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Immunologic-based Diagnosis of Latent Tuberculosis Among Children Younger Than 5 Years of Age Exposed and Unexposed to Tuberculosis in Tanzania

Said, Khadija, PhD*,†,‡; Hella, Jerry, MSc*,†,‡; Ruzegea, Mwajabu, MS*; Solanki, Rajesh, MMed§; Chiryamkubi, Magreth; Mhimbira, Francis, PhD*,†,‡; Ritz, Nicole, PhD‡,‖; Schindler, Christian, PhD†,‡; Mandalakas, Anna M., PhD**; Manji, Karim, MBBS, MMED††; Tanner, Marcel, PhD†,‡; Utzinger, Jürg, PhD†,‡; Fenner, Lukas, MSc‡‡

The Pediatric Infectious Disease Journal: April 2019 - Volume 38 - Issue 4 - p 333–339
doi: 10.1097/INF.0000000000002131
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Background: Childhood tuberculosis (TB) is acquired after exposure to an infectious TB case, often within the household. We prospectively screened children 6–59 months of age, exposed and unexposed to an infectious TB case within the same household, for latent tuberculosis infection (LTBI), in Dar es Salaam, Tanzania.

Methods: We collected medical data and clinical specimens (to evaluate for helminths, TB and HIV coinfections) and performed physical examinations at enrollment and at 3-month and 6-month follow-up surveys. LTBI was assessed using QuantiFERON-TB Gold (QFT) at enrollment and at 3 months.

Results: In total, 301 children had complete data records (186 with TB exposure and 115 without known TB exposure). The median age of children was 26 months (range: 6–58); 52% were females, and 4 were HIV positive. Eight children (3%) developed TB during the 6-month follow-up. We found equal proportions of children with LTBI among those with and without exposure: 20% (38/186) versus 20% (23/115) QFT-positive, and 2% (4/186) versus 4% (5/115) indeterminate QFT. QFT conversion rate was 7% (22 children) and reversion 8% (25 children). Of the TB-exposed children, 72% initiated isoniazid preventive therapy, but 61% of parents/caregivers of children with unknown TB exposure and positive QFT refused isoniazid preventive therapy.

Conclusions: In this high burden TB setting, TB exposure from sources other than the household was equally important as household exposure. Nearly one third of eligible children did not receive isoniazid preventive therapy. Evaluation for LTBI in children remains an important strategy for controlling TB but should not be limited to children with documented TB exposure.

From the *Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania

Swiss Tropical and Public Health Institute, Basel, Switzerland

University of Basel, Basel, Switzerland

§Temeke Municipal Council Hospital, Dar es Salaam, Tanzania

National Tuberculosis and Leprosy Control Program, Dar es Salaam, Tanzania

Basel University Children’s Hospital, Basel, Switzerland

**The Global Tuberculosis Program, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas

††Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

‡‡Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Accepted for publication May 9, 2018.

K.S. has recently obtained her PhD from the Swiss Tropical and Public Health Institute and the University of Basel in Basel, Switzerland.

This work was supported by funding from the Rudolf Geigy Foundation (Basel, Switzerland). K.S. is a beneficiary of the Swiss Government Excellence Scholarship for Foreign Scholars and Artists (ESKAS; Bern, Switzerland). The authors have no other funding or conflicts of interest to disclose.

K.S., J.H., F.M., N.R., A.M., K.M., M.T., J.U. and L.F. designed the study. K.S., J.H., M.R., R.S., M.C. and F.M. collected the data. K.S. and C.S. did the analysis. K.S. wrote the manuscript. J.H., F.M., N.R., C.S., A.M., K.M., M.T., J.U. and L.F. reviewed the manuscript. All the authors authorized the submission and publication of the manuscript.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Khadija Said, MD, PhD, Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania. E-mail: ksaid@ihi.or.tz or Lukas Fenner, MD, MSc, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. E-mail: lukas.fenner@ispm.unibe.ch.

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