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1.
Acta Trop ; 224: 106138, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34562427

RESUMO

Post-exposure prophylaxis (PEP) with single-dose rifampicin (SDR) reduces the risk of developing leprosy among contacts of leprosy patients. Most evidence for the feasibility of the intervention is from highly endemic settings while low-endemic areas present unique challenges including reduced awareness of the disease among the population and in the health system, and the only sporadic occurrence of cases which together make defining any type of routine process challenging. We complemented the retrospective active case finding (RACF) approach with SDR administration to eligible contacts, and piloted the intervention across 31 operational districts in Cambodia. The aim was to demonstrate the feasibility of improving early case detection and administering SDR in a low endemic setting. The intervention focused on leprosy patients diagnosed since 2011 and was implemented between October 2016 - September 2019. The "drives" approach was employed to trace contacts: a trained team systematically contacted all eligible cases in a district, traced and screened contacts, and administered SDR. A total of 555 index patients were traced by the drive team, and 10,410 contacts in their household and 5 immediate neighbor houses listed. Among these contacts, 72.0% could be screened while most others were absent on the screening day. A total of 33 new leprosy cases were diagnosed and 6189 contacts received SDR (82.6% of the screened contacts). Sixty-one contacts refused SDR administration. We conclude that integrating PEP with SDR in RACF campaigns is feasible, and that this approach is appropriate in low resource and low endemic settings. Over time, evidence on whether or not the approach reduced leprosy transmission in Cambodia, may become clear.


Assuntos
Hanseníase , Rifampina , Camboja/epidemiologia , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Profilaxia Pós-Exposição , Estudos Retrospectivos
2.
J Pharm Biomed Anal ; 203: 114205, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34130010

RESUMO

Upon emergence of nitrosamines in various drugs, e.g in valsartan, metformin and ranitidine, 4-methyl-1-nitrosopiperazine (MeNP) was found in rifampicin in August 2020. Rifampicin is used, amongst others, for post-exposure prophylaxis of leprosy. The occurrence of MeNP can be explained by the synthesis, because 1-amino-4-methylpiperazine is concomitantly used with the organic oxidizing reagent isoamyl nitrite. According to a method reported by the FDA, the quantification of MeNP in rifampicin capsules was performed by LC-MS/HRMS. A significant contamination with MeNP was found in all samples, ranging from 0.7 to 5.1 ppm and exceeding the acceptable intake limit proposed by the FDA up to 32-fold. However, the severity of a possible leprosy infection outweighs the risks, which are concomitant with the intake of a single dose of rifampicin for post-exposure prophylaxis. Nevertheless, the extent of contamination is alarming, and countermeasures are needed to minimize public health risks. The presence of nitrosamines in rifampicin illustrates the need for better strategies in impurity profiling and compendial testing once again.


Assuntos
Nitrosaminas , Rifampina , Cápsulas , Cromatografia Líquida , Espectrometria de Massas em Tandem
3.
PLoS Negl Trop Dis ; 15(5): e0009382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939710

RESUMO

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Adulto Jovem
8.
AAPS PharmSciTech ; 22(3): 116, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763801

RESUMO

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol (PG), tween 20, polyethylene glycol-400 (PEG400), oleic acid (OA), N-methyl-2-pyrrolidone (NMP), cremophor-EL (CEL), ethyl oleate (EO), methanol, and glycerol] followed by computational validations and in-silico prediction using GastroPlus. The experimental solubility was conducted over temperature ranges T = 298.2-318.2 K) and fixed pressure (p = 0.1 MPa) followed by validation employing computational models (Apelblat, and van't Hoff). Moreover, the HSPiP solubility software provided the Hansen solubility parameters. At T = 318.2K, the estimated maximum solubility (in term of mole fraction) values of the drug were in order of NMP (11.9 × 10-2) ˃ methanol (6.8 × 10-2) ˃ PEG400 (4.8 × 10-2) ˃ tween 20 (3.4 × 10-2). The drug dissolution was endothermic process and entropy driven as evident from "apparent thermodynamic analysis". The activity coefficients confirmed facilitated RIF-NMP interactions for increased solubility among them. Eventually, GastroPlus predicted the impact of critical input parameters on major pharmacokinetics responses after sub-Q delivery as compared to oral delivery. Thus, NMP may be the best solvent for sub-Q delivery of RIF to treat skin tuberculosis (local and systemic) and cutaneous related disease at explored concentration.


Assuntos
Antibióticos Antituberculose/farmacocinética , Simulação por Computador , Sistemas de Liberação de Medicamentos/métodos , Rifampina/farmacocinética , Termodinâmica , Antibióticos Antituberculose/administração & dosagem , Previsões , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética , Reprodutibilidade dos Testes , Rifampina/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Solubilidade , Absorção Subcutânea
9.
Arq. ciências saúde UNIPAR ; 25(1): 79-85, jan-abr. 2021.
Artigo em Português | LILACS | ID: biblio-1151426

RESUMO

Introdução: O diagnóstico da hanseníase possui números significativos que causam preocupação à saúde pública. Os casos de resistência medicamentosa nessa doença se iniciaram em meados dos anos 60 e diante do problema, a Organização Mundial da Saúde instituiu em 1981 a poliquimioterapia, associação dos antibióticos rifampicina, dapsona e clofazimina, tratamento atual de escolha. A resistência aos fármacos na hanseníase é reportada pela literatura, desvelando um obstáculo à sua eliminação. Apresentamos nessa revisão os principais aspectos da resistência medicamentosa no tratamento para hanseníase e seus impactos. Metodologia: Revisão sistemática sobre os aspectos da resistência medicamentosa utilizando a pesquisa exploratória como metodologia de abordagem. Foram pesquisados os termos resistência medicamentosa, hanseníase, recidiva, alterações genéticas e os operadores booleanos "and" e "or" na busca. Resultados e discussão: A dificuldade de tomar a medicação corretamente foi um dos principais fatores que acarretaram resistência do bacilo Mycobacterium leprae aos fármacos. Homens de países norte e sul-americanos e asiáticos foram os mais atingidos por episódios de resistência. A resistência medicamentosa é uma das principais causas de recidivas em hanseníase. O principal fármaco causador de resistência medicamentosa descrito nos trabalhos foi a dapsona (46,6%) e a maioria das alterações genéticas encontradas estão no gene rpoB; 23,2% dos registros relatados foram de resistência secundária aos fármacos e, também, sete casos de resistência múltipla a esses medicamentos. Conclusão: Os principais aspectos da resistência medicamentosa na hanseníase são os equívocos ao ingerir os medicamentos e as alterações genéticas na bactéria. Os impactos causados estão na dificuldade de refazer o tratamento, a possibilidade de nova transmissão e o aparecimento de sintomas mais graves.


Introduction: The diagnosis of leprosy has significant numbers causing public health concern. Reports of drug resistance in this disease begun in the mid-1960s and due to this problem, the World Health Organization instituted a multidrug therapy with rifampicin, dapsone, and clofazimine antibiotic association in 1981, which is currently the first-choice treatment for leprosy. Cases of drug resistance have been reported in literature, revealing an obstacle to the eradication of the disease. This paper has the purpose of presenting the key aspects and impacts of drug resistance in the treatment for leprosy. Methods: Systematic review of the drug resistance aspects using exploratory research as an approach methodology. The authors searched the terms drug resistance, leprosy, recurrence, genetic alterations, and the Boolean operators "and" and "or" between them. Results and discussion: The difficulty in taking the medication correctly was one of the key factors that led to drug resistance for Mycobacterium leprae. Men from North and South American, as well as from Asian countries, were the most affected by episodes of resistance. Drug resistance is one of the main causes of leprosy recurrences. Dapsone was the most frequently identified drug resistance in the studies (46.6%), while most of the genetic alterations were found in the rpoB gene; 23.2% of the cases were from secondary resistance episodes, and seven cases of multiple resistance were reported. Conclusion: The misconceptions when taking the treatment and the Mycobacterium leprae genetic alterations have been described as the key aspects of drugs resistance in leprosy and the impacts caused are the difficulty in redoing the treatment, the possibility of new transmission, and the appearance of more severe symptoms.


Assuntos
Resistência a Medicamentos/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Mycobacterium leprae/efeitos dos fármacos , Rifampina/efeitos adversos , Bactérias/genética , Preparações Farmacêuticas , Clofazimina/efeitos adversos , Fluoroquinolonas/efeitos adversos , Dapsona/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Hanseníase/tratamento farmacológico , Antibacterianos/efeitos adversos
10.
PLoS Negl Trop Dis ; 15(3): e0009279, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788863

RESUMO

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.


Assuntos
Busca de Comunicante/métodos , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Programas de Rastreamento/métodos , Prevenção Primária/métodos , Brasil , Humanos , Índia , Indonésia/epidemiologia , Hansenostáticos/uso terapêutico , Mianmar/epidemiologia , Nepal/epidemiologia , Profilaxia Pós-Exposição/métodos , Rifampina/uso terapêutico , Sri Lanka/epidemiologia , Tanzânia/epidemiologia
11.
An Bras Dermatol ; 96(2): 224-227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33637399

RESUMO

Leprosy is one of the neglected diseases in the world and Brazil is the second country with more cases. A retrospective study was conducted based on the medical records of 196 leprosy patients diagnosed during the course of 13 years at a university hospital. The aim was to describe the adverse effects of polychemotherapy, as well the most prevalent and most vulnerable populations. In the study, dapsone was the most implicated drug, especially in women, and the risk increased with age. The authors conclude that with this patient profile, greater vigilance should be taken regarding possible adverse effects, especially anemia.


Assuntos
Hansenostáticos , Hanseníase , Brasil , Clofazimina/uso terapêutico , Dapsona/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Estudos Retrospectivos , Rifampina/uso terapêutico
13.
Lancet Glob Health ; 9(1): e81-e90, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129378

RESUMO

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/prevenção & controle , Profilaxia Pós-Exposição/métodos , Saúde Pública/métodos , Rifampina/uso terapêutico , Estudos de Viabilidade , Humanos , Medicina de Precisão/métodos
14.
Jpn J Infect Dis ; 74(2): 110-114, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32863349

RESUMO

Leprosy is a socially stigmatized granulomatous skin disease caused by Mycobacterium leprae. Due to improvements in medicine and hygiene in Taiwan, the incidence is very low, up to one dozen per year; however, leprosy has never been eradicated due to the increased numbers of immigrants from Southeast Asia. This study aimed to characterize the clinical and histopathological features of patients with leprosy in the context of near elimination. Fifteen cases of pathologically proven leprosy were identified from 2000 to 2016 in Kaohsiung Chang Gung Memorial Hospital. The clinical presentations, demographic details, treatment responses, and disease outcomes were reviewed. The mean age was 46 years (range: 26-73 years). Eight cases were native Taiwanese, while 6 cases and 1 case involved foreign workers from Indonesia and Thailand, respectively. The diagnosis was made 3-6 months on average after skin lesions appeared. The most common clinical subtype was lepromatous leprosy (n = 7). Ten patients were multibacillus microscopically. Three cases were deported. The remaining 12 patients received dapsone and rifampicin for 12 months without recurrence to date. In the near leprosy-eradicated country, early diagnosis and physician vigilance are critical in disease control. Immigrants from endemic countries require strict and professional dermatological examinations and regular follow-up.


Assuntos
Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Adulto , Idoso , Dapsona/uso terapêutico , Erradicação de Doenças , Feminino , Humanos , Hanseníase/patologia , Hanseníase Virchowiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/patologia , Taiwan/epidemiologia
15.
s.l; s.n; 2021. 6 p. tab, ilus.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1146794

RESUMO

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective(AU).


Assuntos
Humanos , Masculino , Feminino , Quimioterapia Combinada , Lobomicose/tratamento farmacológico , Rifampina/uso terapêutico , Clofazimina/uso terapêutico , Itraconazol/uso terapêutico , Dapsona/uso terapêutico , Hanseníase/tratamento farmacológico
16.
s.l; s.n; 2021. 9 p. tab.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, SESSP-ILSLACERVO, SES-SP | ID: biblio-1146973

RESUMO

Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established(AU).


Assuntos
Rifampina/uso terapêutico , Profilaxia Pós-Exposição/métodos , Hanseníase/prevenção & controle , Estudos de Viabilidade , Programas de Rastreamento , Saúde Pública/métodos , Medicina de Precisão/métodos , Hansenostáticos/uso terapêutico
17.
s.l; s.l; 2021. 10 p. ilus, tab.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1150427

RESUMO

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6−87.9) and a specificity of 97.0% (95% CI = 94.0−98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0−93.9) and 97.3% (95% CI = 94.3−98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1−92.3) and 96.1% (95% CI = 90.2−98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern(AU).


Assuntos
Farmacorresistência Bacteriana , Hanseníase/terapia , Rifampina/uso terapêutico , Ofloxacino/uso terapêutico , Programas de Rastreamento , Sensibilidade e Especificidade , Análise de Sequência de DNA , Dapsona/uso terapêutico
18.
s.l; s.n; 2021. 14 p. tab, graf.
Não convencional em Inglês | SES-SP, CONASS, HANSEN, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1292662

RESUMO

The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of SDR to eligible contacts of newly diagnosed leprosy patients in states or districts of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. This study investigated the long-term impact of the LPEP program on the leprosy new case detection rate (NCDR). Our results show that LPEP could reduce the NCDR beyond the impact of the routine leprosy control programme and that many new cases could be prevented. The benefit of LPEP increases gradually over time. LPEP could accelerate the time of reaching predicted NCDR levels of 2040 under routine program by up to six years. Furthermore, we highlighted how the impact varies between countries due to differences in the number of contacts per index patient screened and differences in leprosy epidemiology and national control programme. Generally, including both household contacts and neighbours (> 20 contacts per index patient) would yield the highest impact.


Assuntos
Humanos , Prevenção Primária/métodos , Busca de Comunicante/métodos , Profilaxia Pós-Exposição , Hanseníase/prevenção & controle , Hanseníase/epidemiologia , Rifampina/uso terapêutico , Sri Lanka/epidemiologia , Tanzânia/epidemiologia , Brasil , Programas de Rastreamento , Mianmar/epidemiologia , Índia , Indonésia/epidemiologia , Nepal/epidemiologia
20.
Bauru; s.n; 2021. 39 p. ilus, tab, mapa.
Tese em Português | SES-SP, CONASS, HANSEN, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP, SESSP-ESPECIALIZACAOSESPROD, SES-SP | ID: biblio-1178963

RESUMO

Introdução Hanseníase é uma doença infecciosa crônica, causada pelo Mycobacterium leprae. Por causar incapacidades físicas devido às lesões neurais, ainda hoje, é um grave problema de saúde pública no Brasil. Desde a década de 80, o tratamento é realizado por poliquimioterapia (PQT): dapsona, rifampicina e clofazimina. A ofloxacina é a droga alternativa mais amplamente utilizada. Mutações em regiões determinantes de droga resistência (DRDR) nos genes folp1, rpoB e gyrA estão relacionadas com resistência a dapsona, rifampicina e ofloxacina, respectivamente. Desde a década de 60 ocorrem relatos de M. leprae resistentes a uma das drogas ou até mesmo multidrogas resistentes. Objetivos Analisar as mutações não validadas no gene rpoB, a droga bactericida do esquema PQT, e comparar com o que já foi validado na literatura. Materiais e Métodos Isolados de M. leprae que apresentaram mutações no gene rpoB fora das regiões determinantes de resistência à rifampicina foram selecionados do banco de amostras testadas anteriormente por sequenciamento direto na rotina de investigação de resistência em hanseníase do ILSL, no período entre 2015 e 2020. Resultados Um total de 1396 amostras de isolados de pacientes do Instituto Lauro de Souza Lima foram analisadas. Dentre elas, 22 amostras apresentaram mutações em códons já descritos na literatura e 53 amostras apresentaram algum tipo de alteração fora dos códons comumente investigados. Discussão No presente estudo, diversas mutações entre os códons 411 e 530 do gene rpoB foram encontradas. Algumas delas já foram descritas na literatura, enquanto outras não foram encontradas para que fosse possível ter uma base comparativa. Conclusão São necessários estudos mais aprofundados sobre mutações não DRDRs e, até mesmo, novos mecanismos de resistência para elucidar os casos de retratamento. Além disso, a implantação de ações mais eficientes de saúde pública é de fundamental importância para o controle da hanseníase.


Introduction Leprosy is a chronic infectious disease, caused by Mycobacterium leprae. It causes physical disabilities due to neural injuries and it remains as a serious public health problem in Brazil. Since the 1980s, treatment has been carried out by multidrug therapy (MDT): dapsone, rifampicin and clofazimine. Mutations in drug resistance-determining regions (DRDR) in the folp1, rpoB and gyrA genes are related to resistance to dapsone, rifampicin and ofloxacin, respectively. Since the 1960s, there have been reports of M. leprae being resistant to one of the drugs or even multidrug resistant. Objectives To analyze mutations not validated in the rpoB gene and compare with what has already been validated in the literature. Materials and Methods Isolates of M. leprae that showed mutations in the rpoB gene outside the rifampin resistance determining regions were selected from the sample bank tested previously by direct sequencing in the ILSL leprosy resistance investigation routine, between 2015 and 2020. Results Between 2015 and 2020, a total of 1396 samples of isolates from patients in the Lauro de Souza Lima Institute were analyzed. Among them, 22 samples presented mutations in codons already described in the literature and 53 samples presented some type of mutation outside these codons. Discussion In the present work, several mutations between codons 411 and 530 of the rpoB gene were found. Some of them have already been described in the literature, while others have not been found, and could not be compared. Conclusion Further studies on non-DRDR mutations and even new resistance mechanisms are needed to elucidate retreatment cases. In addition, the implementation of more efficient public health actions is of fundamental importance for the control of leprosy.


Assuntos
Humanos , Rifampina/uso terapêutico , Resistência a Medicamentos , Hanseníase/terapia , Mutação
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