Publications
170 results found
Tovar MT, Wingfield TW, Saunders MS, et al., 2016, Risk factors associated with undetected pulmonary TB in a prevalence survey, Callao, Perú, 47th Union World Conference on Lung Health, Publisher: International Union Against Tuberculosis and Lung Disease
Bonadonna LB, Saunders MS, Zegarra RO, et al., 2016, The social determinants underlying tuberculosis diagnostic delay: a mixed methods study, 47th Union World Conference on Lung Health, Publisher: International Union Against Tuberculosis and Lung Disease, Pages: S119-S119, ISSN: 1815-7920
Wingfield T, Tovar MA, Huff D, et al., 2016, The economic effects of supporting tuberculosis-affected households in Peru, European Respiratory Journal, Vol: 48, Pages: 1396-1410, ISSN: 1399-3003
BackgroundThe End TB Strategy mandates that zero TB-affected households face catastrophic costs due to TB. However, evidence is limited evaluating socioeconomic support to achieve this change in policy and practice. Objective To investigate the economic effects of a TB-specific socioeconomic intervention.MethodsSetting-32 shantytown-communities, Peru.Participants-households of consecutive TB-patients throughout TB treatment administered by the national TB program. Intervention-consisted of: social support through household-visits and community-meetings; and economic support through cash transfers conditional upon: TB-screening in household contacts; adhering to TB treatment/chemoprophylaxis; and engaging with social support. Data collection-to assess TB-affected household costs, patient interviews were conducted at treatment initiation and then monthly for six-months. Results From February-2014 to June-2015, 312 households were recruited, of which 135 were randomized to receive the intervention. Cash transfer total value averaged $173 USD (3.5% of TB-affected household’s average annual income) and mitigated 20% of household’s TB-related costs. Households randomized to receive the intervention were less likely to incur catastrophic costs (30%[95%CI=22-38] versus 42%[95%CI=34-51]). The mitigation impact was higher among poorer households.ConclusionsThe TB-specific socioeconomic intervention reduced catastrophic costs and was accessible to poorer households. Socioeconomic support and mitigating catastrophic costs are integral to the End TB strategy and our findings inform implementation of these new policies.
Saunders MJ, Wingfield TW, Tovar MA, et al., 2016, Targeting TB preventive therapy to those at high risk: derivation and validation of a risk score for predicting tuberculosis disease, 47th Union World Conference on Lung Health, Publisher: International Union Against Tuberculosis and Lung Disease (The Union)
Background. Use of tuberculosis preventive therapy (PT) must be urgently scaled up and provided to people at high-risk of developing tuberculosis disease (TB). In high-burden settings, PT is poorly utilised and rarely offered to adult household contacts. Furthermore, the tests for tuberculosis infection used to guide prescription are unreliable for predicting disease, fraught with logistical challenges and unavailable in many settings. In low- and middle-income countries a TB risk score could be used to prioritise PT for contacts most likely to benefit. We therefore aimed to develop a risk score to predict TB disease among adult household contacts of patients with TB in urban Callao, Perú. Methods. We identified index-cases with pulmonary TB (n=715), recruited their household contacts aged ≥15 years (n=2,017) and followed them for TB for a total of 18,988 person-years (PY). Cox proportional-hazards models were fitted to investigate factors associated with TB. 1,009 contacts were selected as a derivation cohort from which a risk score was created. Scores were calculated for each contact and low, intermediate and high-risk groups defined. The score was subsequently validated in the remaining 1,008 contacts. Results. Eight predictors formed the score: age 15-30 or ≥50; history of TB; body-mass-index; prolonged exposure to the index-case; poverty; exposure to indoor air pollution; male index-case and high index-case smear-positivity. In the derivation cohort the incidence rates in the low-, intermediate- and high-risk groups were 331/100,000PY (95%CI:200-550); 942/100,000PY (95%CI: 650-1363) and 2038/100,000PY (95%CI:1501-2768) respectively (p<0.0001). In the validation cohort the rates were similar. The figure shows the cumulative hazard of TB at specific time points. The number-needed-to-treat to prevent one TB case over 2 years in the low, intermediate and high-risk groups is 83, 35 and 18 respectively.Conclusion. A risk score was derived and validate
Dudley MZ, Sheen P, Gilman RH, et al., 2016, Detecting mutations in the Mycobacterium tuberculosis pyrazinamidase gene pncA to improve infection control and decrease drug resistance rates in human immunodeficiency virus coinfection, American Journal of Tropical Medicine and Hygiene, Vol: 95, Pages: 1239-1246, ISSN: 1476-1645
Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.
Ticona E, Huaroto L, Kirwan DE, et al., 2016, Impact of infection control measures to control an outbreak of multidrug-resistant tuberculosis in a human immunodeficiency virus ward, Peru, American Journal of Tropical Medicine and Hygiene, Vol: 95, Pages: 1247-1256, ISSN: 1476-1645
Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.
Boccia D, Pedrazzoli D, Wingfield T, et al., 2016, Towards cash transfer interventions for tuberculosis prevention, care and control: key operational challenges and research priorities, BMC Infectious Diseases, Vol: 16, ISSN: 1471-2334
BackgroundCash transfer interventions are forms of social protection based on the provision of cash to vulnerable households with the aim of reduce risk, vulnerability, chronic poverty and improve human capital. Such interventions are already an integral part of the response to HIV/AIDS in some settings and have recently been identified as a core element of World Health Organization’s End TB Strategy. However, limited impact evaluations and operational evidence are currently available to inform this policy transition.DiscussionThis paper aims to assist national tuberculosis (TB) programs with this new policy direction by providing them with an overview of concepts and definitions used in the social protection sector and by reviewing some of the most critical operational aspects associated with the implementation of cash transfer interventions. These include: 1) the various implementation models that can be used depending on the context and the public health goal of the intervention; 2) the main challenges associated with the use of conditionalities and how they influence the impact of cash transfer interventions on health-related outcomes; 3) the implication of targeting diseases-affected households and or individuals versus the general population; and 4) the financial sustainability of including health-related objectives within existing cash transfer programmes. We aimed to appraise these issues in the light of TB epidemiology, care and prevention. For our appraisal we draw extensively from the literature on cash transfers and build upon the lessons learnt so far from other health outcomes and mainly HIV/AIDS.ConclusionsThe implementation of cash transfer interventions in the context of TB is still hampered by important knowledge gaps. Initial directions can be certainly derived from the literature on cash transfers schemes and other public health challenges such as HIV/AIDS. However, the development of a solid research agenda to address persisting unknowns o
Saunders MS, Zevallos KZ, Tovar MA, et al., 2016, Micronutrient supplementation augments anti-mycobacterial immune responses in TST reactive household contacts, 47th Union World Conference on Lung Health
Saunders MS, Tovar MA, Zevallos KZ, et al., 2016, Can micronutrient supplementation prevent TB in vulnerable household contacts? A randomised controlled trial, 47th Union World Conference on Lung Health
Proaño A, Bravard MA, Tracey BH, et al., 2016, Protocol for studying cough frequency in people with pulmonary tuberculosis, BMJ open, Vol: 6, Pages: e010365-e010365, ISSN: 2044-6055
INTRODUCTION: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed.
Saunders MJ, Evans CA, 2015, Fighting poverty to prevent tuberculosis, Lancet Infectious Diseases, Vol: 16, Pages: 395-396, ISSN: 1473-3099
Wingfield T, Tovar M, Montoya R, et al., 2015, In TB patients from Peruvian shantytowns, catastrophic costs explain as many adverse TB outcomes as MDR TB, Journal of Infection, Vol: 71, Pages: 684-684, ISSN: 1532-2742
Kirwan D, Ugarte-Gil C, Gilman RH, et al., 2015, Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance, Journal of Clinical Microbiology, Vol: 54, Pages: 185-189, ISSN: 1098-660X
In the study, 132 patients with lymphadenopathy were investigated. 52 (39.4%) were diagnosed with TB. MODS provided rapid (13 days), accurate diagnosis (sensitivity 65.4%), and reliable DST. Despite lower sensitivity than other methods, faster results and simultaneous DST are advantageous in resource-poor settings, supporting incorporation of MODS into diagnostic algorithms for extrapulmonary TB.
Wingfield T, Tovar M, Boccia D, et al., 2015, AN OPERATIONAL EVALUATION OF A SOCIOECONOMIC INTERVENTION TO PREVENT TB IN IMPOVERISHED PERUVIAN COMMUNITIES, ASTMH, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 539-540, ISSN: 0002-9637
Westerlund EE, Tovar MA, Lonnermark E, et al., 2015, Tuberculosis-related knowledge is associated with patient outcomes in shantytown residents; results from a cohort study, Peru, JOURNAL OF INFECTION, Vol: 71, Pages: 347-357, ISSN: 0163-4453
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- Citations: 12
Wingfield T, Boccia D, Tovar MA, et al., 2015, Designing and implementing a socioeconomic intervention to enhance TB control: operational evidence from the CRESIPT project in Peru, BMC Public Health, Vol: 15, ISSN: 1471-2458
BackgroundCash transfers are key interventions in the World Health Organisation’s post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented, and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.MethodsNewly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings). To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders. ResultsOver seven months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74%) were achieved, 259 (19%) were not achieved, and 76 (7%) were yet to be achieved. Of those achieved, 885/964 (92%) were achieved optimally and 79/964 (8%) sub-optimally.Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer schemes; and the project being perceived as patient-centred and empowering. Challenges included: participant confidence being eroded through cash transfer delays, hidden ac
Oberhelman RA, Soto-Castellares G, Gilman RH, et al., 2015, A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru, PLOS One, Vol: 10, ISSN: 1932-6203
BackgroundDiagnosing tuberculosis in children is challenging because specimens are difficult to obtainand contain low tuberculosis concentrations, especially with HIV-coinfection. Few studiesincluded well-controls so test specificities are poorly defined. We studied tuberculosis diagnosisin 525 children with and without HIV-infection.Methods and Findings‘Cases’ were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81HIV-positive) and asymptomatic ‘well-control’ children (n = 200 HIV-negative; n = 35 HIVpositive).Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates andstools analyzed by a total of 9688 tests.All specimens were tested with an in-house hemi-nested IS6110 PCR that took <24hours. False-positive PCR in well-controls were more frequent in HIV-infection (P 0.01):17% (6/35) HIV-positive well-controls versus 5.5% (11/200) HIV-negative well-controls;caused by 6.7% (7/104) versus 1.8% (11/599) of their specimens, respectively. 6.7% (116/1719) specimens from 25% (72/290) cases were PCR-positive, similar (P>0.2) for HIV-positiveversus HIV-negative cases.All specimens were also tested with auramine acid-fast microscopy, microscopic-observationdrug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture thattook 6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 wellcontrolswere negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and allmicroscopy-positive specimens were culture-positive. Culture-positivity was less frequent(P 0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negativecases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens,respectively.ConclusionsIn HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458microscopy and culture tests were done per case confirmed and even in children with culture-proventuberculosis most tests and specimens were fa
Gonzales I, Miranda JJ, Rodriguez S, et al., 2015, Seizures, cysticercosis and rural-to-urban migration: the PERU MIGRANT study, Tropical Medicine & International Health, Vol: 20, Pages: 546-552, ISSN: 1365-3156
OBJECTIVES: To examine the prevalence of seizures, epilepsy and seropositivity to cysticercosis in rural villagers (cysticercosis-endemic setting), rural-to-urban migrants into a non-endemic urban shanty town and urban inhabitants of the same non-endemic shanty town. METHODS: Three Peruvian populations (n = 985) originally recruited into a study about chronic diseases and migration were studied. These groups included rural inhabitants from an endemic region (n = 200), long-term rural-to-urban migrants (n = 589) and individuals living in the same urban setting (n = 196). Seizure disorders were detected by a survey, and a neurologist examined positive respondents. Serum samples from 981/985 individuals were processed for cysticercosis antibodies on immunoblot. RESULTS: Epilepsy prevalence (per 1000 people) was 15.3 in the urban group, 35.6 in migrants and 25 in rural inhabitants. A gradient in cysticercosis antibody seroprevalence was observed: urban 2%, migrant 13.5% and rural group 18% (P < 0.05). A similarly increasing pattern of higher seroprevalence was observed among migrants by age at migration. In rural villagers, there was strong evidence of an association between positive serology and having seizures (P = 0.011) but such an association was not observed in long-term migrants or in urban residents. In the entire study population, compared with seronegative participants, those with strong antibody reactions (≥ 4 antibody bands) were more likely to have epilepsy (P < 0.001). CONCLUSIONS: It is not only international migration that affects cysticercosis endemicity; internal migration can also affect patterns of endemicity within an endemic country. The neurological consequences of cysticercosis infection likely outlast the antibody response for years after rural-to-urban migration.
Sathyamoorthy T, Sandhu G, Tezera LB, et al., 2015, Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis, PLOS One, Vol: 10, ISSN: 1932-6203
Tuberculosis (TB) remains a global health pandemic and greater understanding of underlyingpathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrixmetalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TBbut have not been comprehensively studied in plasma, nor have gender differences beeninvestigated. We measured the plasma concentrations of MMPs in a carefully characterised,prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls,and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 wasTB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious ofTB but active disease excluded). Plasma MMP-8 concentrations inversely correlated withbody mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than femaleswith TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specificanalysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB,but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated inpulmonary TB and differ between men and women. Gender must be considered in investigationof TB immunopathology and development of novel diagnostic markers.
Datta S, Sherman JM, Bravard MA, et al., 2014, Clinical evaluation of tuberculosis viability microscopy for assessing treatment response, Clinical Infectious Diseases, Vol: 60, Pages: 1186-1195, ISSN: 1537-6591
Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis.Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate.Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6).Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were respond
Barletta F, Vandelannoote K, Collantes J, et al., 2014, Standardization of a TaqMan-Based Real-Time PCR for the Detection of <i>Mycobacterium tuberculosis</i>-Complex in Human Sputum, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 91, Pages: 709-714, ISSN: 0002-9637
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- Citations: 20
Wingfield T, Schumacher SG, Sandhu G, et al., 2014, The Seasonality of Tuberculosis, Sunlight, Vitamin D, and Household Crowding, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 774-783, ISSN: 0022-1899
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- Citations: 63
Wingfield T, Boccia D, Tovar M, et al., 2014, Defining catastrophic costs and comparing their importance for adverse tuberculosis outcome with multi-drug resistance: a prospective cohort study, Peru, PLOS Medicine, Vol: 11, Pages: 1-17, ISSN: 1549-1277
Background: Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TBaffectedhouseholds) may worsen poverty and health. Extreme TB-associated costs have been termed ‘‘catastrophic’’ but arepoorly defined. We studied TB-affected households’ hidden costs and their association with adverse TB outcome to create aclinically relevant definition of catastrophic costs.Methods and Findings: From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant[MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patientswere interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lostincome) TB-related costs. Costs were expressed as a proportion of the household’s annual income. In poorer households,costs were lower but constituted a higher proportion of the household’s annual income: 27% (95% CI = 20%–43%) in theleast-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatmentabandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a definedtreatment outcome had an adverse outcome. Total costs $20% of household annual income was defined as catastrophicbecause this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95%CI = 43%–61%] versus 38% [95% CI = 34%–41%], p,0.003). Adverse outcome was independently associated with MDR TB(odds ratio [OR] = 8.4 [95% CI = 4.7–15], p,0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell towork pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95
Eisen S, Pealing L, Aldridge RW, et al., 2013, Effects of Ascent to High Altitude on Human Antimycobacterial Immunity, PLOS One, Vol: 8, ISSN: 1932-6203
Background: Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascentto high altitude was historically recommended for treatment. The immunological and mycobacterial mechanismsunderlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude onmycobacteria and antimycobacterial immunity.Methods: Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after theyascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed asthe extent to which participants’ whole blood supported or restricted growth of genetically modified luminescentBacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole bloodassay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growthin participants’ whole blood versus positive-control culture broth and versus negative-control plasma.Results: Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured sixweeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereasascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than inculture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereasascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more thanin plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people whohad recently ascended to high altitude versus long-term high-altitude residents.Conclusions: An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible inlow-resource settings. This demonstrated that ascent to or resi
Martinez L, Arman A, Haveman N, et al., 2013, Changes in Tuberculin Skin Test Positivity Over 20 Years in Periurban Shantytowns in Lima, Peru, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 89, Pages: 507-515, ISSN: 0002-9637
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Toit K, Mitchell S, Balabanova Y, et al., 2012, The Colour Test for drug susceptibility testing of <i>Mycobacterium tuberculosis</i> strains, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 16, Pages: 1113-1118, ISSN: 1027-3719
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- Citations: 18
Sandhu G, Battaglia F, Ely BK, et al., 2012, Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics, PLOS One, Vol: 7, ISSN: 1932-6203
Background: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings isdistinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with coexistingLTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty byproviding a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics.Methods: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru andfrom household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statisticalpattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB fromsymptomatic controls with or without LTBI.Results: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB)were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%).Conclusions: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders usinga plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-careformat will have significant implications for recognition and control of active TB in high prevalence settings.
Nahid P, Kim PS, Evans CA, et al., 2012, Clinical Research and Development of Tuberculosis Diagnostics: Moving From Silos to Synergy, JOURNAL OF INFECTIOUS DISEASES, Vol: 205, Pages: S159-S168, ISSN: 0022-1899
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- Citations: 25
Karlin DM, Evans C, Loiselle C, et al., 2012, DEPRESSION IS COMMON IN TB PATIENTS AND IS ASSOCIATED WITH TREATMENT ABANDONMENT, Western Regional Meeting, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 197-197, ISSN: 1081-5589
Chew R, Calderon C, Schumacher SG, et al., 2011, Evaluation of bleach-sedimentation for sterilising and concentrating Mycobacterium tuberculosis in sputum specimens, BMC Infectious Diseases, Vol: 11, ISSN: 1471-2334
Background: Bleach-sedimentation may improve microscopy for diagnosing tuberculosis by sterilising sputum andconcentrating Mycobacterium tuberculosis. We studied gravity bleach-sedimentation effects on safety, sensitivity,speed and reliability of smear-microscopy.Methods: This blinded, controlled study used sputum specimens (n = 72) from tuberculosis patients. Bleachconcentrations and exposure times required to sterilise sputum (n = 31) were determined. In the light of theseresults, the performance of 5 gravity bleach-sedimentation techniques that sterilise sputum specimens (n = 16) werecompared. The best-performing of these bleach-sedimentation techniques involved adding 1 volume of 5% bleachto 1 volume of sputum, shaking for 10-minutes, diluting in 8 volumes distilled water and sedimenting overnightbefore microscopy. This technique was further evaluated by comparing numbers of visible acid-fast bacilli, slidereadingspeed and reliability for triplicate smears before versus after bleach-sedimentation of sputum specimens (n =25). Triplicate smears were made to increase precision and were stained using the Ziehl-Neelsen method.Results: M. tuberculosis in sputum was successfully sterilised by adding equal volumes of 15% bleach for 1-minute,6% for 5-minutes or 3% for 20-minutes. Bleach-sedimentation significantly decreased the number of acid-fast bacillivisualised compared with conventional smears (geometric mean of acid-fast bacilli per 100 microscopy fields 166,95%CI 68-406, versus 346, 95%CI 139-862, respectively; p = 0.02). Bleach-sedimentation diluted paucibacillaryspecimens less than specimens with higher concentrations of visible acid-fast bacilli (p = 0.02). Smears made frombleach-sedimented sputum were read more rapidly than conventional smears (9.6 versus 11.2 minutes, respectively,p = 0.03). Counting conventional acid-fast bacilli had high reliability (inter-observer agreement, r = 0.991) that wassignificantly reduced (p = 0.03) by bleach-sedimentation (to r
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