Analyses of the PRF1 gene in individuals with hemophagocytic lymphohystiocytosis reveal the common haplotype R54C/A91V in Colombian unrelated families associated with late onset disease.

Familial hemophagocytic lymphohistiocytosis (FHL), is a rare autosomal recessive disorder characterized by an impairment of cytotoxic cells and uncontrolled activation of macrophages. This study presents the first description of four patients with FHL type 2 in Latin America. Patient 1 fulfilled the disease diagnostic criteria since 2 months of age, whereas patients 2, 3 and 4 exhibited the typical manifestations of the disease only later in their childhood. The PRF1 genetic analysis in these patients revealed two previously reported mutations: L17fsx50 and R54C. Interestingly, seven out of the 8 alleles evaluated here in patients carried the haplotype R54C/A91V, suggesting that this is a highly frequent FHL type 2 allele in Colombia. This haplotype confers residual cytotoxic function leading to late onset disease. Therefore, this report highlights the remarkable complexity of FHL diagnostic, emphasizing the importance of the genetic characterization of the disease.

Combined, concurrent, and sequential administration of seasonal influenza and MF59-adjuvanted A/H5N1 vaccines: a phase II randomized, controlled trial of immunogenicity and safety in healthy adults.

OBJECTIVE: We performed a phase II randomized, controlled, open-label, single-center study (Centros de Estudios de Infectología Pediátrica, Colombia) to examine the feasibility of combined administration of seasonal and MF59-adjuvanted A/H5N1 influenza vaccines using extemporaneous mixing or simultaneous administration. METHODS: The primary objective of the study was to assess the immunogenicity of seasonal influenza and A/H5N1 vaccines using European licensure criteria (Committee for Medicinal Products for Human Use [CHMP]); the secondary objective was to assess vaccine reactogenicity and safety. RESULTS: In 401 healthy 18-40-year-old subjects, both vaccines were immunogenic in all settings; the vaccine for seasonal influenza met all CHMP criteria, unaffected by coadministration of A/H5N1 vaccine in separate or mixed injections. Likewise, the immunogenicity of A/H5N1 vaccine was unaffected by seasonal influenza vaccination, with hemagglutination inhibition seroprotection rates of 28%-40% after 1 dose and 67%-80% after 2 doses, sufficient to meet CHMP criteria. Solicited local and systemic adverse events were mainly mild to moderate. No vaccine-related serious adverse events were reported during the study period. CONCLUSIONS: These data demonstrate that seasonal and MF59-adjuvanted A/H5N1 influenza vaccines can be given as a mixed injection or by simultaneous separate injections without affecting immunogenicity or safety, supporting the feasibility of incorporating prepandemic MF59-adjuvanted A/H5N1 vaccines into seasonal influenza vaccination programs and the development of tetravalent influenza vaccines, including pandemic strains. Clinical Trials Registration. NCT00481065.

Virology, immunology and pathology of human rabies during treatment.

BACKGROUND: Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies. METHODS: Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry. RESULTS: The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and cerebrospinal fluid was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem. CONCLUSIONS: Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the central nervous system by 76 days but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain.

Klebsiella pneumoniae bloodstream infections among neonates in a high-risk nursery in Cali, Colombia.

OBJECTIVES: To determine the cause of an outbreak of Klebsiella pneumoniae bloodstream infections (BSIs) among neonates in a high-risk nursery and to institute control measures. DESIGN: During the on-site investigation, a cohort study to identify risk factors for K. pneumoniae BSI, a point-prevalence study to assess K. pneumoniae colonization, a maternal cohort study to determine maternal K. pneumoniae colonization, and an observational study to evaluate healthcare worker (HCW) compliance with infection control practices were conducted. PATIENTS AND SETTING: Neonates in a 40-bed high-risk nursery in a 700-bed university hospital in Cali, Colombia. INTERVENTION: Cohorting of neonates colonized with K. pneumoniae. RESULTS: The overall K. pneumoniae BSI attack rate was 10 of 105 (9.5%). In the retrospective cohort study, the number of blood transfusions (OR, 3.1 per transfusion; P = .02; CI95, 1.4-9.7) and intravenous injections (OR, 1.2 per injection; P = .04; CI95, 1.0-1.5) were independently associated with K. pneumoniae BSI. The overall prevalence of K. pneumoniae colonization was 61% among neonates and 7% among mothers. During the HCW assessment, suboptimal intravenous therapy practices were observed. A cohorting intervention resulted in a significant reduction in K. pneumoniae colonization (12% vs 61%; RR, 0.19; P < .001). During the intervention period, no K. pneumoniae BSIs occurred. CONCLUSIONS: This investigation suggested that the outbreak probably occurred due to widespread colonization and suboptimal infection control and intravenous therapy practices. Cohorting successfully reduced the overall prevalence of K. pneumoniae colonization and, along with improved infection control practices, probably prevented K. pneumoniae BSIs

Combined administration of MF59-adjuvanted A/H5N1 prepandemic and seasonal influenza vaccines: long-term antibody persistence and robust booster responses 1 year after a one-dose priming schedule.

Having previously demonstrated the feasibility of administering A/H5N1 and seasonal influenza vaccine antigens in an MF59-adjuvanted tetravalent formulation, we now report on long-term antibody persistence and responses to a booster dose of a combined seasonal-pandemic, tetravalent influenza vaccine in adults. The primary objective was the evaluation of responses to a booster dose of tetravalent influenza vaccine containing seasonal (A/H1N1, A/H3N2, and B) and avian (A/H5N1, clade 2) influenza virus strains administered to 265 healthy 18- to 40-year-old volunteers 1 year after priming with one or two clade 1 A/H5N1 doses. Secondary objectives were assessment of reactogenicity, safety, and antibody persistence 1 year after priming with a combined seasonal-pandemic, tetravalent vaccine. Responses to seasonal strains met all European licensure criteria; seroprotection rates were 94 to 100%, 100%, and 61 to 90% for A/H1N1, A/H3N2, and B strains, respectively. Anamnestic responses were observed against homologous and heterologous A/H5N1 strains whether priming with one or two A/H5N1 doses, with a monovalent A/H5N1 vaccine, or with a tetravalent vaccine. A single dose of MF59-adjuvanted A/H5N1 vaccine given alone or as part of a fixed combination with a seasonal influenza vaccine was sufficient to prime adult subjects, resulting in robust antigen-specific and cross-reactive antibody responses to heterologous booster immunization 1 year later. These data support the feasibility of incorporating prepandemic priming into seasonal influenza vaccination programs. (This study has been registered at clinicaltrials.gov under registration no. NCT00481065.).

Alteraciones metabólicas con terapia antirretroviral altamente efectiva en niños positivos para VIH, Cali, Colombia / Metabolic alterations with anti-retroviral highly effective therapy in positive children for VIH, Cali, Colombia

Objetivos: describir las alteraciones metabólicas en niños con diagnóstico de VIH y en tratamiento con terapia antirretroviral altamente efectiva (Highly Active Antiretroviral Therapy, HAART). Métodos: se realizó una primera fase descriptiva de los valores de lípidos y glucemia en una cohorte de niños positivos para VIH. De una clínica pediátrica se reclutaron, entre junio de 2003 y junio de 2005, niños mayores de un mes y menores de 16 años en terapia HAART. Estos resultados se compararon con valores de la población. En una segunda fase, se estudió la densidad ósea en estos niños, utilizando DEXA (dual energy X-ray absorptiometry) y antropometría, y se comparó la de controles sanos. Resultados: se incluyeron 38 niños positivos para VIH. En 59,5% de los niños se clasificaron con displidemia. Al compararlo con la población de referencia, el grupo positivo para VIH presentó una prevalencia mayor de hipertrigliceridemia y HDLc (highdensity lipoprotein) anormalmente bajo. Tomando en cuenta la variación por edad, los valores de colesterol total y LDLc (lowdensity lipoprotein), mostraron un aumento en el grupo que recibía inhibidores de proteasa (IP) contra el que no. La diferencia del puntaje Z de BMD (bone mineral density) entre los grupos fue de 0,56 (IC95%: 0,1- 1,0), teniendo un menor puntaje Z el grupo positivo para VIH. El puntaje Z de la densidad de masa ósea mostró un declive con el tiempo de exposición, que no fue evidente en el grupo control. Conclusiones: encontramos alteraciones en los lípidos similares a las descritas en el adulto seropositivo. En el grupo con IP se encontraron alteraciones del colesterol que cambiaban según la edad. Se encontró una pérdida de la densidad ósea, progresiva con el tiempo de exposición e independiente de la edad. Consideramos que esta relación podría ser de origen multifactorial, incluyendo los efectos de la infección y del tratamiento.

Objectives: our goal is to describe metabolic alterations in children with HIV and under highly effective anti-retroviral treatment (HAART). Methodology: a first descriptive phase of lipid levels and glucemia was carried out in a cohort of HIV positive children. In a paediatric hospital, children >1 month and <16 years old under HAART were recruited from June, 2003 to June, 2005. The results were compared to population values. During the second phase, bone density was studied in these children using DEXA and anthropometric values and compared to healthy control subjects. Results: thirty eight positive children were included. 59.5% of the children were classified as having dyslipidemia. Upon comparison to the reference population, the HIV(+) group showed larger hypertrigliceridemia prevalence and abnormally low cHDL. Taking into account age variations, total colesterol values and cLDL showed increase in the group that received PI against those that did not. The difference of the BMD Z-Score among the groups was 0,56 (CI95%: 0.1, 1.0), the HIV(+) group having a smaller Z-Score. The bone mass density Z-Score showed a decline according exposition time, which was not evident in the control group. Conclusions: alterations in lipids similar to those described in the seropositive adult were found. The group with PI showed cholesterol alterations that changed according to age. Progressive bone density loss according to exposition time was found regardless of age. It is considered that this relationship could have multifactorial origin, including infection and treatment effects.

Fortalezas y debilidades en el manejo del catéter venoso central en una unidad de cuidados intensivos neonatales / Strongs and weaks in the management of central venous catheter in a neonatal intensive care unity

Objetivos: se evaluaron, las fortalezas y debilidades para el cumplimiento del protocolo institucional en el manejo de catéteres venosos percutáneos y umbilicales, en una Unidad de Cuidados Intensivos Neonatales (UCIN), de una institución de niveles III y IV de atención.Metodología: Mediante un estudio descriptivo-longitudinal se observaron 67 procedimientos relacionados con la incersión, curación y administración de medicamentos o soluciones por un catéter venosos central percutáneo o umbilical . La calificación del desempeño del personal médico y de enfermería (profesional y auxiliar), se realizó mediante la observación directa y desprevida para evitar sesgos en el estudio. Los instrumentos incluyen listas de revisión de los materiales y procedimientos así como información general de los recién nacidos obtenida de las historias clínicas. Resultados: La principal falla en el cumplimiento de la norma técnica de inserción de catéteres fue la ausencia del lavado quirúrgico de manos en 27/100 de los catéteres percutáneos y en 37/100 de los catéteres umbilicales. La omisión en la toma de radiografía después de la inserción, se presentó en 27/100 de los catéteres percutáneos y en 37/100 de los catéteres umbilicales. Las complicaciones en la inserción de los catéteres son bajas (6/100) y se relacionan con sangrado leve a moderado. En relación con los materiales para la inserción del catéter umbilical, se encontró la ausencia de la llave de tres vías en 25/100 de los procedimientos, y el uso en 100/100 de los procedimientos de un campo de ojo muy grande, que exponía mucha más superficie de la necesaria para el procedimiento y exigía mayor manipulación y riesgo de contaminación por parte del personal. Las principales deficiencias en el cumplimiento del protocolo de curación de los catéteres, se relacionan con la ausencia de guantes limpios en el equipo para manipular apósitos contaminados (47/100). Durante la administración de medicamentos se observaron deficiencias en el no empleo de elementos de protección personal (mascarilla y guantes limpios), así como la no ejecución del lavado de manos clínico antes del procedimiento (42/100). Sin embargo, la preparación de los medicamentos se hace con minuciosa técnica aséptica