A prospective observational safety study on MF59(®) adjuvanted cell culture-derived vaccine, Celtura(®) during the A/H1N1 (2009) influenza pandemic.

BACKGROUND: The present study was a prospective observational study to evaluate the safety profile of Celtura(®), a monovalent, cell culture-derived, inactivated subunit influenza vaccine prepared from A/California/07/2009(H1N1) with the adjuvant MF59(®). Subjects were enrolled prospectively during the H1N1 2009 influenza pandemic at medical centres in Colombia, Chile, Switzerland, and Germany during the period December 2009 to June 2010. METHODS: Subjects ages 18 and older were followed for the occurrence of adverse events (AEs) for six months after vaccination. Adverse events of special interest (AESIs) were neuritis, convulsion (seizure), anaphylaxis, encephalitis, vasculitis, Guillain-Barre syndrome, demyelinating conditions, Bell's palsy, and laboratory-confirmed vaccination failure. RESULTS: Overall, 7348 AEs were reported in 2296 of 3989 enrolled subjects (57.6%). Only two AEs were considered related to injection site reactions. No laboratory-confirmed cases of influenza were reported. There were 108 medically confirmed serious adverse events (SAEs) reported among 73 subjects with 6 such SAEs described as possibly or probably related to vaccination. Three fatal cases were reported and assessed as not related to vaccination. Two AESIs classified as convulsion were reported and assessed as not related to vaccination. Both AESIs occurred well outside the pre-specified 7 day risk window representing the likely timeframe of the occurrence of seizure following vaccination. CONCLUSIONS: The results of this study support the overall good safety profile of MF59 adjuvanted cell culture-derived influenza vaccine as administered in adults during the 2009-2010 H1N1 influenza pandemic. No concern is raised regarding the occurrence of AESIs.

Síndrome de Fisher. A propósito de un caso

Los autores exponen el caso de un paciente de dos años de edad afecto de un cuadro clínico que cumplia todos los criterios diagnósticos del sindrome de Fisher. En esta entidad poco frecuente y de etiopatogenia desconocida se discute si la lesion asienta a nivel periférico -como en la polirradiculoneuritis del síndrome de Guillain-Barré- o por el contrario tiene lugar en el Sistema Nervioso Central. Los hallazgos clínicos en este caso, así como el resultado de alguno ae los exámenes complementarios, apoyan la participación central. La evolución hacia la recuperación fue lenta, pero favorable, como está descrito.

Trauma craneoencefálico severo en la UCIP del Hospital de la Misericordia, 2010-2013

El Trauma Craneoencefálico (TCE) infantil constituye un motivo frecuente de consulta en Urgencias y supone la primera causa de muerte en niños, llegando a ser hasta del 50% en trauma severo. En Colombia se conocen cifras de TCE por algunos estudios descriptivos, pero no existen reportes en Bogotá ni específicamente en TCE severo. Objetivo: Caracterizar el trauma craneoencefálico severo pediátrico en la Unidad de Cuidado intensivo del Hospital de la Misericordia entre los años 2010 y 2013. Materiales y métodos: Un estudio descriptivo retrospectivo fue realizado en el Hospital de la Misericordia mediante revisión de las historias clínicas de los pacientes que ingresaron a la Unidad de Cuidado Intensivo pediátrico con diagnóstico de trauma craneoencefálico severo entre el año 2010 al 2013. Resultados: Se incluyeron 63 pacientes (71,4% hombres) con una edad mediana de 4 años (RIQ 2-8). La mayoría de los traumas fueron originados por caída o accidente de tránsito (79,4%). La principal lesión fue fractura de cráneo (79%). Casi la mitad de los pacientes sufrieron algún tipo de secuela neurológica al egreso (47,1%). La mayoría de los pacientes que murieron (19%) sufrieron choque hipovolémico (83,3%) y presentaron trauma asociado (66,7%). Conclusión: Las características y epidemiología del trauma craneoencefálico en nuestra población muestran claras similitudes con lo reportados en otras series de la literatura mundial y de Colombia, excepto por la mortalidad, que se esperaba más alta al estudiar solo pacientes con TCE severo.

Insect infection model for campylobacter jejuni reveals that O-methyl phosphoramidate has insecticidal activity

Galleria mellonella (wax moth) larvae have elsewhere been shown to be susceptible to pathogens such as Francisella tularensis, Burkholderia mallei, and Pseudomonas aeruginosa. We report that the larvae are rapidly killed by Campylobacter jejuni at 37 degrees C. Three strains of C. jejuni tested, 11168H (human diarrheal isolate), G1 (human Guillain-Barre syndrome isolate), and 81-176 (human diarrheal isolate), were equally effective at killing G. mellonella larvae. A panel of defined mutants of C. jejuni 11168H, in known or putative virulence genes, showed different degrees of attenuation in G. mellonella larvae. A mutant lacking the O-methyl phosphoramidate (MeOPN) capsule side group was attenuated, clearly demonstrating that MeOPN has a role in virulence. This new model of C. jejuni infection should facilitate the identification of novel virulence genes.

Polyradiculoneuropathy and neurocysticercosis: Case report

Report of a patient with the hydrocephalic and meningoencephalitic form of neurocysticercosis who simultaneously developed polyradiculoneuropathy and intracranial hypertension syndrome during the first week of treatment with albendazole. Etiologic agents associated with polyradiculoneuropathy related in the literature are cited. Some comments about the possible physiopathogeny of this entity in the presence of cysticercosis are also done. It is mentioned another case who presented polyradiculoneuropathy as the only manifestation of a probable cysticercosis of the nervous system. In this presented case, including the neurocysticercosis and even a mere coincidence of facts, some factors can have a relationship with the appearance of polyradiculoneuropathy as the surgical stress, the stress due to the severity of the clinical picture and the possible side effect of albendazole.

HIV-assoziierte Neuritis des Nervus vestibulocochlearis. Fallbeschreibung und systematische Literaturanalyse der HIV-assoziierten Polyneuropathien

Die Polyneuropathien sind Komplikationen der Infektion mit dem Human- Immunodeficiency-Virus (HIV). Dazu gehören Polyradikulopathien, distale (sensible) Polyneuropathien, Mono- und Oligoneuropathien und brachiale Neuritiden. Selten gibt es Formen, die sich nicht kategorisieren lassen. In dieser Dissertation präsentieren wir einen aussergewöhnlichen Fall einer bilateralen Neuritis des Nervus vestibulo-cochlearis (N. vestibulocochlearis). In einer ausgedehnten Literaturrecherche ist das erst der dritte beschriebene Fall. Gleichzeitig wurde die Literaturrecherche genutzt, um epidemiologische, klinische und laborchemische Parameter der HIV-assoziierten Polyneuropathien zu analysieren. Dazu wurden Daten von 539 Patientinnen aus 67 Publikationen extrahiert und ausgewertet. Die Daten wurden bezüglich ihrer Qualität gewertet, um den Schlussfolgerungen eine Gewichtung zu geben. Die Literaturanalyse ergab, dass die meisten Daten zu HIVassoziierten – und bezüglich antiretroviraler Therapie (ART) naiven – Polyneuropathien von afrikanischen Patienten stammen. Die meisten europäischen und nordamerikanischen Studien zu diesem Thema wurden vor 1996 publiziert. Polyradikulopathien präsentieren sich typischerweise früh und distale (sensible) Polyneuropathien spät in der HIV-Krankheit. Das Guillain-Barré-Syndrom war das häufigste Krankheitsbild der Polyradikulopathien. Die häufigste Präsentation distaler Polyneuropathien sind Sensibilitätsausfälle an den unteren Extremitäten. Bei den Mono- und Oligoneuropathien hat ein Grossteil der Personen Mononeuropathien, wobei der N. facialis am häufigsten betroffen ist. Die Rolle der ART zur Erholung der Neuropathien konnte nicht beurteilt werden. Unter den HIV-assoziierten Polyneuropathien haben die distalen (sensiblen) Polyneuropathien die schlechtere und die Polyradikulopathien und Mono- oder Oligoneuropathien die bessere Prognose bezüglich Erholung

Fatal case of Epstein-Barr virus primo-infection, haemophagocytic syndrome in a 26-year-old patient treated with azathioprine for Crohn's disease: an autopsy case

Objective: A 26-year-old man with a history of Crohn's disease, treated with azathioprine since 2 years, presented an Epstein-Barr virus (EBV) primo-infection and exacerbation of digestive symptoms. Method: An ileo-colectomy was performed, which showed a fatal EBV lymphoproliferation disorder along with a haemophagocytic syndrome. EBV DNA load in the peripheral blood persisted to be high loaded during hospitalisation (479,000 copies per milliliter) despite triple antiviral treatment. Results: Autopsy revealed a systemic lymphoproliferation involving lymph nodes, gastrointestinal mucosa and solid viscera (heart, kidney, lungs, prostate, brain). This was compounded of a population of large polymorphic B cell, hypertrophic macrophages and T lymphocytes, associated to haemophagocytosis. These massive infiltrations mimicked macroscopically as ulcers in the intestinal mucosa and ranged from polymorphic with plasmocytic differentiation to monomorphic large cells. Autopsy results confirmed the absence of Crohn's disease reactivation. The EBV infection was observed in all organs within the large images of the B cell lymphoproliferations. Further postmortem investigations revealed a deficit of the azathioprine's metabolisation enzyme thiopurine methyltransferase (TPMT). Conclusion: We report and discuss herein the observations of a complete autopsy case along with the postmortem identification of the EBV infection type and TPMT mutation in a patient treated by azathioprine for Crohn's disease. Autopsy findings and further investigations helped explain the complicate clinical evolution and the fatal issue of the patient.

Submandibular and sublingual glands involvement in advanced acquired immunodeficiency syndrome (AIDS): an autopsy-based study

Objective. To assess the histopathological, immunohistochemical (IHC), and in situ hybridization (ISH) features found in the submandibular (SM) and sublingual (SL) glands of 105 acquired immunodeficiency syndrome (AIDS) patients at autopsy. Study design. Gender, age, CD4 cell level, and clinical histories were obtained from clinical charts (SM: n = 103; SL: n = 92). Histologic analysis of hematoxylin and eosin, Gomori-Grocott, and Ziehl-Neelsen stained tissues, IHC to detect infectious agents and characterize inflammatory cells in sialadenitis, and ISH for EBER-1/2 were performed. Results. The mean age of the patients and CD4 cell count were 36 years and 76 cells/mu L, respectively. Fifty-eight cases (SM: n = 51 [49%]; SL: n = 54 [59%]) were considered to be microscopically normal. The most common infectious conditions were mycobacteriosis (SM: n = 11 [10%]; SL: n = 7 [7%]), followed by cytomegalovirus (CMV) (SM: n = 14 [13%]; SL: n = 2 [2%]), and cryptococcosis (SM: n = 3 [3%]; SL: n = 4 [4%]). Human immunodeficiency virus (HIV) p24 (SM: n = 2 [2%]; SL: n = 1 [1%]) and EBER-1/2 (SM: n = 9 [39%]; SL: n = 4 [20%]) were seen only in macrophages and lymphocytes, respectively. The most prevalent cells seen in chronic nonspecific sialadenitis (SM: n = 25; SL: n = 25) were CD8+ T lymphocytes, whereas CD68+ macrophages were predominant in the mycobacteriosis-associated granulomatous and nonspecific diffuse macrophagic sialadenitis. Concomitant infections occurred in 5 cases (SM: n = 4; SL: n = 1) and non-Hodgkin lymphoma in 1 case. Conclusions. Infectious diseases and chronic nonspecific sialadenitis were the main alterations found in the SM and SL glands. These alterations were greater in the SM than in the SL glands. CD8+ T lymphocytes and CD68+ macrophages might be relevant to the pathogenesis of the sialadenitis. Clinicians should consider these diseases when assessing the major salivary glands in advanced AIDS patients and follow biosafety procedures to avoid contamination by HIV, CMV, mycobacteriosis, and cryptococcosis. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: 216-226)

Polymerase chain reaction genotyping of Epstein-Barr virus in scraping samples of the tongue lateral border in HIV-1 seropositive patients

The Epstein-Barr virus (EBV) is the etiological agent of oral hairy leukoplakia (OHL), an oral lesion with important diagnostic and prognostic value in acquired immunodeficiency disease syndrome. The two EBV genotypes, EBV-1 and EBV-2, can be distinguished by divergent gene sequences encoding the EBNA-2, 3A, 3B, and 3C proteins. The purpose of this study was to identify the EBV genotype prevalent in 53 samples of scrapings from the lateral border of the tongue of HIV-1 seropositive patients, with and without OHL, and to correlate the genotypes with presence of clinical or subclinical OHL with the clinic data collected. EBV-1 and EBV-2 were identified through PCR and Nested-PCR based on sequence differences of the EBNA-2 gene. EBV-1 was identified in the 31 samples (15 without OHL, 7 with clinical OHL and 9 with subclinical OHL), EBV-2 in 12 samples (10 without OHL, 1 with clinical and 1 subclinical OHL), and a mixed infection in 10 samples (2 without OHL, 3 with clinical and 5 with subclinical OHL). The presence of EBV-1 was higher in women, but a significant statistical result relating one the EBV genotypes to the development of OHL was not found. We conclude that the oral epithelium in HIV-1 seropositive patients can be infected by EBV-1, EBV-2 or by a mixed viral population.

Extranodal NK/T-Cell Lymphoma without Nasal Cavity Involvement Associated with Epstein-Barr Virus:AMultimodality-Based Diagnosis of Two Cases

We report two cases of extranodal NK/T-cell lymphoma, nasal type, in immunocompetent patients without nasal cavity involvement. In the two cases, the initial presumptive diagnosis was tuberculosis and there was a rapid dissemination of the tumor with short survival after the hospital admittance. An autopsy was performed showing infiltration in several organs including lymph nodes and mesenteric and retroperitoneal fat. Histological sections showed an angiocentric and angiodestructive growth pattern and the immunophenotype was CD45+, CD3+ (cytoplasmic), as well as Granzyme B+ and EBV+. However, CD56 expression was only positive in a case in which the molecular study showed T-cell gene rearrangement with monoclonal appearance and associated with hemophagocytic syndrome. These cases represent rare examples of NK/T-cell lymphoma disseminated outside the nasal cavity highly aggressive that lead to the rapid death of the patients.

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

The paradox of adult respiratory distress syndrome in neonates

Six full-term newborn infants are described who suffered from severe adult respiratory distress syndrome (ARDS). The triggering event was intrauterine/perinatal asphyxia in five, and group B streptococcal (GBS) septicemia in three. All had severe respiratory distress/failure and were ventilated mechanically with high concentrations of inspired oxygen and positive end-expiratory pressure. Radiography of the chest showed dense bilateral consolidation with air bronchograms and reduced lung volume. Persistent pulmonary hypertension (PPH) was documented in all cases. The coincidence of ARDS and PPH rendered respiratory management extremely difficult. For this reason high-frequency ventilation was instituted in all patients in order to improve CO2 elimination and induce respiratory alkalosis. Acute complications of respiratory therapy were encountered in five patients (pneumothorax, pulmonary interstitial emphysema, pneumopericardium). Three infants died (irreversible septic shock, progressive severe hypoxemia, and sudden cardiac arrest) after 17, 80, and 175 h of life. Histologic examination of the lungs was possible in all fatal cases and revealed typical changes of acute to subacute stages of ARDS. Three infants survived, the mean time of mechanical respiratory support being 703 h. Two patients were still dependent on oxygen after 1 month of life, and all survivors had increased interstitial markings and increased lung volumes on their chest roentgenograms at this time.

Bacterial phenotype variants in group B streptococcal toxic shock syndrome

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.

Linfohistiocitose hemofagocítica secundária a infecção por epstein-barr a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014