Influenza Infection In Human. Dr. Zuhaida A. Jalil Surveillance Sector Disease Control Division, MOH Malaysia 3 May 2018

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1 Influenza Infection In Human Dr. Zuhaida A. Jalil Surveillance Sector Disease Control Division, MOH Malaysia 3 May 2018

2 Objective of the session: After completing this session, you will be able to: Understand the definition of terms related to influenza infection Identify the characteristics and severity of types A, B and C influenza Describe the functions of two major proteins in influenza Recognize the origin and biology of an influenza strain from analysing its full name

3 Flu Not So Innocent! Feel sick! Miss work Complications Pneumonia Ear and sinus infections Dehydration Encephalopathy and encephalitis Sepsis-like syndrome in infants Worsening underlying chronic conditions Spread of the infection among close contacts e.g. household members, siblings, co-workers, schoolmates etc.

4 IMPORTANCE OF INFLUENZA Global incidence largely unknown Data available mainly from temperate climate Up to 650,000 deaths annually are associated with respiratory diseases from seasonal influenza, according to new estimates by the US-CDC, WHO and global health partners (A Danielle luliano et al., 2017) Seasonality: In temperate zones, increases in winter months Driven by mutations and viral preference for cold, dry weather conditions In tropical zones, circulates year-round Fall-winter and rainy season increase has been observed Impact of influenza infection: Clinically: outpatient visit / hospitalization / death Economically: direct cost vs. indirect cost (e.g. absenteeism)

5 SEASONALITY Courtesy of Dr. Hithosi Oshitani (Tohoku University Graduate School of Medicine) Temperate zones: Increases in winter months Tropical / Sub-tropical zones: Circulates year round (with rainy season increase has been observed)

6 Flu infection is a common disease in Malaysia too!

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8 Definitions of Terms Seasonal Influenza: Influenza that occurs every year with gradual variations in the previous year s virus surface proteins (antigenic drift) Avian Influenza: A disease of birds that occasionally jumps species and infects humans. Ultimately is the source of new viruses in humans causing pandemics Pandemic Influenza: A worldwide surge in cases caused by the introduction of a new type A surface protein (antigenic shift)

9 Variant Influenza Viruses Human infections with animal-origin influenza A viruses are uncommon, but they do occur Human influenza illnesses caused by swine-origin influenza A viruses (called variant influenza virus infections) have been sporadically identified e.g. H1N1v, H3N2v and H1N2v viruses Most illnesses caused by the H3N2 variant have occurred after direct or indirect contact with an infected pig, often among exhibitors or visitors to agricultural fairs Limited person-to-person transmission has occurred with this virus and the severity of illness has been similar to that seen with seasonal influenza

10 Influenza Virus Negative single stranded RNA virus, part of the Orthomyxoviruses family Classified into types A, B, C and D Influenza A is named by the type of hemagglutinin (H) and neuraminidase (N) glycoproteins that it carries Influenza B and C viruses have no subtypes, although they are further characterized into strains Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people

11 Naming of Influenza Virus

12 Naming of Influenza Virus (cont.) Identifier A/California/7/2009 (H1N1) A/Perth/16/2009 (H3N2) B/Brisbane/60/2008 Type of influenza A A B Location where the strain was first discovered California, USA Perth, Australia Brisbane, Australia Strain identification number Year of discovery Subtype of influenza is the HA and NA that make up the virus (usually noted in the parentheses) H1N1 H3N2 Type B has no designated subtype. Instead, influenza B viruses have diverged into two antigenically distinct virus lineages called the Yamagata and Victoria lineages. NOTE: If the virus infects non-humans (e.g. chickens), the host species is included before the geographical site, as in A/Chicken/Hong Kong/G9/97 (H9N2)

13 Hemagglutinin and Neuraminidase These different combinations are called subtypes; e.g. H1N1, H3N2, H5N1, H7N9 etc. Eighteen different subtype of H glycoproteins (H1-H18) and 11 different subtype N gycoproteins (N1-N11) has been identified globally The natural reservoir of influenza A: Wild aquatic birds (H1-H16 subtypes), with the exception of H17 and H18 subtypes that were recently discovered in bats Hemagglutinin allows the influenza virus to attach to and enter a host cell Once the virus has replicated itself using the machinery of the host cell, neuraminidase allows the mature virus to escape from the host cell

14 These three types of influenza viruses have similar and differing characteristics Characteristics Type A Type B Type C Capable of infecting humans. Capable of infecting swine, birds, horses and other mammals. Causes non-seasonal mild illness in humans. Responsible for seasonal outbreaks. Virulent and quickly spread. Capable of mutation, changing the surface glycoproteins enough to avoid a healthy host cell's built-up antibodies. This ability to drift can cause epidemics. Capable of genetically changing. This ability to shift, along with other characteristics, enables this strain to be more destructive and the source of pandemics.

15 The influenza virus is transmitted primarily by droplets Droplets generally travel about 1 metre before they drop The virus can survive on hard surfaces for up to 48 hours; on hands for 5-10 minutes People can be inoculated with the influenza virus either: By direct contact From hands (or anything else) Thorough hand washing with soap & water for 20 seconds is an effective way to decontaminate hands; 60%-90% of alcohol-based hand rub applied thoroughly on the hands until it dries is equally effective

16 Communicability Viral shedding can begin 1 day before symptom onset Peak shedding first 3 days of illness Subsides usually by 5 th to 7 th day in adults Infants, children and the immunosuppressed may shed virus longer

17 Clinical Symptoms of Influenza Clinical symptoms non-specific Symptoms overlap with many pathogens Coupling with lab data to verify diagnosis Abrupt onset Fever, chills, body aches, sore throat, non-productive cough, runny nose, headache Gastrointestinal symptoms and muscle inflammation more common in young children Influenza infection is not a direct cause of deaths in many influenza associated deaths (bacterial pneumonia, heart failure etc.)

18 Influenza Virus Infections Can Result In Various Disease Condition DEATH Hospitalized Cases (+/- Complications) Medically-Attended Outpatient Cases Mild Disease, Not Medically-Attended (or Asymptomatic Infections)

19 Influenza: Individuals at Increased Risk for Hospitalizations and Death Elderly > 65 years Young children (<2 years) Persons with chronic medical conditions Immunosuppression Conditions that can compromise respiratory function or the handling of respiratory secretions Pregnant women Nursing home residents Children on long-term aspirin therapy

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21 Influenza: What Can I Do To Protect Myself From Getting Sick?

22 Influenza: Essential Health Habits To Protect Your Health And The Health Of Others *Staying at home means that you should not leave your house except to get medical care. Stay away from others as much as possible so you don t make them sick.

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24 Antiviral Treatments Two classes of antiviral drugs are used to treat influenza Neuraminidase inhibitors M2 protein inhibitors Neuraminidase inhibitors Neuraminidase is used to clear a path for the virus to a host cell and facilitates the shedding of virus from an infected cell Inhibition of neuraminidase therefore helps prevent the spread of virus within a host and its shedding to infect other hosts The two main neuraminidase inhibitors currently in clinical use are zanamivir (trade name Relenza) and oseltamivir (trade name Tamiflu) These are effective against influenza A and B, but not influenza C which exhibits a different type of neuraminidase activity

25 Antiviral Treatments (cont.) M2 protein inhibitors The influenza M2 protein forms a pore that allows protons into the capsid, acidifying the interior and facilitating uncoating Drugs such as amantadine (trade name Symmetrel) and rimantadine (trade name Flumadine) block this pore, preventing uncoating and infection However, their indiscriminate use in over-the-counter cold remedies and farmed poultry has allowed many strains of influenza to develop resistance Influenza B has a different type of M2 protein which is largely unaffected by these drugs Why are antibiotics not used to treat influenza? Influenza is a virus, antibiotics only work against bacteria

26 Diagnosis of Influenza Infection Which sites in the body should be sampled for diagnosis? The influenza virus infects the respiratory tract and is spread by coughing and sneezing, so specimens should be taken from the nose, throat or trachea In practice, the best specimens are nasal aspirates or washes, but swabs of the nose or throat may be used if they are taken vigorously enough to obtain cells Ideally, samples should be taken within three days of the onset of illness and specimens need to be placed in a sterile container / transport medium and kept chilled until they reach the laboratory i.e. respectively at 2 o to 8 o C within 48 hours after collection

27 Influenza Testing Methods

28 Conclusions Influenza is a disease that can be contracted several times during a lifetime, but many other infectious diseases are only ever contracted once. To understand this we need to look at how the immune system reacts to different pathogens, and how responses vary depending on the pathogen. Outbreaks of influenza occur regularly, but some epidemics are much more serious than others. This requires an understanding of aspects of virology, immunology, evolutionary biology and epidemiology.

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