Colds and flu – an overview of the management

The common cold, otherwise known as a self-limiting upper respiratory tract infection, is caused by the rhinovirus, coronavirus or the adenovirus1. Symptoms like sneezing, nasal congestion, coughing, sore throat and a low grade fever are often experienced during the winter season2. A person may be contagious after being infected with the virus, but before they present with symptoms, and until after all the symptoms have subsided3. The viruses in question are airborne and spread quickly via hand-to-hand contact, or via the inhalation of airborne droplets from sneezing and coughing1.


REVIEW Introduction
The common cold is a self-limiting upper respiratory tract infection which is caused by the rhinovirus, coronavirus or the adenovirus. 1 Symptoms like sneezing, nasal congestion, coughing, sore throat and a low-grade fever are often experienced during the late autumn and winter season, from about early-May to August in South Africa. 2 A person may be contagious after being infected with the virus. 3The viruses in question are airborne and spread quickly via hand-to-hand contact, or via the inhalation of airborne droplets from sneezing and coughing (also refer to Figure 1  below). 1ter the virus enters the nasal cavity it damages the ciliated cells resulting in the release of inflammatory mediators and causing inflammation of the nasal tissue lining. 1 The increase in permeability of the capillary cell walls results in oedema.Oedema is responsible for symptoms like sneezing and nasal congestion. 1,3 postnasal drip may develop, which leads to a sore throat and coughing, which in turn is responsible for the spread of the virus. 1 Common colds are self-limiting and resolve within seven to ten days without the use of antibiotics.However, some people may end up developing a secondary bacterial infection. 2e common cold is often confused with influenza (flu).However, flu is a viral illness caused by a different virus, the influenza virus.It has a high mortality and hospitalisation rate. 4Influenza can occur all year round but is seen more often from May through winter.Due to the constant evolution of the influenza strains there is a higher fatality rate associated with the virus than with the viruses causing the common cold. 1 This epidemiological pattern reflects the changing nature of the antigenic properties of flu viruses and their subsequent spread, which depends upon multiple factors, including transmissibility of the virus and the susceptibility of the population. 1 The influenza virus is transmitted via air droplets when a person comes into close contact with an infected person or via selfinfection when a person comes into direct contact with an infected person or object. 5

Introduction
The common cold is a self-limiting upper respiratory tract infection which is caused by t rhinovirus, coronavirus or the adenovirus. 1 Symptoms like sneezing, nasal congestio coughing, sore throat and a low-grade fever are often experienced during the late autumn a winter season, from about early-May to August in South Africa. 2 A person may be contagio after being infected with the virus. 3The viruses in question are airborne and spread quick via hand-to-hand contact, or via the inhalation of airborne droplets from sneezing a coughing (also refer to Figure 1 below). 1ter the virus enters the nasal cavity it damages the ciliated cells resulting in the release inflammatory mediators and causing inflammation of the nasal tissue lining. 1 The increase permeability of the capillary cell walls results in oedema.Oedema is responsible for symptom like sneezing and nasal congestion. 1,3A postnasal drip may develop, which leads to a so throat and coughing, which in turn is responsible for the spread of the virus. 1 Common colds are self-limiting and resolve within seven to ten days without the use antibiotics.However, some people may end up developing a secondary bacterial infection.

Figure 1. Transmission of viruses that cause colds 2
The common cold is often confused with influenza (flu).However, flu is a viral illness caus by a different virus, the influenza virus.It has a high mortality and hospitalisation rate Influenza can occur all year round but is seen more often from May through winter.Due to t constant evolution of the influenza strains there is a higher fatality rate associated with t virus than with the viruses causing the common cold. 1 This epidemiological pattern reflec the changing nature of the antigenic properties of flu viruses and their subsequent sprea which depends upon multiple factors, including transmissibility of the virus and t susceptibility of the population.

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Table I.Types of influenza strains and their differences 1

Virus strain
Influenza A Influenza B

Severity of infection
Causes pandemics, like swine flu and bird flu Less severe than influenza A A rapid onset of fever, headaches, myalgia, body aches and pains, sore throat and rhinitis (runny nose) are associated with flu.These symptoms generally last for four to five days and then disappear, however a person may experience coughing and malaise for more than 14 days.

Management of colds and flu
Pharmacotherapy is directed at alleviating associated symptoms.Antibiotics are often prescribed erroneously, and in the absence of a secondary bacterial infection.Antibiotics should only be administered when a bacterial infection has been identified, and should not be used as a preventative measure.The following measures can be used to either prevent or treat the symptoms of a cold and flu (each of these recommendations will be discussed separately) 1,5 : • A flu vaccine is recommended by, amongst others, the Centers for Disease Control and Prevention (CDC) in the United States of America, as a preventative measure against the acquisition of the influenza virus.
• Selected over-the-counter (OTC) products contain a combination of active ingredients which help with symptomatic relief.
• Drinking plenty of fluids, especially water: Water has been shown to be the best fluid with which to hydrate and lubricate the mucous membranes.
• Vitamins and minerals, e.g.vitamin C and zinc sulphate.

Vitamins and minerals
The prophylactic use of vitamin C has been shown to reduce the risk of developing a cold or flu in certain populations, e.g.athletes, with a reduction of approximately 6% in the disease duration.However, the evidence that supports the use of vitamin C in high dosages to reduce the severity of a cold or flu is lacking and inconclusive.
Zinc may inhibit viral growth, and could possibly reduce the duration of cold symptoms.However, not enough high-quality trials support the routine and high-dosage use of zinc in preventing colds or flu.Some reports have been lodged with the US Food and Drug Administration (FDA) that nasal preparations containing zinc may cause loss of smell.Zinc may also reduce the absorption of certain antibiotics.Food containing calcium and phosphorus can impair the absorption of zinc. 7

Importance of hydration
Fluid (especially water) helps to lubricate the mucous membranes (and decreases sputum viscosity) of patients suffering from a cold or influenza.However, some literature contradicts this by suggesting that the provision of extra fluid to patients with acute respiratory conditions may cause hyponatraemia and fluid overload, because of the actions of antidiuretic hormone.This hormone is released in adults and children with lower respiratory tract infections and causes water reabsorption from the renal collecting duct.
The combination of the increased production of the antidiuretic hormone and extra fluid may lead to fluid overload.Research has not clearly illustrated this in upper respiratory infections yet and water hydration still remains of importance in the treatment of colds and flu. 1,8,9

Other strategies used to treat colds and flu
Anticholinergic agents, such as inhaled ipratropium bromide, may be used to treat a cough caused by a cold.Nasal preparations have shown some efficacy in reducing rhinorrhoea and sneezing.Inhaled corticosteroids can be used to reduce the swelling and inflammation of the nasal mucosa, but have not been shown to provide any benefit in patients diagnosed with a cold. 1 Conflicting evidence has emerged about the use of nasal irrigation.Nasal irrigation constitutes a mechanical intervention.It is not classified as a decongestant and does not improve ciliary function.Studies have shown that nasal preparations that contain a certain preservative, namely benzalkonium chloride, may worsen symptoms and infections.Nasal washes that contain a lot of fluid and minimal salt can be used to remove mucus from the nose, removing bacterial products, and improving sinonasal function.Nasal irrigation can be used prior to the administration of topical therapies to ensure true sinus distribution. 1,10ere are several different OTC medications that can be used to alleviate pain and fever associated with colds and flu.The typical active ingredients are aspirin, paracetamol and caffeine.Aspirin, however, is contraindicated in children who have a viral infection as they are at risk of developing Reye's syndrome. 1,2rbal products and supplements include substances like echinacea, Chinese herbal cold and allergy products, elderberry extracts, Andrographis paniculata, Pelargonium sidoides and Acanthopanax senticosus. 1,11Refer to Table II for more information.

Flu, or the influenza vaccine
The influenza vaccine is developed each year to protect you against the most common strains of flu.Flu vaccines provoke an immune response to the antigen found on the surfaces of the viruses.Antigenic drift can occur in the viruses, causing resistance to the vaccine. 12It is for this reason that recommendations are based on the World Health Organization's (WHO) accredited regional laboratories, and changes are made to the composition, in terms of strains of influenza every year. 13,14This antigenic drift is the reason why the vaccine that is released in September every year in the northern hemisphere is not always exactly the same as that released in February in the southern hemisphere.
Antibodies usually develop within two weeks of the vaccine being administered.A peak in immunity occurs four to six weeks after vaccination, which then gradually wanes again.It therefore does not convey lasting immunity against the influenza virus.Immunisation reduces the likelihood of flu developing in healthy adults by approximately 70-90%. 14If a family member or house mate has already developed flu, vaccination of other members of the household, within 36-48 hours, will still provide effective protection against the virus. 14Some individuals require the flu vaccine as a matter of priority; these involve pregnant women, immune-compromised individuals and others (refer to Table III).
In the southern hemisphere, it is recommended that the vaccine be given in April; however, it can be given throughout the winter season.Figure 2 depicts the adverse effects that are associated with the flu vaccine. 1

Combination products used for colds and flu
Treatment is mainly symptomatic and includes many OTC medicines, antivirals and herbal treatment.

Antitussive agents (cough suppressants)
Antitussive agents should only be given for a non-productive, dry, irritating cough (refer to Table IV).Care should be taken when giving antitussive agents as the coughing mechanism serves as a protective function of the body.Coughing clears the throat and the lower respiratory tract of foreign particles and mucus.Coughing that occurs as a result of bronchoconstriction and bronchospasm (coughing in asthma and COPD patients) should be treated with

Echinacea
No evidence supports the use of this product in the treatment of colds and flu.
People who are allergic to Echinacea develop erythema nodosum, which features tender, red nodules under the skin.

Chinese herbal cold and allergy products
No evidence supports the use of this product in colds and flu.
These products also pose the risk of renal damage and cancer as they contain aristolochic acid.
Elderberry extracts Some evidence supports the use of these extracts in shortening the duration of flu symptoms.However this has yet to be confirmed by bigger studies.
These extracts are unsafe when the leaves, stems, unripe fruit or uncooked fruit is consumed.

Pelargonium sidoides (commonly known as African geranium) and Acanthopanax senticosus
Literature has confirmed a reduction in the duration of 10 different flu symptoms.
There are isolated reports of liver toxicity; however, no causative relationship has been linked to the herb itself.
Table III

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bronchodilators.Coughing that is caused by a lower respiratory tract infection should be managed with appropriate antimicrobial agents.

Antihistamines
The first-generation antihistamines, such as chlorpheniramine, brompheniramine and promethazine, are used to reduce certain symptoms of a cold, like rhinitis and sneezing.This is due to the anticholinergic effects of these drugs.Some of the first-generation antihistamines are also used for their antitussive action and are combined in cold medicines to help patients sleep.Literature has stated that antihistamines used alone are of very little benefit in treating symptoms of colds and flu, but they do offer symptomatic relief when used in combination with decongestants and antitussive agents. 5 2006 the FDA issued a warning to parents and healthcare professionals against the use of promethazine-containing medicines which are contraindicated in children under the age of two years due to a fatal respiratory depression. 15

Expectorants and mucolytic agents
Expectorants and mucolytic drugs are used to alter the viscosity of mucous and bronchial secretions, thereby making it easier to cough up sputum. 1,16There are two ways of achieving this through pharmacological action: • By using expectorants to increase the volume of bronchial secretions and reduce the viscosity of these secretions.Guaiphenesin, sodium citrate and ammonium chloride are examples of expectorants.For obvious reasons, the use of cough mixtures containing an expectorant, as well as an antitussive agent, or combined with an antihistamine, should rather be avoided.
• By using mucolytic agents which act by altering the structure of mucus, thus resulting in a low mucus viscosity.Examples are: carbocisteine, bromhexine and N-acetylcysteine.Dornase alfa (recombinant human DNase) is used in patients with cystic fibrosis.
Non-pharmacological methods, like maintaining a good fluid hydration status and inhaling steam, can also reduce the viscosity of mucous secretions.

Oral decongestants
Oral sympathomimetic, systemic decongestants, like pseudoe-phedrine phenylpropanolamine and phenylephrine are now mainly available in combination in South Africa. 5Oral decongestants should only be used for a short period of time and as symptomatic relief for acute coryza, as part of colds and influenza.Topical agents are preferred as they have reduced systemic side-effects. 1Clear warnings should be given to patients about the use of oral decongestants with alcohol or certain drugs such as sedatives. 13,17

Nasal decongestants
Nasal congestion, a result of vasodilation and oedema of the nasal mucosa, can be alleviated using alpha-1 adrenergic agonists topically (nasal sprays), or orally.These topical decongestants are actually vasoconstrictors and, compared to a placebo, have shown a reduction in airway resistance. 1,5,13,17tiviral agents

Neuraminidase inhibitors
Two classes of antiviral therapy are available in South Africa: neuraminidase inhibitors and N-Methyl D-arspartate receptor antagonists.They play a major role in the treatment and prevention of both seasonal and avian influenza. 1,18Zanamivir and oseltamivir are currently available.These drugs are registered for the prophylaxis of the influenza A and B virus, and should be used within the first 24 hours of the onset of the symptoms.These agents act by inhibiting the enzyme involved in viral replication, neuraminidase.Important information regarding the use of these agents is listed in Figure 3. 1,18 Table V denotes the important differences between oseltamivir and zanamivir.

N-methyl D-aspartate receptor antagonists
Amantadine is an antiviral drug that is commonly associated with the treatment of Parkinson's disease.It is, however, also used in the prevention and treatment of influenza A. Amantadine acts by increasing the amount of dopamine from the nigrostriatal

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pathway and inhibits the reuptake of dopamine by the neurons.Amantadine is currently not recommended for treatment or use as an antiviral agent as there is widespread resistance to the drug. 1,13,18 the drug is being used for minor sensitive influenza strains the following should be noted: • Initiation of amantadine should occur within two days after contracting influenza A as it may reduce the duration of the disease.
• It cannot be used against influenza B.
• There is no literature which supports the drug preventing complications of influenza A.

Conclusion
The global rise in antimicrobial resistance is a call for absolute restraint in the use of antimicrobials, which includes both patients and healthcare professionals.Antibiotics should never be used to treat the common cold or flu, unless there is a secondary bacterial infection.There is insufficient evidence in the literature to support the use of OTC products for the prevention of these viral infections; however, vitamin C and zinc can be used as prophylaxis.Receiving the influenza vaccine may reduce the risk of acquiring seasonal influenza.Treatment is symptomatic; however, the use of many of the OTC medicines is not supported by literature.Certain herbal remedies such as P. sidoides extract, A. paniculata and elderberry may be effective, although one should always read the safety profile of these remedies before use.Codeine and antihistamines may be used in combination therapies to treat coughs and other cold symptoms.Paracetamol and other NSAIDs may be used to manage pain and fever in adults.Antivirals, such as the neuraminidase inhibitors, can be used in the prevention and treatment of both influenza A and B.
They are used to prevent/treat Influenza A and B.
If used within the first four days of the symptoms presenting, they can prevent complications of the virus.
They only reduce flu symptoms by one day and this reduction occurs only if the agent was started within 48 hours of the symptoms presenting.
Their use in avian ('bird') flu has not been fully established.
They can reduce the transmission of the virus.
Oseltamivir should be intitated in indviduals who are at a higher risk of contracting influenza and complications of influenza, such as immune-compromised patients.
Oseltamivir has been approved in paediatric patients older than one year.
Reports of fatal neuropsychiatric conditions have been filed.

Figure 3 .
Figure 3. Important information regarding the use of oseltamivir and zanamivir1,18

Table IV .
1,13st of individuals who would require the flu vaccine as a matter of priority1Over-the-counter medicine for the treatment of colds and flu1,13 Patients who suffer from any other disease which leaves them immune-compromised People who suffer from an underlying medical condition, e.g.diabetes mellitus, COPD, heart disease People older than 65 years of age, or infants between 6-49 months of age People staying in old age homes, frail care facilities and rehabilitation centres Healthcare workers who have direct contact with patients on a daily basis Patients who are on glucocorticosteroid therapy for long periods of time Allergic reactions in people who have an egg allergy Flu-like symptoms, which develop with 2-24 hours after vaccination Soreness and tenderness at the site of the injection Please Note: Individuals with allergies to eggs or chicken proteins should not recieve vaccines that are produced via eggbased culturing techniques.

Table V .
1,18rtant differences between zanamivir and oseltamivir1,18 19 the end of World War 2, influenza reappeared and prompted the WHO to co-ordinate a global network of research and surveillance from 1949.Subsequent pandemics, e.g. the so-called Asian flu in 1957, Hong Kong flu in 1968, and the 1976 swine flu scare in the USA, illustrated the role of natural reservoirs, e.g.pigs and wildfowl, as being instrumental in the introduction of new strains of influenza.Immunocompromising conditions such as HIV/AIDS and cancer highlighted the influenza pandemic; however, avian influenza and severe acute respiratory syndrome in the 1990s established new behavioural norms with influenza outbreaks: travel restrictions, mass slaughters of infected livestock, with intensive media interest, and worldwide anxiety.In the early 21st century, influenza remains a substantial cause of mortality.19