World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - XIV - Recommendations on CMA immunotherapy.

Background: The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Prevalence of vitamin D deficiency in exclusively breastfed infants at a tertiary healthcare facility in Nairobi, Kenya.

OBJECTIVE: To determine the prevalence of vitamin D deficiency (VDD) in exclusively breastfed infants at the Aga Khan University Hospital Nairobi, Kenya (AKUHN). The relationships between 25-hydroxyvitamin D; 25OHD, parathyroid hormone (PTH), maternal vitamin D supplementation, and sunlight exposure were also determined. METHODS: Blood from 98 infants was assayed for 25OHD, calcium, phosphate, and PTH. Socio-demographic and clinical characteristics were analyzed using descriptive statistics and inferential analysis (p < 0.05). RESULTS: The prevalence of VDD (25OHD <12 ng/mL), vitamin D insufficiency (VDI, 25OHD 12-20 ng/mL) and vitamin D sufficiency (VDS, 25OHD >20 ng/mL) was 11.2% (95% CI 8.0%-14.4%), 12.2% (95% CI 8.9%-15.5%), and 76.5% (95% CI 72.3%-80.8%) respectively. There was no difference in the mean age, head circumference, length, or weight of infants in VDD, VDI, and VDS groups. PTH was elevated when 25OHD was <12 ng/mL and normal when 25OHD was between 12-20 ng/mL. 25OHD and PTH were normal in infants whose mothers received vitamin D supplements. Infants who received <30 minutes/day of exposure to sunlight were 5 times more likely to have VDI than infants who received ≥30 minutes/day (p = 0.042). CONCLUSION: The prevalence of VDD in exclusively breastfed infants at AKUHN is low. The current national policy that recommends exclusive breastfeeding of infants in the first 6 months of life appears to be effective in staving off vitamin D deficiency but those infants with < 30 minutes sunlight exposure may benefit from low dose supplemental vitamin D during times of low sunlight exposure.

Prevalence of vitamin D deficiency in exclusively breastfed infants at a tertiary healthcare facility in Nairobi, Kenya

ABSTRACT Objective: To determine the prevalence of vitamin D deficiency (VDD) in exclusively breastfed infants at the Aga Khan University Hospital Nairobi, Kenya (AKUHN). The relationships between 25-hydroxyvitamin D; 25OHD, parathyroid hormone (PTH), maternal vitamin D supplementation, and sunlight exposure were also determined. Subjects and methods: Blood from 98 infants was assayed for 25OHD, calcium, phosphate, and PTH. Socio-demographic and clinical characteristics were analyzed using descriptive statistics and inferential analysis (p < 0.05). Results: The prevalence of VDD (25OHD <12 ng/mL), vitamin D insufficiency (VDI, 25OHD 12-20 ng/mL) and vitamin D sufficiency (VDS, 25OHD >20 ng/mL) was 11.2% (95% CI 8.0%-14.4%), 12.2% (95% CI 8.9%-15.5%), and 76.5% (95% CI 72.3%-80.8%) respectively. There was no difference in the mean age, head circumference, length, or weight of infants in VDD, VDI, and VDS groups. PTH was elevated when 25OHD was <12 ng/mL and normal when 25OHD was between 12-20 ng/mL. 25OHD and PTH were normal in infants whose mothers received vitamin D supplements. Infants who received <30 minutes/day of exposure to sunlight were 5 times more likely to have VDI than infants who received ≥30 minutes/day (p = 0.042). Conclusions: The prevalence of VDD in exclusively breastfed infants at AKUHN is low. The current national policy that recommends exclusive breastfeeding of infants in the first 6 months of life appears to be effective in staving off vitamin D deficiency but those infants with < 30 minutes sunlight exposure may benefit from low dose supplemental vitamin D during times of low sunlight exposure.

Pre-albumin as a marker for predicting weight loss in hospitalised children

Objectives: This study sought to determine the diagnostic utility of serum pre-albumin in predicting weight loss in hospitalised children.Design: A hospital-based longitudinal survey was carried out between December 2013 and February 2014.Setting: Aga Khan University Hospital, Nairobi, Kenya, a tertiary care hospital.Subjects: A total of 170children aged 29 days to 15 years who met the inclusion criteria were included in the study.Outcome measures: Serum prealbumin levels and weight were measured at admission and repeated after 48­96 h. Sensitivity,specificity, and positive and negative predictive values were calculated to determine the diagnostic utility of serum pre-albumin in predicting weight loss in hospitalised children.Results: Of the 170 children studied, 57% and 60% had a drop in serum pre-albumin level and weight within the first four days of hospitalisation respectively. A drop in pre-albumin occurred in 68% of the 103 patients who had weight loss (p < 0.001).Using a serum pre-albumin cut off point of < 0.15 g/l at admission, sensitivity and specificity of serum pre-albumin in predicting weight loss were 76.7% and 29.0% (negative predictive value = 42.9%; positive predictive value = 64.2%). Positive and negative likelihood ratios were low at 1.08 and 0.8. The majority of the patients (72.3%) were already at risk of malnutrition as determined by the pre-albumin risk stratification on admission.Conclusion: Serum pre-albumin is not an accurate surrogate for weight loss during hospitalisation.It is, however, useful in identifying patients at risk of malnutrition on admission and during hospitalisation

The global impact of the DRACMA guidelines cow's milk allergy clinical practice.

BACKGROUND: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. OBJECTIVES & METHODS: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. RESULTS: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. CONCLUSIONS: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.

Prevalence and genetic diversity of rotavirus infection in children with acute gastroenteritis in a hospital setting, Nairobi Kenya in post vaccination era: a cross-sectional study.

INTRODUCTION: Rotavirus is the leading cause of severe diarrhoea among infants and young children. Each year more than 611 000 children die from rotavirus gastroenteritis, and two million are hospitalized, worldwide. In Kenya, the impact of recent rotavirus vaccinations on morbidities has not been estimated. The study aimed at determining the prevalence and identity of rotavirus strains isolated from rotavirus-associated diarrhoea in vaccinated children presenting with acute gastroenteritis. METHODS: Two hundred and ninety eight specimen from children presented at Gertrude Childrens' Hospital from January to June 2012 were tested by EIA (Enzyme-linked Immunosorbent Assay) for rotavirus antigens. Molecular characterization was conducted on rotavirus-positive specimens. Extracted viral RNA was separated by polyacrylamide gel electrophoresis (PAGE) and the specific rotavirus VP4 (P-types) and VP7 (G-types) determined. RESULTS: The prevalence rate of rotavirus was 31.5% (94/298). Of the rotavirus dsRNA, 57 (60.1%) gave visible RNA profiles, 38 (40.4%) assigned long electropherotypes while 19 (20.2%) were short electropherotypes. The strains among the vaccinated were G3P [4], G12P [6], G3P [6], G9P [4], G mixed G9/3P [4] and G1/3P [4]. Specifically, the G genotypes were G9/3 (5.3%), G9 (4.3%), G3 (4.3%), G12 (2.1%) and mixed G1/3 (1.1%). The P genotypes detected were P [4] (5.3%) and P [6] (5.3%). CONCLUSION: The present study demonstrates diversity in circulating genotypes with emergence of genotypes G3, G9, G12 and mixed genotypes G9/3 and recommends that vaccines should be formulated with a broad range of strains to include G9 and G12.

Prevalence and genetic diversity of rotavirus infection in children with acute gastroenteritis in a hospital setting, Nairobi Kenya in post vaccination era: a cross-sectional study

Introduction: Rotavirus is the leading cause of severe diarrhoea among infants and young children. Each year more than 611 000 children die from rotavirus gastroenteritis, and two million are hospitalized, worldwide. In Kenya, the impact of recent rotavirus vaccinations on morbidities has not been estimated. The study aimed at determining the prevalence and identity of rotavirus strains isolated from rotavirus-associated diarrhoea in vaccinated children presenting with acute gastroenteritis.Methods: Two hundred and ninety eight specimen from children presented at Gertrude Childrens' Hospital from January to June 2012 were tested by EIA (Enzyme-linked Immunosorbent Assay) for rotavirus antigens. Molecular characterization was conducted on rotavirus-positive specimens. Extracted viral RNA was separated by polyacrylamide gel electrophoresis (PAGE) and the specific rotavirus VP4 (P-types) and VP7 (G-types) determined.Results: The prevalence rate of rotavirus was 31.5% (94/298). Of the rotavirus dsRNA, 57 (60.1%) gave visible RNA profiles, 38 (40.4%) assigned long electropherotypes while 19 (20.2%) were short electropherotypes. The strains among the vaccinated were G3P [4], G12P [6], G3P [6], G9P [4], G mixed G9/3P [4] and G1/3P [4]. Specifically, the G genotypes were G9/3 (5.3%), G9 (4.3%), G3 (4.3%), G12 (2.1%) and mixed G1/3 (1.1%). The P genotypes detected were P [4] (5.3%) and P [6] (5.3%).Conclusion: The present study demonstrates diversity in circulating genotypes with emergence of genotypes G3, G9, G12 and mixed genotypes G9/3 and recommends that vaccines should be formulated with a broad range of strains to include G9 and G12

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D.

BACKGROUND: The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20-30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases. METHODS: Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel's recommendations are conditional and supported by very low certainty evidence. CONCLUSIONS: WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants.

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics.

BACKGROUND: The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20-30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics - non-digestible oligosaccharides that stimulate growth of probiotic bacteria - have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy. METHODS: The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy. We performed a systematic review of randomized controlled trials of prebiotics, and reviewed the evidence about patient values and preferences, and resource requirements (up to January 2015, with an update on July 29, 2015). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Based on GRADE evidence to decision frameworks, the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants. Both recommendations are conditional and based on very low certainty of the evidence. We found no experimental or observational study of prebiotic supplementation in pregnant women or in breastfeeding mothers. Thus, the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding, at this time. CONCLUSIONS: WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy, term infants.

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics.

BACKGROUND: Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20-30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy. METHODS: We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations. RESULTS: Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence. CONCLUSIONS: WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.

Effectiveness of sequential v. standard triple therapy for treatment of Helicobacter pylori infection in children in Nairobi, Kenya.

BACKGROUND: Once the diagnosis of Helicobacter pylori is confirmed, treatment requires at least two antibiotics and an acid inhibitor for a minimum of seven days. Unfortunately, treatment failures are being frequently reported. Treatment regimens that include sequential administration of antibiotics with acid inhibitors have been developed to try and increase the rate of eradication. OBJECTIVE: To determine the effectiveness of a novel 10-day sequential therapy compared with the standard 10-day triple therapy for treatment of H. pylori infection in children. METHODS: A double-blinded, randomised, controlled trial was conducted. Children under the age of 16 years with recurrent abdominal pain associated with dyspepsia and diagnosed with H. pylori by histology were randomly allocated either to a 10-day sequential treatment regimen or to a 10-day conventional triple therapy. Analysis of the outcome of this study was based on clinical improvement and confirmed H. pylori eradication based on stool H. pylori antigen detection and/or repeat endoscopy. RESULTS: Of the 71 patients included in the analysis, 45 (63.4%) were given the 10-day conventional treatment while 26 (36.6%) received the 10-day sequential treatment. There was no difference in clinical improvement after treatment in the two therapies. However, there was a significant difference in the eradication of H. pylori between the conventional v. sequential regimens (48.8% v. 84.6%, respectively; p=0.02, odds ratio 0.19). CONCLUSION: The sequential treatment had a significantly higher H. pylori eradication rate than the conventional treatment.

Cost analysis of care for children admitted to kenyatta national hospital with rotavirus gastroenteritis.

Rotavirus infection is the single most common cause of acute gastroenteritis in children under five years of age. The costs of care and treatment for rotavirus gastroenteritis are high. The objective was to compute average cost of care for children admitted with rotavirus gastroenteritis. A survey was conducted in children admitted with a diagnosis of acute gastroenteritis in Nairobi, Kenya. These were recruited and followed up till discharge or death. The costs they incurred were collected and the average costs were calculated. We concluded that rotavirus gastroenteritis leads to considerable resource utilization in health care settings and the society.

The epidemiology of human rotavirus associated with diarrhoea in Kenyan children: a review.

Rotavirus gastroenteritis still remains a major cause of morbidity and mortality among young children in developing countries, with approximately 150,000-200,000 deaths occurring annually in sub-Saharan Africa. We reviewed papers published over the last 30 years on the epidemiology of rotavirus diarrhoea among the hospitalized and out-patient children in Kenya. The analysis shows rotavirus prevalence of 6-56% with diarrhoea occurring throughout the year and generally exhibiting distinct peaks during the dry months. Among the common genotype, G1 was the most predominant up to the year 2002 but more recently there has been an emergence of genotype G9 as the most predominant genotype and to a less extent G8. It is important to continue rotavirus surveillance in Kenya to determine accurately the burden of rotavirus disease and the emerging new genotypes. This will assist policy makers in decision making on rotavirus vaccine introduction and determining the impact of the vaccine.

Esophagogastric disconnection following failed fundoplication for the treatment of gastroesophageal reflux disease (GERD) in children with severe neurological impairment.

This report describes our experience with esophagogastric disconnection and Roux-en-Y esophagojejunostomy for the treatment of gastroesophageal reflux disease (GERD) in seven neurologically impaired children as a second antireflux operation following failed Nissen fundoplication. After a mean follow-up of 3 years, three children (43%) were completely or almost completely symptom-free and had improved nutritional status. Early complications occurred in three patients (43%): small bowel obstruction, wound infection, and necrosis of the Roux-en-Y loop. Three patients (43%) presented long-term complications: jejunoesophageal bile reflux and bile reflux with gastric irritation. Two patients required reoperation (28%), and two deaths occurred in the postoperative period (28%). In three previous reports in the surgical literature, severe postoperative complications occurred in 0-44%, requiring reoperation in 0-22% of the patients, and the mortality rate was 0-11%. Esophagogastric disconnection for the treatment of GERD in neurologically impaired children is associated with major complications and should be considered after more conservative procedures fail.