ECHO Influenza presentation 15-07-24.pptx

Influenza

1. MOH HIV/TB ECHO INFLUENZA 15 TH July, 2024 Presenters: Dr. Mwaka Monze Dr Chitanika Chalomba

2. Learning Objectives Discuss the Epidemiology of Influenza Discuss Clinical Manifestations of Influenza Discuss the Diagnosis of Influenza Discuss the treatment of Influenza The speaker has no significant financial conflicts of interest to disclose.

3. Poll question 1 Which of the following types of Influenza have been isolated in Zambia? Influenza Type A Influenza Type B Both Influenza Type A and Type B

4. Poll question 2 Serology is a useful clinical tool for the diagnosis of influenza True False

5. Poll question 3 Steroids are a mainstay of treatment in patients with pneumonia due to influenza True False

6. Sentinel Surveillance for Influenza in Severe Acute Respiratory Illnesses (SARI) and Influenza-Like Illnesses (ILI)

7. Overview of SARI/ILI Surveillance in Zambia Established: 2008/9 Target population: General population (all ages) presenting to selected health facilities (sentinel sites) Case definitions : ILI = fever + cough + ≤ 10 days duration SARI = ILI + hospitalization PUI (person under investigation) = SARI + exposure to Highly Pathogenic Avian Influenza risk Sampling: 5 ILI per day All SARI cases Lab testing: Influenza and subtyping A – H1N1 pandemic; H3N2; H5; H7 OR B – Yamagata; Victoria SARS Cov 2 Other respiratory pathogens as indicated Reporting: Weekly surveillance reports shared with stakeholders and uploaded to FluNET / FluID

8. Health Facilities Serving as Sentinel Sites

9. Surveillance Procedure Trained surveillance staff identify patients meeting a case definition: ILI – outpatient clinics SARI – admission wards Get verbal consent. Non-research determination Fill out a case investigation form (CIF): demographic information, case classification information, illness severity, medical history, risk factors including possible disease exposure, vaccination history, outcome Collect denominator data for each facility: total outpatient visits/admissions, total respiratory visits/ admissions etc Collect, store and transport samples to the laboratory Laboratory testing using open PCR systems Results feedback, data analysis and weekly reporting

10. Lab Protocol Reagents from CDC PCR Assays: CDC protocols, reagents distributed to NICS through IRR NGS: Currently using ONT

11. Table 2: Number of specimens collected by districts per epi-week (epi week 24- 27 * , 2024) District Total Specimens PCR Positive Results A/H1N1 (pandemic) A/H3N2 B SARS-CoV-2 Chipata 18 (8.7%) 1 (10.0%) 0 (0.0%) 3 (42.9%) 0 (-) Livingstone 20 (9.6%) 6 (60.0%) 0 (0.0%) 2 (28.6%) 0 (-) Lusaka 59 (28.4%) 2 (20.0%) 0 (0.0%) 2 (28.6%) 0 (-) Nakonde 30 (14.4%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (-) Ndola 51 (24.5%) 1 (10.0%) 10 (100.0%) 0 (0.0%) 0 (-) Solwezi 30 (14.4%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (-) Total 208 (100.0%) 10 (100.0%) 10 (100.0%) 7 (100.0%) 0 (-)

12. Percentage (%) of positive specimens by age per epi-week (epi week 24- 27 * , 2024) Age group Total Specimens PCR Positive Results A/H1N1 (pandemic) A/H3N2 B SARS-CoV-2 <1 16 (7.7%) 0 (0.0%) 2 (20.0%) 0 (0.0%) 0 (-) 1-4 46 (22.1%) 4 (40.0%) 1 (10.0%) 1 (14.3%) 0 (-) 5-17 46 (22.1%) 1 (10.0%) 5 (50.0%) 2 (28.6%) 0 (-) 18-49 76 (36.5%) 3 (30.0%) 2 (20.0%) 4 (57.1%) 0 (-) 50+ 24 (11.5%) 2 (20.0%) 0 (0.0%) 0 (0.0%) 0 (-) Total 208 (100.0%) 10 (100.0%) 10 (100.0%) 7 (100.0%) 0 (-)

13. ILI/SARI Threshold Monitoring for epi week 1 – 26 of 2024

14. Diagnosis Most cases of human influenza are clinically diagnosed especially in an outbreak situation Rapid Diagnostic Tests (RDTs): Can be used in clinical settings but have lower sensitivity During periods of low influenza activity or outside of epidemics situations, further tests required to differentiate other causes of influenza-like illness eg other respiratory viruses like SARS-CoV-2, rhinovirus, respiratory syncytial virus, parainfluenza and adenovirus Nucleic acid tests – real time PCR is often used. These can help to further characterize the virus eg subtype. Multiplex tests can give a one-step answer but may be difficult to interpret. Direct antigenic detection Virus isolation in cell/tissue cultures or eggs is helpful to test for antiviral sensitivity or to select vaccine viruses Sequencing or genotyping – used to enhance surveillance and to identify significant changes or mutations in the virus

15. INTRODUCTION Influenza is an acute respiratory illness caused by infection with influenza viruses : commonly called “the flu” Outbreaks of illness of variable extent and severity occur nearly every year. Such outbreaks result in significant morbidity rates in the general population and in increased mortality rates among certain high-risk patients, mainly as a result of pulmonary complications. The influenza virus comes from the Orthomyxoviridae viruses There are three viral sub-types, namely; type A, type B, Type C These viruses are antigenically distinct with no cross-immunity Influenza A and B viruses are responsible for epidemics of disease throughout the world

16. 18 ORTHOMYXOVIRUSES M1 protein helical nucleocapsid (RNA plus NP protein) HA - hemagglutinin polymerase complex lipid bilayer membrane NA - neuraminidase type A, B, C : NP , M1 protein sub-types: HA or NA protein The designation of influenza viruses as type A, B, or C is based on antigenic characteristics of the nucleoprotein (NP) and matrix (M) protein antigens.

17. history Spanish flu 1918 – 1919 (1/3 world population infected with about 50million deaths) – H1N1 1957: H2N2 1968: H3N2 Avian Flu (1997) H5N1 Swine Flu (2009) H1N1 17000 deaths by early 2010 - The exact timing of the onset, peak, and of influenza activity vary, and cannot be predicted - Peak activity most commonly occurs during the winter - persons of all ages are susceptible to influenza - Influenza incidence is difficult to quantify precisely, as many or most of those infected may not seek medical attention and are therefore not diagnosed.

18. Transmission dynamics and cycle Variable Description Susceptible Elderly, Children without prior exposure, DM, Immunosuppression, and Obesity Infectiousness Peak Np viral RNA peak a day after onset of symptoms Infectious virus in 13% isolated after 8days R0 was 1.3-1.7 Environment Household (secondary rates of 7.5%), school, hospitals Exposure Household, Children (more likely to transmit) Survival time <8 hours

19. Mode of Transmission In Human The virus is spread from person- to- person through respiratory secretions either as droplets (close contact) or as airborne infection by droplet nuclei suspended in the air. Incubation period 1-3 days

20. TRANSMISSION AEROSOL 100,000 TO 1,000,000 VIRIONS PER DROPLET SURFACES - VIRUS CAN SURVIVE APPROX 2 TO 8 HRS 18-72 HR INCUBATION Virus shedding generally stops within 2–5 days after symptoms first appear Human Mobility is a key factor in transmission 24

21. Antigenic Variation Influenza viruses tend to undergo changes from time to time. There are two types of changes: Antigenic variation may involve the hemagglutinin alone or both the hemagglutinin and the neuraminidase. An example of an antigenic shift involving both the hemagglutinin and the neuraminidase is that of 1957, when the predominant influenza A virus subtype shifted from H1N1 to H2N2; this shift resulted in a severe pandemic, with an estimated 70,000 excess deaths (1) antigenic shift: Major antigenic variations, seen only with influenza A viruses and may be associated with pandemics. (2) antigenic drift: minor changes These changes in the antigenic characteristics of influenza viruses determine the extent and severity of influenza epidemics

22. Pandemic Influenza Viruses

23. where do “new” HA and NA come from? ~16 types HA ~9 types NA all circulate in birds pigs can be infected by avian and human influenza viruses 27

24. Where do “new” HA and NA come from? 28

25. Where do “new” HA and NA come from 2009 PANDEMIC H1N1? 29

26. Where do “new” HA and NA come from - can ‘new’ bird flu directly infect humans? 30 Current “Bird flu” H5N1? 1918 influenza

27. H5N1 – in birds Avian H5N1 has spread to humans So far human cases in Asia and Africa 442 cases (12-1-03 through 09-24-09) 262 (59%) fatal Have been a few instances where may have spread human-to-human So far no sustained spread in humans Surveillance continues 31

28. 2009 NOVEL H1N1 PANDEMIC first novel H1N1 patient in the United States confirmed by laboratory testing at CDC on April 15, 2009. Quickly determined that the virus was spreading from person-to-person. By June 3, 2009, all 50 states in the United States and the District of Columbia and Puerto Rico were reporting cases of novel H1N1 infection. 32 http://www.cdc.gov/h1n1flu/update.htm

29. why do we not have influenza B pandemics? So far no shifts have been recorded no animal reservoir known 33

30. SYMPTOMS FEVER HEADACHE MYALGIA COUGH RHINITIS OCULAR SYMPTOMS GI tract symptoms not typically seen but common with 2009 H1N1 influenza (‘swine flu’) vomiting, diarrhea 34

31. PATIENTS SUSEPTIBLE TO COMPLICATIONS VERY YOUNG ELDERLY IMMUNO-COMPROMISED HEART OR LUNG DISEASE 35

32. PULMONARY COMPLICATIONS CROUP (YOUNG CHILDREN) PRIMARY INFLUENZA VIRUS PNEUMONIA SECONDARY BACTERIAL INFECTION Streptococcus pneumoniae Staphlyococcus aureus Hemophilus influenzae M IXED (VIRAL –BACTERIAL PNEUMONIA) EXCERBATION OF CHRONIC PULMONARY DISEASES (ASTHMA AND COPD) 36

33. PRIMARY VIRAL INFLUENZA PNEUMONIA Is the least common but most severe of the pneumonic complications Risk factors are : cardiac and pulmonary disease (has been reported in healthy individuals) It presents as acute influenza that does not resolve but instead progresses with fever, dyspnea , and eventual cyanosis. Sputum production is generally scanty, but the sputum can contain blood. Few physical signs may be evident early in the illness. In more advanced cases, diffuse rales may be noted, imaging findings consistent with diffuse interstitial infiltrates and/or acute respiratory distress syndrome may be present. A rterial blood-gas determinations show marked hypoxia histopathologic examination reveals marked inflammatory reaction of alveolar septa edema and infiltration by lymphocytes,macrophages , occasional plasma cells, and variable numbers of neutrophils. Fibrin thrombi in alveolar capillaries, along with necrosis and hemorrhage , have also been noted. Eosinophilic hyaline membranes can be found lining alveoli and alveolar ducts.

34. SECONDARY BACTERIAL PNEUMONIA Occurs most frequently in high-risk individuals with chronic pulmonary and cardiac disease and in elderly individuals Improvement of the patient’s condition over 2–3 days s followed by a reappearance of fever along with clinical signs and symptoms of bacterial pneumonia Cough, production of purulent sputum, and physical and x-ray signs of consolidation Most common bacterial pathogens in this setting are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae Patients with secondary bacterial pneumonia often respond to appropriate antibiotic therapy when it is instituted promptly.

35. Mixed viral and bacterial pneumonia Most common pneumonic complications during outbreaks Patients experience a gradual progression of their acute illness or may show transient improvement followed by clinical exacerbation. Sputum cultures may contain both influenza A virus and one of the bacterial pathogens described above. Patchy infiltrates or areas of consolidation may be detected by physical examination and chest x-ray. Patients with mixed viral and bacterial pneumonia generally have less widespread involvement of the lung than those with primary viral pneumonia Bacterial infections may respond to appropriate antibacterial drugs. Mixed viral and bacterial pneumonia occurs primarily in patients with chronic cardiovascular and pulmonary diseases.

36. Chest imaging findings from a patient with pneumonia the current outbreak Image courtesy of Levy Mwanawasa University Teaching Hospital department of Radiology

37. Chest imaging findings from a patient with pneumonia the current outbreak Image courtesy of Levy Mwanawasa University Teaching Hospital department of Radiology

38. NON-PULMONARY COMPLICATIONS Myositis (rare, > in children, > with type B) Cardiac complications Encephalopathy 2002/2003 season studies of patients younger than 21 yrs in Michigan - 8 cases (2 deaths) Liver and CNS Reye’s syndrome Peripheral nervous system Guillian -Barré syndrome 42

39. MORTALITY MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH BACTERIAL PNEUMONIA CARDIAC FAILURE 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE 43

40. DIAGNOSIS ISOLATION OF VIRUS NOSE, THROAT SWAB GROW IN TISSUE CULTURE OR EGGS SEROLOGY PCR RAPID TESTS PROVISIONAL- clinical picture + outbreak Other laboratory tests generally are not helpful in dioagnosis Leukocyte counts are variable 44

41. Differential diagnosis During An outbreak ;clinical diagnosis can be made in patients typical febrile In the absence of an outbreak influenza may be difficult to differentiate on clinical grounds an acute respiratory illness can be caused by any of a variety of respiratory viruses or by mycoplasma pneumoniae Severe streptococcal pharyngitis or early bacterial pneumonia may mimic acute influenza, Purulent sputum in which a bacterial pathogen can be detected by Gram’s staining is an important diagnostic feature in bacterial pneumonia.

42. Principles of treatment for influenza pneumonia Therapy for primary influenza pneumonia is directed at maintaining oxygenation and with aggressive respiratory and hemodynamic support as needed Studies have suggested that treatment with oseltamivir may reduce the frequency of lower respiratory complications and hospitalization. Antibacterial drugs should be reserved for the treatment of bacterial complications of acute influenza, such as secondary bacterial pneumonia. Choice of antibiotics should be guided by Gram’s staining and cultur If the etiology of a case of bacterial pneumonia is unclear empirical antibiotics effective against the most common bacterial pathogens in this setting: S. pneumoniae, S. aureus, an H. influenzae

43. ANTI-VIRAL drugs All anti-viral drugs inhibit viral replication, but they act in different ways to achieve this. Drugs that are effective against influenza A viruses: amantadine and rimantadine. Drugs that are effective against influenza A viruses and influenza B viruses: zanamivir and oseltamivir.

44. STEROIDS Unlike COVID-19 , Corticosteroid treatment in influenza is  associated with increased mortality and hospital-acquired infection

45. Symptomatic drugs Symptom(s) OTC Medicine Fever, general body pains, Analgesics Nasal congestion. Sinus pressure Decongestants Sinus pressure, runny nose, watery eyes, cough Antihistamines cough Cough suppressant Sore throat Local anesthetics Hypoxia Oxygen

46. Good Health Habits for Prevention Avoid close contact Stay at home when you are sick Cover your mouth and nose Clean your hands Avoid touching your eyes, nose or mouth Practice other good health habits: plenty of sleep, manage your stress, drink plenty of fluids and eat nutritious foods.

47. 51 http://www.cdc.gov/flu/professionals/acip/flu_vax_children0910.htm#box1

48. 52 http://www.cdc.gov/flu/professionals/acip/flu_vax_adults0910.htm#box2

49. Influenza versus covid-19 Aspect Influenza COVID-19 Causative Agent Influenza virus (Types A, B, C, D) SARS-CoV-2 (a novel coronavirus) Transmission Respiratory droplets, contact Respiratory droplets, contact, aerosol Incubation Period 1-4 days 2-14 days Symptoms Fever, cough, sore throat, muscle aches Fever, cough, shortness of breath, loss of taste/smell, fatigue Severity Generally mild to moderate, can be severe in high-risk populations Can range from mild to severe, higher fatality rate than flu Complications Pneumonia, myocarditis, encephalitis, exacerbation of chronic diseases Pneumonia, ARDS, blood clots, multi-organ failure Seasonality Predominantly in winter months Year-round, with varying peaks

50. Influenza versus covid-19 CNT’D Aspect Influenza COVID-19 Vaccines Annual flu vaccines available COVID-19 vaccines available (mRNA, vector, inactivated) Treatment Antivirals (e.g., oseltamivir), supportive care Antivirals (e.g., remdesivir), monoclonal antibodies, supportive care R0 (Basic Reproduction Number) 1.3-1.8 2-3.5 (varies with variants) Preventive Measures Vaccination, hand hygiene, mask-wearing, social distancing Vaccination, hand hygiene, mask-wearing, social distancing, ventilation Asymptomatic Transmission Less common More common, significant factor in spread Testing Rapid antigen tests, PCR tests Rapid antigen tests, PCR tests, home testing kits Long-term Effects Rare, post-infectious syndromes can occur Long COVID, with persistent symptoms affecting various organs Global Impact Annual epidemics, occasional pandemics (e.g., 1918 Spanish flu) Global pandemic with significant social and economic impact since 2019

51. Poll question 1 Which of the following types of Influenza have been isolated in Zambia? Influenza Type A Influenza Type B Both Influenza Type A and Type B

52. Poll question 2 Serology is a useful clinical tool for the diagnosis of influenza True False

53. Poll question 3 Steroids are a mainstay of treatment in patients with pneumonia due to influenza True False

54. Influenza versus covid-19 Aspect Influenza COVID-19 Causative Agent Influenza virus (Types A, B, C, D) SARS-CoV-2 (a novel coronavirus) Transmission Respiratory droplets, contact Respiratory droplets, contact, aerosol Incubation Period 1-4 days 2-14 days Symptoms Fever, cough, sore throat, muscle aches Fever, cough, shortness of breath, loss of taste/smell, fatigue Severity Generally mild to moderate, can be severe in high-risk populations Can range from mild to severe, higher fatality rate than flu Complications Pneumonia, myocarditis, encephalitis, exacerbation of chronic diseases Pneumonia, ARDS, blood clots, multi-organ failure Seasonality Predominantly in winter months Year-round, with varying peaks

55. Thank you