IgG antibody response to pneumococcal-conjugated vaccine (Prevenar®13) in children with immunodeficiency disorders.

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented.

A surface plasmon resonance based approach for measuring response to pneumococcal vaccine.

Incidence of pneumococcal disease has increased worldwide in recent years. Response to pneumococcal vaccine is usually measured using the multiserotype enzyme-linked immunosorbent assay (ELISA) pneumococcal test. However, this approach presents several limitations. Therefore, the introduction of new and more robust analytical approaches able to provide information on the efficacy of the pneumococcal vaccine would be very beneficial for the clinical management of patients. Surface plasmon resonance (SPR) has been shown to offer a valuable understanding of vaccines' properties over the last years. The aim of this study is to evaluate the reliability of SPR for the anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs quantification in vaccinated. Fast protein liquid chromatography (FPLC) was used for the isolation of total IgGs from serum samples of vaccinated patients. Binding-SPR assays were performed to study the interaction between anti-PnPs IgGs and PCV13. A robust correlation was found between serum levels of anti-PnPs IgGs, measured by ELISA, and the SPR signal. Moreover, it was possible to correctly classify patients into "non-responder", "responder" and "high-responder" groups according to their specific SPR PCV13 response profiles. SPR technology provides a valuable tool for reliably characterize the interaction between anti-PnPs IgGs and PCV13 in a very short experimental time.

Cutaneous and mucocutaneous leishmaniasis: experience of a Mediterranean hospital.

BACKGROUND: Leishmaniasis, considered by the World Health Organization as one of the most important tropical diseases, is endemic in the Mediterranean Basin. The aim of this study was to evaluate epidemiological and clinical characteristics of cutaneous (CL) and mucocutaneous leishmaniasis (MCL) in La Fe University Hospital, Valencia, Spain. The particular focus was on diagnosis techniques and clinical differences according to the immunological status of the patients. METHODS: An eleven-year retrospective observational study of CL and MCL episodes at the hospital was performed. Epidemiological, clinical and therapeutic variables of each case, together with the microbiological and anatomopathological diagnosis, were analyzed. RESULTS: A total of 42 patients were included, 30 of them were male and 28 were immunocompetent. Most of the cases (36/42) were diagnosed in the last 5 years (2013-2017). The incidence of CL and MCL increased from 3.6/100,000 (2006-2012) to 13.58/100,000 (2013-2017). The majority of the patients (37/42) exhibited CL, in 30 cases as single lesions (30/37). Ulcerative lesions were more common in immunosuppressed patients (13/14) than in immunocompetent patients (20/28), (P = 0.2302). The length of lesion presence before diagnosis was 7.36 ± 6.72 months in immunocompetent patients and 8.79 ± 6.9 months in immunosuppressed patients (P = 0.1863). Leishmania DNA detection (92.3%) was the most sensitive diagnostic technique followed by Giemsa stain (65%) and histopathological examination (53.8%). Twelve patients (12/42) had close contact with dogs or were living near to kennels, and 10 of them did not present underlying conditions. Intralesional glucantime (21/42) and liposomal amphotericin B (7/42) were the most common treatments administered in monotherapy. All patients evolved successfully and no relapse was reported. CONCLUSIONS: Some interesting clinical and epidemiological differences were found in our series between immunocompetent and immunosuppressed patients. Future studies can take these results further especially by studying patients with biological therapy. Skin biopsies combining NAAT with histological techniques are the most productive techniques for CL or MCL diagnosis.

Estudio descriptivo de los casos de malaria en la población pediátrica en un hospital de referencia de Valencia, España, entre 1993 y 2015 / Descriptive study of malaria cases in the paediatric population in a reference hospital in Valencia, Spain, between 1993 and 2015

Introducción: La malaria es considerada la cuarta causa de mortalidad infantil después de la neumonía, las complicaciones por parto prematuro y la asfixia perinatal. Material y métodos: Estudio retrospectivo y descriptivo de los casos de paludismo confirmados y tratados en la Unidad de Enfermedades Infecciosas Pediátricas (edad inferior a 15 años) del Hospital La Fe (Valencia) en el período comprendido entre 1993 y 2015. Resultados: Durante el período 1993-2015 se diagnosticaron 54 casos de malaria infantil, el 51,8% en varones. El 46,2% eran menores de 5 años. La mayoría de los niños procedían de Guinea Ecuatorial (68,5%). Solo en el 5,6% de los pacientes se pudo constatar que recibieran profilaxis antimalárica. Se evidenció que Plasmodium falciparum fue la especie causal del 81,4% de los episodios. Siete casos (13%) presentaron malaria complicada. El tratamiento más empleado fue la quinina, sola o en combinación con otros fármacos: atovacuona-proguanil fue empleada a partir del año 2010 y estuvo indicada en el 20,3% de los pacientes. A partir del año 2013 se inició la utilización de: artesunato, piperaquina y dihidroartemisina. No hubo mortalidad ni efectos adversos relevantes, siendo la respuesta clínica favorable en el 100% de los niños. Conclusiones: La malaria sigue siendo una enfermedad vigente en nuestra población, consecuencia de la inmigración y del turismo a países endémicos. Debe ser considerada como diagnóstico probable ante un niño febril que procede o ha viajado a un área endémica en el último año

Introduction: Malaria is considered to be the fourth leading cause of infant mortality after pneumonia, complications related to premature birth, and perinatal asphyxia. Material and methods: A retrospective and descriptive study of cases of malaria confirmed and treated by the Paediatric Infectious Diseases Unit (age lower than 15 years) at the La Fe Hospital, Valencia, over the period 1993 to 2015. Results: A total of 54 cases of paediatric malaria were diagnosed in the period 1993-2015, with 51.8% of these occurring in males, and 46.2% of patients were aged below 5 years. The majority of children came from Equatorial Guinea (68.5%). Only 5.6% had received antimalarial prophylaxis. Plasmodium falciparum was found to be the causal species in 81.4% of cases. Seven patients (13%) presented with complicated malaria. The most widely used treatment was quinine, either alone or in combination with other drugs. Atovaquone/proguanil was used from 2010 onwards and was indicated in 20.3% of the patients. The combination of artesunate/piperaquine/dihydroartemisinin began to be used in 2013. No deaths or relevant side effects were reported, and the clinical response was favourable in all children (100%). Conclusions: Malaria is still a prevalent disease in this population, a consequence of immigration, and tourism to endemic countries. Malaria should be considered as a likely diagnosis in a febrile child who comes from, or has travelled to, an endemic region in the past year

[Descriptive study of malaria cases in the paediatric population in a reference hospital in Valencia, Spain, between 1993 and 2015]. / Estudio descriptivo de los casos de malaria en la población pediátrica en un hospital de referencia de Valencia, España, entre 1993 y 2015.

INTRODUCTION: Malaria is considered to be the fourth leading cause of infant mortality after pneumonia, complications related to premature birth, and perinatal asphyxia. MATERIAL AND METHODS: A retrospective and descriptive study of cases of malaria confirmed and treated by the Paediatric Infectious Diseases Unit (age lower than 15 years) at the La Fe Hospital, Valencia, over the period 1993 to 2015. RESULTS: A total of 54 cases of paediatric malaria were diagnosed in the period 1993-2015, with 51.8% of these occurring in males, and 46.2% of patients were aged below 5 years. The majority of children came from Equatorial Guinea (68.5%). Only 5.6% had received antimalarial prophylaxis. Plasmodium falciparum was found to be the causal species in 81.4% of cases. Seven patients (13%) presented with complicated malaria. The most widely used treatment was quinine, either alone or in combination with other drugs. Atovaquone/proguanil was used from 2010 onwards and was indicated in 20.3% of the patients. The combination of artesunate/piperaquine/dihydroartemisinin began to be used in 2013. No deaths or relevant side effects were reported, and the clinical response was favourable in all children (100%). CONCLUSIONS: Malaria is still a prevalent disease in this population, a consequence of immigration, and tourism to endemic countries. Malaria should be considered as a likely diagnosis in a febrile child who comes from, or has travelled to, an endemic region in the past year.

Update on the diagnosis of invasive fungal infection / Actualización en el diagnóstico de la infección fúngica invasora

The number of patients at risk of suffering invasive fungal infection (IFI) is increasing. Because of its high mortality, new rapid and accurate diagnostic tools are needed. Last advances in invasive candidiasis diagnosis comprise Peptide Nucleic Acid Fluorescent In-Situ Hybridization (PNA-FISH), direct MALDI-TOF or multiplex acid nucleic testing. While all of them rely in positive blood cultures, T2Candida(R) uses PCR coupled with T2Magnetic resonance detection directly in whole blood, allowing detection of 1-3 UFC/mL of Candida in about four hours. Beyond galactomannan (GM), novelties in IFI caused by molds include the international standardization of PCR techniques, with several commercial kits available. A combination of GM and PCR appears to be a good diagnostic strategy for invasive aspergillosis. PCR coupled to electrospray ionization/mass spectrometry and detection of volatile organic compounds in exhaled air by gas chromatography/mass spectrometry are other promising approaches to IFI diagnostic that still need to be validated (AU)

El número de pacientes en riesgo de padecer infección fúngica invasora (IFI) está en aumento. Debido a su elevada mortalidad, es necesario disponer de nuevas herramientas diagnósticas más rápidas, sensibles y específicas que las que disponemos en la actualidad. Los últimos avances en el diagnóstico de la candidiasis invasora incluyen Hibridación In Situ de Ácidos Péptidonucleicos (PNA-FISH), MALDI-TOF directo o PCR múltiple. Mientras que todas estas técnicas se realizan sobre frascos de hemocultivo positivos, T2Candida(R) se basa en una PCR con detección por resonancia magnética T2 directamente en sangre total, y permite la detección de entre 1-3 UFC/mL de Candida en aproximadamente 4 horas. Más allá del galactomanano (GM), una de las últimas novedades en el diagnóstico de IFI causada por hongos filamentosos es la estandarización internacional de las técnicas moleculares, con la aparición de varios kits comerciales. Una buena estrategia para el diagnóstico de aspergilosis invasora es la combinación de GM y PCR. La PCR asociada a ionización por electrospray/espectrometría de masas y la detección de compuestos orgánicos volátiles en aire exhalado mediante cromatografía de gases asociada a espectrometría de masas son otras aproximaciones prometedoras al diagnóstico de IFI que aún deben ser validadas (AU)

[Changing epidemiological aspects of candidemia and their clinical and therapeutic implications]. / Los aspectos epidemiológicos cambiantes de la candidemia y sus implicaciones clinicoterapéuticas.

Candida species are a major cause of healthcare-related bloodstream and invasive infections. Studies assessing nosocomial bloodstream infections during the two last decades ranked Candida species as the fourth most common nosocomial bloodstream pathogen. The incidence of Candida species has risen steadily during this period due to the increase in the number and type of patients at risk for these yeasts. Infections caused by Candida are especially frequent and serious in onco-hematological patients. Over the past decade, the introduction of azole antifungals as prophylactic agents, together with other factors, has led to a shift in the species of Candida that cause infection. During the period under review (1996 to 2005) several studies have confirmed the impact of antifungal prophylaxis with azoles on the emergence of Candida species other than Candida albicans. The widespread use of fluconazole has contributed to a relative decrease in the prevalence of C. albicans, while species inherently less susceptible, such as Candida glabrata and Candida krusei, appear to be isolated with greater frequency. Moreover, laboratory studies to determine the antifungal susceptibilities and virulence of non-albicans Candida species have enabled the design of microbe-specific management strategies. More of these studies will be necessary as we enter an age in which multiple antifungal compounds (echinocandins, new azoles) will become available for clinical use in invasive candidiasis or candidemia. The present review aims to highlight the different trends in the incidence, distribution and behavior of Candida bloodstream infections in the distinct types of patients at risk.

Los aspectos epidemiológicos cambiantes de la candidemia y sus implicaciones clinicoterapéuticas / Changing epidemiological aspects of candidemia and their clinical and therapeutic implications

Las especies de Candida son una causa importante de infecciones invasoras y diseminadas por vía hematógena. En los estudios realizados en las últimas 2 décadas, suponen la cuarta causa como patógenos nosocomiales aislados en hemocultivos. La incidencia de Candida se ha incrementado en este período debido al número y la variedad de pacientes susceptibles a este hongo, que son especialmente frecuentes y graves en los pacientes oncohematológicos. La profilaxis antifúngica con azoles instaurada en la última década, junto con otros factores, han ocasionado una redistribución en las especies de Candida causantes de infección. Durante el período revisado (1996-2005), varios trabajos han confirmado el impacto de las profilaxis con azoles en la emergencia de especies distintas de Candida albicans. El amplio uso de fluconazol ha podido reducir la prevalencia de C. albicans, con un incremento de especies menos sensibles o resistentes a fluconazol, como Candida glabrata y Candida krusei. Con los estudios de sensibilidad y de virulencia disponibles de estas especies de Candida no-albicans se han diseñado estrategias de manejo específicas de especie. Todavía se necesitan muchos estudios para situarnos en la era en la que dispondremos de nuevos antifúngicos (equinocandinas, nuevos azoles) para su uso clínico en el tratamiento de la candidiasis invasora y de la candidemia. El objetivo de esta revisión es subrayar las diferentes tendencias en incidencia, distribución y comportamiento de la candidemia en distintos pacientes de riesgo

Candida species are a major cause of healthcare-related bloodstream and invasive infections. Studies assessing nosocomial bloodstream infections during the two last decades ranked Candida species as the fourth most common nosocomial bloodstream pathogen. The incidence of Candida species has risen steadily during this period due to the increase in the number and type of patients at risk for these yeasts. Infections caused by Candida are especially frequent and serious in onco-hematological patients. Over the past decade, the introduction of azole antifungals as prophylactic agents, together with other factors, has led to a shift in the species of Candida that cause infection. During the period under review (1996 to 2005) several studies have confirmed the impact of antifungal prophylaxis with azoles on the emergence of Candida species other than Candida albicans. The widespread use of fluconazole has contributed to a relative decrease in the prevalence of C. albicans, while species inherently less susceptible, such as Candida glabrata and Candida krusei, appear to be isolated with greater frequency. Moreover, laboratory studies to determine the antifungal susceptibilities and virulence of non-albicans Candida species have enabled the design of microbe-specific management strategies. More of these studies will be necessary as we enter an age in which multiple antifungal compounds (echinocandins, new azoles) will become available for clinical use in invasive candidiasis or candidemia. The present review aims to highlight the different trends in the incidence, distribution and behavior of Candida bloodstream infections in the distinct types of patients at risk