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1.
Front Immunol ; 15: 1298749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440733

RESUMO

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.


Assuntos
Hansenostáticos , Hanseníase , Humanos , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/genética , Hanseníase/prevenção & controle , Rifampina , Imunidade
2.
Microbiol Spectr ; 12(4): e0233923, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38363108

RESUMO

Macrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for Mycobacterium avium complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of M. avium. We examined the applicability of the ARMS-LAMP method to genomic DNA extracted from six genotypes of M. avium clinical isolates. The M. avium isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS-LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS-LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS-LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS-LAMP might be a new clinically beneficial technology for rapid detection of mutations.IMPORTANCEMultidrug therapy for pulmonary Mycobacterium avium complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using M. avium clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS-LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice.


Assuntos
Antibacterianos , Pneumopatias , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Claritromicina/farmacologia , Mycobacterium avium , Azitromicina , Quimioterapia Combinada , Farmacorresistência Bacteriana/genética , Hansenostáticos/uso terapêutico , Mutação , Complexo Mycobacterium avium , Pneumopatias/tratamento farmacológico , Testes de Sensibilidade Microbiana
3.
J Infect Chemother ; 30(6): 531-535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38141720

RESUMO

INTRODUCTION: The importance of DNA repair enzymes in maintaining genomic integrity is highlighted by the hypothesis that DNA damage by reactive oxygen/nitrogen species produced inside the host cell is essential for the mutagenesis process. Endonuclease III (Nth), formamidopyrimide (Fpg) and endonuclease VIII (Nei) DNA glycosylases are essential components of the bacterial base excision repair process. Mycobacterium leprae lost both fpg/nei genes during the reductive evolution event and only has the nth (ML2301) gene. This study aims to characterize the mutations in the nth gene of M. leprae strains and explore its correlation with drug-resistance. METHOD: A total of 91 M. leprae positive DNA samples extracted from skin biopsy samples of newly diagnosed leprosy patients from NSCB Hospital Jabalpur were assessed for the nth gene as well as drug resistance-associated loci of the rpoB, gyrA and folP1 genes through PCR followed by Sanger sequencing. RESULTS: Of these 91 patients, a total of two insertion frameshift mutations, two synonymous and seven nonsynonymous mutations were found in nth in seven samples. Sixteen samples were found to be resistant to ofloxacin and one was found to be dapsone resistant as per the known DRDR mutations. No mutations were found in the rpoB region. Interestingly, none of the nth mutations were identified in the drug-resistant associated samples. CONCLUSION: The in-silico structural analysis of the non-synonymous mutations in the Nth predicted five of them were to be deleterious. Our results suggest that the mutations in the nth gene may be potential markers for phylogenetic and epidemiological studies.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase/genética , Hanseníase/tratamento farmacológico , Filogenia , Farmacorresistência Bacteriana/genética , Mutação , DNA Bacteriano/genética , Índia , Reparo do DNA/genética
4.
J Glob Antimicrob Resist ; 35: 262-267, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852372

RESUMO

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Ofloxacino/farmacologia , Quimioterapia Combinada , Estudos Transversais , Farmacorresistência Bacteriana/genética , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Dapsona/farmacologia , Dapsona/uso terapêutico , Índia/epidemiologia
5.
Int J Mycobacteriol ; 12(3): 254-260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37721229

RESUMO

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.


Assuntos
Bacillus , Hanseníase , Feminino , Humanos , Masculino , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Mycobacterium leprae , Estudos Prospectivos , Fatores Socioeconômicos
8.
Med Trop Sante Int ; 3(2)2023 06 30.
Artigo em Francês | MEDLINE | ID: mdl-37525686

RESUMO

Introduction: Leprosy is a chronic infectious disease that mainly affects the skin, mucous membranes and the peripheral nervous system. Its elimination as a public health problem seems to lead to its ignorance and therefore to a risk of late diagnosis. An analysis of leprosy surveillance data in Mauritania was conducted to determine epidemiological trends and clinical forms of reported cases. Material and method: The retrospective study was based on the epidemiological records of leprosy in Mauritania from 2009 to 2019. The diagnosis of leprosy was made on the basis of the diagnostic criteria of the World Health Organization (WHO). Data were analyzed using Epi Info version 7.2.5.0. The frequencies, proportions, and rates were calculated. Results: Over the past 11 years, 164 cases have been notified. Among the notified cases, 96/164 (58.5%) were males and 68/164 (41.5%) females, with a sex ratio of 1.4. The mean age (± standard deviation) was 44.0 ± 17.1 years [range, 9 - 86 years], and the median was 45 years [interquartile range, 32.5; 57.5]. Children under the age of 16 accounted for 9/164 (5.5%). The wilayas (i.e. "regions") of Nouakchott were the most endemic regions in the country. The multibacillary form (MB) represented 109/164 (66.5%) cases among the observed clinical forms. The average annual incidence was 0.3 case/100,000 population for MB and 0.1 case/100,000 for PB (paucibacillary). All reported cases were treated with multidrug therapy. Conclusion: The results of leprosy surveillance showed a persistence of this disease in Mauritania. It is necessary to relaunch leprosy services at all levels in order to continue to reduce the morbidity associated with this disease, and eventually eliminate it from the country.


Assuntos
Hansenostáticos , Hanseníase , Masculino , Criança , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Mauritânia/epidemiologia , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hanseníase/epidemiologia
9.
Medicine (Baltimore) ; 102(32): e34548, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565881

RESUMO

RATIONALE: The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. PATIENT CONCERNS: A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. DIAGNOSES, INTERVENTIONS AND OUTCOMES: The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. LESSONS: Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.


Assuntos
Coriocarcinoma , Mola Hidatiforme , Neoplasias Uterinas , Humanos , Gravidez , Feminino , Adulto Jovem , Adulto , Neoplasias Uterinas/patologia , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Coriocarcinoma/complicações , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/diagnóstico , Mola Hidatiforme/diagnóstico
10.
Rev Prat ; 73(6): 641-650, 2023 Jun.
Artigo em Francês | MEDLINE | ID: mdl-37458554

RESUMO

TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.


TOXICITÉ DES THÉRAPIES CIBLÉES ET DE L'IMMUNOTHÉRAPIE PAR INHIBITEURS DES POINTS DE CONTRÔLE DANS LE LYMPHOME DE HODGKIN. Chez les patients ayant un risque accru de récidive ou de progression après une autogreffe, ou en cas de rechute après autogreffe ou après au moins deux lignes de traitement quand la polychimiothérapie intensive n'est plus une option, un traitement ciblé anti-CD30 par brentuximab vedotin peut être proposé. Le brentuximab vedotin est un anticorps monoclonal dirigé contre le CD30 et couplé à un agent cytotoxique antimicrotubule, la monométhylauristatine E. Le principal effet indésirable du brentuximab vedotin est la neuropathie périphérique. Chez les patients ayant une rechute après chimiothérapie intensive incluant une autogreffe, et après échec de brentuximab vedotin, une immuno­ thérapie anti-PD1 (nivolumab ou pembrolizumab) peut être proposée. Les effets indésirables des anti-PD1 ( programmed cell death protein 1), liés à l'immunité, sont très variés et assez imprévisibles (endocrinopathies, rash, colite, pneumopathies interstitielles). Les profils de tolérance du brentuximab vedotin et des anti-PD1 et la gestion des principaux effets indésirables de ces traitements sont détaillés pour la pratique clinique.


Assuntos
Doença de Hodgkin , Imunoconjugados , Humanos , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/efeitos adversos , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Imunoterapia/efeitos adversos
11.
Int J Dermatol ; 62(9): 1186-1192, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37408116

RESUMO

BACKGROUND: Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. METHODS: The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. RESULTS: The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. CONCLUSION: Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.


Assuntos
Hanseníase Multibacilar , Hanseníase , Humanos , Hansenostáticos/uso terapêutico , Limeciclina/uso terapêutico , Quimioterapia Combinada , Estudos Retrospectivos , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase/tratamento farmacológico , Organização Mundial da Saúde
12.
Chest ; 164(4): 846-859, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37419144

RESUMO

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Amicacina , Antibacterianos , Lipossomos/uso terapêutico , Clofazimina/uso terapêutico , Azitromicina/uso terapêutico , Macrolídeos/uso terapêutico , Farmacorresistência Bacteriana , Hansenostáticos/uso terapêutico , Fibrose Cística/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Testes de Sensibilidade Microbiana
13.
Acta Derm Venereol ; 103: adv6246, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37144514

RESUMO

A resurgence of leprosy as a public health problem in French Guiana was reported over the period 2007 to 2014, particularly among Brazilians gold miners. Prolonged multidrug therapy and reversal reactions represent a therapeutic challenge. The objective of this study was to assess the evolution of leprosy in this European overseas territory. All patients with leprosy confirmed in histopathology between 1 January 2015 and 31 December 2021 were included. A total of 86 patients were included, including 64 new cases and 22 previously diagnosed cases. Sixty patients (70%) were male, 6 cases were paediatric. Brazilian gold miners represented 44.1% of reported occupations (15/34). Maroons represented the second community (13 patients, 15%). Multibacillary and paucibacillary forms were found in 53 (71%) and 22 (29%) patients, respectively. The annual prevalence never exceeded the threshold of 1/10,000. The mean incidence and prevalence were significantly lower than during the period 2007 to 2014 (p < 0.0001). Reversal reactions were found in 29 patients and almost always required a long course of steroids. Infliximab allowed a reduction in the length of treatment with steroids in 2/2 cases. In conclusion, the prevalence of leprosy has decreased significantly in French Guiana, but remains driven by the population of illegal gold miners. Anti-tumour necrosis factor (anti-TNF) drugs represent a promising option in the management of reversal reactions.


Assuntos
Hanseníase , Saúde Pública , Humanos , Masculino , Criança , Feminino , Guiana Francesa/epidemiologia , Quimioterapia Combinada , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Ouro
15.
N Engl J Med ; 388(20): 1843-1852, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37195940

RESUMO

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 Família
16.
Cad Saude Publica ; 39(5): e00279421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255191

RESUMO

This study aimed to analyze the self-reported clinical history of patients misdiagnosed with leprosy in the State of Mato Grosso, Brazil. This is a cross-sectional study of new leprosy cases diagnosed in the State of Mato Grosso from 2016 to 2019, with individuals who were released from multidrug therapy due to misdiagnosis after starting treatment. Data were collected via telephone interviews. Over the study period, 354 leprosy cases were released from treatment due to misdiagnosis, of which 162 (45.8%) could be interviewed. All interviewees expressed dissatisfaction with their treatment, which prompted them to seek a reevaluation of their diagnosis before they were released due to "misdiagnosis". Among them, 35.8% received a final diagnosis of a musculoskeletal or connective tissue disease - mainly fibromyalgia and degenerative changes in the spine - followed by 13.6% with diagnoses of skin and subcutaneous tissue diseases. For 23.5% of the respondents, no alternative diagnosis was established, whereas 7.4% were later re-diagnosed with leprosy. Fibromyalgia and spinal problems were the most common alternative diagnoses for erroneous leprosy. Although the diagnosis of leprosy is usually clinical and does not require access to technical infrastructure in most cases, some more complex situations require diagnostic support via complementary tests, as well as close collaboration between primary care and reference services.


Assuntos
Fibromialgia , Hanseníase , Humanos , Brasil/epidemiologia , Estudos Transversais , Autorrelato , Quimioterapia Combinada , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Erros de Diagnóstico
17.
Am J Trop Med Hyg ; 109(1): 53-56, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37253443

RESUMO

Leprosy is a chronic infection caused by Mycobacterium leprae and Mycobacterium lepromatosis that preferentially compromises peripheral nerve, skin, and mucous membranes. Colombia achieved the goal of leprosy elimination in 1997. However, in Urabá (Colombia), there has been an increase in leprosy cases beginning in 2020. This case report shows a leprosy relapse 5 decades after the initial infection debuted as a necrotizing erythema nodosum leprosum. Therefore, long-term follow-up of patients with risk factors for relapse is emphasized, especially those treated before the standard of multidrug therapy (dapsone, clofazimine, and rifampin). This case report stresses the importance the importance of clinical follow-up and surveillance of patients with these events of interest for the public health.


Assuntos
Eritema Nodoso , Hanseníase Virchowiana , Hanseníase , Humanos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Eritema Nodoso/diagnóstico , Eritema Nodoso/tratamento farmacológico , Hansenostáticos/uso terapêutico , Quimioterapia Combinada , Hanseníase/tratamento farmacológico , Recidiva
19.
J Theor Biol ; 567: 111496, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37080386

RESUMO

Leprosy is a skin disease and it is characterized by a disorder of the peripheral nervous system which occurs due to the infection of Schwann cells. In this research article, we have formulated a four-dimensional ODE-based mathematical model which consists of the densities of healthy Schwann cells, infected Schwann cells, M. leprae bacteria, and the concentration of multidrug therapy (MDT). This work primarily aims on exploring the dynamical changes and interrelations of the system cell populations during the disease progression. Also, evaluating a critical value of the drug efficacy rate of MDT remains our key focus in this article so that a safe drug dose regimen for leprosy can be framed more effectively and realistically. We have examined the stability scenario of different equilibria and the occurrence of Hopf-bifurcation for the densities of our system cell populations with respect to the drug efficacy rate of MDT to gain insight on the precise impact of the efficiency rate on both the infected Schwann cell and the bacterial populations. Also, a necessary transversality condition for the occurrence of the bifurcation has been established. Our analytical and numerical investigations in this research work precisely explores that the process of demyelination, nerve regeneration, and infection of the healthy Schwann cells are the three most crucial factors in the leprosy pathogenesis and to control the M. leprae-induced infection of Schwann cells successfully, a more flexible version of MDT regime with efficacy rate varying in the range η∈(0.025,0.059) for 100-120 days in PB cases and 300 days in MB cases obtained in this research article should be applied. All of our analytical outcomes have been verified through numerical simulations and compared with some existing clinical findings.


Assuntos
Hansenostáticos , Hanseníase , Humanos , Quimioterapia Combinada , Hansenostáticos/uso terapêutico , Hansenostáticos/farmacologia , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Hanseníase/patologia , Mycobacterium leprae , Organização Mundial da Saúde
20.
Expert Opin Ther Pat ; 33(1): 1-15, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36755421

RESUMO

INTRODUCTION: Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent Mycobacterium leprae. The course of the disease is more aggressive in patients under 15 years of age, but the current treatment offered worldwide consists of solid forms, by the combination of antibiotics such as rifampicin, clofazimine and dapsone. This represents results in lack of adherence in pediatric patients and drug therapy failure, although numerous formulations and technologies have already been developed. AREA COVERED: This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices. EXPERT OPINION: Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.


Assuntos
Hansenostáticos , Hanseníase , Humanos , Criança , Hansenostáticos/uso terapêutico , Preparações Farmacêuticas , Patentes como Assunto , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Rifampina/uso terapêutico
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