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بسم هللا الرحمن الرحيم This sheet was made from record section 1 all information are included - Introduction Our respiratory tract is divided anatomically to upper (URT),middle and lower(lrt). Viruses are considered the most common cause of URT infections. Any part of the respiratory tract is susceptible to viral infections, examples Rhinitis (aka: common cold, coryza): infection of the nasal mucosa and usually isn t limited to the mucosa and involves the paranasal sinuses so is also called Rhinosinusitis parenchyma. Pharyngitis: infection of the pharynx and usually it has tonsillar involvement as well. Bronchiolitis: lower respiratory tract infection in infants and young children in which they have small bronchioles so they can easily be obstructed, it is a serous disease that may hospitalize the infant and associated with respiratory syncitial virus (RSV) Lower respiratory tract usually involves the alveoli and the lung parenchyma resulting in pneumonia. So, we can conclude that many infections can happen in respiratory susceptible organs such as: nasal cavity, paranasal sinuses, tonsils, pharynx, larynx, epiglottis, trachea, bronchi, bronchioles Differences between flu and common cold: Fever is one of the signs that indicates systemic involvement (so It s most probably to be flu). Flu is also an URT infection. In flu, there is fever and the symptoms are more severe and persist for longer time. It also has systemic involvement (fever, myalgia, ). In common cold, the infection has no systemic involvement. Question: Can Influenza cause common flu? Influenza virus has types A, B and C, Influenza type A is the one responsible for endemics and epidemics, we can differentiate between these 3 types by structural differences: What is the structural difference between influenza A/B/C? Nucleoprotein (hemagglutinin, neuraminidase..) Influenza C can cause common cold with milder signs and symptoms 2 P a g e
Why do we care about knowing all this about common cold despite the fact that it isn t associated with high morbidity and has no mortality, but just associated with mild symptoms (cough, sneezing..)? Because there are other diseases that have similar symptoms to common cold but a different underlying cause. For example, allergic rhinitis has similar symptoms to common cold, in the case on allergic rhinitis the patient won t have only one episode of symptoms, instead he will suffer from the symptoms with frequent episodes. Since we can decrease the suffering of a patient with allergic rhinitis, we must know how to differentiate between them. NOTE: Viral infections predispose affected individuals to secondary bacterial infections which would be serious (for example, pneumonia can be preceded by UPT infections. What is the underlying mechanism that increase the susceptibility for patients to secondary bacterial infections? Up regulation of adhesion molecules as a result of inflammation Production of viral factors that expose the bacterial receptors on the epithelium dysfunction of some innate immune system components. Viral rhinitis (common cold, coryza, rhinosinusitis) Common cold is the conventional term of mild URT illness. The hallmark symptoms are nasal stuffiness, nasal discharge (rhinorrhea), sneezing, sore throat, and cough. - common cold is caused by numerous viruses that belong to different families. It is usually a self-limited illness confined to the URT. However, the viral infection in some patients can spread to adjacent organs, This will result in different clinical manifestations, and it could result in secondary bacterial manifestations. - Occasionally, common cold predisposes the individual to a secondary bacterial infection (like any viral infection) - Despite the usually benign nature of the illness, common cold is an enormous economic burden. This might be as a result of that people stay at home and thus work hours are reduced. 3 P a g e
-Transmission is through secretions of URT (nasal secretions, aerosols..) -It is usually mild but there are some Environmental factors and predisposing conditions that contribute to the severity of the infection (more severe infection) : The most important are smoking and pollution since they affect cilia movement. Causes of common cold Rhinoviruses are on the top of the list, most common cause of chronic rhinosinusitis. Notes on the table above: Regardless of method of detection, geographical region and season (since these factors affect the etiology of rhinosinusitis) the most common cause of common cold (chronic rhinosinusitis) is rhinoviruses (~50% of cases). Rhinoviruses are a member of picornaviruses, which is the smallest human RNA virus. All the above viruses are RNA viruses except adenoviruses RNA viruses have high rates of mutations like in flu there is antigenic drift. While antigenic shift is only present in flu virus since it has segmented genome, what does that mean? If a cell is affected by two different influenza viruses with different gene, there might be exchange of different gene segments upon assembly of a new viral particle resulting in a novel virus (which means Antigenic shift happened) that is responsible for pandemics since no one is immunized against it. 4 P a g e
Corona viruses are found in humans circulating for hundred years causing mild common cold except SARS and MARS which cause severe lower respiratory tract infection (more details later on). Again, influenza C is the one associated with common cold Again, RSV is associated with bronchiolitis in infants and young children which is serious LRT infection in children since there is a high probability of obstruction because they have smaller bronchioles. The doctor read the rest of the causes without any addition. No vaccines for common cold (more details later on) The rest 20-30% of cases are of unknown causes this is due to: because researches in the field of common cold gets limited funders since it is not associated with high morbidity and mortality. detection methods aren t sensitive enough for isolation of the underlying etiology. Metapneumovirus was recently described in 2001. So in the next years, there may be characterization of other infectious agents involved in URT infections There may be novel viral agents responsible for rhinosinusitis. The following table is important: 5 P a g e
*Coxsackie virus is one of the enteroviruses as well as echovirus,poliovirus,rhinovirus (those are specific members of enteroviruses that are associated with common cold). *Coxsackie virus A is associated with rhinitis (especially A21 : a last year question) while coxsackie B virus is associated with myocarditis. rhinovirus rhinoviruses are naked (non-enveloped). They are part of the picornaviridae family: named so because they are the smallest RNA viruses. It is a positive sense single-stranded RNA virus, non segmented. Rhinoviruses are divided to more than one species (A, B, and C). Every species has different serotypes. The sum of all types of rhinoviruses is more than 150 (until now)-this is the first reason why we don t have a vaccine others include : No need for vaccination against a mild disease that isn t associated with mortality and only little morbidity If we make a vaccine for the most common serotypes after time it will be ineffective because of the development of new types because of mutations. Why do we get common cold throughout our life? because each time you are infected with a different serotype which doesn t immunize you against other serotypes. Phylogenetic tree of rhinovirus (highly IMPORTANT: the doctor said that there is exam question about it) 6 P a g e
A phylogenetic tree is a representation of the relationships between different strains of any organism including viruses The importance of it is classification of strains for example certain strains don t respond to treatment others don t have vaccine and so on What should we know from a rhinovirus phylogenetic tree? (IMPORTANT) Extensive genetic variability as we have 3 groups (A/B/C) : A ->77 types, B->25 types,c->49 types We say that rhino virus is a picoronaviridae member but it differs from other members by the following : Although it is naked it can't tolerate the acidity of the stomach that's why it doesn t cause GI diseases Optimal temperature for rhino replication isn t 37 which is the optimal for most viruses actually it is 33-35 and that's why it cause upper respiratory tract infection ( remember that nasal mucosa and URT temperature is lower than the core) Receptor for A and B is ICAM1(intra cellular adhesion molecule 1) Receptor for C is LDL receptor ( although it is associated with the liver it is also expressed in URT) Corona virus - It is an enveloped positive sense single-stranded RNA virus. Its nucleocapsid is of helical symmetry( you cant see it below because it is covered by an envelope) what is its importance? RNA associated with the nucleoprotein itself. - It got its name from its spikes described around the viral particle as solar corona under Electron microscope look at the below picture 7 P a g e
-corona causes URT infections except 2 types that cause severe lower respiratory tract infection which are : SARS(severe acute respiratory syndrome ): identified in 2003 and uses ACE2 (angiotensin converting enzyme 2)as a receptor MARS(middle east acute respiratory syndrome) : identified in 2012, we had some cases in Jordan..now it s controlled, it uses carboxy peptidase receptor (identified recently) Seasonal changes of causes of common cold: 8 P a g e
Notes on the graph above which is required: Many common viruses exhibit seasonal variations for example: influenza, respiratory syncytial virus has higher prevalence during winter months. While enteroviruses (such as coxsackie) have higher prevalence in late summer-early autumn IMPORTANT: some viruses are present year-round(in all seasons ) like adenoviruses we call this perennial so we say that adenoviruses is associated with perennial infections. Rotavirus is more common in winter but it isn t associated with respiratory infections. Why are respiratory viruses more common in winter? - No one knows the definitive cause. But the speculation is that in winter people stay inside their homes and don't go out that much; in conditions that are more crowded, so infection is more. Corona viruses in human are not able to establish GI manifestations or to initiate infections in GI tract, but in animals there is evidence that they can make GI manifestations and this can be explained by the presence of a receptor in GI tract. Coronaviruses have different types. Some cause URT infections and others cause SARS (Severe Acute Respiratory Syndrome), each has its own receptors. The most important strains we need to know are NL36, HKU1, 229E and OC43, these use aminopeptidase N as host receptor. While SARS coronavirus use ACE-2 as a receptor. Most coronaviruses spread to susceptible hosts by the respiratory route with the replication first occurring in the epithelial cells. Outbreaks occur primary in winter ( every 2-3 years). 9 P a g e
When you can't find the sunshine, be the sunshine. -Good luck- 10 P a g e