RESUMO
Tuberculosis is one of the oldest known diseases and it remains one of the main causes of morbidity and mortality, especially in developing countries. It is associated with social inequalities and affects different age groups. Tuberculosis in children and adolescents should be considered a sentinel event, since it is linked to a recent infection through contact with bacilliferous adults. We report an immunocompetent 15-year-old adolescent with tuberculosis, exhibiting pulmonary, osteoarticular, and cutaneous involvement. Conventional treatment with tuberculostatic drugs for a year had satisfactory results without sequelae.
Assuntos
Antituberculosos , Imunocompetência , Humanos , Adolescente , Antituberculosos/uso terapêutico , Masculino , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/patologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Osteoarticular/tratamento farmacológico , Tuberculose Osteoarticular/diagnósticoRESUMO
Mycobacterium tuberculosis is the main causative agent of tuberculosis (TB)-an ancient yet widespread global infectious disease to which 1.6 million people lost their lives in 2021. Antimicrobial resistance (AMR) has been an ongoing crisis for decades; 4.95 million deaths were associated with antibiotic resistance in 2019. While AMR is a multi-faceted problem, drug discovery is an urgent part of the solution and is at the forefront of modern research.The landscape of drug discovery for TB has undoubtedly been transformed by the development of high-throughput gene-silencing techniques that enable interrogation of every gene in the genome, and their relative contribution to fitness, virulence, and AMR. A recent advance in this area is CRISPR interference (CRISPRi). The application of this technique to antimicrobial susceptibility testing (AST) is the subject of ongoing research in basic science.CRISPRi technology can be used in conjunction with the high-throughput SPOT-culture growth inhibition assay (HT-SPOTi) to rapidly evaluate and assess gene essentiality including non-essential, conditionally essential (by using appropriate culture conditions), and essential genes. In addition, the HT-SPOTi method can develop drug susceptibility and drug resistance profiles.This technology is further useful for drug discovery groups who have designed target-based inhibitors rationally and wish to validate the primary mechanisms of their novel compounds' antibiotic action against the proposed target.
Assuntos
Descoberta de Drogas , Inativação Gênica , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Descoberta de Drogas/métodos , Humanos , Sistemas CRISPR-Cas , Antituberculosos/farmacologia , Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Farmacorresistência Bacteriana/genética , Tuberculose/microbiologia , Tuberculose/tratamento farmacológicoRESUMO
Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.
Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Pirazinamida , Pirazinamida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana/métodos , Sinergismo Farmacológico , Rifampina/farmacologia , HumanosRESUMO
The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.
Assuntos
Carga Bacteriana , Fezes , Mycobacterium tuberculosis , Tuberculose , Fezes/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/genética , Humanos , Carga Bacteriana/métodos , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , DNA Bacteriano/genética , Escarro/microbiologiaRESUMO
Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many first- and second-line anti-tuberculosis drugs. However, bioinformatic pipelines and mutation catalogs to predict antimicrobial resistances in MTBC isolates are often customized and detailed protocols are difficult to access. Here, we provide a step-by-step workflow for the processing and interpretation of short-read sequencing data and give an overview of available analysis pipelines.
Assuntos
Antituberculosos , Biologia Computacional , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Sequenciamento Completo do Genoma , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Sequenciamento Completo do Genoma/métodos , Testes de Sensibilidade Microbiana/métodos , Humanos , Antituberculosos/farmacologia , Biologia Computacional/métodos , Genoma Bacteriano , Farmacorresistência Bacteriana/genética , Mutação , Tuberculose/microbiologia , Tuberculose/tratamento farmacológicoRESUMO
Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in many countries. WGS protocols usually start with the preparation of a DNA-library: the critical first step in the process. A DNA-library represents the genomic content of a DNA sample and consists of unique short DNA fragments. Although available DNA-library protocols come with manufacturer instructions, details of the entire process, including quality controls, instrument parameters, and run evaluations, often need to be developed and customized by each laboratory to implement WGS technology effectively. Here, we provide a detailed workflow for a DNA-library preparation based on an adapted Illumina protocol optimized for the reduction of reagent costs.
Assuntos
Genoma Bacteriano , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Sequenciamento Completo do Genoma , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Sequenciamento Completo do Genoma/métodos , Testes de Sensibilidade Microbiana/métodos , Humanos , Antituberculosos/farmacologia , Biblioteca Gênica , DNA Bacteriano/genética , Tuberculose/microbiologia , Tuberculose/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.
Assuntos
Antituberculosos , Diarilquinolinas , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Diarilquinolinas/uso terapêutico , Diarilquinolinas/farmacocinética , Humanos , Antituberculosos/uso terapêutico , Antituberculosos/farmacocinética , Antituberculosos/farmacologia , Antituberculosos/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , AnimaisRESUMO
Genital tuberculosis, a form of extrapulmonary tuberculosis (EPTB), exhibits distinct presentations. In the outpatient department, an adolescent girl reported severe pain and a feeling of heaviness in her lower abdomen for the past 6-7 days. An enlarged pelvic mass, resembling a 20-week pregnancy, was observed, seemingly originating from the pelvis. During the local examination, a transverse septum was felt in the lower vagina, with a vaginal length of 2-3 cm. The ultrasound revealed distension of the vagina with fluid containing fine internal echoes, indicating haematocolpos. MRI showed the uterus pushed upward and located at the level of the umbilicus, suggesting hydrocolpos. Based on these findings, a provisional diagnosis of transvaginal septum with haematocolpos was made. Under anaesthesia, a cruciate incision was made over the vaginal septum, resulting in the drainage of 700-800 mL of pus. The drained fluid was sent for microscopic examination, gram staining, acid-fast bacilli smear culture, and Cartridge-based nucleic acid amplification test (CBNAAT). The CBNAAT test confirmed the presence of tubercle bacilli. Antitubercular therapy was initiated, and on completion of the treatment, the girl experienced the onset of menarche. This is a typical case with an unusual presentation of EPTB. What makes this case noteworthy is its initial manifestation as haematocolpos, a condition that shares a similar clinical presentation with Müllerian anomalies.
Assuntos
Antituberculosos , Tuberculose dos Genitais Femininos , Humanos , Feminino , Adolescente , Tuberculose dos Genitais Femininos/diagnóstico , Tuberculose dos Genitais Femininos/tratamento farmacológico , Antituberculosos/uso terapêutico , Vagina/microbiologia , Hematocolpia/diagnóstico , Hematocolpia/etiologia , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , UltrassonografiaRESUMO
A diabetic woman in her fifties presented with a sudden onset of failing vision and diplopia involving the right eye for two days, along with fever and headache. Radiological investigations revealed right sphenoid sinusitis along with inflammation around the right orbital apex and optic nerve. Functional endoscopic sinus surgery, with orbital and optic nerve decompression improved the ocular movements, but not the visual acuity. Histopathology was suggestive of a granulomatous inflammatory lesion, and high-resolution computed tommography (HRCT) of the thorax revealed lung lesions suggestive of an old tubercular infection, and antitubercular treatment (ATT) was then initiated.At the end of two months of ATT, there was complete resolution of ophthalmoplegia, relative afferent pupillary defect, direct and consensual light reflex however, failure of improvement in her visual acuity, indicated damage to the optic nerve.Extrapulmonary tuberculosis involving an isolated sphenoid sinus is rare and elusive. Prompt radiological investigations, followed by orbital decompression and ATT, provide the best possible outcomes.
Assuntos
Antituberculosos , Cegueira , Oftalmoplegia , Seio Esfenoidal , Humanos , Feminino , Pessoa de Meia-Idade , Antituberculosos/uso terapêutico , Seio Esfenoidal/diagnóstico por imagem , Oftalmoplegia/etiologia , Oftalmoplegia/diagnóstico , Cegueira/etiologia , Sinusite Esfenoidal/complicações , Sinusite Esfenoidal/diagnóstico , Sinusite Esfenoidal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Descompressão Cirúrgica , Tuberculose/complicações , Tuberculose/diagnósticoRESUMO
Assuntos
Consumo de Bebidas Alcoólicas , Antituberculosos , Infecções por HIV , Isoniazida , Tuberculose Latente , Humanos , Isoniazida/administração & dosagem , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Uganda/epidemiologia , Tuberculose Latente/tratamento farmacológico , Masculino , Infecções por HIV/tratamento farmacológico , Feminino , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Adulto , Cadeias de Markov , Teste Tuberculínico , Tuberculose/prevenção & controle , Tuberculose/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Assuntos
Antituberculosos , Epididimo , Imunocompetência , Imageamento por Ressonância Magnética , Tuberculose dos Genitais Masculinos , Humanos , Masculino , Adulto Jovem , Antituberculosos/administração & dosagem , Epididimo/patologia , Epididimo/microbiologia , Tuberculose dos Genitais Masculinos/diagnóstico , Tuberculose dos Genitais Masculinos/tratamento farmacológico , Orquiectomia , Convulsões/etiologia , Anticonvulsivantes/administração & dosagem , Tuberculoma Intracraniano/diagnóstico , Tuberculoma Intracraniano/tratamento farmacológicoRESUMO
Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Emirados Árabes Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Feminino , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Pessoa de Meia-Idade , Farmacorresistência Bacteriana , Adolescente , Testes de Sensibilidade Microbiana , Adulto Jovem , Vigilância da PopulaçãoAssuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/farmacologia , Tuberculose/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificaçãoRESUMO
Assuntos
Antituberculosos , Tuberculose Ocular , Humanos , Austrália Ocidental/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Antituberculosos/administração & dosagem , Tuberculose Ocular/tratamento farmacológico , Tuberculose Ocular/diagnóstico , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Resultado do Tratamento , Adolescente , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/tratamento farmacológico , SeguimentosRESUMO
Introduction. Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. However, more and more clinical strains are found to be aminoglycoside antibiotic-resistant. Apramycin is another kind of aminoglycoside antibiotic that is commonly used to treat infections in animals.Hypothesis. Apramycin may have in vitro activity against Mtb.Aim. This study aims to evaluate the efficacy of apramycin against Mtb in vitro and determine its epidemiological cut-off (ECOFF) value.Methodology. One hundred Mtb isolates, including 17 pansusceptible and 83 drug-resistant tuberculosis (DR-TB) strains, were analysed for apramycin resistance using the MIC assay.Results. Apramycin exhibited significant inhibitory activity against Mtb clinical isolates, with an MIC50 of 0.5 µg ml-1 and an MIC90 of 1 µg ml-1. We determined the tentative ECOFF value as 1 µg ml-1 for apramycin. The resistant rates of multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains were 12.12â% (4/33), 20.69â% (6/29) and 66.67â% (14/21), respectively. The rrs gene A1401G is associated with apramycin resistance, as well as the cross-resistance between apramycin and other aminoglycosides.Conclusion. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB.
Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Nebramicina , Nebramicina/análogos & derivados , Nebramicina/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Humanos , Antituberculosos/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Farmacorresistência Bacteriana MúltiplaRESUMO
BACKGROUND: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. METHODS: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants' experiences, thoughts, expectations and attitudes. RESULTS: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. CONCLUSION: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.
Assuntos
Pesquisa Qualitativa , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Noruega/epidemiologia , Masculino , Feminino , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/psicologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Pessoa de Meia-Idade , Emigrantes e Imigrantes/psicologia , Emigrantes e Imigrantes/estatística & dados numéricos , Adulto Jovem , Entrevistas como Assunto , Antituberculosos/uso terapêuticoRESUMO
Introduction: the National Tuberculosis Control Program (NTP) in Cameroon participated between 2016 and 2018 in a multi-country operational study of the Union against Tuberculosis and Lung Disease (The UNION) aiming at demonstrating the efficiency and feasibility of systematic tuberculosis preventive treatment (TPT) with 3 months of an isoniazid/rifampicin (3RH) combination in under-five child contacts of bacilliferous TB patients. Cameroon was one of the participating countries of the study. Despite the promising results communicated following this study, the coverage of TPT with 3RH in Cameroon remains low. We explored the intervention under aspects of acceptability and perceived feasibility. Methods: key participants and stakeholders in this descriptive interpretative study in Cameroon were interviewed in five focus groups or individually (31 individuals). The Focus Group Discussion (FGD) and interview transcripts were analysed for different components of acceptability using a theoretical framework and the results discussed confronting them with the main objective of the study, i.e. demonstrating feasibility. Results: the children's parents expressed overall positive feelings about and acceptance of the intervention, emphasizing the unexpected empathy shown by the health staff. The involved field staff, too, showed unreserved acceptance. On the other hand, managers at the intermediate and central levels showed scepticism as to the process of initiation of the study as well as to its feasibility in the given context, neglecting aspects of resources necessary for a scaling-up and of prioritisation. Conclusion: the adoption of a public health strategy, also internationally recognized as an effective and efficient intervention, requires more than the demonstration of its acceptability or feasibility during the term of a showcase project introduced by an external development partner. Adoption is conditioned by adoption and circumspect planning involving at each stage the stakeholders on all levels of the program.
Assuntos
Antituberculosos , Estudos de Viabilidade , Grupos Focais , Isoniazida , Saúde Pública , Tuberculose , Humanos , Camarões , Antituberculosos/administração & dosagem , Tuberculose/prevenção & controle , Isoniazida/administração & dosagem , Pré-Escolar , Feminino , Masculino , Pais/psicologia , Entrevistas como Assunto , Lactente , Aceitação pelo Paciente de Cuidados de Saúde , AdultoRESUMO
BACKGROUND: Multi-drug or rifamycin-resistant tuberculosis (MDR/RR-TB) is an important public health concern, including in settings with high HIV prevalence. TB drug resistance can be directly transmitted or arise through resistance acquisition during first-line TB treatment. Limited evidence suggests that people living with HIV (PLHIV) might have an increased risk of acquired rifamycin-resistance (ARR). METHODS: To assess HIV as a risk factor for ARR during first-line TB treatment, a systematic review and meta-analysis was conducted. ARR was defined as rifamycin-susceptibility at treatment start with rifamycin-resistance diagnosed during or at the end of treatment, or at recurrence. PubMed/MEDLINE, CINAHL, Cochrane Library, and Google Scholar databases were searched from inception to 23 May 2024 for articles in English; conference abstracts were also searched from 2004 to 2021. The Mantel-Haenszel random-effects model was used to estimate the pooled odds ratio of any association between HIV and ARR among individuals receiving first-line TB treatment. RESULTS: Ten studies that included data collected between 1990 and 2014 were identified: five from the United States, two from South Africa and one each from Uganda, India and Moldova. A total of 97,564 individuals were included across all studies, with 13,359 (13.7%) PLHIV. Overall, 312 (0.32%) acquired rifamycin-resistance, among whom 115 (36.9%) were PLHIV. The weighted odds of ARR were 4.57 (95% CI, 2.01-10.42) times higher among PLHIV compared to HIV-negative individuals receiving first-line TB treatment. CONCLUSION: The available data, suggest that PLHIV have an increased ARR risk during first-line TB treatment. Further research is needed to clarify specific risk factors, including advanced HIV disease and TB disease severity. Given the introduction of shorter, 4-month rifamycin-based regimens, there is an urgent need for additional data on ARR, particularly for PLHIV. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022327337.
Assuntos
Antituberculosos , Infecções por HIV , Rifamicinas , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Rifamicinas/uso terapêutico , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Fatores de Risco , Mycobacterium tuberculosis/efeitos dos fármacos , África do Sul/epidemiologiaRESUMO
Peptide design and drug development offer a promising solution for combating serious diseases or infections. In this study, using an AI-human negotiation approach, we have designed a class of minimal model peptides against tuberculosis (TB), among which K7W6 exhibits potent efficacy attributed to its assembly-induced function. Comprising lysine and tryptophan with an amphiphilic α-helical structure, the K7W6 sequence exhibits robust activity against various infectious bacteria causing TB (including clinically isolated and drug-resistant strains) both in vitro and in vivo. Moreover, it synergistically enhances the effectiveness of the first-line antibiotic rifampicin while displaying low potential for inducing drug resistance and minimal toxicity toward mammalian cells. Biophysical experiments and simulations elucidate that K7W6's exceptional performance can be ascribed to its highly selective and efficient membrane permeabilization activity induced by its distinctive self-assembly behavior. Additionally, these assemblies regulate the interplay between enthalpy and entropy during K7W6-membrane interaction, leading to the peptide's two-step mechanism of membrane interaction. These findings provide valuable insights into rational design principles for developing advanced peptide-based drugs while uncovering the functional role played by assembly.