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1.
Indian J Pathol Microbiol ; 67(2): 435-437, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38391303

RESUMEN

ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a severe and frequently underdiagnosed disorder of systemic immune dysregulation resulting in hypercytokinemia and histologically evident hemophagocytosis, We report a case of a 34-year-old man who presented with breathlessness, generalized weakness, and fever of unknown origin with pancytopenia. Clinically the patient was admitted for febrile illness, and treated symptomatically but his general condition worsened leading to death within 21 hours of admission. A complete autopsy was performed. The deceased had a significant past history of repeated episodes of fever, weight loss, and axillary lymphadenopathy over a period of 8 months with multiple hospital admissions. He was also diagnosed with enteric fever (Widal test and Typhi IgM positive) at the start of these episodes. Hemogram during this period revealed persistent pancytopenia. Serum ferritin, serum triglycerides, and liver function tests were consistently deranged. Investigations for the etiology of fever and blood cultures were negative while the bone marrow aspirate revealed a normocellular marrow. CT abdomen-pelvis showed mild hepatomegaly with enlarged retroperitoneal lymph nodes. Infective endocarditis, lymphoma, and bronchopneumonia were being considered the clinical diagnoses. The significant autopsy findings were hepatosplenomegaly with retroperitoneal lymphadenopathy and multiple gastric ulcers. On microscopy, the liver, spleen, bone marrow, and lymph nodes showed characteristic hemophagocytosis. Post-mortem histopathological examination clinched the diagnosis of HLH and fulfilled six out of eight diagnostic criteria of the HLH-2004 protocol. We discuss the clinical course and diagnosis of this unique case and strive to create awareness about secondary HLH induced by common diseases, such as enteric fever.


Asunto(s)
Autopsia , Linfohistiocitosis Hemofagocítica , Fiebre Tifoidea , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/complicaciones , Masculino , Adulto , Fiebre Tifoidea/complicaciones , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/patología , Resultado Fatal , Médula Ósea/patología , Ganglios Linfáticos/patología , Hígado/patología , Bazo/patología , Hepatomegalia/etiología
2.
Methods Mol Biol ; 2427: 215-234, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35619037

RESUMEN

Efforts to understand molecular mechanisms of pathogenesis of the human-restricted pathogen Salmonella enterica serovar Typhi, the causative agent of typhoid fever, have been hampered by the lack of a tractable small animal model. This obstacle has been surmounted by a humanized mouse model in which genetically modified mice are engrafted with purified CD34+ stem cells from human umbilical cord blood, designated CD34+ Hu-NSG (formerly hu-SRC-SCID) mice. We have shown that these mice develop a lethal systemic infection with S. Typhi that is dependent on the presence of engrafted human hematopoietic cells. Immunological and pathological features of human typhoid are recapitulated in this model, which has been successfully employed for the identification of bacterial genetic determinants of S. Typhi virulence. Here we describe the methods used to infect CD34+ Hu-NSG mice with S. Typhi in humanized mice and to construct and analyze a transposon-directed insertion site sequencing S. Typhi library, and provide general considerations for the use of humanized mice for the study of a human-restricted pathogen.


Asunto(s)
Salmonella typhi , Fiebre Tifoidea , Animales , Modelos Animales de Enfermedad , Ratones , Ratones SCID , Salmonella typhi/genética , Fiebre Tifoidea/microbiología , Fiebre Tifoidea/patología , Virulencia/genética
3.
Sci Rep ; 11(1): 2730, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526848

RESUMEN

Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.


Asunto(s)
Hígado/patología , Malaria/patología , Fiebre Tifoidea/patología , Animales , Coinfección/patología , Modelos Animales de Enfermedad , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Neutrófilos/patología , Plasmodium berghei , Salmonella typhi
4.
Cells ; 10(2)2021 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-33562108

RESUMEN

In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.


Asunto(s)
Progresión de la Enfermedad , Variación Genética , Fiebre Tifoidea/genética , Fiebre Tifoidea/patología , Biomarcadores/metabolismo , Humanos , Inmunidad Innata , Tamaño de la Muestra , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/inmunología
5.
Am J Trop Med Hyg ; 103(6): 2515-2517, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32959766

RESUMEN

In contrast to enteric fever, reports of secondary hemophagocytic lymphohistiocytosis (HLH) in invasive non-typhoidal salmonellosis are scarce. We report a child with ceftriaxone-resistant invasive Salmonella Enteritidis infection with secondary HLH, who was successfully managed with intravenous meropenem. Secondary HLH in the context of S. Enteritidis has not been described before.


Asunto(s)
Ceftriaxona/farmacología , Farmacorresistencia Bacteriana , Linfohistiocitosis Hemofagocítica/complicaciones , Infecciones por Salmonella/microbiología , Salmonella enteritidis/efectos de los fármacos , Fiebre Tifoidea/patología , Antibacterianos/uso terapéutico , Niño , Humanos , Masculino , Meropenem/uso terapéutico , Infecciones por Salmonella/patología
6.
Biotechnol Lett ; 41(12): 1355-1360, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31628577

RESUMEN

OBJECTIVE: Evaluation of the diagnostic potential of freeze dried sera in comparison to thin dry film analysis for recording ATR-FTIR spectra. RESULTS: For this purpose, we compared our novel sample preparation technique i.e. freeze dried with conventional technique i.e. thin dry film sera. Using both methods ATR-FTIR spectra were recorded from Salmonella Typhi infected and healthy control human sera samples. When PCA was applied PC1 scores showed more inter-class variation among infected and healthy controls when freeze dried sample was used (90 %) as compared to thin dry film method (46 %). CONCLUSIONS: Potential of ATR-FTIR for discrimination of bio-molecules between two classes of samples is enhanced when freeze dried sera instead of thin dry film method is used.


Asunto(s)
Análisis Químico de la Sangre/métodos , Liofilización , Suero/química , Manejo de Especímenes/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Fiebre Tifoidea/diagnóstico , Humanos , Sensibilidad y Especificidad , Fiebre Tifoidea/patología
7.
Trans R Soc Trop Med Hyg ; 113(12): 764-770, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31638153

RESUMEN

BACKGROUND: Typhoid fever is endemic in Fiji. We sought to describe the epidemiology, clinical features and case fatality risk of blood culture-confirmed typhoid fever from January 2014 through December 2015. METHODS: Blood culture-positive patients were identified from a typhoid surveillance line list. A standardised case investigation form was used to record data from patients' medical records. RESULTS: Of 542 patients, 518 (95.6%) were indigenous Fijians (iTaukei) and 285 (52.6%) were male. The median (IQR) age was 25 (16-38) y. Mean (SD) time from the onset of illness to admission was 11.1 (6.9) d. Of 365 patients with clinical information, 346 (96.9%) had fever, 239 (66.9%) diarrhoea, 113 (33.5%) vomiting, and 72 (30.2%) abdominal pain. There were 40 (11.0%) patients with complications, including 17 (4.7%) with shock, and 11 (3.0%) with hepatitis. Nine patients died for a case fatality risk of 1.7%. Of the 544 Salmonella Typhi isolates tested, none were resistant to first line antimicrobials; 3(0.8%) were resistant to ciprofloxacin and 5(1.4%) to nalidixic acid. CONCLUSIONS: In Fiji, most blood culture-confirmed typhoid fever cases were in young adults. Common clinical manifestations were fever and gastrointestinal symptoms. Further studies are required to elucidate the factors associated with complications and death.


Asunto(s)
Fiebre Tifoidea/epidemiología , Adolescente , Adulto , Factores de Edad , Antibacterianos/uso terapéutico , Niño , Preescolar , Femenino , Fiji/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Estudios Retrospectivos , Fiebre Tifoidea/tratamiento farmacológico , Fiebre Tifoidea/mortalidad , Fiebre Tifoidea/patología , Adulto Joven
8.
EMBO Mol Med ; 11(10): e10431, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31468702

RESUMEN

Misdiagnosis of enteric fever is a major global health problem, resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying a machine learning algorithm to host gene expression profiles, we identified a diagnostic signature, which could distinguish culture-confirmed enteric fever cases from other febrile illnesses (area under receiver operating characteristic curve > 95%). Applying this signature to a culture-negative suspected enteric fever cohort in Nepal identified a further 12.6% as likely true cases. Our analysis highlights the power of data-driven approaches to identify host response patterns for the diagnosis of febrile illnesses. Expression signatures were validated using qPCR, highlighting their utility as PCR-based diagnostics for use in endemic settings.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/patología , Diagnóstico Diferencial , Humanos , Aprendizaje Automático , Nepal , Curva ROC
9.
Nat Med ; 25(7): 1082-1088, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31270506

RESUMEN

Salmonella Typhi is a human host-restricted pathogen that is responsible for typhoid fever in approximately 10.9 million people annually1. The typhoid toxin is postulated to have a central role in disease pathogenesis, the establishment of chronic infection and human host restriction2-6. However, its precise role in typhoid disease in humans is not fully defined. We studied the role of typhoid toxin in acute infection using a randomized, double-blind S. Typhi human challenge model7. Forty healthy volunteers were randomized (1:1) to oral challenge with 104 colony-forming units of wild-type or an isogenic typhoid toxin deletion mutant (TN) of S. Typhi. We observed no significant difference in the rate of typhoid infection (fever ≥38 °C for ≥12 h and/or S. Typhi bacteremia) between participants challenged with wild-type or TN S. Typhi (15 out of 21 (71%) versus 15 out of 19 (79%); P = 0.58). The duration of bacteremia was significantly longer in participants challenged with the TN strain compared with wild-type (47.6 hours (28.9-97.0) versus 30.3(3.6-49.4); P ≤ 0.001). The clinical syndrome was otherwise indistinguishable between wild-type and TN groups. These data suggest that the typhoid toxin is not required for infection and the development of early typhoid fever symptoms within the context of a human challenge model. Further clinical data are required to assess the role of typhoid toxin in severe disease or the establishment of bacterial carriage.


Asunto(s)
Toxinas Bacterianas/toxicidad , Salmonella typhi/patogenicidad , Fiebre Tifoidea/etiología , Enfermedad Aguda , Adolescente , Adulto , Animales , Método Doble Ciego , Humanos , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Fiebre Tifoidea/inmunología , Fiebre Tifoidea/patología , Adulto Joven
10.
Epidemiol Mikrobiol Imunol ; 68(1): 47-50, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31181952

RESUMEN

Typhoid fever is a disease caused by the highly virulent bacterium Salmonella Typhi. It is transmitted by the oral-faecal route. In the Czech Republic, 53 cases of typhoid fever were reported in 1997-2017. Only seven of these cases were autochthonous. In August 2017, an imported case of typhoid fever was recorded in a 25-year-old unvaccinated woman who participated in the Rainbow Gathering in Italy one week prior to the onset of the disease. During her stay in Italy, she slept in a tent, ate her own food, and drank unboiled water. Presenting with persisting cough, tiredness, muscle and joint pain, and fever up to 40 °C after her return, she was admitted to the Třebíč Hospital where she was diagnosed with S. Typhi. The epidemiological investigation identified six contacts. On discharge from hospital and at follow-up, the patient was tested negative. None of the contacts became ill.


Asunto(s)
Enfermedad Relacionada con los Viajes , Fiebre Tifoidea , Adulto , República Checa/epidemiología , Femenino , Humanos , Italia , Salmonella typhi , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/patología
11.
Semin Diagn Pathol ; 36(3): 197-202, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31072653

RESUMEN

Infections are common during travel, and frontline physicians frequently must evaluate sick returned travelers. Sick travelers can be clinically challenging due to the wide range of endemic diseases in different geographic regions. To guide the diagnostic and treatment plan, consideration of endemic and emerging infections in the region of travel, as well as careful review of the travelers' exposures and preventative measures are necessary. Routine laboratory tests and cultures cannot confirm many tropical infections, and pathogen directed testing is typically required. Common tropical infections that can be severe, such as malaria, dengue, and enteric fever, should always be considered in the diagnostic evaluation. Providers should also be vigilant for rare but highly pathogenic emerging infections such as Ebola virus disease and Middle East respiratory syndrome (MERS).


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Dengue/diagnóstico , Fiebre Hemorrágica Ebola/diagnóstico , Malaria/diagnóstico , Fiebre Tifoidea/diagnóstico , Infecciones por Coronavirus/patología , Dengue/patología , Fiebre Hemorrágica Ebola/patología , Humanos , Malaria/patología , Viaje , Medicina Tropical , Fiebre Tifoidea/patología
12.
Cell Microbiol ; 21(8): e13034, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31013389

RESUMEN

How Salmonella enterica serovar Typhi (S. Typhi), an important human pathogen, survives the stressful microenvironments inside the gastrointestinal tract and within macrophages remains poorly understood. We report here that S. Typhi has a bonafide stringent response (SR) system, which is mediated by (p)ppGpp and regulates multiple virulence-associated traits and the pathogenicity of the S. Typhi Ty2 strain. In an iron overload mouse model of S. Typhi infection, the (p)ppGpp0 (Ty2ΔRelAΔSpoT) strain showed minimal systemic spread and no mortality, as opposed to 100% death of the mice challenged with the isogenic wild-type strain. Ty2ΔRelAΔSpoT had markedly elongated morphology with incomplete septa formation and demonstrated severely attenuated motility and chemotaxis due to the loss of flagella. Absence of the Vi-polysaccharide capsule rendered the mutant strain highly susceptible to complement-mediated lysis. The phenotypes of Ty2ΔRelAΔSpoT was contributed by transcriptional repression of several genes, including fliC, tviA, and ftsZ, as found by reverse transcriptase quantitative polymerase chain reaction and gene complementation studies. Finally, Ty2ΔRelAΔSpoT had markedly reduced invasion into intestinal epithelial cells and significantly attenuated survival within macrophages. To the best of our knowledge, this was the first study that addressed SR in S. Typhi and showed that (p)ppGpp was essential for optimal pathogenic fitness of the organism.


Asunto(s)
Proteínas Bacterianas/genética , Guanosina Pentafosfato/metabolismo , Interacciones Huésped-Patógeno/genética , Salmonella typhi/genética , Salmonella typhi/patogenicidad , Fiebre Tifoidea/microbiología , Animales , Proteínas Bacterianas/metabolismo , Células CACO-2 , Modelos Animales de Enfermedad , GTP Pirofosfoquinasa/deficiencia , GTP Pirofosfoquinasa/genética , Regulación Bacteriana de la Expresión Génica , Células HT29 , Humanos , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/microbiología , Sobrecarga de Hierro/mortalidad , Sobrecarga de Hierro/patología , Hígado/metabolismo , Hígado/microbiología , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Polisacáridos Bacterianos/deficiencia , Pirofosfatasas/deficiencia , Pirofosfatasas/genética , Células RAW 264.7 , Salmonella typhi/crecimiento & desarrollo , Salmonella typhi/metabolismo , Transducción de Señal , Bazo/metabolismo , Bazo/microbiología , Bazo/patología , Análisis de Supervivencia , Células THP-1 , Fiebre Tifoidea/metabolismo , Fiebre Tifoidea/mortalidad , Fiebre Tifoidea/patología , Virulencia
13.
J Cell Biochem ; 120(4): 5687-5694, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30548286

RESUMEN

In this article, we aim to examine the novel effects of ß-sitosterol on murine experimental colitis. ß-Sitosterol significantly reduces the weight loss, colon length, and alleviated microscopic appearances of colitis induced by dextran sulfate sodium. This compound also decreases the levels of TNF-α, IL-6, and IL-1ß in intestinal tissue of mice with experimental colitis in a concentration-dependent manner. ß-Sitosterol treatment to intestinal epithelial cells significantly increases expression of antimicrobial peptides and reduces survival of intracellular Salmonella typhimurium. These results showed the multiple effects of ß-sitosterol against pathogenic bacteria for a novel approach to the treatment of colonic inflammation.


Asunto(s)
Colitis/prevención & control , Sulfato de Dextran/toxicidad , Hipolipemiantes/farmacología , Inflamación/prevención & control , Salmonella typhimurium/efectos de los fármacos , Sitoesteroles/farmacología , Fiebre Tifoidea/complicaciones , Animales , Colitis/etiología , Colitis/patología , Modelos Animales de Enfermedad , Inflamación/etiología , Inflamación/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Fiebre Tifoidea/tratamiento farmacológico , Fiebre Tifoidea/patología
15.
Cell Microbiol ; 20(9): e12939, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30030897

RESUMEN

Although nontyphoidal Salmonella (NTS; including Salmonella Typhimurium) mainly cause gastroenteritis, typhoidal serovars (Salmonella Typhi and Salmonella Paratyphi A) cause typhoid fever, the treatment of which is threatened by increasing drug resistance. Our understanding of S. Typhi infection in human remains poorly understood, likely due to the host restriction of typhoidal strains and the subsequent popularity of the S. Typhimurium mouse typhoid model. However, translating findings with S. Typhimurium across to S. Typhi has some limitations. Notably, S. Typhi has specific virulence factors, including typhoid toxin and Vi antigen, involved in symptom development and immune evasion, respectively. In addition to unique virulence factors, both typhoidal and NTS rely on two pathogenicity-island encoded type III secretion systems (T3SS), the SPI-1 and SPI-2 T3SS, for invasion and intracellular replication. Marked differences have been observed in terms of T3SS regulation in response to bile, oxygen, and fever-like temperatures. Moreover, approximately half of effectors found in S. Typhimurium are either absent or pseudogenes in S. Typhi, with most of the remaining exhibiting sequence variation. Typhoidal-specific T3SS effectors have also been described. This review discusses what is known about the pathogenesis of typhoidal Salmonella with emphasis on unique behaviours and key differences when compared with S. Typhimurium.


Asunto(s)
Fiebre Paratifoidea/patología , Salmonella paratyphi A/patogenicidad , Salmonella typhi/patogenicidad , Fiebre Tifoidea/patología , Factores de Virulencia/metabolismo , Animales , Islas Genómicas , Humanos , Evasión Inmune , Ratones , Fiebre Paratifoidea/microbiología , Fiebre Paratifoidea/fisiopatología , Sistemas de Secreción Tipo III/metabolismo , Fiebre Tifoidea/microbiología , Fiebre Tifoidea/fisiopatología
16.
J Infect ; 77(1): 60-67, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29746945

RESUMEN

OBJECTIVES: Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. METHODS: Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. RESULTS: Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. CONCLUSIONS: Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.


Asunto(s)
Coagulación Sanguínea , Endotelio/patología , Fibrinólisis , Fiebre Tifoidea/sangre , Fiebre Tifoidea/complicaciones , Adulto , Anticoagulantes , Bangladesh , Células Endoteliales/microbiología , Células Endoteliales/patología , Endotelio/citología , Endotelio/microbiología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Protrombina , Salmonella typhi/genética , Salmonella typhi/aislamiento & purificación , Índice de Severidad de la Enfermedad , Trombocitopenia , Fiebre Tifoidea/patología , Adulto Joven
17.
EBioMedicine ; 31: 92-109, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29735417

RESUMEN

Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and "mini-guts," organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies.


Asunto(s)
Regulación de la Expresión Génica/inmunología , Mucosa Intestinal/inmunología , Salmonella typhi/inmunología , Transcripción Genética/inmunología , Fiebre Tifoidea/inmunología , Perfilación de la Expresión Génica , Humanos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Salmonella typhi/patogenicidad , Técnicas de Cultivo de Tejidos , Fiebre Tifoidea/patología
18.
Cell Rep ; 22(7): 1787-1797, 2018 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-29444431

RESUMEN

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.


Asunto(s)
Evolución Biológica , Fagocitos/microbiología , Estallido Respiratorio , Salmonella typhi/fisiología , Serogrupo , Fiebre Tifoidea/microbiología , Fiebre Tifoidea/patología , Adulto , Animales , Anticuerpos/metabolismo , Antígenos Bacterianos/metabolismo , Activación de Complemento , Células HL-60 , Humanos , Ratones , Modelos Biológicos , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo
19.
Paediatr Int Child Health ; 38(3): 227-230, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-28436267

RESUMEN

Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually occur in endemic countries and in patients with underlying risk conditions. A 14-year-old immunocompetent girl was admitted with respiratory distress owing to S. Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had lived in France for 4 years and had not travelled abroad for several years. There were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her family. She recovered completely with ceftriaxone and ciprofloxacin and pleural drainage was not required. An atypical presentation of S. Typhi should be considered even in settings where there are no risk factors.


Asunto(s)
Empiema Pleural/diagnóstico , Empiema Pleural/patología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/patología , Salmonella typhi/aislamiento & purificación , Fiebre Tifoidea/diagnóstico , Fiebre Tifoidea/patología , Adolescente , Antibacterianos/administración & dosificación , Ceftriaxona/administración & dosificación , Ciprofloxacina/administración & dosificación , Drenaje , Empiema Pleural/terapia , Femenino , Francia , Humanos , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/terapia , Resultado del Tratamiento , Fiebre Tifoidea/terapia
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