Toxocara Awareness Among Medical Practitioners in Saudi Arabia.

Human toxocariasis is a zoonotic infection with global and regional impacts. Worldwide it is underestimated and clinically overlooked. Medical practitioners are generally unaware of the extent of the resulting disease spectrum. The objective of the study was to assess knowledge and disease awareness among medical practitioners in Aseer, south-western Saudi Arabia. A questionnaire addressing knowledge about the parasite, its visceral larva migrans and the disease spectrum generated was used to interview participants. The study included 285 participants. In answer to the question what is toxocara, only 27%, answered correctly that it is a nematode, paediatricians being the majority. With regard to years of experience among participants, 56.8% of those who answered correctly had less than 5-year experience, as opposed to 35.4% for those with more than 10-year experience. The cumulative awareness about the disease manifestations and spectrum, i.e. those who knew, was less than 30% across specialties and years of experiences. Lack of awareness regarding Toxocara infection and the disease spectrum it can generate is evident. The consequence for such lack of knowledge within our practising medical community is simply unacceptable as it might translate into misdiagnosis and consequently misguided treatment.

Immunological Factors Associated with Adult Asthma in the Aseer Region, Southwestern Saudi Arabia.

BACKGROUND: The prevalence of asthma is on the rise in Saudi Arabia. Data regarding the immunological profile of asthma in adults in the Aseer region, in southwestern Saudi Arabia, have not been well studied. OBJECTIVES: Our aim was to study the immunological factors associated with sensitization to asthma among adults in the Aseer region. METHODS: A cross-sectional study with a nested case control design in a 1:1 ratio was conducted on a sample of adults attending primary health care centers in the Aseer region. The study used a validated Arabic version of the International study of asthma and allergies in childhood (ISAAC) questionnaire. The presence of wheezing in the past 12 months was used as a proxy for bronchial asthma. Matched age and sex controls were selected. Both groups were tested for complete blood count (CBC), total and differential white blood cell (WBC) count including eosinophils, total immunoglobulin E (IgE) measurement, allergen-specific immunoglobulin E (IgE), and cytokine levels. RESULTS: The present study included 110 cases and 157 age- and sex-matched controls. Rye wheat was found to be a significant outdoor sensitizing agent ((odds ratio) OR = 5.23, 95% CI: 1.06-25.69). Indoors, house dust mites Dermatophagoides petronyssinus (OR = 2.04, 95% CI: 1.04-3.99) and Dermatophagoides farinae (OR = 2.50, 95% CI: 1.09-5.75) were significant. Higher total IgE (OR = 1.84, 95% CI: 1.10-3.06) and eosinophil levels (OR = 2.85, 95% CI: 1.14-7.15) were significantly associated with adult bronchial asthma in Aseer. On the other hand, the role of cytokines was not significant. CONCLUSIONS: In the present study, certain environmental agents were found to be important with regards to sensitization to bronchial asthma in adults. Knowledge about these sensitization agents should be disseminated to health providers and treating physicians in order to enhance preventive environmental control measures and asthma management. Asthma-treating physicians in the region should be alerted to the use of targeted biological therapies in selected asthmatics with difficult-to-control courses.

Uninfected erythrocytes inhibit Plasmodium falciparum-induced cellular immune responses in whole-blood assays.

Whole-blood assays (WBAs) have been successfully used as a simple tool for immuno-epidemiological field studies evaluating cellular immune responses to mycobacterial and viral antigens. Rather unexpectedly, we found very poor cytokine responses to malaria antigens in WBAs in 2 immuno-epidemiological studies carried out in malaria endemic populations in Africa. We have therefore conducted a detailed comparison of cellular immune responses to live (intact) and lysed malaria-infected erythrocytes in WBAs and in peripheral blood mononuclear cell (PBMC) cultures. We observed profound inhibition of both proliferative and interferon-gamma responses to malarial antigens in WBAs as compared with PBMC cultures. This inhibition was seen only for malaria antigens and could not be overcome by increasing either antigen concentration or responder cell numbers. Inhibition was mediated by intact erythrocytes and occurred early in the culture period, suggesting that failure of antigen uptake might underlie the lack of T-cell responses. In support of this hypothesis, we have shown that intact uninfected erythrocytes specifically inhibit phagocytosis of infected red blood cells by peripheral blood monocytes. We propose that specific biochemical interactions with uninfected erythrocytes inhibit the phagocytosis of malaria-infected erythrocytes and that this may impede T-cell recognition in vivo.

Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule.

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-beta plays a crucial role in preventing the severe pathology of malaria in mice and TGF-beta production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-beta (LatTGF-beta) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-beta binding motifs of TSP, all inhibit malaria-mediated TGF-beta activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-beta than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-beta by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-beta represents a novel mechanism for direct modulation of the host response by malaria parasites.

Differential induction of TGF-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections.

Transforming growth factor-beta is an essential moderator of malaria-induced inflammation in mice. In this study, we show that the virulence of malaria infections is dependent upon the cellular source of TGF-beta and the timing of its production. C57BL/6 mice infected with a nonlethal (Py17X) strain of Plasmodium yoelii produce TGF-beta from 5 days postinfection; this correlates with resolution of parasitemia, down-regulation of TNF-alpha, and full recovery. In contrast, infection with the lethal strain Py17XL induces high levels of circulating TGF-beta within 24 h; this is associated with delayed and blunted IFN-gamma and TNF-alpha responses, failure to clear parasites, and 100% mortality. Neutralization of early TGF-beta in Py17XL infection leads to a compensatory increase in IL-10 production, while simultaneous neutralization of TGF-beta and IL-10R signaling leads to up-regulation of TNF-alpha and IFN-gamma, prolonged survival in all, and ultimate resolution of infection in 40% of Py17XL-infected animals. TGF-beta production can be induced in an Ag-specific manner from splenocytes of infected mice, and by cross-linking surface CTLA-4. CD25(+) and CD8(+) cells are the primary source of TGF-beta following Py17X stimulation of splenocytes, whereas Py17XL induces significant production of TGF-beta from adherent cells. In mice immunized against Py17XL, the early TGF-beta response is inhibited and is accompanied by significant up-regulation of IFN-gamma and TNF-alpha and rapid resolution of challenge infections.