A infecção por Mycobacterium tuberculosis e micobactérias nãotuberculosas na infância: um desafio diagnóst / Childhood Mycobacterium tuberculosis and nontuberculous mycobacter: a challenge on the diagnosis

Objetivos: Avaliar a tuberculose e micobaterioses na infância por meio de uma revisão bibliográfica criteriosae crítica, com ênfase na epidemiologia, aspectos clínicos e ferramentas diagnósticas. Métodos: A pesquisa foirealizada nas bases de dados Lilacs, SciELO, PubMed, durante o período de 2000 a 2009. Quarenta e seis artigos foram considerados e onze diretrizes e manuais nacionais e internacionais. Os descritores utilizados foram: criança, infância, tuberculose, micobactérias atípicas, biologia molecular e diagnóstico. Resultados: As crianças portadoras da infecção pelo Mycobacterium tuberculosis são consideradas por diversos autorescomo “órfãos da tuberculose”. Várias características dificultam o estabelecimento do diagnóstico definitivoda tuberculose e micobacterioses na infância, entre elas as clínicas com lesões não extensivas, o caráterpaucibacilar, as formas latentes, a dificuldade de coleta de espécimes clínicos, as falhas das técnicas dabaciloscopia e cultura e a prática rotineira dos países em desenvolvimento de investigar a etiologia tuberculosa após falência terapêutica para patógenos habituais. Conclusões: A detecção da micobactéria permanece como confirmação diagnóstica e a oportunidade de investigação do perfil de sensibilidade, favorecendo o tratamento efetivo para qualquer faixa etária independente de seu papel na transmissão da doença. Nesse cenário, assumem maior importância, novas estratégias diagnósticas, entre elas as técnicas de biologia molecular com a promessa de melhor sensibilidade, especificidade e pronta detecção.

Objectives: To evaluate the tuberculosis and mycobacteriosis in childhood by a careful and critical literature review, with emphasis on epidemiology, clinical features and diagnostic devices. Methods: The study wasmade based on the following databases: LILACS, SciELO and PubMed, between the period of 2000 to 2009. Forty-six papers and eleven national and international guidelines/manuals were considered. The keywords used were: child, childhood, tuberculosis, atypical mycobacteria, molecular biology and diagnosis. Results: Children infected by Mycobacterium tuberculosis were considered by several authors as “orphans of tuberculosis”. To define final diagnosis of tuberculosis and mycobacterial infections is difficult in childhood because of several characteristics such as: the clinical with nonextensive lesions, the paucibacillary nature, the latent forms, the difficulty of collecting clinical specimens, the failures of the smear and culture techniques and routine practice of developing countries to investigate the etiology of tuberculosis after therapeutical failures for usual pathogens. Conclusions: The detection of mycobacteria remains usual to confirm the diagnosis and the opportunity to investigate the sensitivity profile. This promotes effective treatment for all age groups independent of their role in the disease transmission. In this environment, new diagnostic strategies including the interferon-gamma dosage and the molecular biology techniques can provide better sensitivity, specificity and ready detection.

Calicivirus and Giardia lamblia are associated with diarrhea in human immunodeficiency virus-seropositive patients from southeast Brazil.

To study enteropathogens, 100 fecal samples were collected from a Brazilian human immunodeficiency virus (HIV)-seropositive population, with or without diarrhea. Giardia lamblia and calicivirus were significantly associated with diarrhea as were severe immunosuppression and the presence of at least one enteropathogen. No sample was positive for rotavirus and only one asymptomatic individual carried the astrovirus. We concluded that there is a great diversity of pathogens and opportunistic infections in the studied population, with a high prevalence of mixed colonization/infection. Our findings pave the way for future molecular studies related to the expression of virulence factors and to the possibility of pathogen-pathogen interactions, especially between G. lamblia and calicivirus. These findings are relevant to the improvement of therapies and controlling diarrhea in the HIV-seropositive population.

CFTR molecular analysis reveals infrequent allele frequencies in nine cystic fibrosis patients from São Paulo State, Brazil.

Although cystic fibrosis (CF) is the most common autosomal recessive disorder in whites, it is thought to be relatively rare or, alternatively, underdiagnosed in Latin America. In Brazil, different groups have shown a DF508 mutation frequency ranging from 30.7% to 50.8%. Such variation may be explained by the ethnic differences observed in this country, which is genetically very heterogeneous. We describe the molecular analysis for 32 mutations of the CFTR gene in nine unrelated patients with cystic fibrosis from São Paulo State, Brazil. The main observation of this study was the absence of 30 out of the 32 mutations in 12 alleles among these patients. Except for mutations DF508 and N1303K, no other mutation could be detected in any of the studied patients. In one of two alleles, a DF508 mutation was detected in four patients (22% of the total sample) and an N1303K mutation was detected in two patients (11% of the total sample). One patient was a compound heterozygote for DF508/N1303K. Although the sample studied here was small, it may be possible that our patients have infrequent alleles once these can occur at higher frequencies in selected populations and also show relevant regional differences. Additional investigations in a larger sample are currently in progress in our laboratory to confirm our results, and further studies are still needed to determine the frequencies of CF gene mutations in different regions and ethnic groups in the Brazilian population.

Polymorphisms in the DNA repair gene XRCC1 and susceptibility to alcoholic liver cirrhosis in older Southeastern Brazilians.

The population of Southeastern Brazil has a very high mortality rate from liver cirrhosis, a disease that is considered an irreversible pre-malignant condition. This is largely due to the high prevalence of alcohol abuse in the region. Chronic alcohol consumption is associated with the production of free radical intermediates that can cause several DNA lesions. Reduced repair of these DNA lesions would, therefore, constitute a significant risk factor for liver cirrhosis and subsequent cancer. Recently, a number of polymorphisms in several DNA repair genes have been discovered, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate susceptibility to the disease. In this study, we tested the hypothesis that polymorphisms in the DNA repair gene XRCC1 are associated with increased risk of liver cirrhosis in Southeastern Brazilians. We conducted a pilot case-control study of 97 liver cirrhosis cases and 96 controls (matched for age, sex, and ethnicity) to investigate the role of two allelic variants coding for amino acid changes in the XRCC1 gene (the Arg194Trp and the Arg399Gln polymorphisms). Overall, we observed a 1.8-fold increase in the relative risk of liver cirrhosis associated with the 399Gln allele (either the heterozygous Arg/Gln or the homozygous Gln/Gln genotypes). The adjusted odds ratio (OR) was 1.82 (95% confidence limit (CL) 1.10-3.30). The relative risk appears to be highest among the Mestiso ethnic group (OR 2.60, 95% CL 0.92-7.34). There was a significant association between the 399Gln polymorphism and the risk of liver cirrhosis in older individuals over the age of 45 years (OR 2.70 (95% CL 1.14-6.48) compared to an OR of 1.24 (95% CL 0.55-2.78) for those under 45 years of age. No association was observed between the XRCC1 194Trp polymorphism and risk of liver cirrhosis. These preliminary results suggest that the XRCC1 399Gln polymorphism may be a significant risk modifier for alcoholic liver cirrhosis and justifies additional studies in that direction.