Assessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi

Abstract

Since its emergence in 2016, extensively drug resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) has become the dominant cause of typhoid fever in Pakistan. The establishment of sustained XDR S. Typhi transmission in other countries represents a major public health threat. We show that the annual volume of air travel from Pakistan strongly discriminates between countries that have and have not imported XDR S. Typhi in the past, and identify a significant association between air travel volume and the rate of between-country movement of the H58 haplotype of S. Typhi from fitted phylogeographic models. Applying these insights, we analyze flight itinerary data cross-referenced with model-based estimates of typhoid fever incidence to identify the countries at highest risk of importation and sustained onward transmission of XDR S. Typhi. Future outbreaks of XDR typhoid are most likely to occur in countries that can support efficient local S. Typhi transmission and have strong travel links to regions with ongoing XDR typhoid outbreaks (currently Pakistan). Public health activities to track and mitigate the spread of XDR S. Typhi should be prioritized in these countries.

The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

“…The rapid international dissemination of the H58 lineage, starting in South Asia and spreading throughout Southeast Asia 14 , 33 , into Africa 14 , 31 , 48 , 49 , 51 – 53 and more recently, Latin America 54 , suggest that expanded genomic surveillance is warranted to monitor its continued global spread. Such information has also helped to inform the development of transmission dynamics models that predict the spread of newer drug-resistant variants, like XDR, which can also inform TCV introduction decision-making 55 .…”

Recent approaches in computational modelling for controlling pathogen threats

“…The underlying biological causes of the resistance—a combination of new resistance genes (including on a plasmid) as well as mutations in a chromosomal gene—did not need to be incorporated into models of its spread. A modelling analysis assessed the global risk of further outbreaks of XDR Typhi using air travel data in combination with reported cases, finding that countries with more passengers arriving from Pakistan were far more likely to have cases ( Walker et al, 2023 ). This analysis highlighted the probable existence of unreported cases in countries with high air traffic with Pakistan (Saudi Arabia, Turkey, and Malaysia) as well as countries at high risk of XDR Typhi outbreaks.…”

Climate change affects the spread of typhoid pathogens

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Typhoid fever, estimated to cause over 100,000 deaths annually (Walker et al, 2023), is a bacterial infectious disease caused by the gram-negative bacterium Salmonella enterica serovar Typhi (S. Typhi). As an ancient companion of humanity, S. Typhi was identified during the 19th century and disproportionately burdened low-and middle-income countries, especially in Africa and Southeast Asia, where sanitation remains inadequate.

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“…Typhoid fever, estimated to cause over 100,000 deaths annually (Walker et al., 2023 ), is a bacterial infectious disease caused by the gram‐negative bacterium Salmonella enterica serovar Typhi ( S . Typhi).…”