Heterogeneous persistence of Mycobacterium leprae in oral and nasal mucosa of multibacillary patients during multidrug therapy.

BACKGROUND: Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can, however, result in treatment failure and the emergence of drug-resistant strains. OBJECTIVES: Describe the impact of MDT over Mycobacterium leprae viability in patient's oral and nasal mucosa along treatment. METHODS: Mycobacterium leprae viability was monitored by quantitative polymerase chain reaction (qPCR) quantification of 16S rRNA in lateral and contralateral scrapings of oral and nasal mucosa of 10 multibacillary patients along the initial five months of treatment. FINDINGS: The results demonstrated high heterogenicity of M. leprae viability among patients and between nasal and oral samples. Of six patients who presented good adherence and tolerance to the treatment, only four displayed absence of M. leprae viability in both samples three months after the first MDT dose, while for the other two, the absence of M. leprae viability in the oral and nasal cavities was only detected five months after the first dose. MAIN CONCLUSIONS: We concluded that qPCR of 16S rRNA for the determination of M. leprae viability in nasal and oral scraping samples could represent an interesting approach to monitor treatment efficacy.

Heterogeneous persistence of Mycobacterium leprae in oral and nasal mucosa of multibacillary patients during multidrug therapy

BACKGROUND Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can, however, result in treatment failure and the emergence of drug-resistant strains. OBJECTIVES Describe the impact of MDT over Mycobacterium leprae viability in patient's oral and nasal mucosa along treatment. METHODS Mycobacterium leprae viability was monitored by quantitative polymerase chain reaction (qPCR) quantification of 16S rRNA in lateral and contralateral scrapings of oral and nasal mucosa of 10 multibacillary patients along the initial five months of treatment. FINDINGS The results demonstrated high heterogenicity of M. leprae viability among patients and between nasal and oral samples. Of six patients who presented good adherence and tolerance to the treatment, only four displayed absence of M. leprae viability in both samples three months after the first MDT dose, while for the other two, the absence of M. leprae viability in the oral and nasal cavities was only detected five months after the first dose. MAIN CONCLUSIONS We concluded that qPCR of 16S rRNA for the determination of M. leprae viability in nasal and oral scraping samples could represent an interesting approach to monitor treatment efficacy.

Avaliação dos fenótipos de acetilação e hidroxilação predominantes nas populações de cinco macrorregiões do Brasil baseada no genoma: possível influência da farmacogenética na conduta terapêutica da hanseníase / Evaluation of acetylation and hydroxylation phenotypes predominant in the populationsof five geographical regions of Brazil based on the genome: possible influence ofpharmacogenetics in the therapeutic management of leprosy

A hanseníase é uma doença infecciosa crônica, com alto poder incapacitante. O tratamento sebaseia na combinação de três drogas: dapsona, rifampicina e clofazimina, porém, a ocorrênciade reações adversas (ADRs) induzidas principalmente pela dapsona (~70%) é frequentementeobservada. Dentre as ADRs destacam-se: a metemoglobinemia, anemia hemolítica, a hepatitee a síndrome da dapsona. A metabolização da dapsona é baseada em reações enzimáticas deacetilação e hidroxilação, catalisadas, pelas enzimas N-acetiltransferase2 (NAT2) ehidroxilases do citocromo P450 (CYPs). Dentre os vários fatores associados à ocorrência deADRs, o fator genético é primordial. Polimorfismos presentes em genes que codificam paraenzimas metabolizadoras de drogas podem representar alto risco para este desfecho.Paralelamente, outro aspecto importante é a alta variabilidade genética ligada à etnia. O Brasilé um país composto por uma população altamente miscigenada com alta diversidade genética.Sendo a hanseníase uma doença endêmica tratada com um esquema padronizado para toda apopulação, a avaliação destes perfis genéticos é de fundamental relevância para a prevençãode ADRs. Este estudo teve como principal objetivo descrever a variabilidade dos genes NAT2,CYP2E1, CYP3A4 e CYP3A5 em coortes de pacientes de hanseníase provenientes das cincodiferentes macrorregiões do Brasil e realizar um estudo de associação, do tipo caso-controle,entre as variáveis genéticas presentes nesses genes com a ocorrência de reações adversas empacientes com hanseníase em tratamento com esquemas contendo dapsona. Um total de 964indivíduos foram incluidos no estudo descritivo de NAT2 enquanto para o estudo deassociação variou dependendo da região. Vinte e três SNPs de NAT2, foram identificadosnas populações estudadas, dos quais sete: 191 G>A; 282 C>T; 341T>C; 481 C>T; 590 G>A;803 A>G e 857 G>A, são os mais frequentes na população mundial...

Leprosy is a chronic infectious disease with high disabling potential. The treatment is basedon the combination of three drugs: dapsone, rifampicin and clofazimine, however, theoccurrence of adverse drug reactions (ADRs) mainly induced by dapsone (~70%) isfrequently observed with a predominance of methemoglobinemia, hemolytic anemia, hepatitisand dapsone syndrome. The dapsone metabolization is mediated by acetylation andhydroxylation enzymatic reactions catalyzed by the N-acetyltransferase 2 (NAT2) andcytochrome P450 (CYPs). Among the various factors associated with the occurrence ofADRs, the genetic factor is essential. Polymorphisms in genes encoding drug metabolizingenzymes may represent a high risk for this outcome. In paralell, another important aspect isthe high genetic variability related to ethnicity. Brazil is composed of a high mixed populationwith high levels of genetic diversity. Being leprosy is an endemic disease which treatment isa standard regimen for the entire population, the evaluation of these genetic profiles becamerelevant for prevention of ADRs. The main goals of this study was to describe the geneticvariability of NAT2, CYP2E1, CYP3A4 and CYP3A5 in cohorts of leprosy patients from fiveBrazilian geographical regions and to perform an association study (case-control) between thegenetic variants present in these genes and occurrence of ADRs in leprosy patients treatedwith dapsone-containing schemes. A total of 964 individuals were enrolled to the descriptivestudy for NAT2 while for the association study the sample size varied according to theregion.Twenty-three SNPs in NAT2, were identified in the study populatuion, seven of which191 G> A; 282 C> T; 341T> C; 481 C> T; 590 G> A; 803 A> G and 857 G>A are the mostfrequent in the world population...