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We report an autochthonous case of simple, localized cutaneous leishmaniasis in a healthy 18-month-old girl from southern Thailand. The patient presented with a solitary chronic cutaneous nodular lesion on her left cheek for approximately 1 year. Histopathological dissection of the cheek skin biopsy demonstrated remarkably nodular and interstitial infiltrates of lymphocytes and histiocytes full of intracellular oval-shaped amastigotes, consistent with cutaneous leishmaniasis. The Leishmania promastigotes were also cultured successfully from the lesion biopsy and were designated with the WHO code MHOM/TH/2021/CULE5. Using internal transcribed spacer 1-specific polymerase chain reaction, the parasite DNA was demonstrated in both saliva and lesion biopsy. Based on the BLASTn and phylogenetic analysis, the parasite was identified as Leishmania orientalis, clustered in the Mundinia subgenus. The patient responded well to a 6-week course of oral itraconazole, without recurrence. To our knowledge, this is the fourth case of autochthonous leishmaniasis resulting from L. orientalis and the youngest patient of leishmaniasis ever reported in Thailand. More importantly, we also demonstrate the clinical course of the lesion according to the timeline before and after treatment, which can help physicians better understand and provide an accurate diagnosis with appropriate treatment of this emerging parasitic disease.

We conducted a retrospective cohort study of pregnancy and infant outcomes in 670 adolescents and young adult women with perinatally acquired HIV (AYAPHIV), aged 15-24 years, in Thailand and Vietnam. Between January 2013 and December 2018, there were 52 pregnancies, for an incidence of 2.49 (95% CI 1.90-3.27) per 100 person-years. The median age at pregnancy was 17.7 years (IQR 16.8-18.9). Pregnant AYAPHIV had been on cART for a lifetime median of 9.8 years (IQR 7.3-12.4). At the time of conception, the median CD4 was 521 cells/mm

Background A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. Methods A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Results Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1gen, 88% (95% CI 76–95) for Tdap1gen, 80% (95% CI 66–90) for Tdap2gen, 94% (95% CI 83–99) for TdaP5gen, and 78% (95% CI 64–88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. Conclusions All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004.

Objective To describe the clinical characteristics and outcomes of pediatric COVID-19 in Thailand, where favipiravir is the mainstay of antiviral treatment. Methods We conducted a hospital based observational cohort study of COVID-19 among children. The study included children (age

BACKGROUND Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de-escalation recommendations in children who received meropenem. METHODS A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary-care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de-escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem-resistant gram-negative bacteria (CR-GNB) within 30 days. RESULTS From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de-escalation. The overall acceptance of ASP de-escalation recommendations was 57.8% (95%CI: 46.9-68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03). CONCLUSIONS About half of the recommendations to de-escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem-resistant gram-negative bacteria acquisitions was less likely in the de-escalation group. A robust de-escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug-resistant organisms.

Prevention of emerging infections in children is a dynamic arena where substantial medical advances have enabled intervention and prevention of infection outbreaks. This article discusses 5 infections causing significant morbidity and mortality across Asia, Latin America, and Africa. Avian influenza and the Middle East respiratory syndrome are highly contagious zoonoses spread through aerosol and droplets, affecting predominantly Asia. Dengue infection and chikungunya are endemic mosquito-borne viruses in tropical regions across Asia, Latin America, and Africa. Ebola is a highly contagious virus spread through human-to-human contact. The latest information in clinical manifestations, infection, prevention control, chemoprophylaxis, vaccination, and public health measures is reviewed.

Objectives To describe the antibiotic use among hospitalized patients in Thailand. Methods A standardized cross-sectional point prevalence survey (PPS) modified from the WHO PPS protocol was conducted in 41 selected hospitals in Thailand. All inpatients who received an antibiotic at 9 a.m. on the survey date were enrolled. The total number of inpatients on that day was the denominator. Results Between March and May 2021, a total of 8958 inpatients were enumerated; 4745 inpatients received antibiotics on the day of the survey and there were 6619 prescriptions of antibiotics. The prevalence of antibiotic use was 53.0% (95% CI 51.1%–54.0%), ranging from 14.3% to 73.4%. The antibiotic use was highest among adults aged >65 years (57.1%; 95% CI 55.3%–58.9%). From 6619 antibiotics prescribed, 68.6% were used to treat infection, 26.7% for prophylaxis and 4.7% for other or unknown indications. Overall, the top three commonly used antibiotics were third-generation cephalosporins (1993; 30.1%), followed by first-generation cephalosporins (737; 11.1%) and carbapenems (703; 10.6%). The most frequently used antibiotics for community-acquired infections were third-generation cephalosporins (36.8%), followed by β-lactam/β-lactamase inhibitors (11.8%) and carbapenems (11.3%) whereas for the patients with hospital-acquired infections, the most common antibiotics used were carbapenems (32.7%), followed by β-lactam/β-lactamase inhibitors (15.7%), third-generation cephalosporins (11.7%) and colistin (11.7%). The first-generation cephalosporins were the most commonly used antibiotics (37.7%) for surgical prophylaxis. Seventy percent of the patients received surgical prophylaxis for more than 1 day post surgery. Conclusions The prevalence of antibiotic use among hospitalized patients in Thailand is high and one-quarter of these antibiotics were used for prophylaxis. The majority of surgical prophylaxis was inappropriately used for a long duration post operation. Therefore, it is recommended that local guidelines should be developed and implemented.

Urinary tract infection is one of the most common types of healthcare-associated infections. There is currently limited data regarding the incidence and characteristics of healthcare-associated urinary tract infections (HA-UTIs) in children. This study was conducted to determine the incidence of HA-UTIs and their characteristics and associated risk factors.A case-control study was performed from 2016 to 2020 on children under 15 years old who were diagnosed with HA-UTI. Patients who had HA-UTI were compared to non-UTI patients. The incidence rate of HA-UTIs was calculated and reported as events per 1000 patient days. Potential associated risk factors were analyzed using multivariate logistic regression.Eighty cases and 80 controls were included in the study. The incidence of HA-UTIs was 0.32 events per 1,000 patient days. The median time to UTI was 18 days. The most common causative organism was Escherichia coli (43.2%) and the rates of third-generation cephalosporin resistance and carbapenem resistance were 75.6% and 4.9%, respectively. Longer admission than 7 days (OR = 21.61, 95% CI 6.30-74.11; p 0.001), neurogenic bladder (OR = 26.24, 95% CI 3.77-182.87; p 0.001), mechanical ventilation (OR = 3.60, 95% CI 1.23-10.54; p = 0.019), and immunosuppressant (OR = 2.59; 95% CI 1.01-6.60; p = 0.047) were the risk factors significantly associated with HA-UTIs.The incidence of HA-UTIs was low in this single-center experience. Identifying patients with the risk factor is imperative to preventing the development of HA-UTIs.

Background Population pharmacokinetic analysis in critically ill infants remains a challenge for lack of information. Objectives To determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters. Methods A prospective study was conducted on 35 patients. A total of 160 blood samples were collected and determined free of drug concentrations of meropenem. Population pharmacokinetic data were analyzed using NONMEM software. Internal validation methods, including bootstrapping and prediction-corrected visual predictive checks, were applied to evaluate the robustness and predictive power of the final model. Results A one-compartment model with first-order elimination showed the best fit to the data. The typical clearance (CL) values and volume of distribution (Vd) were 1.33 L/h and 2.27 L, respectively. Weight and creatinine clearance were influential covariates for CL, while weight was a significant covariate for Vd of meropenem. The model evaluation results suggested robustness and good predictability of the final model. The standard dosage regimens of meropenem achieved 40% f T>MIC but not enough if a more aggressive target of 80% f T>MIC at MIC value of ≥ 16 µg/mL is desired. Conclusions This population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants.

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 Conclusions Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.

Background The prevalence of syphilis is increasing among adolescents and young adults (AYAs) globally. Use of syphilis rapid diagnostic treponemal tests (RDTs) may improve test coverage and same-day treatment. This study aims to determine sensitivity and specificity of two syphilis RDTs. Methods A cross-sectional study was conducted in men who have sex with men and transgender women aged 15–24 years attending a sexual health clinic in Bangkok. Syphilis RDTs used were Determine Syphilis TP and Bioline Syphilis 3.0, using whole blood from finger pricks and venipuncture. Treponemal pallidum electrochemiluminescence assay was used as standard reference. Results From February to July 2022, 200 AYAs with a mean age 21.1 (SD2.1) years were enrolled, including 50 (25.0%) living with HIV. Prevalence of syphilis was 10.5% (95%CI 6.6–15.6), which was higher among AYAs living with HIV (22.0%) compared with AYAs unaffected by HIV (6.7%). Sensitivities of Determine Syphilis TP and Bioline Syphilis 3.0 were 85.7% (95%CI 63.7–97.0) and 66.7% (95%CI 43.0–85.4), respectively. Specificity of both RDTs was 100% (95%CI 98.0–100.0). Performance of RDTs was similar for both specimens. Conclusions Syphilis RDTs have high sensitivity and specificity in diagnosing syphilis. It should be considered for use in sexual health clinics with high syphilis prevalence to initiate treatment promptly.

Objectives Febrile neutropenia (FN) is severe and potentially life-threatening in oncologic patients. The objective of this study is to define the factors associated with severe adverse outcomes of pediatric FN. Methods A retrospective and prospective descriptive study performed in pediatric patients diagnosed with FN at King Chulalongkorn Memorial Hospital from January 2013 to December 2017. Severe adverse events defined as the presence in one of these following oxygen therapies, mechanical ventilator, shock, admission to ICU, renal dysfunction, and liver dysfunction. Results The study included 267 patients with 563 febrile neutropenia episodes. The median (range) age was 5.1 years (1 month-15 year). Among 563 febrile neutropenia episodes, 115 episodes (20%) developed severe adverse events. The FN patients were classified into low and high-risk groups, 91% of patients with severe adverse events and all 21 patients who died were in high risk group. The overall mortality rate was 3.1%. Factors associated with severe adverse events were fungal infection (aOR 6.51, 95%CI 2.29-18.56), central venous catheter insertion (aOR 4.28, 95% CI 2.51-7.29), CPG defined high risk (aOR 3.35, 95%CI 1.56-7.17), viral infection (aOR 2.72, 95%CI 1.05-7.06), lower respiratory tract infection (aOR 2.52, 95%CI 1.09-5.82) and treatment not according to CPG (aOR 2.47, 95% CI 1.51-4.03). Conclusions Fungal and viral infection, central venous catheter insertion, lower respiratory tract infection, CPG defined high risk and treatment not according to CPG were associated factors of increased risk for severe adverse events. Our current institutional CPG for FN in children was applicable and improved clinical outcomes for this group of patients. .

Background Invasive candidiasis (IC) is a serious infection among children with underlying medical conditions. A shift from C. albicans to non-albicans Candida has been observed worldwide. This study aims to identify species of Candida and factors associated with the overall 30-day mortality rate. Methods A retrospective chart review was conducted among children with culture-confirmed IC aged from birth to 15 years at King Chulalongkorn Memorial Hospital, Thailand. Multivariate Cox regression analysis was performed to determine associated factors with 30-day mortality. Results From 2003 to 2019, 102 episodes of IC in pediatric group with a median age of 16 months (interquartile range 4-65) and 12 episodes of IC in neonatal group with a median age of 18 days (interquartile range 12-22). The species distribution were Candida albicans (35%), Candida parapsilosis (26%), Candida tropicalis (22%), Candida glabrata (6%) and other/unspecified species (11%). Antifungal treatment was given in 88% (67% Amphotericin B deoxycholate, 28% Fluconazole). Overall 30-day mortality rates were 28.5% [95% confidence interval (CI) 20.8%-38.4%] and 8.3% (95% CI 1.2%-46.1%) in pediatrics and neonates, respectively. Mortality rate among the neutropenic group was significantly higher than non-neutropenic group (46.4% vs. 20.6%, P = 0.005). Factors associated with 30-day mortality in pediatric IC were shock [adjusted hazard ratio (aHR) 4.2; 95% CI 1.8-9.4], thrombocytopenia (aHR 7.7; 95% CI 1.8-33.9) and no antifungal treatment (aHR 4.6; 95% CI 1.7-12.1). Conclusions Two-third of children with IC were diagnosed with non-albicans Candida. Children with high mortality rate included those with neutropenia, presented with shock or thrombocytopenia, such that the proper empiric antifungal treatment is recommended.

Background Central line-associated bloodstream infections (CLABSIs) are important hospital-acquired infections. Chlorhexidine-impregnated dressings (also known as chlorhexidine patches, CHG patches) are reported to decrease CLABSIs in adults. This study aims to determine the efficacy of CHG patches in reducing CLABSIs in children. Methods An open-label randomized controlled trial was conducted in children aged 2 months to 18 years, requiring a short-term catheter. Patients were randomized into two groups, allocated to receive CHG patches or standard transparent dressings. Care of the catheter was in accordance with Asia Pacific Society of Infection Control (APSIC) recommendations. Central-line-associated bloodstream infections were defined using National Healthcare Safety Network surveillance criteria. Results From April 2017 to April 2018, 192 children were enrolled. There were 108 CHG patch catheters and 101 standard dressing catheters, contributing to 3,113 catheter days. The median duration of catheter dwelling was 13 days, with an interquartile range (IQR) of 8-20 days. Half were placed at the jugular vein and 22% at the femoral vein. There were 23 CLABSI events. Incidence rates for CHG patches and standard dressings were 7.98 (95% confidence interval (CI), 4.25-13.65) and 6.74 (95% CI, 3.23-12.39) per 1,000 catheter days, respectively (incidence rate ratio 1.18; 95% CI, 0.52-2.70). The CLABSI pathogens were 15 Gram-negative bacteria, six Gram-positive bacteria, and two Candida organisms. Catheter colonization of CHG patches and standard dressings were 2.02 (95% CI, 0.42-5.91) and 3.07 (95% CI, 1.00-7.16) per 1,000 catheter days, respectively. Only local adverse effects occurred in 6.8% of the participants. Conclusions In our setting, there was no difference in CLABSI rates when the chlorhexidine patch dressings were compared with the standard transparent dressings. Strengthening of CLABSI prevention bundles is mandatory.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) young children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among PHIV and PHEU children aged 18-60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers’ symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare prevalence of behavioral problems between groups of participants. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers’ depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to presence of child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

BACKGROUND The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of

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.

Antimicrobial resistance is a global health threat and there is an urgent need to manage antibiotic use to slow its development. However, antimicrobial stewardship interventions in low- and middle-income countries (LMIC) have been limited in terms of their resourcing, feasibility and effectiveness in the face of greater challenges in child mortality. We sought to gather together examples of antibiotic use problems faced by clinicians in LMIC, many of which are unique to these settings, and real-world antimicrobial stewardship solutions identified, with the goal of learning broader lessons that might be applicable across LMIC.

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.

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.

Chulalongkorn Medical Journal, 66, 1, 007-013

Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and

Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to

Combination antiretroviral drug regimens are increasingly preferred for neonatal postexposure prophylaxis (PEP) among HIV-exposed infants with high-risk of transmission. We evaluated the adverse events associated with the use of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) for neonatal PEP during the first 6 weeks of life.A prospective cohort of non-breast-fed HIV-exposed infants was conducted at 5 clinical sites in Thailand. Study population included 100 high-risk HIV-exposed infants (maternal HIV RNA50 copies/mL prior to delivery or received antiretroviral therapy less than 12 weeks) and 100 low-risk HIV-exposed neonates. High-risk infants received ZDV/3TC/NVP for 6 weeks whereas low-risk HIV-exposed neonates received a 4-week regimen of ZDV. Complete blood count, aspartate transaminase and alanine transaminase were assessed at birth, 1, 2 and 4 months of life.From October 2015 to November 2017, 200 infants were enrolled, of which 18.5% had low birth weight2500 g. The proportion of infants with anemia grade 2 or higher at 1 and 2 months of life between ZDV/3TC/NVP and ZDV prophylaxis was 48.5% vs 32.3% (P=0.02); nevertheless, severe anemia (grade 3) was not significantly different; 9.2% vs 10.2% (P=0.81), respectively. At 1 month old, infants on ZDV/3TC/NVP prophylaxis had significantly higher grade 2 anemia versus infants on ZDV alone (33.0% vs 13.4%; P=0.001); however, no difference was observed at 2 months old. No differences in neutropenia or hepatotoxicity between infant prophylactic regimens were observed.Triple antiretroviral neonatal PEP with ZDV/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with ZDV-monotherapy prophylaxis.

ObjectiveTo gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).DesignA web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.Setting39 NNUs from 12 countries.PatientsAny neonate admitted to one of the participating NNUs.InterventionsThis was an observational cohort study.ResultsThe number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions ConclusionAMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

The 24-hour vancomycin area under the serum concentration-time curve (AUC24 ) divided by the minimum inhibitory concentration (MIC) (AUC24 /MIC) is more closely related to patient outcomes than serum trough concentrations (Ctrough ). Two-point simplified equations for calculating AUC based on serum peak concentrations (Cpeak ) and Ctrough , named equation A (EqA) and equation B (EqB), have recently been adopted into clinical use for adult pediatric patients. We aimed to find the agreement between predicted AUC24 using the reference method (ref) relative to EqA and EqB and the correlation between Ctrough and AUC24 . From June to December 2018, 43 pediatric patients with normal renal function, receiving 15 mg/kg of vancomycin intravenously every 6 hours, were enrolled. The pediatric patients' median age was 2.2 years (range 0.1-15.3). At steady state, vancomycin Cpeak and Ctrough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC24 was estimated using ref, EqA, and EqB. From Bland-Altman analysis, the 2 AUC24 s estimated by ref and EqA showed less bias than those estimated by ref and EqB (bias 1.3 and -72.1 mg⋅h/L, respectively). Ctrough and AUC24 using either ref or EqA were correlated more closely (r2 = 0.94) than with EqB (r2 = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC24 ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC24 ≥400 mg⋅h/L was never seen with Ctrough 10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC24 estimation. Ctrough >10 mg/L correlated highly to AUC24 ≥400 mg⋅h/L.

Triple-drug infant antiretroviral prophylaxis containing nevirapine (NVP) is increasingly used to prevent HIV transmission among neonates at high risk of HIV infection. Our aim was to describe NVP concentration from birth through the first month of life.High-risk HIV-exposed neonates were enrolled in a prospective cohort in Thailand. High-risk neonates defined as maternal HIV RNA50 copies/mL before delivery or mother received antiretroviral treatment for12 weeks before delivery. Neonates received zidovudine (4 mg/kg) and lamivudine (2 mg/kg) twice daily, plus NVP (4 mg/kg) once daily (no lead-in) from birth to 6 weeks of life. Infant plasma samples were collected at 1, 2, 14 or 2, 7, 28 days of life. NVP trough concentrations (C24) were estimated using a population pharmacokinetic model and target C24 was ≥0.1 mg/L. "Washout" efavirenz (EFV) concentrations were assessed in infants whose mother received EFV-based antiretroviral treatment.A total of 48 infants were included: 25 (52%) were male and 12 (25%) were preterm (gestational age 34-37 weeks). Median (interquartile range) predicted NVP C24 were 1.34 mg/L (1.13-1.84), 2.24 (2.00-2.59), 2.78 (2.61-3.12), 2.20 (1.86-2.44) and 0.81 (0.58-0.98) on days 1, 2, 7, 14 and 28 of life, respectively. NVP C24 was not significantly different between term and preterm infants. All infants maintained NVP C24 ≥0.1 mg/L. EFV via placental transfer remained detectable in infants up to 7 days of life.NVP 4 mg/kg daily from birth provided adequate prophylactic concentrations during the first month of life in high-risk HIV-exposed neonates.

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.

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.