ABSTRACT Lancet Child Adolesc Health Strong, K., Requejo, J., Agweyu, A., McKerrow, N., Schellenberg, J., Agbere, D. A., Billah, S. M., Boschi-Pinto, C., Horiuchi, S., Lazzerini, M., Maiga, A., Munos, M., Weigel, R., Banerjee, A., Hereward, M., Diaz, T. Pages:259-261, Volume:4, Edition:2/16/2020, Date,Apr Link: https://www.ncbi.nlm.nih.gov/pubmed/32059788 Notes:Strong, Kathleen|Requejo, Jennifer|Agweyu, Ambrose|McKerrow, Neil|Schellenberg, Joanna|Agbere, Diparide Abdourahmane|Billah, Sk Masum|Boschi-Pinto, […]

ABSTRACT Lancet Child Adolesc Health Karianjahi, N., Mbogo, J., Wambugu, C., Tole, J., Agweyu, A. Pages:101-103, Volume:4, Edition:11/20/2019, Date,Feb Link: https://www.ncbi.nlm.nih.gov/pubmed/31740409 Notes:Karianjahi, Njeri|Mbogo, Joyce|Wambugu, Christine|Tole, John|Agweyu, Ambrose|eng|Comment|England|2019/11/20 06:00|Lancet Child Adolesc Health. 2020 Feb;4(2):101-103. doi: 10.1016/S2352-4642(19)30374-8. Epub 2019 Nov 15. ISBN: 2352-4650 (Electronic)|2352-4642 (Linking) Permanent ID: Accession Number: 31740409 Author Address: Gertrude’s Children’s Hospital, P.O Box […]

Introduction: There were almost 1 million deaths in children aged between 5 and 14 years in 2017, and pneumonia accounted for 11%. However, there are no validated guidelines for pneumonia management in older children and data to support their development are limited. We sought to understand risk factors for mortality among children aged 5-14 years hospitalised with pneumonia in district-level health facilities in Kenya. Methods: We did a retrospective cohort study using data collected from an established clinical information network of 13 hospitals. We reviewed records for children aged 5-14 years admitted with pneumonia between 1 March 2014 and 28 February 2018. Individual clinical signs were examined for association with inpatient mortality using logistic regression. We used existing WHO criteria (intended for under 5s) to define levels of severity and examined their performance in identifying those at increased risk of death. Results: 1832 children were diagnosed with pneumonia and 145 (7.9%) died. Severe pallor was strongly associated with mortality (adjusted OR (aOR) 8.06, 95% CI 4.72 to 13.75) as were reduced consciousness, mild/moderate pallor, central cyanosis and older age (>9 years) (aOR >2). Comorbidities HIV and severe acute malnutrition were also associated with death (aOR 2.31, 95% CI 1.39 to 3.84 and aOR 1.89, 95% CI 1.12 to 3.21, respectively). The presence of clinical characteristics used by WHO to define severe pneumonia was associated with death in univariate analysis (OR 2.69). However, this combination of clinical characteristics was poor in discriminating those at risk of death (sensitivity: 0.56, specificity: 0.68, and area under the curve: 0.62). Conclusion: Children >5 years have high inpatient pneumonia mortality. These findings also suggest that the WHO criteria for classification of severity for children under 5 years do not appear to be a valid tool for risk assessment in this older age group, indicating the urgent need for evidence-based clinical guidelines for this neglected population.

BACKGROUND: The malaria prevalence has declined in western Kenya, resulting in the risk of neurological phenotypes in older children. This study investigates the clinical profile of pediatric malaria admissions ahead of the introduction of the RTS,S/AS01 vaccine. METHODS: Malaria admissions in children aged 1 month to 15 years were identified from routine, standardized, inpatient clinical surveillance data collected between 2015 and 2018 from 4 hospitals in western Kenya. Malaria phenotypes were defined based on available data. RESULTS: There were 5766 malaria admissions documented. The median age was 36 months (interquartile range, 18-60): 15% were aged between 1-11 months of age, 33% were aged 1-23 months of age, and 70% were aged 1 month to 5 years. At admission, 2340 (40.6%) children had severe malaria: 421/2208 (19.1%) had impaired consciousness, 665/2240 (29.7%) had an inability to drink or breastfeed, 317/2340 (13.6%) had experienced 2 or more convulsions, 1057/2340 (45.2%) had severe anemia, and 441/2239 (19.7%) had severe respiratory distress. Overall, 211 (3.7%) children admitted with malaria died; 163/211 (77% deaths, case fatality rate 7.0%) and 48/211 (23% deaths, case fatality rate 1.4%) met the criteria for severe malaria and nonsevere malaria at admission, respectively. The median age for fatal cases was 33 months (interquartile range, 12-72) and the case fatality rate was highest in those unconscious (44.4%). CONCLUSIONS: Severe malaria in western Kenya is still predominantly seen among the younger pediatric age group and current interventions targeted for those <5 years are appropriate. However, there are increasing numbers of children older than 5 years admitted with malaria, and ongoing hospital surveillance would identify when interventions should target older children.

The majority of childhood deaths occur in low-income countries, with vaccine-preventable infections contributing greatly. Of the many possible environmental factors that could hamper a child's immune response, mycotoxins rank among the least studied in spite of the high exposure in vulnerable populations. Aflatoxin crosses the placenta, is secreted in breast milk and is consumed widely in weaning diets by children with developing organ systems. This review describes the effects of mycotoxin exposure on immunity in children that may contribute to sub-optimal vaccine effectiveness. We searched electronic databases and references of identified articles for relevant studies on the effects of mycotoxins on the immune system in children. Geographical location, publication year, study design, sample selection, sample size, mean age, route of exposure were extracted on a standard template. Quality was assessed using Joanna Briggs Institute tool for appraisal of systematic reviews for prevalence studies. Our analyses and reporting were conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Out of 806 articles screened, 5 observational studies met criteria for inclusion for review. The definition of exposures to mycotoxins and outcomes varied across the studies. Exposure to mycotoxins was positively associated with low birth weight and concentration of antibodies to asexual malaria parasites and hepatitis B surface antigen, and negatively associated with death and sIgA, antibodies to pneumococcal antigen 23. Despite the far-reaching clinical and public health effects of mycotoxin exposure among children, studies on the effects of mycotoxin exposure on immunity in children were few, small and mostly of low quality. There is an urgent need for carefully designed prospective studies in this neglected field to inform policy interventions for child health in settings where exposure to mycotoxins is high.

BACKGROUND: Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. A vaccine must induce a response over the basal immune response that may be driven by population-specific, environmental or socio-economic factors. Mycotoxins like aflatoxins are immune suppressants that are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity is through the binding of the bio-activated AFB1-8, 9-epoxide to cellular macromolecules. METHODS: We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti-HBs were measured using Bio-ELISA anti-HBs kit. RESULTS: The mean +/- SD of AFB1-lysine adducts in our study population was 45.38 +/- 87.03 pg/mg of albumin while the geometric mean was 20.40 pg/mg. The distribution of AFB1-lysine adducts was skewed to the right. Only 98/205 (47.8%) of the study population tested positive for Hepatitis B surface antibodies. From regression analysis, we noted that for every unit rise in serum aflatoxin level, anti-HBs dropped by 0.91 mIU/ml (-0.9110038; 95% C.I -1.604948, -0.21706). CONCLUSION: Despite high coverage of routine immunization, less than half of the study population had developed immunity to HepB. Exposure to aflatoxin was high and weakly associated with low anti-HBs antibodies. These findings highlight a potentially significant role for environmental factors that may contribute to vaccine effectiveness warranting further research.

BACKGROUND: The World Health Organization (WHO) revised its clinical guidelines for management of childhood pneumonia in 2013. Significant delays have occurred during previous introductions of new guidelines into routine clinical practice in low- and middle-income countries (LMIC). We therefore examined whether providing enhanced audit and feedback as opposed to routine standard feedback might accelerate adoption of the new pneumonia guidelines by clinical teams within hospitals in a low-income setting. METHODS: In this parallel group cluster randomized controlled trial, 12 hospitals were assigned to either enhanced feedback (n = 6 hospitals) or standard feedback (n = 6 hospitals) using restricted randomization. The standard (network) intervention delivered in both trial arms included support to improve collection and quality of patient data, provision of mentorship and team management training for pediatricians, peer-to-peer networking (meetings and social media), and multimodal (print, electronic) bimonthly hospital specific feedback reports on multiple indicators of evidence guideline adherence. In addition to this network intervention, the enhanced feedback group received a monthly hospital-specific feedback sheet targeting pneumonia indicators presented in multiple formats (graphical and text) linked to explicit performance goals and action plans and specific email follow up from a network coordinator. At the start of the trial, all hospitals received a standardized training on the new guidelines and printed booklets containing pneumonia treatment protocols. The primary outcome was the proportion of children admitted with indrawing and/or fast-breathing pneumonia who were correctly classified using new guidelines and received correct antibiotic treatment (oral amoxicillin) in the first 24 h. The secondary outcome was the proportion of correctly classified and treated children for whom clinicians changed treatment from oral amoxicillin to injectable antibiotics. RESULTS: The trial included 2299 childhood pneumonia admissions, 1087 within the hospitals randomized to enhanced feedback intervention, and 1212 to standard feedback. The proportion of children who were correctly classified and treated in the first 24 h during the entire 9-month period was 38.2% (393 out of 1030) and 38.4% (410 out of 1068) in the enhanced feedback and standard feedback groups, respectively (odds ratio 1.11; 95% confidence interval [CI] 0.37-3.34; P = 0.855). However, in exploratory analyses, there was evidence of an interaction between type of feedback and duration (in months) since commencement of intervention, suggesting a difference in adoption of pneumonia policy over time in the enhanced compared to standard feedback arm (OR = 1.25, 95% CI 1.14 to 1.36, P < 0.001). CONCLUSIONS: Enhanced feedback comprising increased frequency, clear messaging aligned with goal setting, and outreach from a coordinator did not lead to a significant overall effect on correct pneumonia classification and treatment during the 9-month trial. There appeared to be a significant effect of time (representing cumulative effect of feedback cycles) on adoption of the new policy in the enhanced feedback compared to standard feedback group. Future studies should plan for longer follow-up periods to confirm these findings. TRIAL REGISTRATION: US National Institutes of Health-ClinicalTrials.gov identifier (NCT number) NCT02817971 . Registered September 28, 2016-retrospectively registered.

Background: Diarrhoea causes many deaths in children younger than 5 years and identification of risk factors for death is considered a global priority. The effectiveness of currently recommended fluid management for dehydration in routine settings has also not been examined. Methods: For this observational, association study, we analysed prospective clinical data on admission, immediate treatment, and discharge of children age 1-59 months with diarrhoea and dehydration, which were routinely collected from 13 Kenyan hospitals. We analysed participants with full datasets using multivariable mixed-effects logistic regression to assess risk factors for in-hospital death and effect of correct rehydration on early mortality (within 2 days). Findings: Between Oct 1, 2013, and Dec 1, 2016, 8562 children with diarrhoea and dehydration were admitted to hospital and eligible for inclusion in this analysis. Overall mortality was 9% (759 of 8562 participants) and case fatality was directly correlated with severity. Most children (7184 [84%] of 8562) with diarrhoea and dehydration had at least one additional diagnosis (comorbidity). Age of 12 months or younger (adjusted odds ratio [AOR] 1.71, 95% CI 1.42-2.06), female sex (1.41, 1.19-1.66), diarrhoea duration of more than 14 days (2.10, 1.42-3.12), abnormal respiratory signs (3.62, 2.95-4.44), abnormal circulatory signs (2.29, 1.89-2.77), pallor (2.15, 1.76-2.62), use of intravenous fluid (proxy for severity; 1.68, 1.41-2.00), and abnormal neurological signs (3.07, 2.54-3.70) were independently associated with in-hospital mortality across hospitals. Signs of dehydration alone were not associated with in-hospital deaths (AOR 1.08, 0.87-1.35). Correct fluid prescription significantly reduced the risk of early mortality (within 2 days) in all subgroups: abnormal respiratory signs (AOR 1.23, 0.68-2.24), abnormal circulatory signs (0.95, 0.53-1.73), pallor (1.70, 0.95-3.02), dehydration signs only (1.50, 0.79-2.88), and abnormal neurological signs (0.86, 0.51-1.48). Interpretation: Children at risk of in-hospital death are those with complex presentations rather than uncomplicated dehydration, and the prescription of recommended rehydration guidelines reduces risk of death. Strategies to optimise the delivery of recommended guidance should be accompanied by studies on the management of dehydration in children with comorbidities, the vulnerability of young girls, and the delivery of immediate care. Funding: The Wellcome Trust.