The Effect of Deworming on Tests of Tuberculosis Infection in Children With Recent Tuberculosis Exposure: A Randomized Controlled Trial.

BACKGROUND: Helminth infestations are associated with T-helper cell type 2 (Th2) immune responses, leading to suppression of Th1 responses required to control Mycobacterium tuberculosis infection. We hypothesized that deworming after documented M. tuberculosis exposure might improve Th1 immune responses. METHODS: This was a randomized controlled trial comparing the effect of early versus delayed (after 3 months) deworming on tuberculin skin testing (TST) and Quantiferon-Gold-in-tube responses among children from a setting with a known high burden of M. tuberculosis and helminth co-infection in Cape Town, South Africa. Children aged 6 to 15 years with documented M. tuberculosis exposure were enrolled. Ascaris lumbricoides status was measured by Ascaris-specific IgE and stool microscopy. RESULTS: A total of 250 children (mean age, 9.6 years) were enrolled; 11.9% (27/227) were Ascaris stool microscopy positive and 54.2% (135/249) were Ascaris stool and/or IgE positive (Ascaris status). In univariable analysis, deworming at enrollment was not associated with a negative TST at 3 months (odds ratio, 0.61; 95% confidence interval, 0.35-1.07; P = 0.08). In stratified analysis, children with a positive Ascaris status were more likely to be TST negative at 3 months if dewormed early (odds ratio, 0.49; 95% confidence interval, 0.23-1.04; P = 0.06). In multivariable analysis, deworming was not associated with TST status (adjusted odds ratios, 0.62; 95% confidence interval, 0.34-1.10; P = 0.10). There was no association between deworming and Quantiferon-Gold-in-tube status. CONCLUSIONS: Deworming in children with recent M. tuberculosis exposure is associated with a trend toward a negative TST result. Timing of deworming might influence interpretation of TST in settings with high burdens of tuberculosis and helminths.

Does an isoniazid prophylaxis register improve tuberculosis contact management in South African children?

SETTING: 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. OBJECTIVES: We determined if the presence of an IPT register was associated with an increase in the number of child contacts identified per infectious case and the proportion of identified children who were started on IPT. DESIGN: We reviewed routine programme data on IPT delivery to children during two time periods (May 2008-October 2008 and May 2011-October 2011), before and after the implementation of an IPT register used by routine clinic personnel. RESULTS: Adult TB case demographic and clinical characteristics from the two observation periods were similar. During the post-register period, more child contacts per adult case were identified (0.7 (54 children) vs. 0.3 (24 children)), more of the identified children were started on IPT (54 vs. 4) and 37% of those who started, completed six months of treatment compared to the pre-register period where no adherence information was recorded. CONCLUSIONS: After pilot implementation of an IPT register, documented identification of child contacts, IPT initiation and IPT adherence documentation in TB exposed children was improved. Our findings support further exploration of the potential impact of using standardised IPT recording and reporting in routine clinics in high-burden TB settings to improve TB prevention efforts targeted at young children. Future efforts to improve IPT delivery should be systematic and comprehensive in order to support a change in current operational IPT delivery practices in TB programs.

Effect of Ascaris Lumbricoides specific IgE on tuberculin skin test responses in children in a high-burden setting: 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.