Introduction

Influenza or simply flu is a communicable disease caused by the Influenza virus. The Flu is mostly an acute disorder which is pretty common by onset and affects approximately 3  to 5 million people worldwide each year. It is estimated that up to 20% of the entire population is infected with influenza each year. Though flu is a vaccine-preventable disease it might cause severe infection depending on personal factors. The best way to combat flu is to get a vaccine each year but in some cases when people are hospitalized or have severe symptoms, an antiviral medicine is prescribed.¹

Though it is very common and is a vaccine-preventable disease,  it causes around 4 to 5 hundred thousand deaths each year.  

Understanding influenza

Influenza viruses belong to the family Orthomyxoviridae and cause respiratory tract infections in the general population. Furthermore, this virus can involve more than one system in the body, most frequently the nose and throat. There are mostly four distinct types of influenza viruses. They are type A, type B, type C, and type D. Among these, types A and B more commonly cause disease in humans. Type A has further subtypes and has caused pandemics in the past. The type C influenza virus is less common and causes milder symptoms. Type D influenza virus does not cause any disease in humans and mostly leads to infection in cattle.^1,2

Influenza spreads quickly and easily, especially in crowded places like schools, poorly ventilated offices, dorms, and hospitals. The most common way it spreads is when someone coughs or sneezes without covering their mouth and nose, releasing tiny droplets filled with viruses into the air. These droplets can infect people nearby. It can also spread when people touch contaminated surfaces and then touch their faces. To prevent it from spreading, people should cover their mouth and nose when sneezing or coughing, use tissues, keep a safe distance from others, and stay home if feeling unwell.^1,2

Once someone catches the flu, it usually takes about 2 days for symptoms to appear, though it can vary from 1 to 4 days. In places with cold winters, flu outbreaks typically happen during those months. However, in warmer areas, influenza can occur at any time of year, causing outbreaks less predictably.^1,2

Common symptoms of the flu are: fever, chills, sore throat, coughing, extreme tiredness, body ache, headache, and runny nose (stuffy nose sometimes). Some uncommon symptoms are diarrhoea, nausea, and vomiting which are mostly seen in older adults and children.^1,2

Antiviral medications for influenza

There aren't many drugs available to tackle influenza because vaccination is considered the most effective option to combat such a widespread disease. However, antivirals are kept in reserve for emergencies when some patients require them due to severe symptoms or during epidemic-like situations.³ 

There are three major types of antivirals recommended for influenza treatment:

1. Neuraminidase inhibitors: These include Tamiflu and Relenza which work by blocking a virus enzyme called neuraminidase. This enzyme helps new viruses escape from infected cells and spread to other cells. Neuraminidase inhibitors are intended to work against both type A and B influenza viruses.⁴
2. Ion channel blockers:  Amantadine and rimantadine are two examples which prevent the virus from entering host cells by blocking a protein called the M2 channel protein. However, these drugs aren't used as much anymore because the flu virus has become highly resistant to them.⁴
3. Polymerase inhibitors: Xofluza is an inhibitor that distorts the virus's ability to copy its genetic material by inhibiting the endonuclease (enzyme involved in DNA repair) activity of the polymerase acidic (PA) protein found in the influenza virus, thereby stopping the infection process.⁴

One drawback of neuraminidase inhibitors is that they need to be started within 48 hours of feeling sick with the flu to be most effective. Therefore, it's important to get diagnosed and treated quickly. If a person waits too long, these medications may not work well.³

Although antiviral drugs can help, they're not perfect. They might not completely eliminate the virus, and some people may experience side effects like nausea or headache. Additionally, the flu virus can sometimes change in a way that reduces the effectiveness of these drugs, a phenomenon known as antiviral resistance.^1,3

Getting vaccinated against the flu is the best way to prevent getting sick in the first place. Vaccines help the body build defences against the flu virus, reducing the likelihood of illness and complications. When vaccination is combined with antiviral drugs, it offers the best chance of staying healthy during flu season.^1,3

Commonly used antiviral medications

Oseltamivir (Tamiflu)

• Mechanism of Action: Oseltamivir belongs to the neuraminidase inhibitor class of antiviral medications. It works by blocking the activity of the neuraminidase enzyme, which the influenza virus needs to spread from infected cells to healthy cells.³
• Dosage and Administration: The recommended dosage of oseltamivir for the treatment of influenza varies depending on the age and weight of the patient. For adults and adolescents aged 13 years and older, the typical dosage is 75 mg twice daily for 5 days. For children younger than 13 years, the dosage is based on weight, ranging from 30 mg to 75 mg twice daily for 5 days.³
• Side Effects: Common side effects of oseltamivir include nausea, vomiting, headache, and stomach pain. In some cases, serious skin reactions and transient neuropsychiatric events (delirious behaviour) have been reported, although these are rare.³

Zanamivir (Relenza)

• Mechanism of Action: Zanamivir is also a neuraminidase inhibitor that works by blocking the activity of the neuraminidase enzyme, thereby preventing the spread of the influenza virus.³
• Dosage and Administration: Zanamivir is administered via inhalation using a special device called a Diskhaler. For treatment of influenza in adults and children aged 7 years and older, the recommended dosage is 10 mg (two 5-mg inhalations) twice daily for 5 days. For prophylaxis, the dosage is 10 mg (two 5-mg inhalations) once daily for 10 days.³
• Side Effects: Common side effects of zanamivir include the risk of bronchospasm (narrowing of the airways), especially in individuals with underlying respiratory conditions such as asthma or COPD. Other side effects may include sinusitis and dizziness. Serious skin reactions and transient neuropsychiatric events have been reported, albeit rarely.³

Peramivir (Rapivab)

• Mechanism of Action: Peramivir is a neuraminidase inhibitor that blocks the activity of the neuraminidase enzyme, similar to oseltamivir and zanamivir.³
• Dosage and Administration: Peramivir is administered intravenously (IV) as a single dose. The recommended dosage for the treatment of influenza varies depending on the age of the patient. For adults and children aged 6 months and older, the typical dosage is one 600 mg IV dose. The duration of treatment is typically one day.³
• Side Effects: Common side effects of peramivir include diarrhoea. Serious skin reactions and transient neuropsychiatric events have been reported, although they are rare.³

Newer generation antiviral medication:

Baloxavir marboxil (Xofluza)

• Mechanism of Action: Baloxavir marboxil is a newer-generation antiviral medication that belongs to the cap-dependent endonuclease inhibitor class. It inhibits the endonuclease activity of the viral polymerase acidic (PA) protein, thereby blocking virus replication.³
• Clinical Trials and Effectiveness: Clinical trials have shown the effectiveness of baloxavir marboxil in reducing the duration of influenza symptoms when compared to the placebo. It has shown excellent efficacy against both influenza type A and type B viruses.³
• Side Effects and Safety Profile: It has been found from the clinical trial that Baloxavir marboxil is well-tolerated, with fewer adverse incidents than other classes of drugs. Common side effects may include gastrointestinal symptoms such as diarrhoea. However, serious adverse events have been rare in clinical studies. Further, long-term safety data is required to come to a conclusion. This is only possible as the medication becomes more widely available in the market for use.³

Public health considerations

Antiviral drugs have an important role in public health, particularly in combating pandemics. It is expected that they are available on time, which requires a strong distribution network and priority of having such medicines should be given to the front-line personnel, vulnerable populations, and healthcare facilities. Despite the great significance of these antiviral medications, problems still exist, in the form of limited resources, manufacturing and distribution cycle, logistics, and the rise of antiviral resistance in the population.⁵

Conclusion

In summary, antiviral drugs are important tools in public health, especially in the fight against influenza and in reducing its severity during pandemics. Even if there are challenges to availability and resistance to antivirals, continued research and joint activities offer promising ways for achieving greater effectiveness and usability. The burden of morbidity and mortality 

from influenza could be reduced significantly if public health authorities focus on vaccination and the proper use of antiviral drugs. Prolonged investment in research, infrastructure, and capacity-building programs is needed to strengthen global health against the threat of new infectious diseases and to enhance preparedness for pandemics.