Biomedical subjects

Khaled S Tabbara

Publications and source records attributed to Khaled S Tabbara.

6 recordsLinked to original sources

PubMed2006

Clinical relevance of virulence genes in Campylobacter jejuni isolates in Bahrain.

There are no data describing the genetic make-up of Campylobacter strains (an important aetiological agent of diarrhoea) circulating in the Arabian Gulf region. Here, the molecular characterization of two virulence genes in Campylobacter jejuni from Bahrain and the relationship with clinical infection are reported. Molecular screening for cytolethal distending toxin (cdtB) and invasion-associated marker (iam) genes was carried out on C. jejuni stool isolates collected from January 2002 to January 2004 in Bahrain. The molecular characterization was correlated with the patients' socio-demographic and clinical parameters. Of the 96 C. jejuni strains tested, 50 (52 %) were cdtB+/iam+, 30 (31 %) were cdtB+/iam- and 16 (17 %) were cdtB-/iam-. Sixty-nine per cent (66/96) of patients were less than 3 years old, with significantly higher detection of cdtB+/iam+ and cdtB+/iam- strains (P < 0.001 and P < 0.01, respectively) in this age group. Seventy patients (73 %) were symptomatic. In the group that were less than 3 years old, 62 and 85 % of those with cdtB+/iam+ and cdtB+/iam- strains, respectively, were symptomatic compared with 100 % for those over 3 years of age. However, the presence of cdtB-/iam- strains still resulted in clinical infection in the children under 3 years but not in the older patients. This is the first report describing the molecular characterization of virulence genes in Campylobacter isolates from this region. The findings indicate that strains of different virulence genetic make-up are circulating in the population, with children under the age of 3 years being most vulnerable. Further work on the molecular characterization, gene expression and determination of the invasive phenotypes of C. jejuni strains circulating in different regions is needed.

Adolescent↗

PubMed2006

Progress towards a Leishmania vaccine.

Leishmaniasis is a vector-born protozoan disease. Approximately 12 million individuals are affected worldwide with an estimated annual incidence of 1.5-2 million. Two clinical manifestations are recognized, cutaneous, and visceral, both of which are common in the Middle East. In both forms, infection is chronic, with potential deformities, persistence following cure, and lifelong risk of reactivation. Attempts to develop an effective human Leishmania vaccine have not yet succeeded. Leishmanization, a crude form of live vaccination historically originated in this part of the world. Experimental vaccination has been extensively studied in model animals in the past 2 decades. In this review, major human killed vaccine trials are surveyed, and modern trends in Leishmania vaccine development, including subunit vaccines, naked DNA vaccines, and transmission blocking vaccines are explored. Recent findings of a link between persistence of live parasites, and maintenance of long-term immunity suggest live vaccination with attenuated strains, as a future vaccination strategy.

Animals↗

PubMed2005

Antigen requirements for efficient priming of CD8+ T cells by Leishmania major-infected dendritic cells.

CD4(+) and CD8(+) T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasite Leishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epitopes. We have analyzed the potential of L. major transgenic parasites, expressing the model antigen ovalbumin (OVA), to be presented by antigen-presenting cells to OVA-specific OT-II CD4(+) or OT-I CD8(+) T cells. Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric protein with L. donovani 3' nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells to proliferate and release gamma interferon. A diminished T-cell response was observed when DC were infected with parasites expressing nonsecreted NT-OVA or with heat-killed parasites. Inoculation of mice with transgenic parasites elicited the proliferation of adoptively transferred OT-I T cells and their recruitment to the site of infection in the skin. Together, these results demonstrate the possibility of targeting heterologous antigens to specific cellular compartments in L. major and suggest that proteins secreted or released by L. major in infected DC are a major source of peptides for the generation of parasite-specific CD8(+) T cells. The ability of L. major transgenic parasites to activate OT-I CD8(+) T cells in vivo will permit the analysis of parasite-driven T-cell expansion, differentiation, and recruitment at the clonal level.

Animals↗

PubMed2005

Conditions influencing the efficacy of vaccination with live organisms against Leishmania major infection.

Numerous experimental vaccines have been developed with the goal of generating long-term cell-mediated immunity to the obligate intracellular parasite Leishmania major, yet inoculation with live, wild-type L. major remains the only successful vaccine in humans. We examined the expression of immunity at the site of secondary, low-dose challenge in the ear dermis to determine the kinetics of parasite clearance and the early events associated with the protection conferred by vaccination with live L. major organisms in C57BL/6 mice. Particular attention was given to the route of vaccination. We observed that the rapidity, strength, and durability of the memory response following subcutaneous vaccination with live parasites in the footpad are even greater than previously appreciated. Antigen-specific gamma interferon (IFN-gamma)-producing T cells infiltrate the secondary site by 1.5 weeks, and viable parasites are cleared as early as 2.5 weeks following rechallenge, followed by a rapid drop in IFN-gamma(+) CD4(+) cell numbers in the site. In comparison, intradermal vaccination with live parasites in the ear generates immunity that is delayed in effector cell recruitment to the rechallenge site and in the clearance of parasites from the site. This compromised immunity was associated with a rapid recruitment of interleukin-10 (IL-10)-producing CD4(+) T cells to the rechallenge site. Treatment with anti-IL-10-receptor or anti-CD25 antibody enhanced early parasite clearance in ear-vaccinated mice, indicating that chronic infection in the skin generates a population of regulatory cells capable of influencing the level of resistance to reinfection. A delicate balance of effector and regulatory T cells may be required to optimize the potency and durability of vaccines against Leishmaniasis and other intracellular pathogens.

Animals↗

PubMed2005

Serodiagnosis of toxoplasmosis in Bahrain.

OBJECTIVE: We report here an analysis of results of anti-Toxoplasma immunoglobulin M (IgM) and immunoglobulin G (IgG) measurements reported from the Central Laboratory of Bahrain over a period of 3 years and 9 months. METHODS: This study included all blood samples received at the Salmaniya Medical Complex, Manama, Bahrain serology laboratory for the determination of Toxoplasma-specific antibodies during the period of January 2000 to September 2003. A total of 4,739 specimens were assayed for IgG and 1,947 for IgM. RESULTS: An overall seropositivity of 21.8% for IgG and 10.3% for IgM antibodies were found with no gender differences for either IgG or IgM. In addition, no statistically significant positivity rate differences (p=0.723) were observed between Bahrainis and non-Bahraini residents. The prevalence of Toxoplasma gondii (T. gondii)-specific IgG amongst post partum women was 15.8% and 6.3% for IgM, while for women of child-bearing age IgG was higher at 22.3% and 11.6% for IgM. The IgG seropositivity in neonates (<1 month old) was 16.5%, decreasing to 9.3% in preschool children, while for IgM, it was 3.7% at birth increasing to 7.3% in the preschool group. The IgG seroprevalence increased within the first 15 years of life, and leveled thereafter, for IgM however, it was low at birth and increased within the first 12 months of life then leveled-off at the age of 20-40 to approximately 11-14%, with a further increase after 40 years to 17%. CONCLUSION: The seropositivity rates of T. gondii in the samples examined during the present study fall within the range of other Gulf Cooperative Council countries. True prevalence in the general population may actually be lower.

Adolescent↗

PubMed2004

Coinfection with Listeria monocytogenes potentlxtes the response of BALB/c mice against Leishmania major.

Protection against L. major is dependent on the stimulation of an anti-leishmanial T helper1 (Th1) response and the production of Interferon (IFN)-y. BALB/c mice develop a Th2 response and fatal infection with Leishmania major. Strategies that boost IL-12 production have shown to be protective. The innate response to Listeria monocytogenes is associated with IL-12 production. The co-infection of BALB/c mice with L. monocytogenes attenuates the course of L. major infection. Lesion sizes were smaller, and co-infected mice out-survived controls injected with L. major alone. The parasite load was reduced at site of injection, in draining lymph nodes (LN) and spleen. During the first week of infection, in-vitro Leishmania-restimulated LN cells from co-infected mice produced higher levels of IFN-7 and undetectable levels of IL-4 compared to controls. Significant IL-4 mRNA expression was detected in LN cells of control but not in co-infected mice.

Animals↗