Search

Background Intestinal infectious diseases are one of the common infectious diseases. Analysis and prediction of their epidemic status can provide certain reference for the prevention and treatment of intestinal infectious diseases. Objective To understand the incidence and mortality of three enteric infectious diseases, including diarrheal diseases, typhoid fever and paratyphoid fever, and invasive non-typhoidal Salmonella intestinal infections in China from 1990 to 2019, and to predict their morbidity and mortality from 2020 to 2030, so as to provide reference for the prevention and control of intestinal infectious diseases. Methods Based on the 2019 Global Burden of Disease Database (GBD), the incidence and mortality data of three enteric infectious diseases, including diarrheal diseases, typhoid fever and paratyphoid fever, and invasive non-typhoidal Salmonella intestinal infections in China from 1990 to 2019 were collected. The change rate (%) and estimated annual percentage change (EAPC) were used to describe the changing trends of the above three intestinal infectious diseases. The autoregressive integrated moving average model (ARIMA) was used to predict the morbidity and mortality of the above three enteric infectious diseases in China from 2020 to 2030. Results There was no statistically significant change in the incidence of diarrheal diseases from 1990 to 2019 (EAPC=0.09, P>0.05), while the incidence of typhoid fever, paratyphoid fever and invasive non-typhoid salmonella intestinal infections showed a downward trend (EAPC were -4.0% and -0.64% respectively, P

We applied a new serosurveillance tool to estimate typhoidal Salmonella burden using samples collected during 2020 from a population in Juba, South Sudan. By using dried blood spot testing, we found an enteric fever seroincidence rate of 30/100 person-years and cumulative incidence of 74% over a 4-year period.

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

Background and Aim: Enteric fever causes serious health problems and brings about significant death and ill health globally because of the absence of decisive diagnostic techniques. The ability of frequently used assaysto authenticate the absence of enteric fever is debatable. This research study aimed to appraise the specificity and sensitivity of typhoid diagnosis for establishing highly accurate diagnostic techniques and to recommend appropriate standardized composite references. Materials and Methods: Published articles indexed in Google scholar, MEDLINE and PubMed were reviewed for hospitalbased findings. An independent sample t-test was utilized to ascertain differences in mean percentage specificity and sensitivity. Results: From the 432 articles identified in this study, 53 were used in the analysis. The resulting outcome reveals that Widal techniques show moderate accuracy with percentage average specificity (55%), sensitivity (53.8%), a positive predictive value of 57.8% and a negative predictive value of 55.6% in comparison to 28%, 29.4%, 29.5%, and 27.8% of Typhidot respectively. 34.4% of the studies used prospective study design. The results revealed a statistically significant association in the sensitivity between Typhidot and Widal at p<0.05. The finding also presented emerging enteric fever diagnostic tests such as protein biomarkers, metabolite biomarkers, nucleic acid biomarkers and genomics. Antigens that were regularly assayed are lipopolysaccharides (LPS) and hemolysin E (HlyE). The highest specificity of 96% and sensitivity of 96% were obtained in anti-LPS IgA. Conclusion: Based on the resulting outcome, it is recommended that blood culture and Widal techniques having a sensitivity of 60% and 53.8% respectively be used as a harmonized composite reference standard for enteric fever diagnosis to improve prevalence appraisals. [ABSTRACT FROM AUTHOR]

• Myanmar had a high incidence of enteric fever among travelers. • Salmonella Paratyphi A infection imported from Myanmar increased in 2015. • Myanmar-related isolates in returning travelers were genetically closely related. • Careful monitoring of the infection in Myanmar is warranted. An unusual increase in Salmonella enterica serovar Paratyphi A infection rate in Japanese travelers returning from Myanmar was observed in 2015. 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. 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. 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. [ABSTRACT FROM AUTHOR]

• This article provides a concise overview of the incidence and prevalence of typhoid and paratyphoid fever in mainland China from 2004 to 2019, alongside a spatiotemporal analysis. • During the period from 2004 to 2019, there was a consistent decrease in the number of typhoid fever cases nationwide, although certain regions in southern China, such as Yunnan, experienced an increase in disease prevalence. • Spatial scanning analysis identified the southwest as a focal area for clustering, with subsequent spread to southeastern regions over time. • Relevant governments should enhance surveillance and focus on vulnerable areas and populations. The findings of this study provide supportive evidence for the development of a typhoid vaccine. Typhoid and paratyphoid fever are systemic infections caused by Salmonella Typhi and Salmonella Paratyphi. These diseases are endemic in many parts of China, occurring periodically throughout the year. Epidemiological features, temporal trends, and spatial distribution of these fevers were analyzed using GraphPad Prism 9 with data collected by China's Public Health Science Data Center from 2004 to 2019. Charts were generated to depict their incidence across provinces, years, age groups, and occupations. Spatial clustering was assessed using ArcGIS 10.5 and Moran's I index. SaTScan 9.5 was employed to analyze their spatiotemporal distribution. From 2004 to 2019, China reported 197,623 cases of typhoid fever, resulting in 72 deaths, and 84,583 cases of paratyphoid fever, with 17 fatalities, showing a yearly reduction. Epidemic zones for these diseases are primarily in Yunnan, Guangxi, Guizhou, and other southwestern regions, affecting predominantly peasants and students. Children and adolescents are particularly vulnerable. Due to the epidemic nature of these diseases, they can occur year-round, with peaks in the summer months. This study provides a comprehensive understanding of their epidemiological characteristics and geographic distribution in China, emphasizing the need for authorities to improve living conditions, implement preventive measures, and develop effective treatments and vaccines in these high-risk areas. Figure 1 Number of typhoid/paratyphoid cases in China, 2004-2019 (a), Distribution of typhoid fever; (b), Distribution of paratyphoid fever [Display omitted] [ABSTRACT FROM AUTHOR]

Typhoid fever caused by Salmonella enterica serovar (S.) Typhi differs in its clinical presentation from gastroenteritis caused by S. Typhimurium and other non-typhoidal Salmonella serovars. The different clinical presentations are attributed in part to the virulence-associated capsular polysaccharide (Vi antigen) of S. Typhi, which prevents phagocytes from triggering a respiratory burst by preventing antibody-mediated complement activation. Paradoxically, the Vi antigen is absent from S. Paratyphi A, which causes a disease that is indistinguishable from typhoid fever. Here, we show that evasion of the phagocyte respiratory burst by S. Paratyphi A required very long O antigen chains containing the O2 antigen to inhibit antibody binding. We conclude that the ability to avoid the phagocyte respiratory burst is a property distinguishing typhoidal from non-typhoidal Salmonella serovars that was acquired by S. Typhi and S. Paratyphi A independently through convergent evolution.

Typhoid, paratyphoid, leptospirosis, scrub typhus, and melioidosis are some of the common bacterial infections which are endemic in the region of South Asia. Typhoid and paratyphoid cause enteric fever which is a common cause of fever in the general population in this region. It is caused by Salmonella through contaminated food and water. Enteric fever is one of the most common causes of fever in travelers in this region. Leptospirosis is a zoonotic disease caused by Leptospira and occurs due to direct contact with animals like or through abraded skin after the monsoon in the endemic area. Fever and jaundice are the most common presentations. Scrub typhus is caused by mite Orientia tsutsugamushi and it has now emerged as one of the most common causes of pyrexia in this region. Melioidosis is an uncommon infection caused by the bacteria Burkholderia pseudomalle, which is endemic in some regions of South Asia and is usually seen in immunocompromised individuals. Melioidosis is often called great mimicker due to a variety of clinical manifestations which might confuse it with other diseases. All these infections can cause fever or other systemic complications involving various organs in transplant recipients, so they should be kept as part of differential diagnosis of pyrexia in transplant recipients. There are no recommendations to screen for these infections in transplant candidates or donors, however, transplant candidates or donors with fever should be investigated for these infections and transplant should be deferred until full recovery and for some time thereafter. [ABSTRACT FROM AUTHOR]

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.

Objective. To study both the molecular discrimination of D-tartrate fermenting and non-fermenting strains of Salmonella enterica subsp. enterica serotype Paratyphi B isolated from patients with paratyphoid fever and the clinical course of this disease.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Abstract 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 I 2 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.

Introduction: Enteric fever, which is endemic in India, is a significant cause for morbidity, particularly among young children. Enteric fever is associated with high fever, abdominal pain, diarrhea, and splenomegaly. Recently, there have been increasing reports of enteric fever due to Salmonella enterica serovar Paratyphi A and multidrug resistance among Salmonella species. Objectives: The objective of this study was to know the relative occurrence of Salmonella Typhi and Salmonella Paratyphi A from blood cultures of enteric fever cases, to study the sensitivity pattern of Salmonella species isolated, to compare the clinical profiles in typhoid and paratyphoid fever, and to know their treatment outcome. Materials and Methods: It was a prospective hospital-based cross-sectional study. The demographic, clinical, and laboratory data were recorded for all cases included in the study. All clinically suspected cases of enteric fever were confirmed by blood culture and/or the Widal test. Antibiotic sensitivity was tested by the Kirby–Bauer disc diffusion method. Results were analyzed using SPSS version 21. Results: One hundred and nineteen cases were confirmed enteric fever. Their clinical profile is discussed. Out of 119 cases, 24 showed blood culture positivity. Salmonella Paratyphi A and Salmonella Typhi were isolated in the ratio of 3:1. The isolates were sensitive to ampicillin, co-trimoxazole, ceftriaxone, and azithromycin. Ceftriaxone was the most commonly used antibiotic for treatment. All patients recovered, and no mortality was encountered. Complications were seen in 33 children (27.7%), which included subclinical hepatitis, bronchitis, and pneumonia. Conclusion: Considering the blood culture results, enteric fever due to S. Paratyphi A was more common in our study. Multidrug resistance was not seen among Salmonella species. The duration of illness and complications were more with typhoid than paratyphoid cases.

Salmonella enterica serovar Paratyphi A is a human-specific serovar that, together with Salmonella enterica serovar Typhi and Salmonella enterica serovar Sendai, causes enteric fever. Unlike the nontyphoidal Salmonella enterica serovar Typhimurium, the genomes of S. Typhi and S. Paratyphi A are characterized by inactivation of multiple genes, including in the flagellum-chemotaxis pathway. Here, we explored the motility phenotype of S. Paratyphi A and the role of flagellin in key virulence-associated phenotypes. Motility studies established that the human-adapted typhoidal S. Typhi, S. Paratyphi A, and S. Sendai are all noticeably less motile than S. Typhimurium, and comparative transcriptome sequencing (RNA-Seq) showed that in S. Paratyphi A, the entire motility-chemotaxis regulon is expressed at significantly lowers levels than in S. Typhimurium. Nevertheless, S. Paratyphi A, like S. Typhimurium, requires a functional flagellum for epithelial cell invasion and macrophage uptake, probably in a motility-independent mechanism. In contrast, flagella were found to be dispensable for host cell adhesion. Moreover, we demonstrate that in S. Paratyphi A, but not in S. Typhimurium, the lack of flagellin results in increased transcription of the flagellar and the Salmonella pathogenicity island 1 (SPI-1) regulons in a FliZ-dependent manner and in oversecretion of SPI-1 effectors via type three secretion system 1. Collectively, these results suggest a novel regulatory linkage between flagellin and SPI-1 in S. Paratyphi A that does not occur in S. Typhimurium and demonstrate curious distinctions in motility and the expression of the flagellum-chemotaxis regulon between these clinically relevant pathogens.

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.

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.

Background: Fever and severe myalgia in a tropical country like India bring to mind leptospirosis, rickettsioses, dengue, and other viral fevers. Enteric fever is widely prevalent in Asia, but myositis has not been previously described in Salmonella paratyphi A bacteremia. Materials and Methods: Retrospectively, we recruited patients with enteric fever admitted to our treating unit over a 6-month period. Demography, historical, clinical, and laboratory data were obtained. Data of culture-positive S. paratyphi A patients were analyzed and were compared with those patients with culture-negative enteric fever. Results: Forty-three cases were found in total with 19 of S. paratyphi A bacteremia. Elevations in creatine kinase (CK) ranged from one-and-half to six times normal. Forty-seven percent had thrombocytopenia and alanine transaminase elevations, while aspartate transaminase elevations were seen in 17 patients, which corresponded to those with elevated CK levels. Conclusions: Myositis associated with S. typhi and S. paratyphi is very rare and is more often due to non-typhoidal Salmonellae. Elevated creatine kinase was seen in most of our patients with S. paratyphi A bacteremia. Such myositis has not been described previously and hence, myalgia with fever in a tropical country could be a harbinger of paratyphoid fever.

Enteric fever (typhoid and paratyphoid)is caused by Salmonella typhi and Salmonella paratyphi. It is spread by fecal-oral route, largely through contamination of water and foodstuff. Developing countries are the worst affected. It takes 7 - 21 days from ingestion of the organism to manifestation of symptoms which are generally Fever, relative bradycardia, and pain abdomen. Hepatosplenomegaly, intestinal bleeding, and perforation are the features at various stages of the disease. The bacteria invade the submucous layer and proliferate in the Payer's patches. Blood culture is the gold standard for diagnosis but it is only rarely positive. Fluroquinolones, cephalosporins, and azithromycin are antibiotics of choice. There is increasing evidence of the development of resistance to all antibiotics. Salmonella sepsis, though uncommon, can occur. Intestinal perforation, peritonitis, and secondary sepsis are complications that may require intensive care unit management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundSalmonella enterica serotype Paratyphi A is a human-restricted cause of paratyphoid fever, accounting for up to a fifth of all cases of enteric fever in Asia.Methodology/principal findingsIn this work, we applied an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), and cDNA hybridization-microarray technology to identify S. Paratyphi A transcripts expressed by bacteria in the blood of three patients in Bangladesh. In total, we detected 1,798 S. Paratyphi A mRNAs expressed in the blood of infected humans (43.9% of the ORFeome). Of these, we identified 868 in at least two patients, and 315 in all three patients. S. Paratyphi A transcripts identified in at least two patients encode proteins involved in energy metabolism, nutrient and iron acquisition, vitamin biosynthesis, stress responses, oxidative stress resistance, and pathogenesis. A number of detected transcripts are expressed from PhoP and SlyA-regulated genes associated with intra-macrophage survival, genes contained within Salmonella Pathogenicity Islands (SPIs) 1-4, 6, 10, 13, and 16, as well as RpoS-regulated genes. The largest category of identified transcripts is that of encoding proteins with unknown function. When comparing levels of bacterial mRNA using in vivo samples collected from infected patients to samples from in vitro grown organisms, we found significant differences for 347, 391, and 456 S. Paratyphi A transcripts in each of three individual patients (approximately 9.7% of the ORFeome). Of these, expression of 194 transcripts (4.7% of ORFs) was concordant in two or more patients, and 41 in all patients. Genes encoding these transcripts are contained within SPI-1, 3, 6 and 10, PhoP-regulated genes, involved in energy metabolism, nutrient acquisition, drug resistance, or uncharacterized genes. Using quantitative RT-PCR, we confirmed increased gene expression in vivo for a subset of these genes.Conclusion/significanceTo our knowledge, we describe the first microarray-based transcriptional analysis of a pathogen in the blood of naturally infected humans.

Summary: Typhoid fever caused by Salmonella enterica serovar (S.) Typhi differs in its clinical presentation from gastroenteritis caused by S. Typhimurium and other non-typhoidal Salmonella serovars. The different clinical presentations are attributed in part to the virulence-associated capsular polysaccharide (Vi antigen) of S. Typhi, which prevents phagocytes from triggering a respiratory burst by preventing antibody-mediated complement activation. Paradoxically, the Vi antigen is absent from S. Paratyphi A, which causes a disease that is indistinguishable from typhoid fever. Here, we show that evasion of the phagocyte respiratory burst by S. Paratyphi A required very long O antigen chains containing the O2 antigen to inhibit antibody binding. We conclude that the ability to avoid the phagocyte respiratory burst is a property distinguishing typhoidal from non-typhoidal Salmonella serovars that was acquired by S. Typhi and S. Paratyphi A independently through convergent evolution.

Background The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan. Methods We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later. From the health care provider perspective, we collected data on quantities and prices of resources used at 3 of the hospitals, to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Pakistani rupees and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. Results We collected patient and caregiver information for 1029 patients with blood culture–confirmed enteric fever or with a nontraumatic terminal ileal perforation, with a median cost of illness per case of US $196.37 (IQR, US $72.89–496.40). The median direct medical and nonmedical costs represented 8.2% of the annual labor income. From the health care provider perspective, the estimated average direct medical cost per case was US $50.88 at Hospital A, US $52.24 at Hospital B, and US $11.73 at Hospital C. Conclusions Enteric fever can impose a considerable economic burden in Pakistan. These new estimates of the cost of illness of enteric fever can improve evaluation and modeling of the costs and benefits of enteric fever prevention and control measures, including typhoid conjugate vaccines. [ABSTRACT FROM AUTHOR]

Background Enteric fever is endemic in Nepal and its economic burden is unknown. The objective of this study was to estimate the cost of illness due to enteric fever (typhoid and paratyphoid) at selected sites in Nepal. Methods We implemented a study at 2 hospitals in Nepal to estimate the cost per case of enteric fever from the perspectives of patients, caregivers, and healthcare providers. We collected direct medical, nonmedical, and indirect costs per blood culture–confirmed case incurred by patients and their caregivers from illness onset until after enrollment and 6 weeks later. We estimated healthcare provider direct medical economic costs based on quantities and prices of resources used to diagnose and treat enteric fever, and procedure frequencies received at these facilities by enrolled patients. We collected costs in Nepalese rupees and converted them into 2018 US dollars. Results We collected patient and caregiver cost of illness information for 395 patients, with a median cost of illness per case of $59.99 (IQR, $24.04–$151.23). Median direct medical and nonmedical costs per case represented ~3.5% of annual individual labor income. From the healthcare provider perspective, the average direct medical economic cost per case was $79.80 (range, $71.54 [hospital B], $93.43 [hospital A]). Conclusions Enteric fever can impose a considerable economic burden on patients, caregivers, and health facilities in Nepal. These new estimates of enteric fever cost of illness can improve evaluation and modeling of the costs and benefits of enteric fever–prevention measures. [ABSTRACT FROM AUTHOR]

Background We conducted a cost of illness study to assess the economic burden of pediatric enteric fever (typhoid and paratyphoid) in Bangladesh. Results can inform public health policies to prevent enteric fever. Methods The study was conducted at 2 pediatric health facilities in Dhaka. For the patient and caregiver's perspective, we administered questionnaires on costs incurred from illness onset until the survey dates to caregivers of patients with blood culture positive cases at enrollment and 6 weeks later to estimate the direct medical, direct nonmedical, and indirect costs. From the perspective of the health care provider, we collected data on quantities and prices of resources used by the 2 hospitals to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Bangladeshi takas and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. Results Among the 1772 patients from whom we collected information, the median cost of illness per case of enteric fever from the patient and caregiver perspective was US $64.03 (IQR: US $33.90 –$173.48). Median direct medical and nonmedical costs per case were 3% of annual labor income across the sample. From the perspective of the healthcare provider, the average direct medical cost per case was US $58.64 (range: US $37.25 at Hospital B, US $73.27 at Hospital A). Conclusions Our results show substantial economic burden of enteric fever in Bangladesh, with higher costs for patients receiving inpatient care. As antimicrobial resistance increases globally, the cost of illness could increase, due to more expensive and potent drugs required for treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The ABO blood groups and Rhesus factor are different in their susceptibility and resistance to various diseases. The role of ABO blood group has long been a subject of investigation and debate. Typhoid and paratyphoid disease is commonly encountered a systemic disease caused by gram negative bacteria Salmonella typhi and Salmonella paratyphi. Because of the presence of favorable predisposing factors for transmission of typhoid disease among children in Kurdistan. Objective: To find the occurrence of Salmonella typhi and Salmonella paratyphi among children, with their distribution among different blood groups. Patients and Methods: A cross-sectional study was carried out on 300 subjects were randomly selected from children who were likely to be infected with typhoid or paratyphoid fever in Raparin Teaching Hospital in Erbil. Blood sample were taken for performing ABO blood grouping, widal test and blood cultures. Results: Result of the study reveals (31.33%) and (34.33%) of children were infected with Salmonella typhi and Salmonella paratyphi. The highest typhoid/paratyphoid was observed among blood group O, thus it was most susceptible group. The least was noticed among blood group AB children which is the most resistant. Conclusion: Results have revealed significant association between ABO blood group and susceptibility to typhoid/paratyphoid infections. [ABSTRACT FROM AUTHOR]

Introduction: Typhoid and paratyphoid fever remain a global health problem, which – in non-endemic countries – are mainly seen in travelers, particularly in VFRs (visiting friends and relatives), with occasional local outbreaks occurring. A rise in anti-microbial resistance emphasizes the role of preventive measures, especially vaccinations against typhoid and paratyphoid fever for travelers visiting endemic countries. Areas covered: This state-of-the-art review recapitulates the epidemiology and mechanisms of disease of typhoid and paratyphoid fever, depicts the perspective of non-endemic countries and travelers (VFRs), and collectively presents current European recommendations for typhoid fever vaccination. We provide a brief overview of available (and developmental) vaccines in Europe, present current data on cross-protection to S. Paratyphi, and aim to provide a background for typhoid vaccine decision-making in travelers. Expert commentary: European recommendations are not harmonized. Experts must assess vaccination of travelers based on current country-specific recommendations. Travel health practitioners should be aware of the issues surrounding vaccination of travelers and be motivated to increase awareness of typhoid and paratyphoid fever risks.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Background Analyses of the global spatial and temporal distribution of enteric fever outbreaks worldwide are important factors to consider in estimating the disease burden of enteric fever disease burden. Methods We conducted a global literature review of enteric fever outbreak data by systematically using multiple databases from 1 January 1990 to 31 December 2018 and classified them by time, place, diagnostic methods, and drug susceptibility, to illustrate outbreak characteristics including spatial and temporal patterns. Results There were 180 940 cases in 303 identified outbreaks caused by infection with Salmonella enterica serovar Typhi (S. Typhi) and Salmonella enterica serovar Paratyphi A or B (S. Paratyphi). The size of outbreak ranged from 1 to 42 564. Fifty-one percent of outbreaks occurred in Asia, 15% in Africa, 14% in Oceania, and the rest in other regions. Forty-six percent of outbreaks specified confirmation by blood culture, and 82 outbreaks reported drug susceptibility, of which 54% had multidrug-resistant pathogens. Paratyphoid outbreaks were less common compared to typhoid (22 vs 281) and more prevalent in Asia than Africa. Risk factors were multifactorial, with contaminated water being the main factor. Conclusions Enteric fever outbreak burden remains high in endemic low- and middle-income countries and, despite its limitations, outbreak data provide valuable contemporary evidence in prioritizing resources, public health policies, and actions. This review highlights geographical locations where urgent attention is needed for enteric fever control and calls for global action to prevent and contain outbreaks. [ABSTRACT FROM AUTHOR]

In‐house loop‐mediated isothermal amplification (LAMP) procedures for the detection of paratyphoid fever‐associated bacteria on serovar level were evaluated. Therefore, LAMP primers for Salmonella genus, for two LAMP schemes for S. Paratyphi A, for S. Paratyphi B and for S. Paratyphi C were tested with DNA from culture isolates from strain collections and spiked blood cultures against published PCR protocols targeting the same micro‐organisms. Sensitivity and specificity for DNA from culture isolates verified by LAMP ranged from 80·0 to 100·0% and 96·1 to 100·0% vs 65 to 100% and 98·7 to 100% for the PCR approaches. For the spiked blood culture materials, sensitivity and specificity for LAMP ranged from 87·5 to 100·0% and 96·7 to 100·0% vs from 60 to 100% and 98·2 to 100% for PCR. In conclusion, LAMP for paratyphoid fever shows comparable performance characteristics as PCR. Due to its easy application, the procedure is well suited for surveillance purposes in resource‐limited settings. Significance and Impact of the Study: The use of easy‐to‐apply, point‐of‐care‐testing‐like loop‐mediated isothermal amplification (LAMP) for the diagnosis of paratyphoid fever is evaluated. This approach can contribute to low‐threshold availability of surveillance options for resource limited settings. Easy‐to‐teach and easy‐to‐apply LAMP schemes with similar performance characteristics as PCR are provided. The described test evaluation is of particular use for surveillance and public health experts. Significance and Impact of the Study: The use of easy‐to‐apply, point‐of‐care‐testing‐like loop‐mediated isothermal amplification (LAMP) for the diagnosis of paratyphoid fever is evaluated. This approach can contribute to low‐threshold availability of surveillance options for resource limited settings. Easy‐to‐teach and easy‐to‐apply LAMP schemes with similar performance characteristics as PCR are provided. The described test evaluation is of particular use for surveillance and public health experts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children. Methods We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old. Results We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months (P <.001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid. Conclusions Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden. [ABSTRACT FROM AUTHOR]

Background: Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children. Methods: We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old. Results: We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months (P <.001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid. Conclusions: Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]