A quick review on flu and the growing role of Oseltamivir

Influenza is regarded to be a highly infectious and fast-spreading contagious disease of the respiratory system and is mainly caused by viruses that usually infect the nose, throat, and lungs. (1) The common influenza viruses are categorized into Types A and B. The seasonal flu epidemics that are encountered each year are a result of these two types primarily. (1)

Disease Burden of Flu-An eye-opening insight-

A major study has highlighted that 2,91,243–6,45,832 seasonal influenza-associated respiratory deaths (4·0–8·8 per 100 000 individuals) occur annually. The team further confirmed that the highest mortality rates were estimated in Sub-Saharan Africa and Southeast Asia, and among people aged 75 years or older. These results underscore the obvious fact that influenza contributes to a substantial annual burden of deaths globally, with the greatest effect among low-income countries. The team also highlighted that, for 92 countries, 9243–1,05, 690 influenza-associated respiratory deaths occur annually among children younger than 5 years. (2)

According to the estimates put forth by the National Foundation for Infectious Diseases, an average of 20,000 children under the age of 5 are hospitalized due to flu complications each year (3).

A sneak peek at the virus-

Types of flu virus-Influenza viruses are members of the family Orthomyxoviridae. There are four genera of this family: types A, B, C, and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans (4).

• Type A-Influenza pandemics are characterized by the occurrence (recurrence) of influenza A subtype against which the majority of the human population is not immune (4). (Type-A possesses an outstanding characteristic of rapid evolution which leads to its great variability. Depending on the antigenic properties of their envelope proteins, influenza A viruses are subdivided into several subtypes (4). To date, 16 different haemagglutinin (HA) and 9 different neuraminidase(NA) subtypes have been identified (4).

While influenza B infections occur only in humans, influenza A viruses can also infect pigs and horses. Wild birds and chickens are considered a reservoir for influenza A viruses (4). Infections with the so-called highly pathogenic A subtypes can occur in chickens and other birds; causing the clinical picture of classical avian plague (highly pathogenic avian influenza; HPAI), often also called bird flu. The cause for this is that the virus can replicate throughout the bird's body, resulting in disease with a very high mortality rate (4).

• Type B-Though the influenza B virus has a similar structure to type A, it is characterized by mechanisms of 'antigen drift' and 'insertion and deletion mutations. Antigen drift refers to the tiny mutations in the genetic structure of the virus causing changes in the surface proteins which are regarded as antigens (5). Thus, this virus has diverged into 2 antigenically distinguishable lineages that have been co-circulating among humans and stable for more than 20 years now (4).

How does the virus spread?

Regarded to be an aerosol infection spreading through relatively large droplets (>5 μm) created particularly while talking, coughing, or sneezing, the influenza virus enters the mucosae through contact at small distances. (4) Research has revealed that virus transmission occurs by so-called droplet cores which are smaller (<5 μm) and are able to remain in the air for longer periods (aerogenic transmission). Direct contact with virus-contaminated surfaces can further aid in transmission (4). The viruses start multiplying in the nasal and laryngeal mucosae, once the transmission is accomplished. Gradually, the lower respiratory airways get infected, as the infection progresses (4).

Managing influenza: The role of neuraminidase inhibitors-

Neuraminidase inhibitors are used globally for the treatment and prophylaxis of influenza (6).

According to recent research reports, neuraminidase inhibitor (NAI) such as Oseltamivir (when given to patients with influenza-related pneumonia within 48 hours of disease onset) has been associated with lowering the likelihood of dying or requiring ventilator assistance, in comparison to those treated at later hours (7).

Studies have now affirmed that the greatest effect is classically seen when therapy is started in the first 24 hours (7). Treatment is recommended for both adults and children with influenza virus infection when they fall under the given criteria (1).

• Laboratory -confirmed as well as highly suspected influenza virus-infected patients, in high-risk groups, within 48 hours after symptom onset.
• Patients requiring hospitalization for laboratory-confirmed or highly suspected influenza disease, regardless of underlying illnesses, if treatment can be initiated within 48 hours after symptom onset.
• Outpatients are at high risk of complications with an illness that shows no signs of improvement.
• Outpatients with a positive influenza test result from a specimen obtained >48 hours after symptom onset (5).

Analyzing the position of Oseltamivir in treating influenza- study testimonials

• Reviews have highlighted that oseltamivir is a commonly used and stockpiled drug employed against seasonal and pandemic influenza based on international and national recommendations; these recommendations are justified owing to the ability of oseltamivir to reduce complications and transmission of influenza (6).
• Analyzing the effect of oseltamivir, a review revealed that in the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.7 hours. This represents a reduction in the time to first alleviation of symptoms from 7 days to 6.3 days in the oseltamivir group compared with the control group (6).
• Prophylaxis trials have highlighted that oseltamivir reduced symptomatic influenza in participants by 55% (6).
• According to the Roche trial program, assessing the effects of oseltamivir in post-exposure prophylaxis, researchers noted that when randomized to oseltamivir 75 mg a day or placebo for seven days, oseltamivir could prevent influenza in contacts by interrupting transmission from index cases (6).

Recommendations- Oseltamivir phosphate is one of the first-line antiviral drugs approved by the FDA and recommended by the CDC to treat flu. This drug has also been recommended by CDC for the treatment of flu in children beginning from birth, while the American Academy of Pediatrics (AAP)recommends oseltamivir for the treatment of flu in children 2 weeks old or older. (8)

Being listed by WHO in the list of World Health Organization essential drugs, Oseltamivir has been advocated for prompt use in patients who have severe or progressive clinical illnesses (9).

Key pointers-

• Oseltamivir is a well-tolerated orally active neuraminidase inhibitor that significantly reduces the duration of symptomatic influenza.
• It is equally effective in patients with naturally acquired influenza and hastens the return to normal levels of activity when initiated promptly.
• It, therefore, represents a useful therapeutic alternative for influenza, both in adults and children.

The way forward-With study results reveal that influenza epidemics are estimated to cause approximately 500,000 deaths per year worldwide (4), and successful management of the disease is a challenge for physicians. While early containment of flu is regarded to be a key factor in controlling the disease spread, the role of antivirals like Oseltamivir cannot be more stressed. A wealth of evidence continues to accumulate supporting the exceptional capacity of Oseltamivir to fight against this much-dreaded disease. As more studies unveil the full potentiality of Oseltamivir, the future direction of influenza epidemics and pandemics, to a large extent, depend on the balanced use of this drug.

References

1. https://www.cdc.gov/flu/index.htm

2. Iuliano, A. D., Roguski, K. M., Chang, H. H., Muscatello, D. J., Palekar, R., Tempia, Set.al (2018). Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. The Lancet, 391(10127), 1285-1300.

3. https://www.nfid.org/infectious-diseases/influenza-and-children/

4. ArbeitskreisBlut, Untergruppe «BewertungBlutassoziierterKrankheitserreger» (2009). Influenza Virus. Transfusion medicine and hemotherapy :offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 36(1), 32–39. https://doi.org/10.1159/000197314

5. https://www.cdc.gov/flu/about/viruses/change.htm

6. Jefferson T, Jones M, Doshi P, Spencer E A, Onakpoya I, Heneghan C J et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments BMJ 2014; 348 :g2545 doi:10.1136/bmj.g2545

7. Moghadami M. (2017). A Narrative Review of Influenza: A Seasonal and Pandemic Disease. Iranian journal of medical sciences, 42(1), 2–13.

8. https://www.cdc.gov/flu/treatment/whatyoushould.htm

9. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1)2009 and other Influenza Viruses Revised February 2010