Flu season nothing to sneeze about

Flu season nothing to sneeze about

Annually, between 290 000 to 650 000 patients die as a result of seasonal influenzarelated complications. In South Africa, an annual fatality range of 7000 to 12 000 has been linked to complications. A recent study looked at the conventional belief that the influenza or flu season in South Africa starts with the onset of winter (June).1

According to Motlogeloa et al, the specific onset of influenza season in the country before their study was unclear, which impacted the healthcare sector’s ability to timeously administer flu vaccinations, and facilities to prepare for a potential increase in cases.1

So, when does influenza season start in South Africa?

Motlogeloa et al set about exploring statistical intensity thresholds to determine the actual start date of influenza season in South Africa. The teams used medical insurance claims data, which showed that South Africa’s influenza season starts in autumn (April) with a spike in cases during winter months (June to August).1

Don’t confuse a common cold with influenza

The common cold and influenza are both contagious but are caused by different viruses. A cold, which has a gradual onset, can be caused by a number of different viruses, including rhinoviruses, para-influenza, and seasonal coronaviruses. Cold symptoms such as sneezing, a stuffy nose and a sore throat, are usually milder than flu symptoms.2

Influenza is characterised by a sudden onset of symptoms such as fever, myalgia, cough, sore throat, rhinitis and headache. Uncomplicated influenza typically resolves after three to seven days, although cough and malaise can persist for >2 weeks. 3

Influenza is only caused by influenza viruses. In humans, the influenza virus is categorised into two main types: A and B. Influenza A is further subdivided into distinct subtypes, including influenza A(H1N1) pdm09 and A(H3N2). The subtype A(H1N1) pdm09 – commonly referred to as swine flu (but the term is frowned upon by the South African National Institute of Communicable Diseases [NICD]) – has similar symptoms to other seasonal influenza strains and should receive similar treatment as uncomplicated influenza, recommends the NICD. 2,3

At the time of writing this article, limited data were available about circulating influenza strains for the 2024 southern hemisphere influenza season. According to information published by the NICD at the end of January 2024, influenza B viruses have been detected earlier this year. According to the institute, clinicians should have a high index of suspicion for influenza in travellers presenting with respiratory symptoms, who have travelled from the northern hemisphere.4

Can influenza be prevented?

Influenza vaccination is the most effective method to prevent and control influenza infection. However, cautioned the NICD, vaccination does not rule out influenza infection. Ideally, vaccines should be administered at least 14 days before the start of the influenza season for the body to build immune responses to protect against infection. So, based on the data by Motlogeloa et al, mid-March is the ideal time to get vaccinated. 5,6

Who should be vaccinated?

Risk groups for severe/complicated influenza disease include:5

• Pregnant women and women up to six weeks post-partum

• People living with HIV

• Individuals living with tuberculosis (TB)

• Individuals of any age with chronic diseases:

• • Pulmonary diseases (eg asthma, chronic obstructive pulmonary disease [COPD])

• • Immunosuppression (eg individuals treated with immunosuppressive medication, or those living with malignancies)

• • Cardiovascular diseases (eg congestive cardiac failure, chronic heart disease, hypertension, stroke)

• • Metabolic disorders (eg diabetes)

• • Renal disease

• • Hepatic disease

• • Neurologic and neurodevelopmental conditions

• • Haemoglobinopathies (eg sickle cell disease)

• Individuals aged ≥65-years

• Individuals ≤18-years receiving chronic aspirin therapy

• Individuals living with morbid obesity (body mass index BMI ≥40/172kg2)

• Young children (particularly <2-years)

• Healthcare workers.

Additional groups that would benefit from influenza vaccination, provided there are sufficient vaccine supplies after prioritising the above-mentioned groups, include:5

• Individuals (adults or children ≥6-months) with an increased risk of influenza and related complications due to underlying medical conditions. This includes those receiving regular medical care for conditions such as TB, chronic renal disease, and metabolic disorders like inherited metabolic disorders and mitochondrial disorders

• Residents of old-age homes, chronic care facilities, and rehabilitation institutions

• Adults and children who are family contacts of individuals at a high risk of severe influenza

• Any individual who wants to minimise the risk of influenza infection – particularly in workplace settings where widespread absenteeism could result in significant economic losses.

Recommended treatment for influenza viral infection

The NICD recommends antiviral therapy as an adjunct to the influenza vaccine. Treatment initiation depends on clinical judgment, considering factors like disease severity, age, underlying conditions, and time since symptom onset.5

Antiviral treatment should ideally start within 48 hours of symptom onset, but it may still be beneficial for severe cases or hospitalisations beyond this timeframe.5

Neuraminidase inhibitors such as oral oseltamivir are recommended, showing reduced symptom duration and potential benefits against severe outcomes, although large-scale trials specifically evaluating severe outcomes are lacking. The standard adult dose for oseltamivir is 75mg twice daily orally for five days.5

Inhaled zanamivir is no longer recommended due to insufficient evidence. Adamantanes (amantadine and rimantadine) are not recommended due to high resistance levels.5

In the context of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-circulation, treatment for influenza remains the same for all patients, irrespective of co-infection.5

Secondary complications

The NICD describes influenza as uncomplicated – until it is not. Influenza is associated with more severe complications including: Lower respiratory tract infection (LRTI), secondary bacterial or viral infection (including pneumonia, sinusitis, acute bronchitis), multi-organ failure, and exacerbations of underlying diseases (eg COPD, chronic bronchitis, and acute bronchiectasis). Rare complications include encephalopathy, encephalitis, transverse myelitis, myocarditis, pericarditis and Reye syndrome.5

Secondary bacterial infections increase the risk of morbidity. Bacterial infections can occur during or after an initial viral infection, particularly from viruses like influenza, RSV, parainfluenza virus, and human metapneumovirus.7

Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are among the bacteria commonly associated with secondary infections, leading to increased disease severity, including complications such as pneumonia.7 S. pneumoniae is the most common bacteria found in viral secondary bacterial infections and is associated with high mortality and morbidity rates during influenza season.7

Secondary H. influenzae infection is also associated with severe complications during influenza season. H. influenzae is a significant cause of bacterial meningitis, otis media and exacerbations of chronic lung disease such as COPD.7

S. aureus is transiently carried in the nose of 30% of the population, whilst 20% of the population have persistent nasal colonisation. Similar to H. influenzae and S. pneumoniae, S. aureus is an opportunistic pathogen and a major cause of bacteraemia and pneumonia –specifically necrotising pneumonia, caused by community acquired Methicillin-resistant S. aureus (MRSA), which is associated with a 30% mortality rate.7

Up to 75% of individuals infected with influenza that progress to pneumonia, have a confirmed bacterial co-infection. In South Africa, influenza is detectable in about 7% of children <5-years hospitalised with pneumonia and 9% of individuals ≥5-years diagnosed with pneumonia, increasing to 20%-40% during the influenza season. Notably, influenza should be considered a potential cause of community-acquired pneumonia (CAP) during influenza season. 5,7

The severity of secondary bacterial infections during viral infection –particularly influenza – is influenced by numerous factors, ranging from surface antigens to the production of specific toxins. The surface antigens haemagglutinin (HA) and neuraminidase (NA) play pivotal roles in viral infectivity.7

HA facilitates virion binding to host cells, with its specificity impacting infection site and severity. The cleavage of HA, influenced by host proteases, is crucial for virion entry into host cells. NA enables the release of newly formed virions by hydrolysing sialic acid.7

In addition to these factors, the production of viral toxins, such as the cytotoxin polymerase basic protein 1-frameshift 2, contributes to increased inflammation, host cell damage, and bacterial adherence, ultimately intensifying morbidity and mortality.7

The molecular co-pathogenesis involves various interactions facilitating bacterial adhesion and penetration. Influenza-induced immunosuppression, impaired immune responses, and altered inflammatory pathways contribute to bacterial superinfection.7

The reduction in phagocytic activity, prolonged bacterial growth, and impaired bacterial clearance exemplify the complex relationship between viral and bacterial infections.7

Furthermore, damaged host cells provide additional adhesion sites, promoting bacterial adherence. Co-infection results in a synergistic increase in pro-inflammatory responses, affecting tissue damage and creating more attachment sites for bacterial infection.7

What are the most common conditions caused by secondary bacterial infections?

World Health Organization (WHO) data show that South Africans between the ages of 55- to 74-years are at greatest risk of mortality due to LRTIs. The National Department of Health recommends following the WHO guidelines for the treatment of LRTIs in paediatric patients. As mentioned above, some of the most common secondary bacterial influenza coinfections include CAP, acute bronchitis, and acute bacterial rhinosinusitis.7,9,10 Antibiotics are not recommended for uncomplicated cases, considering concerns about resistance and potential side effects. Antiviral treatment may be considered for influenza, but the benefits should be carefully weighed against potential adverse effects. Decision regarding treatment should be guided by microbiological testing. Narrow-spectrum agents are most effective against the identified organism.8,11

Community-acquired pneumonia

The latest South African guideline (2018) for the treatment of adult CAP, recommends oral high-dose amoxicillin in patients <65-years without recent antibiotic exposure or comorbidities as initial therapy.8

For the same group but with severe betalactam allergy or low macrolide resistance, an oral macrolide/azalide is an option. Individuals ≥65-years and, those who used antibiotics recently, or with comorbidities should receive oral amoxicillin-clavulanate or a second-generation cephalosporin.8

In the hospital setting, patients <65-years without recent antibiotic use or comorbidities should receive intravenous ampicillin or penicillin. Meanwhile, those ≥65-years, with recent antibiotic use, or comorbidities should get intravenous (IV) amoxicillin-clavulanate, cefuroxime, or a third-generation cephalosporin. Severe pneumonia cases demand a combination of amoxicillin-clavulanate or cefuroxime with a macrolide antibiotic.8

Respiratory fluoroquinolones are an alternative but are not the first-line choice due to their activity against TB. They may be reserved for cases with severe betalactam allergy or as an alternative when no other options are available. Antibiotics are advised to be administered early, preferably within the emergency unit, for confirmed CAP cases.8

Ceftaroline is recommended for highlevel penicillin-resistant S. pneumoniae or MRSA, while ertapenem is suggested for resistant Enterobacteriaceae, such as ESBL-producing pathogens.8

Therapy for Pneumocystis jirovecii pneumonia (PCP) and TB should be considered based on clinical criteria and severity. Oseltamivir is recommended during the influenza season for severe pneumonia, and adjunctive therapies, including statins, macrolides, and corticosteroids, are recommended.8

Duration of antibiotic therapy may be extended for specific scenarios, such as S. aureus bacteraemia or confirmed Legionella pneumonia. Complications, such as para-pneumonic effusion, empyema, lung abscess, CV events, and aspiration pneumonia, require specific considerations and interventions based on clinical responses and imaging findings.8

Acute bacterial bronchitis

Bacterial pathogens play a role in ≤10% or less of cases. Among these bacterial pathogens, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis are the most common.11

Acute bronchitis is typically a self-limiting condition, and symptomatic and supportive therapies are recommended. To alleviate cough, various non-pharmacological methods such as hot tea, honey, ginger, and throat lozenges can be considered, although their efficacy lacks clinical trial evaluation.11

Antitussive agents like dextromethorphan are commonly used in clinical practice, though there’s a lack of specific trials for acute bronchitis. Codeine, due to its addictive potential, should be avoided.11

The role of mucolytic agents is uncertain, with conflicting data on their efficacy. Betaagonists are administered for wheezing, but their benefit for cough remains inconclusive.11

Analgesics and antipyretics manage associated symptoms, and steroids may address inflammation, especially in patients with underlying conditions like COPD or asthma.11

Acute bacterial rhinosinusitis

Acute bacterial rhinosinusitis is categorised based on the duration of symptoms. Acute sinus issues last less than four weeks, subacute cases persist for four to 12 weeks, and chronic instances extend beyond 12 weeks. Recurrent conditions involve four episodes with complete symptom resolution between each, each lasting less than four weeks.12

Causes of acute bacterial rhinosinusitis are S. pneumoniae, H. influenzae, and Moraxella catarrhalis infection. Prescribing decisions should be guided by local antibiotic resistance, patient risk factors, and symptom severity.12

First-line therapy includes amoxicillin/ clavulanate. Alternatives for penicillinallergic individuals include third-generation cephalosporins plus clindamycin or doxycycline. Fluoroquinolones are an option but carry a higher risk of adverse events.12

Antibiotic efficacy, especially in adults, may not significantly impact symptom duration or complication rates, with many cases resolving spontaneously. First-line therapy includes amoxicillin/clavulanate. Symptoms should improve within three to five days.12

Symptomatic relief can be offered with nasal steroids and saline irrigation, as recommended by guidelines, although evidence is limited. Nasal steroids reduce mucosal swelling, aiding obstruction relief. Nasal saline irrigation is effective in reducing obstruction, and antihistamines are only suggested for cases with a clear allergic component.12

Is Mother Nature driving antibiotic resistance?

The rise of antibiotic-resistance, exacerbated by climate change, poses a significant threat to global health. In 2020, antibiotic-resistant infections became at least 15% more common than in 2017, reports the WHO.13

While it is true that antibiotic-resistance are driven by overuse or misuse, climate change-related events such as floods, droughts, and hurricanes can worsen the situation by reducing access to clean water and promoting unsanitary conditions. Furthermore, extreme weather events also drive an increase in injuries and infections, prompting more antibiotic use and increasing the risk of resistance.13

Studies show a correlation between rising temperatures and antibiotic resistance. A 1°C increase in average air temperature is associated with a 14% rise in antibioticresistant Klebsiella pneumoniae.13

Bacteria exposed to higher temperatures can evolve more rapidly, and genes, including those for antibiotic resistance, can be shared more easily. Extreme temperatures may induce genetic changes in bacteria, making them more resistant to antibiotics.13

Researchers are studying the interactions between climate, human behaviour, and antibiotic resistance. Factors such as increased indoor activities during extreme temperatures might contribute to the spread of resistant strains.13

Ongoing surveillance, combining weather data with monitoring antibiotic-resistance genes in wastewater, could improve forecasts and aid in tracking the spread of antibiotic-resistant bacteria.13

While efforts to reduce antibiotic resistance include improving water and sanitation access, awareness about proper antibiotic use remains crucial, concluded Wong.13

Conclusion

The annual toll of influenza-related complications is substantial, with 290 000 to 650 000 global fatalities reported. South Africa faces 7000 to 12 000 annual deaths due to influenza complications. A study by Motlogeloa et al found that the influenza season in South Africa begins in autumn (April) rather than winter (June). Accurate onset data is extremely important for timely vaccinations and healthcare preparedness.

Influenza, distinct from the common cold, exhibits sudden onset symptoms such as fever, myalgia, and cough. Vaccination plays and important role in prevention and is recommended by the NICD – especially for high-risk groups like pregnant women, individuals with chronic diseases, and the elderly.

The severity of secondary bacterial infections during influenza such as CAP necessitates timely and appropriate antibiotic treatment. The threat of antibiotic resistance, exacerbated by climate change, requires a holistic approach involving improved surveillance, targeted vaccination strategies, and heightened awareness to mitigate the impact on public health.

References are available on request. SF