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Utility of the ELISpot Assay in the Diagnosis of Latent Mycobacterium tuberculosis Infection among HIV-infected Patients with Advanced Immunodeficiency in South Africa
Stephen Lawn*1,2, Stephen Lawn*1,2, N Bangani1, R Wilkinson3,4, R Wilkinson3,4, M Vogt1, M Ntobongwana1, M Badri1, L G Bekker1, and R Wood1
1Desmond Tutu HIV Ctr, Univ of Cape Town, South Africa; 2London Sch of Hygiene and Tropical Med, UK; 3Inst of Infectious Disease and Molecular Med, Univ of Cape Town, South Africa; and 4Wellcome Trust Ctr for Res in Clin Tropical Med, Imperial Coll London, UK
Background. ELISPOT
assays incorporating Mycobacterium
tuberculosis-specific antigens (ESAT-6 and CFP-10) are useful in the
diagnosis of tuberculosis (TB) or latent infection and reflect mycobacterial
burden. However, their utility in advanced HIV infection is unknown. We studied
determinants of ELISPOT responses among HIV-infected patients without active TB
living in a South African community with very high TB incidence.
Methods. Tuberculin
skin tests (TSTs) and overnight IFN-γ ELISPOT assays incorporating ESAT-6
and CFP-10 were performed in HIV-infected (HIV+) patients (n=40) and healthy
age / sex-matched HIV-negative (HIV-) controls (n=30). Active TB was carefully
excluded in all study participants. TST and ELISPOT responses were related to
patient characteristics.
Results. Among HIV- controls, TSTs were >10mm and
ELISPOT responses were positive among 77% (n=23) and 70% (n=21), respectively.
In contrast, among HIV+ patients (median CD4 count=114 cells/μl) only 38%
(n=15) had positive ELISPOT responses and 57% had anergic TSTs. However, 48%
(n=19) of HIV+ patients had completed treatment for TB within the preceding 3
years; positive ELISPOT responses were far less frequent among those who had
received TB treatment than those who had not (11% versus 62%, P<0.001). This
strong association remained in multivariate analysis (adjusted OR=0.06,
95%CI=0.10-0.40, P<0.01). ELISPOT responses were, however, independent of
CD4 count and viral load. TSTs responses were not associated with CD4 cell
count, viral load or history of TB treatment.
Conclusions. ELISPOT
responses were independent of CD4 count but had a strong inverse association
with history of TB treatment in HIV+ patients. We have formerly reported from
this patient population that a history of TB treatment is associated with
~5-fold lower risk of active TB, probably reflecting mycobacterial clearance.
Taken together, the results indicate that ELISPOT assays are able to detect
viable M. tuberculosis infection in
patients with advanced HIV, identifying those at increased risk of active TB.
Approximately two-thirds of HIV+ patients who had not previously received TB
treatment had ELISPOT responses indicative of M. tuberculosis infection. This assay potentially has great utility
both for assessment of individual patients with advanced HIV infection and as
an immuno-epidemiological tool in the study of HIV-associated TB.
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