In December, the WHO announced new recommendations for strengthening public health measures in Pakistan in response to an ongoing outbreak of extensively drug-resistant (XDR) typhoid fever, which began in the Hyderabad district of Sindh province in November 2016. Since our last post on this topic in August 2018, the number of cases of XDR typhoid fever has increased from approximately 2,000 to 5,274 cases. The outbreak is currently affecting the Hyderabad district, Karachi district, and multiple other districts in Sindh province in southeastern Pakistan. Since June 2018, there have also been new reports of international transmission of XDR typhoid fever from individuals who traveled through Pakistan.

The outbreak is the first known epidemic of XDR typhoid fever, serving as a reminder of the pressing need to fight global antimicrobial resistance (AMR). Below we provide an update on the outbreak, which “poses a notable public health concern,” according to the WHO.

Continued domestic and international spread

In August 2018, Outbreak Observatory reported on a strain of the bacteria Salmonella typhi that had acquired resistance to first-line recommended drugs for treatment as well as the second-line antibiotic ceftriaxone, which is usually reserved for multi-drug-resistant (MDR) typhoid fever. While epidemics of MDR typhoid fever have been documented in several countries, this is the first known outbreak of XDR typhoid fever. In fact, only 4 total isolated cases of XDR typhoid fever have been previously reported worldwide.

In July 2018, cases of XDR typhoid fever in Sindh were estimated to total at least 2,000. However, the incidence grew to 5,274 cases through December 9, 2018, according to a WHO update released in December. A separate, weekly bulletin provided by the WHO’s Regional Office for the Eastern Mediterranean (EMRO) reported that cases have reached 5,372 between through December 30, 2018. This indicates that the number of cases of XDR typhoid fever in Pakistan has more than doubled since July; however, it is possible that improved surveillance and data sharing on AMR may account for some portion of the increase. Of the 5,372 cases reported by EMRO, 3,709 were recorded in Karachi district; 1,443 in Hyderabad district; and 220 throughout other districts in Sindh province.

In assessing the risk of geographic spread of XDR typhoid fever, the WHO states that the risk is high at the national level, medium at the regional level, and low globally. New reports of international transmission of XDR typhoid fever have been reported in individuals who traveled through Pakistan. In June 2018, the US CDC, which issued a Level 2 travel alert for Pakistan as a result of the outbreak, reported a total of 3 travel-associated cases; however, the WHO update from December notes 6 travel-associated cases (5 in the US and 1 in the UK).

Strengthening the public health response

Currently, azithromycin is the only remaining effective oral antibiotic for treating XDR typhoid fever. Due to the ability of S. typhi to gain new mechanisms of resistance, the WHO “recommends strengthening surveillance of typhoid fever.” This includes laboratory verification and microbiological testing of strains in patients with suspected typhoid fever to detect resistance profiles, monitoring for emerging resistance, and informing treatment practices as well as sharing of data on AMR nationally and internationally. Clinicians in Hyderabad are also being sensitized to the appropriate use of antibiotics. However, the challenge in this regard is that confirmatory laboratory testing is only conducted at major laboratories and tertiary-care hospitals in Pakistan. Limited testing capabilities, along with poor antibiotic prescribing practices by providers, may inhibit the ability to accurately monitor the spread of the disease.

In addition to enhanced surveillance for typhoid fever and AMR, the WHO recommends the continuation of other public health and preventative measures that have been ongoing in Pakistan. This includes a mass vaccination campaign in Hyderabad (since August 2017), which has led to the immunization of approximately 118,000 children aged 6 months to 10 years with either the Vi-polysaccharide typhoid vaccine or the typhoid conjugate vaccine. Pakistan has also applied for support from GAVI for the introduction of the typhoid conjugate vaccine into routine national immunization programs, beginning in 2019.

Finally, the WHO cites “insufficient water, poor sanitation, and hygiene (WASH) practices” as a reason why the risk of national spread of XDR typhoid fever is high. Along with increased vaccination coverage, the primary WHO recommendation for limiting the spread of XDR typhoid fever and containing the outbreak is providing access to safe water, sanitation services, and hygiene among food handlers. Through appropriate public health measures, such as water purification and school awareness campaigns on safe hygiene, it is hoped that the spread of both resistant and non-resistant forms of the disease can be stopped in the long term. If sufficient national and international public health resources are not directed toward the outbreak and other settings at risk of AMR, it is possible that the world may one day witness a deadly and untreatable form of typhoid fever.

Photo: A photomicrograph of myocardial tissue changes due to S. Typhi bacterial infection. Photo courtesy of CDC/Armed Forces Institute of Pathology, Charles N. Farmer

Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.