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Background Diagnosing tuberculosis (TB) in children is challenging due to its paucibacillary nature. Loop-mediated isothermal amplification (TB-LAMP) is a simple, rapid, and specific point-of-care molecular diagnostic test. However, evaluation of its performance remains limited in children. This study aimed to evaluate the diagnostic performance of Eiken TB-LAMP among children with presumed tuberculosis disease. Methods Pulmonary and extrapulmonary specimens were collected from children under 18 years with presumed TB. Each specimen was tested by using TB-LAMP, acid-fast bacilli (AFB) smear microscopy, and one of the two molecular assays (polymerase chain reaction [PCR] or Xpert MTB/RIF). Sensitivity and specificity were estimated compared to mycobacterial culture as reference standard. Results From January 2020 to January 2021, 75 participants with presumed TB were enrolled with median age of 7 years (IQR 2-12). Seventeen specimens from 16 (21.3%) children had bacteriologically confirmed TB: 10 pulmonary and 7 extrapulmonary specimens. Overall sensitivity and specificity of TB-LAMP was 76.5% (95% CI 50.1%-93.2%) and 100% (95% CI 94.3%-100%), respectively. It had significantly higher sensitivity than AFB (52.9%, 95% CI 27.8%-77.0%) and similar to other molecular assays; PCR 82.4% (95% CI 56.6%-96.2%), Xpert MTB/RIF 70.0% (95% CI 34.8%-93.3%). Sensitivity of TB-LAMP for pulmonary, lymph node tissue, and extrapulmonary fluid was 80% (95% CI 44.4%-97.5%), 100% (95% CI 39.8-100), and 33.3% (95% CI 0.8-90.6), respectively. TB-LAMP detected all smear-positive (N = 9) and 50% of smear-negative (N = 8) specimens. Conclusions TB-LAMP had higher sensitivity than AFB microscopy and accuracy similar to other molecular assays in both pulmonary and extrapulmonary specimens. These findings support using TB-LAMP as a point-of-care test in children. [ABSTRACT FROM AUTHOR]

Background Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. Methods We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. Results Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P <.020 and P <.001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. Conclusions Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection., Methods: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies., Results: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay., Conclusions: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.