Typhoid fever—important issues still remain

Pang, Tikki; Levine, Myron M.; Ivanoff, B; Wain, John; Finlay, B. Brett

doi:10.1016/s0966-842x(98)01236-0

Cited by 110 publications

(75 citation statements)

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“…Salmonella enterica serovar Typhi (herein abbreviated as S. typhi) causes typhoid fever in humans, a disease of great public health concern in many developing countries (Pang et al, 1998). The detailed molecular mechanisms specifically involved in the pathogenesis of S. typhi are poorly understood due to the lack of an animal model.…”

Section: Introductionmentioning

confidence: 99%

O-antigen expression in Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene

et al. 2002

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The authors previously reported increased expression of the Salmonella enterica serovar Typhi (S. typhi) rfaH gene when the bacterial cells reach stationary phase. In this study, using a lacZ fusion to the rfaH promoter region, they demonstrate that growth-dependent regulation of rfaH expression occurs at the level of transcription initiation. It was also observed that production of the lipopolysaccharide (

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Section: Introductionmentioning

confidence: 99%

O-antigen expression in Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene

et al. 2002

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“…Typhoid fever, a prolonged, debilitating illness caused by infection with Salmonella enterica serovar Typhi, continues to be a significant global problem, with an estimated 16.6 million cases annually (14). Serovar Typhi is a pathogen only of humans, and many aspects of the pathogenicity of human typhoid are not well understood (8,15).…”

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confidence: 99%

Quantitation of Bacteria in Bone Marrow from Patients with Typhoid Fever: Relationship between Counts and Clinical Features

et al. 2001

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Enteric fever is the only bacterial infection of humans for which bone marrow examination is routinely recommended. A prospective study of the concentrations of bacteria in the bone marrow and their relationship to clinical features was conducted with 120 Vietnamese patients with suspected enteric fever, of whom 89 had confirmed typhoid fever. Ninety-three percent of the Salmonella enterica serovar Typhi samples isolated were resistant to ampicillin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicated typhoid and satisfactory bone marrow aspirates, the number of serovar Typhi CFU in bone marrow aspirates was a median value of 9 (interquartile range [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; range, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of individual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5). The number of bacteria in blood but not bone marrow was correlated inversely with the duration of preceding fever. Thus, with increasing duration of illness the ratio of bone marrow-to-blood bacterial concentrations increased; the median ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, 60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, reflecting the higher concentration of intracellular serovar Typhi in the bone marrow. Effective antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatment than bacteria in the blood. The numbers of bacteria in bone marrow correlated negatively with the white blood cell (R ‫؍‬ ؊0.3, P ‫؍‬ 0.006) and platelet counts (R ‫؍‬ ؊0.32, P ‫؍‬ 0.01) and positively with fever clearance time after treatment (R ‫؍‬ 0.4, P < 0.001). The bacterial load in bone marrow therefore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.

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“…Cytokine production by T cells following in vitro culture of splenocytes from Swiss-Webster mice with WT or mutant S. Typhimurium at an MOI of 1 for 16 h. T cells were then isolated and incubated with irradiated splenocytes from uninfected mice for 72 h. a) IL-6 and b) IFN-γ concentrations in culture supernatants. T cell proliferation following in vitro culture of splenocytes from Swiss-Webster mice with WT or mutant S. Typhimurium at an MOI of 1 for 16 h. c) T cells were then isolated and incubated with irradiated splenocytes from uninfected mice for 72 h. 3 H-thymidine was added during the last 10 h of incubation. Controls were cultured in the absence of S. Typhimurium.…”

Section: Statisticsmentioning

confidence: 99%

“…Diseases associated with Salmonella infections include self-limiting gastroenteritis and septicemia, and humans could be asymptomatic carriers of this pathogen for several years with the organism residing in hepatocytes and the gall bladder [2]. Although infections with salmonellae are of concern in both developing and developed countries, typhoid fever is highly prevalent in developing countries with an annual global incidence of approximately 16 million cases and 600,000 deaths [3]. Among different serogroups of Salmonella, S. enterica serovar Typhimurium is most commonly associated with human infections after consuming contaminated food and water.…”

Section: Introductionmentioning

confidence: 99%

Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: Potential use as live-attenuated vaccines

König

Sha

et al. 2008

Microbial Pathogenesis

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We generated and characterized Salmonella enterica serovar Typhimurium mutants that were deleted for the genes encoding Braun lipoprotein (lpp) alone or in conjunction with the msbB gene, which codes for an enzyme required for the acylation of the lipid A moiety of lipopolysaccharide. Two copies of the lpp gene, designated as lppA and lppB, exist on the chromosome of S. Typhimurium. These mutants were highly attenuated in a mouse infection model and induced minimal histopathological changes in mouse organs compared to those seen in infection with wild-type (WT) S. Typhimurium. The lppB/msbB and the lppAB/msbB mutants were maximally attenuated, and hence further examined in this study for their ability to induce humoral and cellular immune responses. Importantly, infection of out-bred Swiss-Webster mice with the mutant S. Typhimurium generated superior T helper cell type 2 (Th2) responses compared to WT S. Typhimurium, as determined by measuring IgG subclasses and cytokines. WT S. Typhimurium induced higher levels of IgG2a in sera of infected mice, while the lppB/msbB and lppAB/msbB mutants mounted higher levels of IgG1 as determined by an enzyme-linked immunosorbent assay. Mice immunized with lppB/msbB and lppAB/msbB mutants rapidly cleared WT S. Typhimurium upon subsequent rechallenge, and naïve mice passively immunized with sera from animals infected with S. Typhimurium mutants were protected against subsequent challenge with WT S. Typhimurium. Splenic T cells produced higher levels of interferon-gamma following ex vivo exposure to WT S. Typhimurium, while splenic T cells infected with the above-mentioned two mutants evoked higher levels of interleukin-6. Further, mice infected with lppB/msbB and lppAB/msbB mutants showed much higher levels of splenic T cell activation as measured by CD44 + expression on CD4 + T cells by flow cytometry and by incorporation of 3 H-thymidine compared to mice that were infected with WT S. Typhimurium. We expect the lppB/msbB and lppAB/msbB mutants to be excellent live-attenuated vaccine candidates, because they induced minimal inflammatory responses and evoked stronger and specific antibody and cellular immune responses.

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Typhoid fever—important issues still remain

Cited by 110 publications

References 0 publications

O-antigen expression in Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene

O-antigen expression in Salmonella enterica serovar Typhi is regulated by nitrogen availability through RpoN-mediated transcriptional control of the rfaH gene

Quantitation of Bacteria in Bone Marrow from Patients with Typhoid Fever: Relationship between Counts and Clinical Features

Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: Potential use as live-attenuated vaccines

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