Abstract:Treatment with racecadotril did not reduce diarrheal duration, stool volume or the requirement for fluid replacement in children with acute gastroenteritis, both with and without rotavirus infection.
“…In addition, one meta-analysis of seven clinical trials reported that racecadotril treatment is more effective than placebo or no intervention at reducing the duration of illness and stool output in children with acute diarrhoea 162 . However, in Kenya, racecadotril did not alter the number of stools after 48 hours, the duration of hospital stay or the duration of diarrhoea in children with severe gastroenteritis who received ORS and zinc 163 and was not effective in Indian children with acute diarrhoea and vomiting 164 . Thus, racecadotril can be considered for the management of children with severe secretory diarrhoea, but the efficacy is variable.…”
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.
“…In addition, one meta-analysis of seven clinical trials reported that racecadotril treatment is more effective than placebo or no intervention at reducing the duration of illness and stool output in children with acute diarrhoea 162 . However, in Kenya, racecadotril did not alter the number of stools after 48 hours, the duration of hospital stay or the duration of diarrhoea in children with severe gastroenteritis who received ORS and zinc 163 and was not effective in Indian children with acute diarrhoea and vomiting 164 . Thus, racecadotril can be considered for the management of children with severe secretory diarrhoea, but the efficacy is variable.…”
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.
“…Other, novel vaccines are currently undergoing preclinical and clinical trial testing[67], including vaccines using novel reassortant rotavirus strains, and vaccines using alternative delivery methods such as a heat stable oral formulation[69] and intramuscular or intradermal formulations[71]. Strategies to improve the performance of oral rotavirus vaccines in high-mortality countries are currently being explored, including the use of zinc supplementation[55], use of the antisecretory agent racecadotril[72,73], timing of breastfeeding[37,56,57], improved nutrition[35], and alternate dosing schedules[74–76]. These developments in the rotavirus vaccine marketplace and improved effectiveness of oral vaccines are likely to encourage broader and more effective introduction of rotavirus vaccines in African countries, thus providing greater reductions in the burden of rotavirus infection than are estimated in this report.…”
Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent. Areas covered: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321-154,654) hospitalizations and 20,986 (IQR 18,924-22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260-318,102) hospitalizations and 47,741 (39%) (IQR 42,822-52,462) deaths would have been prevented. Expert commentary: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.
“…During study selection we encountered three non‐English articles and obtained help from the Cochrane Infectious Diseases Group (CIDG) with translating them into English (Calatayud 2009; Cojocaru 2002; García 2016). After selecting according to inclusion criteria, we included seven RCTs, involving 1140 participants (Cézard 2001; García 2016; Gharial 2017; [Kang 2016a; Kang 2016b]; Salazar‐Lindo 2000; Santos 2009; Sreenivas 2017). See Figure 1 for a flow diagram of the selection process.Figure 1Study flow diagram.…”
Section: Resultsmentioning
confidence: 99%
“…Two trials were conducted in India ([Kang 2016a; Kang 2016b]; Sreenivas 2017); the rest were conducted in France (Cézard 2001), Spain (Santos 2009), Peru (Salazar‐Lindo 2000), Kenya (Gharial 2017), and Ecuador (García 2016).…”
Section: Resultsmentioning
confidence: 99%
“…Previous reviews did not include this outcome when evaluating the efficacy of racecadotril (Gordon 2016; Lehert 2011; Szajewska 2007). Although several systematic reviews have been conducted in order to assess the efficacy of racecadotril for children with acute diarrhoea, the benefit of using racecadotril is still controversial as newly published trials have inconsistent conclusions on its efficacy (García 2016; Gharial 2017; Kang 2016a; Kang 2016b; Sreenivas 2017). An updated systematic review that carefully assesses risk of bias of available trials and addresses outcomes both on symptomatic relief and success of rehydration was needed.…”
BackgroundAcute diarrhoea is a leading cause of death for children under five years of age. Most deaths are caused by excessive fluid and electrolyte losses. Racecadotril is an anti‐secretory drug that has been used for acute diarrhoea in children as an adjunct to oral rehydration therapy.ObjectivesTo assess the efficacy and safety of racecadotril for treating acute diarrhoea in children under five years of age.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library Issue 3, March 2019); MEDLINE; Embase; LILACS; ClinicalTrials.gov; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), up to 4 March 2019, for clinical trials regardless of publication language or status.Selection criteriaRandomized controlled trials (RCTs) that compared racecadotril to placebo or no intervention in addition to standard care (oral rehydration therapy) in children under five with acute diarrhoea. The primary outcomes were failure of oral rehydration, duration of diarrhoea, and number of stools. The secondary outcomes were stool output, length of the hospital stay, and adverse events.Data collection and analysisTwo review authors independently assessed trial eligibility, extracted the data and assessed risk of bias. We presented dichotomous data with risk ratios (RR) and continuous data with mean difference (MD) or standardized mean difference (SMD). Where appropriate, we combined trials with meta‐analysis and used a random‐effects model if there was significant heterogeneity (I² ≥ 50%). We assessed the certainty of the evidence using the GRADE approach.Main resultsSeven RCTs with a total of 1140 participants met the inclusion criteria. The trials were carried out on children aged three months to five years, in outpatient and inpatient facilities from France, Spain, Peru, India, Kenya, and Ecuador. The efficacy and safety of racecadotril were compared to placebo or no treatment. Racecadotril may reduce the risk of rehydration failure (RR 0.41, 95% CI 0.13 to 1.23; 2 RCTs, 192 participants; low‐certainty evidence). Data on duration of diarrhoea, number of stools in the first 48 hours are insufficient to reach a conclusion; stool output in the first 48 hours appears to be lower in the two trials measuring this, although the data is not combinable. Length of hospital stay was similar in two studies measuring this, and overall there was no evidence that racecadotril increased overall rate of adverse events (RR 0.90, 95% CI 0.66 to 1.22; 5 RCTs, 688 participants; low‐certainty evidence). Most adverse events in the racecadotril group were mild or moderate.Authors' conclusionsRacecadotril seems to be a safe drug but has little benefit in improving acute diarrhoea in children under five years of age. Current evidence does not support routine use of racecadotril in management of acute diarrhoea in children under five outside of the context of placebo controlled RCTs.
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