Reflecting on the patient experience

BackgroundAcute respiratory tract infections (ARTIs) are a major cause of childhood morbidity and mortality. Immunostimulants (IS) may reduce the incidence of ARTIs.ObjectivesTo determine the efficacy and safety of IS in preventing ARTIs in children.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2011, issue 1, which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to February week 4, 2011), EMBASE (1990 to February 2011), Google Scholar (2009 to February 2011), Scopus (2009 to February 2011), PASCAL (1990 to February 2010), SciSearch (1990 to February 2010) and IPA (1990 to February 2010).Selection criteriaWe included all comparative randomized controlled trials (RCTs) which enrolled participants less than 18 years of age. The intervention was IS medication, administered by any method, compared to placebo to prevent ARTIs.Data collection and analysisWe analyzed the outcome on ARTIs both as the mean number of ARTIs by group and as a percent change in the rate of ARTIs. We undertook meta‐analyses using a random‐effects model and presented results as mean differences (MD) with 95% confidence intervals (CI). Two review authors independently assessed the search results and risk of bias, and extracted data. A funnel plot suggested there may be publication bias in the identified trials.Main resultsThirty‐five placebo‐controlled trials (4060 participants) provided data in a form suitable for inclusion in the meta‐analyses. When compared with placebo, the use of IS was shown to reduce ARTIs measured as the total numbers of ARTIs (MD ‐1.24; 95% CI ‐1.54 to ‐0.94) and the difference in ARTI rates (MD ‐38.84%; 95% CI ‐46.37% to ‐31.31%). Trial quality was generally poor and a high level of statistical heterogeneity was evident. The subgroup analysis of bacterial IS, D53 and OM‐85 studies produced similar results, with lower heterogeneity. No difference in adverse events was evident between the placebo and IS groups.Authors' conclusionsThis review shows that IS reduce the incidence of ARTIs by 40% on average in susceptible children. Studies in healthy children are not available. Although the safety profile in the studies was good, some IS may be unsafe. ARTI‐susceptible children may benefit from IS treatment. Further high‐quality trials are needed and we encourage national health authorities to conduct large, multicentre, double‐blind, placebo‐controlled RCTs on the role of IS in preventing ARTIs in children.Plain Language SummaryImmunostimulants to prevent acute respiratory tract infections in childrenAcute respiratory tract infections (ARTIs) are responsible for 19% of all deaths in children younger than five years of age, mainly in low‐income countries in Africa, Asia and Latin America. In high‐income countries ARTIs are among the most frequent illnesses, leading to 20% of medical consultations, 30% of days lost from work and 75% of antibiotic prescriptions. In the USA the total cost of non‐influenza‐related viral ARTIs is around $40 billion annually, while the corresponding cost for influenza is US $87.1 billion. The main signs and symptoms of ARTIs include sneezing, runny nose, sore throat, cough and malaise. Children living in rural communities, not attending daycare centres, suffer about seven ARTI episodes in the first year of life; eight ARTIs per year from the ages of one to four; six per year aged five to nine; and five per year aged 10 to 19. Children exposed to risks factors, such as attendance at daycare centres, overcrowding, contact with older siblings, smoking at home and lack of breast feeding, may suffer more ARTIs.Several treatments have been used to reduce the incidence of ARTIs (vitamin A, vitamin C, zinc, antibiotics). Among them are immunostimulants (herbal extracts, bacterial extracts, synthetic compounds), which aim to increase the immune defences of the respiratory tract. We searched for clinical trials of immunostimulants to prevent ARTIs in children compared to placebo. Our review includes 35 studies with 4060 participants. However, the quality of many of the studies was poor and the results were very diverse.By combining results, immunostimulants reduced 1.24 ARTIs in a six‐month period, equivalent to a 39% reduction in ARTIs compared to the placebo group. Only 20 studies provided adequate data on adverse events: the most frequent were rash, nausea, vomiting, abdominal pain and diarrhea. The main limitations of this review were the poor methodological quality and diverse trial results. We conclude that ARTI‐susceptible children may benefit from immunostimulants, but more high‐quality studies are needed. We suggest that national health authorities conduct high‐quality randomized controlled trials to assess the true effects of immunostimulant preparations.

Cochrane Review: Immunostimulants for preventing respiratory tract infection in children

Del-Río-Navarro

Espinosa-Rosales

Flenady

et al. 2012

Cochrane Review: Antibiotics for whooping cough (pertussis)

Altunaiji

Kukuruzovic

Curtis

et al. 2012

BackgroundWhooping cough is a highly contagious respiratory disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis but its benefit is uncertain.ObjectivesTo assess the risks and benefits of antibiotic treatment of and contact prophylaxis against whooping cough in children and adults.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2010), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue 4, 2010), MEDLINE (1966 to January Week 1, 2011) and EMBASE (1974 to 18 January 2011).Selection criteriaRandomised controlled trials (RCTs) and quasi‐RCTs of antibiotics for treatment of and contact prophylaxis against whooping cough in children and adults.Data collection and analysisThree to four review authors independently extracted data and assessed the quality of each trial.Main resultsThirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; two investigated prophylaxis regimens. The quality of the trials was variable. For eradicating Bordetella pertussis (B. pertussis) from the nasopharynx, short‐term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long‐term (erythromycin for 10 to 14 days) (risk ratio (RR) 1.01; 95% confidence interval (CI) 0.98 to 1.04), but had fewer side effects (RR 0.66; 95% CI 0.52 to 0.83). Trimethoprim/sulphamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long‐term antibiotics. For preventing infection by treating contacts older than six months of age, antibiotics did not significantly improve clinical symptoms, nor the number of cases developing culture‐positive B. pertussis. Side effects were reported with antibiotics and they varied from one antibiotic to another.Authors' conclusionsAlthough antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefits of prophylactic treatment of pertussis contacts.Plain Language SummaryAntibiotics for whooping cough (pertussis)Whooping cough is a highly contagious disease caused by pertussis bacteria and may lead to death, particularly in infants less than 12 months of age. Although it can be prevented by routine vaccination, it still affects many people. Thirteen trials involving 2197 participants were included in this review. We found that several antibiotic treatments were equally effective in eliminating the bacteria infecting patients, but they did not alter the clinical outcome. There was insufficient evidence to decide whether there is benefit for treating healthy contacts. Side effects were reported with antibiotics and they varied from one antibiotic to another. The result of the review should be interpreted with caution since this review is based on a limited number of trials and some of these trials involved small numbers of participants.

Cochrane Review: Neuraminidase inhibitors for preventing and treating influenza in children (published trials only)

Shun-Shin

Gill

Perera

et al. 2012

BackgroundDuring epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed.ObjectivesTo assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children.Search methodsFor this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011).Selection criteriaDouble‐blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies.Data collection and analysisFour review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir.Main resultsSix treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near‐patient influenza testing were included. Of these 2356 children, 1255 had laboratory‐confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory‐confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory‐confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir‐resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory‐confirmed influenza (risk difference (RD) ‐0.14, 95% confidence interval (CI) ‐0.24 to ‐0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD ‐0.08, 95% CI ‐0.12 to ‐0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar.Authors' conclusionsOseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir‐resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high‐quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.Plain Language SummaryNeuraminidase inhibitors for preventing and treating influenza in childrenInfluenza (true 'flu) is an infection of the airways caused by the Influenza group of viruses. Influenza occurs most commonly during winter months and can result in symptoms such as fever, cough, sore throat, headache, muscle aches and fatigue. These are usually self limiting but may persist for one to two weeks. The most common complications of influenza are secondary bacterial infections including otitis media (ear infections) and pneumonia. Influenza infection is also highly contagious and is spread from person‐to‐person by droplets produced when an infected individual coughs or sneezes.This update reviews the randomised controlled trial evidence of a class of drugs called the neuraminidase inhibitors in treating and preventing influenza in children. Neuraminidase inhibitors work against influenza by preventing viruses from being released from infected cells and subsequently infecting further cells. Oseltamivir (Tamiflu), an oral medication, and zanamivir (Relenza), an inhaled medication, are currently licensed, whilst laninamivir is undergoing Phase III clinical trials. Neuraminidase inhibitors are usually prescribed to patients presenting with flu‐like symptoms during epidemic periods to reduce symptoms or prevent spread of the virus.We included six treatment trials involving 1906 children with clinically suspected influenza and 450 children with influenza diagnosed on rapid influenza testing. Of these 2356 children, 1255 had proven influenza infection confirmed on laboratory testing. We also included three trials of neuraminidase inhibitors for the prevention of influenza, which involved 863 children who had been exposed to influenza.This review found that treatment with neuraminidase inhibitors was only associated with modest clinical benefit in children with proven influenza. Treatment with oseltamivir or zanamivir shortened the duration of illness in healthy children by about one day. One trial demonstrated that the new neuraminidase inhibitor drug laninamivir reduces duration of illness by almost three days in children with oseltamivir‐resistant influenza. The effect of neuraminidase inhibitors in preventing transmission of influenza was also modest; 13 children would need to be treated to prevent one additional case. Neuraminidase inhibitors are generally well tolerated but there will be one extra case of vomiting for every 17 children treated with oseltamivir. Other side effects such as diarrhoea and nausea were no more common in children treated with neuraminidase inhibitors compared to placebo. There is currently no high‐quality evidence to support targeted treatment of 'at risk' children (with underlying chronic medical conditions) with neuraminidase inhibitors.