Extensively drug-resistant tuberculosis in a young child after travel to India

doi:10.1016/S1473-3099(15)00356-4

Review

. 2015 Dec;15(12):1485-91.

doi: 10.1016/S1473-3099(15)00356-4. Epub 2015 Nov 16.

Extensively drug-resistant tuberculosis in a young child after travel to India

Affiliations

¹ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pharmacy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Howard County Health Department, Columbia, MD, USA.
⁶ Maryland Department of Health and Mental Hygiene, Laboratories Administration, Baltimore, MD, USA.
⁷ National Jewish Health Mycobacteriology Laboratory, Denver, CO, USA.
⁸ Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁹ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Hospital Epidemiology and Infection Control, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sjain5@jhmi.edu.

PMID: 26607130
PMCID: PMC4843989
DOI: 10.1016/S1473-3099(15)00356-4

Review

Extensively drug-resistant tuberculosis in a young child after travel to India

Nicole Salazar-Austin et al. Lancet Infect Dis. 2015 Dec.

. 2015 Dec;15(12):1485-91.

doi: 10.1016/S1473-3099(15)00356-4. Epub 2015 Nov 16.

Authors

Affiliations

¹ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pharmacy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Howard County Health Department, Columbia, MD, USA.
⁶ Maryland Department of Health and Mental Hygiene, Laboratories Administration, Baltimore, MD, USA.
⁷ National Jewish Health Mycobacteriology Laboratory, Denver, CO, USA.
⁸ Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁹ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Hospital Epidemiology and Infection Control, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sjain5@jhmi.edu.

PMID: 26607130
PMCID: PMC4843989
DOI: 10.1016/S1473-3099(15)00356-4

Abstract

Extensively drug-resistant (XDR) tuberculosis is becoming increasingly prevalent worldwide, but little is known about XDR tuberculosis in young children. In this Grand Round we describe a 2-year-old child from the USA who developed pneumonia after a 3 month visit to India. Symptoms resolved with empirical first-line tuberculosis treatment; however, a XDR strain of Mycobacterium tuberculosis grew in culture. In the absence of clinical or microbiological markers, low-radiation exposure pulmonary CT imaging was used to monitor treatment response, and guide an individualised drug regimen. Management was complicated by delays in diagnosis, uncertainties about drug selection, and a scarcity of child-friendly formulations. Treatment has been successful so far, and the child is in remission. This report of XDR tuberculosis in a young child in the USA highlights the risks of acquiring drug-resistant tuberculosis overseas, and the unique challenges in management of tuberculosis in this susceptible population.

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Figures

**Figure 1. CT imaging**
CT imaging with intravenous contrast was done using the Definition FLASH (Siemens, Malvern, PA, USA) using a protocol customised for children. Lung segmentation and visualisation were done using VivoQuant 1·23 (inviCRO, Boston, MA, USA). The transverse, coronal, sagittal, and 3D views of the lung parenchyma and the pulmonary infiltrates in the left lung are shown. Each panel corresponds to CT done at: initiation of first-line tuberculosis treatment (A, day 0); initiation of individualised extensively drug-resistant (XDR) tuberculosis treatment (B, day 90); and 6 weeks (C, day 131) and 6 months (D, day 270) after initiation of XDR tuberculosis treatment. Several necrotic (hypodense) central areas can be seen in B (green arrows). Note the partial obstruction of the left main bronchus in B (red arrowheads). Marked improvement with resolution of necrotic areas is noted after 6 weeks (C) and near complete resolution of the infiltrate after 6 months (D) of XDR tuberculosis treatment. L = left side.

**Figure 2. Clinical course**
The temperature, total bodyweight, lesion volume on CT imaging, and CRP concentration during the course of the illness and treatment are shown. The dashed red line shows the cutoff for fever; the child’s body temperature was not measured daily after it became normal, but she had a healthy body temperature thereafter (represented by the horizontal, dashed grey line). The solid grey line shows mean (0 Z score) female weight-for-age growth, and the dashed grey lines correspond to the 1, 0·5, −0·5, and −1 female weight-for-age Z scores. Red arrows denote: (a) growth of acid-fast bacilli in liquid broth; (b) identification of *Mycobacterium tuberculosis* complex by 16S rRNA sequencing; (c) persistent left lower lobe infiltrate on chest radiography; (d) Sanger sequencing and initial TREK panel confirming extensively drug-resistant strain; (e) agar proportion results (from the Maryland Department of Health and Mental Hygiene reference laboratory); (f) CT showing substantial reduction in lesion volume; (g) agar proportion results (from the National Jewish Health Mycobacteriology reference laboratory); (h) consistent weight gain. HRZE = isoniazid, rifampicin, pyrazinamide (discontinued at 8 weeks), and ethambutol. S₇ = daily intravenous streptomycin. S₃ = thrice-weekly intravenous streptomycin. PAS = para-aminosalicylic acid. CRP = C-reactive protein.

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Comment in

Extensively drug-resistant tuberculosis in a young child.
Bhagavathula AS, Jamshed SQ. Bhagavathula AS, et al. Lancet Infect Dis. 2016 Apr;16(4):405-6. doi: 10.1016/S1473-3099(16)00122-5. Lancet Infect Dis. 2016. PMID: 27036339 No abstract available.
Extensively drug-resistant tuberculosis in long-term travellers.
Salzer HJF, Terhalle E, Lange C. Salzer HJF, et al. Lancet Infect Dis. 2016 Jun;16(6):642-643. doi: 10.1016/S1473-3099(16)30068-8. Lancet Infect Dis. 2016. PMID: 27301923 No abstract available.
Successful cure of extensively drug-resistant pulmonary tuberculosis in a young child.
Salazar-Austin N, Akinboyo I, Jain SK. Salazar-Austin N, et al. Lancet Infect Dis. 2017 Sep;17(9):898-899. doi: 10.1016/S1473-3099(17)30457-7. Lancet Infect Dis. 2017. PMID: 28845790 Free PMC article. No abstract available.

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References

1. Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575–1580. - PubMed
1. WHO. Global tuberculosis report 2015. [accessed Oct 28, 2015]; http://www.who.int/tb/publications/global_report/en/
1. Michael JS, John TJ. Extensively drug-resistant tuberculosis in India: a review. Indian J Med Res. 2012;136:599–604. - PMC - PubMed
1. Schlagenhauf P, Weld L, Goorhuis A, et al. Travel-associated infection presenting in Europe (2008–12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation. Lancet Infect Dis. 2015;15:55–64. - PubMed
1. Marienau KJ, Burgess GW, Cramer E, et al. Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007-June 2008. Travel Med Infect Dis. 2010;8:104–112. - PubMed

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[1] Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575–1580. - PubMed

[2] Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575–1580. - PubMed

[3] WHO. Global tuberculosis report 2015. [accessed Oct 28, 2015]; http://www.who.int/tb/publications/global_report/en/

[4] WHO. Global tuberculosis report 2015. [accessed Oct 28, 2015]; http://www.who.int/tb/publications/global_report/en/

[5] Michael JS, John TJ. Extensively drug-resistant tuberculosis in India: a review. Indian J Med Res. 2012;136:599–604. - PMC - PubMed

[6] Michael JS, John TJ. Extensively drug-resistant tuberculosis in India: a review. Indian J Med Res. 2012;136:599–604. - PMC - PubMed

[7] Schlagenhauf P, Weld L, Goorhuis A, et al. Travel-associated infection presenting in Europe (2008–12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation. Lancet Infect Dis. 2015;15:55–64. - PubMed

[8] Schlagenhauf P, Weld L, Goorhuis A, et al. Travel-associated infection presenting in Europe (2008–12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation. Lancet Infect Dis. 2015;15:55–64. - PubMed

[9] Marienau KJ, Burgess GW, Cramer E, et al. Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007-June 2008. Travel Med Infect Dis. 2010;8:104–112. - PubMed

[10] Marienau KJ, Burgess GW, Cramer E, et al. Tuberculosis investigations associated with air travel: U. S. Centers for Disease Control and Prevention, January 2007-June 2008. Travel Med Infect Dis. 2010;8:104–112. - PubMed

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Extensively drug-resistant tuberculosis in a young child after travel to India

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Extensively drug-resistant tuberculosis in a young child after travel to India

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