Effect of Ascaris Lumbricoides specific IgE ontuberculin skin test responses in children in a high-burdensetting: a cross-sectional community-based study

Background: M.tuberculosis (M.tb) is associated with enhanced T helper cell type 1 (Th1) immune responses while helminth infection is associated with T helper cell type 2 (Th2) immune responses. Our aim was to investigate whether helminth infection could influence the ability to generate an appropriate Th1 immune response that is characterized by a positive tuberculin skin test (TST), in M.tb exposed children. Methods: We completed a community-based, cross sectional household contact tracing study, using matched enrolment of HIV negative children with and without documented household M.tb exposure. We documented demographics, clinical characteristics, HIV status, M.tb exposure (using a standard contact score) and M.tb infection status (TST > = 10 mm). Ascaris lumbricoides-specific IgE was used as proxy for Ascaris infection/exposure. Results: Of 271 children (median age 4 years (range: 4 months to 15 years)) enrolled, 65 participants (24%) were serum positive for Ascaris IgE. There were 168 (62%) children with a documented household tuberculosis contact and 107 (40%) were (TST) positive overall. A positive TST was associated with increasing age (Odds Ratio (OR) =1.17, p < 0.001), increasing M.tb contact score (OR = 1.17, p < 0.001), previous tuberculosis treatment (OR = 4.8, p = 0.06) and previous isoniazid preventive treatment (OR = 3.16, p = 0.01). A visible bacillus Calmette-Guérin (BCG) scar was associated with reduced odds of being TST positive (OR = 0.42, p = 0.01). Ascaris IgE was not associated with TST status in univariate analysis (OR = 0.9, p = 0.6), but multivariable logistic regression analysis suggested an inverse association between Ascaris IgE status and a positive TST (OR = 0.6, p = 0.08), when adjusted for age, and M.tb contact score. The addition of an age interaction term to the model suggested that the age effect was stronger among Ascaris IgE positive children; the effect of being Ascaris IgE positive significantly reduced the odds of being TST positive amongst younger children while this effect weakened with increasing age. Conclusions: Our preliminary findings highlight a high prevalence of both Ascaris exposure/infection and M.tb infection in children in an urban setting. Helminth exposure/infection may reduce the immune response following M.tb exposure when controlling for epidemiological and clinical covariates. These findings might be relevant to the interpretation of immunological tests of M.tb infection in children

Demographic details of eligible adult tuberculosis cases prior to and after implementation of an IPT register in a clinic in Cape Town, South Africa.

<p>SD = standard deviation.</p>1<p>Bacteriologically confirmed and not on a drug-resistant treatment regimen.</p>2<p>3% of HIV results were unknown overall.</p>3<p>HIV results only available for 57 adults.</p

Flow diagram describing the identification of children documented as eligible for IPT and started on IPT during the pre and post-register study periods.

<p>Flow diagram describing the identification of children documented as eligible for IPT and started on IPT during the pre and post-register study periods.</p

Summary of eligible child contacts¹ identified before and after the implementation of an IPT register in a clinic in Cape Town, South Africa.

<p>IPT = Isoniazid prophylaxis therapy, TB = tuberculosis.</p>1<p>Children less than five years of age exposed to a bacteriologically confirmed TB case (child contacts diagnosed with active disease excluded).</p>2<p>Bacteriologically confirmed and not on a drug-resistant treatment regimen.</p>3<p>Identified from TB register and TB case folders.</p>4<p>Identified from TB register and TB case folders.</p>5<p>Identified from the TB register, TB case folders and individual child folders.</p>6<p>Identified from the IPT register.</p>7<p>Proportion of the child TB contacts identified from the TB register and TB case folders as a proportion of the number of adult TB cases.</p>8<p>Proportion of the child TB contacts identified from the TB register, TB case folders and IPT register as a proportion of the number of adult TB cases.</p

Does an Isoniazid Prophylaxis Register Improve Tuberculosis Contact Management in South African Children?

We compared the change in child household contact management of pulmonary tuberculosis (TB) cases before and after the implementation of an isoniazid preventive therapy (IPT) register in an urban clinic setting in Cape Town, South Africa