Kinetics of Delayed‐Type Hypersensitivity to Tuberculin Induced by Bacille Calmette‐Guérin Vaccination in Northern Malawi

Abstract

During 1986-1989, a bacille Calmette-Guérin (BCG) vaccine trial was carried out in northern Malawi. The effects of age, sex, and prevaccination delayed-type hypersensitivity (DTH) on the time course of the DTH response over 1-36 months after vaccination were studied in 2418 persons. DTH response increased rapidly, to peak at 31-90 days after vaccination, when most persons had a measurable response. This was followed by a marked decline by 181-365 days, particularly in those <15 years old at vaccination, followed by a more gradual decline. Prevaccination DTH was the single best predictor of postvaccination DTH. BCG-induced DTH responsiveness appears to decline more rapidly in tropical than in temperate environments. This may reflect high prevalence of exposure to other infections, which induce a Th2 bias or compete for "space" within the T lymphocyte compartment. The inability of some persons to mount a persistent DTH response probably reflects genetic background and/or environmental exposure history.

Mycobacteria and allergies

“…2). In a large study performed in Malawi, the diameter of TST responses peaked 2-3 months after BCG vaccination, yielding reactions that were similar to those observed after BCG vaccination in areas such as the UK or Denmark (Floyd et al, 2002). However, in Malawians, the sizes of the TST responses waned rapidly and were close to pre-vaccination levels after 2.5 years, whereas most individuals in temperate regions stay TST positive for several years (Black et al, 2001a;Fine et al, 1994;Floyd et al, 2002).…”

“…It is not unusual for untreated water supplies in developing countries to contain 10 9 or more mycobacteria per litre. Therefore it is inevitable that residents of developing countries are sensitized to a multitude of environmental mycobacterial species (Black et al, 2001a;Floyd et al, 2002;Weir et al, 2003), which can be detected by specific IFN-g responses in vitro (Black et al, 2001b), or by skintesting (Stanford et al, 1988). When the same methods are applied to samples from people living in the UK, much lower sensitization rates are found (Dockrell, H.M., Black, G.F., Weir, R.E., personal communication).…”

A systematic review of rapid diagnostic tests for the detection of tuberculosis infection

“…142 There is considerable loss of hypersensitivity over time in several subtropical and tropical countries as trials conducted in Southern India, Malawi, Sri Lanka and the Solomon Islands have shown. 142,[267][268][269] A recent meta-analysis 145 of the effect of BCG vaccination on TST measurements concluded that TST was of value among BCG-vaccinated individuals in an appropriate clinical setting. For example, if BCG vaccination was more than 15 years previously, it may be ignored as a cause of a current positive TST result, especially if the induration is >15 mm.…”

“…Because antigens are shared with other mycobacteria, tuberculin reactivity leading to a positive TST can result from BCG vaccination with a live attenuated mycobacterial strain derived from M. bovis or from exposure to atypical mycobacteria. [141][142][143][144] The effect of BCG vaccination on TST can persist as long as 15 years after vaccination. 145 Reaction due to BCG vaccination tends to be small, but this is not always consistent.…”

Evaluation of the diagnostic utility of a whole-blood interferon-γ assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals

“…However, the participants in their study received BCG vaccine once only at birth perhaps reflecting a waning effect of BCG vaccination (Chadha, 2001;Wang et al, 2002). Repeat vaccinations may have a more discernible and persistent effect on TST responses (Menzies et al, 2000;Floyd et al, 2002). On the contrary, in Nigeria, another high endemic country, TST responsiveness in high risk grouped children was lower than that of QuantiFERON® (49 % vs 74 %), suggesting TST could underestimate risk for infection with TB in children in areas with high incidence of infectious diseases (Nakaoka et al, 2006).…”