Pediatrics – Gastroenterology
RCT: Albendazole–Ivermectin Co-Formulation Achieves Higher Cure Rates for T. trichiura and Hookworms
22 Jan, 2025 | 12:41h | UTCBackground: Soil-transmitted helminthiases (STH) affect an estimated 1.5 billion people worldwide, with Trichuris trichiura and hookworms remaining particularly challenging to treat. Although single-dose albendazole or mebendazole is standard in mass deworming programs, these agents show limited efficacy against T. trichiura and often leave Strongyloides stercoralis under-treated. Ivermectin has demonstrated broad activity against multiple parasites, suggesting that a combined albendazole–ivermectin regimen might enhance treatment outcomes, simplify protocols, and potentially curb emerging drug resistance.
Objective: This trial aimed to evaluate the safety, efficacy, and acceptability of a novel fixed-dose co-formulation (FDC) tablet containing albendazole (400 mg) plus a higher-than-standard, fixed dose of ivermectin (9 mg or 18 mg), administered once daily (FDC×1) or for three consecutive days (FDC×3). Investigators compared these regimens against single-dose albendazole alone for the treatment of T. trichiura, hookworms, and S. stercoralis in children and adolescents.
Methods: In this adaptive, randomized, parallel-group, phase 2/3 trial, 1001 participants aged 5–18 years were recruited from schools in Ethiopia, Kenya, and Mozambique. All were infected with at least one of T. trichiura, hookworms, or S. stercoralis. Eligible participants were allocated (by computer-generated block randomization) to either a single dose of albendazole 400 mg (control), a single-dose FDC of albendazole–ivermectin (FDC×1), or a three-day FDC regimen (FDC×3). Primary endpoints included safety (phase 2) and efficacy (phase 3), determined by cure rates at day 21 using the Kato–Katz and Baermann methods. Laboratory staff were blinded to treatment assignment.
Results: No serious adverse events were reported; mild-to-moderate gastrointestinal symptoms were the most frequent treatment-related events, resolving spontaneously within 48 hours. Cure rates for T. trichiura were 35.9% (95% CI 27.7–44.1) in the albendazole group, 82.9% (78.2–87.5) in FDC×1, and 97.2% (95.2–99.3) in FDC×3. For hookworms, cure rates were 65.1% (56.0–74.2) with albendazole, 79.8% (72.8–86.9) with FDC×1, and 95.0% (91.1–98.9) with FDC×3. Egg reduction rates in FDC arms consistently surpassed those of albendazole alone, especially for multi-day dosing. The sample size for S. stercoralis was insufficient to power a definitive efficacy conclusion, though ivermectin-containing arms trended toward favorable results. Palatability questionnaires indicated the orodispersible FDC was well accepted in taste, texture, and overall ease of administration.
Conclusions: A new co-formulation of albendazole plus ivermectin delivered at higher, fixed doses demonstrated an excellent safety profile and superior efficacy against T. trichiura and hookworms compared with albendazole monotherapy. This approach may streamline programmatic control of multiple STH species, including S. stercoralis, while contributing to reduced transmission in endemic communities.
Implications for Practice: For mass deworming initiatives, a single-dose FDC offers improved cure rates over albendazole alone while preserving simplicity. Where higher efficacy is critical—such as programs targeting near-elimination goals or in clinical settings—the three-day regimen may be preferable. Nonetheless, implementation feasibility, cost considerations, and further confirmation of efficacy against S. stercoralis and other co-endemic parasites remain important next steps.
Study Strengths and Limitations: Strengths include a multicenter design across three countries and a rigorous adaptive protocol that assessed both safety and efficacy. Limitations include the lack of blinding for participants and care providers (though outcome assessors were blinded), the underpowered sample size for S. stercoralis, and reliance on single-stool diagnostics, which may underestimate residual infections.
Future Research: Additional large-scale studies should confirm these findings in varied geographic regions and evaluate the cost-effectiveness of both single-dose and multi-day FDC strategies. Integrating albendazole–ivermectin with treatment programs for other neglected tropical diseases (e.g., onchocerciasis) could further amplify public health benefits. Genomic and pharmacokinetic analyses will clarify resistance patterns and optimize dosing regimens for broader implementation.
Reference: Krolewiecki A, Kepha S, Fleitas PE, van Lieshout L, Gelaye W, Messa A Jr, et al. “Albendazole–ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.” The Lancet Infectious Diseases. Published January 10, 2025. DOI: https://doi.org/10.1016/S1473-3099(24)00669-8
Diagnosis and Management of Eosinophilic Esophagitis: Updated ACG Clinical Guideline Summary
14 Jan, 2025 | 13:46h | UTCIntroduction: This summary highlights the updated American College of Gastroenterology (ACG) Clinical Guideline on eosinophilic esophagitis (EoE), a chronic, immune-mediated disease of the esophagus characterized by esophageal eosinophilia and clinical symptoms of esophageal dysfunction. Over the last decade, the incidence and prevalence of EoE have increased significantly. This guideline incorporates new diagnostic strategies, therapeutic advances, and monitoring practices, aiming to improve patient outcomes and minimize disease complications such as strictures, food impactions, and impaired quality of life. The document underscores the importance of assessing both the inflammatory and fibrostenotic components of EoE through endoscopy, histopathology, and symptom evaluation.
Key Recommendations:
- Diagnosis:
- Diagnose EoE when patients present with symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsies, after exclusion of other causes of esophageal eosinophilia.
- Use a systematic scoring tool such as the EoE Endoscopic Reference Score (EREFS) to assess edema, rings, exudates, furrows, and strictures at every endoscopy.
- Obtain at least six esophageal biopsies from two or more levels (e.g., distal and proximal) to minimize diagnostic miss rates; quantify peak eosinophil counts in each specimen.
- Pharmacologic Therapy:
- Proton Pump Inhibitors (PPIs):
- Consider high-dose PPIs (e.g., twice daily) as a first-line treatment option. Although originally used for acid suppression, PPIs also reduce eotaxin-3 expression and improve esophageal barrier function in EoE.
- Maintain therapy long term in patients who respond, as discontinuation frequently leads to disease recurrence.
- Topical Corticosteroids (Swallowed Steroids):
- Budesonide or fluticasone can be delivered via specially formulated suspensions/tablets or by swallowing inhaler medication.
- Expect histologic remission rates of around 60%–70%.
- Oral/esophageal candidiasis is the most common adverse event. Routine adrenal suppression testing is generally not necessary for short-term use.
- Dietary Elimination:
- Empiric elimination diets (e.g., 2-food or 6-food elimination) help identify specific food triggers. Histologic remission rates can exceed 70%, particularly with the 6-food approach.
- Less-restrictive diets (e.g., milk-only elimination) may be tried first (the “step-up” approach).
- Do not rely on currently available skin prick or Ig-based tests to guide elimination diets, as these have poor predictive value for EoE triggers.
- Biologic Therapy:
- Dupilumab (anti–IL-4 receptor alpha) is recommended in adolescents and adults (≥12 years, ≥40 kg) and is now approved for children as young as 1 year (≥15 kg) with moderate to severe, PPI-refractory EoE. Expect significant histologic, endoscopic, and symptom improvements in most patients, along with an overall favorable safety profile.
- Other biologics (e.g., cendakimab, benralizumab, mepolizumab) remain under investigation; current data are insufficient for routine clinical use.
- Esophageal Dilation:
- Perform endoscopic dilation to treat symptomatic strictures or narrow-caliber esophagi. Dilation reduces dysphagia promptly but does not alter the underlying inflammation.
- Combine dilation with anti-inflammatory therapy to address the disease’s inflammatory component and help prevent recurrent stricture formation.
- Proton Pump Inhibitors (PPIs):
- Maintenance and Monitoring:
- Because EoE is chronic, continue effective therapy over the long term. Abrupt cessation of treatment often leads to relapses in symptoms and inflammation.
- Evaluate treatment response by assessing symptoms, endoscopic findings (e.g., EREFS), and histopathology (peak eosinophil counts).
- A target of <15 eos/hpf and near-normal endoscopic appearance (EREFS ≤2) is commonly used to define remission, although some patients aim for histologic normalization.
- In children, ensure regular assessment of growth, development, and feeding behaviors. Referral to a nutritionist or feeding therapist is recommended if feeding difficulties or failure to thrive are present.
Conclusion: These updated ACG guidelines underscore the importance of a comprehensive, individualized approach to EoE that encompasses diagnosis, treatment of the inflammatory state, dilation of fibrotic strictures, and ongoing monitoring to maintain long-term remission. The introduction of biologics (particularly dupilumab) expands treatment options for patients nonresponsive to PPIs or topical steroids. Clinicians should adopt a structured assessment strategy—integrating clinical history, endoscopic scoring, and histological evaluation—to guide therapy selection, document treatment response, and prevent complications. With improved understanding of disease pathogenesis and evolving therapeutic tools, outcomes for patients with EoE are expected to continue to improve.
Reference: Dellon ES, Muir AB, Katzka DA, Shah SC, Sauer BG, Aceves SS, Furuta GT, Gonsalves N, Hirano I. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. The American Journal of Gastroenterology. 2025;120(1):31–59. DOI: https://doi.org/10.14309/ajg.0000000000003194
RCT: Milk Elimination Diet Comparable to Four-Food Elimination in Pediatric EoE
20 Oct, 2024 | 15:04h | UTCBackground: Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by eosinophil infiltration of the esophageal mucosa, leading to symptoms such as nausea, vomiting, abdominal pain, and dysphagia in children. While elimination of six common food allergens is effective, this approach is highly restrictive and may adversely affect quality of life (QoL). Less restrictive diets could potentially balance efficacy with improved QoL.
Objective: To compare the efficacy of a one-food elimination diet excluding milk (1FED) versus a four-food elimination diet excluding milk, egg, wheat, and soy (4FED) in treating pediatric EoE.
Methods: In this multicenter, randomized, nonblinded trial conducted at ten sites in the United States, 63 children aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to either 1FED (n = 38) or 4FED (n = 25) for 12 weeks. The primary endpoint was symptom improvement measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary endpoints included the proportion achieving histologic remission (<15 eosinophils per high-power field), changes in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome profiling (EoE diagnostic panel), QoL scores, and predictors of remission.
Results: Out of 63 participants, 51 completed the study (1FED, n = 34; 4FED, n = 17). The 4FED group showed a greater improvement in mean PEESS scores compared to the 1FED group (−25.0 vs. −14.5; P = .04). However, histologic remission rates were similar between 4FED and 1FED (41% vs. 44%; P = 1.00). Changes in the histology scoring system (−0.25 vs. −0.29; P = .77), endoscopic reference score (−1.10 vs. −0.58; P = .47), and QoL scores were comparable between groups. The withdrawal rate was higher in the 4FED group compared to the 1FED group (32% vs. 11%; P = .0496).
Conclusions: While the 4FED moderately improved symptoms more than the 1FED, both diets resulted in similar histologic, endoscopic, QoL, and transcriptomic outcomes. Given its comparable effectiveness, better tolerability, and simplicity, the 1FED is a reasonable first-choice therapy for pediatric EoE.
Implications for Practice: Eliminating cow’s milk alone may be preferable as initial dietary therapy for children with EoE due to its simplicity and similar efficacy compared to more restrictive diets. Clinicians should consider starting with a milk elimination diet before progressing to more restrictive elimination diets if necessary.
Study Strengths and Limitations: Strengths of the study include its randomized, multicenter design; standardized treatment instructions; and use of validated symptom and QoL instruments. Limitations include early termination due to low enrollment, a higher withdrawal rate in the 4FED group, nonblinded interventions, and potential bias from participant expectations.
Future Research: Further large-scale, randomized studies are needed to confirm these findings and to identify biomarkers that predict response to dietary therapy in pediatric EoE.
Systematic Review | Necrotizing enterocolitis onset typically in third week for very preterm, low birthweight infants
3 Aug, 2023 | 13:33h | UTC
RCT | Maternal egg intake in early neonatal period does not impact infant egg allergy risk
2 Aug, 2023 | 13:47h | UTCSee also: Visual Abstract
An ESPGHAN position paper on the diagnosis, management and prevention of cow’s milk allergy
31 Jul, 2023 | 14:28h | UTC
Review | Pediatric-onset inflammatory bowel disease: recent developments
27 Jul, 2023 | 12:57h | UTCInflammatory bowel disease: recent developments – Archives of Disease in Childhood
Podcast | Celiac disease pearls
27 Jul, 2023 | 12:53h | UTC#89: Celiac Disease – The Great Mimicker – The Cribsiders
Consensus Paper | Transition of patients with esophageal atresia–tracheoesophageal fistula
19 Jun, 2023 | 13:44h | UTCThe International Network on Oesophageal Atresia (INoEA) consensus guidelines on the transition of patients with oesophageal atresia–tracheoesophageal fistula – Nature Reviews Gastroenterology & Hepatology (if the link is paywalled, try this one)
Cohort Study | 63.1% of uncomplicated appendicitis in children successfully treated non-operatively at 1 year
15 Jun, 2023 | 14:45h | UTC
Commentary on Twitter
1y outcomes of CASCADE examining💊treatment for uncomp🪱itis in kids ➡️overall success: 63.1%, 21.5% req🔪during hospitalisation, 10.4% recurrence @1y. Overall comp: 7.3%🔪vs. 1.3% in success Non🔪treatment. Thoughts?https://t.co/AuIgSKkU6w#SoMe4Surgery #some4peds #emgensurg pic.twitter.com/9mM5NFOEh1
— BJS Open (@BjsOpen) June 7, 2023
Guideline | Managing chemotherapy-induced nausea and vomiting in pediatric cancer
7 Jun, 2023 | 13:43h | UTC
SR | Balanced crystalloid solutions versus 0.9% saline for treating acute diarrhea and severe dehydration in children
25 May, 2023 | 11:15h | UTC
RCT | Anti-TNF in combination with low dose methotrexate vs anti-TNF monotherapy in pediatric Crohn’s disease
26 Apr, 2023 | 13:55h | UTCComparative Effectiveness of Anti-TNF in Combination with Low Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn’s Disease: a Pragmatic Randomized Trial – Gastroenterology (link to abstract – $ for full-text)
Cohort Study | Associations between fetal or infancy pet exposure and food allergies
3 Apr, 2023 | 13:26h | UTC
Review | Constipation in children and adolescents
23 Feb, 2023 | 13:06h | UTCConstipation in Children and Adolescents – Deutsches Ärzteblatt international
SR | Probiotics for management of functional abdominal pain disorders in children
22 Feb, 2023 | 12:20h | UTCProbiotics for management of functional abdominal pain disorders in children – Cochrane Library
Position Paper | Medical Management of pediatric inflammatory bowel disease
15 Feb, 2023 | 16:03h | UTC
RCT | IV ferric carboxymaltose vs. oral ferrous fumarate in anemic children with inflammatory bowel disease
30 Jan, 2023 | 00:18h | UTC
Podcast | Pediatric gastroesophageal reflux disease
20 Jan, 2023 | 14:25h | UTC#75: Stomachs in (re)Flux: Pediatric Gastroesophageal Reflux Disease – The Cribsiders
ACC Guidelines Update | Diagnosis and management of celiac disease
18 Jan, 2023 | 14:40h | UTCCommentaries:
ACG Updates Clinical Guidance on Diagnosing Celiac Disease – HCP Live
SR | Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins.
14 Dec, 2022 | 14:51h | UTCTreatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins – Cochrane Library
Guidance on developing and/or expanding pediatric solid organ transplantation programs in low- and middle-income countries.
6 Dec, 2022 | 13:47h | UTC
Defining the optimum strategy for identifying adults and children with celiac disease: systematic review and economic modeling.
9 Nov, 2022 | 12:16h | UTC
Pediatric acute liver failure: reexamining key clinical features, current management, and research prospects.
12 Aug, 2022 | 14:17h | UTC
Severe acute hepatitis of unknown etiology in children—what is known?
2 Aug, 2022 | 12:39h | UTCSevere acute hepatitis of unknown aetiology in children—what is known? – BMC Medicine
Related:
A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection – New England Journal of Medicine (link to abstract – $ for full-text)
Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause – New England Journal of Medicine (link to abstract – $ for full-text)
Severe acute hepatitis of unknown aetiology in children – Multi-country – World Health Organization
Sudden onset hepatitis in children – Nature Reviews Gastroenterology & Hepatology (if the link is paywalled, try this one)
Outbreak of hepatitis in children: clinical course of children with acute liver failure admitted to the intensive care unit – Intensive Care Medicine (if the link is paywalled, try this one)
Investigating Acute Hepatitis of Unknown Origin in Children – American Society for Microbiology
What’s sending kids to hospitals with hepatitis—coronavirus, adenovirus, or both? – Science
Puzzling pediatric hepatitis cases echo an earlier mysterious illness – STAT
Why COVID is a key suspect in severe hepatitis cases in kids worldwide – CBC
Hepatitis outbreak in children: What do we know so far? – Imperial College London
Explaining the unexplained hepatitis in children – The Lancet Infectious Diseases
Unexplained hepatitis cases in kids rise to 348 in 20 nations – CIDRAP
Multi-Country – Acute, severe hepatitis of unknown origin in children – World Health Organization
WHO says 12 countries have reported unusual cases of hepatitis in kids – STAT
Could Mysterious Hepatitis Cases be Triggered by COVID-19? – Health Policy Watch
U.S., U.K. investigating unusual cases of hepatitis in young children – STAT
Mysterious liver illness seen in kids in US, Europe – Associated Press