Acute 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.