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1.
AIDS Care ; : 1-6, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070118

RESUMO

Delayed presentation to care of perinatally infected children in India continues to be a hindrance to achieving the "end pediatric HIV by 2020" goal. In this study, we characterize this issue by describing the prevalence, risk factors and temporal trends of delayed presentation to care of perinatally infected, antiretroviral therapy (ART) - naïve children using programmatic data from a tertiary care center in western India. Delayed presentation was defined as children presenting in moderate or severe WHO immunodeficiency categories. Of 269 children eligible for inclusion in the analysis, the median age at presentation was 4 years (IQR: 3-6 years) and prevalence of delayed presentation was 52%. Multivariable logistic regression identified domicile distance ≥20km from the ART center (OR: 2.2, 95% CI: 1.02-4.7) to be a risk factor for delayed presentation. An inverse association with increasing age (OR: 0.8, 95% CI: 0.7-0.9) was also seen. The proportion of children with delayed presentation between 2006 and 2016 remained unchanged (p = 0.36), although the median age at presentation over the same time period increased significantly (p < 0.001). Our results indicate the urgency of identifying strategies to improve linkage of perinatally infected ART-naïve children to care, earlier than what is currently observed.

2.
Infect Genet Evol ; 77: 104093, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678649

RESUMO

OBJECTIVE: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. METHODS: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. RESULTS: Among 211 participants, C/C allele was identified in 70% (n = 147); 26% (n = 55) and 4% (n = 9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (p =0.032); ii) smear grade among active TB patients and circulating IP-10 levels (p =0 .032). CONCLUSIONS: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.

3.
Clin Infect Dis ; 70(3): 436-445, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30919881

RESUMO

BACKGROUND: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. METHODS: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. RESULTS: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). CONCLUSIONS: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

4.
Clin Infect Dis ; 70(3): 425-435, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30942853

RESUMO

BACKGROUND: We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. METHODS: We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. RESULTS: From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. CONCLUSIONS: The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

5.
J Infect Dis ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796955

RESUMO

BACKGROUND: Gene expression profiling is emerging as a tool for tuberculosis diagnosis and treatment response monitoring, but limited data specific to Indian children and incident tuberculosis infection (TBI) exist. METHODS: 16 pediatric Indian tuberculosis cases were age- and sex-matched to 32 tuberculosis-exposed controls (13 developed incident TBI without subsequent active tuberculosis). Longitudinal samples were collected for RNAseq. Differential expression analysis generated gene lists that identify tuberculosis diagnosis and tuberculosis treatment response. Data were compared with published gene lists. Population-specific risk score thresholds were calculated. RESULTS: 71 genes identified tuberculosis diagnosis and 25 treatment response. Within-group expression was partially explained by age, sex, and incident TBI. Transient changes in gene expression were identified after both infection and treatment. Application of 27 published gene lists to our data found variable performance for tuberculosis diagnosis (sensitivity 0.38-1.00, specificity 0.48-0.93) and treatment response (sensitivity 0.70-0.80, specificity 0.40-0.80). Our gene lists found similarly variable performance when applied to published datasets for diagnosis (sensitivity 0.56-0.85, specificity 0.50-0.85) and treatment response (sensitivity 0.49- 0.86, specificity 0.50-0.84). CONCLUSIONS: Gene expression profiles among Indian children with confirmed tuberculosis were distinct from adult-derived gene lists, highlighting the importance of including distinct populations in differential gene expression models.

7.
Prostaglandins Other Lipid Mediat ; 147: 106398, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726221

RESUMO

Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.

9.
BMC Infect Dis ; 19(1): 914, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664933

RESUMO

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adolescente , Adulto , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Seguimentos , Humanos , Incidência , Índia/epidemiologia , Isoniazida/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tuberculose/prevenção & controle , População Urbana , Adulto Jovem
10.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
11.
PLoS Med ; 16(9): e1002907, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31509529

RESUMO

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

12.
Clin Infect Dis ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560049

RESUMO

BACKGROUND: Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB), and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX MDR-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. METHODS: Outpatient adults with signs and/or symptoms of pulmonary TB were prospectively enrolled. Sputum smear-microscopy and BD MAX were performed on a single raw sputum, which was then processed for mycobacterial culture and phenotypic drug susceptibility testing (DST), BD MAX and Xpert MTB/RIF (Xpert). RESULTS: 1053 participants with presumptive TB were enrolled with median age of 35 (47% female; 32% HIV-infected, and 32% unknown HIV status). In microbiologically-confirmed TB patients, BD MAX sensitivity was 93% (262/282 [95% CI 89, 95]); specificity was 97% (593/610 [96, 98]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175, [98,100]) for smear-positive samples (florescence smear-microscopy), and 81% (87/107, [73,88]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274, [87,94]) for BD MAX and 90% (246/274 [86,93]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared to phenotypic DST was 90% (9/10 [60,98]) and 95% (211/222 [91,97]), respectively. Sensitivity and specificity for detection of INH resistance was 82% (22/27 [63,92]) and 100% (205/205 [98,100]), respectively. CONCLUSIONS: The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB, and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally.

13.
Lancet HIV ; 6(9): e588-e600, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31371262

RESUMO

BACKGROUND: Antiretroviral therapy (ART) management is challenging for individuals in resource-limited settings presenting for third-line treatment because of complex resistance patterns, partly due to reduced access to viral load monitoring. We aimed to evaluate use of newer antiretroviral drugs and contemporary management approaches, including population-based sequencing, to select appropriate antiretrovirals, plasma viral load monitoring, and interventions to improve adherence in individuals presenting with second-line viral failure. METHODS: A5288 was a phase 4, third-line ART strategy study done at 19 urban sites in ten countries that enrolled adult participants with confirmed plasma HIV-1 RNA (viral load) of 1000 copies per mL or more after more than 24 weeks of protease inhibitor-based second-line ART. The primary objective was to use antiretrovirals (raltegravir, etravirine, and ritonavir-boosted darunavir) and diagnostic monitoring technologies, including viral load, genotyping, and adherence support to achieve viral load suppression (defined as ≤200 copies per mL) in 65% or more of participants. ART history and real-time drug resistance genotypes were used to assign participants to one of four cohorts: cohort A (no lopinavir resistance) stayed on second-line ART and cohorts B (B1, best available nucleoside reverse transcriptase inhibitors [NRTIs] plus ritonavir-boosted darunavir plus raltegravir; B2, ritonavir-boosted darunavir plus raltegravir plus etravirine; B3, ritonavir-boosted darunavir, raltegravir, and either tenofovir plus emtricitabine or tenofovir plus lamivudine), C (ritonavir-boosted darunavir plus raltegravir plus tenofovir-emtricitabine or tenofovir plus lamivudine), and D (best available NRTIs plus ritonavir-boosted darunavir plus raltegravir) were defined by increasing levels of resistance and received appropriate regimens, including new antiretrovirals. Participants in Cohort B without detectable hepatitis B surface antigen were assigned by blocked randomisation to cohorts B1 and B2, and those with detectable hepatitis B surface antigen were assigned to cohort B3. The trial is registered with ClinicalTrials.gov, number NCT01641367. FINDINGS: From Jan 10, 2013, to Sept 10, 2015, 545 participants were enrolled. 287 (53%) were assigned to cohort A, 74 (14%) to B1, 72 (13%) to B2, eight (1%) to B3, 70 (13%) to C, and 34 (6%) to D. Overall, 349 (64%, 95% CI 60-68) participants achieved viral suppression at week 48, with proportions varying from 125 (44%) of 287 in cohort A to 65 (88%) of 74 in cohort B1, 63 (88%) of 72 in B2, eight (100%) of eight in B3, 63 (90%) of 70 in C, and 25 (74%) of 34 in D. Participants in cohort A remained on their second-line protease inhibitor, and had the most participants with grade 3 or higher adverse events (147 [51%]). INTERPRETATION: Targeted real-time genotyping to select third-line ART can appropriately allocate more costly antiretrovirals to those with greater levels of HIV drug resistance. FUNDING: National Institutes of Health.

14.
JMIR Form Res ; 3(3): e13411, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31456581

RESUMO

BACKGROUND: India accounts for nearly one-quarter of the global tuberculosis (TB) burden. Directly observed treatment (DOT) through in-person observation is recommended in India, although implementation has been heterogeneous due largely to resource limitations. Video DOT (vDOT) is a novel, smartphone-based approach that allows for remote treatment monitoring through patient-recorded videos. Prior studies in high-income, low disease burden settings, such as the United States, have shown vDOT to be feasible, although little is known about the role it may play in resource-limited, high-burden settings. OBJECTIVE: The goal of the research was to assess the feasibility and acceptability of vDOT for adherence monitoring within a resource-limited, high TB burden setting of India. METHODS: We conducted a prospective, single-arm, pilot implementation of vDOT in Pune, India. Outcome measures included adherence (proportion of prescribed doses observed by video) and verifiable fraction (proportion of prescribed doses observed by video or verbally confirmed with the patient following an incomplete/unverifiable video submission). vDOT acceptability among patients was assessed using a posttreatment survey. RESULTS: A total of 25 patients enrolled. The median number of weeks on vDOT was 13 (interquartile range [IQR] 11-16). Median adherence was 74% (IQR 62%-84%), and median verifiable fraction was 86% (IQR 74%-98%). More than 90% of patients reported recording and uploading videos without difficulty. CONCLUSIONS: We have demonstrated that vDOT may be a feasible and acceptable approach to TB treatment monitoring in India. Our work expands the evidence base around vDOT by being one of the first efforts to evaluate vDOT within a resource-limited, high TB burden setting. To our knowledge, this is the first reported use of vDOT in India.

15.
PLoS One ; 14(7): e0220507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365583

RESUMO

BACKGROUND: More than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined. METHODS: We conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models. RESULTS: Of 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, p<0.001) and current smokers (aIRR: 3.58, 95% CI: 1.89-6.76, p<0.001). CONCLUSION: Past and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed.

16.
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.

18.
PLoS One ; 14(7): e0219131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283794

RESUMO

Defining occupational latent tuberculosis infection (LTBI) risk among healthcare workers is needed to support implementation of prevention guidelines. Prospective cohort study of 200 medical residents and nursing students in India was conducted May 2016-December 2017. Tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) were performed at study entry and 12 months. Primary outcome was incident LTBI (≥10mm TST induration and/or ≥0.35IU/mL QFT-GIT) at 12 months; secondary outcomes included baseline LTBI prevalence and risk factors for incident and prevalent LTBI using Poisson regression. Among 200, [90 nursing students and 110 medical residents], LTBI prevalence was 30% (95% CI, 24-37); LTBI incidence was 26.8 (95% CI, 18.6-37.2) cases per 100 person-years and differed by testing method (28.7 [95% CI, 20.6-38.9] vs 17.4 [95% CI, 11.5-25.4] cases per 100 person-years using TST and QFT-GIT, respectively). Medical residents had two-fold greater risk of incident LTBI than nursing students (Relative Risk, 2.16; 95% CI, 1.05-4.42). During study period 6 (3%) HCWs were diagnosed with active TB disease. Overall, median number of self-reported TB exposures was 5 (Interquartile Range, 1-15). Of 60 participants with prevalent and incident LTBI who were offered free isoniazid preventive therapy (IPT), only 2 participants initiated and completed IPT. High risk for LTBI was noted among medical residents compared to nursing students. Self-reported TB exposure is underreported, and uptake of LTBI prevention therapy remains low. New approaches are needed to identify HCWs at highest risk for LTBI.

19.
PLoS One ; 14(7): e0211155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260455

RESUMO

BACKGROUND: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected infants and young children is relatively understudied in regions endemic for HIV and TB. We aimed to describe incidence, clinical features and risk factors of pediatric IRIS in Sub-Saharan Africa and India. METHODS AND FINDINGS: We conducted an observational multi-centred prospective clinical study from December 2010 to September 2013 in children <72 months of age recruited from public antiretroviral programs. The main diagnostic criterion for IRIS was a new or worsening inflammatory event after initiating antiretroviral therapy (ART). Among 198 participants, median age 1.15 (0.48; 2.21) years, 38 children (18.8%) developed 45 episodes of IRIS. Five participants (13.2%) had two IRIS events and one (2.6%) had 3 events. Main causes of IRIS were BCG (n = 21; 46.7%), tuberculosis (n = 10; 22.2%) and dermatological, (n = 8, 17.8%). Four TB IRIS cases had severe morbidity including 1 fatality. Cytomegalovirus colitis and cryptococcal meningitis IRIS were also severe. BCG IRIS resolved without pharmacological intervention. On multivariate logistic regression, the most important baseline associations with IRIS were high HIV viral load (likelihood ratio [LR] 10.629; p = 0.0011), recruitment at 1 site (Stellenbosch University) (LR 4.01; p = 0.0452) and CD4 depletion (LR 3.4; p = 0.0654). Significantly more non-IRIS infectious and inflammatory events between days 4 and 17 of ART initiation were noted in cases versus controls (35% versus 15.2%: p = 0.0007). CONCLUSIONS: IRIS occurs commonly in HIV-infected children initiating ART and occasionally has severe morbidity. The incidence may be underestimated. Predictive, diagnostic and prognostic biomarkers are needed.

20.
Diabetes Metab Syndr ; 13(3): 1813-1819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31235099

RESUMO

BACKGROUND: Diabetes prevalence in HIV is not well characterized for India, despite the high burden of both individual diseases. Epidemiology of insulin resistance (IR): a precursor to diabetes, and its associated risk factors are also poorly understood in Asian Indian people living with HIV (PLHIV). We assessed the prevalence of diabetes and IR in Pune, India and the associated risk factors for IR. METHODS: Cross-sectional analysis of adult (≥18 years) PLHIV receiving care at Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, India (BJGMC- SGH). Proportions and medians of PLHIV characteristics by diabetes status and IR were described. Homeostatic Model Assessment (HOMA) index value ≥2 was used to define IR. Line of least squares assessed the relationship between IR and hyperinsulinemia. Association between sociodemographic, clinical factors with IR was determined using logistic regression. RESULTS: Of 485 enrollees, 47% were men, median age was 40 years (IQR: 35-46), median CD4 counts were 389 cells/mm3 (246-609). Thirty-five percent were centrally obese, 75% were adherent to WHO recommended physical activity guidelines. Prevalence of diabetes, prediabetes, IR were 9%, 16% and 38%, respectively. Twenty-nine percent non-diabetics had IR and it occurred much prior to the threshold for hyperinsulinemia. IR was associated with the use of ART drugs (OR: 6.6, 95% CI: 2.9-15.2 and 5.4, 95% CI: 2.2-13.6 for first- and second line ART respectively) and central obesity (OR:1.9, 95% CI: 1.1-3.4). CONCLUSIONS: One fourth of the study population was diabetic or prediabetic and more than a third had IR. Better understanding of diabetes disease progression in relation to IR and the effect of physical activity on central obesity among Asian Indian PLHIV is mandated.


Assuntos
Biomarcadores/análise , Diabetes Mellitus/epidemiologia , Infecções por HIV/complicações , HIV/isolamento & purificação , Hiperinsulinismo/epidemiologia , Resistência à Insulina , Estado Pré-Diabético/epidemiologia , Adulto , Glicemia/análise , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/virologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Infecções por HIV/virologia , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/virologia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/virologia , Prevalência , Prognóstico , Fatores de Risco
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