Background: Migrant farmworkers are among the highest-risk populations for latent TB infection (LTBI) in the United States with numerous barriers to healthcare access and increased vulnerability to infectious diseases. LTBI is usually diagnosed on the border using the tuberculin skin test (TST). QuantiFERON-TB Gold In-Tube (QFT-GIT) also measures immune response against specific Mycobacterium tuberculosis antigens. The objective of this study is to assess the comparability of TST and QFT-GIT to detect LTBI among migrant farmworkers on the border, as well as to examine the effects of various demographic and clinical factors on test positivity. Methods: Participants were recruited using mobile clinics on the San Luis US-Mexico border and tested with QFT-GIT and TST. Demographic profiles and clinical histories were collected. Kappa coefficients assessed agreement between TST and QFT-GIT using various assay cutoffs. Logistic regression examined factors associated with positive TST or QFT-GIT results. Results: Of 109 participants, 59 of 108 (55 %) were either TST (24/71, 34 %) or QFT-GIT (52/106, 50 %) positive. Concordance between TST and QFT-GIT was fair (71 % agreement,kappa= 0.38, 95 % CI: 0.15, 0.61). Factors associated with LTBI positivity included smoking (OR = 1.26, 95 % CI-1.01-1.58) and diabetes/high blood sugar (OR = 0.70, 95 % CI = 0.51-0.98). Discussion: Test concordance between the two tests was fair, with numerous discordant results observed. Greater proportion of positives detected using QFT-GIT may help avoid LTBI under-diagnosis. Assessment of LTBI status on the border provides evidence whether QFT-GIT should replace the TST in routine practice, as well as identifies risk factors for LTBI among migrant populations.

Introdução- A busca ativa de indivíduos infectados pelo Mycobacterium tuberculosis, com o auxílio do teste tuberculínico, principalmente em populações de detentos, moradores de rua, infectados pelo vírus do HIV entre outras, tem como objetivo prevenir a evolução da infecção para a doença tuberculose e auxiliar o conhecimento de novos casos da doença. O teste tuberculínico é uma importante ferramenta, para identificar os indivíduos reatores (infectados) e não reatores (não infectados). Ele pode ser aplicado a partir de várias técnicas, mas a que permite a padronização e a comparação dos resultados é a técnica intradérmica de Mantoux, a mais usada atualmente. No Brasil, a leitura do resultado do teste tuberculínico é realizada, por recomendação do Ministério de Saúde, com régua milimetrada. Para seu uso é necessário um treinamento rigoroso, o que tem contribuído para a diminuição de leitores do teste tuberculínico na rotina dos serviços de saúde. Como alternativa temos outro instrumento, paquímetro, ainda não padronizado no Brasil. Outros países o utilizam nas rotinas dos serviços de saúde para busca de indivíduos reatores ou não ao teste tuberculínico, ele não cabe para aferição ou inquéritos epidemiológicos. Objetivo- Comparar os instrumentos de leitura dos resultados do teste tuberculínico obtidos através da leitura padronizada, feita por régua milimetrada, e a leitura, não padronizada, feita por paquímetro. Métodos- Estudo descritivo realizado numa população prisional de uma Penitenciária e de um Centro de Detenção Provisória, da cidade de Guarulhos, Grande São Paulo, entre os meses de março a junho de 2008. Foi realizada a leitura do teste tuberculínico de forma dupla cega, por dois leitores, com instrumentos diferentes, paquímetro e régua milimetrada. Resultados- Foram administrados testes tuberculínicos em 1954 indivíduos; destes 111 foram excluídos por não terem comparecido à leitura do teste, resultando em uma amostra de 1843 indivíduos divididos em 1059 (57,5 por cento ) na Penitenciária e 784 (42,5 por cento ) no Centro de Detenção Provisória. Os resultados comparativos entre os dois instrumentos, quando avaliados os reatores com os não reatores, foram altos e equivalentes, pois a sensibilidade (93 por cento ) e a especificidade (97 por cento ) foram praticamente as mesmas. A média da concordância foi alta entre os dois instrumentos (95,5 por cento ) e a discordância foi baixa (4,5 por cento ). O Ministério da Saúde preconiza uma concordância acima de 80 por cento para aferição de novos leitores. Conclusões- Com este estudo observamos que o paquímetro pode ser considerado equivalente à régua milimetrada e poderá ser uma alternativa à régua para a leitura do teste tuberculínico no Brasil, principalmente para a busca de casos de tuberculose latente na rotina dos serviços de saúde, por ser um bom instrumento de separação dos indivíduos e não é suficiente para aferir um novo leitor. Entretanto, a régua deverá ser mantida, especialmente para inquéritos epidemiológicos / Introduction- The active search of individuals infected with Mycobacterium tuberculosis aims to prevent the development of infection to the disease tuberculosis and ancillary knowledge of new cases of the disease. The tuberculin test is an important tool to identify individuals (infected) and non-reactors reactors (noninfected). It can be applied from various techniques. Nowadays Mantoux intradermal technique is the most widely used and allows the standardization and comparability of results. In Brazil, the reading of the tuberculin test result is performed with a ruler, by recommendation of the Ministry of health. For its use is required a rigorous training, which has contributed to the decline of tuberculin test readers in routine health services. Alternatively, caliper rule is a technique that can be used, but it is not standardized in Brazil. Objective- Compare the reading instruments of tuberculin skin test results obtained through the standardized reading, made by a millimeter ruler, and reading, not standardized, made with a caliper rule. Method- It was a descriptive study in a prison population of a Penitentiary and a Provisional Detention Centre in the city of Guarulhos, São Paulo, between the months of March to June 2008. Tuberculin test reading was done in a double blind, tuberculin test by two readers, with different instruments, ruler and caliper rule. Results- Tuberculin skin tests were administered to 1,954 individuals; of these 111 was excluded for failing to appear for the reading test, resulting in a sample of 1,843 individuals divided in 1,059 (57.5 per cent ) in Penitentiary and 784 (42.5 per cent ) in the Provisional Detention Center. The comparative results between the two instruments were high and equivalent (sensitivity=93 per cent and specificity=97 per cent ). The average correlation was high among the two instruments (95.5 per cent ) and the disagreement was low (4.5 per cent ). The Ministry of Health recommends a concordance above 80 per cent for benchmarking new readers. Conclusions- We observed that the caliper rule can be considered equivalent to the rule and may be an alternative for reading the tuberculin test in Brazil, especially to search for latent TB cases. However, the rule should be maintained, especially toepidemiological investigations

Introdução- A busca ativa de indivíduos infectados pelo Mycobacterium tuberculosis, com o auxílio do teste tuberculínico, principalmente em populações de detentos, moradores de rua, infectados pelo vírus do HIV entre outras, tem como objetivo prevenir a evolução da infecção para a doença tuberculose e auxiliar o conhecimento de novos casos da doença. O teste tuberculínico é uma importante ferramenta, para identificar os indivíduos reatores (infectados) e não reatores (não infectados). Ele pode ser aplicado a partir de várias técnicas, mas a que permite a padronização e a comparação dos resultados é a técnica intradérmica de Mantoux, a mais usada atualmente. No Brasil, a leitura do resultado do teste tuberculínico é realizada, por recomendação do Ministério de Saúde, com régua milimetrada. Para seu uso é necessário um treinamento rigoroso, o que tem contribuído para a diminuição de leitores do teste tuberculínico na rotina dos serviços de saúde. Como alternativa temos outro instrumento, paquímetro, ainda não padronizado no Brasil. Outros países o utilizam nas rotinas dos serviços de saúde para busca de indivíduos reatores ou não ao teste tuberculínico, ele não cabe para aferição ou inquéritos epidemiológicos. Objetivo- Comparar os instrumentos de leitura dos resultados do teste tuberculínico obtidos através da leitura padronizada, feita por régua milimetrada, e a leitura, não padronizada, feita por paquímetro. Métodos- Estudo descritivo realizado numa população prisional de uma Penitenciária e de um Centro de Detenção Provisória, da cidade de Guarulhos, Grande São Paulo, entre os meses de março a junho de 2008. Foi realizada a leitura do teste tuberculínico de forma dupla cega, por dois leitores, com instrumentos diferentes, paquímetro e régua milimetrada. Resultados- Foram administrados testes tuberculínicos em 1954 indivíduos; destes 111 foram excluídos por não terem comparecido à leitura do teste, resultando em uma amostra de 1843 indivíduos divididos em 1059 (57,5 por cento ) na Penitenciária e 784 (42,5 por cento ) no Centro de Detenção Provisória. Os resultados comparativos entre os dois instrumentos, quando avaliados os reatores com os não reatores, foram altos e equivalentes, pois a sensibilidade (93 por cento ) e a especificidade (97 por cento ) foram praticamente as mesmas. A média da concordância foi alta entre os dois instrumentos (95,5 por cento ) e a discordância foi baixa (4,5 por cento ). O Ministério da Saúde preconiza uma concordância acima de 80 por cento para aferição de novos leitores. Conclusões- Com este estudo observamos que o paquímetro pode ser considerado equivalente à régua milimetrada e poderá ser uma alternativa à régua para a leitura do teste tuberculínico no Brasil, principalmente para a busca de casos de tuberculose latente na rotina dos serviços de saúde, por ser um bom instrumento de separação dos indivíduos e não é suficiente para aferir um novo leitor. Entretanto, a régua deverá ser mantida, especialmente para inquéritos epidemiológicos / Introduction- The active search of individuals infected with Mycobacterium tuberculosis aims to prevent the development of infection to the disease tuberculosis and ancillary knowledge of new cases of the disease. The tuberculin test is an important tool to identify individuals (infected) and non-reactors reactors (noninfected). It can be applied from various techniques. Nowadays Mantoux intradermal technique is the most widely used and allows the standardization and comparability of results. In Brazil, the reading of the tuberculin test result is performed with a ruler, by recommendation of the Ministry of health. For its use is required a rigorous training, which has contributed to the decline of tuberculin test readers in routine health services. Alternatively, caliper rule is a technique that can be used, but it is not standardized in Brazil. Objective- Compare the reading instruments of tuberculin skin test results obtained through the standardized reading, made by a millimeter ruler, and reading, not standardized, made with a caliper rule. Method- It was a descriptive study in a prison population of a Penitentiary and a Provisional Detention Centre in the city of Guarulhos, São Paulo, between the months of March to June 2008. Tuberculin test reading was done in a double blind, tuberculin test by two readers, with different instruments, ruler and caliper rule. Results- Tuberculin skin tests were administered to 1,954 individuals; of these 111 was excluded for failing to appear for the reading test, resulting in a sample of 1,843 individuals divided in 1,059 (57.5 per cent ) in Penitentiary and 784 (42.5 per cent ) in the Provisional Detention Center. The comparative results between the two instruments were high and equivalent (sensitivity=93 per cent and specificity=97 per cent ). The average correlation was high among the two instruments (95.5 per cent ) and the disagreement was low (4.5 per cent ). The Ministry of Health recommends a concordance above 80 per cent for benchmarking new readers. Conclusions- We observed that the caliper rule can be considered equivalent to the rule and may be an alternative for reading the tuberculin test in Brazil, especially to search for latent TB cases. However, the rule should be maintained, especially toepidemiological investigations

Objetivo: A prevalência e incidência da tuberculose na população prisional é muito maior que na população geral. Conhecer a prevalência de infectados, doentes e características físicas, sociais e criminais dos presos, foram objetos deste estudo. Método: Realizou-se uma busca ativa de casos de tuberculose nos 1.052 detentos de 9 Distritos Policiais da Zona Oeste da Cidade de São Paulo, entre 2000-2001. Após a aplicação de um inquérito e da prova tuberculínica, foram realizados os exames de baciloscopia, cultura, identificação e teste de sensibilidade às drogas antituberculose. Resultados: Do total de 1.052 detentos 99,7 por cento eram homens; 71,3 por cento tinham entre 18 e 29 anos; 82,4 por cento eram solteiros ou amasiados; 51,4 por cento eram pretos ou pardos; 64,5 por cento não completaram o 1º grau; 40 por cento praticaram o roubo como principal delito; 3,7 por cento tiveram tuberculose no passado e 32,8 por cento eram sintomáticos respiratórios. Dos 932 que fizeram a prova tuberculínica, 64,5 por cento estavam infectados. Dos 1.017 escarros analisados, 8 (0,8 por cento) foram positivos na baciloscopia e 54 (5,3 por cento) na cultura. Das 54 cepas isoladas, 38,9 por cento eram M. tuberculosis e 61,1 por cento eram micobactérias não tuberculosas. Das 21 cepas de M. tuberculosis, 85,7 por cento eram sensíveis, 9,5 por cento eram resistentes à isoniazida e rifampicina e 4,8 por cento à isoniazida, rifampicina e pirazinamida. Conclusões: Pela baciloscopia, o coeficiente de prevalência de tuberculose (por 100.000 detentos) foi de 787, e pela cultura de 5.310, cerca de 30 e 203 vezes mais que o da população da cidade de São Paulo, respectivamente. O fato de haver 3 detentos com cepas multirresistentes às drogas antituberculose é uma ameaça à saúde pública / Purpose: The prevalence and incidence of tuberculosis in inmates population is much larger than in the general population. The purpose of this study was acquiring good knowledge of the prevalence of infected person and tuberculosis patients, as well as the physical, social and criminal characteristics of inmates. Method: An active search of tuberculosis cases was conducted among the 1,052 inmates of 9 County Jails of the West Section of the São Paulo City between 2000-2001. After application of an inquiry and the tuberculin skin test, laboratory investigations were also conducted such as sputum bacilloscopy, culture, identification and the test of sensitivity to anti-TB drugs. Results: Out of the total number of 1,052 inmates, 99.7 per cent were males; 71.3 per cent were in the group of ages 18 and 29 years old; 82.4 per cent were single or had sexual mates; 51.4 per cent were negroes or mulattos; 64.5 per cent had low education level; 40 per cent had been engaged in thefts/robberies; 3.7 per cent had tuberculosis episodes in the past and 32.8 per cent displayed respiratory symptoms. Out of the 932 which underwent the tuberculin skin test, 64.5 per cent were infected. Out of the 1,017 sputum samples analyzed, 8 (0.8 per cent) had positive bacilloscopy and 54 (5.3 per cent) positive culture. Of the 54 strains isolated, 38.9 per cent were M. tuberculosis and 61.1 per cent were non-tuberculosis mycobacteria. Of the 21 M. tuberculosis strains 85.7 per cent were sensitive, 9.5 per cent were resistant to isoniazide and rifampicin and 4.8 per cent to isoniazide, rifampicin and pyrazinamide. Conclusions: Based on the bacilloscopy, the tuberculosis prevalence rate (per 100,000 inmates) was 787 and based on the culture was 5,310 inmates, around 30 and 203 times higher than that of the São Paulo city population, respectively. The fact that 3 inmates had strains multi-resistant to anti-TB drugs can be deemed a threat to the public health

Introduksjon: QuantiFERON®TB Gold (QFT) er en ny blodtest for påvisning av tuberkulosesmitte, men med få data så langt fra undersøkelse av immigranter. Målet med studien var å sammenligne resultat av QFT og tuberkulin hudtest blant nyankomne asylsøkere i Norge og å vurdere hvilken rolle QFT bør ha i screening for latent tuberkulose. Metode: Alle asylsøkere, 18 år eller eldre, som ankom Tanum asylmottak fra september 2005 ble invitert til å delta og ble inkludert etter informert samtykke. Inkludering pågikk inntil et forhåndsbestemt antall på 1000 inkluderte ble nådd. Siste deltager ble inkludert i juni 2006. Deltagelse innebar en QFT test og standardiserte spørsmål, i tillegg til den lovpålagte tuberkulintesten og lungerøntgen. Resultat: Totalt 2813 asylsøkere ankom Tanum asylmottak i inkluderingsperioden (sept 05-juni 06).  Blant de 1000 deltagerne hadde 912 gyldige testresultater og ble inkludert i analysen, 29 % (264) hadde positiv QFT, mens 50 % (460) hadde positiv tuberkulintest (indurasjon &gt; 6mm). Det indikerer en høy andel smittede personer i denne gruppen. Blant deltagere med positiv tuberkulintest hadde 50 % negativ QFT, mens 7 % av dem med negativ tuberkulintest hadde positiv QFT. Det var en signifikant sammenheng mellom økning i tuberkulinutslag og sannsynligheten for å ha positiv QFT. Samsvar mellom testene var 71-79%, avhengig av grenseverdi for tuberkulin. Det var bedre samsvar mellom testene for ikke-vaksinerte personer. Konklusjon: Ved å implementere QFT som rutine kan videre oppfølging avsluttes for 42% av dem som ville ha blitt henvist basert kun på tuberkulinresultat (&gt; 6mm). Andelen som henvises vil være den samme enten QFT implementeres som erstatning for eller som supplement for å bekrefte en positiv tuberkulinreaksjon, men antallet som testes vil variere mye. Ulike tilnærminger vil identifisere samme andel (88-89%) av asylsøkere med positiv QFT og/eller sterkt positiv tuberkulinutslag (&gt;15mm), men ulike grupper vil mistes. / Introduction: QuantiFERON®TB Gold (QFT), a new blood test that detects tuberculosis infection, currently provides few data from immigrant screening. This study aimed to compare results of QFT and tuberculin skin tests (TST) among newly arrived asylum seekers in Norway and also assess the role of QFT in screening for latent tuberculosis. Methods: All asylum seekers, 18 years or older, who arrived at Tanum reception center from September 2005 were invited to participate and included after informed consent. Enrollment was continued until a fixed sample size of 1000 participants was reached. The last participant was included in June 2006. In addition to mandatory TST and chest X-ray, study participants underwent a QFT test and answered standardized questions. Results: A total of 2813 asylum seekers arrived at Tanum reception center during the inclusion period. Among the 1000 study participants, 912 showed valid test results and were included in analysis; 29% (264) had a positive QFT test and 50% (460) tested positive with TST (indurations &gt;6 mm), indicating a high proportion of latent infection within this population. Among the TST-positive participants, 50% were QFT-negative, whereas 7% of the TST-negative participants were QFT-positive. A significant association occurred between increase in size of TST induration and positive QFT result. Test agreement (71%–79%) depended on the chosen TST cut-off and was higher for nonvaccinated individuals. Conclusions: By implementing QFT as a routine screening test further follow up can be avoided for 42% of asylum seekers who would have been referred based only on a positive TST (&gt;6 mm). The proportion of individuals referred remained the same whether QFT replaced TST or confirmed a positive TST; however, the number of individuals tested varied greatly. Different approaches would identify the same proportion (88%-89%) of asylum seekers with either a positive QFT or a strongly positive TST (&gt;15 mm), but different groups will be missed. / <p>ISBN 978-91-85721-53-5</p>

Objetivo: A prevalência e incidência da tuberculose na população prisional é muito maior que na população geral. Conhecer a prevalência de infectados, doentes e características físicas, sociais e criminais dos presos, foram objetos deste estudo. Método: Realizou-se uma busca ativa de casos de tuberculose nos 1.052 detentos de 9 Distritos Policiais da Zona Oeste da Cidade de São Paulo, entre 2000-2001. Após a aplicação de um inquérito e da prova tuberculínica, foram realizados os exames de baciloscopia, cultura, identificação e teste de sensibilidade às drogas antituberculose. Resultados: Do total de 1.052 detentos 99,7 por cento eram homens; 71,3 por cento tinham entre 18 e 29 anos; 82,4 por cento eram solteiros ou amasiados; 51,4 por cento eram pretos ou pardos; 64,5 por cento não completaram o 1º grau; 40 por cento praticaram o roubo como principal delito; 3,7 por cento tiveram tuberculose no passado e 32,8 por cento eram sintomáticos respiratórios. Dos 932 que fizeram a prova tuberculínica, 64,5 por cento estavam infectados. Dos 1.017 escarros analisados, 8 (0,8 por cento) foram positivos na baciloscopia e 54 (5,3 por cento) na cultura. Das 54 cepas isoladas, 38,9 por cento eram M. tuberculosis e 61,1 por cento eram micobactérias não tuberculosas. Das 21 cepas de M. tuberculosis, 85,7 por cento eram sensíveis, 9,5 por cento eram resistentes à isoniazida e rifampicina e 4,8 por cento à isoniazida, rifampicina e pirazinamida. Conclusões: Pela baciloscopia, o coeficiente de prevalência de tuberculose (por 100.000 detentos) foi de 787, e pela cultura de 5.310, cerca de 30 e 203 vezes mais que o da população da cidade de São Paulo, respectivamente. O fato de haver 3 detentos com cepas multirresistentes às drogas antituberculose é uma ameaça à saúde pública / Purpose: The prevalence and incidence of tuberculosis in inmates population is much larger than in the general population. The purpose of this study was acquiring good knowledge of the prevalence of infected person and tuberculosis patients, as well as the physical, social and criminal characteristics of inmates. Method: An active search of tuberculosis cases was conducted among the 1,052 inmates of 9 County Jails of the West Section of the São Paulo City between 2000-2001. After application of an inquiry and the tuberculin skin test, laboratory investigations were also conducted such as sputum bacilloscopy, culture, identification and the test of sensitivity to anti-TB drugs. Results: Out of the total number of 1,052 inmates, 99.7 per cent were males; 71.3 per cent were in the group of ages 18 and 29 years old; 82.4 per cent were single or had sexual mates; 51.4 per cent were negroes or mulattos; 64.5 per cent had low education level; 40 per cent had been engaged in thefts/robberies; 3.7 per cent had tuberculosis episodes in the past and 32.8 per cent displayed respiratory symptoms. Out of the 932 which underwent the tuberculin skin test, 64.5 per cent were infected. Out of the 1,017 sputum samples analyzed, 8 (0.8 per cent) had positive bacilloscopy and 54 (5.3 per cent) positive culture. Of the 54 strains isolated, 38.9 per cent were M. tuberculosis and 61.1 per cent were non-tuberculosis mycobacteria. Of the 21 M. tuberculosis strains 85.7 per cent were sensitive, 9.5 per cent were resistant to isoniazide and rifampicin and 4.8 per cent to isoniazide, rifampicin and pyrazinamide. Conclusions: Based on the bacilloscopy, the tuberculosis prevalence rate (per 100,000 inmates) was 787 and based on the culture was 5,310 inmates, around 30 and 203 times higher than that of the São Paulo city population, respectively. The fact that 3 inmates had strains multi-resistant to anti-TB drugs can be deemed a threat to the public health

As pessoas vivendo com HIV tÃm probabilidade aumentada de desenvolver, apresentar formar graves, ter cepas multirresistentes e morrer por tuberculose. A profilaxia para infecÃÃo latente por Mycobacteium tuberculosis (ILTB) diminui a chance de ativaÃÃo de tuberculose (TB) numa mÃdia de 62% nessa populaÃÃo. Entretanto, o diagnÃstico da TB na sua forma latente à controverso. O teste tuberculÃnico (TT) à o Ãnico exame aprovado no Brasil para avaliaÃÃo dessa infecÃÃo, embora existam problemas tanto na sua realizaÃÃo quanto na sua interpretaÃÃo. Exames de liberaÃÃo de interferon-gama foram criados recentemente com o objetivo de aumentar a especificidade e a praticidade da investigaÃÃo da ILTB. Esse estudo se propÃs a avaliar como vem sendo feita a investigaÃÃo da ILTB e o desempenho do TT e do QuantiFERON-TB Gold In-Tube (QTF-GIT) em portadores de HIV. Foram selecionados ao todo 351 pacientes portadores de HIV e sem evidÃncia de TB ativa, admitidos em dois centros de referÃncia de Fortaleza-CE, no perÃodo de 2007-2010. Na admissÃo, 41,8% dos pacientes realizaram TT, 36,3% foram avaliados quanto a contato com TB e 28,4% tiveram radiografia de tÃrax. A profilaxia foi realizada para 73,3% dos pacientes com TT positivo. Houve diagnÃstico de ILTB em 25,3% dos pacientes de acordo com o TT e em 6,7% pelo QTF-GIT (p<0,001). A correlaÃÃo entre os resultados dos dois testes foi considerada fraca (k= -0,037). Resultado positivo do TT esteve associado com drogadiÃÃo (OR 7 CI: 1,53-32,11; p=0,01), contato com TB bacilÃfera (OR 13 CI: 2,7-62,83; p=0,001), profilaxia para ILTB prÃvia (OR 17,5 CI: 3,4-90,4; p<0,001), procedÃncia do interior do estado (OR 2,74 CI:1,04-7,22; p= 0,04). NÃo houve associaÃÃo entre QTF-GIT positivo e fatores de risco para TB. A mÃdia de contagem de linfÃcitos T CD4+ nos indivÃduos com TT positivo foi superior à mÃdia dos com TT negativo (535,8 vs. 373,4 cÃl/mm3; p=0,006), enquanto o inverso ocorreu em relaÃÃo ao QTF-GIT (277 vs. 438,3 cÃl/mm3; p= 0,055). A mÃdia do logaritmo da carga viral foi superior naqueles com QTF-GIT positivo (4,81 vs. 2,11 log10 cÃp/ml; p= 0,005). Mais da metade dos pacientes nÃo realizou TT, apesar da alta prevalÃncia de ILTB. O TT contou com maior nÃmero de testes positivos. O QTF-GIT mostrou-se superior para pacientes com elevada viremia e imunossupressÃo. Sugere-se o uso de ambos os testes de forma complementar para aumentar a chance de diagnÃstico de ILTB e diminuir os riscos de progressÃo da doenÃa. / People living with HIV have an enhanced chance to develop and to die of tuberculosis (TB). Many studies demonstrate that chemoprophylaxis for latent tuberculosis infection (LTBI) reduces the progression to active TB. Indeed, the diagnosis of LTBI is controversial. In Brazil, the only test approved for use is the tuberculin skin test (TST), however, this test is complicated by several problems due to application and interpretation of the exam. Recently developed interferon-gamma release assays (IGRA) using Mycobacterium tuberculosis-specific antigens have the advantage of decreased cross-reactivity and, therefore, increased specificity. The purpose of this study is to evaluate the adherence of LTBI diagnosis and to compare the results of the QuantiFERON-TB Gold In-Tube test (QTF-GIT) and TST in a population of HIV-positive individuals from a country with high prevalence of TB. A cross-sectional study was carried out with 351 HIV patients without active tuberculosis, attending outpatient in two reference centers, from November 2007- 2010. At admission, 41.8% had realized TST, 36.3% had been interrogated about TB exposure and 28.4% had performed a chest X-ray. Chemoprophylaxis was offered to 73.3% of TST positive patients. The TST and QTF-GIT results were positive in 25.3% and 6.7% (p<0.001) of the individuals, respectively. The agreement between the two tests was poor (k= -0.037). Drug use (OR 7, 95% CI 1.5-32.1; p=0.01), TB exposure (OR 13, 95% CI 2.7-62.83; p=0.001), previous LTBI prophylaxis (OR 17.5, 95% CI 3.4-90.4; p<0.001), and living outside the state capÃtal (OR 2.7, 95% CI 1-7.2; p= 0.04) were associated with a positive TST result. There is no association between QTF-GIT positive result and risk factors for TB. TST positive individuals had a higher mean CD4+ cell count than those with TST negative result (535.8 cell/mm3 vs. 373.4 cell/mm3; p=0.006), in contrast to QTF-GIT positive result (277 cell/mm3 vs. 438.3 cell/mm3; p= 0.055). Higher viral load was associated with QTF-GIT positive result (4.8 log10 cop/ml vs. 2.1 log10 cop/ml; p= 0.005). Despite of Brazil being a country with a high burden of TB, more than half the patients have not realized TST, which appears to be more sensitive than QTF-GIT for diagnosis of LTBI. Otherwise, QTF-GIT shows better results in patients with advanced immunosuppression and high viral load. We suggest the use of both tests to increase LTBI diagnosis and decrease the risk of disease progression.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2017-03-24T11:22:47Z No. of bitstreams: 2 Dissertação - Tatiana Marlene Galvez Sánchez - 2017.pdf: 3124839 bytes, checksum: 942aa6d4fa9aa30babb4eb0d7e04a805 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-24T12:39:25Z (GMT) No. of bitstreams: 2 Dissertação - Tatiana Marlene Galvez Sánchez - 2017.pdf: 3124839 bytes, checksum: 942aa6d4fa9aa30babb4eb0d7e04a805 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-24T12:39:25Z (GMT). No. of bitstreams: 2 Dissertação - Tatiana Marlene Galvez Sánchez - 2017.pdf: 3124839 bytes, checksum: 942aa6d4fa9aa30babb4eb0d7e04a805 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Outro / Tuberculin skin test (TST) identifies a previous exposed to M. tuberculosis (Mtb) using an intradermal inoculation of purified protein derivates (PPD) that result in a delayed hypersensitivity reaction (DTH). Interferon-gamma release assay (IGRA) was suggested to replace TST. The IGRA uses antigens, ESAT-6 and CFP-10, absent in all BCG strains and some non tuberculous mycobacteria (NTM). However, reproducibility and high cost were limitations for endemic countries. For this reason, the development of new diagnose test for latent TB is necessary. Fusion proteins developed by our group has been recognized by the immune response generated by the infection with Mycobacterium tuberculosis. Thus the aim of this work was to evaluate the capacity of CMX or ECMX to be used in a Skin test for tuberculosis. BALB/c mice infected with Mtb were euthanized forty-five days after infection. Spleens, lungs and draining lymph nodes of infected mice were processed and evaluated by flow cytometry Both CD4 and CD8 IFN+ cells were able to recognize rCMX and rECMX. The skin test followed an evaluation of thickness/swelling ≥ PPD 2UT (positive control) to consider positive DTH. Based on thickness, at 24 h, rCMX 25μg (0.37±0.02) and rECMX 15-25μg (0.38±0.03/0,62±0,12) induced a positive DTH response. At 48h, rCMX 25μg (0.28±0.03) and rECMX 25μg (0.5±0.04) induced also a positive DTH reaction. In conclusion, fusion proteins rCMX and rECMX are recognized by infected mice with Mtb and skin test using rECMX 25μg induced better DTH response that of conventional PPD. / A prova tuberculínica (PT) é um teste cutâneo que identifica a exposição prévia ao M. tuberculosis (Mtb), mediante a inoculação via intradérmica do derivado protéico purificado (PPD) de Mtb, o que resulta em uma reação de hipersensibilidade do tipo tardia (DTH). O ensaio de liberação de IFN-γ (IGRA) foi indicado para substituir a PT. O IGRA usa os antígenos ausentes na BCG e algumas micobactérias não causadoras de TB (MNT), ESAT-6 e CFP-10. Porém, apresenta falta de reprodutibilidade e alto custo quando usado em populações endêmicas para TB. Diante disso, o desenvolvimento de novos testes de diagnóstico é necessário. Nosso grupo desenvolveu proteínas de fusão que são reconhecidas por linfócitos gerados pela infecção com Mtb. Assim, o trabalho propõe avaliar a utilização das proteínas rCMX e rECMX no desenvolvimento de um teste cutâneo de diagnóstico para tuberculose. Camundongos BALB/c foram infectados com Mtb H37Rv. Após 45 dias, a infecção induziu linfócitos T CD4+ e CD8+ produtores de IFN-γ específicos para rCMX e rECMX no baço, pulmões e linfonodos drenantes. Enquanto ao teste cutâneo realizado 45 dias após a infecção, a leitura de espessura/inchaço ≥ PPD 2UT (controle positivo) indicou uma reação de DTH positiva. Avaliando a espessura 24h após o inóculo, rCMX 25μg (0.37±0.02) e rECMX 15-25μg (0.38±0.03/0,62±0,12) induziram reação de DTH positiva. As 48h, rCMX 25μg (0.28±0.03) e rECMX 25μg (0.5±0.04) também apresentaram reação positiva. Enquanto o inchaço as 24h, só a rECMX apresentou DTH positiva. Em conclusão, este trabalho mostra que as proteínas rCMX e rECMX são reconhecidas pela resposta celular de camundongos infectados com Mtb, e quando usadas no teste cutâneo induziram reação de DTH positiva comparável e até superior ao PPD convencional. Dessa forma, é recomendada a avaliação das proteínas de fusão em outros modelos animais e posteriormente em humanos.

Tuberculosis (TB) remains the main cause of death in people living with HIV (PLHIV). Indeed, PLHIV have a 20-30% greater risk of developing TB compared to HIV-uninfected subjects and have lower TB treatment success rates. In 2014, among the 9.6 million incident cases of TB reported worldwide, 12% occurred in PLHIV and 0.4 million deaths from HIV-associated TB were recorded.Mycobacterium tuberculosis is the main etiological agent for TB. For a majority of individuals, the immune response upon infection by M. tuberculosis is sufficient to prevent the development of disease, but insufficient to clear the bacteria. This leads to the persistence of viable M. tuberculosis in diverse cells with no resulting clinical manifestations, an entity known as latent tuberculosis infection (LTBI). The resulting reservoir of M. tuberculosis is vast, and an estimated one third of the world population is concerned. For subjects with LTBI, the life-time risk of reactivation and progression to TB lies between 5 and 10%. However, if co-infected with HIV, the risk is much greater and reaches 10% per year. According to a Cochrane review in 2010, the screening and treatment of LTBI in PLHIV reduces this risk by 30-60%. This prevention strategy is therefore widely recommended. However, the implementation of LTBI screening and treatment into standard HIV-care has been limited. In this work, three different approaches have been used to understand and address this issue, focusing on a low TB-incidence and high-income setting.The first approach was to assess the implementation of LTBI screening in HIV-care across Belgium and identify its barriers as perceived by the caregivers on the field. Raising awareness to this issue was an indirect objective of the study. A multi-choice questionnaire was sent to 55 physicians working in a Belgian AIDS reference center or satellite clinic. A response rate of 62% was obtained. Only 20% of participants performed LTBI screening on all their patients and notable variations in the screening methods used were observed. A large majority of participants were in favor of targeting LTBI screening to HIV-infected patients at highest risk of TB rather than a systematic screening of all PLHIV. These results have been communicated to the Belgian LTBI working group, currently updating the national LTBI screening guidelines. Indeed, targeting screening to those at highest risk of TB is an attractive strategy in low-TB incidence countries and is already recommended in the United Kingdom. However, to date, no score assessing the risk of TB in PLHIV has been validated. Among the barriers to LTBI screening identified by the participants of this first study, the most frequently reported were lack of sensitivity of screening tools, risk associated to polypharmacy and toxicity of treatment. Improving the sensitivity of LTBI screening was the cornerstone of the second approach. The available screening tools for LTBI are the tuberculin skin test (TST) and two Interferon-gamma release assays (IGRAs): the QuantiFERON-TB Gold-IT (QFT-GIT) and the T-SPOT.TB®. All three lack sensitivity in PLHIV. Various strategies to discover superior LTBI screening tools are therefore being explored, including the development of IGRAs in response to alternative M. tuberculosis antigens to those used in the QFT-GIT or T-SPOT.TB®. A potential candidate is the native Heparin-Binding Haemagglutin (nHBHA), a methylated M. tuberculosis protein regarded as a latency-associated antigen. An in-house IGRA based on nHBHA (nHBHA-IGRA) has been shown to be a promising LTBI screening tool both in immunocompetent adults and in hemodialysed patients. The contribution of this nHBHA-IGRA to the detection of M. tuberculosis in PLHIV was therefore investigated. Treatment-naïve HIV-infected subjects were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the nHBHA-IGRA in parallel to the classical method consisting of medical history, chest X-ray, TST and QFT-GIT. Prospective clinical and biological follow-up ensued, with repeated testing with nHBHA-IGRA. Among 48 candidates enrolled for screening, 9 were diagnosed with LTBI by combining the TST and QFT-GIT results (3 TST+/QFT-GIT+, 1 TST+/QFT-GIT- and 5 TST-/QFT-GIT+). All 3 TST+/QFT-GIT+ patients, the TST+/QFT-GIT- patient as well an additional 3 subjects screened positive with the nHBHA-IGRA. These 3 additional patients had known M. tuberculosis exposure risks compatible with LTBI. During follow-up (median 14 months) no case of TB was reported and nHBHA-IGRA results remained globally constant. Multiplex analysis confirmed IFN- as the best read-out for the assay. From this study, we concluded that the nHBHA-IGRA appears complementary to the QFT-GIT for the screening of LTBI in PLHIV and the combination of the two tests may increase the sensitivity of screening. A large-scale study is however necessary to determine whether combining nHBHA-IGRA and QFT-GIT offers sufficient sensitivity to dismiss TST, as suggested by our results. In the same study, a group of HIV-infected adults with clinical suspicion of active TB were also recruited and tested with nHBHA-IGRA. Contrary to results in HIV-uninfected subjects, the nHBHA-IGRA could not discriminate between LTBI and active TB in PLHIV. This is an important caveat as HIV-infected subjects may present subclinical TB.A different angle was used for the third approach to the problem of LTBI in PLHIV. Systemic immune activation (SIA) is one of the principal driving forces in the natural course of HIV-infection. Despite long-term viral suppression by combination antiretroviral treatment (cART), a low-level SIA persists and is associated with an early-onset of age-associated disorders such as cardiovascular disease, dementia and osteoporosis. Causes of SIA in PLHIV are multiple and certain chronic infections appear to be implicated. A recent study in South Africa found that LTBI in PLHIV was associated with an increase in circulating activated CD8+ T-cells. If LTBI should contribute to the persistence of SIA, its screening and treatment could have an additional benefit on the clinical outcome of PLHIV. To investigate this theory, the expression of T-cell activation markers (CD38 and HLADR) as well as the level of plasmatic markers of immune activation (IL-6, sCD14, D-Dimers) were compared between subjects presenting active TB, subjects with LTBI and M. tuberculosis-free persons, with and without HIV-infection. In accordance with previous studies, active TB was associated with higher levels of SIA biomarkers in both HIV-infected and -uninfected groups. Among the HIV-uninfected subjects, no significant difference in biomarker level was found between those presenting LTBI and those with no evidence of M. tuberculosis. The effect of LTBI on activation biomarkers in the HIV-infected groups remained inconclusive because of the small number of individuals in the HIV+/LTBI group. Further investigation is therefore warranted. Interestingly, it was found that plasmatic markers may have a greater sensitivity for the detection of M. tuberculosis-associated SIA than the T-cell activation markers, an important result for future studies.Overall, LTBI in PLHIV is a challenging topic, in particular because of the lack of a gold-standard for the diagnosis of LTBI. Despite suboptimal tools, the evident clinical impact of LTBI screening and treatment in PLHIV on TB incidence justifies its implementation in standard HIV-care. In low TB-incidence countries, who, when and how to screen for LTBI in PLHIV remains unclear. This work offers an overview on the subject with particular focus on possible measures for improvement in the field. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

The original publication is available at http:/www.plosone.org / Introduction: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. Objectives: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Methods: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. Results: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. Conclusion: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. © 2011 Shanaube et al. / Publishers' Version