Only health should not be taken lightly
respiratory syncytial virus , pathogenic threats for infants and young children
Shaanxi CDC Virus Institute Zhang Lei Yu Pengbo
Respiratory virus infection refers to a general term for a group of extremely common respiratory diseases caused by viruses, accounting for about 70 to 80% of acute respiratory infectious diseases. The main pathogenic viruses include influenza virus, respiratory syncytial virus, adenovirus , rhinovirus, coronavirus, parainfluenza virus, enterovirus and herpes simplex virus.
Among the pathogens of human viral respiratory infection, respiratory syncytial virus is one of the most important pathogens. In developing countries, about 50-90% of bronchitis and 40% of pneumonia patients are caused by respiratory syncytial virus, causing more than 3 million people to become ill each year and nearly 200,000 people to die, which is an important pathogen that causes the death of hospitalized infants under one year old.
human respiratory syncytial virus
human respiratory syncytial virus (hRSV) is widely distributed around the world. It is an important pathogenic pathogen of lower respiratory tract disease (LRI) in infants, the elderly and immunity-depressed adults. The RSV virus is widely prevalent, and the main infection targets are children under 5 years old and infants. It is reported that more than 33 million children under 5 years old are infected with RSV virus every year. RSV infection is an important cause of infant death in developing countries. The immunity produced by natural RSV infection is insufficient and cannot produce lasting immunity. Therefore, the prominent feature of RSV infection is that the antibodies produced in the body by the previous infection cannot provide permanent protection. In the same epidemic season, different subtypes of RSV can cause reinfection. Even if multiple natural RSV infections occur, they cannot induce lifelong immune protection against viral infection.
transmission characteristics and clinical symptoms
RSV transmission is mainly transmitted through droplets. Contaminated fingers directly inoculate the virus into the nasal and ocular mucosa. It is also an important transmission route that causes infection. The general incubation period of RSV in the respiratory tract is 4 to 5 days, and the lower respiratory tract symptoms usually occur 1 to 3 days after runny nose. Respiratory syncytial virus mainly causes pneumonia and bronchiolitis, and the clinical manifestations are mainly coughing, wheezing, and dampness and wheezing can be heard in the lungs. Respiratory syncytial virus infection can easily cause wheezing, which in turn induces asthma. The onset of RSV pneumonia infection shows symptoms of rhinitis and pharyngitis, followed by an increase in respiratory secretions and other inflammatory substances accumulate in the tiny bronchioles, resulting in the clinical manifestations of acute bronchioles characterized by cough, wheezing, fever and dyspnea. In addition to causing respiratory symptoms such as cough, wheezing and dyspnea, RSV infection can also cause damage to multiple systems such as the central nervous system, cardiovascular system and digestive system. Severe RSV infection may cause dyspnea and respiratory failure and require mechanical ventilation support. All cases of severe RSV infection have underlying diseases. RSV infection mainly causes bronchiolitis, obstructive pulmonary disease with excessive inflation, restrictive pulmonary parenchymal lesions with diffuse lung consolidation, intrapulmonary shunt and acute respiratory distress syndrome (ARDS). Chest images mainly manifest as interstitial pneumonia and obvious obstructive emphysema. The pathological changes are mainly: bronchioles, epithelial necrosis, cilium deficiency, lymphocyte infiltration, edema and congestion of submucosal and outer membranes, neutrophils and fibrin embolism, resulting in small airway blockage, intrapulmonary shunts, gas retention, decreased lung compliance, excessive inflation, imbalance in the proportion of ventilating blood flow and ventilator fatigue, which can easily cause wheezing and expiratory breathing.
Monitoring data from our province since 2009 showed that about 10.78% of patients were diagnosed with RSV. Among them, the RSV positive rate among hospitalized cases (14.95%) was significantly higher than that of outpatient cases (5.89%). According to age statistics, the RSV positive rate among 0 to 3 years old is relatively high, among which the 1-year-old age group has the highest positive detection rate (31.16%), which is significantly higher than that of other age groups. In addition, RSV infection in the elderly is also higher than that in other adults, and may also be related to the weak and sickly and low resistance of the elderly. Among the surveillance cases, 11.76% of patients with RSV infection were diagnosed with bronchitis and 10.93% of patients with pneumonia, which accounted for a significantly higher proportion than those with only upper respiratory tract infections. In addition, surveillance also found that RSV has certain in-hospital infection characteristics.Among hospitalized cases, most of them were RSV and other viral infections, accounting for 13.51%. Mixed infections may be related to low resistance.
Seasonal popularity characteristics
Geographical location, season and climate factors are the main factors affecting the popularity of RSV, and their popularity characteristics are also different in different regions, seasons and climates. In most countries, RSV infections are significantly seasonal despite some regional differences. In temperate regions, whether in the southern or northern hemispheres, RSV is prevalent in the months with lower temperatures, while RSV infections can be prevalent in areas near the equator. Shaanxi is located in the northern temperate zone and has a subtropical monsoon climate. It has distinct four seasons and is highly seasonal in RSV. Shaanxi Province has monitored RSV since 2009, indicating that the infection in our province is mainly in winter and spring. November to March of the following year is the month of RSV infection, and the positivity rate in November is as high as 14.7%. The RSV positive rate is negatively correlated with the average monthly temperature, total monthly sunshine time and monthly average wind speed, especially closely related to the temperature. The lower the temperature, the stronger the RSV activity. The dry climate in summer interferes with the propagation of aerosols containing RSV, and high temperatures can inactivate RSV, making it lose its infectivity. Sunshine time is also closely related to the epidemic activity of RSV. It may be because of the long sunshine time, high intensity, and strong ultraviolet rays, which have the effect of inactivated viruses, so RSV cannot be exerted. RSV activity is also negatively correlated with wind speed, which is low. The virus is prone to adhere to the skin surface of the body and colonizes the nasal mucosa, thereby increasing the chance of virus infection.
Studies have shown that the effect of seasonal intensive infection control strategies is better than targeted infection control strategies and can effectively prevent in-hospital transmission of RSV. That is, during the high incidence of RSV epidemic, the prevention and control of RSV infection in hospitals should be strengthened. Specific measures such as clear RSV case isolation and medical specialist system, strict disposable protective supplies in RSV wards, disinfection and sterilization measures for items entering and leaving RSV wards, and strict hand disinfection measures for medical staff, etc. The application of multi-channel comprehensive prevention and control measures is the best way to prevent hospital infection of respiratory syncytial virus.
clinical treatment strategy
Currently, the treatment of RSV is mainly supported treatment, hypertonic saline atomization treatment, bronchodilator and epinephrine treatment, glucocorticoid treatment, and there is no specific medicine. In addition, palivizumab can effectively prevent 80% of RSV infection in premature babies and alleviate the severity of the disease, but it is expensive and is only used for prevention and treatment of high-risk children.
symptomatic supportive treatment, and there is no specific treatment plan for RSV infection. For bronchioles caused by RSV, supportive treatment is usually provided, including oxygen, fluid replenishment, and maintaining respiratory tract unobstructed; parents of children should be advised to pay attention to feeding, and ensure sufficient nutrition during the disease period; wash hands frequently to prevent and treat cross-infection. During the course of the disease, closely monitor the children's respiratory rate, nasal fan, inspiratory trifoveal signs and other symptoms, monitor blood oxygen saturation, and prevent respiratory failure.
Other clinical treatment measures include: hypertonic saline (≥3% saline) atomization treatment can increase airway clearance by reducing airway edema, diluting sputum, stimulating cough reflex, etc., which can alleviate the clinical symptoms of children, reduce hospitalization rate, and shorten the hospitalization time. There are not enough clinical trials to prove that inhaled beta2 receptor agonist, ipratropium bromide and adrenaline spray are clearly effective in the treatment of RSV bronchioles. The combination of ipratropium bromide and β2 receptor agonist treatment can improve the clinical score of 24 hours compared with the placebo group. Therefore, it is believed that the concurrent inhalation of ipratropium bromide and β2 receptor agonist may be effective.
Due to the side effects of immunosuppression and other side effects of glucocorticoids, the indications and dose of glucocorticoids for the treatment of RSV are still controversial. Statistical analysis of the clinical treatment of bronchiolitis with glucocorticoids shows that glucocorticoids have the effect of improving clinical symptoms and shortening hospital stays to a relatively small extent. Therefore, it is not recommended to routinely use glucocorticoids for the treatment of bronchiolitis in the international community. The effectiveness of ribavirin in treating RSV infection is controversial. According to large clinical data statistics, the use of this drug to treat RSV bronchiolitis is not supported. At the same time, antibiotics are not advocated for the treatment of children with typical bronchioles.Palivizumab is a monoclonal antibody designed for the RSVF protein antigen epitope. At present, the use of Palivizumab in developed countries in high-risk babies, especially premature babies, can effectively prevent 80% of RSV infections and alleviate the severity of the disease. Due to its high price and the time required for injection, Palivizumab is generally only used in susceptible children with high risk factors. Current status of
vaccine research
There is currently no effective vaccine to prevent RSV infection, and vaccine development is still in the clinical trial stage, mainly targeting subunit vaccines for F proteins and G proteins. The current vaccine research progress is mainly as follows:
1. Live attenuated vaccine: The immune response produced by live attenuated vaccine is similar to that of self-infection, and it induces a balanced immune response. When the vaccinated person is infected with wild-type virus, it will not aggravate the condition, and it can be infected and replicated when maternal antibodies are present in the newborn. Cold passage (cp)RSV is the most mature live vaccine currently studied, with good genetic stability in rodents, chimpanzees and humans. At present, some attenuated strains have been obtained by further attenuating mutations and screening of low-temperature passage cells. These strains overcome the barriers of genetic instability and are not pathogenic in serologically negative adults and children, but have mild virulence in serologically negative infants and can be transmitted through contact. The mutant strains that are further attenuated are now being screened for satisfactory results.
2. Subunit vaccine: The development of subunit vaccine mainly targets two main antigens in RSV. It has good tolerance and moderate immunogenicity in older and high-risk children. It is also suitable for maternal immunity during pregnancy. The purified F glycoprotein (PFP), BBG2Na, fusion F, G and matrix protein M entered the clinical trial stage. The PFP vaccine is made from F full-length protein adsorption aluminum agent purified in RSV virus. Currently, there are 3 generations of PFP, namely PFP-1, PFP-2 and PFP-3. PFP is safe and immunogenic for healthy adults, children over 12 months of age and pregnant women. Results of phase II clinical trials of PFP-3 in children with cystic fibrosis show that the vaccine is safe, tolerated and immunogenic. But subunit vaccines cannot change Th2 dominant response.
3.DNA Vaccine: DNA vaccines can not only produce humoral immunity, but also produce cellular immunity. ① Vaccinia viral vector vaccine: Research on the expression of RSV antigens with vaccinia virus can be traced back to the mid-1980s. In 2004, the experiment of a recombinant RSV vaccine expressing RSVF and G proteins constructed with the modified modified vacciniavirus Ankara (MVA) vector failed in newborn monkeys and failed to induce it to produce effective immune protection. Since then, the research on the RSV vaccine vector that lasted more than 20 years has basically ended. ② adenovirus vector vaccine: Adenovirus type 4 and 7 have a long history of application in the US military. It induces immune protection effects through oral live adenovirus vaccines to prevent adenovirus respiratory infection. Therefore, adenovirus vector vaccine has better safety.
4. Recombinant Viral Vector Vaccine: Recombinant vaccines that use viruses as vectors to express RSVF and G glycoproteins have been tested in rodents and primates, such as vaccinia virus and adenovirus. Vac-F and vac-G immunized cotton mice have immunogenicity and protective effects. However, this vaccine does not produce lower respiratory tract protection when chimpanzees are weak and RSV is reinfected. In addition, the recombinant vaccination vaccine also has safety problems in infants. The new pox virus expresses RSV protein, but does not replicate infectious viruses in humans and can be considered for application in humans.
Preventive and Control Measures
1. Strengthening hand hygiene is an important means to prevent and control RSV hospital infection. Medical staff and patients’ families should pay special attention to hand hygiene to prevent cross-infection of RSV.
2. Isolation and treatment of respiratory diseases is an important measure to prevent and treat mixed RSV infection. It is also important to detect children with RSV infection as soon as possible and isolate them in time. Rapid bedside RSV detection can effectively improve the detection efficiency and provide a basis for timely isolation of children with RSV infection.
3. RSV is in high season, strengthen the disinfection and care of ward environment and medical items to prevent the cross-epidemic spread of various respiratory viruses.
4. In the high season of RSV, respiratory children should be treated in groups to reduce the chance of in-hospital infection.
