Chronic Typhoid Carriers Research Articles

Whole genome sequence analysis of Salmonella Typhi provides evidence of phylogenetic linkage between cases of typhoid fever in Santiago, Chile in the 1980s and 2010-2016.

Typhoid fever epidemiology was investigated rigorously in Santiago, Chile during the 1980s, when Salmonella enterica serovar Typhi (S. Typhi) caused seasonal, hyperendemic disease. Targeted interventions reduced the annual typhoid incidence rates from 128–220 cases/105 population occurring between 1977–1984 to <8 cases/105 from 1992 onwards. As such, Santiago represents a contemporary example of the epidemiologic transition of an industrialized city from amplified hyperendemic typhoid fever to a period when typhoid is no longer endemic. We used whole genome sequencing (WGS) and phylogenetic analysis to compare the genotypes of S. Typhi cultured from acute cases of typhoid fever occurring in Santiago during the hyperendemic period of the 1980s (n = 74) versus the nonendemic 2010s (n = 80) when typhoid fever was rare. The genotype distribution between “historical” (1980s) isolates and “modern” (2011–2016) isolates was similar, with genotypes 3.5 and 2 comprising the majority of isolations, and 73/80 (91.3%) of modern isolates matching a genotype detected in the 1980s. Additionally, phylogenomically ‘ancient’ genotypes 1.1 and 1.2.1, uncommon in the global collections, were also detected in both eras, with a notable rise amongst the modern isolates. Thus, genotypes of S. Typhi causing acute illness in the modern nonendemic era match the genotypes circulating during the hyperendemic 1980s. The persistence of historical genotypes may be explained by chronic typhoid carriers originally infected during or before the 1980s.

Biofilm and Chronic Typhoid Carriers with Special Reference to Bacteriophage Therapy

Biofilm and Chronic Typhoid Carriers with Special Reference to Bacteriophage Therapy

Point-of-Care Ultrasound by Nonexpert Operators Demonstrates High Sensitivity and Specificity in Detecting Gallstones: Data from the Samoa Typhoid Fever Control Program.

ABSTRACT.Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a “Typhoid Epidemiologic SWAT Team” to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.

Establishment of Chronic Typhoid Infection in a Mouse Carriage Model Involves a Type 2 Immune Shift and T and B Cell Recruitment to the Gallbladder.

Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S Typhi), is a life-threatening systemic disease responsible for significant morbidity and mortality worldwide. Three to 5% of individuals infected with S Typhi become chronic carriers due to bacterial persistence in the gallbladder. We have demonstrated that Salmonella forms biofilms on gallstones to establish gallbladder carriage. However, an in-depth molecular understanding of chronic carriage in the gallbladder, from the perspective of both the pathogen and host, is poorly defined. To examine the dynamics of the gallbladder in response to Salmonella infection, we performed transcriptional profiling in the mouse gallbladder at early (7 days) and chronic (21 days) time points. Transcriptome sequencing (RNA-Seq) revealed a shift from a Th1 proinflammatory response at 7 days postinfection (dpi) toward an anti-inflammatory Th2 response by 21 dpi, characterized by increased levels of immunoglobulins and the Th2 master transcriptional regulator, GATA3. Additionally, bioinformatic analysis predicted the upstream regulation of characteristic Th2 markers, including interleukin-4 (IL-4) and Stat6. Immunohistochemistry and fluorescence-activated cell sorter (FACS) analysis confirmed a significant increase in lymphocytes, including T and B cells, at 21 dpi in mice with gallstones. Interestingly, the levels of Salmonella-specific CD4 T cells were 10-fold higher in the gallbladder of mice with gallstones at 21 dpi. We speculate that the biofilm state allows Salmonella to resist the initial onslaught of the Th1 inflammatory response, while yet undefined events influence a switch in the host immunity toward a more permissive type 2 response, enabling the establishment of chronic infection.IMPORTANCE The existence of chronic typhoid carriers has been in the public eye for over 100 years in part because of the publicity around Typhoid Mary. Additionally, it has been known for decades that the gallbladder is the main site of persistence and recently that gallstones play a key role. Despite this, very little is known about the physiological conditions that allow Salmonella enterica serovar Typhi to persist in the gallbladder. In this study, we analyze the transcriptional profile of the gallbladder in a mouse model of chronic carriage. We found a shift from an early proinflammatory immune response toward a later anti-inflammatory response, which could explain the stalemate that allows Salmonella persistence. Interestingly, we found a 10-fold increase in the number of Salmonella-specific T cells in mice with gallstones. This work moves us closer to understanding the mechanistic basis of chronic carriage, with a goal toward eradication of the disease.

Is Salmonella enterica serovar Typhi associated with carcinoma gall bladder?

Introduction: Gallbladder carcinoma is a common hepatobiliary malignancy with poor prognosis. It is 3rd commonest malignancy in north India. Salmonella typhi is one of risk factor for gallbladder cancer. India is high endemic area for typhoid in the world. Various authors reported association between the two but without doing testing for typhoid carrier, association cannot be proven. Aim: The present study was designed to explore the association of the chronic typhoid carrier state and carcinoma gall bladder by detecting Salmonella typhi in specimens of gallbladder from patients with malignant and benign gallbladder diseases using a Nested PCR. Methods and material: In this prospective case control study, we have got 39 samples from Carcinoma Gall Bladder (GBC) patients as cases and 75 samples from benign Gall Bladder Diseases (GBD) patients as controls in two years duration. We have done Indirect haemagglutination test for typhoid carrier from five milliliters of blood which was collected from each patient before surgery. Nested PCR was done from gall bladder tissue, which was taken at operation, from both GBC and GBD patients. Result: Nested PCR showed 59% positivity for Salmonella typhi in the GBC and 56% in GBD, so association of Salmonella typhi with GBC was not statistically significant. Vi antibody was present 33% in GBC and 37% in GBD by IHA. It is also not statistically significant. Conclusion: A large number of sample size is require for proving association between carcinoma gall bladder and Salmonella typhi by using definite marker for Vi antibodies.

Role of Gallstones in Typhoid Carriage in Egyptian Patients

Objectives: Salmonella typhi forms biofilm on the surface of gallstones promoting colonization and carrier state. The aims are to detect its frequency in chronic calcular cholecystitis patients, to find out their antibiotic resistance pattern, and also to examine biofilm on the surface of gallstones and detect its correlation to antibiotic susceptibility pattern. Materials and methods: The study group included 257 patients with chronic calcular cholecystitis. S. typhi was isolated from gall bladder specimens. Antibiotics susceptibility tests of the isolates were done. Biofilm on surface of gallstones were visualized using scanning electron microscopy. Virulence (Vi) antibodies against S. typhi were studied in sera of 257 healthy controls. Results: 10.9% of patients were chronic typhoid carriers compared to only 3.5% of the controls (OR= 3.37, p=0.002). Multidrug resistance was detected in 35.7% of isolates. S. typhi biofilms on the surface of the 21/28 (75%) gallstones were detected. Ninety percent of the strains that produced maximum amount of biofilm were multidrug-resistant. Conclusion: Chronic calcular cholecystitis patients are more prone to typhoid carriage due to biofilm formation of S. typhi on the surface of gallstones. J Microbiol Infect Dis 2012; 2(4): 142-149

Acid exposure induces multiplication of Salmonella enterica serovar Typhi.

Salmonella enterica serovar Typhi faces several environmental stresses while going through the stomach (acidic pH) to the small intestine (basic pH) and intracellularly in macrophages (acidic pH) in humans. The acidic pH followed by alkaline pH in the small intestine might be responsible for expression of certain stress-induced genes, resulting in not only better survival but also induction of multiplication and invasion of the bacterium in the small intestine. Based on this hypothesis, we developed a process wherein we exposed the blood, urine, and stool specimens from 90 acute typhoid fever patients and 36 chronic typhoid carriers to acidic pH to see the effect on isolation rate of S. Typhi. About 5 g of freshly passed unpreserved stool, a centrifuged deposit of 15 ml of urine, and 5 ml of blood clot were subjected to 5 ml of Luria-Bertani (LB) broth (pH 3.5) for 20 min, followed by enrichment in bile broth-selenite F broth. When the combined isolation from all 3 specimens, i.e., blood, urine, and stool, after acid exposure was considered, a total of 77.7% of the acute typhoid patients were observed to be positive for the isolation of the S. Typhi serotype, compared to 8.8% by the conventional method. Similarly, 42% (15/36) of chronic carriers yielded positive for S. Typhi growth after acid exposure, compared to 5.5% (2/36) by the conventional method. It therefore can be concluded that acid shock triggers the multiplication of the bacteria, resulting in better isolation rates from blood clot, stool, and urine specimens.

Typhoid fever in Fiji: a reversible plague?

The country of Fiji, with a population of approximately 870 000 people, faces a growing burden of several communicable diseases including the bacterial infection typhoid fever. Surveillance data suggest that typhoid has become increasingly common in rural areas of Fiji and is more frequent amongst young adults. Transmission of the organisms that cause typhoid is facilitated by faecal contamination of food or water and may be influenced by local behavioural practices in Fiji. The Fijian Ministry of Health, with support from Australian Aid, hosted a meeting in August 2012 to develop comprehensive control and prevention strategies for typhoid fever in Fiji. International and local specialists were invited to share relevant data and discuss typhoid control options. The resultant recommendations focused on generating a clearer sense of the epidemiology of typhoid in Fiji and exploring the contribution of potential transmission pathways. Additionally, the panel suggested steps such as ensuring that recommended ciprofloxacin doses are appropriate to reduce the potential for relapse and reinfection in clinical cases, encouraging proper hand hygiene of food and drink handlers, working with water and sanitation agencies to review current sanitation practices and considering a vaccination policy targeting epidemiologically relevant populations.

Proteomics-based identification of plasma proteins and their association with the host–pathogen interaction in chronic typhoid carriers

SummaryBackgroundCurrent diagnostic tests are inadequate to detect typhoid cases, as well as the chronic carrier state, the sole reservoir of Salmonella enterica serovar Typhi. The current study was conducted to find new molecular signatures of pathogen/disease to understand the mechanism behind the host–pathogen interaction in enteric fever.MethodsProteomics-based studies were done to determine the expression of differentially expressed proteins in the plasma of controls, acute typhoid cases, and chronic typhoid carriers. Further, transcriptome-based analysis using reverse-transcriptase PCR (RT-PCR) was done in controls, acute typhoid cases, and chronic typhoid carriers.ResultsResults showed the upregulation of proprotein convertase subtilisin, furin, haptoglobin, and albumin in the plasma of chronic typhoid carriers. The elevation in mRNA expression of four differentially expressed proteins confirms the changes at the transcriptional level. Further, the increase in albumin and haptoglobin in chronic typhoid carriers shows their role in free radical generation, inflammation, and monocyte cell signaling.ConclusionThrough proteomics techniques, this study identified four proteins in the chronic typhoid carrier host that may have a role in the disease pathogenesis of enteric fever.

Targeting of putative fimbrial gene for detection of S. Typhi in typhoid fever and chronic typhoid carriers by nested PCR

It is important to identify Salmonella Typhi infection quickly to treat acute fever patients and to prevent transmission by chronic typhoid carriers; therefore, a very specific and sensitive diagnostic technique is highly desirable, especially in endemic areas. The objective of this study was to develop a PCR protocol targeting the putative fimbrial staA gene of S. Typhi. This is a preferred target gene that is specifically amplified in the S. Typhi serotype compared to the commonly targeted fliC gene which may also be amplified from the non-typhoidal Salmonella Munchen serotype. A new nested PCR primer methodology was designed to target the staA gene, which is a member of the fimbrial gene family specific to Salmonella Typhi only. The primers were found to be very specific as the desired amplicon (377 bp) could be generated exclusively from S. Typhi strains including the reference strain (MTCC 3216) and 78 clinical isolates . Restriction digestion with HinfI confirmed the identity of the amplified DNA fragment in clinical specimens of S. Typhi origin. Furthermore, these primers were able to detect a minimum of three colony forming units per ml (1fg) in spiked blood samples. The detection sensitivity of the described primers is comparable to that of previously published primers targeting fliC gene sequences. This study indicates that the primers targeting the putative fimbrial staA gene are very specific to the Typhi serotype and may be a better alternative to fliC targeted amplification based diagnosis.

Isolation of Salmonella typhi from apparently healthy liver

It is suggested that Salmonella typhi resides mostly in hepatobiliary system especially in gallbladder in chronic typhoid carriers. It is not very clear whether in gallbladder lumen or on its wall or in liver. However, we had been successful in detecting S. typhi in liver by PCR targeting flagellin gene sequences. Therefore, in the present study, we tried to isolate the bacterium from liver tissue collected from dead bodies brought for post mortem examination. We could isolate S. typhi in 2 of 20 such liver tissues examined by using conventional isolation techniques. The isolates were identified by routine phenotypic characters and were confirmed by amplification and sequencing of two conserved genes i.e. 16S rDNA and flagellin (fliC) gene followed by blasting on www.ncbi.nlm.nih.gov.

Does Salmonella Typhi primarily reside in the liver of chronic typhoid carriers?

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Association of carcinoma of the gallbladder with typhoid carriage in a typhoid endemic area using nested PCR

Although well studied the association between chronic typhoid carrier state and carcinoma of the gallbladder (CaGB) remains unproven. The study was performed at a tertiary care medical center in North India and involved 52 patients with CaGB, 223 patients with benign gallbladder diseases, 508 healthy individuals and, 424 corpses. For the detection of Salmonella enterica serovar Typhi, hepatobiliary specimens were subjected to DNA extraction for specific nested- PCR amplification of the S. Typhi flagellin gene. Anti-Vi S. Typhi antibodies were detected in serum samples from patients by indirect haemagglutination. Thirty five of the 52 (67.3%) CaGB patients were PCR-positive for the S. Typhi flagellin gene; significantly higher than for patients with benign gallbladder diseases (95/223, 42.6%; p<0.01) and corpses (35/424, 8.2%; p<0.001). The numbers of individuals that had significant anti-Vi antibody titres (> or = 160) in their serum were 20/52 (38.5%) for CaGB patients, 31/223 (13.9%) for patients with benign gallbladder diseases, and 47/508 (9.2%) for healthy individuals. Specific nested-PCR amplification of the S. Typhi flagellin gene in hepato-biliary specimens was more sensitive for detection of S. Typhi carriage than anti-Vi antibody titres in serum. The results demonstrate an association between typhoid carriage and gallbladder diseases, both CaGB and benign. S. Typhi specific immunosuppression is also suggested in patients with gallbladder diseases.

Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder

OBJECTIVE: The aim of this study was to identify risk factors for carcinoma of the gallbladder (CaGB) among patients with gallstones (GS) with special reference to role of chronic Salmonella typhi carrier state. METHODS: A prospective case-control study was conducted in a tertiary care center in India. Cases were defined as consecutive patients with CaGB and GS, whereas controls were patients with GS alone. All were assessed clinically and their demographic data, diet, and smoking history recorded. Patients were detected to be typhoid carriers on the basis of Vi serology by enzyme linked immunosorbent assay. Cases (n = 37) and controls (n = 80) were compared by univariate and logistic regression analysis. RESULTS: The mean age of the cases and the controls were 53.4 ± 11 yr and 43.5 ± 14 yr, respectively. Among the cases, six (16%) patients were detected to be typhoid carriers, in contrast to two (2.5%) among controls ( p = 0.01). Compared to controls, cases were more often older ( p = 0.0002), of a lower socioeconomic status ( p = 0.0005), and smokers ( p = 0.0002). Stepwise logistic regression analysis identified typhoid carrier state (OR = 14; CI 2–92), age ≥47 yr (OR = 5; CI 2–14) and smoking (OR = 11; CI 2–71) as the three independent risk factors for development of CaGB among patients with GS. CONCLUSION: Chronic typhoid carrier state was the most important risk factor among patients with CaGB and gallstones.

Cancer risk in chronic typhoid and paratyphoid carriers

Cancer risk in chronic typhoid and paratyphoid carriers

Efficacy of ciprofloxacin in the treatment of chronic typhoid carriers.

Journal Article Efficacy of Ciprofloxacin in the Treatment of Chronic Typhoid Carriers Get access Catterine Ferreccio, Catterine Ferreccio Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Glenn Morris, Jr., J. Glenn Morris, Jr. Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Please address requests for reprints to Dr. J. Glenn Morris, Jr., Division of Geographic Medicine, University of Maryland School of Medicine, 9th Floor MSTF, 10 South Pine Street, Baltimore, Maryland 21201. Search for other works by this author on: Oxford Academic PubMed Google Scholar Carmen Valdivieso, Carmen Valdivieso Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar Ingeborg Prenzel, Ingeborg Prenzel Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar Viviana Sotomayor, Viviana Sotomayor Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar George L. Drusano, George L. Drusano Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar Myron M. Levine Myron M. Levine Divisions of Geographic Medicine and of Infectious Diseases, Department of Medicine, and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; and the Typhoid Fever Control Program, Ministry of Health, and the Roberto del Rio Hospital, Santiago, Chile Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 157, Issue 6, June 1988, Pages 1235–1239, https://doi.org/10.1093/infdis/157.6.1235 Published: 01 June 1988 Article history Received: 26 October 1987 Revision received: 07 January 1988 Published: 01 June 1988

Typhoid fever in Santiago, Chile: a study of household contacts of pediatric patients.

We obtained clinical, epidemiological, and laboratory data (including three stool cultures) from 155 (96%) of 161 household contacts of 24 patients less than 16 years old with culture-confirmed typhoid fever; these 24 patients represented approximately 40% of such patients seen in three hospitals in Santiago during a 12-week period. A chronic typhoid carrier was identified in only one household, with concurrent or secondary cases seen in two other households. When index cases were matched with household members nearest in age, no specific risk factors for illness could be identified. There was evidence of generalized exposure to enteric pathogens within these households, with nine persons from seven different households culture-positive for non-typhoidal Salmonella, and nine, from eight different households, culture-positive for Shigella; transmission of these pathogens within households did not appear to be common since no household had more than one family member with the same serotype or species of either pathogen.

ASSOCIATION BETWEEN HEPATOBILIARY CANCER AND TYPHOID CARRIER STATE

A case-control study of deceased typhoid carriers registered by the New York City Health Department between 1922 and 1975 was carried out to test for an association between the typhoid-carrier state and death due to hepatobiliary cancer. 471 carriers were matched with 942 controls for sex, age at death, year of death, borough in which the carrier died, and where they were born. The results show that chronic typhoid carriers die of hepatobiliary cancer six times more often than the matched controls and that this difference is significant (P<0·001) by simple χ 2 test and by the Mantel-Haenszel method of χ 2 for matched triples. Possible mechanisms for this association are discussed.

Treatment of typhoid carriers with amoxicillin. Correlates of successful therapy.

Fifteen chronic enteric carriers of Salmonella typhi were treated with amoxicillin trihydrate, 2 g by mouth, three times per day. Nine of ten patients who were able to take the full amoxicillin regimen were cured; among five patients treated with a lower daily amoxicillin dosage because of gastrointestinal (GI) side effects, only two were cured (P less than .05). The mean serum amoxicillin concentration at termination of therapy was higher (P less than .01) in five patients who were cured (10.4 +/- 1.6 microgram/ml) than in the four who failed (3.0 +/- 0.7 microgram/ml), although the latter values were all above the minimal inhibitory concentrations for infecting organisms. This study suggests that amoxicillin treatment of chronic typhoid carriers could be enhanced by treating with doses sufficient to provide suprainhibitory serum concentrations of the antibiotic. However, GI intolerance to amoxicillin could limit this therapeutic approach.

Chemotherapy of typhoid fever: a review of literature.

Until the last few years, chloramphenicol was recognized positively as the drug of choice in the treatment of acute typhoid fever. Its hematoxicity, as well as the recently observed epidemic and the present endemic occurrence of S. typhi strains with R-factor-mediated resistance to chloramphenicol in Mexico, India and South-EAst Asia, render the clinical evaluation of new antibacterial agents extremely important. By means of a literature review on controlled comparative trials, the value of thiamphenicol, ampicillin, amoxycillin, furazolidone and co-trimoxazole as alternative drugs for the treatment of acute typhoid fever is examined. Co-trimoxazole seems to be the drug of choice in the treatment of acute typhoid fever. For the treatment of the chronic typhoid carrier ampicillin is most frequently used, but amoxycillin and co-trimoxazole seem to be just as effective.