VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile

OBJECTIVE: To evaluate the influence of ApaI, BsmI and TaqI polymorphisms of the VDR gene and HLA-DQB1* alleles in type 1 diabetic children and to assess their possible relationship with circulating levels of 25-hydroxyvitamin D(3), auto-antibodies, and INFgamma/TGFbeta1 cytokines levels in Chilean cases and controls. METHODS: DNA and serum samples from 216 newly diagnosed type 1 diabetic and 203 unrelated control children were evaluated for IA-2 and GAD(65) auto-antibodies, 25-hydroxyvitamin D(3) levels, HLA-DQB1* alleles, and VDR gene polymorphisms. RESULTS: The frequency of the b allele and the bb genotype in type 1 diabetic patients was significantly lower compared with the control group (0.635 versus 0.749, p<0.01 and 0.370 versus 0.567, p<0.04). 25-Hydroxyvitamin D(3) levels showed no differences between type 1 diabetic and healthy children. In cases, 25-hydroxyvitamin D(3) levels were not associated with a special auto-antibodies profile according to the presence or absence of GAD(65)(+) or IA-2(+). The haplotype combination BAT was higher in cases (0.062 versus 0.019, p<0.0022) and bAT was more frequent in controls (0.266 versus 0.180, p<0.003). In cases, the aaBbTT genotype showed the most significant increase in TGFbeta1 level across the VDR categories. Finally, when considering the HLA class II risk genotype (DQB1*0302) and the VDR genotypes (AabbTT and aabbTT), higher levels of GAD(65), IA-2 and TGFbeta1 were observed among diabetic children. CONCLUSION: We found an association between a VDR polymorphism (BsmI) and type 1 diabetes. An association was found of AabbTT and aabbTT genotypes and the HLA-DQB1*0302 allele with high levels of GAD(65), IA-2 and TGFbeta1.     

Molecular epidemiology of Haemophilus influenzae within families in Santiago, Chile

Thirty-six consecutive patients with invasive Haemophilus influenzae type b (Hib) infections at Roberto del Rio Children's Hospital, Santiago, Chile, were enrolled in a prospective study. Throat cultures were obtained from household contacts of each index case, adjacent neighbors, and matched community control households. Colonization rates for H. influenzae were comparable among groups; however, among household contacts 18% of colonizing isolates were Hib, compared with 2% and 3% among neighbor and community controls. When selected isolates were evaluated further by outer membrane protein (OMP) profiles and multilocus enzyme electrophoresis, only one of the four Hib isolates from household members matched the corresponding index case isolate. One serologically nontypeable isolate from a household contact had an OMP profile and electrophoretic type identical to that of the corresponding Hib index case isolate; hybridization studies with a 9-kb capsular gene probe showed a profile consistent with a capsule-deficient mutant. Hib strains were isolated more frequently from household contacts than from control persons living in Santiago, but colonizing Hib strains were often unrelated to the index case strain.     

Prevalence of malignant tumors at autopsy in chilean children from Santiago,with particular reference to leukaemia

Summary An investigation on the prevalence of cancer at autopsy in children from the city of Santiago was made. Autopsies were performed from 1945–1966. Of the 6431 autopsy cases, 142 (2.21%) showed cancer. Leukaemia (50.70%), intracraneal and other neural tumours (25.35%), and malignant lymphomas (14.08%) were the most frequent groups of childhood cancer. Leukaemia accounted for 1.12% of all autopsies, and showed a corrected male: female ratio of 10.61. Acute leukaemia accounted for 42.95% of tumour cases.

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Häufigkeit von maligen Tumoren bei Autopsien von chilenischen Kindern aus Santiago mit besonderer Berücksichtigung von Leukämie

Zusammenfassung Von 6431 Autopsien, die an Kindern von 1945–1966 durchgeführt wurden, zeigten 142 (2,21%) bösartige Tumoren, unter denen Leukämie (50,70%), intrakraniale und andere neurogene Tumoren (25,35%) sowie maligne Lymphome (14,08%) die häufigsten waren. Leukämien fanden sich in 1,12% aller Autopsien und wiesen ein Verhältnis von 10,61 zu Gunsten der Männer auf. Akute Leukämien machten 42,95% aller malignen Tumoren der Kinder aus.

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This investigation was supported in part by an American Cancer Society Institutional Research Grant to the University of Tennessee.     

Prevalence of intrahepatic cholestasis of pregnancy in Chile

The prevalence of intrahepatic cholestasis of pregnancy was studied immediately postpartum in 869 women from three distant Chilean cities differing in climate and food supply. Cholestatic jaundice of pregnancy was detected in 2.4% and pruritus gravidarum in 13.2%, without significant differences between the three cities. Every woman was then ethnically classified as predominantly Caucasoid, Araucanian Indian, or Aimara Indian. A significantly higher prevalence of cholestatic jaundice of pregnancy (5.5%) and pruritus gravidarum (22.1%) was found in Araucanians than in Caucasoids (2.5% and 12.6% respectively) or in the Aimaras (0 and 11.8% respectively). The prevalence of intrahepatic cholestasis of pregnancy in Araucanians increased directly with the degree of "ethnic purity." Recurrence of the disease in multiparous women was also greater in Araucanians (13.8%) than in Caucasoids (5.5%) or in the Aimaras (3.9%). We propose that an ethnic predisposition to develop intrahepatic cholestasis of pregnancy is present in Araucanian women and that the high prevalence of the disease in Chile is mainly influenced by ethnic admixture with this South American Indian (ethnic) group.     

Typhoid fever in Santiago, Chile: a study of household contacts of pediatric patients

We obtained clinical, epidemiological, and laboratory data (including three stool cultures) from 155 (96%) of 161 household contacts of 24 patients less than 16 years old with culture-confirmed typhoid fever; these 24 patients represented approximately 40% of such patients seen in three hospitals in Santiago during a 12-week period. A chronic typhoid carrier was identified in only one household, with concurrent or secondary cases seen in two other households. When index cases were matched with household members nearest in age, no specific risk factors for illness could be identified. There was evidence of generalized exposure to enteric pathogens within these households, with nine persons from seven different households culture-positive for non-typhoidal Salmonella, and nine, from eight different households, culture-positive for Shigella; transmission of these pathogens within households did not appear to be common since no household had more than one family member with the same serotype or species of either pathogen.     

Congenital Chagas disease of second generation in Santiago, Chile. Report of two cases

Congenital Chagas disease (CChD) has been reported in different countries, mostly in Latin America. In 1987 a fatal case of CChD of second generation (CChDSG) was published. Within a period of six months--1989-1990--two cases of CChDSG were diagnosed and studied in the city of Santiago. Two premature newborns, sons of two sisters, with moderate liver and spleen enlargement, were found to have positive serology for Chagas disease and xenodiagnoses. The mothers, urban residents all their lives, without antecedents of triatomine bugs contact or blood transfusions, showed positive serology and xenodiagnoses. Their mother (grandmother of the infants), lived 20 years in a Northern rural Chagas disease endemic locality, in a triatomine infested house. Afterwards, she moved to Santiago, where she married and has resided up to now. Serology and xenodiagnoses were also positive. All the Trypanosoma cruzi infected individuals were successfully treated with nifurtimox.     

Search of amantadine-resistance in influenza A strains isolated in Santiago, Chile, 2001-2002

Amantadine has been used for prevention and treatment of influenza A infection. It blocks the proton through the M2 ion channel. Drug-resistant viruses appear quickly when this therapy is used. Single amino acids changes in the H2 protein can confer resistance, being the most frequent one in position 31. Different methods to detect resistant strains have been described. The objectives were to determine the existence of amantadine resistance of influenza A strains isolated in a virologic laboratory in Santiago, Chile, between 2001-2002, and to validate a new molecular method to detect resistant strains. A PCR restriction fragment length polymorphism analysis was employed for the detection of resistant viruses. In 31 processed strains no mutation in the position 31 was found. This result supports that amantadine resistance is very low or absent in Chile. This could be explained by a limited use of this drug in the study population. This method could be used as a monitoring system to survey resistant viruses.     

Age-specific prevalence of antibodies to hepatitis A in Santiago,Chile: risk factors and shift in age of infection among children and young adults

Transition from high to lower endemicity of hepatitis A virus (HAV) infection may portend increased public health burden with the shift of infection to older ages and increasing morbidity and mortality. This report describes age-specific prevalence of antibodies to HAV (anti-HAV) among children and young adults in Santiago, Chile, compared with previous prevalence data and assesses factors predictive for anti-HAV. In 1998, a serosurvey was performed in Metropolitan Santiago, designed to enroll a representative, age-stratified population on the basis of area of residence. A total of 784 individuals (age range, 1-24 years) were enrolled. Anti-HAV prevalence by year of life was as follows: ages 1 to 4, 12.5%; 5 to 9, 26.2%; 10 to 14, 43.4%; 15 to 19, 57.4%; 20 to 24, 73.9%. Adjusting for age, factors associated (inversely) with anti-HAV included residential areas of higher socioeconomic status (SES), parental education, and household characteristics of potable water, municipal sewage system, and the presence of a toilet or refrigerator in the house. In logistic regression analysis, only maternal years of education and residence in areas of higher SES remained independently associated with anti-HAV. Excluding those from higher SES areas, comparison of the age-specific anti-HAV prevalence data from previous studies of similar methodology in areas of lower SES revealed consistent decreases across all age groups; the age-standardized prevalence for this age range (1-24 years) dropped from 53.7% in 1990 to 40.6% in 1998. In light of the growing pool of susceptible individuals at older ages, with HAV continuing to circulate in the communities, evaluation of the feasibility of vaccination programs would be judicious.     

Efficient diagnosis of giardiasis among nursery and primary school children in Santiago, Chile by capture ELISA for the detection of fecal Giardia antigens

Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary school in the city of Santiago, Chile. Microscopy of formol-ether concentrates showed that 33% of the children were infected with Giardia lamblia. Prevalences among primary school students (5-10 years of age) of G. lamblia (38%), Endolimax nana (43%), and Entamoeba coli (25%) were overall higher than among nursery school students (3 months-5 years of age; prevalences 29%, 21%, and 16%, respectively). There was no apparent association between socio-economic intake and levels of G. lamblia infection: the private nursery school had the highest recorded level of infection (40%). One hundred sixty-two triplicate stool specimens were used to compare microscopy with an enzyme-linked immunosorbent assay (ELISA) for the detection of Giardia fecal antigens. The ELISA was highly sensitive and specific either visually (95% and 97%, respectively) or by optical density determination (99% and 96%, respectively). Incorporation of non-immune rabbit immunoglobulin-coated control wells did not enhance sensitivity and specificity. The antigen detection ELISA is an extremely effective tool for the epidemiological investigation of giardiasis.     

Case-control study of the efficacy of BCG immunization against pulmonary tuberculosis in young adults in Santiago, Chile.

We performed a case-control study of the efficacy of BCG immunization against pulmonary tuberculosis in 15- to 35-year-old Chilean patients born during a period when BCG coverage was incomplete. Our aims were to determine BCG efficacy against pulmonary tuberculosis in young adults, to determine if repeated BCG immunization increased its protective effect, and to determine factors that could explain the failure of BCG immunization in patients with tuberculosis. We studied 68 patients who had pulmonary tuberculosis based on positive AFB in at least 1 of 2 sputum smears, a positive confirmatory culture and compatible chest roentgenogram abnormalities. The control group were 188 individuals without pulmonary tuberculosis seeking medical care for other ailments. The percentage of non-immunized individuals was 13.2 among patients with tuberculosis and 12.2 among controls. The vaccine efficacy calculated from these data was 10%. There was no difference in the percentage of individuals with 1, 2 and 3 BCG scars between tuberculosis patients and controls. The number and percent of individuals exposed to tuberculosis among BCG-immunized and non-immunized tuberculosis patients and controls were similar. No significant differences between BCG-immunized and non-immunized individuals were detected in tuberculosis patients or in the control group. However, tuberculosis patients as a group had significantly lower weight, education level, employment rate and family income than controls. These observations suggest that the development of pulmonary tuberculosis in BCG-immunized young adults is favored by the presence of genetic and/or acquired predisposing factors capable of overriding protective immunity induced by BCG vaccination.     

Clustering of cases of type 1 diabetes in high socioeconomic communes in Santiago de Chile: spatio-temporal and geographical analysis

The objective of this study was to describe spatial and space–time patterns of type 1 diabetes in children less than 15 years old, diagnosed between 2000 and 2005 with residence in the Metropolitan Region of Chile. Knox and Mantel tests were used to detect space–time interaction between cases. An ecological Bayesian model adjusted by socioeconomic factor and year was proposed to estimate the incidence by communes. Initially, there was no space–time interaction between cases, but there is evidence of clustering effect in urban areas of the region. The incidence rate for the overall study period was estimated by 6.18/100,000 (95% CI: 5.69–6.70), with a significant annual trend of 8.2% (P < 0.01). The geographical incidence could be explained by the human development index, as a socioeconomic factor. These results suggest that children living in communes with higher socioeconomic levels may be at higher risk of developing type 1 diabetes. Our findings support the hypothesis of an aetiological role of environmental factors in the onset of type 1 diabetes.