Those of you that know me understand that I do not cry out an alarm in the absence of substantial justification. If you cannot learn from history, you will be damned with the consequences of your actions or inactions.
We have had recent notification from our public health 'experts' that a potentially deadly viral agent has 'crossed species,' in this case from birds to cattle. It is a short jump going from one mammalian specie to another, in this case: Homo Sapiens.
Just as my practice and laboratory partners have done in the past, with COVID-19, we are getting ahead of the problem by developing PCR testing for the H1N5 variant, ultimately with 24 hour turn around time. This is expensive, but my organization is going to 'pony up' with the necessary resources, in order to be pre-emptive, as the public health risk and the personal risk to myself, my family, patients and public, is substantial.
H5N1 Avian Influenza
First Severe Human Case in the U.S.: The Centers for Disease Control and Prevention (CDC) confirmed the first severe human case of H5N1 in the United States. A patient in Louisiana was hospitalized after exposure to sick and dead backyard poultry. Despite this case, the CDC maintains that the risk to the general public remains low.
Spread to Dairy Cattle: H5N1 has been detected in dairy cattle across multiple states, including California, Colorado, and Texas. This cross-species transmission is concerning due to the potential implications for both animal and human health.
State of Emergency in California: In response to the outbreak, California Governor Gavin Newsom declared a state of emergency to enhance the state's response capabilities. The declaration aims to provide government agencies with the necessary resources and flexibility to address the situation effectively.
USDA Initiates Milk Testing: The U.S. Department of Agriculture (USDA) has begun nationwide testing of unprocessed milk to track the virus's spread, following detections of H5N1 in dairy herds. This initiative is part of broader efforts to monitor and contain the outbreak.
Global Concerns: Internationally, there have been reports of human cases, including a teenager in Canada who was hospitalized in critical condition after contracting H5N1. These instances underscore the importance of global vigilance and preparedness.
While the emergence of new influenza variants is always a possibility, current surveillance and reporting have not indicated any significant developments related to an H1N5 strain. Public health authorities continue to monitor influenza viruses closely to detect and respond to any potential threats promptly. Unfortunately, recent history suggests that a rapid increase in case load can occur in a matter of a few weeks to 3 or 4 months.
How do you test for this potentially deadly virus?
Testing for H1N5 Influenza is difficult to arrange on an emergency or local basis.
When the H1N5 influenza variant emerges as a concern, and this may have just occurred, diagnostic testing would rely on well-established methodologies for detecting influenza viruses. Here's a general approach to testing for such infections. Unfortunately, the virus is 'special' enough to warrant making arrangements in advance.
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Sample Collection sounds very much like what we just experienced with Covid19.
1. Sample Collection
Testing typically begins with the collection of respiratory specimens. Suitable samples include:
• Nasopharyngeal or Oropharyngeal Swabs
• Nasal Aspirates
• Bronchoalveolar Lavage Fluid (for severe cases or hospitalized patients)
Collected samples should be stored in viral transport media and kept at appropriate temperatures to preserve the virus for testing.
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2. Molecular Testing, PCR
The primary diagnostic method for influenza, including novel strains, is molecular testing:
• Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR):
o The gold standard for influenza virus detection.
o RT-PCR assays can be tailored to identify specific subtypes, including H1N5, if specific primers and probes are available.
o Public health laboratories can update their protocols to include emerging strains once genetic information becomes available.
NOTE WELL:
It takes a long time for the 'public health laboratories to become calibrated and validated for any single antigen.
The public health and state laboratories are incredibly slow to react and they generally do not get ahead of any problem, note the slow response to the COVID -19 epidemic and the number of people that had to wait weeks to get test results.
By the time you get results at these facilities, the 'animals are out of the barn,' and there is little you can do to treat the problem or mitigate the risks.
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3. Viral Culture
• Culturing the virus from patient samples in appropriate cell lines allows for further characterization.
• Viral culture is typically reserved for reference labs and used for research, vaccine development, or epidemiological studies, as it is time-intensive and requires biosafety precautions.
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4. Antigen Detection
• Rapid Influenza Diagnostic Tests (RIDTs):
Can detect influenza A viruses but have limitations in sensitivity and subtype differentiation.
Not reliable for confirming novel subtypes like H1N5.
• Immunofluorescence Assays:
Detect viral antigens in respiratory cells.
Require trained personnel and specialized equipment.
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Key Actions for Clinicians: Prevention and Treatment
• Early recognition of symptoms in individuals with relevant exposure risks.
• Prompt sample collection and referral to specialized labs if H1N5 is suspected.
IF H1N5 influenza is suspected, the specialized labs become harder to find.
• Notify public health authorities immediately in the case of unusual or novel influenza presentations.
By leveraging these diagnostic tools and protocols, healthcare systems can efficiently identify and respond to novel influenza infections like H1N5.
Treatment of H1N5 influenza:
1. Antiviral Medications
Neuraminidase Inhibitors
• Oseltamivir (Tamiflu):
First-line treatment for most influenza infections.
Dose: Typically 75 mg twice daily for 5 days (adjusted for weight, renal function, or severity).
Duration may be extended for critically ill or immunocompromised patients.
• Zanamivir (Relenza):
Administered via inhalation; not for patients with respiratory issues like asthma or COPD.
Alternative for patients who cannot tolerate oseltamivir.
• Intravenous Peramivir:
Used in hospitalized patients when oral or inhaled options are not feasible.
Endonuclease Inhibitor
• Baloxavir Marboxil (Xofluza):
Single-dose oral antiviral targeting viral replication.o May be an option for certain patients, though not commonly used in severe cases.
Amantadine and Rimantadine
• These older antivirals target the M2 protein but are generally ineffective against most contemporary influenza A strains, including H5 subtypes.
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2. Supportive Care
Hospitalization
• Patients with severe or complicated influenza (e.g., pneumonia, acute respiratory distress syndrome [ARDS]) may require hospitalization for intensive monitoring and treatment.
• Oxygen Therapy: Supplemental oxygen for hypoxia; advanced respiratory support (e.g., high-flow oxygen, non-invasive ventilation, or mechanical ventilation) for severe cases.
• Hydration: Intravenous fluids to maintain hemodynamic stability.
• Nutritional Support: Enteral or parenteral feeding in critically ill patients.
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3. Management of Complications
• Secondary Bacterial Infections:
Common pathogens include Streptococcus pneumoniae, Staphylococcus aureus (including MRSA), and Haemophilus influenzae.
Empiric antibiotics (e.g., ceftriaxone plus vancomycin) may be initiated until specific pathogens are identified.
• Pneumonia:
Antiviral therapy combined with antibiotics if bacterial co-infection is suspected.
Consider imaging (chest X-ray or CT scan) for diagnosis and monitoring.
• ARDS:
Requires advanced ventilatory support and lung-protective strategies.
May involve prone positioning or extracorporeal membrane oxygenation (ECMO) in severe cases.
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4. Immunomodulatory Therapy
• Corticosteroids: Generally avoided in influenza as they can worsen outcomes, but may be used in specific complications like adrenal insufficiency or refractory shock.
• Immunoglobulins: Considered in severe cases with immune dysregulation or secondary immune deficiency.
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This framework aligns with the treatment of severe influenza infections, including zoonotic strains like H1N5, ensuring tailored, evidence-based care while addressing individual patient needs.
The take-home question: "What can you do to help yourself and your family?" Prevent and Treat Influenza
N-acetylcysteine (NAC) and colostrum have garnered interest in both the prevention and treatment of influenza due to their immunomodulatory and antiviral properties. Below is an analysis of their potential effects based on existing evidence:
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NAC is a derivative of the amino acid cysteine and acts as both a precursor to glutathione and a mucolytic agent.
Effects in Influenza Treatment:
1. Antioxidant and Anti-inflammatory Properties:
o NAC replenishes intracellular glutathione, a critical antioxidant that helps mitigate oxidative stress induced by viral infections.
o Reduces inflammatory cytokines (e.g., TNF-α, IL-6), potentially preventing cytokine storm, a severe complication in influenza.
o May attenuate lung injury caused by excessive reactive oxygen species (ROS).
2. Reduction in Symptom Severity:
o In preclinical studies, NAC reduced replication of influenza virus in epithelial cells.
o Clinical trials suggest NAC could decrease symptom severity and duration by reducing inflammation and improving mucociliary clearance.
3. Adjunctive Use with Antivirals:
o NAC may enhance the efficacy of antiviral drugs by mitigating the cellular damage caused by oxidative stress.
Effects in Influenza Prevention:
1. Immune Modulation:
o Boosts the function of immune cells, including T cells and natural killer (NK) cells.
o Reduces viral replication in preclinical studies, potentially lowering the risk of infection.
2. Evidence in Human Studies:
o A double-blind placebo-controlled study (De Flora et al., 1997) found that NAC supplementation (600 mg twice daily for 6 months) reduced the frequency and severity of influenza-like episodes in elderly individuals. Although some participants became infected, their symptoms were milder compared to the placebo group.
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Colostrum, the first milk produced by mammals after giving birth, is rich in immunoglobulins, growth factors, and bioactive peptides.
Effects in Influenza Treatment:
1. Antiviral Activity:
Contains immunoglobulins (IgG, IgA) that may neutralize influenza virus.
Lactoferrin, a glycoprotein in colostrum, has demonstrated antiviral properties by inhibiting viral attachment and replication.
2. Reduction in Inflammation:
Growth factors and peptides in colostrum modulate immune responses, reducing excessive inflammation during infection.
3. Improved Recovery:
May promote mucosal healing and enhance recovery from influenza-related respiratory damage.
Effects in Influenza Prevention:
1. Enhanced Immune Defense:
Strengthens the mucosal immune system, providing a first-line defense against respiratory infections.
Regular supplementation may prime the immune system to respond effectively to viral threats.
2. Evidence from Studies:
A randomized controlled trial compared colostrum with influenza vaccination and found that colostrum was at least three times more effective in preventing influenza episodes in high-risk cardiovascular patients (Cesarone et al., 2007).
In another study, individuals receiving colostrum supplementation experienced fewer influenza-like episodes compared to controls, suggesting its prophylactic potential.
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Mechanisms of Action of NAC
Mechanism of action: N-Acetylcysteine (NAC)
Antiviral Effects: Reduces viral replication; boosts cellular antioxidants
Immune Modulation: Lowers inflammation; enhances T-cell function
Symptom Relief: Reduces oxidative lung damage and mucus production
Preventive Effects: Mitigates susceptibility by enhancing immunity
Mechanisms of Action of Lactoferrin Containing Colostrum
Mechanism: Neutralizes viruses with antibodies
Antiviral Effects: Provides passive immunity; primes innate and adaptive immunity
Immune Modulation: Lowers inflammation; enhances T-cell function
Symptom Relief: Promotes mucosal healing
Preventive Effects: Strengthens mucosal barrier
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Dosage and Safety
• Typical dose: 600–1200 mg daily for prevention; higher doses may be used in acute treatment.
• Generally well-tolerated but may cause gastrointestinal symptoms in some individuals.
• Dose: 3–10 g daily for prevention or as directed by the product.
• Safe for most individuals but should be used with caution in those with dairy allergies or lactose intolerance. This remote issue may need to be balanced with the real risk of severe illness and/or death from the virus.
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Conclusion
• NAC: Strong evidence supports its use as an adjunct therapy for reducing symptom severity and preventing complications in influenza. It also shows promise in prevention, especially in elderly or high-risk populations.
• Colostrum: Provides robust immune support and may serve as an effective prophylactic measure. Its direct antiviral properties and immune-modulating effects make it a valuable tool in both prevention and recovery.
While neither NAC nor colostrum should replace established antiviral treatments or vaccination, they can complement these strategies, particularly in high-risk individuals or during influenza outbreaks.
References
N-Acetylcysteine (NAC)
1. De Flora, S., Grassi, C., & Carati, L. (1997). Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. European Respiratory Journal, 10(7), 1535-1541.
2. Geiler, J., Michaelis, M., Naczk, P., Leutz, A., Langer, K., Doerr, H. W., & Cinatl, J. (2010). N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochemical Pharmacology, 79(3), 413-420.
3. Ungheri, D., Pisani, C., Sanson, G., Bertani, A., Schioppacassi, G., & Ghezzi, P. (2000). Protective effect of N-acetylcysteine in a model of influenza infection in mice. International Journal of Immunopathology and Pharmacology, 13(3), 123-128.
4. Ghezzi, P., & Ungheri, D. (2004). Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model. International Journal of Immunopathology and Pharmacology, 17(1), 99-102.
5. Garozzo, A., Tempera, G., Ungheri, D., Timpanaro, R., & Castro, A. (2007). N-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection. International Journal of Immunopathology and Pharmacology, 20(2), 349-354.
6. Rasmussen, L. E., & Glanville, R. W. (1995). N-acetylcysteine inhibits influenza virus replication and expression of pro-inflammatory molecules. Antiviral Research, 27(3), 237-249.
7. Aldini, G., Altomare, A., Baron, G., Vistoli, G., Carini, M., Borsani, L., & Sergio, F. (2018). N-acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radical Research, 52(7), 751-762.
8. Mokhtari, V., Afsharian, P., Shahhoseini, M., Kalantar, S. M., & Moini, A. (2017). A review on various uses of N-acetylcysteine. Cell Journal (Yakhteh), 19(1), 11-17.
9. Aitio, M. L. (2006). N-acetylcysteine – passe-partout or much ado about nothing? British Journal of Clinical Pharmacology, 61(1), 5-15.
10. Zafarullah, M., Li, W. Q., Sylvester, J., & Ahmad, M. (2003). Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences, 60(1), 6-20.
Colostrum
1. Ng, W. C., Wong, V., Muller, B., Rawlin, G., & Brown, L. E. (2010). Prevention and Treatment of Influenza with Hyperimmune Bovine Colostrum Antibody. PLoS ONE, 5(10), e13622.
2. Cesarone, M. R., Belcaro, G., Di Renzo, A., Dugall, M., Cacchio, M., Ruffini, I., ... & Vinciguerra, G. (2007). Prevention of influenza episodes with colostrum compared with vaccination. Clinical and Applied Thrombosis/Hemostasis, 13(2), 130-136.
3. Belcaro, G., Cesarone, M. R., Dugall, M., Cacchio, M., Ruffini, I., Ledda, A., ... & Vinciguerra, G. (2010). Prevention of flu episodes with colostrum and Bifivir compared with vaccination: An epidemiological, registry study during the influenza season 2007-2008. Panminerva Medica, 52(4), 269-275.
4. Korhonen, H., Marnila, P., & Gill, H. S. (2000). Bovine milk antibodies for health. British Journal of Nutrition, 84(S1), 135-146.
5. Playford, R. J., MacDonald, C. E., & Johnson, W. S. (2000). Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. American Journal of Clinical Nutrition, 72(1), 5-14.
6. Struff, W. G., & Sprotte, G. (2007). Bovine colostrum as a biologic in clinical medicine: A review – Part II: Clinical studies. International Journal of Clinical Pharmacology and Therapeutics, 45(5), 211-225.
7. He, F., Tuomola, E., Arvilommi, H., & Salminen, S. (2001). Modulation of human humoral immune response through orally administered bovine colostrum. FEMS Immunology & Medical Microbiology, 31(2), 93-96.
8. Rump, J. A., Arndt, R., Arnold, A., Bendick, C., Dichtelmüller, H., Franke, M., & Helm, E. B. (1992). Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Clinical Investigator, 70(7), 588-594.
9. Davidson, G. P., & Whyte, P. B. (1990). Bovine colostrum in oral rehydration solutions for the treatment of rotavirus diarrhea: A randomized, double-blind, controlled clinical trial. Journal of Pediatric Gastroenterology and Nutrition, 10(4), 465-470.
10. Marnila, P., & Korhonen, H. (2002). Colostrum-derived specific antibodies: Are they ready for therapeutic applications? Revue Scientifique et Technique (International Office of Epizootics), 21(3), 321-331.
11. Huppertz, H. I., Rutkowski, S., & Busch, D. H. (1999). Bovine colostrum ameliorates diarrhea in infection with human rotavirus but not with porcine rotavirus. Journal of Pediatric Gastroenterology and Nutrition, 29(4), 452-456.
12. Shah, N. P. (2000). Effects of milk-derived bioactives: An overview. British Journal of Nutrition, 84(S1), 3-10.
13. Pakkanen, R., & Aalto, J. (1997). Growth factors and antimicrobial factors of bovine colostrum. International Dairy Journal, 7(5), 285-297.
14. Kelly, G. S. (2003). Bovine colostrums: A review of clinical uses. Alternative Medicine Review, 8(4), 378-394.
15. Thapa, B. R. (2005). Bovine colostrum in pediatric practice. Indian Journal of Pediatrics, 72(10), 849-852.
David S. Klein, MD, FACA, FACPM
1917 Boothe Circle
Longwood, Florida 32750
Tel: 407-679-3337
Fax: 407-678-7246