No 21 - 2023

Typhoid fever in travellers returning from Pakistan with resistance to the first-choice treatment

Nine cases of highly resistant Salmonella enterica serovar Typhi (S. Typhi) have been recorded in Denmark in the past five years among travellers returning from Pakistan. Ceftriaxone, which is the first-choice treatment for typhoid fever, has not been effective in these cases. Patients who become infected with S. Typhi in Pakistan are therefore at risk of receiving ineffective treatment in the period that passes until it is established that another treatment is needed. Without treatment, typhoid fever carries an approx. 10-20% mortality. To avoid treatment delay, it may be considered to use other empirical antibiotics when treating a typhoid fever patient who has recently returned from Pakistan. Such therapies could be, e.g., meropenem or, in mild cases, azithromycin.

Furthermore, two vaccines are available against S. Typhi. Both vaccines may be used as travel vaccination for persons travelling to Pakistan.

What is typhoid fever?

The S. Typhi bacterium causes typhoid fever, a disease that may require hospitalisation and treatment with intravenous antibiotics. Left untreated, the condition has a high mortality of approx. 10-20%. Typhoid fever typically presents with fever, and subsequent diarrhoea may be observed. The condition, which is notifiable in Denmark, is only rarely caused by transmission within Denmark. Infections that have been acquired in Denmark include transmission within a household or infection of the healthcare or laboratory staff who handle typhoid fever patients or their samples. In contrast, the bacterium is found endemically in many countries, e.g., Pakistan, where transmission primarily occurs via water or foods that have become contaminated with faeces from humans who carry S. Typhi in their intestines.

Vaccination and hygiene measures

Reducing the risk of S. Typhi infection can be done by maintaining good hand hygiene, ensuring that drinking water is clean and by handling and preparing foods under good hygienic conditions.
Furthermore, two vaccines are available against S. Typhi. Adults and children from two years and up be vaccinated with the intramuscular vaccine Typhim Vi. Another vaccine, Vivotif, is takenby mouth and may be used from five years of age. Both vaccines provide protection for a minimum period of three years. However, protection is not 100% and therefore the hygiene recommendations should be followed regardless of vaccination status. Read more about travel vaccination recommendations.

Travellers who visit their family and friends in endemic areas

Travelling to endemic areas to visit family and friends can present unique challenges, especially when it comes to receiving travel prophylaxis such as vaccines. There are several reasons why this group of travellers may opt out of prophylaxis.They may not percieve prophylaxis as needed, they may be discouraged from prophylaxis because of the cost, or the need to travel may have arisen acutely, and timely vaccination was not possible (e.g., due to a sick family member abroad). Alternatively, opting out of prophylaxis may be due to lack of knowledge about current recommendations.

This group of travellers often comes into close contact with and share the same activities as the local population (e.g., drink tap water).

This specific type of traveller constitutes a large share of the imported typhoid fever cases. Vaccination is recommended for this group, regardless of the length of their stay.

Nine cases in Denmark

Several other countries (including Ireland, Sweden, Holland, Germany and New Zealand) have recently reported S. typhi isolates that have carried resistance genes, which make them resistant to a wide range of antibiotics, including ceftriaxone. Most of the cases described internationally have had a travel history, and Pakistan has been the primary travel destination.

Among the 61 laboratory-notified cases recorded in Denmark since 2017, nine cases were phenotypically resistant to ceftriaxone, and whole-genome sequencing showed that they carried the blaCTX-M-15 gene: one case in 2018, two in 2019, two in 2020 and four in 2022, whereas no cases have currently been reported in 2023. Travelling data for the nine Danish cases show that five had returned from travels in Pakistan, one had visited Iraq and no information was provided about the travel destination for the last three cases. The nine isolates were also resistant to other antibiotics, including: ciprofloxacin, ampicillin and trimethoprim with sulphamethoxazole.

More information

Read more about typhoid fever (in Danish)

See the annual number of Danish cases here. 

Read more about the Danish cases registered in the 2019-2021 period. (in Danish)

(T. Larsen, Department of Infectious Disease Epidemiology and Prevention and P. Gymoese, E. Litrup, Department of Bacteria, Parasites and Fungi).