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D-trans allethrin, a pyrethroid, is commonly used as a coil mosquito repellant. There are very few reports of human toxicity due to D-trans allethrin. We present the case of an 11-month-old boy who presented to us with excessive salivation, altered sensorium and convulsions following alleged accidental ingestion of a coil containing D-transallethrin. He required mechanical ventilation for a brief period and made a full recovery. Although rare, the possibility of pyrethroid poisoning should be kept in mind in children who present with sudden onset unconsciousness or convulsions [ABSTRACT FROM AUTHOR]

Hemorrhagic cystitis as a complication of influenza A has been described. There is only one case report describing hemorrhagic cystitis in a child with novel pandemic 2009 H1N1 influenza A infection. We report two children with confirmed novel pandemic 2009 H1N1 infection who had hemorrhagic cystitis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of an 11-year-old girl diagnosed to have influenza H1N1 virus infection by Reverse-Transcription-Polymerase Chain Reaction (RT-PCR), in whom a routine random blood sugar showed hyperglycemia.

Background Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. Methods We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. Results Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. Conclusions Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI. [ABSTRACT FROM AUTHOR]

The article discusses the lessons learned from the management of the Hemagglutinin Type 1 and Neuraminidase Type 1 (H1N1) pandemic in Pune, India. As of April 19, 2010, 4,466.067 patients have been screened for H1N1 with 2,034 patients testing positive. It mentions that the pandemic was managed by laying out a national plan and having the awareness of potential consequences and measures to educate the public about H1N1 through media. It suggests better border control, contact tracing and school closures.

Background Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration NCT02958709. [ABSTRACT FROM AUTHOR]

Background: HIV-related stigma is associated with poor quality of life and poor healthcare-seeking behaviours in young people living with HIV (YPLHIV) and young people affected by HIV (YPAHIV). India has an estimated 120,000 YPLHIV and 4 million YPAHIV, but efforts to measure HIV-related stigma in them are sparse, impeded by the lack of measuring instruments. Here, we describe the development of the Pune HIV-Stigma Scale (PHSS) and modified-PHSS to measure HIV-related stigma among YPLHIV and YPAHIV, respectively, in India.Methods: We used data from a mental health study for YPLHIV and YPAHIV aged 15-25 years, conducted at Byramjee Jeejeebhoy Government Medical College & Sassoon General Hospitals, Pune, India, between August 2018 and June 2021. Findings from multiple confirmatory factor analyses and cognitive interviews guided the development of the 12-item PHSS. The modified-PHSS was developed by confirming the structure of the PHSS for YPAHIV. Convergent validity with Center for Epidemiological Studies Depression (CES-D) and UCLA Loneliness scales was assessed using Spearman's correlation coefficients.Results: Model fit indices were good for both the PHSS (χ2 = 65.0, df = 48, p value: 0.052; root mean square error of approximation (RMSEA): 0.054; comparative fit index (CLI): 0.980; Tucker-Lewis index (TLI): 0.972; and standardized root mean square residual (SRMR): 0.067), and the modified-PHSS (χ2 = 56.9, df = 48, p value: 0.176; RMSEA: 0.045; CLI: 0.983; TFI: 0.976, and SRMR: 0.078). Spearman's correlation coefficients indicated low to moderate convergent validity (ρ: 0.03-0.52) across different subscales of the PHSS and modified-PHSS. Cronbach's alpha for the PHSS was 0.82 and for the modified-PHSS 0.81.Conclusion: We developed the first scales to measure HIV-related stigma among YPLHIV and YPAHIV in India. These concise scales can facilitate measurement of HIV-related stigma more frequently in research studies. We recommend that they be tested in different Indian languages. [ABSTRACT FROM AUTHOR]

Mosquitoborne diseases (e.g., malaria, dengue, and chikungunya) are endemic to India and pose diagnostic challenges during pregnancy. We evaluated an intensified short symptom screening program in India to diagnose dengue during pregnancy. During October 2017-January 2018, we screened pregnant women during antenatal surveillance for symptoms of mosquitoborne diseases (fever only, fever with conjunctivitis, fever with rash, or all 3 symptoms) within the previous 15 days. Of 5,843 pregnant women screened, 52 were enrolled and tested for dengue, chikungunya, and Zika viruses by using a Trioplex real-time reverse transcription PCR. Of 49 who had complete results, 7 (14%) were dengue positive. Of these ocular pain was seen in 4 (57%) and conjunctivitis in 7 (100%). Intensified symptom screening using conjunctivitis, in addition to rash, in pregnant women with fever might improve dengue case detection and can be included in routine symptom screening during pregnancy. [ABSTRACT FROM AUTHOR]

Background Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)–infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1–infected pregnant women. Methods Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks’ gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker. Results In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24–4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43–10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18–4.41) but not log2 CRP (aOR, 0.72; 95% CI,.48–1.09). Conclusions Our results show that select immune markers can identify women at higher risk for PTB in HIV-1–infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB. Clinical Trials Registration NCT00061321. [ABSTRACT FROM AUTHOR]

Background. Antibiotic resistance mechanisms originating in low- and middle- income countries are among the most common worldwide. Reducing unnecessary antibiotic use in India, the world's largest antibiotic consumer, is crucial to control antimicrobial resistance globally. Limited data describing factors influencing Indian clinicians to start or stop antibiotics are available. Methods. Febrile adults and children admitted to a public tertiary care hospital in Pune, India, were enrolled. Antibiotic usage and clinical history were recorded. Immunoassays for mosquito-borne disease and bacterial cultures were performed by protocol and clinician-directed testing. Clinical factors were assessed for association with empiric antibiotic initiation and discontinuation by day 5 using multivariable logistic regression and propensity score--matched Cox proportional hazard models. Results. Among 1486 participants, 683 (82%) adults and 614 (94%) children received empiric antibiotics. Participants suspected of having mosquito-borne disease were less likely to receive empiric antibiotics (adjusted odds ratio [AOR], 0.5; 95% confidence interval [CI], .4-.8). Empiric antibiotics were discontinued in 450 (35%) participants by day 5. Dengue or malaria testing performed before day 4 was positive in 162 (12%) participants, and was associated with antibiotic discontinuation (AOR, 1.7; 95% CI, 1.2-2.4). In a propensity score--matched model accounting for admission suspicion of mosquito-borne disease, positive dengue or malaria tests increased hazard of antibiotic discontinuation (hazard ratio, 1.6; 95% CI, 1.2-2.0). Conclusions. Most patients with acute febrile illness in an Indian public hospital setting receive empiric antibiotics. Mosquitoborne disease identification is associated with reduced empiric antibiotic use and faster antibiotic discontinuation. [ABSTRACT FROM AUTHOR]

Background: In India, antimicrobial consumption is high, yet systematically collected data on the epidemiology, risk factors, and outcomes of antimicrobial-resistant infections are limited.Methods: A prospective study of adults and children hospitalized for acute febrile illness was conducted between August 2013 and December 2015. In-hospital outcomes were recorded, and logistic regression was performed to identify independent predictors of community-onset antimicrobial-resistant infections.Results: Among 1524 patients hospitalized with acute febrile illness, 133 isolates were found among 115 patients with community-onset infections; 66 isolates (50.0%) were multidrug resistant and, of 33 isolates tested for carbapenem susceptibility, 12 (36%) were resistant. Multidrug-resistant infections were associated with recent antecedent antibiotic use (adjusted odds ratio [aOR], 4.17; 95% confidence interval [CI], 1.19-19.7) and were independently associated with mortality (aOR, 6.06; 95% CI, 1.2-55.7).Conclusion: We found a high burden of community-onset antimicrobial-resistant infection among patients with acute febrile illness in India. Multidrug-resistant infection was associated with prior antibiotic use and an increased risk of mortality. [ABSTRACT FROM AUTHOR]

Elevated soluble CD14 (sCD14) concentrations, a marker of monocyte activation, predicts adverse outcomes in human immunodeficiency virus (HIV)-infected adults. To examine the association of sCD14 concentrations with the risk of mother-to-child transmission (MTCT) of HIV, we nested a case-control study (49 pairs of infants and their HIV-infected mothers) within the Six-Week Extended-Dose Nevirapine trial. Median peripartum maternal log2 sCD14 concentration was higher among transmitters (defined as pairs in which maternally transmitted HIV infection occurred by 12 months of age) than nontransmitters (20.29 pg/mL vs 19.41 pg/mL; P = .005). There was an increased odds of MTCT for every log2 increase in maternal sCD14 concentration, after adjustment for maternal HIV load, CD4 count and cART exposure (adjusted odds ratio, 3.51; 95% confidence interval, 1.21-10.21). Maternal monocyte activation may adversely influence the risk of MTCT of HIV. [ABSTRACT FROM AUTHOR]

Pediatric tuberculosis (TB) remains a major global health problem. Improved pediatric diagnostics using readily available biosources are urgently needed. We used liquid chromatography-mass spectrometry to analyze plasma metabolite profiles of Indian children with active TB (n = 16) and age- and sex-matched, Mycobacterium tuberculosis-exposed but uninfected household contacts (n = 32). Metabolomic data were integrated with whole blood transcriptomic data for each participant at diagnosis and throughout treatment for drug-susceptible TB. A decision tree algorithm identified 3 metabolites that correctly identified TB status at distinct times during treatment. N-acetylneuraminate achieved an area under the receiver operating characteristic curve (AUC) of 0.66 at diagnosis. Quinolinate achieved an AUC of 0.77 after 1 month of treatment, and pyridoxate achieved an AUC of 0.87 after successful treatment completion. A set of 4 metabolites (gamma-glutamylalanine, gamma-glutamylglycine, glutamine, and pyridoxate) identified treatment response with an AUC of 0.86. Pathway enrichment analyses of these metabolites and corresponding transcriptional data correlated N-acetylneuraminate with immunoregulatory interactions between lymphoid and non-lymphoid cells, and correlated pyridoxate with p53-regulated metabolic genes and mitochondrial translation. Our findings shed new light on metabolic dysregulation in children with TB and pave the way for new diagnostic and treatment response markers in pediatric TB. [ABSTRACT FROM AUTHOR]

Background: Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India.Methods: Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization.Results: Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0-8.5).Conclusions: Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission. [ABSTRACT FROM AUTHOR]

In this prospective cohort of 2006 individuals with drug-susceptible tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: We described mortality and loss to follow-up (LTFU) in children and adolescents who were under care for more than 5 years following initiation of antiretroviral therapy (ART)., Methods: Patients were followed from 5 years after ART until the earlier of their 25th birthday, last visit, death, or LTFU. We used Cox regression to assess predictors of mortality and competing risk regression to assess factors associated with LTFU., Results: In total, 4488 children and adolescents initiating ART between 1997 and 2016 were included in the analysis, with a median follow-up time of 5.2 years. Of these, 107 (2.2%) died and 271 (6.0%) were LTFU. Mortality rate was 4.35 and LTFU rate 11.01 per 1000 person-years. Increased mortality was associated with AIDS diagnosis (adjusted hazard ratio [aHR] 1.71; 95% confidence interval [CI] 1.24-2.37), current CD4 count <350 cells/mm 3 compared with ≥500 (highest aHR 13.85; 95% CI 6.91-27.76 for CD4 <200), viral load ≥10 000 copies/mL compared with <400 (aHR 3.28; 95% CI 1.90-5.63), and exposure to more than one ART regimen (aHR 1.51; 95% CI 1.14-2.00). Factors associated with LTFU were male sex (adjusted subdistribution hazard ratio [asHR] 1.29; 95% CI 1.04-1.59), current viral load >1000 copies/mL compared with <400 (highest asHR 2.36; 95% CI 1.19-4.70 for viral load 1000-9999), and ART start after year 2005 compared with ≤2005 (highest asHR 5.96; 95% CI 1.98-17.91 for 2010-2016)., Conclusion: For children and adolescents surviving 5 years on ART, both current CD4 and viral load remained strong indicators that help to keep track of their treatment outcomes. More effort should be made to monitor patients who switch treatments., (© 2024 British HIV Association.)

Over investigations contribute to escalating health costs driven by multiple factors including physician decisions, patient requests, information overload, technological advances, marketing, hospital management policies, insurance requirements and defensive practices. The reconciliation between knowledge and clinical wisdom while dealing with uncertainties in medicine is the primary way forward through this ethical maze. A case scenario illustrates what pediatricians need to reflect upon while facing decisions on rational investigations to maximize beneficence while being aware of economics of healthcare delivery.

Rifampicin-resistant (RR) tuberculosis (TB) in children is a major global health concern but is often neglected in economics research. Accurate cost estimations across the spectrum of paediatric RR-TB treatment regimens are critical inputs for prioritisation and budgeting decisions, and an existing knowledge gap at local and international levels. This normative cost analysis was nested in a Phase I/II pharmacokinetics, safety, tolerability, and acceptability trial of TB medications in children in South Africa, the Philippines and India. It assessed the pharmaceutical costs of 36 childhood RR-TB regimens using combinations from 16 different medicines in 34 oral formulations (adult and child-friendly) in 11 weight bands in children <15 years of age. The analysis used local and Global Drug Facility pricing, and local and international guideline recommendations, including adaptions of BPaL and BPaLM regimens in adults. Costs varied significantly between regimen length, age/weight banding, severity of disease, presence of fluroquinolone resistance, and different country guideline recommendations. WHO recommended regimen costs ranged 12-fold: from US$232 per course (short regimen in non-severe disease) to US$2,761 (long regimen in severe, fluroquinolone-resistant disease). Regimen treating fluoroquinolone-resistant infection cost US$1,090 more than comparable WHO-recommended regimen. Providing child-friendly medicine formulations in <5-year-olds across all WHO-recommended regimens is expected to cost an additional $380 (range $212-$563) per child but is expected to have wider benefits including palatability, acceptability, adherence, tolerability, and dose accuracy. There were substantial differences in regimen affordability between countries when adjusted for purchasing power and domestic spending on health. Appropriate, effective, and affordable treatment options are an important component of the fight against childhood RR-TB. A comprehensive understanding of the cost and affordability dynamics of treatment options will enable national TB programs and global collaborations to make the best use of limited healthcare resources for the care of children with RR-TB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wilkinson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial., Methods: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH., Results: Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P = .07) but more underweight (weight-for-age z score, -2.3; (3.3, -0.8 versus -1.0; -1.8, -0.2; P < .01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P < .01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241-1134), and CD4% was 16% (10-26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3-4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42)., Conclusions: We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV. Clinical Trials Registration. ISRCTN63579542., Competing Interests: Potential conflicts of interest. C. C., E. W., S. H., Vi. M., and A. C. H. report institutional funding to participate as SHINE trial sites from the UK MRC–Clinical Trials at University College, London, through a prime grant award from UK MRC, Wellcome Trust, and Department for International Development (grant MR/L004445/1). A. T., A. K., and D. G. report a COVID 19 Grant Extension Allocation award 181573 from UK Research Innovation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival., Methods: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated., Results: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding., Conclusion: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic., Objective: The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods., Methods: We analyzed data from 15,381 patients tested for RSV between 2017 and 2023., Results: Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses., Conclusion: Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses., (© 2024. The Author(s).)

Background: Neonatal intravenous cannulation, especially in preterms, is more challenging than in children or adults. Placement of an intravenous cannula is painful and many cannulas need frequent changing due to complications. Each attempt at cannulation creates an entry for skin flora to cause systemic bacteraemia. This study was undertaken at a level III NICU. The team attempted to prolong the existing cannula longevity to reduce the frequency of intravenous cannulation thereby reducing handling and pain., Objectives: To improve the longevity of peripherally inserted intravenous cannula in sick neonates in NICU from the current 25.7 hours to 36 hours or more, over a span of 6 weeks., Materials and Methods: The quality improvement (QI) team comprised resident doctors and staff nurses. A fishbone analysis was used to identify factors that affected the longevity of intravenous cannulas. Five WHYs technique was used to identify the cause behind early cannula removal. Both techniques identified the fixation technique used at the study centre for target intervention. Plan-Do-Study-Act cycles were planned to explore different fixation techniques to improve cannula longevity. The unpaired t-test and the χ 2 tests were applied to analyse statistical significance., Results: We achieved significant improvement in cannula longevity from 25.7 hours to 39.6 hours just by improving the fixation technique over 6 weeks with a p=0.0006., Conclusions: The QI study was successful and is adopted for routine practice. Such initiatives would greatly impact babies in low-resource settings and in transit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011-2013 to 6.7 in 2017-2020, median CD4 count doubled from 237 cells/μl to 466 cells/μl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011-2013 and 2017-2020. Lower hazard of OIs were found in those with age at first ART 2-14 years, current CD4 ≥200 cells/μl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AHS receives grants to her institution from ViiV Healthcare. All other authors report no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sornillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training., Methods: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training. Using a modified Delphi method, United States-based neurologists participated in 3 rounds of voting on a survey with potential competencies rated on a 4-point Likert scale. A final group discussion was held to reach consensus. Proposed competencies were then subjected to a formal review from a group of 7 neurologists from low- and middle-income countries (LMICs) with experience working with neurology trainees from high-income countries (HICs) who commented on potential gaps, feasibility, and local implementation challenges of the proposed competencies. This feedback was used to modify and finalize competencies., Results: Three rounds of surveys, a conference call with United States-based experts, and a semistructured questionnaire and focus group discussion with LMIC experts were used to discuss and reach consensus on the final competencies. This resulted in a competency framework consisting of 47 competencies across 8 domains: (1) cultural context, social determinants of health and access to care; (2) clinical and teaching skills and neurologic medical knowledge; (3) team-based practice; (4) developing global neurology partnerships; (5) ethics; (6) approach to clinical care; (7) community neurologic health; (8) health care systems and multinational health care organizations., Discussion: These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology., (© 2023 American Academy of Neurology.)

The WHO recommends the integration of routine HIV services within maternal and child health (MCH) services to reduce the fragmentation of and to promote retention in care for pregnant and postpartum women living with HIV (WWH) and their infants and children exposed to HIV (ICEH). During 2020-2021, we surveyed 202 HIV treatment sites across 40 low- and middle-income countries within the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We determined the proportion of sites providing HIV services integrated within MCH clinics, defined as full [HIV care and antiretroviral treatment (ART) initiation in MCH clinic], partial (HIV care or ART initiation in MCH clinic), or no integration. Among sites serving pregnant WWH, 54% were fully and 21% partially integrated, with the highest proportions of fully integrated sites in Southern Africa (80%) and East Africa (76%) compared to 14%-40% in other regions (i.e., Asia-Pacific; the Caribbean, Central and South America Network for HIV Epidemiology; Central Africa; West Africa). Among sites serving postpartum WWH, 51% were fully and 10% partially integrated, with a similar regional integration pattern to sites serving pregnant WWH. Among sites serving ICEH, 56% were fully and 9% were partially integrated, with the highest proportions of fully integrated sites in East Africa (76%), West Africa (58%) and Southern Africa (54%) compared to ≤33% in the other regions. Integration was heterogenous across IeDEA regions and most prevalent in East and Southern Africa. More research is needed to understand this heterogeneity and the impacts of integration on MCH outcomes globally., Competing Interests: KA has received funding from ViiV Healthcare which is unrelated to this project. All other authors declare that they have no competing interests., (© 2023 Humphrey, Nagel, Carlucci, Edmonds, Kinikar, Anderson, Leroy, Machado, Yin, Tulio Luque, Amorissani-Folquet, Mbewe, Suwanlerk, Munyaneza, Patel, Musick, Abuogi and Wools-Kaloustian.)

Background: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level., Methods: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC 0-24 ) and peak plasma concentration ( C max ) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC 0-24 and C max were assessed with linear mixed-effects models., Results: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC 0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L -1 ), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L -1 ), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L -1 ) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L -1 ). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC 0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC 0-24 for isoniazid and pyrazinamide. N -acetyltransferase 2 rapid acetylators had lower isoniazid AUC 0-24 and slow acetylators had higher isoniazid AUC 0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC 0-24 ., Conclusions: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring., Competing Interests: Conflict of interest: H.S. Schaaf reports grants from the NIH/IMPAACT; and honoraria from Ann Lake publications (sponsored by Johnson & Johnson) for an educational publication on the management of MDR-TB in children. A. Bekker reports grants from IMPAACT, UNITAID; lecture honoraria from Sandoz; support for attending PENTA PIM meeting; and received generic LPV/r, 3TC and ABC for the PETITE study. D.J. Bell reports support for attending a meeting from ViiV pharmaceuticals; and attendance fees for an advisory board meeting from ViiV pharmaceuticals. L. Choo reports grants from the UKRI MRC DFID Wellcome NIHR Joint Global Health Trials, TB Alliance Support for trial drug purchase and UKRI COVID-19 Grant Extension Allocation Award. P. Denti reports a grant for WHO expert review for TB drugs in children. S.M. Graham reports participation on a data safety monitoring board for the TB CHAMP trial; and leadership roles as a co-chair for the Guidelines Development Committee of the WHO updated recommendations and consolidated guidelines on child and adolescent TB, and as a core member for the WHO Child and Adolescent TB Working Group. S.K. Heysell reports grants from the NIH, DANIDA and EDTCP; royalties or licences from UpToDate; and honoraria for lectures from Henry Stewart Talks. A. Kwara reports a grant from the NIH/NICHD. V. Mave reports grants from the NIH and CDC. C.A. Peloquin reports a grant from the NIH. V. Roy reports a grant from the Delhi State TB Association; and leadership roles as a member of the Delhi State TB Association and the MAMC TB Committee. E.M. Svensson reports grants from the NWO personal Veni, IMI UNITE4TB consortium, TB Alliance, UNITAID BenefitKids consortium, WHO expert review, NIH support for IMPAACT studies, Blueprint, Probex, ACTG study Clo-FAST, Janssen Pharmaceuticals, EDCTP support PanTB-HM and Legochem; and leadership or fiduciary roles in the ISOP DI&E committee and BenNeLux PMX organising committee. U. Thatte reports participation on a data safety monitoring board for an ICMR TB trial. T.A. Thomas reports grants from the NIH and the University of Virginia. D.J. Touw reports a grant from Chiesi; consulting fees from Pure IMS and Sanguin; and participation on a data safety monitoring board for the FORMAT trial. A. Turkova reports grants from the UKRI MRC DFID Wellcome NIHR Joint Global Health Trials and MRC Grants for core funding of the Medical Research Council Clinical Trials Unit at the UCL; and TB Alliance Support for SHINE trial drug purchase. All of this work was declared by the authors to be outside the submitted work. All other authors declare no competing interests., (Copyright ©The authors 2023.)

Introduction: Women play an essential role in health care delivery, and it is vital that they have equal representation in health leadership for equity, innovation, and the strengthening of health systems globally. Yet women remain vastly underrepresented in global health leadership positions, providing a clear example of the deeply rooted power imbalances that are central to the calls to decolonize global health. We conducted a multi-country study in Haiti, Tanzania, India, and the USA to examine gender-based challenges to career advancement for women in the global health workforce. Quantitative data on the type and prevalence of gender-based challenges has been previously reported. In this study, we analyze qualitative data collected through focus group discussions and in-depth interviews to understand women's experiences of gender-based obstacles to career advancement, their perceptions of underlying drivers, and perspectives on effective solutions. Guided by an adaptation of the Social Action Theory, we conducted focus group discussions and in-depth interviews with women at 4 major academic centers for clinical care and research in Haiti, India, Tanzania, and the United States. In total, 85 women participated in focus groups and 15 also participated in in-depth interviews. Discussions and interviews were conducted in the local language, by an experienced local facilitator unaffiliated with the participating institution, between 2017 and 2018. Discussions were recorded, transcribed, and translated. Data were analyzed by interpretive phenomenological methods for emergent themes. Three transcendent themes on gender-based challenges were identified: 1) cultural power imbalance, referring to the prevailing norms and engrained assumptions that women are less capable than men and that women's primary responsibility should be to their families; 2) institutional power imbalance, referring to the systematic gender bias upheld by existing leadership and power structures, and ranging from exclusion from career development opportunities to sexual harassment and assault; and 3) restricted agency, referring to women's limited ability to change their circumstances because of unequal cultural and institutional structures. Participants also described local, actionable solutions to address these barriers. These included: 1) formal reporting systems for sexual harassment and assault; 2) peer support and mentorship; and 3) accessible leadership training and mandatory gender equity training. Participants proposed feasible strategies to address gender-based challenges that could improve women's retention in health careers and foster their rise to leadership. Increasing the representation of women in global health leadership positions responds directly to efforts to decolonize global health and is integral to strengthening health systems and improving health outcomes for women and children worldwide., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2023 Riche et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy., Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667., Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette-Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST 5/15 mm ]) at 2.88 (95% CI 1.69-4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97-8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17-25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82-7.51 for TST 5/15 mm ) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58-7.35 for TST 5/15 mm VS. 7.18, 95% CI 4.48-11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23-2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98-3.01 for TST 5/15 mm ). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST 5/15 mm ) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST 5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST 15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST 15 mm and p = 0.68 for QFT-GIT)., Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results., Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council [MC&#95;UU&#95;00004/07]., Competing Interests: YH and MXR report donation of QIAreach, an IGRA, by QIAGEN for a LTBI infection survey. YH, MXR, and IA report donations of Cy-TB, a TB-specific skin test for detection of LTBI, by the Serum Institute of India for a study on the feasibility and patient-important outcomes. They had no role in the submitted work. RD declared the receipt of payment for lectures from Qiagen and Oxford Immunotec. JD declared honoraria for lectures from Oxford Immunotec. AG declared receipt of research grants from the US National Institute of Health (NIH) and membership in NIH Council and IndoUS Science Technology Forum. CL provided consultation service to INSMED and received speakers honoraria from INSMED, GILEAD, JANSSEN and is a member of the Data Safety Board of trials from Medicines sans Frontiers, all outside of the submitted work. ILR has a patent (PCT/EP2019/064885), in vitro method for the diagnosis or detection of non-tuberculous mycobacteria. MS reports receipt of test kits free of charge from Qiagen and Oxford Immunotec. MS also reports receipt of research grants from Biotest and Astellas, consulting fees and honoraria from Biotest, Moderna, Qiagen, and Takeda, support for travel from Biotest, and participation on advisory board for Biotest and Moderna, all outside of this work. GS reports receipt of consulting fees from Pfizer, Diasorin, and INSMED. All other authors declare no competing interests., (© 2022 The Author(s).)

Background: SARS-CoV-2 was first reported in China in December 2019 and quickly spread across the world. Non-pharmaceutical interventions (NPIs) are the key to control the transmission of respiratory viruses. To stop the spread, NPI is widely recommended and is still followed by most countries., Methods: At the National Influenza Center of the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), the surveillance of severe acute respiratory illness and acute respiratory illness cases for influenza and other respiratory viruses is in place. In this study, we analyzed surveillance data on respiratory viruses and/or SARS-CoV-2 testing from January 2017 to December 2021. Multiplex real-time PCR was used to detect the respiratory viruses., Results: Our findings indicate that during the pandemic, the positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus, and human coronavirus declined significantly., Conclusion: The annual distinct seasonal outbreaks of influenza, RSV, and other respiratory viruses as observed during the pre-COVID-19 period were not observed during the COVID-19 pandemic in years 2020 and 21. Social distancing, lock-downs, and non-pharmaceutical interventions may play an important role in the reduction of respiratory viruses. Understanding the seasonal respiratory virus decline could help public health experts prepare for future respiratory virus pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhardwaj, Choudhary, Jadhav, Vipat, Ghuge, Salvi, Kulkarni, Kinikar, Padbidri, Bafna, Bavdekare, D'costa, Gujar and Potdar.)

Background: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV., Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression., Results: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018)., Conclusions: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen., Methods: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment., Results: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups)., Conclusions: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.)., (Copyright © 2022 Massachusetts Medical Society.)

Justification: Recent research has provided evidence for lack of transmission of SARS-CoV-2 through human milk and breastfeeding. Updating the practice guidelines will help in providing appropriate advice and support regarding breastfeeding during the coronavirus 2019 (COVID-19) pandemic., Objectives: To provide evidence-based guidelines to help the healthcare professionals to advise optimal breastfeeding practices during the COVID-19 pandemic., Process: Formulation of key questions was done under the chairmanship of President of the IAP. It was followed by review of literature and the recommendations of other international and national professional bodies. Through Infant and Young child (IYCF) focused WhatsApp group opinion of all members was taken. The final document was prepared after the consensus and approval by all members of the committee., Recommendations: The IYCF Chapter of IAP strongly recommends unabated promotion, protection and support to breastfeeding during the COVID-19 pandemic with due precautions.

Purpose of Review: In 2019, vaccine hesitancy (VH) was named as one of the top 10 threats to global health by the World Health Organization (WHO). We highlight the factors affecting VH, the role of VH in limiting vaccine uptake and inability to achieve collective immunity, and possible solutions., Recent Findings: There are still uncertainties and concerns about the safety and efficacy of vaccines, which promote VH and undermine public confidence in immunization. WHO has designed the behavioral and social drivers (BeSD) tools and survey instruments that can be used by countries to assess reasons for poor vaccine uptake in childhood for COVID-19 and plan national vaccination programs to counter these misconceptions., Summary: Vaccines are one of the best preventative measures that public health care has to offer. Evidence from across the world both in high-income countries (HICs) and low/middle-income countries (LMICs) show that VH is a significant phenomenon which is translating into geographical clustering of epidemics. A reasonably high acceptance and coverage rates are necessary for an immunization program to be successful. A context-specific and multifactorial intervention with more high-quality research is needed globally., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: There are few reports of COVID-19 in neonates and most are suspected to be due to postnatal transmission. Vertical transmission has been proven in only a couple of cases so far., Methods: We describe early-onset, severe COVID-19 disease in a neonate with very strong evidence of vertical transmission of SARS-CoV-2., Results: A COVID-19 suspected mother, who tested negative by RT-PCR for COVID, but tested positive for SARS-CoV-2 by serology, delivered a term baby. The neonate was kept in strict isolation. Molecular tests for SARS-CoV-2 on umbilical stump, placenta, and nasopharyngeal aspirate of the neonate, collected at birth were positive. On day 2, the neonate developed clinical features of COVID in the form of fever, poor feeding, and hyperbilirubenemia along with elevated inflammatory markers. Antibiotics were started empirically pending cultures. Blood, CSF, and urine cultures were sterile. Baby tested RT-PCR positive for SARS-CoV-2 on two more occasions before testing positive for antibodies and was discharged on day 21 of life., Conclusion: This report highlights a very strong possibility of vertical transmission of COVID-19 from a mildly symptomatic, RT-PCR negative but antibody-positive mother with significant symptomatic, early-onset neonatal infection.

Objectives: Household air pollution (HAP) is a risk factor for respiratory disease, however has yet to be definitively associated with tuberculosis (TB). We aimed to assess the association between HAP and TB., Methods: A matched case-control study was conducted among adult women and children patients with TB and healthy controls matched on geography, age and sex. HAP was assessed using questionnaires for pollution sources and 24-hour household concentrations of particulate matter <2.5 μm in diameter (PM 2.5 )., Results: In total, 192 individuals in 96 matched pairs were included. The median 24-hour time-weighted average PM 2.5 was nearly seven times higher than the WHO's recommendation of 25 µg/m 3 , and did not vary between controls (179 µg/m 3 ; IQR: 113-292) and cases (median 157 µg/m 3 ; 95% CI 93 to 279; p=0.57). Reported use of wood fuel was not associated with TB (OR 2.32; 95% CI 0.65 to 24.20) and kerosene was significantly associated with TB (OR 5.49, 95% CI 1.24 to 24.20) in adjusted analysis. Household PM 2.5 was not associated with TB in univariate or adjusted analysis. Controlling for PM 2.5 concentration, kerosene was not significantly associated with TB, but effect sizes ranged from OR 4.30 (95% CI 0.78 to 30.86; p=0.09) to OR 5.49 (0.82 to 36.75; p=0.08)., Conclusions: Use of kerosene cooking fuel is positively associated with TB in analysis using reported sources of exposure. Ubiquitously high levels of particulates limited detection of a difference in household PM 2.5 between cases and controls., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Household air pollution (HAP) is poorly characterized in low-income urban Indian communities., Materials and Methods: A questionnaire assessing sources of HAP and 24 h household concentrations of particulate matter less than 2.5 microns in diameter (PM 2.5 ) were collected in a sample of low-income homes in Pune, India., Results: In 166 homes, the median 24 h average concentration of PM 2.5 was 167 μg/m 3 (IQR: 106-294). Although kerosene and wood use were highly prevalent (22% and 25% of homes, respectively), primarily as secondary fuel sources, high PM 2.5 concentrations were also found in 95 (57%) homes reporting LPG use alone (mean 141 μg/m 3 ; IQR: 92-209). In adjusted linear regression, log PM 2.5 concentration was positively associated with wood cooking fuel (GMR 1.5, 95% CI: 1.1-2.0), mosquito coils (GMR 1.5, 95% CI: 1.1-2.1), and winter season (GMR 1.7, 95% CI: 1.4-2.2). Households in the highest quartile of exposure were positively associated with wood cooking fuel (OR 1.3, 95% CI: 1.1-1.5), incense (OR 1.1, 95% CI: 1.0-1.3), mosquito coils (OR 1.3, 95% CI: 1.1-1.6), and winter season (OR 1.2, 95% CI: 1.1-1.4)., Discussion: We observed high concentrations of PM 2.5 and identified associated determinants in urban Indian homes.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.

Syphilis is associated with increased human immunodeficiency virus acquisition and sexual transmission; we examined impact on human immunodeficiency virus mother-to-child transmission among mother-infant pairs enrolled in the India Six-Week Extended-Dose Nevirapine study. Maternal syphilis, diagnosed serologically using Venereal Disease Research Laboratory titer plus Treponema Pallidum Hemagglutination Assay, was associated with 2.5-fold greater risk.

Background: HIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life., Methods: Using data from a prevention of mother-to-child transmission (PMTCT) trial (India SWEN), where HIV-exposed breastfed infants were given extended nevirapine, we measured 12-month infant all-cause and cause-specific hospitalization rates and hospitalization risk factors., Results: Among 737 HIV-exposed Indian infants, 93 (13%) were HIV-infected, 15 (16%) were on HAART, and 260 (35%) were hospitalized 381 times by 12 months of life. Fifty-six percent of the hospitalizations were attributed to infections; gastroenteritis was most common accounting for 31% of infectious hospitalizations. Gastrointestinal-related hospitalizations steadily increased over time, peaking around 9 months. The 12-month all-cause hospitalization, gastroenteritis-related hospitalization, and in-hospital mortality rates were 906/1000 PY, 229/1000 PY, and 35/1000 PY respectively among HIV-infected infants and 497/1000 PY, 107/1000 PY, and 3/1000 PY respectively among HIV-exposed, uninfected infants. Advanced maternal age, infant HIV infection, gestational age, and male sex were associated with higher all-cause hospitalization risk while shorter duration of breastfeeding and abrupt weaning were associated with gastroenteritis-related hospitalization., Conclusions: HIV-exposed Indian infants experience high rates of all-cause and infectious hospitalization (particularly gastroenteritis) and in-hospital mortality. HIV-infected infants are nearly 2-fold more likely to experience hospitalization and 10-fold more likely to die compared to HIV-exposed, uninfected infants. The combination of scaling up HIV PMTCT programs and implementing proven health measures against infections could significantly reduce hospitalization morbidity and mortality among HIV-exposed Indian infants.