Burden of Respiratory Syncytial Virus-Associated Acute Respiratory Infections During Pregnancy.

BACKGROUND: With the licensure of maternal respiratory syncytial virus (RSV) vaccines in Europe and the United States, data are needed to better characterize the burden of RSV-associated acute respiratory infections (ARI) in pregnancy. The current study aimed to determine among pregnant individuals the proportion of ARI testing positive for RSV and the RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review, following PRISMA 2020 guidelines, using 5 databases (Medline, Embase, Global Health, Web of Science, and Global Index Medicus), and including additional unpublished data. Pregnant individuals with ARI who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with ARI that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% confidence interval [CI], 1.9%-54%). The pooled incidence rate of RSV among pregnant individuals was 26.0 (95% CI, 15.8-36.2) per 1000 person-years. RSV hospitalization rates reported in 2 studies were 2.4 and 3.0 per 1000 person-years. In 5 studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in the odds of miscarriage, stillbirth, low birth weight, and small size for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio, 3.6 [95% CI, 1.3-10.3]). CONCLUSIONS: Data on RSV-associated hospitalization rates are limited, but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions.

Feasibility and Performance of Self-Collected Nasal Swabs for Detection of Influenza Virus, Respiratory Syncytial Virus, and Human Metapneumovirus.

BACKGROUND: We assessed performance of participant-collected midturbinate nasal swabs compared to study staff-collected midturbinate nasal swabs for the detection of respiratory viruses among pregnant women in Bangkok, Thailand. METHODS: We enrolled pregnant women aged ≥18 years and followed them throughout the 2018 influenza season. Women with acute respiratory illness self-collected midturbinate nasal swabs at home for influenza viruses, respiratory syncytial viruses (RSV), and human metapneumoviruses (hMPV) real-time RT-PCR testing and the study nurse collected a second midturbinate nasal swab during home visits. Paired specimens were processed and tested on the same day. RESULTS: The majority (109, 60%) of 182 participants were 20-30 years old. All 200 paired swabs had optimal specimen quality. The median time from symptom onsets to participant-collected swabs was 2 days and to staff-collected swabs was also 2 days. The median time interval between the 2 swabs was 2 hours. Compared to staff-collected swabs, the participant-collected swabs were 93% sensitive and 99% specific for influenza virus detection, 94% sensitive and 99% specific for RSV detection, and 100% sensitive and 100% specific for hMPV detection. CONCLUSIONS: Participant-collected midturbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

Impact of Vitamin D and Calcium Supplementation on Bone Mineral Density and Bone Metabolism Among Thai Adolescents With Perinatally Acquired Human Immunodeficiency Virus (HIV) Infection: A Randomized Clinical Trial.

BACKGROUND: To evaluate the impact of vitamin D and calcium supplementation (VitD/Ca) on lumbar spine bone mineral density (LSBMD) and bone metabolism among Thai adolescents with perinatally acquired HIV (PHIVA). METHODS: A multicenter, randomized, active-control, open-labeled trial was conducted. PHIVA (aged 10-20 years) who were on stable cART were enrolled. Baseline LSBMD status was defined as low (z-score ≤ -2) and normal (> -2). Eligible PHIVA were randomly assigned to receive standard-dose (400 IU/1200 mg/day) or high-dose (400 IU/1200 mg/day plus ergocalciferol 20 000 IU/week) VitD/Ca supplementation for 48 weeks (ratio 1:1, stratified by baseline LSBMD). Study outcomes were changes in LSBMD, LSBMD z-scores, and bone metabolism-related biomarkers (25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone [iPTH], C-terminal telopeptide [CTX], procollagen type I amino-terminal propeptide [PINP]) from baseline to week 48. RESULTS: Among 200 enrolled PHIVA, median age was 16 (IQR:14-18) years; 61% were on NNRTI-based cART. Median 25(OH)D level was 25.5 (IQR: 20.8-33.0) ng/mL. After 48-week VitD/Ca supplementation, LSBMD significantly increased in both treatment groups (high-dose: median: +0.07 [IQR: +0.04 to +0.11] g/cm2; P < .001; standard-dose: +0.09 [+0.03 to +0.13] g/cm2; P < .001). Notably, the change in LSBMD z-scores was significantly greater in high-dose versus standard-dose groups (median: +0.4 [IQR: -0.1 to +0.9] vs +0.1 [-0.4 to +0.7]; P = .02). Levels of 25(OH)D increased, whereas iPTH, CTX, and PINP declined significantly in both groups (P < .05), but no between-group differences were demonstrated. CONCLUSIONS: Over 48-week VitD/Ca supplementation, significant increases in LSBMD, and significant decreases in bone metabolism-related markers were observed among our Thai PHIVA in both treatment groups. The improvement in LSBMD z-score was more enhanced with high-dose VitD/Ca supplementation than standard-dose. High-dose VitD/Ca supplementation might be considered to promote bone health in this population. CLINICAL TRIALS REGISTRATION: NCT02426840.

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.

A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Hospitalizations in Children.

BACKGROUND: Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. METHODS: We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months-17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012-2013 to 2016-2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. RESULTS: We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7-10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012-2013 to 2016-2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. CONCLUSIONS: Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

Tolerability of trivalent inactivated influenza vaccine among pregnant women, 2015.

BACKGROUND: Thailand recommends influenza vaccination among pregnant women. We conducted a cohort study to determine if the prevalence of adverse events following immunization (AEFIs) with influenza vaccine among Thai pregnant women was similar to that often cited among healthy adults. METHODS: Women who were ≥17 gestational weeks and ≥18 years of age were recruited. Demographic and health history data were collected using structured questionnaires. Women were provided with symptom diary, ruler to measure local reaction(s), and thermometer to measure body temperature. AEFIs were defined as any new symptom/abnormality occurring within four weeks after vaccination. The diaries were abstracted for frequency, duration, and level of discomfort/inconvenience of the AEFIs. Serious adverse events (SAEs) and the likelihood of AEFIs being associated with vaccination were determined using standard definitions. RESULTS: Among 305 women enrolled between July-November 2015, median age was 29 years. Of these, 223 (73%) were in their third trimester, 271 (89%) had completed secondary school or higher, and 20 (7%) reported ≥1 pre-existing conditions. AEFIs were reported in 134 women (44%; 95% confidence interval [CI] 38-50%). Soreness at the injection site (74, 24%; CI 19-29%), general weakness (50, 16%; CI 12-21%), muscle ache (49, 16%; CI 12-21%), and headache (45, 15%; CI 1-19%) were most common. Of those with AEFIs, 120 (89%) reported symptom/abnormality occurred on day 0 or day 1 following vaccination. Ten women (7%) reported the AEFIs affected daily activities. The AEFIs generally spontaneously resolved within 24 h of onset. There were two vaccine-unrelated SAEs. Of 294 women with complete follow-up, 279 (95%) had term deliveries, 12 (4%) had preterm deliveries, and 3 (1%) had miscarriage or stillbirth. CONCLUSION: In our cohort, AEFIs with influenza vaccine occurred with similar frequency to those reported among healthy adults in other studies, and were generally mild and self-limited. No influenza vaccine-associated SAEs were identified.

Standardized Interpretation of Chest Radiographs in Cases of Pediatric Pneumonia From the PERCH Study.

BACKGROUND.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. RESULTS.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (κ = 0.50) and between arbitrators was 84% (κ = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (κ = 0.25) and 48.5% (κ = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). CONCLUSIONS.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process.

Risk factors and outcomes of influenza infection among children presenting with influenza-like illness.

OBJECTIVE: Limited data were available to guide management, counseling, and/or diagnostic investigation among children presenting with influenza-like illness (ILI). During a recent period of high influenza activity, we wished to determine the frequency, outcomes, and factors associated with influenza infection among children presenting with ILI. MATERIAL AND METHOD: During September and October 2010, children presenting with ILI were enrolled. Nasal swabs were sent for polymerase chain reaction (PCR) to determine the frequency and types of influenza. Information of demographic characteristics, potential risk factors, and short-term outcomes of study participants were collected. RESULTS: Among 300 enrolled subjects, influenza infections were identified in 170 (56.7%) cases; 45.7% (n = 137) were influenza A and 11% (n = 33) were influenza B. Most cases recovered uneventfully with a 3.7% (n = 11) hospitalization rate. Risks for hospitalization did not differ by infection status (2.4% vs. 5.4% between those with and without influenza infection, respectively) or types of influenza infection. Logistic regression analysis indicated that older age, having a household member with acute respiratory illness (ARI) during the previous 7 days, having an underlying co-morbidity, and a history of premature birth were associated with influenza, with adjusted odds ratios and 95% confidence intervals of 1.19 (1.087, 1.30), 3.21 (1.096, 9.424), 2.15 (1.244, 3.728), and 0.08 (0.007, 0.876), respectively. CONCLUSION: The outcomes of influenza-associated ILI were generally favourable, with no fatalities and 2.4% risk for hospitalization. Among children presenting with ILI, age, household contact with ARI, and co morbidities increased the likelihood of influenza, whereas history of premature birth was negatively associated with influenza.

Antigenic distance between primary and secondary dengue infections correlates with disease risk.

Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease through a mechanism known as antibody-dependent enhancement. However, it remains unclear whether the antigenic distances between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years. Here, we develop a framework that combines detailed antigenic and genetic characterization of viruses with details on hospitalized cases from 21 years of dengue surveillance in Bangkok, Thailand, to identify the role of the antigenic profile of circulating viruses in determining disease risk. We found that the risk of hospitalization depended on both the specific order of infecting serotypes and the antigenic distance between an individual's primary and secondary infections, with risk maximized at intermediate antigenic distances. These findings suggest that immune imprinting helps determine dengue disease risk and provide a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.

The serial intervals of seasonal and pandemic influenza viruses in households in Bangkok, Thailand.

The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11-14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.

The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.

OBJECTIVES: To evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. METHODS: A randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. RESULTS: During February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). CONCLUSION: The extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children.

Objective: To compare the immune response of hybrid immunity - arising from SARS-CoV-2 infection and mRNA BNT162b2 vaccination - to that of 2-doses of vaccine. Methods: In a subanalysis of BNT162b2 vaccine trial in 5 to 11-year-old children, There were 179 children who had hybrid immunity compared with 134 children with solely 2-dose vaccine. The immunological outcome was a surrogate virus neutralization test (sVNT) against the Omicron strain, BA.1, (%inhibition). An sVNT level ≥68 % inhibition was considered as protective immune response. Results: From February to April 2022, 179 children had COVID-19 natural infection resulting in hybrid immunity included: Group1;prior vaccination(n = 17), Group2;after the first dose(n = 61), and Group3;after the second dose(n = 97). The proportion of children with protective immune response was higher in Group 3 and Group 1 - 61.9 % and 58.8 %, compared to 36.1 % and 34.3 % in Group 2 and comparator group (2 doses of vaccine), respectively. The geometric mean % inhibition of sVNT was higher in Group 1 (68.5, 95 %CI 55.5-84.6) and Group 3 (63.5, 95 %CI 55.5-72.6), followed by comparator group (49.6, 95 %CI 44.8-54.9) and Group 2 (42.1, 95 %CI 34.6-51.3), p < 0.001. Conclusions: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.

Antigenic diversity and dengue disease risk.

Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection. In addition, for some pathogens such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease, through a mechanism known as antibody-dependent enhancement. However, it remains a mystery whether the antigenic distance between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalisations across years. Here we develop an inferential framework that combines detailed antigenic and genetic characterisation of viruses, and hospitalised cases from 21 years of surveillance in Bangkok, Thailand to identify the role of the antigenic profile of circulating viruses in determining disease risk. We find that the risk of hospitalisation depends on both the specific order of infecting serotypes and the antigenic distance between an individual's primary and secondary infections, with risk maximised at intermediate antigenic distances. These findings suggest immune imprinting helps determine dengue disease risk, and provides a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting.

BACKGROUND: Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: A retrospective chart review was conducted at 8 Thai sites of children who switched to PI -based regimens due to failure of NNRTI -based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks. RESULTS: Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002). CONCLUSION: Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases.

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12-18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7-16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7-74.2) and 233.6 (95% CI 79-690.6); adolescents with cancer 62.3 (95% CI 29.2-133.1) and 214.9(95% CI 34.2-1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4-84.8) and 849.8 (95% CI 393.4-1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3-98.8) and 3240.3 (95% CI 2699-3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3-98.9) and 3818.5 (95% CI 3490.4-4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8-62.4) and 178.7 (95% CI 91.2-350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4-92.8) and 1037.1 (95% CI 933.3-1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required.

Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand.

INTRODUCTION: Efavirenz (EFV) is commonly used for first-line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48-week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV- to RPV-based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV. METHODS: We conducted an open-label, single-arm, multi-centre study in Thailand in virologically suppressed adolescents aged 12-18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018. RESULTS: One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4-17.0), median CD4 count was 664 cells/mm3 (29.9%); 58% were receiving tenofovir-DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV-related symptoms, depression score or health-related QOL were observed over time; however, there was significant improvement in performance-based assessments of executive function at week 24. CONCLUSIONS: A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.

Pharmacokinetics and Safety of WHO-Recommended Dosage and Higher Dosage of Levofloxacin for Tuberculosis Treatment in Children: a Pilot Study.

OBJECTIVES: To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage. METHODS: Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100. RESULTS: The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events. CONCLUSION: Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.

Temporal trend of drug-resistant tuberculosis among Thai children during 2006-2021.

Background: The prevalence of drug-resistant tuberculosis (DR-TB) in adults has stabilized in the past decade. Our study aimed to describe the prevalence of DR-TB in Thai children between 2006 and 2021. Materials and methods: Children younger than 15 years old who had culture-confirmed Mycobacterium tuberculosis complex (MTB), positive PCR-MTB, or positive Xpert MTB/RIF were included in this cohort. Drug susceptibility testing (DST) was performed using phenotypic and/or genotypic methods. The prevalence of DR-TB was compared using the chi-square test. Results: Among 163 confirmed TB cases (44% as pulmonary TB, 27% as extrapulmonary TB, and 29% with both), the median age (IQR) was 12.2 (7.3-14.2) years. DST was performed in 139 cases (85%), revealing prevalences of all DR-TB, isoniazid-resistant TB (Hr-TB), and rifampicin monoresistant/multidrug-resistant TB (Rr/MDR-TB) of 21.6% (95% CI 14.7-28.4), 10.8% (95% CI 5.6-16.0%), and 2.9% (95% CI 0.1-5.7%), respectively. The DR-TB rates did not differ significantly between 2006-2013, 2014-2018, and 2019-2021 (p > 0.05). Two pre-extensively DR-TB (pre-XDR) cases with fluoroquinolone resistance were detected after 2014. Conclusion: The prevalence of DR-TB in Thai children was stable. However, one-tenth of DR-TB cases confirmed with DST were Hr-TB, which required adjustment of the treatment regimen. The pre-XDR cases should be closely monitored.

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.

Clinical and epidemiological characteristics of respiratory syncytial virus and influenza virus associated hospitalization in urban Thai infants.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza infections are among the leading cause of hospitalized lower respiratory tract infections (LRTI) in children especially among those younger than 1 year of age. Few descriptions of these 2 important viruses in Thai children less than 1 year of age have been published. MATERIAL AND METHOD: The authors conducted a prospective study of children 1-12 months old hospitalized at a pediatric tertiary-care hospital in Bangkok with LRTI during the period December 2007 to August 2009. Respiratory specimens were tested for influenza A/B virus and RSV using a reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Twenty-six (7.3%) had RT-PCR positive for influenza and 104 (29.4%) for RSV from 354 infants. Clinical diagnoses included pneumonia (73.4%), bronchiolitis (17.55%), croup (6.5%) and bronchitis (2.5%) and were similar among groups except the proportion of croup was significantly lower in RSV (p = .018). The proportion of RSV infection was highest between July and October (42-76%). RSV patients were more likely to present with higher temperature than the negative RT-PCR patients (p = .031). Oseltamivir was prescribed in 7.7% of influenza infections. Intravenous antibiotics were prescribed in 69.2%, 56.7% and 60.7% of the influenza, RSV and negative group respectively (p = .736). Percentages of patients requiring mechanical ventilation were 3.8, 6.7 and 6.3% among the influenza, RSV and negative group respectively (p = .861). Three patients died: 2 from RSV and 1 from the negative group. All three fatality cases had existing co-morbidity. CONCLUSION: A high proportion of RSV was detected in infants hospitalized with LRTI especially during July to October. High proportion of antibiotic prescription and relatively low rate of oseltamivir treatment were identified. Surveillance data and the availability of a rapid and reliable viral diagnostic test may help guide treatment, thereby improve outcome of this vulnerable population.