Functional Outcomes and Morbidity in Pediatric Sepsis Survivors: A Tanzanian Experience

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was “decline in functional status,” as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a “decline in functional status.” Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS.

Developing a prediction model to estimate the true burden of respiratory syncytial virus (RSV) in hospitalised children in Western Australia

Respiratory syncytial virus (RSV) is a leading cause of childhood morbidity, however there is no systematic testing in children hospitalised with respiratory symptoms. Therefore, current RSV incidence likely underestimates the true burden. We used probabilistically linked perinatal, hospital, and laboratory records of 321,825 children born in Western Australia (WA), 2000–2012. We generated a predictive model for RSV positivity in hospitalised children aged < 5 years. We applied the model to all hospitalisations in our population-based cohort to determine the true RSV incidence, and under-ascertainment fraction. The model’s predictive performance was determined using cross-validated area under the receiver operating characteristic (AUROC) curve. From 321,825 hospitalisations, 37,784 were tested for RSV (22.8% positive). Predictors of RSV positivity included younger admission age, male sex, non-Aboriginal ethnicity, a diagnosis of bronchiolitis and longer hospital stay. Our model showed good predictive accuracy (AUROC: 0.87). The respective sensitivity, specificity, positive predictive value and negative predictive values were 58.4%, 92.2%, 68.6% and 88.3%. The predicted incidence rates of hospitalised RSV for children aged < 3 months was 43.7/1000 child-years (95% CI 42.1–45.4) compared with 31.7/1000 child-years (95% CI 30.3–33.1) from laboratory-confirmed RSV admissions. Findings from our study suggest that the true burden of RSV may be 30–57% higher than current estimates.

PREVALENCE OF FAT-SOLUBLE VITAMIN DEFICIENCIES ASSOCIATED WITH SEVERE ACUTE MALNUTRITION: A PROSPECTIVE OBSERVATIONAL STUDY

Background: Severe acute malnutrition (SAM), among children below five years of age is global health problem contributing to childhood morbidity, mortality and remains a major embarrassment to optimal human capital development in India. Objectives: Study aim was to accesses fat soluble vitamins deficiencies among children with SAM and outcomes after treatments with F-75/F-100 plus vitamins mix. Methods: The study was prospective observational conducted in the nutritional rehabilitation center (NRC) at district general hospital for 6 months. Anthropometric measurements were taken to determine their nutritional status. Results: 100 patients of NRC were enrolled in the study. Sixty nine percent (69) patients had weight/height (WT/HT) Z score<−3 standard deviation (3 SD), 16 % with Z score<−2 and 15% of them had Z score<−4 malnutrition. Out of 100 children, 46% children were males, and 56% children were females. Vitamin E deficiencies (54%) were highly prevalent in hospitalized SAM groups, followed by 28% vitamin D and 18% were vitamin A deficient. Conclusion: Micronutrient deficiencies were highly prevalent with fat soluble vitamins and recovered on application of WHO protocols during hospitalization induced satisfactory fat-soluble vitamin status recovery significant (p<0.05).

Ampicillin & Gentamicin V/S 3rd Generation Cephalosporin for the Management of Community-Acquired Pneumonia in Children; A Comparative Analysis

Background: Community acquired pneumonia (CAP) is a common cause of childhood morbidity, attributed to every 1 in 500 hospitalization of children under the age of 5 years. While science made therapeutic advancements to battle CAP, the pathogens too have acquired resistance to many drugs. In this fight for dominance, Ampicillin plus Gentamicin and 3rd Gen Cephalosporins are nowadays the cornerstone of treatment. However, their efficacy varies in different parts of the world owing to differing levels of drug resistance. Objective: To compare the effect of Ampicillin and Gentamicin vs. third generation cephalosporin in treatment of severe community acquired pneumonia. Methodology: This Randomized Controlled Trial was conducted at the Dept. of Pediatrics (Ziauddin University Hospital) upon a sample of 74 patients (in two equal groups) of either gender, aged 2 months to 5 years, presenting with CAP. After taking written informed consent, data was recorded onto a pre-structured questionnaire containing inquiries pertaining to basic biodata, sociodemographic details, presenting complaints, immunization status of the pneumococcal and HIB vaccine, laboratory values, and treatment outcome. Results: The mean age of the sample stood at 15 months (SD ± 3) with a majority of the sample comprising of male children (52.7%). The mean weight stood at 8.7 kg (SD ± 0.9) and the mean height was recorded to be 74.2 cm (SD ± 11). The commonest symptoms included fever, fast breathing, chest in-drawing and added sounds. It was revealed that both treatments achieved successful treatment outcomes in all patients with no mortality. The resolution of symptoms however varied with faster resolution observed in the Cephalosporin group. Conclusion: After careful consideration, it can be concluded that 3rd generation cephalosporins is more efficacious at treatment of CAP with significantly faster resolution of disease symptoms.

MODERN VIEWS ON THE СLINIC-GENETIC ASPECTS OF POLYHYDRAMNIOS.

The article analyzes the literature data on the etiopathogenetic aspects of polyhydramnios, taking into account the leading risk factors for development. Despite the knowledge of the etiological aspects, the development of diagnostic tactics and predictive methods, the frequency of polyhydramnios does not tend to decrease, but remains at the level of 3-12% of the total number of births. Being a leading medical and social problem, which leads to high childhood morbidity, disability, as well as death, negatively affecting the quality of life not only of a single family, but also on the gene pool of the nation.

Complement component 3 mutations alter the longitudinal risk of pediatric malaria and severe malarial anemia

Severe malarial anemia (SMA) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions. To gain enhanced understanding of predisposing factors for SMA, we explored the relationship between complement component 3 (C3) missense mutations [rs2230199 (2307C>G, Arg>Gly102) and rs11569534 (34420G>A, Gly>Asp1224)], malaria, and SMA in a cohort of children (n = 1617 children) over 36 months of follow-up. Variants were selected based on their ability to impart amino acid substitutions that can alter the structure and function of C3. The 2307C>G mutation results in a basic to a polar residue change (Arg to Gly) at position 102 (β-chain) in the macroglobulin-1 (MG1) domain, while 34420G>A elicits a polar to acidic residue change (Gly to Asp) at position 1224 (α-chain) in the thioester-containing domain. After adjusting for multiple comparisons, longitudinal analyses revealed that inheritance of the homozygous mutant (GG) at 2307 enhanced the risk of SMA (RR = 2.142, 95%CI: 1.229–3.735, P = 0.007). The haplotype containing both wild-type alleles (CG) decreased the incident risk ratio of both malaria (RR = 0.897, 95%CI: 0.828–0.972, P = 0.008) and SMA (RR = 0.617, 95%CI: 0.448–0.848, P = 0.003). Malaria incident risk ratio was also reduced in carriers of the GG (Gly102Gly1224) haplotype (RR = 0.941, 95%CI: 0.888–0.997, P = 0.040). Collectively, inheritance of the missense mutations in MG1 and thioester-containing domain influence the longitudinal risk of malaria and SMA in children exposed to intense Plasmodium falciparum transmission.

Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia

Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) &lt; 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored.Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children (n = 44, aged &lt;48 mos) with either mild malarial anemia (MlMA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb &lt;6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT2 Profiler PCR Array containing a set of 84 human ubiquitination genes.Results: In children with SMA, 10 genes were down-regulated (BRCC3, FBXO3, MARCH5, RFWD2, SMURF2, UBA6, UBE2A, UBE2D1, UBE2L3, UBR1), and five genes were up-regulated (MDM2, PARK2, STUB1, UBE2E3, UBE2M). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes.Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.

Measle Outbreak investigation, Bale Zone, Oromia Region, Ethiopia

Purpose Measles is still an important cause of childhood morbidity and mortality even in developed countries. It is a leading cause of vaccine-preventable deaths among young children. The Bale zone reported a measle outbreak on 1/15/2019. This study was conducted to describe the magnitude of the measle outbreak in the Bale Zone. Methods We conducted a descriptive cross-sectional study from September 20 to November 15, 2019, by reviewing the line lists of the cases. We checked the data for completeness and analyzed using epi-info version 7 and Microsoft Office Excel 2016. Results A total of 2753 measle cases with attack rate (AR) 201per 100,000 population and 7 death (0.25% case fatality rate) were reported during this confirmed outbreak (all five samples positive for measle IgM test). Males (0.21%) and females (0.19%) were almost equally affected. The AR was 736 per 100,000 population among 9months-4years age groups followed by an age group less than 9months (682 per 100,000 population). Most of the cases were unvaccinated (74.9%). Conclusion The majority of the cases were unvaccinated and 9months to 4years followed by less than 9months of age groups. We recommend strengthening the routine immunization and surveillance to prevent the occurrence of the measle outbreak.

“Clinical masks” of congenital malformations of urinary system in children of early age

Nowadays there is an increase in nephropathy in young children, which is associated not only with environmental impacts, but also with an increase in the incidence of congenital and hereditary caused forms of diseases, an increase in the incidence of mothers, and an improvement in diagnosis. In order to analyze the frequency of congenital malformations of the urinary system in young children under the “clinical masks” of various somatic pathologies, 864 cards of inpatients that were treated in the Early Childhood Department of the Regional Children's Clinical Hospital “OKHMATDYT” during 2013 were analyzed. The authors came to the conclusion that congenital malformations of the urinary system in young children are a frequent pathology, diagnosed in 44.6% of children admitted to the To the Department of the early age for acute pyelonephritis to get 10.3% of all children who were admitted to hospital treatment. The introduction of a two-stage algorithm for the diagnosis of congenital malformations of the urinary system allows us to recognize their various “clinical masks” and timely establish a clinical diagnosis of anomalies. This approach makes it possible to conduct adequate therapy and reduce high rates of childhood morbidity and disability, and has significant medical and social effects.

Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study

Background: Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality. Methods: We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose. Findings: We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries. Interpretation: Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified. Funding: Bill and Melinda Gates Foundation, World Health Organization