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1.
Trends Immunol ; 41(10): 856-859, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32863134

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mainly affects the lungs. Sarcoidosis is an autoinflammatory disease characterized by the diffusion of granulomas in the lungs and other organs. Here, we discuss how the two diseases might involve some common mechanistic cellular pathways around the regulation of autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autofagia/genética , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Isoniazida/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/virologia , Edema Pulmonar/epidemiologia , Edema Pulmonar/genética , Edema Pulmonar/virologia , Rifampina/uso terapêutico , Sarcoidose/epidemiologia , Sarcoidose/genética , Sarcoidose/virologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença
2.
BMC Infect Dis ; 20(1): 654, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894070

RESUMO

BACKGROUND: Brucellosis is a zoonotic disease caused by brucella. It has been an increasing trend in recent years (Wang H, Xu WM, Zhu KJ, Zhu SJ, Zhang HF, Wang J, Yang Y, Shao FY, Jiang NM, Tao ZY, Jin HY, Tang Y, Huo LL, Dong F, Li ZJ, Ding H, Liu ZG, Emerg Microbes Infect 9:889-99, 2020). Brucellosis is capable to invade multiple systems throughout the body, lacking in typical clinical manifestations, and easily misdiagnosed and mistreated. CASE PRESENTATION: We report a case of a male, 5-year-and-11-month old child without relevant medical history, who was admitted to hospital for 20 days of fever. When admitted to the hospital, we found that he was enervated, irritable and sleepy, accompanied with red eyes phenomenon. After anti-infection treatment with meropenem, no improvement observed. Lumbar puncture revealed normal CSF protein, normal cells, and negative culture. Later, doppler echocardiography suggested coronary aneurysms, and incomplete Kawasaki Disease with coronary aneurysms was proposed. The next day, brucellosis agglutination test was positive. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid suggested B.melitensis, which was confirmed again by blood culture. The child was finally diagnosed as brucellosis with meningocephalitis, coronary aneurysm and keratitis. According to our preliminary research and review, such case has never been reported in detail before. After diagnosis confirmation, the child was treated with rifampicin, compound sulfamethoxazole, and ceftriaxone for cocktail anti-infection therapy. Aspirin and dipyridamole were also applied for anticoagulant therapy. After medical treatment, body temperature of the child has reached normal level, eye symptoms alleviated, and mental condition gradually turned normal. Re-examination of the doppler echocardiographic indicated that the coronary aneurysm was aggravated, so warfarin was added for amplification of anticoagulation treatment. At present, 3 months of follow-up, the coronary artery dilatation gradually assuaged, and the condition is continued to alleviate. CONCLUSION: Brucellosis can invade nervous system, coronary artery, and cornea. Brucellosis lacks specific signs for clinical diagnosis. The traditional agglutination test and the new mNGS are convenient and effective, which can provide the reference for clinical diagnosis.


Assuntos
Brucella melitensis/isolamento & purificação , Brucelose/complicações , Brucelose/diagnóstico , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico , Ceratite/complicações , Ceratite/diagnóstico , Meningoencefalite/complicações , Meningoencefalite/diagnóstico , Testes de Aglutinação , Animais , Anti-Infecciosos/uso terapêutico , Anticoagulantes/uso terapêutico , Brucelose/tratamento farmacológico , Ceftriaxona/uso terapêutico , Pré-Escolar , Erros de Diagnóstico , Febre/tratamento farmacológico , Humanos , Ceratite/tratamento farmacológico , Masculino , Meningoencefalite/tratamento farmacológico , Rifampina/uso terapêutico , Sulfametoxazol/uso terapêutico , Resultado do Tratamento , Zoonoses/diagnóstico , Zoonoses/tratamento farmacológico
3.
BMC Infect Dis ; 20(1): 711, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993535

RESUMO

BACKGROUND: Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children. CASE PRESENTATION: A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency. CONCLUSIONS: A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.


Assuntos
Linfo-Histiocitose Hemofagocítica/complicações , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose/complicações , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Antibióticos Antituberculose/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Subunidade gama Comum de Receptores de Interleucina/genética , Isoniazida/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/microbiologia , Masculino , Mutação , Alta do Paciente , Reação em Cadeia da Polimerase , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
4.
PLoS Negl Trop Dis ; 14(9): e0008583, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936818

RESUMO

BACKGROUND: Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation. CONCLUSIONS/SIGNIFICANCE: The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.


Assuntos
Infecções Assintomáticas/terapia , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/efeitos dos fármacos , Profilaxia Pós-Exposição/métodos , Animais , Carga Bacteriana/efeitos dos fármacos , Claritromicina/uso terapêutico , Combinação de Medicamentos , Hanseníase/transmissão , Camundongos , Camundongos Nus , Minociclina/uso terapêutico , Moxifloxacina/uso terapêutico , Mycobacterium leprae/crescimento & desenvolvimento , Rifampina/análogos & derivados , Rifampina/uso terapêutico
5.
PLoS One ; 15(9): e0239018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970722

RESUMO

BACKGROUND: Tuberculosis (TB) is amongst the top five causes of death in women of childbearing age (15-≤44 years). Little is known about treatment of pregnant women with drug-resistant TB (DR-TB). Treatment for pregnant women remains challenging and more complex in DR-TB/HIV co-infection, where an evidence-based guide to clinical practice is limited. The study reviewed treatment and pregnancy outcomes and birth outcomes of their new-born in a cohort of pregnant women with DR-TB from three MDR-TB hospitals during 2010 and 2018. DESIGN/METHODS: Data were extracted from: TB register and patient clinic notes using a standardized case record form. Information on DR-TB treatment, pregnancy and Adverse Drug Events (ADEs) of twenty-six pregnant women treated with individualized second-line TB medications were captured. The frequency of favourable and adverse outcomes regarding disease and pregnancy were evaluated. RESULTS: The mean age was 29 years (SD ±5.1), with the minimum and maximum age of 21 and 40 years, respectively. Eleven (42.3%) were previously treated with first-line TB drugs, 11 (42.3%) never treated before and 4 (15.4%) were previously treated for DR-TB. Of the 26 women, 15 (57.7%) had at least one ADE, but most had more than one ADE. Seventeen women were successfully treated, and 22 live births recorded. Live birth outcome was significantly associated with trimester of initiation of DR-TB treatment (p = 0.036). The proportion of live births for the pregnancy trimester when DR-TB treatment was initiated, were 60.0%, 90.9% and 100.0%, for first, second and third trimester, respectively. CONCLUSION: DR-TB treatment should be delayed until after the first trimester. Routine pharmacovigilance surveillance integrated antenatal and delivery services with an integrated record of DR-TB treatment during pregnancy is recommended. Prospective studies using standardised case record forms for DR-TB treatment for pregnant women could provide more insight on the effect of DR-TB treatment on the birth outcome.


Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Resultado da Gravidez/epidemiologia , Tuberculose/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Estudos de Coortes , Coinfecção/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Rifampina/uso terapêutico , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
7.
Brasília; CONITEC; ago. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1121782

RESUMO

INTRODUÇÃO: A tuberculose (TB), conhecida anteriormente como tísica, é uma doença que pode ser causada por sete espécies do gênero do complexo Mycobacterium sendo a mais importante, do ponto de vista de saúde pública, a M. tuberculosis. Globalmente cerca de 10 milhões de pessoas tiveram TB no ano de 2018. No Brasil, em 2018, foram diagnosticados 72.788 casos novos de TB o que representa uma incidência de 34,8 casos por 100 mil habitantes. A TB pode ser classificada como pulmonar e extrapulmonar, sendo a primeira forma mais prevalente. Além disso, a TB pode ser classificada conforme a resistência à medicamentos, tais como: RR-TB, MDR-TB e XDR-TB. PERGUNTA DE PESQUISA: A bedaquilina (BDQ) associada ao tratamento padrão para pacientes adultos com RR-TB, MDR-TB ou XDR-TB, é mais eficaz, efetiva e segura comparado ao tratamento padrão utilizado pelo SUS (levofloxacino, moxifloxacino, amicacina, capreomicina, etionamida, terizidona, linezolida, clofazimina, pirazinamida, etambutol, isoniazida, rifampicina e paraminossalicílico) ou placebo? TECNOLOGIA: Bedaquilina (Sirturo®). EVIDÊNCIAS CIENTÍFICAS: A revisão sistematizada recuperou nove estudos (uma revisão sistemática [RS] com meta-análise em rede [network meta-analysis - NMA], um ensaio clínico randomizado [ECR] com dois relatos e sete estudos de coorte [seis retrospectivas e uma prospectiva]). A RS, com NMA, avaliou a BDQ em comparação aos medicamentos delamanida, metronidazol, moxifloxacino e levofloxacino. A RS avaliou os desfechos conversão de cultura do escarro e aceitabilidade, e não foram verificados resultados estatisticamente significantes. Os estudos de coorte avaliaram a BDQ em comparação aos mais diversos tratamentos disponíveis para RR-TB, MDR-TB e XDR-TB. As coortes avaliaram os seguintes desfechos: sobrevida sucesso no tratamento, tratamento completo, cura, conversão da cultura do escarro e mortalidade. Os resultados não foram estatisticamente significantes na meta-análise de modelo de efeitos randomizados para todos os desfechos avaliados, porém os resultados dos efeitos fixos demostraram resultados estatisticamente significantes favorecendo o tratamento com BDQ em comparação ao tratamento sem BDQ. Vale salientar que foram realizadas análises de subgrupos com o ECR, TMC207, que avaliou eficácia e segurança da BDQ associado ao tratamento padrão em comparação ao grupo placebo associado ao tratamento padrão em até 120 semanas para os desfechos de conversão da cultura do escarro, cura e segurança (mortalidade), porém não mudaram a direção dos resultados nas duas modelagem da meta-análise. AVALIAÇÃO ECONÔMICA (AE): Os tratamentos com BDQ comparado aos tratamentos do SUS mostraram-se dominados na avaliação de custo-efetividade, para o desfecho paciente curado. Assim, os tratamentos do SUS para RR-TB, MDR-TB e XDR-TB dominaram todos os tratamentos com BDQ, ou seja, todos os tratamentos com BDQ foram menos efetivos e mais caros que os tratamentos do SUS para obter a cura dos indivíduos com RR-TB, MDR-TB e XDR-TB. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO (AIO): A AIO, para os pacientes com RR-TB, variou entre um custo incremental R$ 936 mil no caso base a uma economia de -R$ 1 milhão ao final do quinto ano no cenário alternativo; para MDR-TB variou entre uma economia de -R$44 mil no caso base a um gasto de R$ 110 mil ao final do quinto ano no cenário alternativo; e para XDR-TB variou entre um custo incremental de R$ 188 mil no caso base a R$ 4 mil no cenário alternativo ao final do quinto ano. MONITORAMENTO DO HORIZONTE TECNOLÓGICO (MHT): Cinco medicamentos foram detectados no MHT para pacientes com MDR-TB e XDR-TB (canamicina, cicloserina, sutezolida, pretomanide e protionamida). CONSIDERAÇÕES FINAIS: Há resultados conflitantes nas evidências encontradas no relatório. O ECR, analisado como de alto risco de viés (Risk of Bias 2.0) mostrou que a BDQ associada ao tratamento padrão é eficaz em comparação ao grupo de tratamento placebo associado ao tratamento padrão, porém com maior número de mortes e episódios de náusea em comparação ao grupo de tratamento sem a BDQ. Os resultados da RS, com NMA, de qualidade moderada, não demonstraram diferenças estatisticamente significantes entre as tecnologias avaliadas. Os resultados das meta-análises dos estudos de coorte de baixa qualidade metodológica (Newcastle-Ottawa Scale), em combinação com o ECR da BDQ, foram demonstrados em efeitos fixos e randomizados. Os desfechos sucesso no tratamento, tratamento completo, cura, conversão da cultura do escarro e mortalidade não foram estatisticamente significantes no modelo de efeito randomizados na meta-análise. No entanto, foram estatisticamente significantes no modelo de efeito fixos da metaanálise, e favoreceram o tratamento com BDQ em comparação aos pacientes não tratados sem BDQ. A AE demonstrou que os tratamentos com BDQ foram dominados em relação aos tratamentos disponibilizados no SUS sem BDQ, para o desfecho paciente tratado, sendo, portanto, mais custosos e menos efetivos. A AIO, para pacientes com RR-TB, variou entre R$ 936 mil no caso base a uma economia de -R$ 1 milhão no cenário alternativo ao final do quinto ano, para MDRTB variou entre uma economia de -R$44 mil no caso base a um custo de R$ 110 mil ao final do quinto ano no cenário alternativo e para XDR-TB variou entre um custo adicional de R$ 188 mil no caso base a um custo adicional de R$ 4 mil ao final do quinto ano no cenário alternativo. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 87ª reunião ordinária, realizada nos dias 03 e 04 de junho de 2020, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação no SUS da bedaquilina para pacientes com tuberculose resistente à rifampicina (RR-TB), a tuberculose multirresistente (MDR-TB) e para tuberculose extensivamente resistente a medicamentos (XDR-TB), condicionada ao monitoramento e apresentação dos dados de vida real, efetividade e segurança, da utilização da bedaquilina pela população brasileira e conforme critérios estabelecidos em protocolo do Ministério da Saúde. CONSULTA PÚBLICA: A Consulta Pública nº 24/2020 foi realizada entre os dias 22/06/2020 a 13/07/2020. Foram recebidas 66 contribuições no total, das quais 19 (29%) foram pelo formulário para contribuições técnico-científicas e 47 (71%) pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Das 19 contribuições de cunho técnico-científico, 95% submeteram a contribuição com opinião concordando totalmente com a recomendação preliminar da comissão. Apenas uma contribuição discordou da recomendação preliminar da Conitec, mas foi uma contribuição equivocada e se tratava de outro tema de consulta pública, portanto, foi excluída da análise. Das 47 contribuições recebidas sobre experiência ou opinião, apenas 15 foram analisadas, pois 32 estavam em branco, se tratavam de outro tema ou foram preenchidas inadequadamente. As 15 contribuições remanescentes concordaram 100% com a decisão preliminar da comissão. Após a apreciação das contribuições encaminhadas na consulta pública nº 24/2020, o plenário da Conitec considerou que: I) Foi apresentado um novo preço de USD 340 da bedaquilina pela Johnson & Johnson, sendo proposto um desconto de 15% no preço utilizado no relatório de recomendação preliminar (USD 400); II) Foram enviadas novas estimativas de incidência para pacientes com tuberculose multirresistente, bem como evidência de possíveis limitações na análise de impacto orçamentário; III) A nova análise de impacto orçamentário, utilizando os novos parâmetros enviados na consulta pública, aponta para economia de recursos na população com tuberculose multirresistente e um custo incremental com tuberculose resistente à rifampicina e tuberculose extensivamente resistente no cenário sem taxa de difusão gradual da bedaquilina (100% no primeiro ano de incorporação). No entanto, ao adotarmos o cenário com taxa difusão gradual da bedaquilina, 30% no primeiro ano de incorporação a 70% no quinto ano, os resultados mudam e proporcionam economia de recursos para pacientes com tuberculose resistente à rifampicina e um custo incremental para pacientes com tuberculose multirresistente e tuberculose extensivamente resistente. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 89ª reunião ordinária, no dia 05 de agosto de 2020, deliberaram por unanimidade recomendar a incorporação da bedaquilina para pacientes com tuberculose resistentes à rifampicina, multirresistentes e extensivamente resistente a medicamentos, condicionado a apresentação de dados de vida real e conforme preconizado pelo Ministério da Saúde. Foi assinado o Registro de Deliberação nº 538/2020. DECISÃO: Incorporar a bedaquilina para pacientes com tuberculose resistentes à rifampicina, multirresistentes e extensivamente resistente a medicamentos, condicionado a apresentação de dados de vida real e conforme preconizado pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS, conforme Portaria nº 36, publicada no Diário Oficial da União nº 168, seção 1, página 77, em 01 de setembro de 2020.


Assuntos
Humanos , Ácido Aminossalicílico/uso terapêutico , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Capreomicina/uso terapêutico , Amicacina/uso terapêutico , Clofazimina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Etionamida/uso terapêutico , Diarilquinolinas/uso terapêutico , Levofloxacino/uso terapêutico , Linezolida/uso terapêutico , Moxifloxacina/uso terapêutico , Isoniazida/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
8.
PLoS One ; 15(8): e0236057, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756559

RESUMO

BACKGROUND: Diagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings. METHODS: Data were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort. RESULTS: Of the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18). CONCLUSION: This project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Adolescente , Antibióticos Antituberculose/uso terapêutico , Criança , Pré-Escolar , Feminino , Pessoal de Saúde , Humanos , Índia/epidemiologia , Lactente , Masculino , Programas de Rastreamento , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
9.
PLoS Negl Trop Dis ; 14(8): e0008521, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32750059

RESUMO

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.


Assuntos
Programas Governamentais , Hanseníase/tratamento farmacológico , Hanseníase/prevenção & controle , Profilaxia Pós-Exposição/economia , Quimioprevenção/economia , Análise Custo-Benefício , Humanos , Índia , Hansenostáticos/economia , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/economia , Profilaxia Pós-Exposição/métodos , Anos de Vida Ajustados por Qualidade de Vida , Rifampina/economia , Rifampina/uso terapêutico
10.
PLoS One ; 15(8): e0237787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822375

RESUMO

INTRODUCTION: Afghanistan is affected by one of the world's longest protracted armed conflicts, frequent natural disasters, disease outbreaks and large population movements and it suffers from a high burden of tuberculosis (TB), including rifampicin-resistant TB (RR-TB). The study shows Médecins Sans Frontières' experiences with care for patients with RR-TB in Kandahar Province. We describe the uptake of RR-TB treatment, how World Health Organisation criteria for the choice between the short and an individualized regimen were implemented, and treatment outcomes. METHODS: This is a retrospective cohort analysis of routinely collected data from RR-TB patients enrolled in care from 2016 until 2019. Descriptive analysis was performed to present characteristics of patients and treatment outcomes. Multivariable Cox analysis was performed to identify risk factors for having an unfavourable treatment outcome. RESULTS: Out of 146 enrolled RR-TB patients, 112 (76.7%) started treatment: 41 (36.6%) and 71 (63.4%) with the short and individualized treatment regimen, respectively. Of 82 with results for fluoroquinolone susceptibility, 39 (47.6%) had fluoroquinolone-resistant TB. Seven patients with initially fluoroquinolone-resistant TB and three pregnant women started the short regimen and 18 patients eligible for the short regimen started the injectable-free individualized regimen. Overall, six-month smear and culture conversion were 98.7% and 97.1%, respectively; treatment success was 70.1%. Known initial fluoroquinolone resistance (aHR 3.77, 95%CI:1.53-9.27) but not choice of regimen predicted having an unfavourable outcome. CONCLUSION: Even though criteria for the choice of treatment regimen were not applied strictly, we have achieved acceptable outcomes in this cohort. To expand RR-TB care, treatment regimens should fit provision at primary health care level and take patient preferences into account.


Assuntos
Antituberculosos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Afeganistão/epidemiologia , Feminino , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
11.
Cochrane Database Syst Rev ; 8: CD013359, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853411

RESUMO

BACKGROUND: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis. OBJECTIVES: Primary objectives • To determine the diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for (a) pulmonary tuberculosis in children presumed to have tuberculosis; (b) tuberculous meningitis in children presumed to have tuberculosis; (c) lymph node tuberculosis in children presumed to have tuberculosis; and (d) rifampicin resistance in children presumed to have tuberculosis - For tuberculosis detection, index tests were used as the initial test, replacing standard practice (i.e. smear microscopy or culture) - For detection of rifampicin resistance, index tests replaced culture-based drug susceptibility testing as the initial test Secondary objectives • To compare the accuracy of Xpert MTB/RIF and Xpert Ultra for each of the four target conditions • To investigate potential sources of heterogeneity in accuracy estimates - For tuberculosis detection, we considered age, disease severity, smear-test status, HIV status, clinical setting, specimen type, high tuberculosis burden, and high tuberculosis/HIV burden - For detection of rifampicin resistance, we considered multi-drug-resistant tuberculosis burden • To compare multiple Xpert MTB/RIF or Xpert Ultra results (repeated testing) with the initial Xpert MTB/RIF or Xpert Ultra result SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the International Standard Randomized Controlled Trials Number (ISRCTN) Registry up to 29 April 2019, without language restrictions. SELECTION CRITERIA: Randomized trials, cross-sectional trials, and cohort studies evaluating Xpert MTB/RIF or Xpert Ultra in HIV-positive and HIV-negative children younger than 15 years. Reference standards comprised culture or a composite reference standard for tuberculosis and drug susceptibility testing or MTBDRplus (molecular assay for detection of Mycobacterium tuberculosis and drug resistance) for rifampicin resistance. We included studies evaluating sputum, gastric aspirate, stool, nasopharyngeal or bronchial lavage specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), fine needle aspirates, or surgical biopsy tissue (lymph node tuberculosis). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality using the Quality Assessment of Studies of Diagnostic Accuracy - Revised (QUADAS-2). For each target condition, we used the bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: For pulmonary tuberculosis, 299 data sets (68,544 participants) were available for analysis; for tuberculous meningitis, 10 data sets (423 participants) were available; for lymph node tuberculosis, 10 data sets (318 participants) were available; and for rifampicin resistance, 14 data sets (326 participants) were available. Thirty-nine studies (80%) took place in countries with high tuberculosis burden. Risk of bias was low except for the reference standard domain, for which risk of bias was unclear because many studies collected only one specimen for culture. Detection of pulmonary tuberculosis For sputum specimens, Xpert MTB/RIF pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 64.6% (55.3% to 72.9%) (23 studies, 493 participants; moderate-certainty evidence) and 99.0% (98.1% to 99.5%) (23 studies, 6119 participants; moderate-certainty evidence). For other specimen types (nasopharyngeal aspirate, 4 studies; gastric aspirate, 14 studies; stool, 11 studies), Xpert MTB/RIF pooled sensitivity ranged between 45.7% and 73.0%, and pooled specificity ranged between 98.1% and 99.6%. For sputum specimens, Xpert Ultra pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 72.8% (64.7% to 79.6%) (3 studies, 136 participants; low-certainty evidence) and 97.5% (95.8% to 98.5%) (3 studies, 551 participants; high-certainty evidence). For nasopharyngeal specimens, Xpert Ultra sensitivity (95% CI) and specificity (95% CI) were 45.7% (28.9% to 63.3%) and 97.5% (93.7% to 99.3%) (1 study, 195 participants). For all specimen types, Xpert MTB/RIF and Xpert Ultra sensitivity were lower against a composite reference standard than against culture. Detection of tuberculous meningitis For cerebrospinal fluid, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 54.0% (95% CI 27.8% to 78.2%) (6 studies, 28 participants; very low-certainty evidence) and 93.8% (95% CI 84.5% to 97.6%) (6 studies, 213 participants; low-certainty evidence). Detection of lymph node tuberculosis For lymph node aspirates or biopsies, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 90.4% (95% CI 55.7% to 98.6%) (6 studies, 68 participants; very low-certainty evidence) and 89.8% (95% CI 71.5% to 96.8%) (6 studies, 142 participants; low-certainty evidence). Detection of rifampicin resistance Xpert MTB/RIF pooled sensitivity and specificity were 90.0% (67.6% to 97.5%) (6 studies, 20 participants; low-certainty evidence) and 98.3% (87.7% to 99.8%) (6 studies, 203 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We found Xpert MTB/RIF sensitivity to vary by specimen type, with gastric aspirate specimens having the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%. Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher and specificity slightly lower. Xpert MTB/RIF was accurate for detection of rifampicin resistance. Xpert MTB/RIF was sensitive for diagnosing lymph node tuberculosis. For children with presumed tuberculous meningitis, treatment decisions should be based on the entirety of clinical information and treatment should not be withheld based solely on an Xpert MTB/RIF result. The small numbers of studies and participants, particularly for Xpert Ultra, limits our confidence in the precision of these estimates.


Assuntos
Tipagem Molecular/métodos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Meníngea/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Antibióticos Antituberculose/uso terapêutico , Viés , Criança , Fezes/microbiologia , Conteúdo Gastrointestinal/microbiologia , Humanos , Tipagem Molecular/normas , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/microbiologia , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
12.
BMC Infect Dis ; 20(1): 556, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736602

RESUMO

BACKGROUND: There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa. METHODS: Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI). RESULTS: Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR = 10.11 (95% CI: 1.56-116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR = 12.69 (95% CI: 1.82-141.60) and AR = 0.25 (95% CI: 0.06-0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor. CONCLUSIONS: The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.


Assuntos
Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/genética , Tuberculose/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Isoniazida/uso terapêutico , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Filogenia , Rifampina/uso terapêutico , África do Sul , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
13.
BMC Infect Dis ; 20(1): 570, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758165

RESUMO

BACKGROUND: In sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis (TB) and developing TB infection but are mostly missed due to poor access to healthcare. Active case-finding (ACF) of TB in prisons facilitates early diagnosis and treatment of inmates and prevent the spread. We explored literature and described evidence on TB ACF interventions and approaches for prisoners in SSA prisons. METHODS: Guided by the Arksey and O'Malley framework, we searched PubMed, Google Scholar, SCOPUS, Academic search complete, CINAHL and MEDLINE with full text via EBSCOhost for articles on prisoners and ACF from 2000 to May 2019 with no language restriction. Two investigators independently screened the articles at the abstract and full-text stages in parallel guided by the eligibility criteria as well as performed the methodological quality appraisal of the included studies using the latest mixed-method appraisal tool. We extracted all relevant data, organized them into themes and sub-themes, and presented a narrative summary of the results. RESULTS: Of the 391 eligible articles found, 31 met the inclusion criteria. All 31 articles were published between 2006 and 2019 with the highest six (19.4%) in 2015. We found evidence in 11 countries. That is, Burkina Faso, Cameroon, Coˆte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Malawi, Nigeria, South Africa, Uganda, and Zambia with most 41.9% (13/31) recorded in Ethiopia. These intervention studies were conducted in 134 prisons between 2001 and 2018 using either a single or combination of mass, facility-led, entry, peer educators for routine screening, and exit ACF approaches. The majority (74%) of the studies utilized only a mass screening approach. The most (68%) reported study outcome was smear-positive TB cases only (68%). We found no evidence in 16 SSA countries although they are classified among the three high-burden country lists for TB TB/HIV and Multidrug resistant-TB group. CONCLUSION: Our review highlights a dearth of evidence on TB ACF interventions in most SSA countries prisons. Hence, there is the need to scaling-up ACF interventions in SSA prisons, particularly countries included in the three high-burden country lists for TB, TB/HIV, and MDR-TB.


Assuntos
Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Prisioneiros , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , África ao Sul do Saara/epidemiologia , Antibióticos Antituberculose/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Rifampina/uso terapêutico , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
14.
BMC Infect Dis ; 20(1): 594, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787869

RESUMO

BACKGROUND: Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. METHODS: Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. RESULTS: The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). CONCLUSION: Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as 'WhatsApp' and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different contexts.


Assuntos
Diagnóstico Tardio/prevenção & controle , Testes Diagnósticos de Rotina/métodos , Monitoramento Epidemiológico , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Antibióticos Antituberculose/uso terapêutico , Comunicação , Farmacorresistência Bacteriana Múltipla , Instalações de Saúde , Humanos , Laboratórios , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Projetos Piloto , Estudos Prospectivos , Pesquisa Qualitativa , Rifampina/uso terapêutico , Manejo de Espécimes/métodos , Tanzânia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
15.
Medicine (Baltimore) ; 99(34): e21751, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846799

RESUMO

INTRODUCTION: Chryseobacterium arthrosphaerae is a gram-negative bacteria, known for its intrinsic multidrug resistance, which can lead to treatment difficulties. PATIENT CONCERNS: A 56-year-old male had an indwelling external ventricular drainage catheter for 6 months and had been frequently treated with antibiotics for nosocomial infections. He showed cerebrospinal fluid pleocytosis and an abrupt fever during hospitalization. DIAGNOSIS: He was diagnosed as a ventriculitis caused by Chryseobacterium arthrosphaerae (C arthrosphaerae). INTERVENTION: Initially, we used ciprofloxacin as the backbone in combination with minocycline (and rifampin). However, fever and pleocytosis persisted, and improvement was slow. We then switched the minocycline and rifampin regiment to trimethoprim/sulfamethoxazole. Following this switch of antibiotics, the patient's pleocytosis rapidly improved, allowing the replacement of his external ventricular drainage catheters. C arthrospharae was no longer growing in cerebrospinal fluid and he was recovered from ventriculitis. OUTCOMES: The patient remains alive without any incidence of C arthrosphaerae recurrence. CONCLUSION: We propose trimethoprim/sulfamethoxazole alone or in combination with ciprofloxacin to be good candidates for the treatment of ventriculitis by C arthrosphaerae.


Assuntos
Antibacterianos/uso terapêutico , Ventriculite Cerebral/tratamento farmacológico , Chryseobacterium , Antibacterianos/administração & dosagem , Cateteres de Demora , Ventriculite Cerebral/complicações , Ventriculite Cerebral/diagnóstico , Drenagem , Quimioterapia Combinada , Humanos , Leucocitose/etiologia , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Rifampina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
16.
PLoS One ; 15(8): e0236362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797053

RESUMO

BACKGROUND: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia. METHOD: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables. RESULTS: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development. CONCLUSIONS: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region.


Assuntos
Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Humanos , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Rifampina/uso terapêutico , Fatores de Risco , Escarro/efeitos dos fármacos , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adulto Jovem
17.
PLoS One ; 15(8): e0236054, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750053

RESUMO

INTRODUCTION: Multi-drug resistance is a major challenge in the control of tuberculosis. Despite newer modalities for diagnosis and treatment, people are still suffering from this disease. Understanding the common gene mutations conferring rifampicin and isoniazid resistance is crucial for the implementation of effective molecular tools at local and national levels. Hence, this study aimed to evaluate the molecular detection of rifampicin and isoniazid-resistant gene mutations in M.tuberculosis isolates in Addis Ababa, Ethiopia. METHOD: Health Center-based cross-sectional study was conducted between January and September 2017 in Addis Ababa, Ethiopia. The collected sputum samples were processed for mycobacterial isolation and Region of difference 9 based polymerase chain reaction for species identification. To characterize the rifampicin and isoniazid-resistant M. tuberculosis isolates, a molecular genetic assay (GenoType MTBDRplus) was used; the assay is based on DNA-STRIP technology. RESULT: Culture positivity was confirmed in 82.6% (190/230) of smear-positive newly diagnosed pulmonary tuberculosis cases enrolled in the study. From 190 isolates 93.2% were sensitive for both rifampicin and isoniazid, and 6.8% of the isolates were resistant to at least one of the tested anti-TB drugs. Gene mutations were observed in all studied multidrug resistance-associated gene loci (rpoB, katG, and inhA). Two isolates exhibited heteroresistance, a mutated, as well as wild type sequences, were detected in the respective strains. MDR-TB case was observed in 1.1% (2/190) of the cases. All the MDR-TB cases were positive for HIV and found to have a history of prior hospital admission. CONCLUSION: In our finding a relatively high prevalence of any drug resistance was observed and the overall prevalence of multidrug-resistant tuberculosis was 1.1%.The majority of drug-resistant isolates demonstrated common mutations. Heteroresistant strains were detected, signaling the existence of an M.tuberculosis population with variable responses to anti-tuberculosis drugs or of mixed infections.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapêutico , Estudos Transversais , Análise Mutacional de DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Etiópia , Feminino , Genes Bacterianos/genética , Loci Gênicos/genética , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase , Rifampina/farmacologia , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
18.
Medicine (Baltimore) ; 99(32): e21641, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769931

RESUMO

RATIONALE: Intestinal tuberculosis (TB) is rarely seen in patients with end-stage renal disease (ESRD). We report an intestinal TB case with a clinical presentation similar to that of colon cancer in a patient with ESRD on hemodialysis. PATIENT CONCERNS: A 49-year-old man presented with a 3-month history of general weakness and anorexia. He had been treated for stage 5 chronic kidney disease (CKD) due to diabetic nephropathy for the last 3 years. His blood urea nitrogen and serum creatinine levels were 96.9 and 8.1 mg/dL, respectively, at the time of admission; azotemia was accompanied by severe anemia, hypoalbuminemia, hyperkalemia, and metabolic acidosis. Hemodialysis was initiated for suspected exacerbation of uremia; however, intermittent fever, night sweats, and abdominal discomfort persisted. DIAGNOSES: Abdominal computed tomography (CT) and whole-body F-fluorodeoxyglucose positron emission tomography were indicative of ascending colon cancer with lymph node metastases. However, colonoscopy with biopsy revealed the formation of submucosal caseating granuloma and acid-fast bacillus. INTERVENTIONS: We initiated quadruple therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol. The patient continued the quadruple regimen for the first 2 months before switching to dual therapy and received anti-TB medications for a total of 12 months. OUTCOMES: After 9 months of standard anti-TB chemotherapy, polypoid residual lesions were noted during follow-up colonoscopy. Laparoscopy-assisted ileocecal resection was performed. No findings suggestive of recurrence of colonic TB were observed on follow-up abdominal CT at 6 months after discontinuation of anti-TB medications. LESSONS: If non-specific uremic symptoms persist in patients with advanced CKD, the possibility of extrapulmonary TB such as intestinal TB must be considered. Also, in patients with radiologic suspicion of colon cancer, endoscopy with biopsy should be performed promptly to exclude colonic TB with similar clinical manifestations.


Assuntos
Falência Renal Crônica/complicações , Tuberculose Gastrointestinal/etiologia , Anorexia/etiologia , Antituberculosos/uso terapêutico , Combinação de Medicamentos , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Pirazinamida/uso terapêutico , Diálise Renal/métodos , República da Coreia , Rifampina/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Tuberculose Gastrointestinal/fisiopatologia
19.
Niger J Clin Pract ; 23(8): 1172-1177, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788498

RESUMO

Background: Multidrug-resistant tuberculosis (MDR-TB) is a global health challenge. The emergence of MDR TB has contributed remarkably to the spread of tuberculosis and also poses a threat, which if not effectively addressed may wipe out the achievements of previous efforts in controlling tuberculosis. Objective: This study was aimed at detecting MDR-TB among patients in a setting prevalent with tuberculosis and HIV in Southeast, Nigeria. Method: Sputum specimens collected from 740 suspected tuberculosis (TB) patients were screened for acid-fast bacilli (AFB). All the 111 AFB positive samples were subjected to culture on Lowenstein-Jensen (LJ) medium and Mycobacterium Growth Indicator Tube (MGIT) 960 TB system. The isolates were then confirmed as Mycobacterium tuberculosis using SD Bioline Rapid Diagnostic Tests before being subjected to drug susceptibility testing to first-line anti-TB drugs. MDR-TB was determined by isolates being resistant to both isoniazid and rifampicin. HIV testing was performed for participants included in the study using standard rapid diagnostic tests. Result: Out of the 111 AFB-positive sputum samples, 65 (58.6%) were culture-positive for Mycobacterium tuberculosis. MDR-TB was found in 2 ([3.1%] 95% CI = 0.0-7.3) of the culture-positive samples. The rate of TB and HIV coinfection was 7.7%. Maximum single-drug resistance was seen in ethambutol 12 ([18.5%] 95% CI = 9.0-27.9). Conclusion: The MDR-TB rate of 3.1% found in this study was relatively low and efforts should be intensified to keep it low.


Assuntos
Antituberculosos/farmacologia , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Antituberculosos/uso terapêutico , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Nigéria/epidemiologia , Valor Preditivo dos Testes , Prevalência , Rifampina/farmacologia , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
20.
BMC Infect Dis ; 20(1): 543, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711457

RESUMO

BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Rifampina/uso terapêutico , Tempo para o Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Federação Russa , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
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