Immune-compromised Children Research Articles

Population Pharmacokinetics of Posaconazole in Immune-Compromised Children and Assessment of Target Attainment in Invasive Fungal Disease.

Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure. The goal of this study was to characterize the population pharmacokinetics (PK) of PSZ in immunocompromised children and assess therapeutic target attainment. Serum concentrations of PSZ were collected retrospectively from records of hospitalized patients. A population PK analysis was performed in a nonlinear mixed-effects modeling framework with NONMEM (v7.4). The PK parameters were scaled to body weight, then potential covariate effects were assessed. The final PK model was used to evaluate recommended dosing schemes through simulation of target attainment (as a percentage of the population having steady-state trough concentrations above the recommended target) using Simulx (v2021R1). Repeated measurement data of 202 serum concentrations of total PSZ were acquired from 47 immunocompromised patients between 1 and 21 years of age receiving PSZ either intravenously or orally, or both. A one-compartment PK model with first-order absorption and linear elimination best fit the data. The estimated absolute bioavailability (95% confidence interval) for suspension (Fs) was 16% (8-27%), which was significantly lower than the reported tablet bioavailability (Ft) [67%]. Fs was reduced by 62% and 75% upon concomitant administration with pantoprazole (PAN) and omeprazole (OME), respectively. Famotidine resulted in a reduction of Fs by only 22%. Both fixed dosing and weight-based adaptive dosing provided adequate target attainment when PAN or OME were not coadministered with the suspension. The results of this study revealed that both fixed and weight-based adaptive dosing schemes can be appropriate for target attainment across all PSZ formulations, including suspension. Additionally, covariate analysis suggests that concomitant proton pump inhibitors should be contraindicated during PSZ suspension dosing.

Perceptions on the use of distance learning by families of children with visual impairment and deafblindness

The purpose of our qualitative study was to explore what distance-based teaching and learning practices have been supportive to students with visual impairments and their families. Using purposive sampling, interviews, and qualitative analysis, we found that supportive approaches for distance learning (DL) included parental involvement and participation, as well as tailored instructional approaches and accommodations for the student. In some instances, DL was identified as being more supportive for immune-compromised children. Negative facets of the practice included diminished richness in socializing, and the lack of certain strengths of in-person education. Families’ experiences ranged from finding DL helpful, to considering the practice as unfit for their child’s education, as well as a poor fit for family life. Flags for future research include family preparation for future DL needs, including culturally-diverse families in research opportunities, and evaluating what DL supports lead to improved outcomes for children and families.

Parasitic infections in Swiss children: Are we overtesting?

BackgroundA wide variation of causes can lead to gastrointestinal symptoms in children- an infection with parasites is one of them. The expansion of international travel might lead to an increase in testing children for a correspondent infection. Currently there are no guidelines available, which patients should be tested for a possible parasitical infection.The aim of the study was to characterize Swiss children suffering from intestinal parasites, in order to provide more knowledge for the clinician who should be tested.MethodsThis is a retrospective study of Swiss pediatric patients, whose stools have been tested for parasites and helminths.ResultsA total of 1855 stool samples, belonging to 572 different children with an average age of 7.9 years, were tested within a 10-year period. The prevalence of a positive result was 4.2%, of which all were positive for Blastocystis, and 12.5% had a co-infection with Endolimax nana.ConclusionImmigrants, immune compromised children with diarrhea and pediatric patients with bloody or protracted diarrhea should have 2 different stool specimens examined for a possible parasitical infection.

Study of pattern of morbidity in children under 5 years and effect of Swarnaprashan on morbidity status

Background: Infant and child mortality and morbidity remain a challenge especially in the developing world. More than half of the children (53.7%) are suffering from some form of illness. Recurrent respiratory infection, recurrent diarrhea, recurrent fever, etc. are the most common causes of morbidity in immune-compromised children. In India, 15% of death occurs during infancy and 1-5 years of age are due to respiratory infections. Diarrhea constitutes the most important cause of chronic morbidity followed by malnutrition. The objective of this research was to study the effect of swarnaprashan on morbidity status of the children under five years of age. Methods: A randomized, open-label study was conducted on 60 children of 06 months to 5 years of age and were randomly divided into two groups (30 in each). In Group A, trial drug (Swarnaprashan) was given and in Group B, there was regarded as 'No treatment concurrent control'. Results: In group A where trial drug (Swarnaprashan) was given, improvement in morbidity features were found whereas in group B which was 'No treatment concurrent control', 'not significant' results were obtained. Conclusion: Present research reveals that swarnaprashan works as an immune-modulator which decreased the morbidity rate and therefore can be a simple remedy to bring down the morbidity rate in children.

Acute Flaccid Myelitis-Possible Link with Electro-Magnetism? A Hypothesis Stimulating Study

“Wonder grows when knowledge fails” (Francis Bacon 1561-1626) A new polio-like condition mainly affecting children (mean 5 years old) is being observed, starting with viral and respiratory symptoms, followed by a demyelination paralysis. Known as Acute Flaccid Myelitis, first identified in 2010 in America, 28% to 95% of cases are associated with Enterovirus EVD68. Yet EVD68 itself was identified decades previously in China and the Netherlands. Prior to hospitalisation some children had no evidence of neurological symptoms, hinting a possible environmental trigger. Acute hospitals have multiple sources of background Electro-Magnetic-Field (EMF), some above recommended safety levels. Hence the hypothesis “Are critical rises in human background electromagnetism, interacting with other environmental factors, possibly a casual factor, in Acute Flaccid Myelitis? “There is evidence that low frequency EFM creates cellular oxidative stress leading to neurodegeneration. Mechanisms are unclear but could ubiquitous background EMF play a role in children’s vulnerability to EVD68? The context of the hypothesis is the evidence of accelerating rates of neurological morbidity in the 21st Century and whether the range and multiplicity of environmental factors are impacting upon an immune-compromised child’s neurology. As health environmental factors were ignored in the past, e.g. smoking and asbestos, another possible environmental linked anomaly is feared, though we note the recent establishment of the UK Acute Flaccid Paralysis Task Force in 2019. This hypothesis, whilst remaining speculative, needs to be refuted through independent research to ensure that AFM is not another children’s neurological condition, which once were rare but now becoming more commonplace.

A STUDY ON DEMOGRAPHIC STATUS OF MORBIDITY PATTERN IN CHILDREN UNDER 5 YEARS

Children are more susceptible to infections due to less immunity power. Frequent illnesses among children influence adversely on their growth and development. So the health status of this vulnerable age group (under 5 years age) is very much important as morbidities affect their health which influences the overall health status of the country. More than half of the children (53.7%) are suffering from some form of illness. Recurrent respiratory infection, recurrent diarrhea, recurrent fever, etc. are the most common causes of morbidity in immune-compromised children. The present study was planned to provide the demographic status of the morbidity pattern in children less than 5 years in a defined population. A cross sectional study was conducted from July 2018 to February 2019 by attending and participating in various health camps in various villages in periphery of Jaipur organized by PG Department of Kaumarabhritya, NIA, Jaipur. The sample size was calculated 501 (n = 501). All children from 06 months to 5 years were included in the study. During the study period, the sample size was 501, in which 187 (37.33%) children were found with morbidity features of either sex. Mainly 161 (32.14%) subjects were infected with recurrent RTIs, 98 (19.56%) subjects with anemia, 63 (12.57%) subjects with recurrent fever, 26 (5.19%) subjects with recurrent diarrhea and 17 (3.39%) subjects with skin infections. For enhancing the immunity of children and awareness about health, many Swarnaprashana camps and health checkup camps in various preschools situated in Jaipur were organized by PG Department of Kaumarabhritya, NIA and Jaipur.

COVID Operation Theatre- Advisory and Position Statement of Indian Society of Anaesthesiologists (ISA National).

COVID Operation Theatre- Advisory and Position Statement of Indian Society of Anaesthesiologists (ISA National).

Evaluating the Effect of Nutritional Supplementation Combined with Counseling on Nutritional Recovery in Immune-Compromised Indian Children

Background: Malnutrition in an HIV-infected child leads to muscle wasting, micronutrient deficiency, impaired immune system and reduced ability to fight infections. It also increases the susceptibility to infections due to an increased oxidative stress. Chronic oxidative state can weaken immune systems fight against HIV. Aim: The present study was undertaken to assess the impact of nutritional supplementation on the HIV progression. Methods: This open, prospective, interventional, case control pilot study was conducted in 100 HIV infected children, age between 6 months to 15 years, fulfilling criteria of Moderate Acute Malnutrition (MAM) and criteria of thinness based on Body Mass Index as per WHO definition, either not on ART and/or on ART but failing to gain weight as observed in 2 consecutive visits. Study and control group had 50 subjects each. Intervention comprised of multigrain-micronutrient-rich laddus along with counseling for a period of 6 months for cases. Controls received nutritional counseling along with standard care. Results: The male to female ratio was 2:1, median age being 132 months in cases and 120 months in controls. The mean weight was 24.53 kg in cases and 21.46 kg in controls after 6 months (p=0.03). The mean gain in height after 6 months of intervention was 2.96 cm in cases and 2.19 cm in controls (p=0.007). The CD4 counts and antioxidant levels were statistically non-significant but showed improving trends. Conclusions: Energy dense micronutrient rich supplementation will prevent the HIV progression.

Incidence and consequences of varicella in children treated for cancer in Guatemala.

Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many highincome countries, but in most low-income and middleincome countries, the burden of varicella in children treated for malignancy is poorly defined. We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost. Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquantile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD. Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden.

Safety and effectiveness of percutaneous cholecystostomy in critically ill children who are immune compromised.

Acalculous cholecystitis is known to develop in critically ill patients without cystic duct obstruction. In the past, treatment for acalculous cholecystitis has been cholecystectomy; however, many children who are critically ill are Percutaneous cholecystostomy is likely the procedure of choice in this subgroup of patients. To assess the safety and effectiveness of percutaneous cholecystostomy in critically ill and immune-compromised children with acalculous cholecystitis. Retrospective review of immune-compromised and critically ill children who underwent percutaneous cholecystostomy between 2006 and 2013. Diagnostic imaging performed included ultrasound, CT and hepatobiliary scintigraphy. Every percutaneous cholecystostomy was performed using imaging guidance. Ten critically ill and immune-compromised children with acalculous cholecystitis underwent percutaneous cholecystostomy. Seven boys and 3 girls, ranging in age from 10months to 15years 8months, were treated. Six of the immune-compromised children had received a bone marrow transplant for leukemia (5 children) or severe combined immunodeficiency (SCID) (1 child), and ranged from 18 to 307days post bone marrow transplant at the time of their percutaneous cholecystostomy. Of the remaining four immune-compromised children with acalculous cholecystitis who underwent percutaneous cholecystostomy, two had leukemia, one had SCID and lymphoma, and the fourth was undergoing treatment for undifferentiated germ cell tumor. The 10 percutaneous gallbladder drains were placed using a transhepatic approach, except one unintentional transperitoneal approach. There were no complications. Three gallbladder drains were removed in Interventional Radiology. Those three patients had a return to normal gallbladder function and didn't require cholecystectomy. Two drains were removed during cholecystectomy and another as an outpatient. Four patients died in the hospital due to multiorgan system failure, with indwelling gallbladder drains. Percutaneous cholecystostomy is a safe procedure in immune-compromised and critically ill children with acalculous cholecystitis. Percutaneous cholecystostomy may obviate the need for future cholecystectomy.

Clinical Profile of Dengue Infection in Immune-compromised Children.

Review of records of children admitted with dengue infection was carried out to compare clinical and laboratory parameters, course of illness, and outcome between immune-compromised and immune-competent patients. Statistically significant differences were found in days to platelet recovery (P=0.03), hepatic dysfunction (P= 0.04), and higher requirement of fluid (P= 0.01) in immune-compromised group.

Vaccines, School Mandates, and California's Right to Education

California recently enacted Senate Bill 277, which abolishes the personal-beliefs exemption to school immunization requirements. One possible challenge to the law’s constitutionality is that it impermissibly limits the right to education. This Essay rebuts such positions. California’s jurisprudence regarding access to education applies to protected categories; it does not limit the ability of the state to impose health and safety regulations such as immunization requirements. Moreover, the requirement would withstand even strict scrutiny, if applied, because disease prevention in the school context is a compelling interest and there is no alternative that is as effective. Finally, the law actually protects the right of access to education for those whose parents do not have the luxury of choice, such as immune-compromised children, while still reasonably preserving parental choice overall.

Demographic and Clinical Characteristics of Campylobacter Bacteremia in Children With and Without Predisposing Factors

Campylobacter, a common cause of childhood gastroenteritis, rarely causes bacteremia, which is reported mainly in immune-compromised children. Our aim was to compare demographic and clinical characteristics of childhood campylobacter bacteremia (CB) between children with and without risk factors for CB. A retrospective, population-based study, conducted between 1989 and 2010. Risk factors were defined as immunodeficiency, malignancy, extreme prematurity or chronic diseases with malnutrition. Seventy-six CB episodes (1 per child/month) were identified in 14 children with risk factors (30 episodes) and 46 children without risk factors (46 episodes). Children with risk factors were older (mean age 120.0±72.8 vs. 16.2±27.6 months) with higher proportion of males (90.0% vs. 60.9%), less gastrointestinal symptoms (43.3% vs. 69.9%) and higher hospitalization rates (96.7% vs. 69.6%) compared with children without risk factors. Campylobacter jejuni and Campylobacter coli (46/47 of identified species) were the most common species in both groups. Positive campylobacter stool cultures were found only in children without risk factors (0% vs. 38.5%). No mortality cases were observed. All isolates tested for antibiotic susceptibility were sensitive to macrolides and carbapenems. Childhood CB is rare in southern Israel. The disease manifests as a single gastroenteritis complication in a previously healthy young child or as recurrent episodes in an older, immune-compromised child, usually without gastrointestinal symptoms. This disparity may reflect pathogenesis differences, with disease in the immune-competent being dependent on pathogen virulence, whereas disease in the immune-compromised being host dependent. Disease outcome is usually favorable, and macrolides remain the antibiotic treatment of choice.

P2.170 Outcomes of Isoniazid Prophylaxis Among HIV-Infected Children in Routine Clinical Settings in Kenya

BackgroundIn 2011, the TB and HIV control programmes commenced a phased isoniazid prophylaxis therapy (IPT) implementation in selected public hospitals in Kenya. We report outcomes from the first three public...

Current ciprofloxacin usage in children hospitalized in a referral hospital in Paris

BackgroundFluoroquinolones are used with increasing frequency in children with a major risk of increasing the emergence of FQ resistance. FQ use has expanded off-label for primary antibacterial prophylaxis or treatment of infections in immune-compromised children and life-threatening multi-resistant bacteria infections. Here we assessed the prescriptions of ciprofloxacin in a pediatric cohort and their appropriateness.MethodsA monocenter audit of ciprofloxacin prescription was conducted for six months in a University hospital in Paris. Infected site, bacteriological findings and indication, were evaluated in children receiving ciprofloxacin in hospital independently by 3 infectious diseases consultants and 1 hospital pharmacist.ResultsNinety-eight ciprofloxacin prescriptions in children, among which 52 (53.1%) were oral and 46 (46.9%) parenteral, were collected. 45 children had an underlying condition, cystic fibrosis (CF) (21) or an innate or acquired immune deficiency (24). Among CF patients, the most frequent indication was a broncho-pulmonary Pseudomonas aeruginosa infection (20). In non-CF patient, the major indications were broncho-pulmonary (25), urinary (8), intra-abdominal (7), operative site infection (5) and bloodstream/catheter (2/4) infection. 62.2% were microbiologically documented. Twenty-three (23.4%) were considered “mandatory”, 48 (49.0%) “alternative” and 27 (27.6%) “unjustified”.ConclusionIn our university hospital, only 23.4% of fluoroquinolones prescriptions were mandatory in children, especially in Pseudomonas aeruginosa healthcare associated infection. Looking to the ecological risk of fluoroquinolones and the increase consumption in children population we think that a control program should be developed to control FQ use in children. It could be done with the help of an antimicrobial stewardship team.

PA02.14. A review on immunomodulator activity of Yashtimadhu (Glycyrriza Glabra).

Purpose:Recurrent respiratory infection, diarrhoea etc. are the most common causes of morbidity in immune compromised children. Majority of children below the age of 5 years do get 7–8 episodes of cold per year. In developing countries about 15 million children under the age of 5 years die each year. Respiratory infection account for 4 million of deaths. In India 15% of death occurs during infancy and 1–5 years of age are due to respiratory infections. This statistic shows that children are more vulnerable to infection because their immune system is less or under developed. At this age any intervention which could motivate their immune system, may prove boon to them. Ayurveda with its concept of Rasayana is holding various medicinal plants which are excellent immunomodulator and capable to reduce the morbidity status.Method:Peer review journals were searched to list all medicinal plants with immunomodulator activities, particularly acting on recurrent respiratory infection and recurrent diarrhoeal episodes. Only full texts in English were accepted for the present study.Result:Out of all research Yashtimadhu (Glycyrrhiza glabra) was found potent to reduce morbidity rate. It is very cost effective, easily available with highest immunomodulator properties.Conclusion:Review suggests there are studies which confirms immunomodulatory effect of Yashtimadhu but recommend further extensive study.

Acute Encephalopathy in the Immune-compromised Child

Toxoplasma gondii is an opportunistic parasite, which very unusually may cause acute encephalitis in patients undergoing chemotherapy or hematopoietic stem cell transplant. The prognosis is usually dismal also because of late diagnosis, depending on the limited availability of specific diagnostic tools. An early diagnosis allows effective intervention with specific antibiotics, which may provide a chance for cure. We report 2 cases of cerebral toxoplasmosis in which the use of polymerase chain reaction on cerebrospinal fluid allowed a prompt diagnosis and specific therapy, which was followed by clinical response and negativization at follow-up studies of T. gondii genome on cerebrospinal fluid by polymerase chain reaction and by brain imaging.

Interferon-γ Release Assays for the Diagnosis of Mycobacterium Tuberculosis Infection in Children: A Literature Review

The role of interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51-93 percent for QFT-G/QFT-G-IT and 40-100 percent for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35 percent). Most of the studies on young (less than 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4 percent. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children less than 5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.

Erratum: Treatment with oral ribavirin and IVIG of severe human metapneumovirus pneumonia (HMPV) in immune compromised child

Erratum: Treatment with oral ribavirin and IVIG of severe human metapneumovirus pneumonia (HMPV) in immune compromised child

Treatment with oral ribavirin and IVIG of severe human metapneumovirus pneumonia (HMPV) in immune compromised child

Treatment with oral ribavirin and IVIG of severe human metapneumovirus pneumonia (HMPV) in immune compromised child