Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil.

INTRODUCTION AND OBJECTIVE: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. MATERIAL AND METHODS: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. RESULTS: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p<0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1-18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5-12.7; p 0.005) significantly increased the risk of hepatotoxicity. CONCLUSION: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis.

Neonatal BCG vaccine and response to the tuberculin test in BCG vaccinated children in contact with tuberculosis patients in Recife, Brazil.

This case-control study analyses the association between the tuberculin response and the neonatal BCG vaccine in 330 children under 15 who are home contacts of tuberculosis patients, taking into account risk factors for the transmission of infection. Interviews were conducted with 330 children, their parents or legal guardians. Chest X-rays were taken and the tuberculin test (TT) applied using 0.1 ml of PPD RT23, taking an induration reading of > or = 10 mm as the cut-off point for a positive test result. Prior BCG vaccination was ascertained by observing the presence of a scar on the deltoid region of the right arm. Six children were excluded because they had signs/symptoms of pulmonary tuberculosis, thereby reducing the final sample to 324 children. The multivariate analysis showed that being exposed to a patient with pulmonary lesions with cavities (OR = 3.14; CI: 1.59-6.20; p = 0.000), a positive sputum smear (OR = 3.65; CI: 1.52-8.78; p = 0.002) or a positive culture (OR = 4.42; CI: 1.39-14.1; p = 0.005), being under five (OR = 0.47; CI: 0.22-0.99; p = 0.045) are independently associated with a positive TT. The fact that a prior BCG scar is not associated with a positive response to the TT indicates the need to re-open discussion of the guidelines which exist in many poor countries where tuberculosis is still a serious public health problem. Such guidelines include those issued by the Brazilian Ministry of Health, which considers the child under 15 in contact with a tuberculosis case to be infected only if there is a TT of 10 mm or more and the child received no prior BCG vaccination.

Evaluation of PCR for diagnosis of American cutaneous leishmaniasis in an area of endemicity in northeastern Brazil.

PCR-based approaches targeting kinetoplast DNA were evaluated for the diagnosis of American cutaneous leishmaniasis (ACL) in regions of endemicity in northeastern Brazil. A total of 119 cutaneous biopsy specimens from patients with ACL and nonleishmaniasis cutaneous lesions were studied. Two PCR-based systems were used; one was specific for the subgenus Viannia, and the other was specific for the genus Leishmania. The PCR specific for the subgenus Viannia had a sensitivity of 95.4%, whereas the genus-specific PCR detected the target DNA in 88.2% of the samples tested. The specificities of the assays, determined with samples from a group with nonleishmaniasis cutaneous lesions, was 100%. The results of the conventional tests indicate that the sensitivities of the PCR-based methods were significantly higher than those of smear examination, histological staining, and isolation by culture (P < 0.05). Antibodies specific for Leishmania braziliensis were detected by indirect immunofluorescence in 82.9% of the patients tested. Parasites were isolated from 40 of 86 patients (46.5%). Sixty-seven percent of dermal scrapings and 66.2% of stained tissue sections were positive by microscopy. Amplified products from the subgenus-specific PCR hybridized with the Leishmania panamensis minicircle, confirming infection consistent with L. braziliensis. The evidence available at present incriminates L. braziliensis as the only causative agent of ACL in the state of Pernambuco in Brazil.