Well-quantified tuberculosis exposure is a reliable surrogate measure of tuberculosis infection

Mandalakas, Anna M.; Kirchner, H. Lester; Lombard, Carl; Walzl, Gerhard; Grewal, Harleen M. S.; Gie, Robert P.; Hesseling, Anneke C.

doi:10.5588/ijtld.12.0027

Cited by 86 publications

(97 citation statements)

References 3 publications

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“…The level of exposure was reported as a contact score of 1-10 derived from 82 combined data assuming that the level of exposure was a product of proximity, duration and 83 infectivity of exposure. 12 …”

Section: Page 3 Of 29mentioning

confidence: 99%

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Wiseman¹,

Mandalakas²,

Kirchner³

et al. 2015

int j tuberc lung dis

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201 wordsKey Words: Tuberculosis, paediatric, diagnosis, case definition, NIH Running head title: NIH paediatric TB research definitionSummary: We apply and compare recently proposed International Consensus (NIH) with protocol-specified case definitions for paediatric TB and describe the disease spectrum and severity in a community-based prospective cohort diagnostic TB study using household contact tracing.

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Section: Page 3 Of 29mentioning

confidence: 99%

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Wiseman¹,

Mandalakas²,

Kirchner³

et al. 2015

int j tuberc lung dis

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“…Pediatric-specific exposure data from a subset of children negative for HIV with documented TB exposure were used to derive a contact score (range, 0-10) assigning a higher value as exposure intensity increases (20). Additional detail on these methods is provided in the online supplement.…”

Section: Study Measuresmentioning

confidence: 99%

“…We used well-quantified TB exposure as a surrogate measure of M. tuberculosis infection (20). Pediatric-specific exposure data from a subset of children negative for HIV with documented TB exposure were used to derive a contact score (range, 0-10) assigning a higher value as exposure intensity increases (20).…”

Section: Study Measuresmentioning

confidence: 99%

Optimizing the Detection of Recent Tuberculosis Infection in Children in a High Tuberculosis–HIV Burden Setting

Mandalakas

Kirchner²,

Walzl

et al. 2015

Am J Respir Crit Care Med

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Rationale: Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.Objectives: Identify improved testing to detect pediatric TB infection.Methods: This was a prospective community-based study assessing use of the tuberculin skin test and IFN-g release assays among children (n = 1,343; 6 mo to ,15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.Measurements and Main Results: Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-g release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-g release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-g release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.Conclusions: Where resources allow, use of IFN-g release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.Keywords: HIV; latent tuberculosis infection; pediatrics; IFN-g release tests; tuberculin test Following infection with Mycobacterium tuberculosis, the 5-year risk of tuberculosis (TB) is 33% in children younger than 5 years and 20% for 5-14 years of age (1).TB risk is greatest in the year following infection and highest among young, malnourished, and immune-compromised children; up to 50% of children infected during the first year of life develop disease in the absence of preventive therapy (PT) (2). PT decreases TB morbidity and mortality among adult contacts (3, 4) and Author Contributions: A.M.M., H.L.K., R.P.G., and A.C.H. designed the study. A.M.M. and A.C.H. alternately served as on-site project leaders during study implementation. A.M.M. and H.L.K. planned and executed the statistical analyses, which were reviewed by all authors. All authors contributed to the interpretation of the findings. A.M.M. wrote the first draft of the paper. All authors commented extensively, critically revised the report, and approved the final version.Correspondence and requests for reprints should be addressed to Anna M. Mandalakas, M.D., Sect...

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“…1 Following infection with Mycobacterium tuberculosis, young children are at high risk of primary disease progression and disseminated disease in the absence of appropriate preventive therapy. 2 Accurate identifi cation of M. tuberculosis-infected children is possible using contact tracing and characterisation of epidemiological risk factors 3 without tests for M. tuberculosis infection. 4 Nevertheless, delivery of isoniazid preventive therapy (IPT) is sub-optimal in high-burden TB settings, with as few as 5-66% of eligible child contacts receiving therapy.…”

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confidence: 99%

“…Over the past 5 years, the three communities have jointly hosted a household contact study aimed at diagnosing M. tuberculosis infection in children. 3 Following evaluation to rule out TB, this study routinely refers child contacts to the local TB services for IPT 21 after the study counsellors have educated participants on the rationale and benefi ts of post-exposure IPT. All three communities have also hosted IPT audits, 9,10 and clinic personnel have disseminated the results.…”

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confidence: 99%

It's hard work, but it's worth it: the task of keeping children adherent to isoniazid preventive therapy

Skinner

Francis

et al. 2013

public health action

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HIV-infected children, previously paralysed postexposure IPT programmes have been enhanced through the introduction of IPT registers and the increased availability of single-drug dispersible paediatric isoniazid (INH) formulations.South Africa, an upper middle-income country, has a medium human development index, but it fi gures among the 22 countries with the highest burden of TB disease. 12 Although the South African National TB Programme (SANTP) has been recommending postexposure IPT for many years for child contacts aged <5 years, IPT uptake ranges from <5% 10 to 21% in routine health care settings, 9 to 73% in clinical research settings, 5,13 while adherence is approximately 24%. 5,13 Among South African children hospitalised for TB, opportunities for IPT are missed in up to 70% of young children. 14,15 A growing body of literature shows that obstacles to the effective delivery of postexposure IPT are many and inter-related. 9,10 Many of the major barriers identifi ed in a recent review of problems in IPT implementation have been resolved in South Africa using a standardised screening protocol for children. However, the issues of maintaining adherence to extended prophylactic treatment programmes and the negotiation of care giver acceptability needs further consideration. 16 A recent survey of parents currently administering IPT in Cape Town found very positive responses to IPT once these barriers had been overcome. 17 We completed a qualitative assessment to understand factors infl uencing parents' decisions to allow IPT to be administered to their children and completion of the 6-month course of treatment. RESEARCH SETTINGThe study was set in three impoverished urban communities in Cape Town, Western Cape Province, South Africa. Study Communities 1 and 2 are geographically adjacent and their ethnicity is classifi ed as 'coloured' or 'mixed race'. The third community is of predominantly black ethnicity. In 2011, the overall TB notification rate in the Western Cape Province was 994 per 100 000 population and >1000/100 000 in the communities studied; TB reported in children aged 0-13 years accounted for 17% of the disease and an age-specifi c TB notifi cation rate of 620/100 000 in 2008 (unpublished data, Western Cape Department of Health, 2009). The estimated annual risk of M. tuberculosis infection was 4.1% in the fi rst two communities, where 30% of children aged 6-9 years were tuberculin skin test (TST) positive. 18 In the third community, 26% of In-depth interviews were conducted with two parents of children adherent to IPT and two staff members from three primary health care clinics in high TB prevalence communities. Themes explored were knowledge and attitudes towards IPT, problems in accessing and adhering to treatment, and community responses. Results: Parents administering treatment valued it positively, realised their children's risk of TB, and were positive about the clinic. Nurses acknowledged that resistance to treatment remained, with some parents not wanting to acknowledge risk nor willing to...

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Well-quantified tuberculosis exposure is a reliable surrogate measure of tuberculosis infection

Abstract: Well-quantified TB exposure is a good surrogate measure of M. tuberculosis infection in child household contacts in a high-burden setting, and could guide targeted preventive treatment in children at highest risk of M. tuberculosis infection.

Cited by 86 publications

References 3 publications

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Optimizing the Detection of Recent Tuberculosis Infection in Children in a High Tuberculosis–HIV Burden Setting

It's hard work, but it's worth it: the task of keeping children adherent to isoniazid preventive therapy

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