An integrated structural intervention to reduce vulnerability to HIV and sexually transmitted infections among female sex workers in Karnataka state, south India

BACKGROUND: Structural factors are known to affect individual risk and vulnerability to HIV. In the context of an HIV prevention programme for over 60,000 female sex workers (FSWs) in south India, we developed structural interventions involving policy makers, secondary stakeholders (police, government officials, lawyers, media) and primary stakeholders (FSWs themselves). The purpose of the interventions was to address context-specific factors (social inequity, violence and harassment, and stigma and discrimination) contributing to HIV vulnerability. We advocated with government authorities for HIV/AIDS as an economic, social and developmental issue, and solicited political leadership to embed HIV/AIDS issues throughout governmental programmes. We mobilised FSWs and appraised them of their legal rights, and worked with FSWs and people with HIV/AIDS to implement sensitization and awareness training for more than 175 government officials, 13,500 police and 950 journalists. METHODS: Standardised, routine programme monitoring indicators on service provision, service uptake, and community activities were collected monthly from 18 districts in Karnataka between 2007 and 2009. Daily tracking of news articles concerning HIV/AIDS and FSWs was undertaken manually in selected districts between 2005 and 2008. RESULTS: The HIV prevention programme is now operating at scale, with over 60,000 FSWs regularly contacted by peer educators, and over 17,000 FSWs accessing project services for sexually transmitted infections monthly. FSW membership in community-based organisations has increased from 8,000 to 37,000, and over 46,000 FSWs have now been referred for government-sponsored social entitlements. FSWs were supported to redress > 90% of the 4,600 reported incidents of violence and harassment reported between 2007-2009, and monitoring of news stories has shown a 50% increase in the number of positive media reports on HIV/AIDS and FSWs. CONCLUSIONS: Stigma, discrimination, violence, harassment and social equity issues are critical concerns of FSWs. This report demonstrates that it is possible to address these broader structural factors as part of large-scale HIV prevention programming. Although assessing the impact of the various components of a structural intervention on reducing HIV vulnerability is difficult, addressing the broader structural factors contributing to FSW vulnerability is critical to enable these vulnerable women to become sufficiently empowered to adopt the safer sexual behaviours which are required to respond effectively to the HIV epidemic

Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2

Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin

International audienceIntravenous immunoglobulin (IVIG), a pooled normal IgG formulation prepared from thousands of healthy donors’ plasma, is extensively used for the immunotherapy of autoimmune and inflammatory disorders. Recent reports demonstrate that IVIG exerts anti-inflammatory actions by stimulating the activation and expansion of regulatory T (Treg) cells by multiple mechanisms via antigen-presenting cells (APCs)

Immune Response and Viral Persistence in Indian Buffaloes (Bubalus bubalis) Infected with Foot-and-Mouth Disease Virus Serotype Asia 1 ▿

Despite their potential role in the spread of foot-and-mouth disease (FMD), the immune response and viral persistence in FMD virus (FMDV)-infected Indian buffaloes (Bubalus bubalis) have been unexplored. We found similar kinetics of neutralizing antibody responses in the sera and secretory fluids of buffaloes following experimental FMDV Asia 1 infection, but the lymphocyte-proliferative response in infected buffaloes was of low magnitude. Despite inducing a significant systemic and secretory immune response, viral persistence seems to be a common outcome in buffaloes following FMDV Asia 1 infection, which is associated with a weak cellular immune response

Natural Antibodies: from first line defense against pathogens to perpetual immune homeostasis

International audienceNatural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases

Host immune response to pathogens and predisposition to infections due to autoimmunity.

<p>Antigens from invading pathogens are recognized and presented by innate immune cells (A) such as macrophages and dendritic cells to CD4+ and CD8+ T cells (CTL) (B). CD8+ T cells recognize endogenous antigens presented by MHC class I molecules and exert cytotoxic functions upon activation. CD4+ T cells recognize antigens presented in the context of MHC class II molecules, and under the influence of innate cells and cytokine milieu, CD4+ T cells can be polarized into different subsets such as Th1, Th2, Th17, and regulatory T cells (Tregs) that secrete distinct cytokines. CD4+ T cells provide help to B cells to produce antigen-specific antibodies (C). However, due to autoimmunity, neutralizing autoantibodies can be produced against any of these key components of the immune system critical for mounting anti-microbial responses and might either predispose to an increased risk of bacterial, viral, and opportunistic fungal infections or exacerbate the ongoing infectious diseases. Indeed, in patients with infections, the occurrence of neutralizing autoantibodies against several key cytokines such as IFN-γ, IL-6, GM-CSF, IL-17, and IL-22 (highlighted in red boxes) that interfere with the host immune response to pathogens have been demonstrated. In addition, autoantibodies are also reported against type I IFNs and IL-12 that might play role in predisposition to infections (highlighted in blue boxes). CTLA-4, cytotoxic T lymphocyte antigen-4; CTL, cytotoxic T lymphocyte; FasL, Fas ligand; GM-CSF, granulocyte/macrophage–colony stimulating factor.</p