Treatment of childhood tuberculosis: caregivers' practices and perceptions in Cape Town, South Africa.

BACKGROUND: A child's caregiver is key to the successful drug delivery and outcome of tuberculosis (TB) treatment. Understanding caregivers' practices and perceptions is important in the management of childhood TB. OBJECTIVE: To investigate caregivers' practices and perceptions regarding TB treatment of children. METHODS: A prospective, questionnaire-based study at Red Cross War Memorial Children's Hospital, Cape Town, South Africa of caregivers of children receiving TB treatment. During the children's follow-up visits at 1 (M1), 3 (M3) and 6 (M6) months after initiation of TB treatment, caregivers were interviewed face-to-face. RESULTS: Caregivers of 253 children being treated for TB were interviewed and 434 surveys were completed between May 2011 and April 2013. 168 (39%) questionnaires were completed at M1, 165 (39%) at M3 and 94 (22%) at M6. Median age of children was 41 months (IQR 20-81). TB drugs were generally obtained from clinics most commonly visited 1-3 times a week. Only 86/162 (53%) and 109/155 (70%) children had been weighed at the clinic at M1 and M3, respectively. Drugs were most commonly administered after meals (69%). Two-thirds of interviewees crushed, dissolved or mixed the tablets with beverages or food. Most (88%) respondents reported easy drug administration. Few adverse drug reactions were reported. In 54/427 (13%) of surveys, concomitant antiretroviral treatment was given, most commonly before TB medication. CONCLUSION: Administration of TB drugs was regarded as easy, but differed substantially from recommended practice. Children were not weighed so that dosage could be adjusted, most caregivers crushed, dissolved or mixed the tablets with beverages or food, and administered medication after meals, all potentially contributing to sub-therapeutic drug levels.

Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study.

BACKGROUND: Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. METHODS: We prospectively recruited children (aged ≤ 15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral fl ow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. FINDINGS: 535 children (median age 42.5 months, IQR 19.1 ­ 66.3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral fl ow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48.3% (95% CI 37.6 ­ 59.2), specificity of 60.8% (56.1 ­ 65.3), and an area under the receiver operating characteristic curve of 0.53 (0.46 ­ 0.60) for children without HIV and 0.64 (0.51 ­ 0.76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3.0%, 95% CI 0.4 ­ 10.5) and children with HIV (0%, 0.0 ­ 14.3); overall specificity was 95.7% (93.4 ­ 97.4). INTERPRETATION: Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population.

Xpert MTB/RIF testing of stool samples for the diagnosis of pulmonary tuberculosis in children.

In a pilot accuracy study, stool Xpert testing from 115 children with suspected pulmonary tuberculosis (PTB) detected 8/17 (47%) culture-confirmed tuberculosis cases, including 4/5 (80%) HIV-infected and 4/12 (33%) HIV-uninfected children. Sputum Xpert detected 11/17 (65%) cases. Stool holds promise for PTB diagnosis in HIV-infected children.

Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens.

BACKGROUND: A rapid diagnosis of pediatric pulmonary tuberculosis (PTB) using Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) automated testing on induced sputum (IS) is possible, but the capacity for performing IS is limited. The diagnosis using a nasopharyngeal aspirate (NPA), which can be non-invasively obtained, is desirable. METHODS: Paired specimens (NPA and IS) were tested using smear, liquid culture and Xpert. The diagnostic accuracy of Xpert and smear was compared with culture for different specimens in children with suspected PTB. RESULTS: There were 535 children [median age 19 months, 117 (21·9%) HIV-infected] who had one IS and one NPA specimen; 396 had two paired specimens. A positive smear, Xpert test or culture occurred in 30 (5.6%), 81 (15.1%) and 87 children (16.3%), respectively. The culture yield was higher from IS (84/87, 96.6%) vs NPA (61/87, 70.1%, P < .001). Amongst children with two paired specimens, 63 culture-confirmed cases occurred [60 (95.2%) IS vs 48 (76.2%) NPA, P = .002]. The sensitivity of two Xpert tests was similar for IS and NPAs [(45/63) 71% vs (41/63) 65%, P = .444)]; the sensitivity of smear was lower for IS (21/63, 33%) and NPA (16/63, 25%). The incremental yield from a second IS was 9 cases (17.6%) by culture and 9 (25%) by Xpert testing; a second NPA increased the culture yield by 10 (26.3%) and Xpert by 11 (36.7%). Xpert specificity was 99.1% (98.1-100) for IS and 98.2% (96.8-99.6) for NPAs. Xpert testing provided faster results than culture (median 0 vs 15 days, P < .001). CONCLUSIONS: Xpert testing on 2 NPAs is useful in children with suspected PTB, particularly in settings where IS and culture are not feasible.

Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study.

BACKGROUND: WHO recommends that Xpert MTB/RIF replaces smear microscopy for initial diagnosis of suspected HIV-associated tuberculosis or multidrug-resistant pulmonary tuberculosis, but no data exist for its use in children. We aimed to assess the accuracy of the test for the diagnosis of pulmonary tuberculosis in children in an area with high tuberculosis and HIV prevalences. METHODS: In this prospective, descriptive study, we enrolled children aged 15 years or younger who had been admitted to one of two hospitals in Cape Town, South Africa, with suspected pulmonary tuberculosis between Feb 19, 2009, and Nov 30, 2010. We compared the diagnostic accuracy of MTB/RIF and concentrated, fluorescent acid-fast smear with a reference standard of liquid culture from two sequential induced sputum specimens (primary analysis). RESULTS: 452 children (median age 19·4 months, IQR 11·1-46·2) had at least one induced sputum specimen; 108 children (24%) had HIV infection. 27 children (6%) had a positive smear result, 70 (16%) had a positive culture result, and 58 (13%) had a positive MTB/RIF test result. With mycobacterial culture as the reference standard, MTB/RIF tests when done on two induced sputum samples detected twice as many cases (75·9%, 95% CI 64·5-87·2) as did smear microscopy (37·9%, 25·1-50·8), detecting all of 22 smear-positive cases and 22 of 36 (61·1%, 44·4-77·8) smear-negative cases. For smear-negative cases, the incremental increase in sensitivity from testing a second specimen was 27·8% for MTB/RIF, compared with 13·8% for culture. The specificity of MTB/RIF was 98·8% (97·6-99·9). MTB/RIF results were available in median 1 day (IQR 0-4) compared with median 12 days (9-17) for culture (p<0·0001). INTERPRETATION: MTB/RIF testing of two induced sputum specimens is warranted as the first-line diagnostic test for children with suspected pulmonary tuberculosis. FUNDING: National Institutes of Health, the National Health Laboratory Service Research Trust, the Medical Research Council of South Africa, and Wellcome Trust.