RESUMO
Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.
RESUMO
Single skin lesion, paucibacillary (SSL-PB) leprosy is considered an early diseasemanifestation. This study evaluated the clinical outcome of a cohort of 259 newlydiagnosed SSL-PB treated with one dose of rifampicin, ofloxacin, minocycline (ROM)and followed-up for three-years. Patients were recruited from the North, Central Westand Southeast regions in Brazil (1997-2001). The result expected with ROM therapywas disappearance or the reduction of lesion size. Manifestations that required additional intervention were considered as poor clinical outcome: type-1 reaction (T1R) with orwithout neuritis, neuritis alone, increase in lesion size and shift from paucibacillary tomultibacillary. The incidence of poor clinical outcome was calculated by personmonthand with the Kaplan-Meier methods. 61.8% of the participants were females,mean age 32.2, and 67.2% had borderline tuberculoid (BT) or tuberculoid forms. T1Rwas the predominant event; shift from paucibacillary to multibacillary was rare. 92.0%of the volunteers shown no events during the first year, the same occurring to 80.6%of them after 3 years of clinical monitoring. The probability of remaining event-freewas highest among those 40 years old or younger. Poor outcome predominated amongBT patients. Extended monitoring of SSL-PB leprosy cases under minimal therapyprovided valuable case management information for reference centers.
Lesão única paucibacilar (SSL-PB) é considerada manifestação clínica inicial dahanseníase. Este estudo avaliou resultado clínico de coorte de 259 pacientes SSL-PBrecém-diagnosticados, tratados com esquema de dose única Rifampicina, Ofloxacina,Minociclina (ROM) e acompanhados por 3 anos (1997-2001) nas regiões Norte,Centro-Oeste e Sudeste. O resultado esperado do tratamento ROM compreendedesaparecimento ou diminuição da lesão. O desfecho foi definido como qualquerevento clínico com indicação de terapia adicional: reação tipo 1 (T1R) com ou semneurite, neurite, aumento de tamanho de lesão e mudança de paucibacilar paramultibacilar. Estas manifestações foram consideradas eventos clínicos desfavoráveis,calculados por densidade de incidência (pessoa-tempo) e por Kaplan-Meier. 61,8%dos participantes eram mulheres (32,2 média idade), 67,2% borderline-tuberculoide(BT) e tuberculoide. T1R foi o desfecho predominante; mudança de paucibacilar paramultibacilar foi rara. 92,0% não apresentaram eventos desfavoráveis no primeiro anoe 80,6% ao final de três anos de monitoramento clínico. Participantes com idade d?40 anos tiveram maior probabilidade de permanecerem sem evento e evolução clínicadesfavorável predominou entre pacientes BT. Monitoramento prolongado de hanseníaselesão-única PB tratados com esquema mínimo forneceu dados importantes sobremanejo clínico para os centros de referência.
RESUMO
Single skin lesion, paucibacillary (SSL PB) leprosy is considered an early disease manifestation. This study evaluated the clinical outcome of a cohort of 259 newly diagnosed SSL PB treated with one dose of rifampicin, ofloxacin, minocycline (ROM) and followed up three years. Patients were recruited from the North, Central West and Southeast regions in Brazil (1997-2001). The result expected with ROM therapy was disappearance or the reduction of lesion size. Manifestations that required additional intervention were considered as poor clinical outcome: type 1 reaction (T1R) with or without neuritis, neuritis alone, increase in lesion size and shift from paucibacillary to multibacillary. The incidence of poor clinical outcome was calculated by person month and with the Kaplan Meier methods. 61,8 percent of the participants were females, mean age 32.2 and 67,2 percent had borderline tuberculoid (BT) or tuberculoid forms. TIR was the predominant event; shift from paucibacillary to multibacillary was rare. 92 percent of the volunteers shown no events during the first year, the same occurring to 80,6 percent of them after 3 years of clinical monitoring. The probability of remaining event free was highest among those 40 years old or younger. Poor outcome predominated among BT patients. Extended monitoring of SSL PB leprosy cases under minimal therapy provided valuable case management information for reference centers.
Assuntos
Hanseníase/terapia , Brasil , Estudos de CoortesRESUMO
Single skin lesion, paucibacillary (SSL-PB) leprosy is considered and early disease manifesation. This study the clinical outcome of a cohort of 259 newly diagnosed SSL-PB treated with one dose of rifampicin, ofloxacin, minocycline (ROM) and followed-up for three-years. Patients were recruited from the North, Central West and Southeast regions in Brazil (1997-2001). The result expected with ROM therapy was disappearance or the reduction of lesion size. Manifestation that required additional intervention were considered as poor clinical outcome: type-1 reaction (T1R) with or without neuritis alone, increase in lesion size and shift from paucibacillary to multibacillary. The incidence of poor clinical outcome was calculated by person-month and with the Kaplan-Meier methods. 61.8% of the participants were females, mean age 32.2, and 67,2% had borderline tuberculoid (BT) or tuberculoid forms. T1R was the predominant event; shift from paucibacillary to multibacillaru was rare. 92.0% of the volunteers shown no events during the first year, the same occurring to 80.6% of them after 3 years of clinical monitoring. The probability of remaining event-free was highest among those 40 years old or younger. Poor outcome predominated among BT patients. Extended monitoring of SSL-PB leprosy cases under minimal therapy provided valuable case management information for reference centers.
Assuntos
Dose Única/métodos , Hanseníase/epidemiologia , Hanseníase/fisiopatologia , Hanseníase/imunologia , Saúde Pública/métodosRESUMO
Leprosy affects skin and peripheral nerves, and acute inflammatory type 1 reactions (reversal reaction) can cause neurologic impairment and disabilities. Single skin lesion paucibacillary leprosy volunteers (N = 135) recruited in three Brazilian endemic regions, treated with single-dose rifampin, ofloxacin, and minocycline (ROM), were monitored for 3 years. Poor outcome was defined as type 1 reactions with or without neuritis. IgM anti-phenolic glycolipid I, histopathology, Mitsuda test, and Mycobacterium leprae DNA polymerase chain reaction (ML-PCR) were performed at baseline. chi(2) test, Kaplan-Meir curves, and Cox proportional hazards were applied. The majority of volunteers were adults with a mean age of 30.5 +/- 15.4 years; 44.4% were ML-PCR positive. During follow-up, 14.8% of the patients had a poor clinical outcome, classified as a type 1 reaction. Older age (> or = 40 years), ML-PCR positivity, and lesion size > 5 cm were associated with increased risk. In multivariate analysis, age (> or = 40 years) and ML-PCR positivity remained baseline predictors of type 1 reaction among monolesion leprosy patients.
Assuntos
DNA Bacteriano/isolamento & purificação , Eritema Nodoso/epidemiologia , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Minociclina/uso terapêutico , Mycobacterium leprae/isolamento & purificação , Ofloxacino/uso terapêutico , Rifampina/uso terapêutico , Adolescente , Adulto , Envelhecimento , Estudos de Coortes , Eritema Nodoso/sangue , Eritema Nodoso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Fatores de TempoRESUMO
This paper aims to describe the histomorphologic features of skin biopsies of single lesion leprosy patients recruited at outpatient clinics in four Brazilian states in the Northeast (Amazonas and Rondonia), Southeast (Rio de Janeiro) and Center-West (Goiás) between October 1997 and December 1998. Patients clinically diagnosed as single skin lesion paucibacillary (SSL-PB) leprosy had a standard 4-mm punch biopsy taken from the lesion before rifampin, ofloxacin, minocycline (ROM) therapy. The features of the cellular inflammatory infiltrates, the presence of nerve involvement and acid-fast bacilli (AFB) were used to categorize SSL-PB biopsies into different histopathological groups. Two-hundred-seventy-eight (93.0%) out of 299 patients had a skin biopsy available. Seven single lesion patients were diagnosed as BL or LL leprosy types (MB) by the histopathological exams and 12 cases were excluded due to other skin diseases. Therefore, 259 patients had skin lesions with histomorphological features compatible with PB leprosy categorized as follows: 33.6% (N = 87) of the biopsies represented well-circumscribed epithelioid cell granuloma (Group 1); 21.6% (N = 56) less-circumscribed epithelioid cell granuloma (Group 2); 12.0% (N = 31) were described as mononuclear inflammatory infiltrate permeated with epithelioid cells (Group 3), and 29.7% (N = 77) had perivascular/periadnexal mononuclear inflammatory infiltrate (Group 4). Minimal/no morphological alteration in the skin was detected in only 8 (3.1%) SSL-PB patients categorized as Group 5, who were considered to have leprosy by clinical parameters. SSL-PB leprosy patients recruited in a multicentric study presented histomorphology readings comprising the whole PB leprosy spectrum but also a few MB cases. These results indicate heterogeneity among SSL-PB patients, with a predominance of well-circumscribed and less-circumscribed epithelioid cell granulomas (Groups 1 and 2) in the sites studied and the heterogeneity of local cellular immune response.