Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

First report of acute Chagas disease by vector transmission in Rio de Janeiro State, Brazil / Primeiro relato de doença de Chagas aguda por transmissão vetorial no Estado do Rio de Janeiro, Brasil

SUMMARYChagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro.

RESUMOA doença de Chagas é antropozoonose endêmica na América Latina que tem como principal mecanismo de transmissão humana o contato da pele lesada ou da mucosa com as fezes de triatomíneos infectados por Trypanosoma cruzi. Neste artigo descrevemos o primeiro caso de doença de Chagas aguda adquirida no Estado do Rio de Janeiro por transmissão vetorial com confirmação parasitológica, sorológica e pela PCR. O paciente apresentou miocardite aguda e derrame pericárdico de evolução benigna. Juntamente com as manifestações sistêmicas da fase aguda, foi notada pápula eritematosa de três cm de diâmetro compatível com chagoma em punho esquerdo. Este relato de caso chama a atenção para a possibilidade de transmissão da doença de Chagas por vetores nativos não domiciliados e em áreas consideradas indenes. Portanto, a doença de Chagas aguda deve ser incluída entre os diagnósticos diferenciais de doenças febris e miopericardites agudas no Rio de Janeiro.