Healthcare provider perspectives on COVID-19 vaccination for children in India.

BACKGROUND: The rapid development and deployment of effective COVID-19 vaccines have been critical to halt the spread of the pandemic. India started vaccinating children in early 2022, however, vaccine uptake has been suboptimal. METHODS: Between September and November 2022, we conducted an online survey that was disseminated to eligible participants via email, text messages and social media platforms across India. The survey aimed to gather the perspectives of Indian healthcare providers regarding key factors related to the rollout of paediatric COVID-19 vaccines. Descriptive statistics were used to analyse participant demographics and responses on knowledge about paediatric COVID-19 vaccines, perceived risks and benefits, and vaccine rollout strategies. RESULTS: The survey yielded 805 respondents from 23 Indian states; 63.5% were men, 97.3% were paediatricians, median age was 44 years (IQR 25-81). Eighty-one per cent and 65.2% respondents had heard about the most common paediatric COVID-19 vaccines in India, Covaxin and Corbevax, but only 52.9%, 53.7% and 62.1% felt adequately informed about their safety, efficacy and vaccination schedules, respectively. Thirty per cent of respondents were unaware of vaccination guidelines. Eighty-five per cent of respondents felt that vaccines would reduce the incidence of severe disease, hospitalisation and deaths, and 60.6% felt children with comorbidities should be prioritised for vaccination. Perceived supply side barriers included lack of enforcement of guidelines (45.2%) and adverse effects following immunisation monitoring systems (37.6%), and on the demand side, parental vaccine hesitancy (64.4%). Eighty-one per cent believed that school-based vaccination strategies would be highly effective in increasing uptake. CONCLUSIONS: Most respondents were in support of the COVID-19 paediatric vaccination, although just over half did not feel adequately informed. Concerns about vaccine hesitancy among caregivers were the leading reported barrier. Targeted interventions are needed to provide adequate knowledge support to healthcare providers and evidence-based public health messaging to reduce vaccine hesitancy among caregivers.

The effect of the COVID-19 pandemic on influenza-related hospitalization, intensive care admission and mortality in children in Canada: A population-based study.

Background: The COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on the impact on paediatric influenza-related hospitalisations is limited. We describe influenza-related hospitalisation in children in Canada following the onset of the COVID-19 pandemic. Methods: Data on influenza-related hospitalisations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunisation Monitoring Program, ACTive (IMPACT). This national active surveillance initiative comprises 90% of all tertiary care paediatric beds in Canada. The study period included eleven influenza seasons, from the 2010/2011 season until the 2020/2021 season inclusive. Time series modelling was used to compare the observed to predicted influenza-related hospitalisations following the COVID-19 pandemic. Results: Following the COVID-19 pandemic there was a significant decrease in paediatric influenza-related hospitalisations compared to predicted influenza-related hospitalisations for this time period (p < 0•0001). No paediatric influenza-related hospitalisations, ICU admission or deaths were reported for the 2020/2021 influenza season. Conclusions: We show complete absence of paediatric influenza infection-related hospitalisation in a Canadian National Surveillance Network during the 2020/2021 influenza season. This significant decrease is likely related in large part to non-pharmacological public health interventions implemented during the COVID-19 pandemic, although the potential role of viral interference is unknown. Funding: The Canadian Immunisation Monitoring Program, Active (IMPACT) influenza surveillance is a national surveillance initiative managed by the Canadian Paediatric Society and conducted by the IMPACT network of paediatric investigators on behalf of the Public Health Agency of Canada's Centre for Immunisation and Respiratory Infectious Diseases.

COVID-19 vaccine acceptance among healthcare workers in India: Results from a cross-sectional survey.

Remarkable scientific progress has enabled expeditious development of effective vaccines against COVID-19. While healthcare workers (HCWs) have been at the frontline of the pandemic response, vaccine acceptance amongst them needs further study. We conducted a web-based survey to assess vaccine acceptance among HCWs in India between January and February 2021, shortly after the launch of India's vaccination campaign. Descriptive statistics were used to examine respondent demographics and Likert scale responses. Binomial logistic regression analyses were used to identify factors associated with vaccine acceptance. The survey yielded 624 respondents from 25 states and five union territories in India; 53.5% were male, and median age was 37 years (IQR 32-46). Amongst all respondents, 84.1% (525/624) supported COVID-19 vaccines, and 63.2% (141/223) of those unvaccinated at the time of survey administration were willing to accept a vaccine. Trust in government sources, healthcare providers or scientific journal articles for COVID-19 related information was reported by 66.8%, while confidence in social media for this information was reported by only 4.5%. Amongst those who had not yet received a COVID-19 vaccine, factors independently associated with vaccine acceptance included age (aOR 3.50 [95% CI, 1.04-11.76] for those above 45 years compared to younger HCWs aged 18-29 years), belief in vaccine effectiveness and safety (aOR 3.78 [95% CI 1.15-12.38]), and provision of free/no-cost vaccine (aOR 2.63 [95% CI, 1.06-6.50]). Most respondents (80%) were confident about their hospital being equipped to efficiently rollout COVID-19 vaccines to the general population. While overall attitudes towards COVID-19 vaccination were positive among HCWs in India, acceptance was lower among healthier and younger HCWs. Data availability on vaccine safety and effectiveness, and cost considerations were important for acceptance. Targeted interventions are needed to improve vaccine acceptance amongst HCWs, since they are critical in promoting vaccine acceptance amongst the general population.

Antiviral Use in Canadian Children Hospitalized for Influenza.

OBJECTIVES: Antivirals are recommended for children hospitalized with influenza but are underutilized. We describe antiviral prescribing during influenza admissions in Canadian pediatric centers and identify factors associated with antiviral use. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from 2010-2011 to 2018-2019. Logistic regression analyses were used to identify factors associated with antiviral use. RESULTS: Among 7545 patients, 57.4% were male; median age was 3 years (interquartile range: 1.1-6.3). Overall, 41.3% received antiviral agents; 72.8% received antibiotics. Antiviral use varied across sites (range, 10.2% to 81.1%) and influenza season (range, 19.9% to 59.6%) and was more frequent in children with ≥1 chronic health condition (52.7% vs 36.7%; P < .001). On multivariable analysis, factors associated with antiviral use included older age (adjusted odds ratio [aOR] 1.04 [95% confidence interval (CI), 1.02-1.05]), more recent season (highest aOR 9.18 [95% CI, 6.70-12.57] for 2018-2019), admission during peak influenza period (aOR 1.37 [95% CI, 1.19-1.58]), availability of local treatment guideline (aOR 1.54 [95% CI, 1.17-2.02]), timing of laboratory confirmation (highest aOR 2.67 [95% CI, 1.97-3.61] for result available before admission), presence of chronic health conditions (highest aOR 4.81 [95% CI, 3.61-6.40] for cancer), radiographically confirmed pneumonia (aOR 1.39 [95% CI, 1.20-1.60]), antibiotic treatment (aOR 1.51 [95% CI, 1.30-1.76]), respiratory support (1.57 [95% CI, 1.19-2.08]), and ICU admission (aOR 3.62 [95% CI, 2.88-4.56]). CONCLUSIONS: Influenza antiviral agents were underused in Canadian pediatric hospitals, including among children with high-risk chronic health conditions. Prescribing varied considerably across sites, increased over time, and was associated with patient and hospital-level characteristics. Multifaceted hospital-based interventions are warranted to strengthen adherence to influenza treatment guidelines and antimicrobial stewardship practices.

Shifting research priorities in maternal and child health in the COVID-19 pandemic era in India: A renewed focus on systems strengthening.

BACKGROUND: The remarkable progress seen in maternal and child health (MCH) in India over the past two decades has been impacted by the COVID-19 pandemic. We aimed to undertake a rapid assessment to identify key priorities for public health research in MCH in India within the context and aftermath of the COVID-19 pandemic. METHODS: A web-based survey was developed to identify top research priorities in MCH. It consisted of 26 questions on six broad domains: vaccine preventable diseases, outbreak preparedness, primary healthcare integration, maternal health, neonatal health, and infectious diseases. Key stakeholders were invited to participate between September and November 2020. Participants assigned importance on a 5-point Likert scale, and assigned overall ranks to each sub-domain research priority. Descriptive statistics were used to examine Likert scale responses, and a ranking analysis was done to obtain an "average ranking score" and identify the top research priority under each domain. RESULTS: Amongst the 84 respondents from across 15 Indian states, 37% were public-health researchers, 25% healthcare providers, 20% academic faculty and 13% were policy makers. Most respondents considered conducting systems strengthening research as extremely important. The highest ranked research priorities were strengthening the public sector workforce (vaccine preventable diseases), enhancing public-health surveillance networks (outbreak preparedness), nutrition support through community workers (primary care integration), encouraging at least 4-8 antenatal visits (maternal health), neonatal resuscitation to reduce birth asphyxia (neonatal health) and screening and treatment of tuberculosis (infectious diseases). Common themes identified through open-ended questions primarily included systems strengthening priorities across domains. CONCLUSIONS: The overall focus for research priorities in MCH in India during the COVID-19 pandemic is on strengthening existing services and service delivery, rather than novel research. Our results highlight pivotal steps within the roadmap for advancing and sustaining maternal and child health gains during the ongoing COVID-19 pandemic and beyond.

Re-thinking treatment strategies for febrile neutropenia in paediatric oncology population: the perspective from a developing country.

BACKGROUND: This study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly. METHODS: A prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. One hundred and thirty children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS. RESULTS: One hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 48 (52.2%) Gram negative isolates followed by 33 (35.8%) Gram positive isolates, six (6.5%) fungal isolates and five (5.5%) poly-microbial cultures. Lactose fermenting Gram negative bacilli (20 isolates, 31.5%) were the most frequently isolated in the Gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst the Gram positive coagulase negative staphylococcus was the most common (twenty seven isolates, 29%). Escherichia coli and Non lactose fermenting gram negative bacteria (NFGNB) had only 36, 25% sensitivity to ceftazidime, respectively. Most Gram negative bacilli were found to have better sensitivity to amikacin (mean: 57%). There was a higher prevalence of extended spectrum beta lactamase producing organisms. Pan drug resistance, Extreme drug resistance and Multi drug resistance was found in three, twenty and thirteen Gram negative isolates respectively.Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with Gram negative isolates (eight deaths out of the thirteen deaths, 61.5%). CONCLUSIONS: Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant Gram negative bacilli, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.

Comparing COVID-19 vaccine allocation strategies in India: A mathematical modelling study.

BACKGROUND: The development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions. METHODS: We used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations. RESULTS: Prioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination. CONCLUSIONS: Our findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.

Burden of cytomegalovirus DNAemia among pediatric renal transplant patients on antiviral prophylaxis: A hospital-based analysis.

INTRODUCTION: We examined the burden of CMV DNAemia and time to such events among renal transplant patients receiving CMV prophylaxis. We targeted the first year after transplantation, with the primary focus being on the first 3 months. METHODS: We conducted a retrospective review of renal transplant patients (<18 years) who were transplanted and followed at our center between January 2007, and December 2017. Clinical and laboratory data were obtained from the medical records and laboratory databases. RESULTS: Among 141 patients, the median age at transplant was 12.7 years (range 0.87-17.83 years). CMV DNAemia was detected in 33 of 77 patients eligible for prophylaxis (42.9%; 95% CI 31.6-54.6) during the first post-transplant year. Proportionately more D+R- patients were present among patients with DNAemia compared with those without DNAemia (15/38, 39.5% vs 16/103, 15.5%, P = .005). Median time to first positivity was 134 days (range 0-304 days). Eight patients had a positive PCR during the first 3 months (5.7% of all patients). Among those eligible for prophylaxis, 6.5% had DNAemia during the first 3 months while on prophylaxis. Among patients whose first positive PCR was after 3 months post-transplant, the median time to positivity was 52 days (range 13-214 days) after the end of prophylaxis. CONCLUSIONS: Breakthrough CMV DNAemia was documented among children receiving antiviral prophylaxis. While routine monitoring while on prophylaxis might not be warranted for the majority of patients, studies are needed to determine the optimal indications for CMV PCR testing while on prophylaxis.

Disclosure of HIV Status to Infected Children in South India: Perspectives of Caregivers.

This study was designed to examine the rates of HIV serostatus disclosure in a sample of HIV-infected children in the state of Karnataka in South India, their reactions to learning their HIV-positive status and the reasons for and barriers to disclosure from the point of view of their caregivers. We enrolled 233 HIV-infected children, aged 5-18 years and their caregivers between July 2011 and February 2013 at HIV clinics in three tertiary care centers. Caregiver interviews included information about demographic characteristics, medical history, type of disclosure to the child and other related factors, including disclosure barriers. Three quarters (n = 185) of the caregivers reported that there had been no disclosure to the child, 15.4% (n = 38) reported partial disclosure (e.g. telling the child he or she had a 'chronic illness') and only 9.7% (n = 24) reported full disclosure, at a mean age of 10.9 (SD: 2.5) years. Caregivers, who planned to disclose in the future, stated on average that 16 years would be the right age. Those who favored a later disclosure reported that they feared strong negative emotional reactions from the child (p = 0.03) and social isolation (p < 0.001) following disclosure. These results show that that the level of full disclosure is low among South Indian youth living with HIV, and that when disclosure occurs, it is most likely to be partial. The majority of children who learned their status had been informed by a health-care provider, possibly reflecting the difficulty for a caregiver of having this conversation. The caregivers reported multiple disadvantages of disclosure, mostly because of fears of stigma and discrimination. Despite some evidence from the literature that disclosure can have positive effects on a child's health, it is thus clear that we need to develop, implement and evaluate community-based stigma reduction programs to reduce the social barriers to disclosure.

Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.

Nevirapine, a component of antiretroviral therapy (ART) in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period'), and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC) at days 7, 14 (lead-in period) and 28 (full dose period) after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years) included in the study, sub-therapeutic trough plasma nevirapine concentration (<4µg/ml) was seen in 65% (13/20) of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 µg/ml, significantly lower than 8 µg/ml, the concentration achieved at week 4 (p = 0.034). Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4µg/ml) during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

The Epidemiology of IRIS in Southern India: An Observational Cohort Study.

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon but dynamic phenomenon seen among patients initiating antiretroviral therapy (ART). We aimed to describe incidence, risk factors, clinical spectrum, and outcomes among ART-naive patients experiencing IRIS in southern India. Among 599 eligible patients monitored prospectively between 2012 and 2014, there were 59.3% males, with mean age 36.6 ± 7.8 years. Immune reconstitution inflammatory syndrome incidence rate was 51.3 per 100 person-years (95% confidence interval: 44.5-59.2). One-third (31.4%) experienced at least 1 IRIS event, at a median of 27 days since ART initiation. Mucocutaneous infections and candidiasis were common IRIS events, followed by tuberculosis. Significant risk factors included age >40 years, body mass index <18.5 kg/m2, CD4 count <100 cells/mm3, viral load >10 000 copies/mL, hemoglobin <11 g/dL, and erythrocyte sedimentation rate >50 mm/h. Immune reconstitution inflammatory syndrome-related morality was 1.3% (8 of 599); 3 patients died of complicated diarrhea. These findings highlight the current spectrum of IRIS in South India and underscore the importance of heightened vigilance for anemia and treatment of diarrhea and candidiasis during ART initiation.

Prevalence and Correlates of HIV Disclosure Among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review.

OBJECTIVE: Disclosure of HIV status among children and adolescents living with HIV has both beneficial and challenging aspects. To address existing knowledge gaps and update the literature on childhood disclosure, we conducted a systematic review on caregivers' perceptions and practices of HIV disclosure in low- and middle-income countries (LMICs). METHODS: Standard databases were searched for studies conducted in LMICs, published in English between 2004 and 2015. Excluded articles were reviews or case reports, and those not reporting childhood disclosure. Data regarding prevalence, correlates and impact of disclosure, were presented as frequencies. RESULTS: Two authors independently screened 982 articles. After applying eligibility criteria, 22 articles representing 12 countries and 2,843 children were reviewed. The proportion of fully disclosed children ranged from 1.7% to 41.0%. Up to 49.5% children were provided "deflected" information (use of a non-HIV-related reason for explaining illness and health care visits). Factors associated with full disclosure included antiretroviral treatment initiation and caregivers' felt need for maintaining optimal adherence. Barriers to disclosure included fear of negative psychological reactions and inadvertent disclosure to others. Caregivers perceived a strong need for active participation from health care providers to aid the process of disclosure. CONCLUSIONS: Full disclosure of HIV status was not common among children and adolescents in LMICs, while the practice of deflected disclosure was prominent. Caregivers perceived the need for support from health care providers during the disclosure process. Evidence-based guidelines incorporating the developmental status of the child, locally prevalent cultures, and caregiver perceptions are prerequisite to enhancing disclosure in these settings.

Hepatitis A Associated with Chylothorax: An Uncommon Presentation of a Common Infection.

Extra-hepatic manifestations have seldom been described with hepatitis A, which usually manifests as mild hepatic dysfunction. We report a 3-year-old boy presenting with 3 days of fever, vomiting, abdominal distention and scleral icterus. On examination, he had tachypnea, hepatosplenomegaly, ascites and right-sided pleural effusion. A diagnostic pleural tap yielded a milky, lymphocyte-predominant exudative aspirate, with pleural fluid triglycerides of 175 mg/dl, suggestive of chylothorax. Serology for anti-HAV IgM was positive in both blood and pleural fluid. The massive effusion causing collapse of the underlying lung was drained by tube thoracostomy, which was followed by complete resolution within 2 weeks. This is the first reported case of chylothorax associated with hepatitis A infection. This report highlights that pleural effusion associated with hepatitis A infection is usually a benign, self-limiting condition which should be considered in the differential diagnosis of pleural effusion or chylothorax in a patient with acute viral hepatitis.

Clinical profile, aetiology and outcome of afebrile seizures in children.

INTRODUCTION: Clinical and outcome profiles of childhood seizures can be different in resource limited settings where neurologists face lots of challenges in diagnosis and management of seizure. This study was conducted to investigate the clinical profile, causes and outcome of afebrile seizures in children in resource limited settings. METHODS: This was a prospective hospital based study. Children with afebrile seizures were followed up with exclusion of febrile and acute provoked seizures. Clinical, investigation, treatment and outcome parameters were analyzed. RESULTS: Study included 308 (age one month to 20 years) children. Median age at first seizure was 39 (inter quartile range 12-96) months. History of status epilepticus was present in 26.0%. Cause of seizure was known in 44.2%. Seizure was generalized in 79.2%, partial in 14.0% and unclassified in 6.8%. Common causes of seizure were - birth asphyxia (12.3%), neurocysticercosis (8.8%), sequel of nervous system infection (6.5%) and structural brain abnormalities (7.1%). Neurological examination, electroencephalography and computed tomography (CT) were abnormal in 24.4%, 70.5% and 27.9% cases respectively. Seizure control was achieved in 79.3% and by monotherapy in 85.0 % cases. Seizure control with single drug, seizure without recurrence and idiopathic seizure were associated with favourable outcome. CONCLUSIONS: Prevention and control of birth asphyxia, neurocysticercosis and nervous system infections are needed to reduce the burden of afebrile seizures in this area. CT is a valuable diagnostic tool and response to monotherapy is good. Seizure control with single drug, seizure without recurrence and idiopathic seizure are favourable prognostic factors.