Highlighting the need for more infection control practitioners in low- and middle-income countries.

Background: Many low- and middle-income countries struggle to implement, monitor and evaluate the efficacy of infection control (IC) measures within health care facilities. This hampers their ability to prevent nosocomial infections, identify emerging pathogens and rapidly alert officials to possible outbreaks. The lack of dedicated and trained IC practitioners (ICPs) is a serious deficit in the health care workforce, and is worsened by the lack of institutions that offer IC training. Discussion: While no single individual can entirely eliminate the risk of nosocomial transmission, there is literature to support the value of designated IC persons. Recommendations from the World Health Organization in 2008 and 2009 describe the need for this specialized cadre of workers, but many countries lack the national regulations to authorize, train and manage such professionals at the national or local level. This article provides an overview of how ICPs are trained and credentialed in several countries, and discusses approaches countries can use to train ICPs. Conclusion: Trained ICPs can help prevent future outbreaks and control nosocomial transmission of diseases in health care facilities. For this to occur, supportive national policies, availability of training institutions and local administrative support will be required.

Contexte : De nombreux pays à revenu faible et moyen ont du mal à mettre en œuvre, suivre et évaluer l'efficacité des mesures de lutte contre l'infection (CI) au sein des structures de santé. Ceci entrave leur capacité à prévenir les infections nosocomiales, à identifier les pathogènes émergents et à alerter rapidement les autorités en vue de flambées épidémiques éventuelles. La pénurie de praticiens dédiés et formés à la lutte contre les infections (PCI) est une lacune sérieuse dans la force de travail et elle est aggravée par le manque d'institutions qui offrent une formation en matière de CI.Discussion : Même si aucune personne isolée ne peut entièrement éliminer le risque de transmission nosocomiale, la littérature est en faveur de l'implication de personnes désignées pour la lutte contre les infections. Les recommandations de l'Organisation Mondiale de la Santé en 2008 et 2009 décrivent le besoin de cette cohorte de travailleurs spécialisés, mais de nombreux pays ne possèdent pas les règlements nationaux requis pour autoriser, former et gérer de tels professionnels au niveau national ou local. Cet article offre une vue d'ensemble de la façon dont les praticiens de la lutte contre les infections sont formés et accrédités dans plusieurs pays et il discute les approches auxquelles les pays peuvent recourir pour former les PCI.Conclusion : Des PCI peuvent contribuer à prévenir les futures flambées épidémiques et à contrôler la transmission nosocomiale des maladies dans les structures de santé. Pour aboutir à ce résultat, il est nécessaire de mettre en œuvre des politiques nationales de soutien, et de mettre à disposition des institutions de formation et un soutien administratif local.

Marco de referencia: Muchos países de ingresos bajos y medianos afrontan dificultades en la ejecución, la supervisión y la evaluación de las medidas de control de las infecciones (CI) en los establecimientos de atención de salud. Esta situación obstaculiza la capacidad de prevenir las infecciones nosocomiales, impide la detección de nuevos patógenos e impide la notificación oportuna a los funcionarios sobre los posibles brotes epidémicos. La carencia de personal médico capacitado y dedicado al control de las infecciones (PCI) constituye una importante deficiencia del personal de atención de salud y se agrava con la inexistencia de instituciones que dispensen una formación en este campo.Discusión: Si bien una sola persona no puede eliminar totalmente el riesgo de transmisión intrahospitalaria de las infecciones, las publicaciones científicas respaldan la utilidad de designar personas encargadas del CI en los establecimientos de salud. Las recomendaciones de la Organización Mundial de la Salud del 2008 y el 2009 describen la necesidad de contar con este grupo especializado de profesionales; sin embargo, muchos países carecen de normas nacionales que autoricen, capaciten y dirijan estos profesionales a escala nacional y local. En el presente artículo se ofrece una visión general sobre los métodos de capacitación y acreditación de los PCI en diversos países y se analizan las estrategias que pueden adoptar los países con el objeto de formar los PCI.Conclusión: La capacitación de PCI ayuda a prevenir la aparición de futuros brotes epidémicos y a controlar la transmisión de las infecciones en los establecimientos de atención sanitaria. Con el fin de lograrlo, se precisan políticas nacionales propicias, instituciones que dispensen la capacitación y apoyo administrativo al nivel local.

Enhancement of the HIV-1 inhibitory activity of RANTES by modification of the N-terminal region: dissociation from CCR5 activation.

Although selected chemokines act as natural inhibitors of human immunodeficiency virus (HIV) infection, their inherent proinflammatory activity may limit a therapeutic use. To elucidate whether the antiviral and signaling functions of RANTES can be dissociated, several recombinant analogues mutated at the N terminus were generated and functionally compared with the wild-type (WT) molecule, as well as with three previously described mutants. Substitution of selected residues within the N-terminal region caused a marked loss of antiviral potency. By contrast, two unique analogues (C1.C5-RANTES and L-RANTES) exhibited an increased antiviral activity against different CXCR4-negative HIV-1 isolates grown in primary mononuclear cells or in macrophages. This enhanced HIV-blocking activity was associated with an increased binding affinity for CCR5. Both C1.C5-RANTES and L-RANTES showed a dramatically reduced ability to trigger intracellular calcium mobilization via CCR3 or CCR5, while potently antagonizing the action of the WT chemokine. By contrast, two previously described analogues (RANTES(3-68) and AOP-RANTES) maintained a WT ability to trigger CCR5-mediated signaling, while a third one (RANTES(9-68)) showed a dramatic loss of antiviral activity. These data demonstrate that the antiviral and signaling functions of RANTES can be uncoupled, opening new perspectives for the development of chemokine-based therapeutic approaches for HIV infection.

Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages.

CXCR4 is a functional coreceptor for infection of human macrophages by CXCR4-dependent primary HIV-1 isolates.

The identification of HIV-1 coreceptors has provided a molecular basis for the tropism of different HIV-1 strains. CXC chemokine receptor-4 (CXCR4) mediates the entry of both primary and T cell line-adapted (TCLA) syncytia-inducing strains. Although macrophages (M phi) express CXCR4, this coreceptor is assumed to be nonfunctional for HIV-1 infection. We addressed this apparent paradox by infecting human monocyte-derived M phi with primary and TCLA isolates that were rigorously characterized for coreceptor usage and by adding the natural CXCR4 ligand, stem cell differentiation factor-1, to specifically block CXCR4-mediated entry. Our results show that primary HIV-1 isolates that selectively use CXCR4 productively infected both normal and C-C chemokine receptor-5-null M phi. By contrast, M phi supported the entry of CXCR4-dependent TCLA strains with variable efficiency but were not productively infected. Thus, the tropism of HIV isolates results from complex virus/host cell interactions both at the entry and postentry levels.

C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

Antiidiotypic antibodies mimic molecular and functional properties of human IL-1 beta in vitro and in vivo.

We obtained affinity-purified polyclonal anti-id antibodies against mAb MhC1 and BrhC3, which recognize amino acids 133-147 at the N-terminus of mature human IL-1 beta. mAb MhC1 and BrhC3 have been shown to inhibit binding of IL-1 beta to type I IL-1R, and to neutralize IL-1 beta bioactivity in a number of in vitro assays. We show that affinity-purified antibodies against the MhC1 and BrhC3 idiotypes specifically bind to type I IL-1 beta IL-1R and that this binding is inhibited by both IL-1 beta and IL-1ra; anti-id antibodies were also able to trigger IL-1R-dependent events, such as IL-8 secretion by human skin fibroblasts and pyrogenic effect after injection in mice. These anti-id antibodies, therefore, behave as structural and functional "images" of IL-1 beta, both in vivo and in vitro. These data indicate the idiotypic strategy as a powerful tool to study the fine specificity of receptor-ligand interactions. Moreover, this is, to our knowledge, the first report showing that the "internal image" of a cytokine can be active in vivo.