Evaluation of the transcriptional immune biomarkers in peripheral blood from warao indigenous associate with the infection by mycobacterium tuberculosis

Abstract INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

Factores de riesgo para infección por VIH en indígenas de la etnia warao del Municipio Antonio Díaz, Estado Delta Amacuro, Venezuela. Octubre ­ diciembre 2015

Delta Amacuro asienta la mayor población indígena de la etnia Warao en comunidades de difícil acceso y limitadas condiciones de vida. En 2007, la Cruz Roja venezolana diagnosticó los primeros casos de infección por VIH en este estado; posteriormente, diversas publicaciones han reportado que la prevalencia de infección por VIH en comunidades de la etnia Warao es 10 veces mayor a la prevalencia mundial. El objetivo de la investigación fue evaluar factores de riesgo para infección por VIH en indígenas del municipio Antonio Díaz, Estado Delta Amacuro durante octubre ­ diciembre 2015. Los factores de riesgo fueron agrupados en: características socioeconómicas, estatus migratorio, hábitos psicobiológicos y conocimiento sobre la enfermedad. Se realizó un estudio analítico de tipo casos y controles. Se evaluaron 50 pacientes VIH positivo de 7 comunidades y 100 controles del mismo sexo, comunidad y edad. A todos se les realizó una entrevista directa. Se compararon los resultados utilizando pruebas Chi cuadrado y se determinaron los Odds Ratio. La inestabilidad en la pareja sexual, las prácticas de hombres que tienen sexo con hombres, las relaciones sexuales fortuitas y durante viajes, el inicio precoz de relaciones sexuales, el sexo oral, sexo anal y el no uso de métodos de barrera constituyeron factores de riesgo para infección por VIH en la población estudiada. El desconocimiento de la forma de trasmisión y prevención resultaron también estadísticamente significativos. La falta de conocimiento, movimientos migratorios frecuentes y las prácticas sexuales de riesgo pueden explicar la elevada prevalencia de infección por VIH en esta población.

In Delta Amacuro state is established the biggest Amerindian community belonging to the Warao ethnic. This people live in difficult access communities with precarious life conditions. In 2007 the Venezuelan Red Cross diagnosed the first HIV infection cases in the state. Later, many publications have reported HIV prevalence in Waraos communities ten times higher than worldwide prevalence. The main objective was to evaluate risk factors for HIV infection in Waraos Amerindians who live in Antonio Diaz municipality, Delta Amacuro state between October and December 2015. Risk factors were grouped in: socioeconomic conditions, migratory status, sexual and psychobiologic habits and disease knowledge. An analytic case-control study was conducted. Fifty HIV patients from seven communities and 100 controls were evaluated. The information from cases and controls was collected through a direct interview. The results were compared using chi square test, odds ratios were calculated. No stability in sexual partners, men who have sex with other men, casual sex, sex during trips, early sexual initiation, oral sex and anal sex and lacking in use of barrier contraceptive methods were risk factors for HIV infection in the study group. Lack of knowledge about transmission and prevention of the disease were also statistically significant risk factors. Lack of knowledge, frequent migratory movements and risk sexual behavior may explain the high prevalence of HIV infection in this population.

Concordance between IFNγ gene +874 A/T polymorphism and interferon-γ expression in a TB-endemic indigenous setting

Abstract INTRODUCTION: Interferon-γ (IFN-γ) plays a crucial role in resistance to mycobacterial diseases; accordingly, variants of the gene encoding this cytokine may be associated with elevated risk of contracting pulmonary tuberculosis (TB). METHODS: Blood samples were collected from 135 Warao indigenous individuals with newly diagnosed sputum culture-positive TB. Of these, 24 were diagnosed with active tuberculosis (ATB). The study comprised 111 participants, who were grouped as follows: 1) 14 tuberculin skin test (TST)-positive Warao indigenous individuals and 4 that were QuantiFERON-TB?Gold In-Tube (QFT-IT) test-positive, collectively comprising the latent TB infection group (LTBI), n = 18), and 2) healthy controls who were QFT-IT- and TST-negative, comprising the control group (CTRL, n = 93). Detection of the IFN γ gene (IFNG) +874A/T polymorphism was performed via PCR and quantification of IFNG expression via qPCR. RESULTS: Relative to indigenous and white Americans, ATB and CTRL groups had a higher frequency of the IFNG SNP (+874A): 23 (95.8%) and 108 (97.3%), respectively. Indigenous Warao individuals homozygous for the IFNG (+874) A allele exhibited 3.59-fold increased risk of developing TB (95% confidence interval, 2.60-4.96, p =0.0001). A decreased frequency of the AT genotype was observed in individuals with pulmonary TB (4.16%) and controls (0.90%). The frequency of the TT genotype was decreased among controls (1.80%); none of the patients with TB were found to have this genotype. The differences in IFNG expression between the groups, under unstimulated and stimulated conditions, were not statistically significant. CONCLUSIONS: Preliminary results demonstrate concordance between IFNG +874 A/A genotype and low expression of IFNG.

Seropositivity for ascariosis and toxocariosis nd cytokine expression among the indigenous people in the Venezuelan delta region / Seropositividad para ascariosis y toxocariosis y expresión de citocinas entre la población indígena de la región del delta Venezolano

The present study aimed at measuring seropositivities for infection by Ascaris suum and Toxocara canis using the excretory/secretory (E/S) antigens from Ascaris suum (AES) and Toxocara canis (TES) within an indigenous population. In addition, quantification of cytokine expressions in peripheral blood cells was determined. A total of 50 Warao indigenous were included; of which 43 were adults and seven children. In adults, 44.1% were seropositive for both parasites; whereas children had only seropositivity to one or the other helminth. For ascariosis, the percentage of AES seropositivity in adults and children was high; 23.3% and 57.1%, respectively. While that for toxocariosis, the percentage of TES seropositivity in adults and children was low; 9.3% and 14.3%, respectively. The percentage of seronegativity was comparable for AES and TES antigens in adults (27.9%) and children (28.6%). When positive sera were analyzed by Western blotting technique using AES antigens; three bands of 97.2, 193.6 and 200.2 kDas were mostly recognized. When the TES antigens were used, nine major bands were mostly identified; 47.4, 52.2, 84.9, 98.2, 119.1, 131.3, 175.6, 184.4 and 193.6 kDas. Stool examinations showed that Blastocystis hominis, Hymenolepis nana and Entamoeba coli were the most commonly observed intestinal parasites. Quantification of cytokines IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 and IL-4 expressions showed that there was only a significant increased expression of IL-4 in indigenous with TES seropositivity (p < 0.002). Ascaris and Toxocara seropositivity was prevalent among Warao indigenous.

El objetivo del presente estudio fue determinar la seropositividad de infección por Ascaris suum y Toxocara canis, utilizando antígenos de excreción/secreción (E/S) de Ascaris suum (AES) y Toxocara canis (TES) en una población indígena. Adicionalmente, se cuantificó la expresión de citocinas a partir de células de sangre periférica. Un total de 50 indígenas Warao se incluyeron en el estudio; 43 fueron adultos y 7 niños. Entre los adultos, 44,1% fueron seropositivos para ambos parásitos; mientras que los niños sólo mostraron seropositividad a uno u otro de los helmintos. Para ascariosis, el porcentaje de seropositividad para los antígenos AES fue alto tanto en adultos como en niños; 23,3% y 57,1%, respectivamente. Para toxocariosis, el porcentaje de seropositividad para los antígenos TES fue bajo en adultos así como en niños; 9,3% y 14,3%, respectivamente. El porcentaje de seronegatividad fue similar tanto para los antígenos AES como para TES en adultos (27,9%) y niños (28,6%). Cuando la seropositividad fue analizada a través de la técnica de Western blotting utilizando los antígenos AES; 3 bandas de 97,2, 193,6 y 200,2 kDas fueron principalmente reconocidas. Para los antígenos TES, 9 bandas fueron mayormente identificadas; 47,4, 52,2, 84,9, 98,2, 119,1, 131,3, 175,6, 184,4 y 193,6 kDas. Los análisis coproparasitológicos mostraron que los parásitos Blastocystis hominis, Hymenolepis nana y Entamoeba coli fueron los parásitos intestinales más comúnmente observados. La cuantificación de la expresión de las citocinas IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 e IL-4 mostró que hubo un significante incremento de la expresión de IL-4 entre los indígenas con seropositividad para los antígenos TES (p < 0.002). La seropositividad para Ascaris y Toxocara fue prevalente entre los indígenas Warao.

Evaluación del estado del Hierro y la Vitamina A en niños de la etnia Warao del estado Sucre, Venezuela / Assessing ofIronand Vitamin A status in children of Warao ethnic group of Sucre state in Venezuela

El propósito del estudio fue evaluar el estado del hierro y la vitamina A, en niños de la etnia Warao, perteneciente a las comunidades de María López y Los Barrancos, del estado Sucre. Se evaluó el consumo de alimentos,indicadores bioquímicos y antropométricos a 64 niños Warao en edades comprendidas entre los 3 y 10 años. Se encontró una adecuación deficiente del consumo de hierroen 56,8%,la mayoría provino defuentes no hem: cereales (37,8%), harina de maíz precocida fortificada (33,47%), harina de trigo (2,72%) y casabe (32,98%); el hierro hémico provino de pescados (37,49%). Se presentó déficit en la adecuación del consumo de la vitamina A en 97,3%, las fuentes fueron cereales (harina de maíz precocida), huevos y lácteos. El diagnóstico nutricional antropométrico por combinación de indicadores de dimensión corporal, arrojó que el 75,0% se encuentra en normalidad. Para los estudios bioquímicos: el 93,76% tiene deficiencia de retinol; 40,63% deficiencia severa. El 100% y 70,3% presentó niveles normales de hierro y ferritina sérica, respectivamente. La concentración de hemoglobina, reveló 70,3% de anemia. Existe prevalencia de 92,45% de parasitosis intestinal (Trichuristrichura, Ascarislumbricoides y Ancylostomideos). Se observaron diferencias estadísticamente significativas de niveles séricos de ferritina y asociaciones parasitarias. La alta prevalencia de anemia, deficiencia de vitamina A y parasitosis, indican la existencia de un déficit nutricional en cuanto al hierro y la vitamina A, que puede deberse a la baja disponibilidad de alimentos, el consumo insuficiente de nutrientes y un aprovechamiento biológico disminuido.

The purpose of this study was to assess the iron and vitamin A status in children of Warao ethnic group, belonging to communitiesMaríaLópez and Los Barrancos in Sucre State. We evaluated food intake, anthropometric and biochemical markers in 64 Warao children with ages between 3 and 10 years. A deficient consumption of iron was found in 56,8%, most from non-heme sources: cereals (37,8%), corn flour fortified (33,47%), wheat flour (2,72%) andcasabe (32,98%);heme iron came from fish(37,49%).In the intake of vitamin A the deficit was presented in97,3%,sources were cereals (corn flour fortified), eggs and dairy. The anthropometric-nutritional diagnosis by combination of body dimension indicators showed that 75.0% is in normality.For biochemical studies: 93.76% has retinol deficiency;40,63% severe deficiency. The 100% and 70.3% had normal levels of serum iron and ferritin, respectively. The hemoglobin concentration revealed 70.3% of anemia. There was a high prevalence (92,45%) of intestinal parasitosis (Trichuristrichura, Ascarislumbricoides y Ancylostomideos). There were statistically significant differences in serum ferritin and parasitic associations.The high prevalence of anemia, vitamin A deficiency and parasitosis,indicate the existence of nutritional deficit in iron and vitamin A,which may be due to the low availability of food, insufficient consumption of nutrients and biological utilization decreased.

Frecuencia de síndrome metabólico en indígenas de la etnia Warao de Barrancas del Orinoco, estado Monagas: Venezuela

Objetivo: Determinar la frecuencia de Síndrome Metabólico (SM) en indígenas de la etnia Warao de Barrancas del Orinoco, Estado Monagas. Marzo, 2011. Materiales y Métodos: Tipo de estudio descriptivo, observacional y de corte transversal. Universo de 140 personas, muestra de 61 personas, con edades comprendidas entre 30-69 años. Se determinaron datos de identificación, parámetros antropométricos, determinación del perfil lipídico y glicemia en ayunas. El diagnóstico de SM se realizó de acuerdo a los criterios del Adult Panel Treatment III (ATP III), Federación Internacional de Diabetes (IDF) y la Asociación Latinoamericana de Diabetes (ALAD). Resultados: El promedio de circunferencia abdominal fue de 91,02±11,50 cm (femenino 91,44±9,95 cm; masculino 90,48±13,39 cm). La frecuencia de obesidad abdominal fue de 54,1% según ALAD; 75,4% según IDF y 44,3% por ATP III. La frecuencia de HDL-c bajo fue de 67,21% (85,3% femenino y 44,4% masculino). El 29,51% tuvieron triglicéridos altos. La frecuencia de glicemia ≥ 100 mg/dL fue de 9,84% (14,7% en mujeres y 3,7% en hombres). El 49,2% tenían cifras tensionales ≥130/85 mm Hg (41,2% femenino y 59,3% masculino). El 32,79% presentaron criterios para SM según la ALAD, el 40,98% según la IDF y el 27,87% según la ATP III. Conclusión: Los indígenas de la etnia Warao de Barrancas del Orinoco, Estado Monagas, presentaron una alta frecuencia de síndrome metabólico.

Objective: To determine the frequency of metabolic syndrome (MS) in Warao Indians from the Barrancas del Orinoco, Monagas State, Venezuela. Materials and Methods: Cross sectional study, descriptive and observational. The population was 140 subjects and the sample was 61 subjects of both sexes with ages between 30-69 years. Identification data, anthropometric parameters, lipid profile and fasting glucose were determined. The diagnosis was made according to the criteria of the Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF) and the American Diabetes Association (ALAD). Data were analyzed using SPSS 19. Results: The average of the abdominal circumference was 91.02 ± 11.50 cm (91.44±9.95 cm in female, 90.48±13.39 cm in male). The frequency of abdominal obesity was 54.1% according ALAD; the 75.4% and 44.3% according to IDF and ATP III respectively. The frequency of low HDL-c was 67.21% (85.3% in female and 44.4% in male). The 29.51% had high triglycerides. The frequency of blood glucose ≥ 100 mg/dl was 9.84% (14.7% in female and 3.7% in men). The 49.2% had blood pressure ≥ 130/85 mm Hg (41.2% in female and 59.3% in male). The 32.79% showed criteria for MS according to ALAD, 40.98% according to the IDF and 27.87% according to ATP III. Conclusion: The Warao Indians of the Orinoco Barrancas, Monagas State, presented a high frequency of metabolic syndrome.

Bacterias patógenas aisladas en la nasofaringe de niños indígenas warao: Estado Sucre,Venezuela / Pathogenic bacteria isolated from the nasopharynx of indigenous Warao children: Sucre state, Venezuela

Para determinar la frecuencia de bacterias patógenas y su susceptibilidad antimicrobiana en muestras nasofaringeas de niños indígenas waraos de la comunidad María López, municipio Benítez del estado Sucre, con edades comprendidas entre 0 y 10 años, se procesaron 49 muestras recolectadas durante el período enero-marzo de 2008. La identificación bacteriana se realizó aplicando estudios bacteriológicos convencionales y la susceptibilidad antimicrobiana mediante el método de difusión en disco, siguiendo lineamientos del Instituto de Estándares de Laboratorios Clínicos (CLSI). Los resultados indicaron la presencia de Moraxella catarrhalis (28,6%), Streptococcus pneumoniae (26,5%), Staphylococcus aureus (14,3%) y Haemophilus influenzae (6,1%) en niños con y sin sintomatología. Las bacterias patógenas aisladas del tracto respiratorio superior fueron más frecuentes en el grupo de 0 a 5 años de edad, identificándose, principalmente, S. pneumoniae. Con respecto a la susceptibilidad antimicrobiana, S. pneumoniae mostró resistencia a tetraciclina (46,2%), trimetoprim-sulfametoxazol (38,5%), clindamicina (33,3%) y penicilina (23,1%). Los aislados de S. aureus expresaron sensibilidad a todos los antimicrobianos ensayados. El total de aislados de M. catarrhalis mostró resistencia a ampicilina y penicilina, además, resultaron productores de β-lactamasas. La presencia de bacterias patógenas a nivel nasofaríngeo en la población infantil, representa un riesgo para el desarrollo de infecciones severas del tracto respiratorio.

We collected and `processed 49 nasopharynx samples taken from indigenous Warao children 0-10 years old who lived at the María Lopez community of the Benitez Municipalit at Sucre State, with the purpose of determining the frequency of pathogenic bacteria and their antimicrobial sensitivity in samples collected from these children during the January-March 2008 period. The bacterial identification was obtained by applying conventional bacteriological methods and the antimicrobial sensitivity was determined by the disc diffusion method, following the guidelines of the Clinical Laboratory Standards Institute. The results showed presence of Moraxella catarrhalis (28.6%), Streptococcus pneumoniae (26.5%), Staphylococcus aureus (14.3%) and Haemophilus influenza (6.1%) in children with and without symptoms. The pathogenic bacteria isolated from the upper respiratory tract were more frequent in the 0-5 year old group and the most frequent identification was S. pneumoniae. Regarding antimicrobial sensitivity, S. pneumoniae was resistant to tetracycline (46.2%), trimetoprim-sulphametoxazol (38.5%), clindamicyn (33.3%) and penicillin (23.1%). The S. aureus isolates were sensitive to all the antimicrobials studied. All the M. catarrhalis isolates were resistant to ampicillin and penicillin and were also β-lactamase producers. The presence of pathogenic bacteria at the nasopharynx level in child populations signifies a risk for the development of severe respiratory tract infections.

Lactancia materna: [revisión] / Breast feeding: [review]

La leche materna constituye el alimento natural ideal para los recién nacidos y lactantes. Sus características nutricionales permiten el crecimiento armónico del niño y la prevención de la morbi-mortalidad infantil, especialmente por enfermedades diarreicas. Los diferentes tipos de leche que se producen en la glándula mamaria (pre-calostro, calostro, leche de transición, leche de pretérmino, y madura), se adaptan a los requerimientos del niño en el tiempo, permitiendo que los elementos constitutivos (grasas carbohidratos, proteínas y enzimas) se absorban y digieran fácilmente, favoreciendo la formación de un sistema inmunitario eficiente. La leche materna contiene componentes que conforman su función protectora contra virus, bacterias y parásitos. Factores Constitutivos: Quelantes: Lactoferrina, Proteína fijadora de Vitamina B12 (Haptocorrina), Proteína fijadora de Acido Fólico; Enzimas: Lactoperoxidasa, Lizosima con efecto bactericida y bacteriostático. Factores anti-infecciosos: Factor Bífido (N-acetilglucosamina), Factor de crecimiento epidérmico; Factor estimulante de fibroblastos; Gangliósidos y Oligosacáridos, Lactadherina, Factor de resistencia antiestafilococo. Factores Inducidos: son inducidos por antígenos presentes en el tubo digestivo y en el árbol bronquial: macrófagos, linfocitos T y B; Inmunoglobulinas A, G, M, K-caseína que inhibe la adherencia de Helicobacter Pylori. Varios estudios indican que algunos factores de la leche humana inducen una maduración más rápida del sistema inmunológico en relación a niños alimentados artificialmente. Se recomienda que el niño alimentado al pecho no suspenda la lactancia si presenta algún trastorno diarreico; por el contrario, debe aumentar el número de mamadas para garantizar una adecuada ingesta calórica y de nutrientes. Esto se ha demostrado en estudios que reportan menor incidencia de enfermedad diarreica en lactantes alimentados con lactancia materna.

Breast milk is the ideal food for infants from birth. Its nutritional features allow an armonic child development and the prevention of morbidity and mortality in infants, especially from diarrheal illness. The different types of milk produced by the mammary glands (pre-calostral, calostral, transitional, pre-term milk, and mature), adapt to the child’s requirements, changing its composition, energy content, volume and density. This facilitates absorption of fats, carbohydrates, proteins, and enzymes, and builds an efficient immune system to grant optimal child health. Breast milk has huge amounts of immunological components which contribute to the protective function against virus, bacteria, and parasites: Constituent factors: 1.-Binders: Lactoferin, binding proteins for vitamin B12 (Haptocorin) and Folic Acid. 2.-Enzymes: Lactoperoxidase and Lisozims, with bactericide and bacteriostatic effects. Anti-infection factors: Bífidus Factor (N-Acetil-glucosamine), Epidermal Development Factor, gangliosides and oligosaccharides, Lactadherin and Anti-staphylococcal factor. Induced Factors: The anti-infective activity is specific for each woman; these factors are induced by antigens in the digestive system and respiratory tract: macrophages, T and B lymphocytes, A, G, M immunoglobulins. Also K-casein, related with anti-adhesive action of Helicobacter Pylori. Human milk induces the maturation of the child’s immune system earlier than formula. It is recommended not to withhold breastfeeding in infants affected by diarrhea. On the contrary, the number and duration of feedings should be increased to guarantee an adequate nutritional and caloric intake. Clinical trials which compare the morbidity in infants according with the feeding pattern show a lower incidence of diarrhea in breast fed children.

Comparison of serological responses in two different populations with pulmonary tuberculosis

Observational studies on the humoural immune responses of the Warao indigenous people from Delta Amacuro, an isolated area, were compared with urban residents of the Venezuelan capital. Mycobacterium tuberculosis-specific reactivities (IgM, IgE, sIgA, IgG and IgG subclasses) were measured by ELISA using PPD and 38-kDa M. tuberculosis antigens. A total of 294 individuals were studied, 162 Warao (indigenous people) and 132 Creole (non-indigenous people). The patient group consisted of 87 Warao patients and 58 Creole patients, while the control group consisted of 75 Warao controls and 74 Creole controls. Combinations among the isotypes studied were performed. The findings showed that for the Warao people, sensitivity to the combination including anti-PPD IgG and IgE was 92.0 percent, while for the Creole people, sensitivity to the combination including anti-PPD IgG but more so anti-PPD IgG1 and IgG2 was 90.0 percent. Simple tests were able to show higher specificities, which were population-specific; specificities were anti-PPD IgG3, 100.0 percent and anti-PPD IgM, 97.4 percent for the Warao and Creole peoples, respectively. In conclusion, while simple tests reached high specificity, the multi-isotype tests improved sensitivity; the latter shows this approach may be useful in diagnostic testing.

Estudio de la respuesta inmunitaria en niños Warao de comunidades con alta prevalencia de tuberculosis.

Resumen. En una población de niños Warao menores de 15 años con una tasa de prevalencia de tuberculosis (TBC) de 3190/100.000 se planteó como objetivo, estudiar ciertos parámetros de la respuesta inmunitaria en una población de 107 niños, de éstos, 32 presentaban TBC (27 PPD positivos y 5 PPD negativos) y 75 eran controles sin clínica de TBC (45 PPD positivos y 30 PPD negativos). Se evaluaron la inmunidad humoral, celular y algunos aspectos de la inmunidad innata. Entre los niños pacientes y controles, no se encontraron diferencias significativas en los componentes C3 y C4 del complemento. En cuanto a la inmunidad humoral, el grupo de pacientes presentó un alto porcentaje de niños con niveles totales de IgA e IgG elevados (13,8% y 79,3%, respectivamente) en comparación con los niños controles (0% y 69,2%). En el grupo control, un alto porcentaje de niños presentaron niveles totales de IgM e IgAs elevados (69,2% y 56,16%, respectivamente) en comparación con los pacientes (48,3% y 31,25%). El 100% de los niños presentó altos niveles séricos de IgE. Los estudios de la respuesta celular retardada mostraron que los niños de mayor edad presentaron las mayores medidas de induraciones. Los niños menores de 7 años presentaron similar reactividad positiva al PPD independientemente de la presencia o no de cicatriz de BCG. Un alto porcentaje de niños sin y con cicatriz (46,8% y 27,6% respectivamente) presentaron medidas de induraciones a la tuberculina de 0 mm. La reactividad a Candida mostró un 80% de niños con estados de anergia no específica. Sin embargo, el mayor porcentaje de niños con TBC estaba vacunado y presentaba positividad a la prueba de tuberculina. En conclusión, en los niños Warao se observó un aumento en los niveles de los componentes C3 y C4 del complemento y una hipergammaglobulinemia. Los resultados de los isotipos mostraron que, la disminución de IgAs podría ser un marcador de enfermedad activa, mientras que el aumento de IgM un marcador de infección reciente. La policlonalidad fue independiente de la reactividad al PPD.

Abstract. The present study was carried out in a Warao childhood population with extremely high tuberculosis (TB) rate of 3190/100,000 in 0-15 years old children. One hundred seven serum and saliva samples were tested, 32 from patients with active TB (27 positive and 5 negative for the tuberculin skin test, TST) and 75 apparently healthy contact children (45 positive and 30 negative for the TST). The innate, immunoglobulin and cellular responses were studied. The results showed that both, patients and controls, had a high percentage of children with increased levels of complement C3 and C4 components. A high percentage of children with increased total serum IgA and IgG (13.8% and 79.3% respectively) was observed in children with TB in comparison to control children (0% and 69.2%). A high percentage of control children had increased levels of IgM and sIgA (69.2% and 56.16%, respectively) in comparison to patients (48.3% and 31.25%). Both groups showed children with increased levels of IgE. The results concerning to the cellular immune response to PPD and the BCG vaccination status showed that there was a correlation between an increase in PPD reactivity and age. The PPD reactivity in children less than 7 years old was similar and also independent of the BCG vaccination status. A significant number of children without or with scars (46.8% and 27.6%, respectively) showed induration values of 0 mm to tuberculin skin test. The Candida reactivity showed a high percentage of children (80%) with anergy status. In conclusion, an increase in the levels of complement components C3 and C4 and hypergammaglobulinemia was observed in Warao children, and these results were independent from PPD reactivity and BCG vaccination. The isotype results showed that the decrease in sIgA could be and active disease marker, while the increase in IgM levels could represent a marker of recent disease.