RESUMO
BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ≥15â years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6â h·week-1; and randomly selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place. FINDINGS: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13â points had 4.2-fold (95% CI 2.3-7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6â months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.
Assuntos
Qualidade de Vida , Tuberculose Resistente a Múltiplos Medicamentos , Atividades Cotidianas , Adolescente , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Pyrazinamide (PZA) is the most important drug against the latent stage of tuberculosis (TB) and is used in both first and second line treatment regimens. The continued increase in multi-drug resistant TB and the prevalence of PZA resistance makes the development of alternative assays for prompt identification of PZA resistance all the more important. METHODS: We standardized and evaluated a quantitative variant of the Wayne assay (QW) for determining PZA resistance in Mycobacterium tuberculosis strains. This assay quantifies M. tuberculosis metabolism of PZA and production of pyrazinoic acid (POA) using visible spectrophotometry. We evaluated this method using PZA concentrations of 400 µg/ml and 800 µg/ml at incubation periods of 3, 5 and 7 days. M. tuberculosis strains from 68 sputum samples were also tested with the standard Wayne assay, Tetrazolium Microplate Assay (TEMA), Bactec 460TB and pncA sequencing. We compared QW and standard Wayne assay against a dichotomous reference classification using concordant Bactec 460TB and pncA sequencing. Secondarily, we determined the quantitative correlation between both QW values and TEMA's minimum inhibitory concentration (MIC) against Bactec 460TB percentage growth. RESULTS: The standard Wayne showed sensitivity of 88% and specificity of 97.5%, giving a Youden Index (YI) of 0.855 against reference tests. The QW showed maximum YI of 0.934 on day 7 at 400 µg/ml PZA with 96% sensitivity and 97.4% specificity. Absorbance OD values for 400 µg/ml PZA were more accurate than 800 µg/ml PZA. Although QW showed high accuracy for PZA susceptibility, it did not correlate quantitatively with Bactec percentage growth. TEMA testing was unreliable and did not correlate with Bactec results. CONCLUSIONS: The proposed QW assay is an inexpensive method capable of providing standardization and automation of colorimetric PZA resistance testing, with better discriminatory than the standard Wayne assay.
Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/uso terapêutico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/metabolismo , Área Sob a Curva , Calibragem , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/normas , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/metabolismo , Valor Preditivo dos Testes , Pirazinamida/análogos & derivados , Pirazinamida/metabolismo , Curva ROC , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria , Escarro/microbiologia , Tuberculose Pulmonar/microbiologiaRESUMO
Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The objective of this study was to explore the potential for extending the MODS assay to rapid second-line DST and to identify critical concentrations of candidate drugs for prospective testing. Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan-Meier survival curve analysis. Candidate critical concentrations were determined for capreomycin (10 µg·mL(-1)), ciprofloxacin (1.25 µg·mL(-1)), cycloserine (40 µg·mL(-1)), ethambutol (10 µg·mL(-1)), ethionamide (5 µg·mL(-1)), kanamycin (5 µg·mL(-1)), para-aminosalicylic acid (10 µg·mL(-1)) and streptomycin (10 µg·mL(-1)). No cut-off point was identified for the other second-line drugs or for pyrazinamide. At particular concentrations of some second-line TB drugs this novel Kaplan-Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity.
Assuntos
Antituberculosos/uso terapêutico , Testes de Sensibilidade Microbiana/métodos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla , Humanos , Peru , Fenótipo , Curva ROC , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnósticoRESUMO
An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes.
Assuntos
Annonaceae/química , Anti-Infecciosos/farmacologia , Mikania/química , Extratos Vegetais/química , Animais , Anti-Infecciosos/química , Linhagem Celular Tumoral , Sobrevivência Celular , Diterpenos/química , Diterpenos/farmacologia , Feminino , Humanos , Leishmania/efeitos dos fármacos , Lignanas/química , Lignanas/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Testes de Sensibilidade Parasitária , Peru , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Timol/química , Timol/farmacologia , Árvores , Trypanosoma cruzi/efeitos dos fármacosRESUMO
BACKGROUND: Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program. METHODS: Longitudinal cohort study following up 93 adults initiating tuberculosis therapy in Lima, Peru. Baseline culture and drug susceptibility tests (DSTs) were performed using the MBBacT, proportion, and microscopic observation drug susceptibility (MODS) methods. Smear microscopy and MODS liquid culture were performed at baseline and weekly for 4 weeks then every other week for 26 weeks. RESULTS: Median conversion time from culture positivity to culture negativity of 38.5 days was unaffected by baseline smear status. Patients with fully susceptible tuberculosis had a median time to culture conversion of 37 days; 10% remained culture positive at day 60. Delayed culture conversion was associated with multidrug resistance, regardless of DST method used; non-multidrug resistance as defined by the proportion method and MODS (but not MBBacT) was also associated with delay. Persistent day 60 smear positivity yielded positive and negative predictive values of 67% and 92%, respectively, for detecting multidrug resistance. CONCLUSIONS: Smear and culture conversion in treated tuberculosis patients takes longer than is conventionally believed, even with fully susceptible disease, and must be accounted for in tuberculosis treatment and prevention programs. Persistent day 60 smear positivity is a poor predictor of multidrug resistance. The industrialized-world convention of universal baseline DST for tuberculosis patients should become the standard of care in multidrug resistance-affected resource-limited settings.
Assuntos
Antituberculosos/uso terapêutico , Derrame de Bactérias , Terapia Diretamente Observada , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto , Animais , Técnicas Bacteriológicas , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes de Sensibilidade Microbiana , Microscopia , Pessoa de Meia-Idade , Peru , Escarro/microbiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS: A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS: Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS: MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.
Assuntos
Antituberculosos/administração & dosagem , Técnicas de Tipagem Bacteriana/métodos , Infecções por HIV/microbiologia , Isoniazida/administração & dosagem , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/diagnóstico , Adulto , Técnicas de Tipagem Bacteriana/economia , Distribuição de Qui-Quadrado , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/economia , Microscopia/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes , Escarro/microbiologia , Fatores de Tempo , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Tuberculose/virologiaRESUMO
A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, Plagiochila disticha and Ambrosia peruviana, led to the isolation and characterization of three ENT-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A ( 1), I ( 2), and R ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their in vitro antileishmanial, trypanocidal, and antituberculosis activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes, as well as against MDR and sensitive strains of Mycobacterium tuberculosis, respectively.
Assuntos
Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/química , Azulenos/isolamento & purificação , Compostos de Epóxi/isolamento & purificação , Piranos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Peru , Plantas Medicinais/químicaRESUMO
A multidisciplinary and international team of scientists was assembled in the early 1990s to conduct an ethnobotanical study of plants used by the Aguaruna people of the Peruvian Amazon forest. The initial ethnobotanical project, carried out under the auspices of an International Cooperative Biodiversity Grant (ICBG), led to the collection of approximately 4000 plant species. Some members of the original team of scientists have continued this collaboration by focusing on potential sources of new anticancer, anti-infective, and wound-healing agents. This effort has uncovered several secondary metabolites representing a wide variety of chemical diversity. In this short review we describe some bioactive compounds of interest as part of our continuing collaboration.
Assuntos
Plantas Medicinais/química , Etnobotânica , Humanos , Medicina Tradicional , Estrutura Molecular , PeruRESUMO
Synthesis of a cytotoxic dihydrochalcone, first isolated from a traditional Amazonian medicinal plant Iryanthera juruensis Warb (Myristicaceae), followed by a comprehensive SAR analysis of saturated and unsaturated chalcone synthetic intermediates, led to the identification of analogues with selective and significant in vitro anti- Trypanosoma cruzi activity. Further SAR studies were undertaken with the synthesis of 21 new chalcones containing two allyloxy moieties that resulted in the discovery of 2',4'-diallyloxy-6'-methoxy chalcones with improved selectivity against this parasite at concentrations below 25 microM, four of which exhibited a selectivity index greater than 12.
Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Células 3T3 , Animais , Antiprotozoários/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Myristicaceae/química , Testes de Sensibilidade Parasitária , Extratos Vegetais/síntese química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A pharmacological screening of the ethanol extract and fractions of Blepharodon nitidum led to the isolation of fourteen compounds, two of which, 24-hydroperoxycycloart-25-en-3beta-ol and 25-hydroperoxycycloart-23-en-3beta-ol, exhibited in vitro anti- Mycobacterium tuberculosis and antileishmanial activities, as well as significant cytotoxic activity against a panel of human tumor cell lines.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apocynaceae/química , Linhagem Celular Tumoral , Humanos , Estrutura MolecularRESUMO
The antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2',4'-dihydroxy-6'-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13-acetate (7), respectively. Eight human tumor cell lines and two nontumorigenic cell lines were used in this investigation. Their in vitro activity against Mycobacterium tuberculosis is also reported.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Plantas Medicinais/química , Strychnos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Triterpenos Pentacíclicos , Peru , Triterpenos/química , Células Tumorais Cultivadas , Ácido BetulínicoRESUMO
Human cystic echinococcosis (hydatid disease) continues to be a substantial cause of morbidity and mortality in many parts of the world. Elimination is difficult to obtain and it is estimated that, using current control options, achieving such a goal will take around 20 years of sustained efforts. Since the introduction of current (and past) hydatid control campaigns, there have been clear technological improvements made in the diagnosis and treatment of human and animal cystic echinococcosis, the diagnosis of canine echinococcosis, and the genetic characterisation of strains and vaccination against Echinococcus granulosus in animals. Incorporation of these new measures could increase the efficiency of hydatid control programmes, potentially reducing the time required to achieve effective prevention of disease transmission to as little as 5-10 years.
Assuntos
Equinococose/prevenção & controle , Echinococcus/crescimento & desenvolvimento , Echinococcus/imunologia , Animais , Cães , Equinococose/epidemiologia , Equinococose/imunologia , Echinococcus/genética , Saúde Global , Humanos , Imunoterapia Ativa , Controle de Infecções/tendências , Programas Nacionais de Saúde/tendências , Ovinos/parasitologiaRESUMO
In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sites caused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis.
Assuntos
Pele/efeitos dos fármacos , Teste Tuberculínico/normas , Tuberculose/diagnóstico , Zinco/deficiência , Zinco/farmacologia , Administração Tópica , Adulto , Diagnóstico Diferencial , Método Duplo-Cego , Reações Falso-Negativas , Feminino , Humanos , Masculino , Estado Nutricional , Peru , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Classe Social , Fatores Socioeconômicos , Oligoelementos/sangue , Oligoelementos/farmacologia , Teste Tuberculínico/métodos , Zinco/sangueRESUMO
An ethanol extract of the Peruvian plant Clavija procera, a member of the rare Theophrastaceae family, was fractionated using a colorimetric bioassay-guided protocol against Mycobacterium tuberculosis (MTB), yielding the oleanane triterpenoid aegicerin (1) as the active constituent. Its MIC values ranged between 1.6 and 3.12 microg/mL against 37 different sensitive and resistant MTB strains (1 H37Rv, 21 susceptible clinical isolates, 2 INH-resistant clinical isolates, and 13 MDR clinical isolates).
Assuntos
Antituberculosos , Mycobacterium tuberculosis/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Plantas Medicinais/química , Triterpenos , Animais , Antituberculosos/química , Antituberculosos/isolamento & purificação , Antituberculosos/farmacologia , Chlorocebus aethiops , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Células VeroRESUMO
Decades of social and political unrest have contributed to the urbanization of the population of Peru with large-scale migration from rural Andean and Amazonian communities to overcrowded shantytowns around Lima. We administered a face-to-face survey questionnaire to 116 patients with suspected and proven tuberculosis (TB) in northern Lima to determine the extent to which the use of traditional therapies from indigenous regions persists and the impact of any such use on TB control. Sixty-three percent of participants reported some form of self-treatment prior to presentation to the National Tuberculosis Program; 52% of them used traditional remedies. Symptom duration was longer among self-remedy users than non-users (median = 25 versus 15 days; P = 0.07) and among those exclusively using western remedies rather than traditional remedies (median = 30 versus 15 days; P = 0.01). We thus found no evidence that use of traditional remedies has an appreciable effect on diagnostic delay in Lima.
Assuntos
Antituberculosos/administração & dosagem , Medicina Tradicional , Tuberculose/prevenção & controle , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Peru/epidemiologia , Plantas MedicinaisRESUMO
BACKGROUND: The relative-dose-response (RDR) test is used to identify subjects with marginal liver vitamin A stores, but its use has not been evaluated during episodes of infection. OBJECTIVE: The objective was to assess, with the RDR test, the vitamin A status of children recovering from pneumonia. DESIGN: As part of a double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima, Peru, we examined the association of treatment group, nutritional status, severity of disease, and induction of the acute phase response [on the basis of serum C-reactive protein (CRP)] on serum retinol and the RDR test. RESULTS: Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery. Serum CRP had a significant, inverse association with retinol at both admission and discharge. Serum retinol and CRP concentrations never differed significantly between the treatment groups. Among subjects with CRP > or =10 mg/L, 21% in the vitamin A group and 20% in the placebo groups (P = 0.83) had a positive RDR test result. Among subjects with CRP <10 mg/L, 56% in the placebo group but only 6% in the vitamin A group had positive RDR test results (P = 0.002). CONCLUSION: The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were <10 mg/L but not when CRP concentrations were higher.