COMMON COLD Dr.M.Shahparianpour

Common Cold Syndrome is a general term of acute inflammatory disease of the upper respiratory tracts such as nasal cavity, tonsils, pharynx and larynx etc.

Common Cold Syndrome includes rhinitis, tonsilitis, pharyngitis, laryngitis (including croup), pharyngo-laryngitis etc. Sometimes Influenza (the flu) and sinusitis are characterized as a common cold syndrome.

Subjective symptoms are variously related with the region of upper respiratory tracts such as: snivel, nasal obstruction, sneezing, sore throat (pain, thirst feeling and hoarseness), cough, sputum, headache, fever, general malaise (laziness), muscle pains, arthralgia (joints pain) Digestive troubles such as nausea, vomiting, diarrhea and abdominal pain are often recognized with various subjective symptoms mentioned above.

In influenza infection (flu), these subjective symptoms are seen acutely and strongly.

Comparison of Influenza and the Common Cold

Common cold Influenza Features More gradual Abrupt Onset Uncommon Common Fever Severe, common Myalgia Arthralgia Anorexia Mild, uncommon Headache

Very mild, short lasting Mild to moderate Common, severe Cough (dry) Mild Severe Malaise Very mild, short lasting More common than with the common cold; lasts 2 to 3 weeks Fatigue, weakness Chest discomfort Common Occasional Stuffy nose Sneezing Sore throat

The common cold may be caused by more than 100 different viruses.

Medications can help relieve cold symptoms, but only time can cure a cold.

Although many people are convinced that a cold results from: 1. exposure to cold weather 2. from getting chilled or overheated 3. fatigue, or sleep deprivation. these conditions have little or no effect on the development or severity of a cold.

On the other hand, research suggests that : psychological stress allergic disorders affecting the nasal passages or throat menstrual cycles may have an impact on a person's susceptibility to colds.

Viruses Associated with Respiratory Infections

Common cold Acute respiratory infections, predominantly rhinovirus infections, are estimated to cause 30-50% of time lost from work by adults and 60-80% of time lost from school by children.

Common cold UP TO 6 COMMON COLDS/YEAR IN ADULTS AND 8 COMMON COLDS/YEAR IN CHILDRENS ACCEPTABLE.

Common Cold Viruses Common colds account for one-third to one-half of all acute respiratory infections in humans. Rhinoviruses are responsible for 30-50% of common colds, coronaviruses 10-30%. The rest are due to adenoviruses, enteroviruses, RSV, influenza, and parainfluenza viruses, which may cause symptoms indistinguishable to those of rhinoviruses and coronaviruses.

Common Cold Viruses % COLD SEROTYPE VIRUSES 60 +100 RHINOVIRUS 15 2 CORONAVIRUS < 10 3 INFLUENZA 4 PARA INFLUENZA <10 R S V 47 ADENOVIRUS +40 ENTROVIRUS

Rhinovirus Belong to the picornavirus family ssRNA virus acid-labile at least 100 serotypes are known

Rhinovirus

Rhinovirus Rhinovirus infections are chiefly limited to the upper respiratory tract but may include otitis media and sinusitis. Rhinovirus plays a role in exacerbations of asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and patients who are immunocompromised. Although infections occur year-round, the greatest incidence is in the fall and spring. Of persons exposed to the virus, 70-80% have symptomatic disease.

Pathophysiology Rhinoviruses are transmitted to susceptible individuals by : direct contact aerosol particles infecting both ciliated areas of the nose and nonciliated areas of the nasopharynx through receptors, most frequently ICAM-1 (found in high quantities in the posterior nasopharynx). Few cells are actually infected by the virus, and the infection involves only a small portion of the epithelium.

Pathophysiology Symptoms develop 1-2 days after viral infection, peaking 2-4 days after inoculation, although reports have described symptoms as early as 2 hours after inoculation with primary symptoms 8-16 hours later.

Pathophysiology Detectable histopathology causing the associated nasal obstruction, rhinorrhea, and sneezing is lacking: which leads to the hypothesis that the host immune response plays a major role in rhinovirus pathogenesis. Infected cells release interleukin-8 (IL-8), which is a potent polymorphonuclear (PMN) chemoattractant. Concentrations of IL-8 in secretions correlate proportionally with the severity of common cold symptoms. Inflammatory mediators, such as kinins and prostaglandins, may cause vasodilatation, increased vascular permeability, and exocrine gland secretion. These, together with local parasympathetic nerve-ending stimulation, lead to cold symptoms

Pathophysiology Viral clearance is associated with the host response and is due, in part, to the local production of nitric oxide. Serotype-specific neutralizing antibodies are found 7-21 days after infection in 80% of patients. Although these antibodies persist for years, providing long-lasting immunity, recovery from illness is more likely related to cell-mediated immunity. Persistent protection from repeat infection by that serotype appears to be partially attributable to immunoglobulin A (IgA) antibodies in nasal secretions, serum immunoglobulin G (IgG), and, possibly, serum immunoglobulin M (IgM).

Pathophysiology The virus has a limited temperature range in which it can grow (33-35°C) and cannot tolerate an acidic environment. Thus, finding the virus outside of the nasopharynx is unlikely because of the acidic environment of the stomach and the temperature elevation in both the lower respiratory and gastrointestinal tracts.

Pathophysiology

Pathophysiology Deficient interferon beta production by asthmatic bronchial epithelial cells has been proposed as a mechanism for increased susceptibility to rhinoviral infections in individuals who are asthmatic.

Rhinovirus Sex: Some reports indicate a male predominance of infection in children younger than 3 years, which switches to a female predominance in children older than 3 years. No difference in rates of infection in adults is apparent. Age: Disease occurs most frequently in children, with decreasing incidence as they approach adulthood. Children are instrumental in transmission of infection, commonly passing infection to family members after contracting the virus in nurseries, day care facilities, or schools.

Rhinovirus Rhinovirus transmission occurs with close exposure to infected respiratory secretions, including: hand-to-hand, self-inoculation of eyes or nose, possibly, large- and small-particle aerosolization. The virus has been cultured from the skin for up to 2 hours and up to 4 days on inanimate objects in ideal conditions. Donors are typically symptomatic with a cold at the time of transmission, and virus is detected on their hands and nasal mucosa.

Rhinovirus Higher rates occur in humid, crowded conditions, as found in nurseries, day care centers, and schools, especially during cooler months in temperate regions and rainy season in tropical regions.

RISK FACTOR FOR MORE SEVER COMMON COLD LOW NEUTRALIZING Ab CHRONIC LUNG DISEASE EXTREMES AGE ASTHMA ALLERGY Ig E CYTOKINE PRODUCTION I F N -gamma I L-5

Physical examination Red nose with dripping nasal discharge may be present. Nasal mucous membranes have a glistening, glassy appearance without obvious erythema and edema. Yellow or green nasal discharge does not indicate bacterial infection because a large number of white blood cells migrate to the site of viral infection. Auscultation of the chest may reveal rhonchi

Physical examination If marked: 1. erythema, edema, exudates, or small vesicles are observed in the oropharynx 2. conjunctivitis 3. polyps in the nasal mucosa occur, consider other etiologies, including: adenovirus, herpes simplex virus, mononucleosis, diphtheria, Coxsackie A virus, or group A streptococcus (GAS).

TREATMENT

TREATMENT

TREATMENT Rhinovirus infections are predominately mild and self-limited: thus, treatment is generally focused on symptomatic relief and prevention of person-to-person spread and complications. The mainstays of therapy include: rest, hydration, antihistamines, nasal decongestants.

TREATMENT Antibacterial agents are not effective unless bacterial superinfection occurs.

TREATMENT Development of effective antiviral medications has been hampered by the short course of these infections. Because peak symptom severity occurs at 24-36 hours after inoculation, only a narrow window of time exists in which antivirals could positively impact upon this infection. In addition, the cause of the common cold is not always rhinovirus. Therefore, rapid and accurate diagnostic tests would be needed if a specific antiviral therapy were developed.

TREATMENT Because of the large number of rhinovirus immunotypes and the inaccessibility of the conserved region of the viral capsid (the most likely effective site for targeting a vaccine), no rhinovirus vaccine is on the horizon.

TREATMENT Because infection is spread by: hand-to-hand contact, autoinoculation, possibly, aerosol particles, emphasize appropriate hand washing, avoidance of finger-to-eyes or finger-to-nose contact, use of nasal tissue.

TREATMENT One study suggests that hand cleansers with salicylic acid and pyroglutamic acid prevent the transmission of rhinovirus as well as the number of patients who become clinically infected.

TREATMENT Heated, humidified air has been used for decades for the alleviation of symptoms due to rhinovirus infections but has never been shown to improve objective outcome measures

TREATMENT Pleconaril inhibits approximately 92% of rhinovirus serotypes. Susceptibility to pleconaril is dependent on the viral capsid surface protein VP1. 400 mg PO tid for 5 days, initiated within 24 hours of symptom onset, resulted in a decrease in the duration of symptoms by 1 day.

TREATMENT intranasal interferon-alpha-2b + ipratropium + oral naproxen started within 24 hours of rhinovirus inoculation resulted in a decrease in viral shedding, geometric mean virus titers, and symptoms in the treatment group.

Recombinant interferon-alpha-2b TREATMENT Recombinant interferon-alpha-2b applied topically to the nose at 5 million U or more a day prevented experimental infections. Unfortunately, the effect of this agent on symptomatic illness was limited.

TREATMENT A recombinant soluble ICAM-1 administered intranasally after rhinovirus challenge was analyzed in a randomized, double-blinded study. Neither strategy affected the incidence of infection, but combining results from both treatment groups found : 23% decrease in clinical colds, 45% decrease in total symptom score, 56% decrease in total nasal secretion weight.

TREATMENT ruprintrivir, a 3C protease inhibitor delivered as a nasal spray was well tolerated and resulted in decreased positive viral culture results and improved symptom scores but did not decrease the frequency of colds. These drugs act by interfering with the cleaving of a single large polyprotein that produces individual structures and enzymatic proteins of the virus.

TREATMENT Dietary supplements have been touted as possible therapeutic or preventive measures. large doses of vitamin C have been used for prevention and treatment of colds, controlled trials reveal minimal therapeutic benefit and no preventive qualities. Zinc has been found to inhibit rhinovirus replication in vitro but no proven benefit has been shown in vivo on virus activity or immune modulation

TREATMENT Echinacea purpurea has recently been studied and did not show any differences in rates of infection or severity of illness when compared with placebo

TREATMENT Patients may limit their activity during the course of the infection, with clinical improvement occurring 48-72 hours after the prodrome of symptoms.

MEDICATION Drugs used in the symptomatic treatment include: nonsteroidal anti-inflammatory drugs (NSAIDs) antihistamines anticholinergic nasal solutions These agents have no preventive activity and appear to have no impact on complications.

MEDICATION The combined effect of NSAIDs and antihistamines often relieves nasal obstruction; therefore, decongestion therapy is rarely needed. Oral (pseudoephedrine) and topical (oxymetazoline and phenylephrine) decongestants are commonly used for symptomatic relief.

MEDICATION First-generation antihistamines reduce rhinorrhea by 25-35%, as do: topical anticholinergics ipratropium bromide (spray) Second-generation or nonsedating antihistamines appear to have no effect on common cold symptoms. Corticosteroids may actually increase viral replication and have no impact on cold symptoms.

Complications Sinusitis: Viral infection of the sinus mucosa leads to alterations of sinus cavities, resulting in obstruction and entrapment of bacteria, such as Streptococcus pneumoniae unencapsulated strains of Haemophilus influenzae leading to bacterial sinusitis. The maxillary sinuses are involved most frequently.

Complications pathogens Otitis media: Rhinoviruses have been suggested as both rare pathogens copathogens with bacteria in the etiology of otitis media. They have been recovered in middle ear fluid of people with otitis media and potentially allow secondary bacterial infection from obstruction secondary to mucosal changes in the eustachian tubes.

Complications Precipitation of asthma: People with asthma have a greater number of viral respiratory infections than people without asthma. Rhinoviruses are also detected at the onset of symptoms; however, in a rhinovirus challenge model, exacerbations of wheezing was shown in a minority of adults, only 20% had a 10% or greater decrease in forced expiratory volume in 1 second (FEV1).

Complications Acute infectious episodes in patients with chronic bronchitis: Although rhinoviral invasion of the bronchial tree is unclear, alterations in ventilation and exacerbations of bronchitis have been described with rhinovirus infections.

Complications Deep respiratory tract infections: have been described in patients who are immunosuppressed elderly persons infants and children with cystic fibrosis however, determining the true impact of rhinovirus is difficult because it may be a marker of disease severity or an inciting event for other infectious process.

THANKS FOR YOUR ATTENTION !!!

Coronavirus ssRNA Virus Enveloped, pleomorphic morphology 2 serogroups: OC43 and 229E

Influenza Virus RNA virus, genome consists of 8 segments enveloped virus, with haemagglutinin and neuraminidase spikes 3 types: A, B, and C Type A undergoes antigenic shift and drift. Type B undergoes antigenic drift only and type C is relatively stable

Influenza A Virus Undergoes antigenic shifts and antigenic drifts with the haemagglutinin and neuraminidase proteins. Antigenic shifts of the haemagglutinin results in pandemics. Antigenic drifts in the H and N proteins result in epidemics. Usually causes a mild febrile illness. Death may result from complications such as viral/bacterial pneumonia.

Epidemiology Pandemics - influenza A pandemics arise when a virus with a new haemagglutinin subtype emerges as a result of antigenic shift. As a result, the population has no immunity against the new strain. Antigenic shifts had occurred 3 times in the 20th century. Epidemics - epidemics of influenza A and B arise through more minor antigenic drifts as a result of mutation.

Past Antigenic Shifts 1918 H1N1 “Spanish Influenza” 20-40 million deaths 1957 H2N2 “Asian Flu” 1-2 million deaths 1968 H3N2 “Hong Kong Flu” 700,000 deaths 1977 H1N1 Re-emergence No pandemic At least 15 HA subtypes and 9 NA subtypes occur in nature. Up until 1997, only viruses of H1, H2, and H3 are known to infect and cause disease in humans.

Avian Influenza H5N1 An outbreak of Avian Influenza H5N1 occurred in Hong Kong in 1997 where 18 persons were infected of which 6 died. The source of the virus was probably from infected chickens and the outbreak was eventually controlled by a mass slaughter of chickens in the territory. All strains of the infecting virus were totally avian in origin and there was no evidence of reassortment. However, the strains involved were highly virulent for their natural avian hosts. H9N2 Several cases of human infection with avian H9N2 virus occurred in Hong Kong and Southern China in 1999. The disease was mild and all patients made a complete recovery Again, there was no evidence of reassortment

Theories Behind Antigenic Shift 1. Reassortment of the H and N genes between human and avian influenza viruses through a third host. There is good evidence that this occurred in the 1957 H2N2 and the 1968 H3N2 pandemics. 2. Recycling of pre-existing strains – this probably occurred in 1977 when H1N1 re-surfaced. 3. Gradual adaptation of avian influenza viruses to human transmission. There is some evidence that this occurred in the 1918 H1N1 pandemic.

Reassortment

Laboratory Diagnosis Detection of Antigen - a rapid diagnosis can be made by the detection of influenza antigen from nasopharyngeal aspirates and throat washings by IFT and ELISA Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs. Serology - a retrospective diagnosis may be made by serology. CFT most widely used. HAI and EIA may be used to give a type-specific diagnosis

Management Amantidine is effective against influenza A if given early in the illness. However, resistance to amantidine emerges rapidly Rimantidine is similar to amantidine but but fewer neurological side effects. Ribavirin is thought to be effective against both influenza A and B. Neuraminidase inhibitors are becoming available. They are highly effective and have fewer side effects than amantidine. Moreover, resistance to these agents emerge slowly

Prevention Inactivated split/subunit vaccines are available against influenza A and B. The vaccine is normally trivalent, consisting of one A H3N2 strain, one A H1N1 strain, and one B strain. The strains used are reviewed by the WHO each year. The vaccine should be given to debilitated and elderly individuals who are at risk of severe influenza infection. Amantidine can be used as an prophylaxis for those who are allergic to the vaccine or during the period before the vaccine takes effect.

Adenovirus ds DNA virus non-enveloped At least 47 serotypes are known classified into 6 subgenera: A to F

Clinical Syndromes 1. Pharyngitis 1, 2, 3, 5, 7 2. Pharyngoconjunctival fever 3, 7 3. Acute respiratory disease of recruits  4, 7, 14, 21 4. Pneumonia 1, 2, 3, 7 5. Follicular conjunctivitis 3, 4, 11 6. Epidemic keratoconjunctivitis 8, 19, 37 7. Pertussis-like syndrome 5 8. Acute haemorrhaghic cystitis 11, 21 9. Acute infantile gastroenteritis 40, 41 10. Intussusception 1, 2, 5 11. Severe disease in AIDS and other immunocompromized patients 5, 34, 35 12. Meningitis 3, 7

Laboratory Diagnosis Detection of Antigen - a rapid diagnosis can be made by the detection of adenovirus antigen from nasopharyngeal aspirates and throat washings. Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates, throat swabs, and faeces. Serology - a retrospective diagnosis may be made by serology. CFT most widely used.

Treatment and Prevention There is no specific antiviral therapy. A vaccine is available against Adult Respiratory Distress Syndrome. It consists live adenovirus 4, 7, and 21 in enterically coated capsules. It is given to new recruits into various arm forces around the world.

Parainfluenza Virus ssRNA virus enveloped, pleomorphic morphology 5 serotypes: 1, 2, 3, 4a and 4b No common group antigen Closely related to Mumps virus

Clinical Manifestations Croup (laryngotraheobroncitis) – most common manifestation of parainfluenza virus infection. However other viruses may induce croup e.g. influenza and RSV.

Clinical Manifestations Other conditions that may be caused by parainfluenza viruses include: Bronchiolitis Pneumonia Flu-like tracheobronchitis Coryza-like illnesses

Laboratory Diagnosis Detection of Antigen - a rapid diagnosis can be made by the detection of parainfluenza antigen from nasopharyngeal aspirates and throat washings. Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs. Serology - a retrospective diagnosis may be made by serology. CFT most widely used.

Management No specific antiviral chemotherapy available. Severe cases of croup should be admitted to hospital and placed in oxygen tents. No vaccine is available.

Respiratory Syncytial Virus (RSV) ssRNA eveloped virus. belong to the genus Pneumovirus of the Paramyxovirus family. Considerable strain variation exists, may be classified into subgroups A and B by monoclonal sera. Both subgroups circulate in the community at any one time. Causes a sizable epidemic each year.

Clinical Manifestations Most common cause of severe lower respiratory tract disease in infants, responsible for 50-90% of Bronchiolitis and 5-40% of Bronchopneumonia Other manifestations include croup (10% of all cases). In older children and adults, the symptoms are much milder: it may cause a coryza-like illness or bronchitis.

Infants at Risk of Severe Infection 1. Infants with congenital heart disease - infants who were hospitalized within the first few days of life with congenital disease are particularly at risk. 2. Infants with underlying pulmonary disease - infants with underlying pulmonary disease, especially bronchopulmonary dysplasia, are at risk of developing prolonged infection with RSV. 3. Immunocompromized infants - children who are immunosuppressed or have a congenital immunodeficiency disease may develop lower respiratory tract disease at any age.

Laboratory Diagnosis Detection of Antigen - a rapid diagnosis can be made by the detection of RSV antigen from nasopharyngeal aspirates. A rapid diagnosis is important because of the availability of therapy Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates. However, this will take several days. Serology - a retrospective diagnosis may be made by serology. CFT most widely used.

Treatment and Prevention Aerosolised ribavirin can be used for infants with severe infection, and for those at risk of severe disease. There is no vaccine available. RSV immunoglobulin can be used to protect infants at risk of severe RSV disease.