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1.
Am J Trop Med Hyg ; 90(6): 1024-1030, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24615129

ABSTRACT

We assessed interferon-gamma (IFN-γ) responses via enzyme-linked immunosorbent spot (ELISPOT) to a number of S. Typhi antigens in samples from humans with S. Typhi bacteremia and typhoid fever in Bangladesh. Compared with responses in healthy endemic zone controls, there were significantly increased IFN-γ responses at the time of clinical presentation (acute phase) and at convalescence 14-28 days later. The majority (80-90%) of IFN-γ expressing T cells were CD4+. We observed a significant increase in interleukin-17 (IL-17) positive CD4 + T cells at convalescent versus acute stage of infection using an intracellular cytokine staining assay. We also found that stimulated peripheral blood mononuclear cells (PBMCs) produced significantly increased levels of a number of cytokines at the convalescent versus acute phase of infection, including IFN-γ, MIP-1ß, sCD40L, TNF-ß, IL-13, and IL-9. These results suggest that S. Typhi antigens induce a predominantly Th1 response, but that elevations in other cytokines may be modulatory.


Subject(s)
Antigens, Bacterial/immunology , Cytokines/immunology , Interferon-gamma/immunology , Salmonella typhi/immunology , Typhoid Fever/immunology , Adolescent , Bacteremia , Bangladesh/epidemiology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Child , Child, Preschool , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Typhoid Fever/microbiology
2.
Expert Rev Anti Infect Ther ; 11(4): 395-409, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23566149

ABSTRACT

Unprecedented levels of antimicrobial resistance in bacterial isolates have prompted great concerns globally. In 2012 the WHO released a publication outlining the evolving threat of antimicrobial resistance in order to raise awareness and to stimulate coordinated international efforts. The carbapenem class of antibiotics is largely considered as an antibiotic of last-resort when treating infections. Now carbapenem resistance further limits treatment options. In this article the authors discuss carbapenem resistance in Acinetobacter baumannii, a bacterial isolate often implicated in nosocomial infections. Virulence factors, intrinsic and acquired resistance mechanisms, together with laboratory challenges in the detection and antibiotic susceptibility testing of A. baumannii make this a truly problematic isolate. Therapeutic options are exceedingly limited, relying on polymyxins in combinations with other antibiotics, with few, if any, new active agents in the pipeline.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Cross Infection/epidemiology , beta-Lactam Resistance/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Aminoglycosides/therapeutic use , Carbapenems/therapeutic use , Cross Infection/microbiology , Disease Management , Epidemiological Monitoring , Humans , Polymyxins/therapeutic use , Porins/deficiency , Porins/genetics , beta-Lactam Resistance/drug effects , beta-Lactamases/genetics
3.
J Infect Dis ; 198(7): 1055-61, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18729782

ABSTRACT

BACKGROUND: Infection with Vibrio cholerae induces durable immunity against subsequent disease, a process hypothesized to reflect anamnestic immune responses at the intestinal mucosa. The presence of antigen-specific memory B cells may therefore be a more direct measure of protection than serum antibody responses. METHODS: We measured immunoglobulin (Ig) G memory B cells specific to cholera toxin B subunit (CTB) in 14 patients up to 90 days after V. cholerae O1 infection, by polyclonal stimulation of peripheral blood mononuclear cells followed by standard enzyme-linked immunospot assay. RESULTS: All patients generated CTB-specific IgG memory B cell responses by day 30 (mean, 0.10% of total circulating IgG memory B cells; range, 0.037%-0.28%), which persisted to day 90 (mean, 0.07%; range, 0.003%-0.27%). In contrast, circulating CTB-specific IgG antibody-secreting cells and serum vibriocidal and anti-CTB antibody responses peaked on day 7 and declined to undetectable or significantly lower levels by day 90. CONCLUSIONS: CTB-specific IgG memory B cell responses are detectable in the circulation at least 3 months after V. cholerae O1 infection and remain measurable even after serum antibody titers have declined to undetectable or considerably lower levels. This suggests that antigen-specific memory B cells may be an important long-term marker of the immune response to cholera.


Subject(s)
B-Lymphocytes/immunology , Cholera Toxin/immunology , Cholera/immunology , Diarrhea/immunology , Immunologic Memory , Vibrio cholerae O1 , Antibodies, Bacterial/blood , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood
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