Reversal of Tuberculin Reaction in Early Tuberculosis

Adams, John M.; Kalajan, Vaughan A.; Mork, Byron O.; Rosenblatt, Maxwell; Rothrock, W.J.; O’Loughlin, Bernard J.

doi:10.1378/chest.35.4.348

Cited by 20 publications

(18 citation statements)

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“…This finding is consistent with earlier, smaller studies in which researchers found higher reversion rates among individuals with lower baseline QFTs (,3.0 IU/ml) (14). Similarly, reversion trends according to quantitative result have previously been observed with TSTs (29,30). Of note, the QFT reversion risk was much higher (23.7%) 12 months after conversion than it was in those with baseline positive QFTs (4.5%), many of whom likely converted in the more distant past.…”

Section: Discussionsupporting

confidence: 71%

The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents

Andrews

Hatherill

Mahomed

et al. 2015

Am J Respir Crit Care Med

116

102

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Rationale: Interferon-g release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described.Objectives: To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosisendemic setting.Methods: Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to 5 years.Measurements and Main Results: Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (k = 0.74), but poor for reversions (k = 0.12). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P , 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011).Conclusions: In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.

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Section: Discussionsupporting

confidence: 71%

The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents

Andrews

Hatherill

Mahomed

et al. 2015

Am J Respir Crit Care Med

116

102

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“…Many additional studies had similar findings over the next 100 years and explored factors associated with reversion. Consistent findings across multiple studies suggest that reversion is more common in children (115)(116)(117), less common in those with a higher-magnitude initial conversion (113,118), and possibly more common in females (115,119). Rates of spontaneous reversion may depend on several variables, including BCG vaccination, exposure to nontuberculous mycobacteria (NTM), a booster phenomenon from prior TSTs, duration of positivity before reversion, age, and magnitude of the conversion and reversion (118,120).…”

Section: Is Reducing Tb Acquisition Risk By Vaccination Plausible?mentioning

confidence: 67%

“…Together, these data suggest that reverters have a minimal risk of developing active TB over 5 years (0.72% versus 23.3% of the entire cohort). In addition, the same study as well as others demonstrated that some reverters develop evidence of substantial TB disease that subsequently heals with calcified granulomas (113,116). Together, these studies support the concept that reverters are individuals who possess protective immune responses to M. tuberculosis that could be immunologically interrogated to discover correlates of protective immunity.…”

Section: Is Reducing Tb Acquisition Risk By Vaccination Plausible?mentioning

confidence: 72%

“…Is there evidence from natural history studies that such "natural immunity" exists? Although the majority of individuals with a positive TST will remain positive for their lifetime, the phenomenon of reversion has been recognized for over a century (113). Spontaneous reversion (in the absence of INH treatment) may represent a successful host response, and these individuals can be studied to identify correlates of protective immunity.…”

Section: Is Reducing Tb Acquisition Risk By Vaccination Plausible?mentioning

confidence: 99%

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Tuberculosis Vaccines and Prevention of Infection

Hawn

Day

Scriba

et al. 2014

Microbiol Mol Biol Rev

138

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SUMMARY Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation.

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“…however, claimed that the tuberculin test remained positive after isoniazid treatment," and still other investiga¬ tors reported tuberculin reversion without isoniazid therapy. 5,7,8 The crucial question is whether all the cases reported were infected by Mycobacterium tuberculosis (tubercle bacilli) because it is now known that nontuberculous mycobacteria also may induce tuberculin sensitivity. Such cross-sen¬ sitivity is unstable and tends to revert to a negative reaction on successive tests.…”

mentioning

confidence: 99%

Tuberculin Reaction in Children Treated With Isoniazid

Hsu¹

1983

Arch Pediatr Adolesc Med

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Reversal of Tuberculin Reaction in Early Tuberculosis

Cited by 20 publications

References 1 publication

The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents

The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents

Tuberculosis Vaccines and Prevention of Infection

Tuberculin Reaction in Children Treated With Isoniazid

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