Recombinant bovine IL17A acts as an adjuvant for bovine herpesvirus vaccine.

The Bovine herpes virus type 5 glycoprotein D (gD) is essential for viral penetration into host permissive cells. The Herpes virus gD glycoprotein has been used for bovine immunization, being efficient in reduction of viral replication, shedding and clinical signs, however sterilizing immunity is still not achieved. Recombinant subunit vaccines are, in general, poorly immunogenic requiring additional adjuvant components. Interleukin 17A (IL17A) is a pro-inflammatory cytokine produced by T helper 17 cells that mediate mucosal immunity. IL17 production during vaccine-induced immunity is a requirement for mucosal protection to several agents. In this study, we investigated the potential of a recombinant IL17A to act as an adjuvant for a recombinant BoHV-5 glycoprotein D vaccine in cattle. Three cattle groups were divided as: group 1) rgD5 + alumen + rIL-17A; 2) rgD5 + alumen; and 3) PBS + alumen. The cattle (3 per group) received two doses of their respective vaccines at an interval of 21 days. The group that received rIL17 in its vaccine formulation at the 7th day after the prime immunization had significant higher levels of specific rgD-IgG than the alumen group. Addition of rIL17 also led to a significant fold increase in specific anti-rgD IgG and neutralizing antibodies to the virus, respectively, when compared with the alumen group. Cells stimulated with rIL17A responded with IL17 transcription, as well IL2, IL4, IL10, IL15, Bcl6 and CXCR5. Our findings suggest that the rIL17A has adjuvant potential for use in vaccines against BoHV-5 as well as potentially other pathogens of cattle.

Evidencias clínico-epidemiológicas vinculadas a Lissachatina fulica en un adulto con meningoencefalitis eosinofílica causada por Angiostrongylus cantonensis / Clinical-epidemiological evidence related to Lissachatina fulica in an adult with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

Introducción: El helminto Angiostrongylus cantonensis es un parásito habitual en los pulmones de la rata y puede ocasionar meningoencefalitis eosinofílica en el hombre cuando se pone en contacto con las larvas por ingestión accidental. En Cuba es endémico y el riesgo de contraerlo aumenta con la entrada del caracol gigante africano en el país. Objetivo: Describir las acciones desarrolladas por las autoridades sanitarias locales para el control del caracol gigante africano entre 2016 y 2018 y la aparición de un paciente en 2018 con meningoencefalitis eosinofílica causada por Angiostrongylus cantonensis vinculado epidemiológicamente con la presencia de este caracol. Métodos: Se realizó un estudio cualitativo a partir de un grupo focal con el que se trabajó ante la aparición del caracol gigante africano en un área de salud del municipio San Miguel del Padrón. Se realiza una encuesta semi-estructurada. Resultados: Se trazaron las estrategias para la erradicación de la especie invasora a partir de un trabajo comunitario. Dos años después, se observa nuevamente el caracol gigante africano y un paciente con meningoencefalitis eosinofílica epidemiológicamente asociado a Angiostrongylus cantonensis. Conclusiones: Las acciones realizadas entre 2016 y 2018 resultaron ser insuficientes por el nuevo avistamiento del caracol en el área, con el agravante de encontrar un paciente con meningoencefalitis eosinofílica epidemiológicamente asociado con el molusco(AU)

Introduction: Helmint Angiostrongylus cantonensis is a natural parasite in the lungs of ratas. Ocassionally it can produced an eosinophilic meningoencephalitis in men by larvae accidental ingestion. Methods: A qualitative study was performed from a focal group by a semi-structural survey in a health area from San Miguel del Padrón municipality. Objectives: To describe the actions developed by the local sanitarian authorities for the control of African giant snails between 2016 and 2018 and the appearance of a patient suffering from eosinophilic meningoencephalitis due to Angiostrongylus cantonensis linked to the presence of this snail. Results: It has been established an eradication strategy for the elimination of this invasive species based on a community work. Two years later, it was observed again the giant African snail in the area with a patient suffering from Angiostrongylus cantonensis eosinophilic meningoencephalitis epidemiologically associated. Conclusions: The 2016 actions were not efficient due to the emerging vector and the further finding of a patient linked with the parasite(AU)

Actualización de la situación epidemiológica de las meningoencefalitis / Update on the epidemiological situation of meningoencephalitis

En el siguiente apartado se analizarán los casos de meningitis desde la Semana epidemiológica (SE) 1 a la 48 del 2016 (hasta 03/12/2016) provenientes de la notificación a través del SNVS (tanto del módulo C2 como SIVILA). Incluye las notificaciones recogidas de efectores públicos y privados de la Ciudad. Todos los casos fueron analizados de manera individual, evitando duplicaciones de datos e integrando la información en una base unificada. Para la construcción de los corredores endémicos se tomaron los datos hasta la cuatrisemana epidemiológica 12 completa que culmina el 03/12/2016. La construcción de las tasas, se realizó en base a las proyecciones poblacionales aportadas por la Dirección de Estadística y Censos (DGEyC) de la Ciudad Autónoma de Buenos Aires. (AU)

Situación epidemiológica de las meningoencefalitis / Epidemiological situation of meningoencephalitis

La meningoencefalitis son enfermedades endemoepidémicas de distribución universal, generalmente graves, que requieren un rápido tratamiento por la velocidad de su evolución y la posibilidad de secuelas o muerte. La meningitis de etiología infecciosa es una patología de notificación obligatoria, inmediata y universal, lo que permite conocer su incidencia, distribución etaria, ubicación geográfica, estacionalidad, características de su evolución, entre otras variables, para orientar las estrategias de prevención y control. Se analizan los casos de meningitis desde la SE 1 a la 37 del 2016, (17 de Septiembre) provenientes de la notificación a través del Sistema Nacional de Vigilancia Sanitaria, y la situación epidemiológica en la Ciudad de Buenos Aires

Vaccination Is More Effective Than Prophylactic Oseltamivir in Preventing CNS Invasion by H5N1 Virus via the Olfactory Nerve.

BACKGROUND: Influenza A viruses can replicate in the olfactory mucosa and subsequently use the olfactory nerve to enter the central nervous system (CNS). It is currently unknown whether intervention strategies are able to reduce or prevent influenza virus replication within the olfactory mucosa and subsequent spread to the CNS. Therefore, we tested the efficacy of homologous vaccination and prophylactic oseltamivir to prevent H5N1 virus CNS invasion via the olfactory nerve in our ferret model. METHODS: Ferrets were vaccinated intramuscularly or received oseltamivir (5 mg/kg twice daily) prophylactically before intranasal inoculation of highly pathogenic H5N1 virus (A/Indonesia/05/2005) and were examined using virology and pathology. RESULTS: Homologous vaccination reduced H5N1 virus replication in the olfactory mucosa and prevented subsequent virus spread to the CNS. However, prophylactic oseltamivir did not prevent H5N1 virus replication in the olfactory mucosa sufficiently, resulting in CNS invasion via the olfactory nerve causing a severe meningoencephalitis. CONCLUSIONS: Within our ferret model, vaccination is more effective than prophylactic oseltamivir in preventing CNS invasion by H5N1 virus via the olfactory nerve. This study highlights the importance of including the olfactory mucosa, olfactory nerve, and CNS tissues in future vaccine and antiviral studies, especially for viruses with a known neurotropic potential.

α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets.

INTRODUCTION: Natalizumab blocks α4-integrins and is a prototypic agent for a series of anti-inflammatory drugs that impair trafficking of immune cells into the CNS. However, modulation of the access of immune cells to the CNS is associated with impaired immune surveillance and detrimental viral infections of the CNS. Here, we explored the potency of cellular immune responses within the CNS to protect against viral encephalitis in mice with T cell conditional disruption of VLA-4 integrin (α4ß1) expression. RESULTS: While VLA-4 expression in virus specific Th1 cells is non-redundant for their ability to access the CNS, α4-integrin deficient Th17 cells enter the CNS compartment and generate an inflammatory milieu upon intrathecal vaccinia virus (VV) infection. However, in contrast to Th1 cells that can adopt direct cytotoxic properties, Th17 cells fail to clear the virus due to insufficient Eomes induced perforin-1 expression. CONCLUSION: The quality of the intrathecal cellular antiviral response under conditions of impaired VLA-4 function jeopardizes host protection. Our functional in vivo data extend our mechanistic understanding of anti-viral immunity in the CNS and help to estimate the risk potential of upcoming therapeutic agents that target the trafficking of immune cells into distinct anatomical compartments.

[Chagas disease and immunodeficiency: HIV infection and transplantation]. / Maladie de Chagas et immunodépression: infection par le VIH et transplantation.

In the immunocompromised patients, the main features of Chagas disease are severe clinical manifestations during the acute phase and reactivations occurring during the chronic phase. Reactivation is defined by a demonstration of trypomastigots on microscopic examination of blood or the identification of amastigots on biopsy samples and/or acute clinical manifestations during the chronic phase. In HIV patients, meningo-encephalitis and myocarditis are the major clinical syndromes of reactivation. In transplanted patients, cutaneous lesions often reveal the reactivation. A parasiticidal treatment (nifurtimox or benznidazole) should be initiated immediately. A secondary prophylaxis is indicated for HIV patients with CD4 cells count < 200/mm3. In the near future, quantitative PCR could allow to diagnose early reactivation, to initiate preemptive therapy and to closely monitor the therapeutic response. Due to the severe manifestations and prognosis of Chagas disease in the immunocompromised host, two serologic tests must be performed in the patient with an history of residency in endemic countries.

CpG oligodeoxynucleotides protect newborn mice from a lethal challenge with the neurotropic Tacaribe arenavirus.

The innate immune system is key to limiting the early spread of most pathogens and directing the development of Ag-specific immunity. Recently, a number of synthetic molecules that activate the innate immune system by stimulating TLRs have been identified. Among them, synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing B cells, macrophages, and dendritic cells to induce a strong proinflammatory milieu and a type 1-biased immune response that protects mice from a variety of parasitic, bacterial, and viral infections. Although the protective effect of CpG ODN in adult mice was well established, its effectiveness in neonates, which have lower numbers of dendritic, B, and T cells and tend to favor Th2 responses, was unclear. This study uses the New World arenavirus Tacaribe, a neurotropic pathogen that is lethal in newborn mice, to explore the effectiveness of TLR-mediated innate immune responses. Neonatal BALB/c mice treated with CpG ODN at the time of infection had reduced viral load (p < 0.01) and increased survival (52%, p < 0.001 i.p.; 36%, p < 0.05 intranasally). Protection was achieved in mice treated no later than 3 days postchallenge and appears to be mediated by an increase in Ag-specific Abs (IgG and IgM) and to require inducible NO synthase expression and NO production. To our knowledge, this is the first study assessing the mechanisms by which CpG ODN can protect mice from a neurotropic viral infection.

Vaccination with a gE-negative bovine herpesvirus type 1 vaccine confers insufficient protection to a bovine herpesvirus type 5 challenge.

In the present study, cross-protection to bovine herpesvirus type 5 (BHV-5) induced by bovine herpesvirus type 1 (BHV-1) vaccination was examined following inoculation of rabbits and calves with a glycoprotein E (gE)-negative BHV-1 vaccine and subsequent challenge with BHV-5. Rabbits (n=5) and calves (n=8) were vaccinated [five rabbits intranasally (IN), four calves IN and four intramuscularly (IM)] with 7.1 log(10)median tissue culture infective dose (TCID(50)) of the BHV-1 vaccine. Rabbits and calves were challenged IN [rabbits 2 weeks post-vaccination (pv); calves 5 weeks pv] with 9.1log(10)TCID(50) of BHV-5. Two out of five vaccinated rabbits died after challenge with typical BHV-5 disease, as did 3/5 non-vaccinated controls. In calves, 4/8 vaccinated animals displayed mild signs of disease, whereas 6/6 non-vaccinated controls developed signs of disease, so severe that 2/6 had to be killed. Besides, nasal virus shedding post-challenge was not reduced by vaccination. At necropsy, on day 21 post-challenge, typical BHV-5 lesions were evident in brain tissues of both vaccinated and non-vaccinated calves. Dexametasone administration at 180 days post-infection did not reactivate clinical signs despite BHV-5 shedding in nasal secretions of both vaccinated and non-vaccinated calves. These results show that the BHV-1 vaccine evaluated here did not confer protection to BHV-5 in rabbits. In calves, BHV-1 vaccination did confer some protection to BHV-5 induced clinical disease, but it did not prevent infection and had no effect on nasal virus shedding or on the development of encephalitic lesions.

Meningoencefalitis por Mycobacterium avium: complex en una mujer con SIDA / Meningoencephalitits due to Mycobacterium avium: complexin a woman with AIDS

La infección diseminada por Mycobacterium avium Complex (MAC) es una complicación relativamente frecuente en estadios avanzados de la enfermedad por el virus de la inmunodeficiencia humana. Con el advenimiento de la terapia antiretroviral de gran eficacia, la incidencia de MAC ha disminuido sustancialmente, pero los pacientes con un bajo recuento de linfocitos CD4+ permane-cen en riesgo. Pese a ello, el compromiso meningoencefálico es infrecuente. Presentamos un caso de meningoencefalitis por MAC en una mujer con Sida con inmunodepresión severa. La presencia de MAC debe ser considerada en todo paciente con Sida que presente síntomas compatibles con micobacteriosis diseminada y compromiso neurológico

High affinity mimotope of the polysaccharide capsule of Cryptococcus neoformans identified from an evolutionary phage peptide library.

Cryptococcus neoformans causes a life-threatening meningoencephalitis in a significant percentage of AIDS patients. Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid (TT) produce Abs that, based on the epitope recognized, can be either protective or nonprotective. Since nonprotective Abs block the efficacy of protective Abs, we are interested in developing a vaccine that would focus the immune response specifically to protective epitopes. Previously, we screened a phage display library with 2H1, a protective anti-GXM mAb, and isolated PA1, a representative peptide that had a K(d) of 295 nM for 2H1. Mice immunized with PA1 conjugated to keyhole limpet hemocyanin developed high anti-peptide (1/13,000), but low anti-GXM (maximum, 1/200) titers. We now report our efforts to improve this vaccine by screening a sublibrary with six random amino acids added to either end of the PA1 motif to identify higher affinity peptides. P206.1, a peptide isolated from this sublibrary, had 80-fold higher affinity for 2H1 (K(d) = 3.7 nM) than PA1. P206.1 bound protective, but not nonprotective, anti-GXM Abs. Mice immunized with P206.1 conjugated to various carriers did not mount an Ab response to GXM despite developing high anti-peptide titers. However, mice primed with GXM-TT and boosted with P206.1-TT developed significant anti-GXM titers (maximum, 1/180,000). This latter immunization scheme focused the immune response on protective epitopes, since only 2-5% of these titers were directed against nonprotective de-O-acetylated GXM epitopes compared with 20-60% in animals primed and boosted with GXM-TT.

Systemic immunization induces protective CD4+ and CD8+ T cell-mediated immune responses in murine Listeria monocytogenes meningoencephalitis.

The immune mechanisms underlying immunization-induced protection of mice from lethal central nervous system (CNS) listeriosis were evaluated by immunohistochemistry, flow cytometry of leukocytes isolated from the brain, reverse transcription-polymerase chain reaction analysis of intracerebral (i.c.) tumor-necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-1 beta, IL-10, granulocyte/macrophage colony-stimulating factor, and inducible nitric oxide synthase mRNA expression, and T cell depletion experiments. The data demonstrate that active immunization of mice prior to an i.c. infection with Listeria monocytogenes prevents the development of a fatal necrotizing encephalitis and accelerates the recruitment of an increased number of alpha beta T cell receptor (TcR)+ CD4+ and CD8+ T cells, gamma delta TcR+ T cells, B cells, granulocytes and macrophages to the brain compared to non-immunized animals. In addition, immunization induced a pronounced activation of i.c. macrophages and microglial cells as shown by an increased expression of MHC class II antigens. In parallel, transcript levels for all cytokine mRNA analyzed were higher in the brains of immunized mice. The protective effects of immunization were completely abolished by depletion of CD4+, CD8+, or both T cell subsets. All groups of T cell-depleted immunized mice developed a fatal necrotizing encephalitis with an increased i.c. bacterial load. In addition, cytokine mRNA synthesis was significantly impaired. The severity of disease was only slightly different between CD4+, CD8+ and CD4+/CD8+ T cell depleted mice, indicating that both subsets of T cells are required for an effective i.c. immune response to L. monocytogenes. This is in marked contrast to systemic listeriosis, and points to CNS-specific features of the immune response.

Prevención de la meningoencefalitis por Haemophilus influenzae b y por Neisseria meningitidis / Prevention of meningoencephalitis by Haemophilus influenzae b and Neisseria meningiditis

Las meningitis bacterianas son un importante problema de salud pública en la población pediátrica. En este capítulo se tratarán conjuntamente a dos de los más relevantes agentes etiológicos, Haemophilus influenzae del serotipo b y Neisseria meningitidis, debido a que los cuadros clínicos que provocan son prácticamente indistinguibles y a que además tienen varias características en común: a) forman parte de la flora normal de la faringe de individuos sanos; b) se transmiten de persona a persona a través de objetos; c) presentan reactividad cruzada con antígenos de otras especies bacterianas; d) poseen una cápsula prominente de naturaleza polisacarídica; e) tienen una membrana externa formada por varias clases de proteínas; y f) cuentan con la capacidad de elaborar protesas extracelulares contra inmunoglobulina. En México las enfermedades invasivas causadas por H. influenzae no han recibido la atención que requieren y el conocimiento que se tiene es insuficiente para poder evaluar su impacto real como problema de salud. Hasta la fecha en México, se han hecho un gran número de estudios en relación con estos padecimientos, aunque la mayoría se han basado en su diagnóstico clínico o bacteriológico, el reconocimiento de sus complicaciones tales como las secuelas neurológicas en el caso de la meningitis y su tratamiento con medicamentos antimicrobianos. Con base a estos estudios sólo se cuenta con datos sobre la frecuencia de casos de meningitis purulenta en la población infantil, los que indican que H. influenzae es el agente causal más frecuente, encontrándose aproximadamente en el 25 por ciento de los casos, seguido por Streptococcus pneumoniae. H. influenzae también es la causa bacteriana principal de secuelas neurológicas graves hasta en el 50 por ciento de los pacientes que sobrevivien a la infección meníngea

[Results of neuroleukemia prevention in children with acute lymphoblastic leukemia]. / Rezul'taty profilaktiki neiroleikoza u detei s ostrym limfoblastnym leikozom.

The follow-up of 318 children with acute lymphoblastic leukemia given program therapy that included different treatments including chemo- and radioprevention of neuroleukemia demonstrated the high efficacy of the measures carried out, which reduced the incidence of neuroleukemia to 5.6%. No gross changes on the part of the neuropsychic status were revealed in the course of the follow-up of children who received the combined prophylaxis of neuroleukemia. The derangement of the CNS was recorded in 17 patients and ran its course in the form of leukemic meningitis and meningoencephalitis.

[Inflammatory reaction in neurocysticercosis in experimental studies in rabbits]. / Reacción inflamatoria en la neurocisticercosis estudio experimental en conejo.

In order to know if dexamethasone is a satisfactory protector to the inflammatory effect of cysticercosis in the central nervous system and if the rabbit is an useful animal for this experimentation twenty five rabbits were infected in the cisterna magna some with an emulsions of scolex and others with the fluid of the vesicle. The animals were sacrificed after two weeks and the brains were studied by the pathologist. The results indicate that dexamethasone is useful as a protector of the rabbit brain in cases of cysticercosis and that this animal is an adequate tool for this sort of experimental work.

Monoclonal antibodies against the fusion protein are protective in necrotizing mumps meningoencephalitis.

A monoclonal antibody against the fusion (F) protein of mumps virus was found to confer marked protection in mumps virus-induced encephalitis. Almost total prevention of extensive brain necrosis was found. This study indicates that the virus F protein is directly involved in the pathogenesis of brain necrosis.

The epidemiology and control of primary amoebic meningoencephalitis with particular reference to South Australia.

This paper reviews the history, epidemiology and control of primary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, with particular reference to South Australia. The intention has been to outline misconceptions and uncertainties pervading the earlier literature. Although PAM infections elsewhere have been attributed to cysts in air-borne dust, we believe that contact with water in the domestic environment was not adequately considered as a potential source of these infections. Several reports have cast doubt on the effectiveness of chlorine in controlling N. fowleri, although there is laboratory and South Australian field experience to the contrary. These reports can be traced to a misunderstanding of the circumstances surrounding cases of PAM reported by other workers. Provided that a continuous free chlorine residual of 0.5 mg/l can be maintained in water accessible to N. fowleri, the risk of disease should be negligible. The failure of amphotericin B therapy to save recent victims of the disease, despite relatively prompt intervention, is disappointing. Possible reasons for this, and the reports that rifampin or tetracycline combined with amphotericin might be more successful, are discussed.