Vaccine value profile for Salmonella enterica serovar Paratyphi A.

In Asia, there are an estimated 12 million annual cases of enteric fever, a potentially fatal systemic bacterial infection caused by Salmonella enterica serovars Typhi (STy) and Paratyphi A (SPA). The recent availability of typhoid conjugate vaccines (TCV), an increasing incidence of disease caused by SPA and growing antimicrobial resistance (AMR) across the genus Salmonella makes a bivalent STy/SPA vaccine a useful public health proposition. The uptake of a stand-alone paratyphoid vaccine is likely low thus, there is a pipeline of bivalent STy/SPA candidate vaccines. Several candidates are close to entering clinical trials, which if successful should facilitate a more comprehensive approach for enteric fever control. Additionally, the World Health Organization (WHO) has made advancing the development of vaccines that protect young children and working aged adults against both agents of enteric fever a priority objective. This "Vaccine Value Profile" (VVP) addresses information related predominantly to invasive disease caused by SPA prevalent in Asia. Information is included on stand-alone SPA candidate vaccines and candidate vaccines targeting SPA combined with STy. Out of scope for the first version of this VVP is a wider discussion on the development of a universal Salmonella combination candidate vaccine, addressing both enteric fever and invasive non-typhoidal Salmonella disease, for use globally. This VVP is a detailed, high-level assessment of existing, publicly available information to inform and contextualize the public health, economic, and societal potential of pipeline vaccines and vaccine-like products for SPA. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and "Full Vaccine Value Assessment" that will inform the value proposition of an SPA vaccine. This VVP was developed by an expert working group from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations as well as in collaboration with stakeholders from the WHO South-East Asian Region. All contributors have extensive expertise on various elements of the VVP for SPA and collectively aimed to identify current research and knowledge gaps.

Outbreak of Paratyphoid Fever Caused by Contaminated Street-Vended Food at Qingyang Town, China, 2016.

In 2016, an outbreak of paratyphoid fever occurred in 40 cases at Qingyang town, in China. A case-control study was carried out to determine the source of this outbreak. Case-control study was conducted to identify the risk factors of this outbreak. The cases were identified as patients with isolation of S. Paratyphi, controls were confirmed cases' healthy classmates, colleagues or neighbors and matched by age (±5 y) and gender. Pulsed-field gel electrophoresis was performed to source tracking. Totally, 40 cases were reported: 24 cases were students, and 20 (20/24) of them were Qingyang High School students. For the case-control study, consuming Chinese egg pancakes was detected as a risk factor (OR1:1 = 5.000; 95% CI: 1.710-14.640), and hand-washing before meals was protective behavior compared with seldom hand-washing (OR1:1 = 23.256; 95% CI: 2.451-200.000). S. Paratyphi was cultured from a well water sample used for washing contents of the pancakes. Isolates from well water and paratyphoid cases showed the same PFGE patterns. Contaminated well water and Chinese egg pancakes were likely source and vehicle of this outbreak. Health education, especially handwashing, and food safety supervision should be promoted particularly in schools.

Epidemiologic and genomic investigations of an unusual increase in Salmonella enterica serovar Paratyphi A infection among travelers returning from Myanmar in 2015.

OBJECTIVES: An unusual increase in Salmonella enterica serovar Paratyphi A infection rate in Japanese travelers returning from Myanmar was observed in 2015. METHODS: We analyzed epidemiologic data of returned travelers with enteric fever from 2005-2019. We also analyzed 193 Salmonella Paratyphi A isolates, including 121 isolates with published genomes. RESULTS: Annual notification trends showed a rapid increase in Salmonella Paratyphi A infection in travelers returning from Myanmar in 2015: 2-4 cases/100,000 travelers in 2012-2014 and 13 cases/100,000 travelers in 2015 (P <0.001). The genomic analyses revealed that 11 Myanmar-related isolates in 2015 formed a tight cluster in clade 3 with a single nucleotide variant (SNV) distance of 0-11 (primarily 0-7), yielding a wider SNV range than outbreak-associated isolates from Cambodia in 2013 (0-6 SNVs) or China in 2010 (0-5 SNVs). Although all Cambodia-related isolates in 2013 harbored the wild-type gyrA sequence, all Myanmar-related isolates in 2015 had a single, identical mutation (Ser83Phe) in the gyrA gene. CONCLUSION: The epidemiologic and molecular investigations suggested an increase in the infection rate with genetically closely related Salmonella Paratyphi A in travelers returning from Myanmar in 2015. Careful monitoring of the infection in Myanmar as an endemic country is warranted, considering the resumption of cross-border travel during the COVID-19 pandemic.

Paratyphoid Fever A: Infection and Prevention.

Enteric fever is caused by Salmonella enterica serovar Typhi, Salmonella enterica serovar Paratyphi A, B, and C. While S. Typhi remains the primary causative agent of enteric fever, S. Paratyphi A is responsible for an increasing portion of enteric fever incidence. However, the current available vaccines for enteric fever are all developed from S. Typhi, and lack adequate cross immune protection against paratyphoid fever A. Therefore, paratyphoid A vaccines are urgently needed. The present paper reviews the latest progresses in pathogenesis, global burden, infection features of paratyphoid fever A, as well as the status of vaccine development, highlighting the necessity for the development of vaccines against paratyphoid fever A.

Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete.

During the late 3rd millennium BCE, the Eastern Mediterranean and Near East witnessed societal changes in many regions, which are usually explained with a combination of social and climatic factors.1-4 However, recent archaeogenetic research forces us to rethink models regarding the role of infectious diseases in past societal trajectories.5 The plague bacterium Yersinia pestis, which was involved in some of the most destructive historical pandemics,5-8 circulated across Eurasia at least from the onset of the 3rd millennium BCE,9-13 but the challenging preservation of ancient DNA in warmer climates has restricted the identification of Y. pestis from this period to temperate climatic regions. As such, evidence from culturally prominent regions such as the Eastern Mediterranean is currently lacking. Here, we present genetic evidence for the presence of Y. pestis and Salmonella enterica, the causative agent of typhoid/enteric fever, from this period of transformation in Crete, detected at the cave site Hagios Charalambos. We reconstructed one Y. pestis genome that forms part of a now-extinct lineage of Y. pestis strains from the Late Neolithic and Bronze Age that were likely not yet adapted for transmission via fleas. Furthermore, we reconstructed two ancient S. enterica genomes from the Para C lineage, which cluster with contemporary strains that were likely not yet fully host adapted to humans. The occurrence of these two virulent pathogens at the end of the Early Minoan period in Crete emphasizes the necessity to re-introduce infectious diseases as an additional factor possibly contributing to the transformation of early complex societies in the Aegean and beyond.

Prospects of Future Typhoid and Paratyphoid Vaccines in Endemic Countries.

Low- and middle-income countries face a high burden of typhoid and paratyphoid fever due to poor water quality and inadequate sanitation. The World Health Organization (WHO) recommends the use of typhoid conjugate vaccines (TCV) in endemic settings and Gavi, the Vaccine Alliance, supports TCV introduction. There are currently 2 WHO-prequalified TCVs with Typbar TCV introduced in Pakistan, Liberia, and Zimbabwe. Countries should assess disease burden and consider introduction of TCV for programmatic use. Several paratyphoid vaccine candidates are in early stages of development. An effective bivalent vaccine would be the most efficient way to control typhoid and paratyphoid fever.

Salmonella Paratyphi Infection: Use of Nanopore Sequencing as a Vivid Alternative for the Identification of Invading Bacteria.

In our study we present an overview of the use of Oxford Nanopore Technologies (ONT) sequencing technology on the background of Enteric fever. Unlike traditional methods (e.g., qPCR, serological tests), the nanopore sequencing technology enables virtually real-time data generation and highly accurate pathogen identification and characterization. Blood cultures were obtained from a 48-year-old female patient suffering from a high fever, headache and diarrhea. Nevertheless, both the initial serological tests and stool culture appeared to be negative. Therefore, the bacterial isolate from blood culture was used for nanopore sequencing (ONT). This technique in combination with subsequent bioinformatic analyses allowed for prompt identification of the disease-causative agent as Salmonella enterica subsp. enterica serovar Paratyphi A. The National Reference Laboratory for Salmonella (NIPH) independently reported this isolate also as serovar Paratyphi A on the basis of results of biochemical and agglutination tests. Therefore, our results are in concordance with certified standards. Furthermore, the data enabled us to assess some basic questions concerning the comparative genomics, i.e., to describe whether the isolated strain differs from the formerly published ones or not. Quite surprisingly, these results indicate that we have detected a novel and so far, unknown variety of this bacteria.

Tracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal Salmonella.

The rising prevalence of antimicrobial resistance in Salmonella enterica serovars Typhi and Paratyphi A, causative agents of typhoid and paratyphoid, have led to fears of untreatable infections. Of specific concern is the emerging resistance against azithromycin, the only remaining oral drug to treat extensively drug resistant (XDR) typhoid. Since the first report of azithromycin resistance from Bangladesh in 2019, cases have been reported from Nepal, India, and Pakistan. The genetic basis of this resistance is a single point mutation in the efflux pump AcrB (R717Q/L). Here, we report 38 additional cases of azithromycin-resistant (AzmR) Salmonella Typhi and Paratyphi A isolated in Bangladesh between 2016 and 2018. Using genomic analysis of 56 AzmR isolates from South Asia with AcrB-R717Q/L, we confirm that this mutation has spontaneously emerged in different Salmonella Typhi and Paratyphi A genotypes. The largest cluster of AzmR Typhi belonged to genotype 4.3.1.1; Bayesian analysis predicts the mutation to have emerged sometime in 2010. A travel-related Typhi isolate with AcrB-R717Q belonging to 4.3.1.1 was isolated in the United Kingdom, increasing fears of global spread. For real-time detection of AcrB-R717Q/L, we developed an extraction-free, rapid, and low-cost mismatch amplification mutation assay (MAMA). Validation of MAMA using 113 AzmR and non-AzmR isolates yielded >98% specificity and sensitivity versus phenotypic and whole-genome sequencing assays currently used for azithromycin resistance detection. With increasing azithromycin use, AcrB-R717Q/L is likely to be acquired by XDR strains. The proposed tool for active detection and surveillance of this mutation may detect pan-oral drug resistance early, giving us a window to intervene.IMPORTANCE In the early 1900s, with mortality of ∼30%, typhoid and paratyphoid ravaged parts of the world; with improved water, sanitation, and hygiene in resource-rich countries and the advent of antimicrobials, mortality dwindled to <1%. Today, the burden rests disproportionately on South Asia, where the primary means for combatting the disease is antimicrobials. However, prevalence of antimicrobial resistance is rising and, in 2016, an extensively drug resistant Typhi strain triggered an ongoing outbreak in Pakistan, leaving only one oral drug, azithromycin, to treat it. Since the description of emergence of azithromycin resistance, conferred by a point mutation in acrB (AcrB-R717Q/L) in 2019, there have been increasing numbers of reports. Using genomics and Bayesian analysis, we illustrate that this mutation emerged in approximately 2010 and has spontaneously arisen multiple times. Emergence of pan-oral drug resistant Salmonella Typhi is imminent. We developed a low-cost, rapid PCR tool to facilitate real-time detection and prevention policies.

Characterization and protective efficacy of a sptP mutant of Salmonella Paratyphi A.

BACKGROUND: Salmonella Paratyphi A causes paratyphoid A, a severe systemic disease of people and remains a major public health problem in many parts of the world. In the interest of researching the roles of sptP on Salmonella Paratyphi A and developing a live-attenuated vaccine candidate, an sptP mutant of Salmonella Paratyphi A SPA017 (SPA017ΔsptP) was constructed, and then its characterization, immunogenicity, and protective ability were evaluated. RESULTS: The deletion of sptP had no effect on growth and biochemical properties. Adhesion and invasion assays showed that the lack of sptP did not affect the adhesion of Salmonella Paratyphi A, but the invasive ability of the mutant strain was significantly decreased, the half-lethal dose (LD50 ) of the mutant strain was 1.43 × 104 times of the parent strain in intraperitoneally injected mice. Single intraperitoneal vaccination with SPA017ΔsptP (1 × 105 CFU) in mice did not affect the body weight or elicit clinical symptoms relative to the control group, SPA017ΔsptP bacteria were isolated from livers and spleens of vaccinated mice at 14 days postvaccination. Notably, specific humoral and cellular immune responses were significantly induced. The protective assessment showed that the mutant strain could provide high-level protection against subsequent challenge with the wild-type SPA017 strain. CONCLUSIONS: These results demonstrated that SptP plays an essential role in the pathogenicity of Salmonella Paratyphi A, and Salmonella Paratyphi A lacking sptP is immunogenic and protective in mice.

Laboratory Diagnosis of Paratyphoid Fever: Opportunity of Surface Plasmon Resonance.

Paratyphoid fever is caused by the bacterium Salmonella enterica serovar Paratyphi (A, B and C), and contributes significantly to global disease burden. One of the major challenges in the diagnosis of paratyphoid fever is the lack of a proper gold standard. Given the absence of a licensed vaccine against S. Paratyphi, this diagnostic gap leads to inappropriate antibiotics use, thus, enhancing antimicrobial resistance. In addition, the symptoms of paratyphoid overlap with other infections, including the closely related typhoid fever. Since the development and utilization of a standard, sensitive, and accurate diagnostic method is essential in controlling any disease, this review discusses a new promising approach to aid the diagnosis of paratyphoid fever. This advocated approach is based on the use of surface plasmon resonance (SPR) biosensor and DNA probes to detect specific nucleic acid sequences of S. Paratyphi. We believe that this SPR-based genoassay can be a potent alternative to the current conventional diagnostic methods, and could become a rapid diagnostic tool for paratyphoid fever.

Salmonella Typhi and Paratyphi A infections in Cambodian children, 2012-2016.

OBJECTIVES: Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children. METHODS: Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016. RESULTS: Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A. CONCLUSIONS: In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.

Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature.

Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.

[Epidemiology profil of fever typhoid in Meknes (Morocco) 2013-2016]. / Profil épidémiologique de la fièvre typhoïde, Meknès, 2013­2016.

INTRODUCTION: Twenty million cases of typhoid and paratyphoid fever (TF) are observed annually worldwide with more than 200,000deaths. These fevers occur in areas where hygiene is precarious, mainly in developing countries. The objective of this study was to describe epidemiological patterns of TF in Meknes, Morocco in order to improve preventive measures. METHODS: We conducted a case series study based on data from 2013 to 2016 in the Meknes TF surveillance system. Data collected included socio-demographic variables, place of residence, season, mode of water supply, and food consumed. Diagnosis of TF was confirmed with the Widal test. Data were analyzed with Epi-info version 7 and mapping was done with Qgis version 2.18.1. RESULTS: Three hundred and twenty-two cases were reported with a male/female sex ratio of 0.9. Average age was 26±20years. Incidence increased from 13 per 100.000inhabitants in 2013 to 8 per 100.000 inhabitants in 2016. Two hundred and seventy-nine (87%) cases occurred in urban areas and 174 (54%) cases developed in summer. One death was recorded. CONCLUSION: Public awareness campaigns on health education for hygiene are needed. Focus should be placed on transmission by food handlers.

Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.

Attenuated Salmonella Typhimurium expressing Salmonella Paratyphoid A O-antigen induces protective immune responses against two Salmonella strains.

Salmonella enterica serovar Paratyphi A is the main causative agent of paratyphoid fever in many Asian countries. As paratyphoid is spread by the fecal-oral route, the most effective means of controlling S. Paratyphi A infection is through the availability of clean water supplies and working sanitation services. Because sanitation facilities improve slowly in these poor areas and antibiotic resistance is severe, the development of a safe and effective vaccine remains a priority for controlling the spread of paratyphoid disease. In this study, we investigated the strategy of heterologous O-antigenic O2 serotype (S. Paratyphi A characterized) conversion in S. Typhimurium to prevent paratyphoid infections. A series of S. Typhimurium mutants were constructed with replacement of abe, wzxB1 and wbaVB1 genes with respective prt-tyvA1, wzxA1 and wbaVA1, and the results showed that only three genes including prt, wbaVA1 and wzxA1 from S. Paratyphi A presence enable S. Typhimurium to sufficiently express O2 antigen polysaccharide. We also constructed a series of live attenuated S. Typhimurium vaccine candidates expressing heterologous O2 O-antigens, and a mouse model was used to evaluate the immunogenicity of live vaccines. ELISA data showed that vaccine candidates could induce a comparatively high level of S. Paratyphi A and/or S. Typhimurium LPS-specific IgG and IgA responses in murine model, and IgG2a levels were consistently higher than IgG1 levels. Moreover, the functional properties of serum antibodies were evaluated using in vitro C3 complement deposition and opsonophagocytic assays. Our work highlights the potential for developing S. Typhimurium live vaccines against S. Paratyphi A.

Characterization and protective efficacy of a Salmonella pathogenicity island 2 (SPI2) mutant of Salmonella Paratyphi A.

Paratyphoid fever caused by Salmonella Paratyphi A is a serious public health problem in many countries. In order to and develop a live attenuated candidate vaccine of Salmonella Paratyphi A, a Salmonella pathogenicity island 2 (SPI2, approximate 40 kb) deletion mutant of Salmonella Paratyphi A was constructed by lambda Red recombination, then the biological characteristics and protective ability of the Salmonella Paratyphi A SPI2 mutant were evaluated. Our results showed that the growth and biochemical properties of the SPI2 mutant were consistent with that of its parent strain, and the mutant was stable with the loss of SPI2. The mice lethal test showed that the virulence of the SPI2 mutant was significantly decreased, it can colonize and persistent more than 14 days in the liver and spleen of mice. Vaccination with the SPI2 mutant in mice revealed no significant effect on body weight and clinical symptoms compared to control animals, and specific humoral and cellular immune responses were also significantly induced. Immunization of mice offered efficient protection against Salmonella Paratyphi A strain challenge at 14 days post vaccination based on mortality and clinical symptoms relative to control group. Overall, these findings suggested that SPI2 plays an important role in pathogenicity of Salmonella Paratyphi A, and the SPI2 mutant showed its potential to develop a live attenuated vaccine candidate.

Direct Medical Costs of 3 Reportable Travel-Related Infections in Ontario, Canada, 2012-2014.

Immigrants traveling to their birth countries to visit friends or relatives are disproportionately affected by travel-related infections, in part because most preventive travel health services are not publicly funded. To help identify cost-effective policies to reduce this disparity, we measured the medical costs (in 2015 Canadian dollars) of 3 reportable travel-related infectious diseases (hepatitis A, malaria, and enteric fever) that accrued during a 3-year period (2012-2014) in an ethnoculturally diverse region of Canada (Peel, Ontario) by linking reportable disease surveillance and health administrative data. In total, 318 case-patients were included, each matched with 2 controls. Most spending accrued in inpatient settings. Direct healthcare spending totaled $2,058,196; the mean attributable cost per case was $6,098 (95% CI $5,328-$6,868) but varied by disease (range $4,558-$7,852). Costs were greatest for enteric fever. Policies that address financial barriers to preventive health services for high-risk groups should be evaluated.

Salmonella infections in Canadian children.

Nontyphoidal Salmonella (NTS) infections are primarily transmitted by contaminated food or water or contact with carrier animals (particularly reptiles), and present with diarrhea. Antibiotics do not decrease the severity or duration of diarrhea and may increase the incidence of NTS carriage, so they should only be used with suspected or proven bacteremia or invasive infection. Typhoid/paratyphoid fever manifests as bacteremia within 60 days of travel to resource-poor countries and presents with fever and variable abdominal complaints. Therefore, blood cultures are indicated for unexplained fever and a relevant travel history. When blood cultures are positive or when a child is unwell pending blood culture results, ceftriaxone is indicated. A switch to oral antibiotics (usually azithromycin) is often possible after blood cultures have cleared and the child is improved.

Incidence of Typhoid and Paratyphoid Fevers Among Adolescents and Adults in Yangon, Myanmar.

BACKGROUND: Accurate estimates of typhoid disease burden are needed to guide policy decisions, including on vaccine use. Data on the incidence of enteric fever in Myanmar are scarce. We estimated typhoid and paratyphoid fever incidence among adolescents and adults in Yangon, Myanmar, by combining sentinel hospital surveillance with a healthcare utilization survey. METHODS: We conducted a population-based household health care utilization survey in the Yangon Region 12 March through 5 April 2018. Multipliers derived from this survey were then applied to hospital-based surveillance of Salmonella Typhi and Paratyphi A bloodstream infections from 5 October 2015 through 4 October 2016 at Yangon General Hospital (YGH) to estimate the incidence of typhoid and paratyphoid fevers among person ≥12 years of age. RESULTS: A total of 336 households representing 1598 persons were enrolled in the health care utilization survey, and multipliers were derived based on responses to questions about healthcare seeking in the event of febrile illness. Of 671 Yangon residents enrolled over a 1-year period at YGH, we identified 33 (4.9%) with Salmonella Typhi and 9 (1.3%) with Salmonella Paratyphi A bloodstream infection. After applying multipliers, we estimated that the annual incidence of typhoid was 391 per 100 000 persons and paratyphoid was 107 per 100 000 persons. CONCLUSIONS: Enteric fever incidence is high in Yangon, Myanmar, warranting increased attention on prevention and control, including consideration of typhoid conjugate vaccine use as well as nonvaccine control measures. Research on incidence among infants and children, as well as sources and modes of transmission is needed.