Miguel Cordero

Human Dirofilariasis in the European Union

The dog parasites Dirofilaria immitis and D. (Nochtiella) repens, well known as zoonotic agents, are widely distributed in southern Europe. Although both species are canine parasites, infection with immature worms has been found in humans, who develop nodules, mainly in subcutaneous tissue or in lung parenchyma arising from branches of the pulmonary artery. In humans, the parasites do not usually reach the adult stage and microfilaremia is absent, as has been shown by diagnosis using invasive methods for removing the nodules. In this article, Antonio Muro, Claudio Genchi, Miguel Cordero and Fernando Simón review the current situation concerning the clinical and epidemiological aspects, immune response and diagnosis of human dirofilariases.

Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy.

Summary: Antiretroviral therapy (ART) has led to marked decreases in morbidity and mortality rates among HIV-1-positive patients; however, immune recovery is not complete. Although dendritic cells (DCs) were shown to be involved in HIV-1 pathogenesis, few studies have investigated the effect of ART on DCs. We have analyzed the effect of ART on numerical distribution, expression of chemokine receptors, and ex vivo production of inflammatory cytokines by peripheral blood (PB) monocytes and DCs in a cohort of chronically infected HIV-1-positive patients. Patients were tested before therapy and at weeks +2, +4, +8, +12, and +52 after starting ART. Our results show an incomplete T-cell immune reconstitution in chronically infected patients who had undetectable plasma viremia while taking ART for 1 year. This was associated with persistent abnormalities at week +52 of ART, corresponding to increased numbers of CD16+ DCs and monocytes, as well as altered expression of CXC chemokine receptors, in the form of increased CXCR1 expression on monocytes and decreased reactivity for CXCR2 and/or CXCR4 on myeloid and plasmacytoid DCs. In addition, an abnormally high spontaneous ex vivo secretion of inflammatory cytokines by CD16+ DCs and monocytes was still detected after 1 year of ART. These abnormalities were especially pronounced in patients with less than 200 CD4+ T cells/&mgr;L, which could be related to the persistence of undetected viral replication and sustained immune activation.

Hidatidosis en la provincia de Salamanca: ¿debemos bajar la guardia?

INTRODUCTION Hydatid disease is a major health problem in endemic countries. In Spain, this disease was notifiable from 1981 to 1996, although its incidence kept increasing until the end of this period. From 1997 on, hydatid disease is only surveyed by endemic autonomous regions. Thus, true incidences for human hydatid disease in Spain are currently unknown. In this study the cases recorded from 1996 to 2003 at the Hospital Universitario (Salamanca) which receives patients from all Salamanca province, were analyzed. Method. We obtained epidemiological and clinical data from patients at the University Hospital (reference hospital in Salamanca province) with registered CIE-10 codification 122.0 to 122.9 (hydatid disease), from January 1996 to December 2003, excluding those patients not arriving from Salamanca. We estimated the incidence of hydatid disesase in Salamanca province regarding the total population of the province. RESULTS Our data show that the mean incidence (1996-2003) was 10,8/100.000 inhabitants, twice as many as previously reported by the notifiable diseases scheme. 30% of infected patients were younger than 45. In addition, during the last three years of study, several cases of paediatric hydatid disease were observed. The analysis of the origin of the cases showed a broad distribution throughout the whole province of Salamanca. CONCLUSIONS The real incidence of this disease seems to be higher than previously estimated. Importantly, the several cases of paediatric hydatid disease detected within the last two years of our study, suggest a possible re-emergence of hydatid disease.Introduccion La hidatidosis humana es un problema importante de salud en paises endemicos. En Espana, esta enfermedad fue de declaracion obligatoria (EDO) desde 1981 hasta 1996; el numero de casos en Castilla y Leon aumento desde 1985 a 1996. En 1997 la hidatidosis paso a ser vigilada por las Comunidades Autonomas con hidatidosis endemica. Actualmente el numero de casos y la incidencia anual son desconocidos. En este trabajo, investigamos la situacion actual de la hidatidosis humana en la provincia de Salamanca. Metodo Se seleccionaron pacientes del Hospital Universitario (hospital de referencia de la provincia de Salamanca) cuya codificacion en la novena Clasificacion Internacional de Enfermedades (CIE-9) fue 122.0 a 122.9 (hidatidosis) desde enero de 1996 hasta diciembre de 2003, excluyendose los pacientes residentes en otras provincias. Se obtuvieron datos epidemiologicos y clinicos de los registros informaticos y de las historias clinicas de los pacientes. Se estimo la incidencia provincial segun datos del censo poblacional. Resultados Nuestros resultados demuestran una incidencia media (1996-2003) de 10,8 casos por 100.000 habitantes/ano, 2 veces mayor que la registrada previamente mediante el sistema EDO. El 30% de los casos fueron en menores de 45 anos. En los anos 2000-2003 reaparecieron casos en pacientes en edad pediatrica. Tambien se demostro una amplia distribucion de casos en toda la provincia. Conclusiones La incidencia real de esta parasitosis es superior a la previamente estimada. La reaparicion de casos pediatricos y el mantenimiento del 30% de los casos en menores de 45 anos apuntan a una posible reemergencia de esta enfermedad.

Relationship between CD38 expression on peripheral blood T-cells and monocytes, and response to antiretroviral therapy: a one-year longitudinal study of a cohort of chronically infected ART-naive HIV-1+ patients.

HIV‐1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD8+ and CD4+ T‐cells, which has been related with poor prognosis in untreated HIV‐1+ patients. In turn, CD38 expression on PB monocytes from HIV‐1+ individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied.

Utility of antibodies against a 22 kD molecule of Dirofilaria immitis in the diagnosis of human pulmonary dirofilariasis.

Summary To assess the characteristics of an ELISA test for the diagnosis of human pulmonary dirofilariasis, we studied the sera of 24 subjects with other helmintoses and of 37 patients suffering from non‐parasitic focal lung diseases, comparing them with negative and positive sera. ELISA and Western blot with complete somatic antigen and ELISA with protein Di22 (specifically recognized in cases of lung dirofilariasis) were performed. With ELISA SA the false positive rate was 25% in cases with other parasitoses and 30% in cases with focal lung diseases. ELISA Di22 decreases this positivity levels. Only 2 cases with visceral larva migrans (8.3%) and a case with lung nodules metastatic from renal adenocarcinoma (2.7%) were positive. ELISA Di22 therefore greatly decreases the false positive rate of ELISA SA.

Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection.

HIV-1 infection is associated with dysregulation of cytokine production by peripheral blood (PB) monocytes and dendritic cells (DC), but controversial results have been reported. We aimed to analyze the effect of antiretroviral therapy (ART) on the in vitro production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin -CD33(high+ ) myeloid DC (mDC) and CD33(+)/CD14(-/dim+)/CD16(high+) DC- from HIV-1+ patients and its relationship with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro cytokine production was analyzed at the single cell level in 32 HIV-1+ patients, grouped according to the number of CD4+ T-cells/microl in PB (<200 CD4 versus >200 CD4). Patients were tested prior to therapy and at weeks +2, +4, +8, +12 and +52 after ART. Prior to ART, production of IL-6, TNF-alpha and IL-12 by mDC and of IL-8 and IL-12 by CD16+ DC was significantly increased among >200 CD4 patients. After one year of ART, increased production of IL-8 by monocytes, of TNF-alpha by mDC and of IL-1beta, IL-6 and TNF-alpha by CD16+ DC was specifically observed among <200 CD4 HIV-1+ individuals showing a high recovery of PB CD4+ T-cell counts. In turn, we found that the significantly reduced percentage of IL-1beta, IL-6, IL-8 and TNF-alpha-producing monocytes and of IL-6 and IL-8-producing mDC and CD16+ DC, as well as the significantly diminished mean amount of IL-6 produced per monocyte, mDC and CD16+ DC and of IL-12 produced per CD16+ DC observed at week +52 for the >200 CD4 patients, were related to the presence of co-infection with HCV. In summary, HIV-1+ individuals show abnormal production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin even after one year of ART, such abnormalities being associated with the degree of recovery of PB CD4+ T-cell counts in more immunocompromised patients and HCV co-infection in more immunocompetent HIV-1+ individuals.

Diagnóstico de helmintiasis importadas

In recent years, there has been an increase in cases of imported helminthiasis in Spain because of two complementary causes: immigration and international travel. Although the prevalence of helminthiasis is high in the immigrant population, the risk of transmission to the Spanish population is low. In this review, we provide clues to aid in the diagnosis of the helminthiasis, highlighting the geographic characteristics, clinical findings and analytical results of the most frequent types. The low sensitivity of the classic parasitological diagnostic test, mainly in tissue helminthiasis, is described. In addition, the advantages and limitations of the common serological methods for detecting related circulating antigens and antibodies are presented. Certain molecular methods used in the diagnosis of imported helminthiasis and the best strategies for screening of this condition are discussed.

Application of an ELISA test using schistosoma bovis adult worm antigens in travellers and immigrants from a schistosomiasis endemic area and its correlation with clinical findings

We have recently evaluated an ELISA for the diagnosis of human schistosomiasis using S. bovis adult worm antigens (AWA Sb), showing a sensitivity of 94% and a specificity of 97% for patients diagnosed by egg detection. Nevertheless, the comparison of this AWA Sb ELISA with direct parasitological findings as the gold standard could introduce a selection bias, due to the well-known lack of sensitivity of direct methods in the detection of acute schistosomiasis and of low burden infections. The objective of the present work is to compare it with parasitological methods and commercial indirect haemagglutination test using S. mansoni antigens (WA Sm IHA) in 254 immigrants and travellers with different clinical settings; in addition, to find specific bands in the EITB of different phases of schistosomiasis. The AWA Sb ELISA showed 72% of seropositivity in patients with Katayama fever, while patients with eosinophilia and genito-urinary complaints showed 27% and 93%, respectively. The diagnosis yield was globally higher than direct egg detection or WA Sm IHA test with regard to the clinical setting. Finally, the utilization of EITB with S. bovis AWA permits the confirmation of diagnosis in chronic and acute phases of the disease.

CD38 on peripheral blood cells: The value of measuring CD38 expression on CD8 T-cells in patients receiving highly active anti-retroviral therapy

Abstract As in other viral infections, human immunodeficiency virus type 1 (HIV-1) induces an immune response, which translates into an increased lymphoid activation, despite CD4+ T-cell depletion. Such activation of the immune system is reflected not only by increased production of cytokines and other soluble factors, but also by modulation of the expression of T-cell activation-associated antigens, such as CD38, usually increasing their levels on the cell membrane. Since the first report showing that CD38 levels on CD8+ PB T-cells increase in subjects infected with the HIV-1, several studies have shown that such increased CD38 expression is a strong predictive marker for disease progression in HIV-1 infection. The levels of CD8+CD38+ T-cells not only predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) and death, but also offer additional independent predictive value to that of CD4 counts. In recent years, the introduction of highly active anti-retroviral therapy (HAART) has led to the suppression of HIV-1 replication with a dramatic decrease in plasma viral load levels in many HIV-1 infected subjects. However, success of HAART-based treatment is not achieved in all patients. Therefore, a need exists for adequate prognostic markers capable of predicting, in advance or in an early phase of treatment, lack of response to HAART. Also in this area, the measurement of CD8+CD38+ T-cells has been proposed as a useful tool for monitoring HIV-1 positive patients, given that an increased expression of CD38 on CD8+ PB T-cells could be an early marker of either viral replication or HAART failure.

Imported cystic echinococcosis in western Spain: a retrospective study.

BACKGROUND In Spain, 12% of the population are immigrants. The impact of immigration in Spain on cystic echinococcosis (CE) is unknown. The aim of this study was to describe the epidemiology of CE in immigrants in western Spain. METHODS First, a retrospective descriptive study of patients diagnosed with CE in the University Hospital of Salamanca (CAUSA) between January 1998 and December 2014 was designed. Second, we studied the seroprevalence of CE in sera from foreigners who received treatment in the Tropical Medicine Unit. RESULTS A total of 550 patients with new CE-related diagnoses were registered; of these, 16 (2.9%) were immigrants, of whom 10 (63%) were male. The age (mean±SD) was 34.6±12.8 years. The incidence rate of CE in immigrants was 8.76 cases per 105 person-years. Eight (50%) cases presented asymptomatically. Seroprevalence of CE in foreign patients was 2.3%. It was higher in North African population (4.2%), followed by sub-Saharan (2.4%) and Latin American (1.8%) (p=0.592) populations. The seroprevalence was higher in those who arrived recently (<12 months) vs those who arrived earlier (≥12 months), 3.5% vs 1.3% (p=0.077). CONCLUSIONS The epidemiological and clinical characteristics of CE in immigrants are different than those of the native population, and their influence on CE burden in our endemic area is still limited.