Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus.

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.

Seroprevalence of mumps among children and adolescents in Thailand, 2020.

Thailand has implemented single-dose mumps-containing vaccines since 1997 and two doses since 2010. This study aimed to describe the seroprevalence of mumps among children who received one- or two-dose mumps vaccines. A cross-sectional study of 145 children (aged 3-9 years) and 422 adolescents (10-18 years) was conducted. Mumps IgG seropositivity was defined as ≥ 22 RU/mL by EUROIMMUN ELISA method. The mumps seroprevalence was higher in children (82.1%, 95% CI 74.8-87.9) compared to adolescents (41.7%, 95% CI 37.0-46.6) who had received at least one dose of the mumps vaccine. Among those receiving 2 doses of mumps vaccine at ≥ 5 years after their last mumps vaccination, only 51.3% had maintained IgG ≥ 22 RU/ml. There was a reverse correlation between mumps IgG titer and the time interval from the second dose of mumps vaccine (R = -0.44, p < 0.001). A booster dose of MMR vaccine in young adults may be needed.

Diagnostic Accuracy of Loop-Mediated Isothermal Amplification (TB-LAMP) for Tuberculosis in Children.

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.

Immunogenicity of 2-dose pre-exposure rabies vaccine co-administered with quadrivalent influenza vaccine in children.

OBJECTIVES: The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). METHODS: Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. RESULTS: From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). CONCLUSIONS: The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV.

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.