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3.
Trop Med Int Health ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31944502

RESUMO

BACKGROUND: Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3- and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. METHODS: New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3- or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H3 R3 Z3 E3 /4R3 H3 ) [C]. The 4 test regimens were 3R7 H7 Z7 E7 M7 [M3], 2R7 H7 Z7 E7 M7 /2R7 H7 M7 [M4], 2R7 H7 Z7 E7 M7 /2R3 H3 M3 [M4-I] or 2R7 H7 Z7 E7 M7 /2R3 H3 E3 M3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The primary end point was TB recurrence post-treatment. RESULTS: Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimens and 93% in the control  regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI -3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification. CONCLUSION: The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.

5.
Sci Rep ; 9(1): 17892, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784670

RESUMO

The major human pathogen Mycobacterium tuberculosis is rarely reported to cause disease in other animals. Cases in livestock are thought to occur through contact with infected handlers, but previous studies evaluating putative livestock-human transmission used typing techniques with limited resolution. Here, we undertook cross-sectional surveillance for tuberculosis in 271 livestock handlers and 167 cattle on three farms in Chennai, India and defined the relatedness of cultured isolates using whole genome sequencing. Humans and livestock were screened for active mycobacterial infection, and opportunistic post-mortem examination was performed on comparative intradermal test-positive cattle that died. Four cattle and 6 handlers on two farms were culture-positive for M. tuberculosis; M. bovis was not isolated. All 10 isolates (one from each case) belonged to Lineage 1. Pairwise genome comparisons of single nucleotide polymorphism (SNP) differences ranged from 1 to 600 SNPs, but 3 isolate pairs were less than 5 SNPs different. Two pairs were from handlers and the third pair were from two cattle on the same farm. The minimum pairwise SNP difference between a cattle and human isolate was >250 SNPs. Our study confirms the presence of M. tuberculosis infection in cattle in India, sequencing of which characterised relatedness between human and cattle-derived isolates.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31820812

RESUMO

BACKGROUND: To measure and compare economic burden at the household level for tuberculosis (TB) patients who were detected through active case finding (ACF) and passive case finding (PCF) in rural areas. METHODS: This study was conducted in the Thiruvallur district from October 2016 to March 2018. TB patients diagnosed through ACF were included in this study. For the comparison, patients diagnosed through ACF were recruited in the ratio of 1:2 from the same study area during the same period. Costs between the groups were compared and a multiple regression model was used to identify factors associated with catastrophic costs due to TB. RESULTS: Of the 336 individuals, 110 were diagnosed through ACF and 226 through PCF. A total of 29% of patients diagnosed through PCF and 9% of patients diagnosed through ACF experienced catastrophic costs due to TB. The multiple logistic model shows that catastrophic costs due to TB had a significant association with higher income status (adjusted odds ratio [aOR] 4.91 [confidence interval {CI} 2.39 to 10.08]; p<0.001), alcohol use (aOR 2.78 [CI 1.33 to 5.81]; p=0.007), private as a first point of care (aOR 3.91 [CI 2.01 to 7.60]; p<0.001) and PCF (aOR 3.68 [CI 1.62 to 8.33]; p=0.002). CONCLUSIONS: Findings highlight that ACF significantly averted catastrophic costs due to TB among patients. ACF as a strategy could ensure financial protection of TB patients and limit their risk of poverty.

7.
J Glob Health ; 9(2): 020701, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673343

RESUMO

Background: Millennium Development Goal 4 (MDGs) mobilised countries to reduce child mortality by two thirds the 1990 rate in 2015. While India did not reach MDG 4, it considerably reduced child mortality in the MDG-era. Efficient and targeted interventions and adequate monitoring are necessary to further progress in improvements to child health. Looking forward to the Sustainable Development Goal (SDG)-era, the Indian Council of Medical Research and The INCLEN Trust International conducted a national research priority setting exercise for maternal, child, newborn health, and maternal and child nutrition. Here, results are reported for child health. Methods: The Child Health and Nutrition Research Initiative (CHNRI) method for research priority setting was employed. Research ideas were crowd-sourced from a network of child health experts from across India; these were refined and consolidated into research options (ROs) which were scored against five weighted criteria to arrive weighted Research Priority Scores (wRPS). National and regional priority lists were prepared. Results: 90 experts contributed 596 ideas that were consolidated into 101 research options (ROs). These were scored by 233 experts nationwide. National wRPS for ROs ranged between 0.92 and 0.51. The majority of the top research priorities related to development of cost-effective interventions and their implementation, and impact evaluations, improving data quality; and monitoring of existing programs, or improving the management of morbidities. The research priorities varied between regions, the Economic Action Group and North-Eastern states prioritised questions relating to delivering interventions at community- or household-level, whereas the North-Eastern states and Union Territories prioritised research questions involving managing and measuring malaria, and the Southern and Western states prioritised research questions involving pharmacovigilance of vaccines, impact of newly introduced vaccines, and delivery of vaccines to hard-to-reach populations. Conclusions: Research priorities varied geographically, according the stage of development of the area and mostly pertained to implementation sciences, which was expected given diversity in epidemiological profiles. Priority setting should help guide investment decisions by national and international agencies, therefore encouraging researchers to focus on priority areas. The ICMR has launched a grants programme for implementation research on maternal and child health to pursue research priorities identified by this exercise.

8.
Lancet Oncol ; 20(11): e637-e644, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31674322

RESUMO

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

10.
Microbiol Resour Announc ; 8(40)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582446

RESUMO

Here, we report the isolation of Mycobacterium orygis from dairy cattle in Chennai, India. Spoligotyping assigned the isolate to spoligotype 587 (ST587), which belongs to M. orygis This species was confirmed as M. orygis using whole-genome sequencing.

13.
Indian J Med Res ; 149(4): 517-527, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411176

RESUMO

Background & objectives: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. Methods: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. Results: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. Interpretation & conclusions: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.


Assuntos
Tuberculose Latente/epidemiologia , Modelos Teóricos , Tuberculose/epidemiologia , Humanos , Índia/epidemiologia , Tuberculose Latente/microbiologia , Tuberculose Latente/prevenção & controle , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Organização Mundial da Saúde
15.
PLoS One ; 14(7): e0218034, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318864

RESUMO

Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.

16.
Indian J Pediatr ; 86(8): 703-706, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31240568
17.
BMC Infect Dis ; 19(1): 529, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208430

RESUMO

BACKGROUND: Tuberculosis (TB)-associated Immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response in TB patients with advanced human immunodeficiency virus coinfection, after antiretroviral therapy commencement. CASE PRESENTATION: We present a rare case of a 51-year-old woman living with HIV who developed a series of TB-IRIS events occurring at multiple sites sequentially, highlighting the clinical complexity in diagnosis and management. CONCLUSION: This case illustrates how complicated a clinical scenario of successive TB-IRIS episodes can be, in terms of clinical management.


Assuntos
Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/etiologia , Tuberculose Pulmonar/complicações , Fármacos Anti-HIV/efeitos adversos , Coinfecção/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Pessoa de Meia-Idade
18.
J Glob Antimicrob Resist ; 19: 348-353, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31226332

RESUMO

OBJECTIVES: The emergence of drug-resistant tuberculosis (TB) poses a serious challenge to existing anti-TB therapies. Hence, there is a direct need for identification of new drugs and effective combination regimens. METHODS: In this study, minimum inhibitory concentrations (MICs) of the anti-TB drugs bedaquiline (BDQ), delamanid (DEL) and moxifloxacin (MFX) were evaluated using a resazurin microtiter assay (REMA) against five drug-resistant clinicalMycobacterium tuberculosis (MTB) isolates as well as the drug-susceptible reference strain H37Rv. In addition, their fractional inhibitory concentration indices (FICIs) were evaluated using a REMA-based calorimetric chequerboard assay to assess their interaction profiles against the MTB isolates. RESULTS: The FICI indicated that BDQ acted synergistically with DEL against isoniazid (INH)-monoresistant, rifampicin (RIF)-monoresistant and extensively drug-resistant (XDR) clinical MTB isolates. In addition, the combination of DEL acted synergistically with MFX against INH-monoresistant, RIF-monoresistant and XDR clinical MTB isolates. Moreover, the combination of BDQ and MFX showed a synergistic effect against RIF-monoresistant and pre-XDR clinical MTB isolates. DEL at 0.125×MIC (i.e. 0.015µg/mL) used in combination with BDQ at 0.25×MIC (i.e. 0.015µg/mL) had a stronger bactericidal effect against the XDR-TB clinical isolate than DEL alone at 1×MIC (i.e. 0.125µg/mL). CONCLUSION: Synergistic and additive effects between these two-drug combinations offer an attractive chemotherapeutic regimen against drug-resistant clinical MTB isolates.

20.
Clin Infect Dis ; 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31075166

RESUMO

BACKGROUND: The relationships between first-line drug concentrations and clinically-important outcomes among patients with tuberculosis (TB) remain poorly understood. METHODS: We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. Maximum plasma concentration of each drug was determined at month 1 and 5 using blood samples drawn 2 hours post-dose. Sub-therapeutic cut-offs were: rifampicin <8µg/mL; isoniazid <3µg/mL; pyrazinamide <20µg/mL. Factors associated with lower log-transformed drug concentrations, unfavourable outcomes (composite of treatment failure, all-cause mortality, and recurrence) as well as individual outcomes were examined using Poisson regression models. RESULTS: Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were sub-therapeutic in 85%, 29%, and 12% at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with HIV co-infection (1.6 µg/ml vs 4.6 µg/ml; p = 0.015). Unfavourable outcome was observed in 19%; a 1 ug/ml decrease in rifampicin concentration was independently associated with unfavourable outcome (aIRR 1.21, 95% CI: 1.01 - 1.47) and treatment failure (aIRR: 1.16; 95% CI: 1.05 - 1.28). A 1 ug/ml decrease in pyrazinamide concentration was associated with recurrence (aIRR: 1.05; 95% CI: 1.01-1.11). CONCLUSIONS: Rifampicin concentrations were sub-therapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.

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