Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

Abstract Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 hours for reading. A TST of ≥10mm if HIV negative or ≥ 5mm if HIV positive, was considered positive. Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1%, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95%CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95%CI 1.2,1.8), having a BCG scar (OR 1.5,95%CI 1.2,1.8), living in a rural area (OR 1.4, 95%CI 1.1,1.9), and being out of school (OR 1.8, 95%CI 1.4,2.3). Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

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Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

10.21203/rs.2.9381/v3 ◽

2019 ◽

Author(s):

Videlis Nduba ◽

Anna H. van’t Hoog ◽

Annefleur de Bruijn ◽

Ellen M.H. Mitchell ◽

Kayla Laserson ◽

...

Keyword(s):

Previous History ◽

Target Group ◽

Western Kenya ◽

Target Populations ◽

Vaccine Trials ◽

History Of ◽

Latent Tb ◽

Latent Tb Infection ◽

Annual Risk ◽

Hiv Negative

Abstract Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 hours for reading. A TST of ≥10mm if HIV negative or ≥ 5mm if HIV positive, was considered positive. Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1%, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95%CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95%CI 1.2,1.8), having a BCG scar (OR 1.5,95%CI 1.2,1.8), living in a rural area (OR 1.4, 95%CI 1.1,1.9), and being out of school (OR 1.8, 95%CI 1.4,2.3). Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

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Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

10.21203/rs.2.9381/v2 ◽

2019 ◽

Author(s):

Videlis Nduba ◽

Anna H. van’t Hoog ◽

Annefleur de Bruijn ◽

Ellen M.H. Mitchell ◽

Kayla Laserson ◽

...

Keyword(s):

Tuberculin Skin Test ◽

Skin Test ◽

Positive Tuberculin Skin Test ◽

Target Group ◽

Hiv Positive ◽

Tuberculous Infection ◽

Western Kenya ◽

Vaccine Trials ◽

Annual Risk ◽

Hiv Negative

Abstract Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 hours for reading. A TST of ≥10mm if HIV negative or ≥ 5mm if HIV positive, was considered positive. Results: Of 5004 adolescents enrolled, 4808 (96%) returned for TST readings. Of these 2327(48.4%) were female, 861 (17.9%) had no BCG scar, and 23 (0.5%) were HIV positive. The baseline prevalence of tuberculous infection was 32% (95% CI 29-35%) with a corresponding ARTI of 2.6% (95% CI 2.2-3.1%). Male gender (OR 1.3, 95%CI 1.2,1.5), having a BCG scar (OR 1.4,95%CI 1.3,1.7) and not being enrolled in school (OR 1.8, 95%CI 1.4,2.3) were independent predictors of a positive tuberculin skin test at baseline. Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

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Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study

BMC Public Health ◽

10.1186/s12889-021-11271-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sivaporn Gatechompol ◽

Weerakit Harnpariphan ◽

Ruamthip Supanan ◽

Gompol Suwanpimolkul ◽

Jiratchaya Sophonphan ◽

...

Keyword(s):

Latent Tuberculosis ◽

Cross Sectional Study ◽

Preventive Therapy ◽

Sectional Study ◽

Cross Sectional ◽

Ltbi Prevalence ◽

History Of ◽

Chest X Ray ◽

Latent Tb ◽

Latent Tb Infection

Abstract Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

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BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case

Journal of Clinical Medicine ◽

10.3390/jcm9103224 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3224

Author(s):

Angeliki Syggelou ◽

Nikolaos Spyridis ◽

Kyriaki Benetatou ◽

Eleni Kourkouni ◽

Georgia Kourlaba ◽

...

Keyword(s):

Index Case ◽

Close Contact ◽

Cross Sectional Study ◽

Protective Role ◽

Bcg Vaccine ◽

Cross Sectional ◽

History Of ◽

Latent Tb ◽

Latent Tb Infection ◽

History Of Migration

The Bacille Calmette–Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23–0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15–0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13–4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27–9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.

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Histological observations on Montenegro's reaction in man

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651989000400008 ◽

1989 ◽

Vol 31 (4) ◽

pp. 256-261 ◽

Cited By ~ 10

Author(s):

Wilson Mayrink ◽

Antonio Pedro M. Schettini ◽

Paul Williams ◽

Pedro Raso ◽

Paulo Araujo Magalhães ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Skin Test ◽

Diagnostic Method ◽

Previous History ◽

Histological Changes ◽

Histological Studies ◽

Vaccine Trials ◽

American Cutaneous Leishmaniasis ◽

History Of

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.

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Prospective evaluation of latent tuberculosis with interferon-γ release assays in drug and alcohol abusers

Epidemiology and Infection ◽

10.1017/s0950268809002131 ◽

2009 ◽

Vol 137 (9) ◽

pp. 1342-1347 ◽

Cited By ~ 10

Author(s):

I. RIVAS ◽

I. LATORRE ◽

A. SANVISENS ◽

J. DOMÍNGUEZ ◽

J. TOR ◽

...

Keyword(s):

Latent Tuberculosis ◽

Interferon Γ ◽

Alcohol Abusers ◽

High Prevalence ◽

History Of ◽

Latent Tb ◽

Latent Tb Infection ◽

Drug And Alcohol ◽

Good Agreement

SUMMARYIn vitro tests have been developed for the diagnosis of tuberculosis (TB) infection. The objective was to analyse latent TB infection in drug and alcohol abusers through two interferon-γ techniques. One hundred and thirty-nine patients were admitted between February 2006 and May 2007. Mean age was 39·8 years [31% HIV positive]. The enzyme immunoassay (EIA) and enzyme-linked immunospot (ELISPOT) interferon-γ assays were positive in 34% of patients with an agreement of 83% (κ=0·63). Tuberculin skin test (TST) was positive in 29% of patients and the agreement of TST with EIA and ELISPOT interferon-γ assays was 85% (κ=0·62) and 83% (κ=0·57), respectively. Almost 50% of patients with history of TB had a positive in vitro test. In conclusion, we observed a high prevalence of latent TB and good agreement between the new in vitro tests that otherwise may continue to be positive long after developing TB disease.

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Longitudinal Mycobacterium tuberculosis specific interferon-γ responses in Ethiopian HIV-negative women during pregnancy and post-partum

Journal of Clinical Microbiology ◽

10.1128/jcm.00868-21 ◽

2021 ◽

Author(s):

Fregenet Tesfaye ◽

John Walles ◽

Erik Sturegård ◽

Niclas Winqvist ◽

Taye Tolera Balcha ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Post Partum ◽

Interferon Γ ◽

Inclusion Criteria ◽

Dynamic Changes ◽

Cellular Immune Responses ◽

Latent Tb ◽

Latent Tb Infection ◽

Cellular Immune ◽

Hiv Negative

Background: Pregnancy may influence cellular immune responses to Mycobacterium tuberculosis (Mtb). We investigated Mtb-specific interferon-γ responses in women followed longitudinally during pregnancy and post-partum. Methods: Interferon-γ levels (stimulated by Mtb antigens [TB1 and TB2] and mitogen included in the QuantiFERON-TB Gold Plus assay) were measured in blood from pregnant HIV-negative women identified from a prospective cohort at Ethiopian antenatal care clinics. Longitudinal comparisons included women without active TB with Mtb-triggered interferon-γ responses ≥0.20 IU/ml, sampled on two and/or three occasions (1 st /2 nd trimester, 3 rd trimester and 9 months post-partum). Results: Among 2093 women in the source cohort, 363 met inclusion criteria for longitudinal comparisons of Mtb-stimulated interferon-γ responses. Median Mtb-triggered interferon-γ concentrations were higher at 3 rd compared to 1 st /2 nd trimester (in 38 women with samples available from these timepoints; TB1: 2.8 vs 1.6 IU/ml, p=0.005; TB2: 3.3 vs 2.8 IU/ml, p=0.03) and post-partum (in 49 women with samples available from these timepoints; TB1: 3.1 vs 2.2 IU/ml, p=0.01; TB2: 3.1 vs 2.3 IU/ml, p=0.03). In contrast, mitogen-stimulated interferon-γ levels were lower at 3 rd compared with 1 st /2 nd trimester (in 32 women with samples available from these timepoints: 21.0 vs 34.9 IU/ml, p=0.02). Results were similar in 22 women sampled on all three occasions. Conclusions: In HIV-negative women, Mtb-stimulated interferon-γ responses were higher during the 3 rd trimester compared to earlier stages of pregnancy and post-partum, despite decreased mitogen-triggered responses. These findings suggest increased Mtb-specific cellular responses due to dynamic changes of latent TB infection during pregnancy.

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Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

10.21203/rs.2.9381/v1 ◽

2019 ◽

Author(s):

Videlis Nduba ◽

Anna H. van’t Hoog ◽

Annefleur de Bruijn ◽

Ellen M.H. Mitchell ◽

Kayla Laserson ◽

...

Keyword(s):

Demographic Data ◽

Positive Tuberculin Skin Test ◽

Skin Tests ◽

Tuberculous Infection ◽

Risk Of Infection ◽

Western Kenya ◽

Vaccine Trials ◽

Prevention Studies ◽

Study Participants ◽

Annual Risk

Abstract Setting Siaya District, Western Kenya, with the highest TB notification rates in Kenya (400/100,000) Objective To determine the prevalence and annual risk of infection with M. tuberculosis (ARTI) among adolescents aged 12-18 years Design Adolescents aged 12-18 years were enrolled in an area under continuous health and demographic surveillance in 2008-2009. At enrolment, clinical and demographic data were collected and study participants screened for tuberculosis (TB) and for tuberculous infection using tuberculin skin tests (TST). Results Of 5004 adolescents enrolled, 4808 (96%) returned for TST readings. Of these 2327(48.4%) were female, 861 (17.9%) had no BCG scar, and 23 (0.5%) were HIV positive. The baseline prevalence of tuberculous infection was 32% (95% CI 29-35%) with a corresponding ARTI of 2.6% (95% CI 2.2-3.1%). Male gender (OR 1.3, 95%CI 1.2,1.5), having a BCG scar (OR 1.4,95%CI 1.3,1.7) and not being enrolled in school (OR 1.8, 95%CI 1.4,2.3) were independent predictors of a positive tuberculin skin test at baseline. Conclusion We found a high ARTI indicating very high TB transmission rates, suggesting that in this population prevention studies including TB vaccine trials would be both highly relevant and efficient.

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