Low TB Incidence Countries Research Articles

Treatment of latent tuberculosis infection in migrants in primary care versus secondary care.

Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care. This was a pragmatic cluster-randomised, parallel group, superiority trial (ClinicalTrials.gov: NCT03069807) conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking ≥90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB incidence and a cost-effectiveness analysis. Analyses were performed on an intention-to-treat basis. Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82.6% versus 86.0%; adjusted OR (aOR) 0.64, 95% CI 0.31-1.29). There was no difference in drug-induced liver injury between primary and secondary care (0.7% versus 2.3%; aOR 0.29, 95% CI 0.03-2.84). Treatment acceptance was lower in primary care (65.2% (146/224) versus 94.2% (130/138); aOR 0.10, 95% CI 0.03-0.30). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of GBP 315.27 (95% CI 313.47-317.07). The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care.

Readability of Patient-Facing Information of Antibiotics Used in the WHO Short 6-Month and 9-Month All Oral Treatment for Drug-Resistant Tuberculosis

ObjectivesReadability of patient-facing information of oral antibiotics detailed in the WHO all oral short (6 months, 9 months) has not been described to date. The aim of this study was therefore to examine (i) how readable patient-facing TB antibiotic information is compared to readability reference standards and (ii) if there are differences in readability between high-incidence countries versus low-incidence countries.MethodsTen antibiotics, including bedaquiline, clofazimine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, pretomanid, pyrazinamide, were investigated. TB antibiotic information sources were examined, consisting of 85 Patient Information Leaflets (PILs) and 40 antibiotic web resouces. Of these 85 PILs, 72 were taken from the National Medicines Regulator from six countries (3 TB high-incidence [Rwanda, Malaysia, South Africa] + 3 TB low-incidence [UK, Ireland, Malta] countries). Readability data was grouped into three categories, including (i) high TB-incidence countries (n = 33 information sources), (ii) low TB-incidence countries (n = 39 information sources) and (iii) web information (n = 53). Readability was calculated using Readable software, to obtain four readability scores [(i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index], as well as two text metrics [words/sentence, syllables/word].ResultsMean readability scores of patient-facing TB antibiotic information for FRE and FKGL, were 47.4 ± 12.6 (sd) (target ≥ 60) and 9.2 ± 2.0 (target ≤ 8.0), respectively. There was no significant difference in readability between low incidence countries and web resources, but there was significantly poorer readability associated with PILs from high incidence countries versus low incidence countries (FRE; p = 0.0056: FKGL; p = 0.0095).ConclusionsReadability of TB antibiotic PILs is poor. Improving readability of PILs should be an important objective when preparing patient-facing written materials, thereby improving patient health/treatment literacy.

Investigation of genomic mutations and their association with phenotypic resistance to new and repurposed drugs in Mycobacterium tuberculosis complex clinical isolates.

WGS has the potential to detect resistance-associated mutations and guide treatment of MDR TB. However, the knowledge base to confidently interpret mutations associated with the new and repurposed drugs is sparse, and phenotypic drug susceptibility testing is required to detect resistance. We screened 900 Mycobacterium tuberculosis complex genomes from Ireland, a low TB incidence country, for mutations in 13 candidate genes and assessed their association with phenotypic resistance to bedaquiline, clofazimine, linezolid, delamanid and pretomanid. We identified a large diversity of mutations in the candidate genes of 195 clinical isolates, with very few isolates associated with phenotypic resistance to bedaquiline (n = 4), delamanid (n = 4) and pretomanid (n = 2). We identified bedaquiline resistance among two drug-susceptible TB isolates that harboured mutations in Rv0678. Bedaquiline resistance was also identified in two MDR-TB isolates harbouring Met146Thr in Rv0678, which dated back to 2007, prior to the introduction of bedaquiline. High-level delamanid resistance was observed in two isolates with deletions in ddn, which were also resistant to pretomanid. Delamanid resistance was detected in two further isolates that harboured mutations in fbiA, but did not show cross-resistance to pretomanid. All isolates were susceptible to linezolid and clofazimine, and no mutations found were associated with resistance. More studies that correlate genotypic and phenotypic drug susceptibility data are needed to increase the knowledge base of mutations associated with resistance, in particular for pretomanid. Overall, this study contributes to the development of future mutation catalogues for M. tuberculosis complex isolates.

Reducing the burden of TB among migrants to low TB incidence countries.

BACKGROUND: International migrants to low TB incidence countries are disproportionately affected by TB compared to the native population: migrants are at increased risk for TB transmission and TB disease due to a variety of personal, environmental and socio-economic determinants experienced during the four phases of migration (pre-departure, transit, arrival and early settlement, return travel).OBJECTIVE: To provide an up-to-date overview of the determinants that drive the TB burden among migrants, as well as effective and feasible interventions to address this for each migration phase.METHODS: We conducted a literature review by searching PubMed and the grey literature for articles and reports on determinants and interventions addressing migrant health and TB.RESULTS: Lowering the risk of TB transmission and TB disease among migrants would be most effective by improving the socio-economic position of migrants pre-, during and after migration, ensuring universal health coverage, and providing tailored and migrant-sensitive care and prevention activities.CONCLUSION: In addition to migrant-sensitive health services and cross-border collaboration between low TB incidence countries, there is a need for international financial and technical support for endemic countries.

Immuno-Diagnosis of Active Tuberculosis by a Combination of Cytokines/Chemokines Induced by Two Stage-Specific Mycobacterial Antigens: A Pilot Study in a Low TB Incidence Country.

Active tuberculosis (aTB) remains a major killer from infectious disease, partially due to delayed diagnosis and hence treatment. Classical microbiological methods are slow and lack sensitivity, molecular techniques are costly and often unavailable. Moreover, available immuno-diagnostic tests lack sensitivity and do not differentiate between aTB and latent TB infection (LTBI). Here, we evaluated the performance of the combined measurement of different chemokines/cytokines induced by two different stage-specific mycobacterial antigens, Early-secreted-antigenic target-6 (ESAT-6) and Heparin-binding-haemagglutinin (HBHA), after a short in vitro incubation of either peripheral blood mononuclear cells (PBMC) or whole blood (WB). Blood samples were collected from a training cohort comprising 22 aTB patients, 22 LTBI subjects and 17 non-infected controls. The concentrations of 13 cytokines were measured in the supernatants. Random forest analysis identified the best markers to differentiate M. tuberculosis-infected from non-infected subjects, and the most appropriate markers to differentiate aTB from LTBI. Logistic regression defined predictive abilities of selected combinations of cytokines, first on the training and then on a validation cohort (17 aTB, 27 LTBI, 25 controls). Combining HBHA- and ESAT-6-induced IFN-γ concentrations produced by PBMC was optimal to differentiate infected from non-infected individuals in the training cohort (100% correct classification), but 2/16 (13%) patients with aTB were misclassified in the validation cohort. ESAT-6-induced-IP-10 combined with HBHA-induced-IFN-γ concentrations was selected to differentiate aTB from LTBI, and correctly classified 82%/77% of infected subjects as aTB or LTBI in the training/validation cohorts, respectively. Results obtained on WB also selected ESAT-6- and HBHA-induced IFN-γ concentrations to provided discrimination between infected and non-infected subjects (89%/90% correct classification in the training/validation cohorts). Further identification of aTB patients among infected subjects was best achieved by combining ESAT-6-induced IP-10 with HBHA-induced IL-2 and GM-CSF. Among infected subjects, 90%/93% of the aTB patients were correctly identified in the training/validation cohorts. We therefore propose a two steps strategy performed on 1 mL WB for a rapid identification of patients with aTB. After elimination of most non-infected subjects by combining ESAT-6 and HBHA-induced IFN-γ, the combination of IP-10, IL-2 and GM-CSF released by either ESAT-6 or HBHA correctly identifies most patients with aTB.

Tackling TB in migrants arriving at Europe’s southern border

Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants.

Effects of migration on tuberculosis epidemiological indicators in low and medium tuberculosis incidence countries: A systematic review

BackgroundTuberculosis (TB) remains one of the top ten causes of death each year globally. While the risk of migrant TB is linked to the TB incidence in their country of origin, the migration process can increase the TB risk. ObjectiveWe aimed to synthesis the evidence on key differences in the epidemiological profile of TB between migrants from high TB incidence birth countries and non-migrants resident in low to medium incidence TB countries. MethodsWe conducted a systematic review where the population was all active TB cases in countries with low to medium TB incidence (<40/100,000 population), the exposure was migration to a low or medium TB incidence country and the comparator was non-migrant TB cases in low or medium incidence countries. Overall proportions were compared between migrants and non-migrants, using Fisher’s exact test. Meta-analysis of proportions was carried out for the primary outcome (active TB) while meta-analyses of odds ratios (ORs) were performed using a random effects model for secondary outcomes; sputum-smear positivity, any first line drug resistance, multi-drug resistance (MDR), clustered cases, HIV coinfections and successful treatment. Heterogeneity was evaluated and sources were investigated using subgroup and sensitivity analysis. ResultsSignificant differences were found in the overall proportions of high TB incidence migrants and non-migrants for MDR cases, clustered cases, HIV coinfections and successful treatment, as well as a significant difference in the OR among MDR cases (3.91). ConclusionThis review has demonstrated significant differences in key epidemiological indicators between high TB incidence migrants and non-migrants, indicating policy implications.

Multidrug-Resistant Tuberculosis In A Referral Center In Rome: 2011- 2016.

PurposeMultidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in low incidence countries in Europe. The aim of this study was to attempt to have a better insight into the trends of MDR-TB in the metropolitan area of Rome, within the Italian and the foreign-born population, based on microbiological and demographic data.Patients and methodsWe performed a prospective study, collecting microbiological data based on phenotypic drug-resistant testing (DST) of TB strains consecutively isolated in a referral hospital in Rome, the capital city of a low TB incidence country, over a 6-year period, and correlated them to the geographical origin of patients. This study was carried out in a referral hospital for patients with drug-resistant TB from the whole region.ResultsDrug-resistance data from 926 patients with a microbiological diagnosis of TB from 2011 to 2016 show a 5.5% rate of MDR-TB, mostly occurring in patients born in a single East European country, that has a high incidence of MDR-TB. The strains isolated from these patients frequently carry additional resistances, leading to an increased risk of developing extensively drug-resistant (XDR) TB.ConclusionIn the great metropolitan area of Rome, MDR-TB more frequently occurs in patients who were born in a single country from Eastern Europe known to have high rates of MDR-TB and long-time residents in Italy. Recent immigrants from non-European countries do not appear to contribute to the rates of MDR-TB reported in this article. This knowledge of local TB trends could help improve the measures of surveillance and prevention of disease.

The global prevalence of latent tuberculosis: a systematic review and meta-analysis.

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model.Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7-30.0%) and 21.2% (95% CI 17.9-24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

Building a European database to gather multi-country evidence on active and latent TB screening for migrants

Background and aimScreening for active and latent TB among migrants in low TB incidence countries may constitute an important contribution to TB elimination. E-DETECT TB, a European multi-county collaboration, aims to address the present lack of evidence on effectiveness of migrant TB screening by collating data in an international database and perform cross-country pooled and comparative analyses of screening coverage, results and linkage to care. MethodA database was established using migrant TB screening data from participating countries’ national screening programs, national screening pilots and local research projects. All partner countries contributed to a common agreed protocol with standardized variables, pooling available numerator and denominator screening data from participating countries and sites. ResultsAll collaborating members drafted and agreed upon a data sharing accord as well as a protocol that clearly defined responsibilities and data governance principles. The database has been created and data transfer is ongoing. ConclusionBy persistence and focus the project has overcome considerable administrative, practical and legal challenges. This international collaboration provides greater power of analysis of harmonized data and thereby a unique opportunity to contribute migrant TB screening evidence. E-DETECT TB has started to invite other countries to contribute data to the database.

759. Molecular Characterization and Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) and Identification of Possible Cases of Local Transmission of MDR-TB in Kuwait

BackgroundIncreasing incidence of multidrug-resistant tuberculosis (MDR-TB) is hampering efforts to control TB. Kuwait is a low (25/100,000) TB incidence country and ~1% of Mycobacterium tuberculosis strains are resistant to rifampin, RIF and isoniazid, INH (MDR-TB). Analysis of resistance conferring mutations in seven genes was combined with spoligotyping for detecting local transmission of MDR-TB in Kuwait.MethodsMDR-TB strains (n = 131) from 88 TB patients and 50 susceptible strains were used. Susceptibility testing was done by MGIT 960 system, gMTBDRplus assay and PCR-sequencing of three regions of rpoB, katG codon 315 (katG315) + inhA regulatory region, embB (embB306/embB406/embB497 regions), rpsL + rrs-500–900 regions and pncA for RIF, INH, ethambutol (EMB), streptomycin (SM) and pyrazinamide (PZA), respectively. Sequencing data were used to construct phylogenetic tree by MEGA7 software. Spoligotypes were identified by SITVIT2 and phylogenetic tree was made by MIRU-VNTRplus software.ResultsMutations were detected in most isolates in rpoB, katG+inhA, embB, rpsL+rrs and pncA which confer resistance to RIF, INH, EMB, SM and PZA, respectively. Phylogenetic analysis of multi-locus concatenated sequences showed unique patterns for 51 patient’s isolates while 37 patient’s isolates grouped in 14 clusters. Spoligotyping identified 35 patterns (19 unique patterns and 69 patients’s isolates in 16 patterns) including 11 orphan patterns. Sixteen isolates yielded six clusters (each containing two to five isolates) by both fingerprinting methods.ConclusionOur study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified six potential cases of local transmission of MDR-TB involving two to five subjects (including five Kuwaiti patients) which had escaped detection by routine surveillance studies. Prospective detection of resistance conferring mutations thus identifies possible cases of local transmission of MDR-TB in low TB incidence countries.Disclosures All authors: No reported disclosures.

Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection.

BackgroundA quarter of the world’s population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA’s), tests which have low sensitivity in immunocompromised. IL-7 is an important cytokine for T-cell function with potential to augment cytokine release in in-vitro assays. This study aimed to determine whether the addition of IL-7 in interferon-gamma release assays (IGRAs) improves its diagnostic performance of Mtb infection.Methods44 cases with confirmed TB and 45 household contacts without TB were recruited and 1ml of blood was stimulated in two separate IGRA’s tube set: one set of standard Quantiferon TB gold tubes mitogen, TB antigen and TB Nil; one set of customized Quantiferon TB gold tubes with added IL-7. Following IFN-γ and IP-10 release was determined using ELISA.ResultsWe found that the addition of IL-7 led to significantly higher release of IFN-γ in individuals with active TB from 4.2IU/ml (IQR 1.4–6.9IU/ml) to 5.1IU/ml (IQR 1.5–8.1IU/ml, p = 0.0057), and we found an indication of a lower release of both IFN-γ and IP-10 in participants with negative tests.ConclusionsIn TB cases addition of IL-7 in IGRA tubes augments IFN-γ but not IP-10 release, and seems to lower the response in controls. Whether IL-7 boosted IGRA holds potential over standard IGRA needs to be confirmed in larger studies in high and low TB incidence countries.

The Global Prevalence of Latent Tuberculosis: A Systematic Review and Meta-Analysis

Background: In 1999, the WHO estimated that one-third of the world's population had latent tuberculosis (LTBI) which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-gamma release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence. Methods: We conducted a systematic review and meta-analysis of LTBI estimates based on IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model. Findings: Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI: 19.7-30.0%) based on IGRA and 21.2% (95% CI: 17.9-24.4%) and 24.1% (95% CI: 19.7-29.9%) based on a 5 and 10 mm TST cut-offs, respectively. The prevalence estimates correlated significantly to WHO incidence rates. Interpretation: In the first study of the global prevalence of LTBI derived from both IGRA and TST, we found that one-fourth of the world's population is infected. This is of relevance as both tests, although imperfect, are used to identify individuals for preventive therapy. Enhanced efforts are needed to target the large pool of latently infected as they continuously constitutes a source of potential active TB. Funding Statement: This study was supported by NovoNordisk Foundation (NNF15OC0018034; CW), the Swedish Research Council (201602043; TS) and the Swedish Heart and Lung Foundation (20150236; TS). Declaration of Interests: The authors declare no competing interests.

Discordance across Phenotypic and Molecular Methods for Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates in a Low TB Incidence Country.

With increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line drugs has become crucial for proper patient management. We evaluated concordance of DST results for 70 M. tuberculosis isolates across two phenotypic and two molecular methods: BACTEC 460TB, MGIT 960 system, GenoType MTBDRplus and DNA sequencing of gene segments most commonly implicated in conferring resistance to anti-TB drugs. Most (84%) M. tuberculosis isolates were multidrug-resistant. Twenty-four isolates yielded discrepant DST results. For rifampicin, isoniazid and streptomycin, 96%, 97% and 93% of isolates, respectively, were susceptible or resistant by all four methods, whereas for ethambutol, this agreement was observed for only 76% of isolates (P <0.05 for rifampicin or isoniazid or streptomycin versus ethambutol). Occurrence of rare mutations in three isolates that confer low-level resistance caused lower agreement for rifampicin among the four methods (kappa coefficient (κ) range, 0.84 to 0.95). For isoniazid, there was perfect agreement among phenotypic methods and molecular methods (κ, 1.00) but lower agreement between phenotypic and molecular methods. Three isolates were detected as polydrug-resistant by MGIT 960 system but as multidrug-resistant by DNA sequence-based method. The agreement was higher for streptomycin among the two phenotypic methods (κ, 0.97) while targeted sequencing yielded lower agreement (κ range, 0.86 to 0.89). The discrepancy for ethambutol resulted largely due to lower concordance of MGIT 960 results (κ range, 0.53 to 0.64). The MGIT 960 system is an accurate method for DST of M. tuberculosis against isoniazid and streptomycin while the results of rifampicin susceptibility should be complemented with DNA sequencing-based method when the suspicion for resistance is high. The possibility of false susceptibility to ethambutol with MGIT 960 system suggests that molecular or other phenotypic methods may be more useful when accurate ethambutol susceptibility results are warranted.

Interferon gamma inducible protein-10 in the diagnosis of paediatric tuberculosis infection in a low TB incidence country.

To assess interferon-gamma inducible protein 10 (IP-10) as a diagnostic marker for tuberculous infection in children, particularly in relation to its differential diagnostic performance in young children. A case-control study was conducted among 161 children and adolescents (mean age 6.3 years ± standard deviation 1.7; males n = 79, 49%). Fifty-four (33.5%) had active TB, 53 (33%) had latent tuberculous infection (LTBI), and 54 (33.5%) were non-LTBI controls. Unstimulated IP-10 levels did not differ between groups (P > 0.05 for all comparisons). TB-specific antigen stimulated IP-10 levels were more profoundly increased in infected groups than in controls (P < 0.001 for all comparisons). None of the IP-10-based diagnostic indexes demonstrated the ability to discriminate active disease from LTBI. A value of IP-10 ⩾ 1222 pg/ml had 83.3% sensitivity, 79.6% specificity, 80.4% positive predictive value and 82.7% negative predictive value for the diagnosis of LTBI. IP-10 based indexes demonstrated a trend towards better performance in the population group aged <5 years. The IP-10 assay could be useful in improving the diagnosis of LTBI in patients aged <5 years in combination with existing interferon-gamma release assays.

Implementation of latent tuberculosis screening in HIV care centres: evaluation in a low tuberculosis incidence setting.

The screening and treatment of latent tuberculosis infection (LTBI) to prevent active tuberculosis (TB) is recommended by the WHO in all HIV-infected patients. The aim of this study was to evaluate its implementation within Belgium's HIV care. A multiple-choice questionnaire was sent to 55 physicians working in the country's AIDS reference centres. Response rate reached 62%. Only 20% screened all their HIV-infected patients for LTBI. Screening methods used and their interpretation vary from one physician to another. The main barriers to the implementation of LTBI screening and treatment, as perceived by the participants, are lack of sensitivity of screening tools, risks associated with polypharmacy and toxicity of treatment. The poor coverage of LTBI screening reported here and the inconsistency in methods used raises concern. However, this was not unexpected as, in low-TB incidence countries, who, when and how to screen for LTBI remains unclear and published guidelines show important disparities. Recently, a targeted approach in which only HIV-infected patients at highest risk of TB are screened has been suggested. Such a strategy would limit unnecessary exposure to LTBI treatment. This methodology was approved by 80% of the participants and could therefore achieve greater coverage. Its clinical validation is still pending.

1689Performance Comparison of Two Commercial Tests for Rapid Molecular Diagnosis of Exprapulmonary Tuberculosis in a Low TB Incidence Country

1689Performance Comparison of Two Commercial Tests for Rapid Molecular Diagnosis of Exprapulmonary Tuberculosis in a Low TB Incidence Country

FRI0281 The Rate of Positive Conversion in the Quantiferon-TB Gold Test over 2 Years among Patients Treated with CT-P13 or Innovator Infliximab in the Extension Studies of Planetas and Planetra

BackgroundLong-term treatment of anti-TNF agents in patients with immune mediated disease can increase the risk of active tuberculosis infection (ATBI) by reactivation of latent tuberculosis infection (LTBI) or de novo...

P2.045 Serial Testing with an Interferon-Gamma Release Assay in HIV-1-Infected Individuals

BackgroundThe clinical utility of serial screening for tuberculosis (TB) by interferon-gamma release assays has not been established in HIV-1-infected individuals.MethodsIn this prospective study HIV-1-infected subjects underwent repeated QuantiFERON-TB Gold In-Tube...

Risk Stratification of Latent Tuberculosis Defined by Combined Interferon Gamma Release Assays

BackgroundMost individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. Here, we provide an approach to stratify LTBI based on IFN-γ responses to two antigens, the recombinant Early-Secreted Antigen Target-6 (rESAT-6) and the latency antigen Heparin-Binding Haemagglutinin (HBHA).MethodsWe retrospectively analyzed results from in-house IFN-γ-release assays with HBHA (HBHA-IGRA) and rESAT-6 (rESAT-6-IGRA) performed during a 12-year period on serial blood samples (3 to 9) collected from 23 LTBI subjects in a low-TB incidence country. Both the kinetics of the absolute IFN-γ concentrations secreted in response to each antigen and the dynamics of HBHA/rESAT-6-induced IFN-γ concentrations ratios were examined.ResultsThis analysis allowed the identification among the LTBI subjects of three major groups. Group A featured stable HBHA and rESAT-6-IGRA profiles with an HBHA/rESAT-6 ratio persistently higher than 1, and with high HBHA- and usually negative rESAT-6-IGRA responses throughout the study. Group B had changing HBHA/rESAT-6 ratios fluctuating from 0.0001 to 10,000, with both HBHA and rESAT-6 responses varying over time at least once during the follow-up. Group C was characterized by a progressive disappearance of all responses.ConclusionsBy combining the measures of IFN-γ concentrations secreted in response to an early and a latency antigens, LTBI subjects can be stratified into different risk groups. We propose that disappearing responses indicate cure, that persistent responses to HBHA with HBHA/rESAT-6 ratios ≥1 represent stable LTBI subjects, whereas subjects with ratios varying from >1 to <1 should be closely monitored as they may represent the highest-risk group, as illustrated by a case report, and should therefore be prioritized for preventive treatment.