RESUMO
Some anti-mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life-threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE-PEOPLE trial evaluating the safety of bedaquiline-enhanced post-exposure prophylaxis (bedaquiline and rifampicin, BE-PEP, versus rifampicin, SDR-PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post-exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L-ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L-ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (p < 0.001), with a strong correlation (r = 0.793). The mean absolute QTc difference between both modalities was 11 ± 10 ms. Mean manual and automated 12L-ECG QTc were 394 ± 19 and 409 ± 19 ms, respectively (n = 636; p < 0.001), corresponding to moderate agreement (r = 0.655). The use of a mECG device for QT interval monitoring was feasible and yielded a median absolute QTc error of 8 ms. Automated QTc measurements were less accurate, yielding longer QTc intervals.
Assuntos
Diarilquinolinas , Eletrocardiografia , Estudos de Viabilidade , Hanseníase , Rifampina , Humanos , Diarilquinolinas/administração & dosagem , Diarilquinolinas/efeitos adversos , Masculino , Adulto , Feminino , Hanseníase/tratamento farmacológico , Hanseníase/diagnóstico , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Pessoa de Meia-Idade , Hansenostáticos/efeitos adversos , Hansenostáticos/administração & dosagem , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Adulto Jovem , Quimioterapia Combinada/métodosRESUMO
BACKGROUND: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007â2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. OBJECTIVES: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. METHODS: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. RESULTS: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. CONCLUSIONS: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.
Assuntos
Clofazimina , Dapsona , Quimioterapia Combinada , Hansenostáticos , Recidiva , Rifampina , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Brasil , Estudos de Casos e Controles , Clofazimina/uso terapêutico , Clofazimina/administração & dosagem , Dapsona/uso terapêutico , Dapsona/administração & dosagem , Hansenostáticos/uso terapêutico , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Hanseníase Multibacilar/tratamento farmacológico , Rifampina/uso terapêutico , Rifampina/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP. METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed. FINDINGS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109â436 individuals, of whom 95â762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline. INTERPRETATION: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. FUNDING: European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Assuntos
Hansenostáticos , Hanseníase , Profilaxia Pós-Exposição , Rifampina , Humanos , Hanseníase/prevenção & controle , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Masculino , Feminino , Adulto , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Hansenostáticos/uso terapêutico , Hansenostáticos/administração & dosagem , Profilaxia Pós-Exposição/métodos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Madagáscar/epidemiologia , Criança , Análise por Conglomerados , Incidência , Mycobacterium lepraeAssuntos
Clofazimina , Humanos , Clofazimina/efeitos adversos , Clofazimina/administração & dosagem , Feminino , Pigmentação da Pele/efeitos dos fármacos , Masculino , Hiperpigmentação/induzido quimicamente , Hansenostáticos/efeitos adversos , Hansenostáticos/administração & dosagem , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).
Assuntos
Hansenostáticos , Hanseníase , Mycobacterium leprae , Rifampina , Humanos , Incidência , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , Rifampina/administração & dosagem , Rifampina/análogos & derivados , Hansenostáticos/administração & dosagem , Hansenostáticos/uso terapêutico , Características da FamíliaRESUMO
INTRODUCTION: One of the biggest drug disasters in history has not prevented thalidomide from being used to treat various clinical conditions. Currently, Brazil has a worrying scenario: high consumption of the drug and, cases of pregnant women using thalidomide, even after adopting restrictive legislation. AREAS COVERED: This review of the literature and legislation sought to comparatively analyze the monitoring of thalidomide use in Brazil and other countries that use this drug. Finally, we discuss the differences between the countries. EXPERT OPINION: This analysis allows us to think beyond the safe use of thalidomide, but the safety provided by any type of monitoring system. It seems that out-patients that use unsafe drugs are exposed to some degree of risk. To improve safety, more extensive improvements are needed than monitoring systems related to the use of thalidomide. Its safe use depends on a drastic reduction in the incidence of leprosy and Erythema Nodosum Leprosum in the world; investment in research and development of safe and effective therapeutic alternatives to thalidomide; improvement of health systems and their health surveillance systems, particularly in primary health care; awareness of health professionals and patients for greater responsibility in the use of medicines, especially thalidomide.
Assuntos
Monitoramento de Medicamentos/métodos , Hansenostáticos/administração & dosagem , Talidomida/administração & dosagem , Brasil , Eritema Nodoso/tratamento farmacológico , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Hanseníase Virchowiana/tratamento farmacológico , Gravidez , Talidomida/efeitos adversosRESUMO
The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.
Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.
Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Aldeídos , Antioxidantes , Carga Bacteriana , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae , Estresse Oxidativo , Carbonilação Proteica , Pele/metabolismo , Pele/patologiaAssuntos
Inseticidas/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase Virchowiana/diagnóstico , Mycobacterium leprae/efeitos dos fármacos , Sarcoptes scabiei/efeitos dos fármacos , Escabiose/diagnóstico , Adulto , Animais , Clofazimina/administração & dosagem , Humanos , Ivermectina/administração & dosagem , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Masculino , Doenças Negligenciadas , Permetrina/administração & dosagem , Rifampina/administração & dosagem , Escabiose/tratamento farmacológico , Escabiose/parasitologia , Escabiose/patologia , Pele/microbiologia , Pele/parasitologia , Pele/patologia , Medicina TropicalRESUMO
Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.
Assuntos
Dapsona/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Antígeno HLA-B13/genética , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Adolescente , Adulto , Alelos , Biomarcadores , Estudos de Casos e Controles , Clofazimina/administração & dosagem , Dapsona/administração & dosagem , Hipersensibilidade a Drogas/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Indonésia , Hansenostáticos/administração & dosagem , Modelos Logísticos , Masculino , Rifampina/administração & dosagem , Medição de Risco , Síndrome , Adulto JovemRESUMO
BACKGROUND: The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations. RESEARCH DESIGN AND METHODS: From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies. RESULTS: Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively). CONCLUSIONS: Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.
Assuntos
Dapsona/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Antígeno HLA-B13/genética , Hansenostáticos/efeitos adversos , Adulto , Idoso , Povo Asiático/genética , Criança , Dapsona/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/genética , Feminino , Genótipo , Humanos , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Sistema de Registros , República da Coreia , Fatores de RiscoRESUMO
INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.
Assuntos
Interações Medicamentosas , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Polimedicação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Hansenostáticos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients, and has been associated with resistance to antimicrobial agents such as atovaquone. Given the rising incidence of babesiosis in the United States, novel drugs are urgently needed. In the current study, we tested whether clofazimine (CFZ), an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti. METHODS: Mice with severe combined immunodeficiency were infected with 107B. microti-infected erythrocytes. Parasites were detected by means of microscopic examination of Giemsa-stained blood smears or nested polymerase chain reaction. CFZ was administered orally. RESULTS: Uninterrupted monotherapy with CFZ curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by days 10 and 50 of therapy, respectively. A 7-day administration of CFZ delayed the rise of parasitemia by 22 days. This rise was caused by B. microti isolates that did not carry mutations in the cytochrome b gene. Accordingly, a 14-day administration of CFZ was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites. CONCLUSIONS: Clofazimine is effective against B. microti infection in the immunocompromised host. Additional preclinical studies are required to identify the minimal dose and dosage of CFZ for babesiosis.
Assuntos
Babesia microti/efeitos dos fármacos , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Clofazimina/uso terapêutico , Hospedeiro Imunocomprometido , Hansenostáticos/uso terapêutico , Sequência de Aminoácidos , Animais , Babesia microti/genética , Babesia microti/imunologia , Babesiose/imunologia , Clofazimina/administração & dosagem , Clofazimina/efeitos adversos , Citocromos b/química , Citocromos b/genética , DNA de Protozoário , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Resistência a Medicamentos , Eritrócitos/parasitologia , Hansenostáticos/administração & dosagem , Hansenostáticos/efeitos adversos , Camundongos , Parasitemia/parasitologia , Resultado do TratamentoRESUMO
With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."
Assuntos
Imunoterapia/métodos , Hansenostáticos/administração & dosagem , Hanseníase/prevenção & controle , Hanseníase/transmissão , Ensaios Clínicos como Assunto/métodos , Quimioterapia Combinada , Humanos , Imunoterapia/tendências , Hanseníase/epidemiologia , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/isolamento & purificaçãoRESUMO
BACKGROUND: Dapsone has been the mainstay for the treatment of leprosy since its discovery in the 1940s. However, hematological disturbances are not uncommon in leprosy patients on daily dapsone therapy. Hence, the present study was conducted to document the hematologic alterations observed in lepromatous leprosy patients treated with Dapsone 100 mg daily. METHODOLOGY: A cross-sectional observational study was conducted amongst 32 lepromatous leprosy patients treated with Dapsone 100 mg daily. A complete hemogram was conducted for all the study recruits. The test results were compared against the standard average values for adults for the given variables. The one sample t-test was employed to compare the difference between the study values and the standard normal values for adults. The statistical significance was considered at p < 0.05. RESULTS: The study reveals a marked decrease in hemoglobin concentration in patients on dapsone, 100 mg daily. Other hematological alterations found were reduced platelet count, reduced mean platelet volume, reduced Hematocrit, reduced Mean Corpuscular hemoglobin, reduced Mean Corpuscular hemoglobin concentration. (p < 0.05). CONCLUSION: Treatment of lepromatous leprosy with 100 mg daily Dapsone therapy may lead to hematological alterations. These findings are suggestive of dapsone-induced hemolysis.