Perfil de parámetros hematológicos en el HIV pediátrico y los cambios asociados al tratamiento antirretroviral / Hematological parameters profile in pediatric HIV and changes associated with antiretroviral treatment / Perfil de parâmetros hematológicos no HIV pediátrico e as alterações associadas ao tratamento anti-retroviral

Resumen Las alteraciones hematológicas son comunes durante la infección por el virus de la inmunodeficiencia humana (HIV). El objetivo de este trabajo fue describir los perfiles hematológicos e inmunológicos de niños infectados, antes y después de 36 meses de implementado el tratamiento antirretroviral (TARV). Se revisaron historias clínicas de niños expuestos, atendidos en este hospital en el período 2008-2018, con edades entre 6 meses y 14 años. Fueron empleados un contador hematológico (ADVIA 2120), un citómetro de flujo (FACScalibur BD) y una PCR en tiempo real Nuclisens EasyQ (bioMérieux). En 486 historias clínicas se encontraron 58 pacientes sin TARV, 30 por diagnóstico reciente y 28 por adherencia incorrecta o abandono de tratamiento. En ambos grupos se observó disminución porcentual de hemoglobina (Hb) (53% y 43%), volumen corpuscular medio (VCM) (43% y 7%) y LTCD4+ (37% y 57%), respectivamente, sin alteraciones significativas en otros parámetros hematológicos. Veintidós niños con correcta adherencia al TARV incrementaron significativamente los niveles de LTCD4+ (t0:18,8±9%, t1:32,7±6%), Hb (t0:10,9±1,6 g/dL, t1:12,6±1,1g/dL) y VCM (t0:78,7±4,5 fL, t1:101,9±5,6 fL), con disminución simultánea de la carga viral (CV) (t0:4,4±0,75 log t1:<1,70 log) después del seguimiento. La disminución de Hb observada aproximadamente en el 50% de los pacientes sin TARV estaría asociada a la acción viral y al tiempo de evolución de la infección. El incremento en los niveles, asociados a macrocitosis, se relacionaría con el aumento de LTCD4+ y disminución de la CV.

Abstract Hematologic abnormalities are common during human immunodeficiency virus (HIV) infection. Our aim was to describe hematological and immunological profiles present in antiretroviral treatment (ART)-naïve infected children and the changes observed after 36 months of ART initiation. Medical records of exposed children attended at this hospital in the 2008-2018 period were reviewed. Children between 6 months and 14 years were included. An automated blood analyser ADVIA 2120, a FACScalibur BD flow cytometer, and a Nuclisens EasyQ bioMérieux real-time PCR were used to determine different parameters. In 486 medical records evaluated, 58 patients ART-naïve were found, 30 due to recent diagnosis and 28 for incorrect adherence or abandoned treatment. In both groups, a percentage decrease in hemoglobin (Hb) (53% and 43%), mean corpuscular volume (MCV) (43% and 7%) and LTCD4+ (37% and 57%) levels respectively, was observed, without significant alterations in other hematological parameters. Twenty-two children with ART correct adherence increased significantly CD4+T cells (t0:18.8±9%, t1:32.7±6%), Hb (t0:10.9±1.6 g/dL, t1:12.6±1.1 g/dL) and MCV (t0:78.7±4.5 fL, t1:101.9±5.6 fL) levels, with simultaneous decrease of viral load (VL), (t0:4.4±0.75 log, t1:<1.70 log), after 36 months of follow-up. The reduction in Hb levels observed in 50% approximately of patients without ART would be associated with viral action and time of evolution of the infection. The increase in Hb levels and an associated macrocytosis would be related to the CD4+ T cells increase and VL decrease.

Resumo Alterações hematológicas são comuns durante a infecção pelo vírus da imunodeficiência humana (HIV). Nosso objetivo foi descrever os perfis hematológicos e imunológicos em crianças infectadas, antes e após 36 meses de implementar o tratamento antirretroviral (TARV). Foram revisados os prontuários das crianças expostas atendidas neste hospital no período 2008-2018, com idade entre 6 meses e 14 anos. Um contador hematológico (ADVIA 2120), um citômetro de fluxo (FACScalibur BD) e um PCR em tempo real Nuclisens EasyQ (bioMérieux), foram usados. Em 486 prontuários foram encontrados 58 pacientes livres de TARV, 30 por diagnóstico recente e 28 por adesão incorreta ou abandono do tratamento. Em ambos os grupos, observou-se diminuição percentual de hemoglobina (Hb) (53% e 43%), volume corpuscular médio (VCM) (43% e 7%) e LTCD4+ (37% e 57%), respectivamente, sem alterações significativas nos demais parâmetros hematológicos. Vinte e duas crianças com adesão correta ao TARV aumentaram significativamente os níveis de LTCD4+ (t0:18,8±9%, t1:32,7±6%), Hb (t0:10,9±1,6 g/dL, t1:12,6±1,1 g/dL) e VCM (t0:78,7±4,5 fL, t1:101,9±5,6 fL), com diminuição simultânea da carga viral (CV) (t0:4,4±0,75 log, t1:<1,70 log), depois do seguimento. A diminuição dos níveis de Hb observada em aproximadamente 50% dos pacientes sem TARV estaria associada à ação viral e ao tempo de evolução da infecção. O aumento nos níveis, associados a macrocitose, estaria relacionado com o aumento de LTCD4+ e diminuição da CV.

Mixed T Helper1/T Helper2/T Cytotoxic Profile in Subjects with Chronic Chagas Disease with Hypersensitivity Reactions to Benznidazole.

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

Restoration of recent thymic emigrant CD4+ T cells is associated with sustained adherence to antiretroviral treatment in HIV-infected children.

To evaluate the levels of recent thymic emigrant (RTE) CD4+ T cells in HIV-infected children and to explore the associations among their frequency, antiretroviral treatment (ART) adherence, and CD4+ T cell restoration. The group evaluated comprised 85 HIV-infected patients classified as subjects with moderate or severe immunosuppression or as those with no evidence of immunosuppression. To evaluate the association between the frequency of RTE CD4+ T cells and ART adherence, 23 of the 85 patients were evaluated at two different time points during a one-year follow-up period. Children with severe immunosuppression had lower frequencies of RTE CD4+ T cells compared with children without evidence of immunosuppression (P < .001). The frequency of RTE CD4+ T cells in children with a high rate of adherence was significantly higher (P < .05) than that observed among those with suboptimal adherence. The latter group presented with infectious intercurrences on admission that decreased after initiation of treatment along with improved CD4+ and RTE naïve CD4+ T cells counts. The adequate ART adherence is essential for immune reconstitution, which might be reflected by the levels of RTE CD4+ T cells.

Inmunodeficiencia combinada con compromiso cutáneo asociada a mutación en DOCK8 / Combined immunodeficiency with cutaneous manifestations associated with DOCK8 mutation

Diferentes inmunodeficiencias primarias se caracterizan por niveles elevados de IgE e infecciones cutáneas de origen viral. Describimos el caso de un niño de 2 años y 8 meses de edad, con inmunodeficiencia combinada, dermatitis y molusco contagioso diseminado. El paciente presentaba niveles aumentados de IgE, eosinofilia y marcada linfopenia a predominio de TCD8. Se encontraron alteraciones en los ensayos funcionales por cultivo y en la respuesta a la vacunación. Resultados normales de la proteína ZAP-70, funcionalidad NK y niveles de HLA I, tendientes a verificar alteraciones cuantitativas y funcionales de las células citotóxicas, llevaron a la sospecha de deficiencia en el gen DOCK8. El resultado positivo del estudio molecular, junto con las características clínicas e inmunológicas del paciente, confirmaron el diagnóstico de esta nueva inmunodeficiencia, que, de acuerdo con nuestro conocimiento, sería el primer caso diagnosticado en un hospital pediátrico en nuestro país.

Different primary immunodeficiencies present increased levels of IgE and cutaneous infections of viral etiology. We report a case of a 2 y, 8 m old boy with combined immunodeficiency, dermatitis and disseminated molluscum contagiosum. The patient presented high titers of IgE, eosinophilia and pronounced TCD8 lymphopenia. Impaired proliferation assays and abnormal antibody response to vaccination were found. Normal results of ZAP-70 protein, NK function, and HLA I levels, to test quantitatives and functional defects of cytotoxic cells, lead us to suspect a mutation in DOCK8 gene. Positive result in molecular study together with clinical and immunology features in the patient confirmed the diagnosis of this new immunodeficiency, being to the authors ́ knowledge the first case recorded in a paediatric hospital in our country.

[Combined immunodeficiency with cutaneous manifestations associated with DOCK8 mutation]. / Inmunodeficiencia combinada con compromiso cutáneo asociada a mutación en DOCK8.

Different primary immunodeficiencies present increased levels of IgE and cutaneous infections of viral etiology. We report a case of a 2 y, 8 m old boy with combined immunodeficiency, dermatitis and disseminated molluscum contagiosum. The patient presented high titers of IgE, eosinophilia and pronounced TCD8 lymphopenia. Impaired proliferation assays and abnormal antibody response to vaccination were found. Normal results of ZAP-70 protein, NK function, and HLA I levels, to test quantitatives and functional defects of cytotoxic cells, lead us to suspect a mutation in DOCK8 gene. Positive result in molecular study together with clinical and immunology features in the patient confirmed the diagnosis of this new immunodeficiency, being to the authors' knowledge the first case recorded in a paediatric hospital in our country.

Inmunodeficiencia combinada con compromiso cutáneo asociada a mutación en DOCK8. / [Combined immunodeficiency with cutaneous manifestations associated with DOCK8 mutation].

Different primary immunodeficiencies present increased levels of IgE and cutaneous infections of viral etiology. We report a case of a 2 y, 8 m old boy with combined immunodeficiency, dermatitis and disseminated molluscum contagiosum. The patient presented high titers of IgE, eosinophilia and pronounced TCD8 lymphopenia. Impaired proliferation assays and abnormal antibody response to vaccination were found. Normal results of ZAP-70 protein, NK function, and HLA I levels, to test quantitatives and functional defects of cytotoxic cells, lead us to suspect a mutation in DOCK8 gene. Positive result in molecular study together with clinical and immunology features in the patient confirmed the diagnosis of this new immunodeficiency, being to the authors knowledge the first case recorded in a paediatric hospital in our country.

[Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/AIDS]. / Relación entre adherencia al tratamiento antirretroviral y subpoblaciones linfocitarias en niños con HIV/ Sida.

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.

Relación entre adherencia al tratamiento antirretroviral y subpoblaciones linfocitarias en niños con HIV/Sida / Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/Aids

El curso de la infección por HIV se caracteriza principalmente por una depleción grave de los linfocitos TCD4+ y una activación inmune marcada, hallazgos centrales que conducen a variaciones numéricas y fenotípicas de las poblaciones linfocitarias TCD4+. El tratamiento antirretroviral (TARV) combinado ha modificado sustancialmente el curso de la infección por HIV, y la correcta adherencia al mismo resulta en una disminución de la carga viral a niveles indetectables, y a un incremento significativo en la repoblación de los linfocitos T periféricos. En este trabajo se evaluó en 28 niños HIV (+) la relación entre los cambios en los niveles de las poblaciones linfocitarias y la adherencia al TARV, luego de 9 meses en promedio de iniciado el mismo. El grupo de 18 niños con buena adherencia, superior al 95%, presentó un aumento significativo en los porcentajes de células naive CD4+CD45RA+CD62L+ y un descenso en las células de memoria central CD4+CD45RA-CD62L+, entre ambos momentos del seguimiento. Por el contrario, los 10 niños con fallas en la adherencia no mostraron diferencias significativas en los niveles de tales poblaciones. La buena adherencia al TARV produce el rápido y significativo descenso de la replicación viral lo cual se asocia a la progresiva reconstitución cuantitativa y funcional del sistema inmune.

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.

Relación entre adherencia al tratamiento antirretroviral y subpoblaciones linfocitarias en niños con HIV/Sida / Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/Aids

El curso de la infección por HIV se caracteriza principalmente por una depleción grave de los linfocitos TCD4+ y una activación inmune marcada, hallazgos centrales que conducen a variaciones numéricas y fenotípicas de las poblaciones linfocitarias TCD4+. El tratamiento antirretroviral (TARV) combinado ha modificado sustancialmente el curso de la infección por HIV, y la correcta adherencia al mismo resulta en una disminución de la carga viral a niveles indetectables, y a un incremento significativo en la repoblación de los linfocitos T periféricos. En este trabajo se evaluó en 28 niños HIV (+) la relación entre los cambios en los niveles de las poblaciones linfocitarias y la adherencia al TARV, luego de 9 meses en promedio de iniciado el mismo. El grupo de 18 niños con buena adherencia, superior al 95%, presentó un aumento significativo en los porcentajes de células naive CD4+CD45RA+CD62L+ y un descenso en las células de memoria central CD4+CD45RA-CD62L+, entre ambos momentos del seguimiento. Por el contrario, los 10 niños con fallas en la adherencia no mostraron diferencias significativas en los niveles de tales poblaciones. La buena adherencia al TARV produce el rápido y significativo descenso de la replicación viral lo cual se asocia a la progresiva reconstitución cuantitativa y funcional del sistema inmune.(AU)

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.(AU)

Relación entre adherencia al tratamiento antirretroviral y subpoblaciones linfocitarias en niños con HIV/ Sida. / [Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/AIDS].

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95

, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.

[Prevalence of thrombocytopenia in HIV infected children]. / Prevalencia de trombocitopenia en niños con HIV/sida.

Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of thrombocytopenia was evaluated in a cohort of HIV infected children analyzing the clinical features and the association with the immunological and virological status of the disease in a 14 year-follow-up period. Thrombocytopenia prevalence was of 8.5% (29 out 339 children evaluated). Chronic and acute thrombocytopenia was observed in 22 and 7 children respectively. The percentages of CD4+ T cells were variable and not related with the presence of thrombocytopenia. Thrombocytopenic patients showed viral load levels significantly increased; being the thrombocytopenia the initial clinical manifestation of HIV infection in 10 out 29 children. Mild chronic thrombocytopenia bleeding found in 23% of children evaluated was not correlated with the immunologic status of the disease. In contrast, the severity of acute thrombocytopenia depended on the evolution of associated clinical conditions. Constant viral activity and failure in the use of antiretroviral agents might induce the development of thrombocytopenia in HIV-infected children.

Prevalencia de trombocitopenia en niños con HIV/sida / Prevalence of thrombocytopenia in HIV infected children

La trombocitopenia es una de las múltiples alteraciones hematológicas presentes en pacientes infectados con el virus de la inmunodeficiencia humana (HIV). Puede ser de curso crónico, en la cual la destrucción inmune, el secuestro esplénico o el daño en la producción son los mecanismos primariamente involucrados, o aguda, acompañando a otra intercurrencia. En este trabajo se evaluó la prevalencia de trombocitopenia en un lapso de 14 años, en una población pediátrica con HIV/sida, analizando las características clínicas y la relación con el estado inmuno-virológico. La prevalencia de trombocitopenia fue de 8.5%, (29 de los 339 niños en seguimiento). En 22 fue de curso crónico y en 7 aguda. Los pacientes evaluados presentaron niveles porcentuales de TCD4+ variables y la presencia de trombocitopenia no estuvo en relación con el compromiso inmunitario. Los pacientes trombocitopénicos tuvieron niveles de carga viral significativamente mayores que los que no la presentaron. En 10 de los 29 niños con recuentos plaquetarios disminuidos, la trombocitopenia fue la manifestación inicial de la infección por HIV. Las manifestaciones hemorrágicas de las trombocitopenias crónicas fueron leves, presentes en el 23% de los niños y no se asociaron al deterioro inmunológico, mientras que en las agudas fueron más graves y condicionadas a la evolución de la enfermedad coexistente. El desarrollo de trombocitopenias se ve favorecido por la continua actividad viral y la falla en la implementación del tratamiento antirretroviral adecuado.

Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of thrombocytopenia was evaluated in a cohort of HIV infected children analyzing the clinical features and the association with the immunological and virological status of the disease in a 14 year-follow-up period. Thrombocytopenia prevalence was of 8.5% (29 out 339 children evaluated). Chronic and acute thrombocytopenia was observed in 22 and 7 children respectively. The percentages of CD4+ T cells were variable and not related with the presence of thrombocytopenia. Thrombocytopenic patients showed viral load levels significantly increased; being the thrombocytopenia the initial clinical manifestation of HIV infection in 10 out 29 children. Mild chronic thrombocytopenia bleeding found in 23% of children evaluated was not correlated with the immunologic status of the disease. In contrast, the severity of acute thrombocytopenia depended on the evolution of associated clinical conditions. Constant viral activity and failure in the use of antiretroviral agents might induce the development of thrombocytopenia in HIV-infected children.

[Intestinal cryptosporidiosis in HIV infected children]. / Criptosporidiosis intestinal en niños con HIV/Sida.

Cryptosporydium parvum is an intracellular parasite that infects gastrointestinal epithelium and produces diarrhea that is self-limited in immunocompetent persons but potentially life-threatening in immunocompromised, especially those with the acquired immunodeficiency syndrome (AIDS). C. parvum enteric infection's incidence in a pediatric HIV/AIDS cohort, during a 6 years period, was studied. Clinical and immunologic characteristics of the dual infection were also recorded. Highly active antiretroviral therapy (HAART) was started or continued by all the patients during follow-up. Azithromicyn was used as antiparasitic drug. Cryptosporidiosis incidence was 13.7%; 33 out 240 children showed chronic diarrhea lasting 14 days at least, or recurrent, without dehydration and electrolytic disturbance. Peripheral blood T CD4+ percentage levels of the patients were variable and without relationship with C. parvum presence. Viral load levels in 31 out 33 patients were over cut-off at the enteric episode time. Mild or moderate eosinophilia were recorded in 23% of the patients and other intestinal parasites were present in 11 children. When the number of enteric episodes were compared with the clinical and immunological patient's status, not significant differences were recorded. HAART is the best treatment to improve immune function in HIV patients avoiding potentially fatal complications that accompany acute diarrhea during concomitant infection with C. parvum.

Criptosporidiosis intestinal en niños con HIV/SIDA / Intestinal cryptosporidiosis in HIV infected children

El Cryptosporidium parvum, protozoo parásito intracelular, infecta el epitelio gastrointestinal produciendo diarrea autolimitada en individuos inmunocompetentes pero potencialmente grave en pacientes inmunocomprometidos, especialmente en aquellos con Sida. En este trabajo se evaluó, durante un lap-so de 6 años, la incidencia de infección intestinal por C. parvum en una población pediátrica con HIV/Sida analizando las características clínicas e inmunológicas de la coinfección. Todos los pacientes iniciaron o continuaron el tratamiento antirretroviral de alta eficacia HAART durante el período de estudio, mientras que la infección intestinal fue tratada con azitromicina. La incidencia de criptosporidiosis fue de 13.7%. 33 de los 240 niños en seguimiento presentaron diarrea crónica de más de 14 días de evolución o recurrente, sin complicaciones hidroelectrolíticas. Los pacientes evaluados presentaron niveles porcentuales variables de células T CD4+ en sangre periférica, y la presencia del parásito no estuvo en relación con el compromiso inmunitario. Al momento del cuadro entérico 31 de los 33 pacientes tuvieron niveles plasmáticos de carga viral que superaban el límite de detección. Se observó eosinofilia leve o moderada en el 23% de los pacientes y la coinfección con otros parásitos fue detectada en 11 niños. No se obtuvieron diferencias significativas al relacionar el número de episodios intestinales con los estadios clínico-inmunológicos de los pacientes. La correcta implementación del HAART con la subsecuente restauración de la función inmune se relacionaría con la ausencia de cuadros diarreicos agudos y de las complicaciones hidroelectrolíticas derivadas de la coinfección con C. parvum.

Cryptosporydium parvum is an intracellular parasite that infects gastrointestinal epithelium and produces diarrhea that is self-limited in immunocompetent persons but potentially life-threatening in immunocompromised, especially those with the acquired immunodeficiency syndrome (AIDS). C. parvum enteric infection's incidence in a pediatric HIV/AIDS cohort, during a 6 years period, was studied. Clinical and immunologic characteristics of the dual infection were also recorded. Highly active antiretroviral therapy (HAART) was started or continued by all the patients during follow-up. Azithromicyn was used as antiparasitic drug. Cryptosporidiosis incidence was 13.7%; 33 out 240 children showed chronic diarrhea lasting 14 days at least, or recurrent, without dehydration and electrolytic disturbance. Peripheral blood T CD4+ percentage levels of the patients were variable and without relationship with C. parvum presence. Viral load levels in 31 out 33 patients were over cut-off at the enteric episode time. Mild or moderate eosinophilia were recorded in 23% of the patients and other intestinal parasites were present in 11 children. When the number of enteric episodes were compared with the clinical and immunological patient's status, not significant differences were recorded. HAART is the best treatment to improve immune function in HIV patients avoiding potentially fatal complications that accompany acute diarrhea during concomitant infection with C. parvum.

[L-selectin expression on T lymphocytes and neutrophils in HIV infected children]. / Expresión de L-selectina en linfocitos T y neutrófilos de niños infectados con HIV.

The ability of leukocytes to leave the circulation and migrate into tissues is a critical feature of the immune response. L-selectin (CD62L), the leukocyte selectin, mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in lymphocyte, neutrophil and monocyte attachment to vascular endothelium at sites of inflammation. In this study L-selectin expression on peripheral T cells and neutrophils was evaluated in 25 HIV infected children, who had not received antiretroviral therapy, and 25 healthy controls. The expression level of L-selectin on T cells was also evaluated in 10 out 25 patients after 6 months of antiretroviral therapy. L-selectin expression on CD3+, CD4+ and CD8+ T cells were significantly lower in HIV infected children than in the control group. The percentage of neutrophils expressing CD62L was significantly reduced in patients with severe immunologic suppression. A positive correlation between the number of CD4+ T cells and the percentage of neutrophils CD62L+ was found. L-selectin expression on both CD4+ and CD8+ T cells did not significantly vary after 6 months of treatment. Altered leukocyte functions such as migration and homing resulting from reduced expression of CD62L may be an important contributor of the progressive dysfunction of the immune system in HIV infected children.

Expresión de L-selectina en linfocitos T y neutrófilos de niños infectados con HIV. / [L-selectin expression on T lymphocytes and neutrophils in HIV infected children]

The ability of leukocytes to leave the circulation and migrate into tissues is a critical feature of the immune response. L-selectin (CD62L), the leukocyte selectin, mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in lymphocyte, neutrophil and monocyte attachment to vascular endothelium at sites of inflammation. In this study L-selectin expression on peripheral T cells and neutrophils was evaluated in 25 HIV infected children, who had not received antiretroviral therapy, and 25 healthy controls. The expression level of L-selectin on T cells was also evaluated in 10 out 25 patients after 6 months of antiretroviral therapy. L-selectin expression on CD3+, CD4+ and CD8+ T cells were significantly lower in HIV infected children than in the control group. The percentage of neutrophils expressing CD62L was significantly reduced in patients with severe immunologic suppression. A positive correlation between the number of CD4+ T cells and the percentage of neutrophils CD62L+ was found. L-selectin expression on both CD4+ and CD8+ T cells did not significantly vary after 6 months of treatment. Altered leukocyte functions such as migration and homing resulting from reduced expression of CD62L may be an important contributor of the progressive dysfunction of the immune system in HIV infected children.

Comportamiento de la forma soluble de L-selectina en niños infectados con HIV / Behavior of soluble L-selectin in HIV infected children

La L-selectina es una molécula de adhesión responsable de la adhesión inicial de los leucocitos al endotelio. Esta molécula es liberada desde la superficie celular por clivaje proteolítico después de la activación leucocitaria. Se midieron los niveles séricos de la forma soluble de la L-selectina (sL-selectina) en 51 niños HIV(+) y en 15 controles sanos HIV(-). Estos valores se compararon con parámetros de activación inmune y de progresión de enfermedad. La concentración de sL-selectina se encontró significativamente aumentada en el grupo de pacientes HIV(+). Dichos niveles eran más altos en los pacientes con mayor inmunosupresión. Se encontró una correlación positiva entre los niveles de sL-selectina y el número relativo de LTCD8, y entre sL-selectina y los niveles de la forma soluble de la molécula de adhesión intercelular-1(sICAM-1) y la inmunoglobulina A(IgA). No se obtuvo correlación significativa entre sL-selectina y los valores de la carga viral (CV) plasmática. El aumento en los niveles de sL-selectina sería otro componente entre las múltiples alteraciones inmunológicas producidas por el HIV

Comportamiento de la forma soluble de L-selectina en niños infectados con HIV / Behavior of soluble L-selectin in HIV infected children

La L-selectina es una molécula de adhesión responsable de la adhesión inicial de los leucocitos al endotelio. Esta molécula es liberada desde la superficie celular por clivaje proteolítico después de la activación leucocitaria. Se midieron los niveles séricos de la forma soluble de la L-selectina (sL-selectina) en 51 niños HIV(+) y en 15 controles sanos HIV(-). Estos valores se compararon con parámetros de activación inmune y de progresión de enfermedad. La concentración de sL-selectina se encontró significativamente aumentada en el grupo de pacientes HIV(+). Dichos niveles eran más altos en los pacientes con mayor inmunosupresión. Se encontró una correlación positiva entre los niveles de sL-selectina y el número relativo de LTCD8, y entre sL-selectina y los niveles de la forma soluble de la molécula de adhesión intercelular-1(sICAM-1) y la inmunoglobulina A(IgA). No se obtuvo correlación significativa entre sL-selectina y los valores de la carga viral (CV) plasmática. El aumento en los niveles de sL-selectina sería otro componente entre las múltiples alteraciones inmunológicas producidas por el HIV

Comportamiento de parámetros eritrocitarios y del metabolismo del hierro en el VIH pediátrico / Erythrocyte parameters and iron metabolism changes in pediatric AIDS

Las anormalidades hematológicas están entre las manifestaciones más comunes de la infección por VIH, siendo las citopenias, especialmente la anemia, la más frecuente. El propósito de este estudio fue determinar el comportamiento de parámetros eritrocitarios y del metabolismo del hierro en el curso de la infección pediátrica por VIH. Fue evaluada la correlación de estos parámetros y el estado inmunológico de los pacientes a través de los valores relativos de LTCD4+. Se estudiaron 73 niños infectados por el VIH, 37 niños y 36 niñas, con edades comprendidas entre 7 meses y 8 años, y un grupo control de 30 niños sanos. La concentración media de hemoglobina en los distintos estadíos inmunológicos fue menor que en el grupo control (p<0,05), correlacionándose su descenso con los valores de LTCD4+ (r:0,26, p<0,05). El valor medio de hierro en los distintos estadíos inmunológicos fue menor que en el grupo control (p<0,05), disminuyendo en paralelo con los valores de LTCD4+ (r:0,36, p<0,05). Se encontró correlación negativa entre las concentraciones séricas de ferritina y los niveles de LTCD4+ (r:-45, p<0,01). Durante la infección pediátrica se establece una anemia progresiva. La estimulación crónica del sistema inmune y la liberación de citoquinas específicas, estarían asociadas con cambios en el metabolismo del hierro y el desarrollo de anemia