Highlights
- REPJPP01 is an emerging strain of extensively drug-resistant Salmonella Typhi, the bacteria that cause typhoid fever. This strain has caused illnesses in the United States since 2018.
- REPJPP01 has caused illness in travelers to Pakistan and neighboring countries and in people who did not leave the United States.
- Getting vaccinated against typhoid fever before international travel – especially to South Asia – and following safe eating and drinking habits while traveling can prevent illness.
Key findings
What is a REP strain?
REPJPP01 is an emerging strain of Salmonella Typhi, the bacteria that cause typhoid fever. This strain was first identified in Pakistan in 2016, and illness caused by this strain was first reported in the United States in 2018. CDC monitors this strain due to its unusual resistance pattern – it was the first strain of Salmonella Typhi in Pakistan to show resistance to ceftriaxone, an antibiotic commonly recommended for treatment of typhoid fever. Most REPJPP01 isolates also are resistant to ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole. Isolates resistant to all 5 of these antibiotics are commonly called extensively drug-resistant, or XDR. Antibiotics are recommended for all patients with typhoid fever, and typhoid fever caused by XDR Salmonella Typhi can be difficult to treat.
Illnesses caused by this strain occur year round, but are most common in summer and winter.
In the past, the REPJPP01 strain has spread to people in the United States during travel to Pakistan and neighboring countries.
This strain is relatively diverse genetically. Bacteria in REPJPP01 are within 13 allele differences of one another by whole genome sequencing, which is more diverse than typical typhoid fever outbreaks in which bacteria generally fall within 5 allele differences of one another. Increased diversity can occur over time as strains pass among human hosts in diverse settings with different selective pressures.
What the data show
Epidemiology
As of December 31, 2023, information from 150 U.S. patients with laboratory-confirmed REPJPP01 infection was reported to PulseNet, a national laboratory network that tests for and tracks enteric pathogens in humans. However, lab-confirmed cases comprise only a portion of the true number of illnesses that occur. Some people with typhoid fever do not seek medical care and even fewer submit a clinical specimen for testing.
The median age of patients was 11 years (interquartile range, 5–23 years), and 51% were male. The isolate source was blood in 87% and stool in 13% of cases. Among patients with available information, 92% traveled internationally in the 30 days before illness began. Ninety-one percent of patients were hospitalized for their illness for a median of 8 days (interquartile range, 6–11 days), and no patients died. No patients reported receiving vaccination for typhoid fever in the five years before their illness began.
Summary of international travel in the 30 days before illness began: REPJPP01
Year | Travel destination(s) | Reported illnesses |
---|---|---|
2018 | Pakistan | 9 |
2019 | Pakistan | 31 |
2019 | Pakistan, United Arab Emirates | 2 |
2019 | Iraq, Pakistan | 1 |
2019 | Norway, Pakistan, Saudi Arabia | 1 |
2019 | Pakistan, Saudi Arabia, United Arab Emirates | 1 |
2019 | Pakistan, Turkey | 1 |
2019 | No international travel | 1 |
2020 | Pakistan | 16 |
2020 | Pakistan, Saudi Arabia | 1 |
2020 | No international travel | 8 |
2021 | Pakistan | 16 |
2021 | Pakistan, United Arab Emirates | 1 |
2021 | No international travel | 1 |
2021 | Unknown | 1 |
2022 | Pakistan | 25 |
2022 | Afghanistan | 1 |
2022 | Germany, Pakistan | 1 |
2022 | Maldives, Pakistan | 1 |
2022 | Pakistan, Turkey | 1 |
2022 | Pakistan, Saudi Arabia | 1 |
2023 | Pakistan | 22 |
2023 | Afghanistan, United Arab Emirates | 1 |
2023 | India | 1 |
2023 | No international travel | 2 |
2023 | Unknown | 3 |
Timeline
People with typhoid fever caused by the REPJPP01 strain, by month of isolate collection, 2018–2023
Map
Typhoid fever caused by the REPJPP01 strain, by state, 2018–2023
Selected publications
- Extensively drug-resistant typhoid fever in the United States
- Extensively drug-resistant Salmonella Typhi infections among U.S. residents without international travel
- Update on extensively drug-resistant Salmonella serotype Typhi infections among travelers to or from Pakistan and report of ceftriaxone-resistant Salmonella serotype Typhi infections among travelers to Iraq—United States, 2018–2019
- Emergence of extensively drug-resistant Salmonella Typhi infections among travelers to or from Pakistan—United States, 2016–2018
- Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins
- Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: a matched case-control study
Laboratory data
Bacteria in REPJPP01 are within 13 allele differences of one another by core genome multilocus sequence typing (cgMLST), which is more diverse than typical typhoid fever outbreaks where bacteria generally fall within 5 allele differences of one another.
Due to the clonal nature of Salmonella Typhi, 31 additional isolates that are related to REPJPP01 isolates are within the same 13-allele range, but these isolates lack ceftriaxone resistance. Most patients with ceftriaxone-susceptible infections also traveled to Pakistan in the 30 days before their illness began.
Summary of international travel in the 30 days before illness began: ceftriaxone-susceptible isolates related to REPJPP01
Year | Travel destination(s) | Reported illnesses |
---|---|---|
2018 | Pakistan | 1 |
2019 | Pakistan | 1 |
2020 | Canada, Pakistan | 1 |
2020 | Pakistan | 1 |
2020 | No international travel | 4 |
2021 | Pakistan | 5 |
2021 | No international travel | 1 |
2022 | Pakistan | 8 |
2023 | Pakistan | 9 |
The National Center for Biotechnology Information (NCBI) advances science and health by providing access to biomedical and genomic information.
SNP cluster associated with isolate: PNUSAS044905
Antimicrobial-resistant isolates
The National Antimicrobial Resistance Monitoring System (NARMS) is a national public health surveillance system that tracks antimicrobial resistance for certain intestinal bacteria from ill people in the United States. The NARMS program helps protect public health by providing information about emerging antimicrobial resistance, the ways in which resistance is spread, and how resistant infections differ from susceptible infections.
Bacteria from most (90%) ill people's samples showed resistance to the antibiotics ampicillin, ceftriaxone, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole. Consideration should be given to the first-choice antibiotic used for treatment of typhoid fever. More information about treatment of typhoid fever is available.
Percentage of Salmonella Typhi REPJPP01 isolates from ill people that were antimicrobial resistant, by antibiotic (n = 149), as of December 31, 2023 — NARMS
Collaborate with CDC
Interested in collaborating on a project related to this strain? Contact CDC at REPStrains@cdc.gov.
About the data
Epidemiology
Information is based on patient interviews conducted by state and local health departments and reported to CDC.
Missing data were excluded from percentage calculations.
Timeline
N = 150 for whom information was reported as of December 31, 2023. Some illness onset dates may have occurred earlier than the month of isolate collection.
PulseNet transitioned to using whole genome sequencing (WGS) as the standard subtyping method for Salmonella in July 2019. Before then, not all Salmonella isolates reported to PulseNet had WGS data available. Isolates are identified as part of this strain based on WGS. As a result, the number of people with lab-confirmed illness caused by this strain before 2019 may be underrepresented.
Map
The map shows the state of residence for people with typhoid fever caused by REPJPP01. However, most patients (92%) traveled internationally in the 30 days before becoming ill and are presumed to have acquired their infection outside of the United States.
Antimicrobial-resistant isolates
Resistance was determined based on the results of antimicrobial susceptibility testing when available (n = 118 isolates); otherwise, resistance was predicted based on whole genome sequencing (n = 31). No isolates were resistant to amoxicillin-clavulanic acid, cefoxitin, colistin, gentamicin, kanamycin, or tetracycline.
Resistance results include isolates with intermediate interpretation to ciprofloxacin (n = 13; 9%) or those carrying a single quinolone-resistance mutation (n = 7; 5%); a single mutation typically results in interpretation of "intermediate" for ciprofloxacin on antimicrobial susceptibility testing.