Salmonella Typhi strains from Central Africa. If this strain would spread around it could have a deadly impact,” said Prof. Jan Jacobs, head of ITM’s Tropical Laboratory Medicine Unit.

The pedigree of a super-resistant strain

To understand the genetic background of this super-resistant Salmonella Typhi strain, the Diagnostic Bacteriology Unit of ITM sequenced the genome of the strain and identified the genes that are responsible for the observed resistance. The analysis of the genome also revealed that the ESBL gene is carried by a mobile genetic element, that could be acquired from other bacterial species.

“By comparing the strain’s genome with 1800 other Salmonella Typhi genomes from around the world, we showed that the closest siblings of this strain originate from DRC as well, suggesting that the strain was not imported from elsewhere. The strain probably became resistant by transfer of genetic material from another bacteria, like Klebsiella. This adds to the concern: such transfer can occur anywhere and at any time, particularly in environments with high antibiotic resistance,” explained Dr. Sandra Van Puyvelde, who coordinated the genome analysis at the Diagnostic Bacteriology Unit.

The Tropical Laboratory Medicine Unit and the Diagnostic Bacteriology Unit are both part of the multidisciplinary ’Bacterial Infections in the Tropics’ (BIT) project at ITM, which is funded by the Baillet Latour Fund. BIT uses a multidisciplinary approach to investigate and stop the spread of antibiotic resistance in the tropics.

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• Salmonella enterica serovar Typhi Producing CTX-M-15 Extended Spectrum β-Lactamase in the Democratic Republic of the Congo (Clinical Infectious Diseases)
• Bacterial Infections in the Tropics-project (BIT)