Analytical Study of a Case Series of Vancomycin Associated Adverse Drug Reactions in Paediatric Population at a Tertiary Care Hospital: A Brief Report

Background: Red man syndrome (RMS) is frequently reported from pediatric ward in patients receiving vancomycin, at the medical store of SGH, Pune. Though common in pediatric patients, not all patients receiving vancomycin developed Red man syndrome. Hence, this study was done to analyse the demographic, pathophysiological, and pharmacological aspects of the subject who experience adverse drug reactions with vancomycin and to determine if this predisposition is associated with any of these factors. Methods: All adverse drug reactions (ADR) to injection vancomycin in the pediatric ward that were reported from April 2018 - January 2022 were included. Controls were a similar number of randomly selected pediatric cases from the same ward who had received Intravenous vancomycin during the same period but did not experience the adverse drug reactions Results: The mean age was 29.91 ± 34.87 months in subjects who experienced ADR and 57.37 ± 41.58 months, in non-ADR group (p=0.0286). 37.4% were infants, 29.69% toddlers in ADR Group. Seventy four percent of patients who manifested with ADR were below age of 3 compared to barely 38% in controls (p=0.03). 66.6% were malnourished in the ADR group compared to 27.6% in controls (p=0.007). There was no association between the ADR and ethnicity, religion, gender, diagnosis, co-morbidities, co-administered drugs, or administered dose of vancomycin among the children. There was no apparent seasonal variation in occurrence of the ADR.Conclusion: RMS is more common in paediatric population than adults and is usually uneventful. Around 75% of the reactions occur within first 4 days of start of Vancomycin and usually occurs within 30 min of the preceding dose. Younger age groups (infants) and malnourishment were the two factors significantly associated with occurrence of RMS. We may also consider using lower than conventional doses and much slower infusions in such at-risk population

Screening of Extended Family Members of Thalassemia Major Children as a Thalassemia Preventive Strategy

BACKGROUND: Thalassemia is considered as the most common single gene disorder worldwide. Preventive measures include identification of thalassemia carriers (traits) through screening, genetic counselling and prenatal diagnosis to reduce the incidence. This study aims at estimating the prevalence of carrier status detection among the extended family members of children having thalassemia major so as to use it as a screening prevention strategy with appropriate counselling. METHODS: This cross-sectional study was conducted in thalassemia unit of Pediatric Department of a tertiary care teaching hospital over a period of 18 months. Blood samples were collected from 117 extended family members (EFM) of 23 children with thalassemia major to carry out investigations such as Complete Blood Counts (CBC), Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT), Reticulocyte count, High Performance Liquid Chromatography(HPLC) and serum ferritin. Reports were analysed to find out the prevalence of carriers. RESULTS: Among 117 EFM, 62 (52.9%) were males while 55(47.1%) were females. Mean age distribution in this study was 16.49 years (8.5). Prevalence of thalassemia trait (carrier) was 35%. NESTROFT test was positive in 57(48.7%) participants. The binary logistic regression found only positive NESTROFT test as a predictor (adjusted OR=0.022, P=0.001) of having raised HbA2 (HbA2≥3.5 %). CONCLUSION: Screening of thalassemia carrier by targeting extended family members of thalassemia major children could yield more carrier cases and targeted counselling could help effectively in decreasing the number of children born with thalassemia major. This strategy could be included in future plan of national prevention programme for thalassemia

Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

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

High Rates of All-cause and Gastroenteritis-related Hospitalization Morbidity and Mortality among HIV-exposed Indian Infants

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Integration of HIV care into maternal and child health services in the global IeDEA consortium

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

Integration of HIV care into maternal and child health services in the global IeDEA consortium

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

Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.

BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial

Background: Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. Methods/design: SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Discussion: Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smearnegative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. Trial registration: International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017