First field and laboratory evaluation of LAMP assay for malaria diagnosis in Cubal, Angola.

BACKGROUND: Malaria is a globally distributed infectious disease. According to the World Health Organization, Angola is one of the six countries that account for over half the global malaria burden in terms of both malaria cases and deaths. Diagnosis of malaria still depends on microscopic examination of thin and thick blood smears and rapid diagnostic tests (RDTs), which often lack analytical and clinical sensitivity. Molecular methods could overcome these disadvantages. The aim of this study was to evaluate, for the first time to our knowledge, the performance of a loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria in an endemic area in Cubal, Angola, and to assess the reproducibility at a reference laboratory. METHODS: A total of 200 blood samples from patients attended at Hospital Nossa Senhora da Paz, Cubal, Angola, were analysed for Plasmodium spp. detection by microscopy, RDTs, and LAMP. LAMP assay was easily performed in a portable heating block, and the results were visualized by a simple colour change. Subsequently, the samples were sent to a reference laboratory in Spain to be reanalysed by the same colorimetric LAMP assay and also in real-time LAMP format. RESULTS: In field tests, a total of 67/200 (33.5%) blood samples were microscopy-positive for Plasmodium spp., 98/200 RDT positive, and 112/200 (56%) LAMP positive. Using microscopy as reference standard, field LAMP detected more microscopy-positive samples than RDTs (66/67; 98% vs. 62/67; 92.5%). When samples were reanalysed at a reference laboratory in Spain using both colorimetric and real-time assays, the overall reproducibility achieved 84.5%. CONCLUSIONS: This is the first study to our knowledge in which LAMP has been clinically evaluated on blood samples in a resource-poor malaria-endemic area. The colorimetric LAMP proved to be more sensitive than microscopy and RDTs for malaria diagnosis in field conditions. Furthermore, LAMP showed an acceptable level of reproducibility in a reference laboratory. The possibility to use LAMP in a real-time format in a portable device reinforces the reliability of the assay for molecular diagnosis of malaria in resource-poor laboratories in endemic areas.

Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement.

BACKGROUND: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries. METHODS: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram. RESULTS: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram. CONCLUSIONS: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.

Unexpected Loa loa Finding in an Asymptomatic Patient From The Gambia: A Case Report.

A 17-year-old asymptomatic male from The Gambia presented for a routine health examination after migration to Spain. Laboratory diagnosis confirmed the presence of Loa loa microfilariae. This unusual finding emphasizes the importance of screening in newly arrived migrants and the need of an extended anamnesis including migratory route and previous travels.

Rickettsioses imported by travellers and migrants to Spain attended in the +Redivi network, 2009-2020.

BACKGROUND: Rickettsioses are emerging zoonotic diseases with worldwide prevalence, recognized as a cause of imported fever in travellers and migrants. Our objective is to describe the microbiological, clinical and epidemiological characteristics of imported rickettsioses in travellers and migrants included in a Spanish collaborative network database. METHODS: This multicentre retrospective observational study was nested in +Redivi, the Cooperative Network for the Study of Infections Imported by Immigrants and Travellers. We asked collaborating centres for microbiological, clinical and epidemiological data on the rickettsiosis cases from the inception of the network in 2009 to December 2020. RESULTS: Fifty-four cases of imported rickettsioses were included; 35 (64.8%) patients were men, and the median age was 37 years (interquartile range 26, 51.2). Only 7.4% of patients were travellers visiting friends and relatives, and 5.6% were migrants. The most frequent travel destination (38.9%) was South Africa, and 90.7% engaged in a high-risk activity. Twenty-seven patients (50.0%) started presenting symptoms after their return to Spain. The most frequent symptoms were febrile syndrome (55.6%) and cutaneous manifestations (27.8%). Most diagnoses (63.0%) were confirmed by serology. Only a few cases (9.3%) required hospitalization. All participants had a full recovery. CONCLUSIONS: Clinicians should suspect rickettsial diseases in travellers coming from high-risk areas, especially Southern Africa, who have engaged in activities in rural areas and natural parks. Doxycycline should be considered in the empiric treatment of imported fever of travellers coming from those areas or who have engaged in high-risk activities. There is a need to improve access to molecular diagnosis of rickettsiosis in Spain.

Post-infectious irritable bowel syndrome following a diagnosis of traveller's diarrhoea: a comprehensive characterization of clinical and laboratory parameters.

BACKGROUND: Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller's diarrhoea (TD), even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical and microbiological characteristics of patients with post-infectious irritable bowel syndrome (PI-IBS) after returning from tropical or subtropical areas. METHODS: We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral centre in Barcelona with persistent gastrointestinal symptoms following a diagnosis of TD. PI-IBS was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least 6 months after the diagnosis of TD, a negative stool culture for bacterial pathogens and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical and microbiological variables were collected. RESULTS: We identified 669 travellers with a diagnosis of TD. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed PI-IBS. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14-96). A microbiological diagnosis of TD was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of TD. The multivariate analysis revealed that parasitic infections were independent risk factors for PI-IBS (OR 3.0, 95%CI 1.2-7.8). Pre-travel counselling reduced the risk of PI-IBS (OR 0.4, 95%CI 0.2-0.9). CONCLUSIONS: In our cohort, almost 10% of patients with travellers' diarrhoea developed persistent symptoms compatible with PI-IBS. Parasitic infections, mainly giardiasis, seem to be associated with PI-IBS.

Evaluation of Two Different Strategies for Schistosomiasis Screening in High-Risk Groups in a Non-Endemic Setting.

A consensus on the recommended screening algorithms for schistosomiasis in asymptomatic high-risk subjects in non-endemic areas is lacking. The objective of this study was to evaluate the real-life performance of direct microscopy and ELISA serology for schistosomiasis screening in a high-risk population in a non-endemic setting. A retrospective cohort study was conducted in two out-patient Tropical Medicine units in Barcelona (Spain) from 2014 to 2017. Asymptomatic adults arriving from the Sub-Saharan region were included. Schistosomiasis screening was conducted according to clinical practice following a different strategy in each setting: (A) feces and urine direct examination plus S. mansoni serology if non-explained eosinophilia was present and (B) S. mansoni serology plus uroparasitological examination as the second step in case of a positive serology. Demographic, clinical and laboratory features were collected. Schistosomiasis cases, clinical management and a 24 month follow-up were recorded for each group. Four-hundred forty individuals were included. The patients were mainly from West African countries. Fifty schistosomiasis cases were detected (11.5% group A vs. 4 % group B, p = 0.733). When both microscopic and serological techniques were performed, discordant results were recorded in 18.4% (16/88). Schistosomiasis cases were younger (p < 0.001) and presented eosinophilia and elevated IgE (p < 0.001) more frequently. Schistosomiasis is a frequent diagnosis among high-risk populations. Serology achieves a similar performance to direct diagnosis for the screening of schistosomiasis in a high-risk population.

Opportunistic Community Screening of Chronic Chagas Disease Using a Rapid Diagnosis Test in Pharmacies in Barcelona (Catalonia, Spain): Study Protocol and Pilot Phase Results.

Objectives: This study aimed to report the protocol and results from the pilot phase of an opportunistic CP-based CD screening program in Barcelona, Spain. Methods: Three strategies according to recruitment approach were designed: passive, active and active-community. The study process consisted of signing the informed consent form, recording the patient's data in a web-based database system, and performing the rapid test and blood collection on dry paper. Results: Nineteen pharmacies participated and 64 patients were included during the pilot phase of the study. The rapid diagnostic test (RDT) was positive in 2/64 (3.13%) cases. Of the 49 DBS samples that arrived at the laboratory, 22 (45%) were collected incorrectly. After quantitative and qualitative assessment of the program, the dry paper sample and passive strategy were ruled out. Conclusion: DBS sampling and the passive strategy are not suitable for CD screening in community pharmacies. There is a need to expand the number of participating pharmacies and individuals to determine whether conducting a RDT in community pharmacies is an effective screening method to increase access to CD diagnosis in a non-endemic area.

Health and Vaccination Status of Unaccompanied Minors After Arrival in a European Border Country: A Cross-sectional Study (2017-2020).

BACKGROUND: Unaccompanied and separated children (UASC) are a high-risk group for infectious diseases and information on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study was to describe the health status and serological protection against different vaccine-preventable diseases among UASC to inform public health decision-making. METHODS: Retrospective study of all UASC seen at an international health reference center in Barcelona (Spain) between January 2017 and February 2020. Screening results were analyzed using binary logistic regression with adjustment for symptoms, geographic origin, and time since arrival. RESULTS: We studied 289 UASC (88.9% males; median age, 17 years). At least one infection was diagnosed in 136 minors (47.1%). There was a high prevalence of intestinal parasites (22.8%), latent tuberculosis infection (22.5%), and hepatitis B (5.2%), even in asymptomatic individuals, and especially among UASC from sub-Saharan Africa (odds ratio, 2.5; 95% confidence interval, 1.5-4.0, P < 0.001). We did not observe a significant association between clinical symptoms and the presence of infection or differences in the prevalence of different infections according to number of months since arrival. Protection against hepatitis B virus (36%), measles (80%), and varicella (83%) was suboptimal. CONCLUSIONS: Our results highlight the importance of screening and vaccination programs for UASC arriving in Europe, especially border countries. Protocols should be adjusted according to geographic origin. Absence of symptoms does not necessarily rule out infection, highlighting the importance of screening in asymptomatic minors. These programs are a public health priority and should not be neglected during the current COVID-19 pandemic.

Association of HLA-B∗35 and moderate or severe cutaneous reactions secondary to benznidazole treatment in chronic chagas disease.

OBJECTIVES: Benznidazole is the first-line treatment for Chagas disease. Adverse events appear in more than 50% of patients, leading to discontinuation in approximately 15%. Cutaneous reactions are one of the most frequent adverse events. Human leucocyte antigen (HLA) genotyping studies identified an association between cutaneous reactions to benznidazole and carrying the specific allele HLA-B∗35:05. We designed the present study to prospectively confirm this association. METHODS: This is a prospective observational study including Chagas disease patients aged 18 years or more who accepted to receive benznidazole treatment following current guidelines. Allele genotyping of HLA-B was determined in all patients. Clinical and analytical follow up was performed at days 0, 7, 14, 30 and 60 of treatment. RESULTS: Two-hundred and seven individuals were included. Seventy per cent were female with a mean age of 45.1 (SD ± 9.86) years mainly from Bolivia (92.8%). In 102 (49.3%) cases a cutaneous reaction was diagnosed. Forty-eight (46.6%) were classified as mild, 37 (35.9%) as moderate and 18 (17.5%) as severe. Thirty-two (15.4%) patients had to definitively interrupt the treatment because of a cutaneous reaction. Female sex (OR 4.49; 95% CI 1.62-12.47), new-onset eosinophilia before cutaneous symptoms (OR 2.55; 95% CI 1.2-5.43) and carrying the HLA-B∗35 allelic group (OR 2.58; 95% CI 1.2-5.51) were all predictors of moderate to severe cutaneous reactions. No statistical significance was found when the specific allele HLA-B∗35:05 was analysed. CONCLUSIONS: Patients carrying the HLA-B∗35 allelic group are at higher risk of moderate to severe reactions when taking benznidazole treatment.

Analytical Evaluation of Dried Blood Spot and Rapid Diagnostic Test as a New Strategy for Serological Community Screening for Chronic Chagas Disease.

Background: Chagas disease is a public health problem not only in Latin America, but also in other regions, including Spain, due to migration movements. Conventional serological diagnosis requires an invasive sample (plasma or serum) and a well-equipped laboratory. To circumvent those limitations, blood samples dried on filter paper (DBS) or Rapid Diagnostic Test (RDT) could be a practical alternative to reference protocol for serological screening in epidemiological studies. We evaluated the usefulness of dried blood sampling and a rapid diagnostic test (Trypanosoma Detect™) for the detection of antibodies against T. cruzi for their use in community-based screening. Methodology/Principal Findings: A total of 162 stored paired whole-blood and serum samples from Latin American migrants and 25 negative-control blood samples were included. Diagnosis of chronic Chagas disease was performed in serum according to WHO algorithms. Blood samples were retrospectively collected as dried spots and then analyzed using two different serological techniques, enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (E-CLIA). Whole-blood samples were also used to evaluate a rapid diagnostic test based on immunochromatography. A better correlation with conventional serum was observed in dried blood elutes using E-CLIA than ELISA (97% vs. 77% sensitivity, respectively). Both assays reported 100% specificity. The median cut-off index values of E-CLIA for dried blood were significantly lower than those for serum (138.1 vs. 243.3, P<0.05). The Trypanosoma Detect™ test presented a sensitivity and specificity of 89.6% and 100%, respectively. Conclusions: The detection of antibodies against T. cruzi in dried blood samples shows a higher sensitivity when using E-CLIA compared with ELISA. Trypanosoma Detect™ is easier to use but has a lower sensitivity. Hence, we propose a sequential strategy based on performing the rapid test first, and a negative result will be confirmed by DBS-ECLIA for use in community Chagas disease screening programs.

Epidemiological and clinical profile of immunosuppressed patients with imported strongyloidiasis: a substudy from a larger cohort of the +REDIVI Spanish Collaborative Network.

The aim of this study was to describe the clinical and epidemiological profile of immunosuppressed patients with imported strongyloidiasis in a non-endemic setting, and to compare these results with non-immunosuppressed patients. This is a case-control substudy from a larger observational retrospective study that included all patients with strongyloidiasis registered in the +REDIVI Spanish Collaborative Network. Overall, 1245 patients with imported strongyloidiasis were included. From these, 80 (6.4%) patients had some kind of immunosuppression. Three (3.8%) patients had a hyperinfection syndrome, and 34 (52.3%) patients had eosinophilia. The percentages of positive results of the formalin-ether technique, the fecal culture and serology were 12.3%, 21.1% and 95.4%, respectively. When comparing the main characteristics, immunosuppressed patients had higher proportion of severe clinical manifestations and lower proportion of eosinophilia. No differences were found regarding yield of microbiological techniques and treatment response. These results stress the importance of strongyloidiasis screening among immunosuppressed patients coming from endemic areas. Serological tests have an acceptable sensitivity to be used as a screening tool.

A Community-Based Intervention for the Detection of Chagas Disease in Barcelona, Spain.

Chagas disease (CHD) has become a challenge in Spain due to the high prevalence of immigrants coming from endemic areas. One of the main difficulties for its control and elimination is its underdiagnosis. The identification and integral treatment of CHD are key to increasing rates of diagnosis, overcoming psycho-social barriers and avoiding CHD progression. Community interventions with in situ screening have proven to be a useful tool in detecting CHD among those with difficulties accessing health services. To determine the underdiagnosis rate of the population most susceptible to CHD among those attending two different Bolivian cultural events celebrated in Barcelona; to describe the sociodemographic characteristics of the people screened; and to analyse the results of the screening. The community interventions were carried out at two Bolivian cultural events held in Barcelona in 2017. Participants were recruited through community health agents. A questionnaire was given to determine the participants' prior knowledge of CHD. In situ screening was offered to those who had not previously been screened. Those who did not wish to be screened were asked for the reason behind their decision. Results were gathered in a database and statistical analyses were performed using STATA v14. 635 interviews were carried out. 95% of the subjects reported prior knowledge of CHD. 271 subjects were screened: 71.2% women and 28.8% men, of whom 87.8% were of Bolivian origin. The prevalence of CHD was 8.9%. Community health interventions with in situ screening are essential to facilitating access to diagnosis.

Estrategia secuencial para el cribado de la ITBL en inmigrantes recién llegados en situación social vulnerable / Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations

INTRODUCCIÓN: Algunos estudios indican altas prevalencias de infección tuberculosa latente (ITBL) en población inmigrante, lo que es relevante, pues el 5-10% de los casos desarrollaran una tuberculosis activa. El objetivo de este estudio es describir los resultados de una estrategia secuencial en población inmigrante recién llegada para el diagnóstico de ITBL usando la prueba de tuberculina (PT) e IGRAs. MÉTODOS: Se realizó un estudio descriptivo retrospectivo con inmigrantes entre 6 y 35años de edad de centros de acogida, derivados a una unidad de salud internacional entre julio de 2013 y junio de 2016. Se realizó la PT, y cuando fue ≥ 5 mm, se determinaron los IGRAs. La ITBL se definió como aquellos con IGRAs ≥ 0,35 UI/ml y radiografía de tórax normal. RESULTADOS: De los 184 casos, 138 (75,0%) eran hombres, de 23,0años de edad. Las áreas geográficas de origen más frecuente fueron: 63 (34,2%) de Asia, 42 (22,8%) de Europa del Este y 41 (22,3%) del África subsahariana. La PT fue ≥10mm en 79 (42,9%). La prevalencia de ITBL usando la estrategia secuencial fue de 33/184 (17,9%). El índice kappa de Cohen (entre PT ≥ 10mm e IGRAs) fue de 0,226. CONCLUSIÓN: Basar el diagnóstico de la ITBL tan solo en la PT puede representar una sobreestimación. Algunos estudios demuestran que el cribado secuencial sería el más coste-efectivo, y ello parece más evidente en las poblaciones vacunadas con BCG

INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥ 5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥ 0.35IU/ml and normal chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥ 10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST ≥ 10mm and IGRAs) was 0.226. CONCLUSION: Basing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations

Persistence of Zika virus in semen 93 days after the onset of symptoms / Persistencia del virus Zika en semen 93 días tras el comienzo de los síntomas

Introduction: Zika virus is mainly transmitted through the bites of infected Aedes mosquitoes, although mother-to-child and sexual transmission have also been described. The presence of Zika virus in semen after infection seems to be not uncommon, but the duration of viral persistence has not been well-determined. Methods: Molecular, serological and cell culture methods were used for the diagnosis and follow up of a case of Zika virus infection imported from Venezuela. Serial samples of serum, urine and semen were analyzed to investigate the persistence of the Zika virus. Results: Zika virus was detected in semen samples up to 93 days after the onset of symptoms. Conclusions: Our results confirm the persistence of Zika virus in semen samples for long periods after infection (AU)

Introducción: El virus Zika se transmite fundamentalmente por la picadura de mosquitos Aedes infectados, aunque también es posible la transmisión de madre a hijo y la transmisión sexual. La presencia del virus Zika en semen tras la infección parece ser algo relativamente frecuente, pero la duración de la persistencia viral no es bien conocida. Métodos: Mediante técnicas moleculares, serológicas y cultivo celular se diagnosticó un caso de Zika importado de Venezuela y se tomaron muestra seriadas de suero, orina y semen para investigar la persistencia del virus. Resultados: El virus Zika fue detectado en muestras de semen recogidas 93días después del inicio de los síntomas. Conclusiones: Nuestros resultados confirman la persistencia del virus Zika en semen por períodos prolongados de tiempo después de la infección (AU)

Persistence of Zika virus in semen 93 days after the onset of symptoms.

INTRODUCTION: Zika virus is mainly transmitted through the bites of infected Aedes mosquitoes, although mother-to-child and sexual transmission have also been described. The presence of Zika virus in semen after infection seems to be not uncommon, but the duration of viral persistence has not been well-determined. METHODS: Molecular, serological and cell culture methods were used for the diagnosis and follow up of a case of Zika virus infection imported from Venezuela. Serial samples of serum, urine and semen were analyzed to investigate the persistence of the Zika virus. RESULTS: Zika virus was detected in semen samples up to 93 days after the onset of symptoms. CONCLUSIONS: Our results confirm the persistence of Zika virus in semen samples for long periods after infection.

Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations. / Estrategia secuencial para el cribado de la ITBL en inmigrantes recién llegados en situación social vulnerable.

INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥0.35IU/ml and normal chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST≥10mm and IGRAs) was 0.226. CONCLUSION: Basing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations.