Acute respiratory infections are common diseases worldwide with the highest incidence and
mortality rates, especially among children. Vietnam is one of the 15 countries with the
highest pneumonia rates in the world, with an estimated 2.9 million cases occurring
annually. The age group most susceptible to acute respiratory infections is children
under 5 years old, especially bronchiolitis, which often occurs in children under 2 years
old. The incidence of acute respiratory infections varies with the seasons, with the
highest prevalence of viral respiratory infections typically occurring during the winter
and spring. In tropical regions, acute respiratory infections are more common during the
rainy months, while in temperate regions, they are more prevalent during the winter
months. Approximately 30-60% of outpatient visits for medical care are due to acute
respiratory infections.
Currently, the prevention of acute respiratory infections in children still faces certain
limitations. Although there is a vaccine available for influenza, there are no vaccines
yet for RSV and adenovirus in children, and influenza vaccination needs to be repeated
annually to achieve optimal effectiveness. Therefore, maintaining respiratory and throat
hygiene is essential for both treatment and prevention, ensuring respiratory health for
children and reducing the risk of bacterial co-infections. Here, the investigators
propose that direct nasal spraying of probiotics may be a safe and effective method for
preventing respiratory diseases.
The objective of this study is to investigate the safety and preventive effects of two
types of nasal-spraying Bacillus probiotics: LiveSpo Navax (1 billion/mL x 30 mL B.
subtilis and B. clausii) and LiveSpo Navax Kid (containing 0.6 billion/mL x 30 mL B.
subtilis and B. clausii) in preventing respiratory diseases in healthy children attending
preschools. The investigators will evaluate the preventive efficacy in terms of reducing
the number of respiratory disease episodes and the number of courses of antibiotics in
children after 2 weeks and 4 weeks of using LiveSpo Navax and LiveSpo Navax Kid.
A randomized, double-blind, and controlled clinical trial will be conducted. Parents of
the will be required to provide various information about their children, including their
full names, sex, ages, respiratory infection history, and history of antibiotic use...
After obtaining informed consent, 600 children will be randomly assigned to three groups
(n = 200/group): the control group (referred to as the "Control" group) will receive 0.9%
NaCl physiological saline, the experimental group 1 (referred to as the "Probiotic 1"
group) will receive the probiotic LiveSpo Navax product, and the experimental group 2
(referred to as the "Probiotic 2" group) will receive the probiotic LiveSpo Navax Kid.
Children will be provided with coded nasal sprays in blinded samples to ensure the
objectivity of the study. Clinical examinations and monitoring will be conducted after 2
weeks and 4 weeks of the experiment. Nasopharyngeal samples will be collected at the same
time as the clinical examinations to assess the presence of probiotic spores in the
children's nasal mucosa. During the trial, children's typical clinical symptoms of
respiratory tract infections are monitored, including runny nose, stuffy nose, sneezing,
sore throat, cough, and fatigue. Data is collected on the number of cold or illness
episodes, the average duration of each illness episode, the number of days absent from
school, and medication history after 2 weeks and 4 weeks of participating in the study.
The children's health conditions are observed by caregivers, and the information is
recorded in medical records. During this study, parents or caregivers are asked to
refrain from giving their children other probiotics, whether via nasal spray or oral
administration, and to avoid cleaning their children's noses with other 0.9% NaCl
physiological saline sprayers. Data collection and statistical analysis will involve
collecting individual medical records and systematically organizing the children's
information into a dataset.
The prevention efficacy of LiveSpo Navax product (Probiotic 1 group) and LiveSpo Navax
Kid (Probiotic 2 group) is evaluated and compared to 0.9% NaCl physiological saline
(Control group) based on the following clinical and survey criteria: (i) reduction in the
percentage (%) of children with respiratory infections; (ii) reduction in the number of
colds, illnesses, or respiratory tract infections in children; (iii) reduction in the
duration of medication usage and the number of medication episodes in the treatment of
respiratory diseases. Tabular analysis is performed on dichotomous variables using the χ2
test or Fisher's exact test when the expected value of any cell is below five. Continuous
variables are compared using either the t-test or the Mann-Whitney test when the data is
not normally distributed. Statistical and graphical analyses are conducted using GraphPad
Prism v8.4.3 software (GraphPad Software, CA, USA). The significance level for all
analyses is set at p < 0.05.
Detection of B. subtilis ANA4 and B. clausii ANA39 in nasopharyngeal samples was
conducted at 2 weeks and 4 weeks using real-time PCR with SYBR Green following the ISO
17025:2017 guidelines. This testing was performed at the Spobiotic Research Center.