Mycology & Virology: Hepatitis A, B, C, D, & E PDF

Mycology and Virology | MLS-415 F1: Hepatitis A, B, C, D, & E Professor: Thynee Tago, MSMT Date: April 27, 2024 HEPATITIS A CLASSIFICATION: Genus: Hepatovirus Family: Picornaviridae STRUCTURE: 27 to 32 nm spherical particle Cubic symmetry A linear single stranded RNA 7.5 kb CONTENT: Capsid Viral Pro...

Mycology and Virology | MLS-415 F1: Hepatitis A, B, C, D, & E Professor: Thynee Tago, MSMT Date: April 27, 2024 HEPATITIS A CLASSIFICATION: Genus: Hepatovirus Family: Picornaviridae STRUCTURE: 27 to 32 nm spherical particle Cubic symmetry A linear single stranded RNA 7.5 kb CONTENT: Capsid Viral Protein Genome PEOPLE W/ INCREASED RISK OF HEPATITIS A: Hepa A = Infection of the Liver through ingestion of contaminated Fecal material Natural host → HUMANS Eyes may appear Jaundiced due to it being a liver disease Incubation: 10-50 days; Averaging 25-30 People w/ occupational risk for exposure to Hepa A People in developed countries adopting children from underdeveloped countries People w/ Chronic Liver Diseases Most prominent Sign and Symptom: YELLOWING of the SKIN/SCLERA For some there could be fever, stomach pain, darkened urine and stool is light colored Joint pain may also occur (They feel tired) Children may appear ASYMPTOMATIC; Adults are usually SYMPTOMATIC Symptoms develop and appear 2-7 weeks after infection which may last < 2 months but for some it can reach up to 6 months (the longevity depends on the stability of the immune system) Travels Internationally Men who have Sex with Men (MSM) Users of injection and Non-injection drugs Homeless people People w/ Hepa B/C or with HIV Laboratory Diagnosis Serologic assays: ○ PCR ○ ELISA HAV in Stool – Usually detected 1st ; Basically, 2 weeks before and after the onset of jaundice, HAV can be detected in the stool. Anti-HAV IgM – Usually peaks 2 weeks after the elevation of LIVER ENZYMES Anti-HAV IgG – Usually detected AFTER the onset of disease and could persist for a long time Treatment, Prevention and Control TREATMENT No specific treatment – usually you are advised to rest or have an adequate nutrition; fluids also are needed since the virus itself is self-limiting; Does not usually progress to Chronic Liver Disease unless the patient has an underlying condition on the liver. COPY FOR: ORIT, ANNE CHELSEA R. | 1 VIRUS INACTIVATION Heating food to above 85 deg C for at least 1 minute ○ The longer, the better ○ Also depends on the quality of the food Surface disinfection with Sodium Hypochlorite or Bleach (1:100) VIRUS DESTRUCTION Autoclaving Boiling in water Dry heat (180 deg C for 1 hour) or (160 deg C for 2 hours) Ultraviolet Irradiation (1 min at 11 watts) Treatment with FORMALIN or treatment with CHLORINE (10-15 ppm for 30 mins) ○ Formalin (1:4000) 3 days @ 37 deg C Natural Host → HUMANS Can survive OUTSIDE the body and can remain infectious for at least 7 days Most people with chronic HBV infection are ASYMPTOMATIC and have no evidence of liver disease or injury Average of 90 days or Weeks up to 6 months (could be longer) TRANSMISSION: Sexual Intercourse Sharing of Needles/ Syringes Through birth Contact w/ contaminated blood PREVENTION AND CONTROL Vaccination of Hepatitis A - Best prevention method ○ Specially for Frontliners, Staffing for child care, Food handlers, Military personnel, etc. Practicing Good Hand Hygiene HEPATITIS B Enveloped dsDNA; Icosahedral capsid 3 forms: ○ Spherical (22nm) ○ Tubular/ Filamentous (22-200nm) ○ Dane Particle (42nm) Complete virion (w/ genome) CLASSIFICATION: Genus: Orthohepadnavirus Family: Hepadnaviridae CONTENTS: Hepatitis B surface antigen (HBsAg) Hepatitis B core antigen (HBcAg) Viral DNA genome Clinical Manifestations PEOPLE W/ INCREASED RISK OF HEPATITIS B: Infants born from mothers w/ Hepa B Sex with someone who has HBV MSM Patients that are constantly exposed to needles (Dialysis indiv.) Users of injection and Non-injection drugs Healthcare workers MOST COMMON SYMPTOMS: Jaundice, Loss of Appetite, Nausea and Vomiting, Fever and Fatigue Laboratory Diagnosis & Identification HEPATITIS B ANTIGENS HEPATITIS B ANTIBODY Hepatitis B surface antigen (HBsAg) 1st to appear in the SERUM (once there is Hepatitis B surface antibody (anti-HBs) infxn) Hepatitis B core antigen (HBcAg) CANNOT be detected in the serum but can be detected through LIVER BIOPSY Found inside HEPATOCYTES Total hepatitis B core antibody (anti-HBc) Means that the virus is actively multiplying in the liver (Viral Replication) Perform Immunohistochemistry COPY FOR: ORIT, ANNE CHELSEA R. | 2 Treatment, Prevention and Control TREATMENT There is no medication available Rest, adequate nutrition and fluids Patients with more severe symptoms may need to be hospitalized Take medication indefinitely (under the guidance of the attending physician) ○ To avoid damaging the liver PREVENTION AND CONTROL Getting vaccinated Proper handwashing Never share needles, syringes or even water Follow universal precautions Use birth controls to prevent the spread of sexually transmitted disease Hepatitis B envelope antigen (HBeAg) Appears in the serum Hepatitis B envelope antibody (anti-HBe) Presence indicates INFECTIVITY of the individuals (Viral Infection) Used to identify whether the patient has Acute or Chronic HBV infection Also used to identify immune status of the individual (either susceptible or Immune) Interpretation HEPATITIS C HBsAg (+) Acute infection → (+) for IgM and Total Anti-HBc Chronic infection → (+) ONLY for Total Anti-HBc ○ Meaning only IgG is detected, and the body stopped producing IgM anti-HBc HBsAg (-) Immune due to PREVIOUS INFECTION → (+) for Anti-HBs and Total Anti-HBc ○ Patient has Core Antigen, meaning the virus got into the patient which produced HBcAg Immune due to VACCINATION → (+) ONLY for Anti-HBs ○ Patient has no Core Antigen, meaning the virus did not reach the patient → no HBcAg → no Anti-HBc Susceptible → (-) for BOTH Anti-HBs and Total Anti-HBc Acute Infection Acute Infection w/ (↑) Infectivity Convalescent Immune due to previous infection HBsAg + + + - HBeAg - + - - Anti-HBs - - - + Anti-HBe - - + + CLASSIFICATION: Genus: Hepacivirus Family: Flaviviridae STRUCTURE: Single-stranded RNA genome surrounded by icosahedral capsid with envelope. COPY FOR: ORIT, ANNE CHELSEA R. | 3 Non-cytopathic virus; usually enters the liver cell and undergoes replication simultaneously causing cell necrosis by several mechanisms, like Immune mediated cytolysis and other phenomena such as: ○ Hepatic steatosis, ○ Oxidative stress ○ Insulin Resistance Natural Host → HUMANS TRANSMISSION: Sexual Intercourse Sharing of Needles/ Syringes Through birth Contact w/ contaminated blood Sharing of Toothbrush or Razors for shaving EIA → RIBA → PCR If both positive for EIA and RIBA then proceed to PCR testing PEOPLE W/ INCREASED RISK OF HEPATITIS C: People with HIV People who is in Hemodialysis People who donated/Received blood or from Organ transplants Healthcare and emergency medical and public safety personnel Medtechs (constant exposure to needles) Mucosal exposures Children who are born from mothers with HCV infxn. CLINICAL MANIFESTATIONS People with newly acquired HCV infection usually are ASYMPTOMATIC The average period from exposure to symptom onset is 2-12 weeks Most people with Chronic HCV infection are asymptomatic ○ May also lead to diseases that is not only related to the liver such as: Diabetes Glomerulonephritis Porphyria Cutanea Tarda Non-Hodgkin's Lymphoma SIGNS & SYMPTOMS Loss of appetite Nausea vomiting Joint pain Jaundice Fever fatigue Dark urine Clay-colored stool Abdominal pain CONFIRMATORY TESTING: Qualitative and Quantitative assays for HCV RNA: RT-PCR or Recombinant Immunoblot Assay (RIBA) HCV genotyping Serologic testing Liver Biopsy – to determine the degree of liver damage; chronic HCV TREATMENT PEGylated interferon combined with ribavirin ○ PEG + Interferon + Ribavirin ○ Polyethylene Glycol will serve as a VESICLE/ CONTAINER for the interferon ○ Ribavirin is an antiviral drug Antiviral therapy Telaprevir and boceprevir Sofosbuvir Orthotopic liver transplantation People living with Hepatitis C should: Be vaccinated against hepatitis A and Hepatitis B Avoid alcohol Check with their doctor taking any prescription pills, herbs, supplements or over the counter medications (Medicol; ibuprofen) Be tested for HIV PREVENTION AND CONTROL Safe and appropriate use of healthcare injections; Safe handling and disposal of sharps and waste; Provision of comprehensive harm reduction services to people who inject drugs Testing of donated blood for HBV and HCV (as well as HIV and syphilis) Training of health personnel Prevention of exposure to blood during sex LABORATORY DIAGNOSIS SCREENING TESTS FOR ANTIBODY to HCV (anti-HCV): Enzyme Immunoassay (EIA) ○ In low-risk patients w/ (+) EIA, they will have to undergo confirmatory testing using RIBA COPY FOR: ORIT, ANNE CHELSEA R. | 4 HEPATITIS D CLINICAL MANIFESTATION More severe than the other type of Hepatitis viruses ○ Can run either acute or chronic course 3-7 weeks of incubation period ○ Fatigue ○ Lethargy ○ Nausea ○ Anorexia Symptoms last for about 3-7 days Jaundice occurs in the next phase of symptoms ○ Fatigue and nausea continues ○ Abnormal Serum Bilirubin Level ○ Clay-colored stool ○ Dark urine Left: Hepatitis D virus sans the capsid as it borrows structures from HBsAg, Right: Hepatitis B virus CLASSIFICATION: Genus: Deltavirus (hence the letter D) Family: Kolmioviridae SMALLEST virus known to infect animals, therefore it is not really a full virus, but considered a SATELLITE VIRUS/SUBVIRAL AGENT. Why? ○ Because of its special structure STRUCTURE: Small, Spherical, Single-stranded, enveloped particle with Hepa B surface antigen, and negative-sense RNA molecule Genetic material is wrapped in HBsAg ○ Usually present if Hepatitis B is primarily present (Coexisting infection) PATHOGENESIS The production and transmission of HDV is ENTIRELY DEPENDENT on HBV to provide HBsAg Replicates only in the hepatocytes HDV antigens ○ Small delta antigen – usually produced in the early stages of infection ○ Large delta antigen – produced in the later stages of infection High Risk of Infection: People with Chronic HBV, Injection-drug users, commercial sex workers, Men-having-sex with men ➔ ➔ ➔ ➔ ➔ Transmission: Broken skin Contact with infected blood ◆ E.g. blood transfusion, sharing of syringes, sharp objects, etc. Mother to child (Rare case) (at birth) Unprotected Sexual Intercourse Sharing toothbrushes, razors, etc. Complications HDV is known to occur either as a co-infection or a superinfection Co-infection Superinfection occurs when both HDV and HBV contracted simultaneously Acute HDV & HBV infection occurs when Chronic HBV carriers are infected with HDV Severe acute hepatitis and Chronic Hepatitis D infection in 80% of the cases LABORATORY DIAGNOSIS & IDENTIFICATION The diagnosis of Hepatitis D infection is made following serologic tests for the virus Radioimmunoassay (RIA) & Enzyme Immunoassay (EIA): Detects the total anti-HDV antibodies Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR): To monitor any ongoing HDV infection Detects 10-100 copies of HDV genome in infected serum TREATMENT No specific treatment for HDV PEGylated interferon alpha PREVENTION AND CONTROL Prevention of Hepatitis D virus is based on prevention of Hepatitis B virus Co-infection: the HBV or post exposure prophylaxis can be used to prevent the infection Superinfection: educate chronic HBV carriers about transmission and risky behaviors; proper health infection COPY FOR: ORIT, ANNE CHELSEA R. | 5 HEPATITIS E Other names: Enteric Hepatitis; Self-limiting Hepatitis; Most common cause of Acute Hepatitis ○ Acquired through contaminated water or food that is not properly cooked Replication only occurs in the LIVER ○ Incubation may go from 20-40 days (slow) Reactivation is possible CLASSIFICATION Genus: Hepevirus Species: Hepeviridae STRUCTURE: Small, nonenveloped virus with a single-stranded RNA genome; 4 genotypes Transmission Fecal-Oral; vertical transmission is possible; zoonotic transmission; breastfeeding Disease Hepatitis similar to that caused by hepatitis A virus except for extraordinarily high case fatality rate (10%-20%) among pregnant women Diagnosis Serology Treatment Supportive Prevention Avoid contact with the virus PATHOGENESIS Characteristics Genotype 1 Genotype 2 Genotype 3 Genotype 4 Geographic location Africa and Asia Mexico, West Africa Developed Countries China, Taiwan, Japan Transmission route Waterborne fecal-oral; person-to-person Waterborne fecal-oral Food-borne Food-borne Groups at high risk for infection Young adults Young adults Older Adults (>40 years) and males, Immuno-compromis ed persons Young adults Zoonotic transmission NO YES Chronic infection Occurrence of Outbreaks Common Smaller scale outbreaks YES NO Uncommon Uncommon CLINICAL MANIFESTATIONS When they occur, the signs and symptoms of Hepatitis E are similar to those of other types of acute viral hepatitis and liver injury Fever Fatigue Loss of appetite Nausea Vomiting Abdominal pain Jaundice LABORATORY DIAGNOSIS AND IDENTIFICATION Diagnosis can be confirmed only by testing for the presence of antibody against HEV or HEV RNA Liver function tests ○ Increased levels of serum bilirubin (↑) ○ Increased AST (↑) ○ Increased ALT (↑) CONFIRMATORY TEST: Nucleic acid testing is recommended to confirm positive serology results in areas where HEV is not endemic TREATMENT AND MANAGEMENT Hepatitis E usually resolves on its own without treatment (Typically advised to rest) There is no specific antiviral therapy for acute hepatitis E Patients who do develop fulminant liver failure need liver transplantation PREVENTION & CONTROL Good sanitation COPY FOR: ORIT, ANNE CHELSEA R. | 6 Mycology and Virology | MLS-415 F2−3: RNA VIRUSES Professor: Thynee Tago, MSMT Date: April 29, 2024 PICORNAVIRIDAE Enterovirus, Hepatovirus and Rhinovirus Apthovirus (foot-and-mouth disease) Cardiovirus Invades local lymphoid tissue → Bloodstream → Infect cells of the CNS (Able to cross the BBB) → Destruction of motor neurons → Distinctive paralysis CLASSIFICATION AND STRUCTURE Agent of Polio or Poliomyelitis Enterovirus C serotype (Most Common) 3 poliovirus serotypes: Types 1, 2, and 3 (Infectious) positive-sense ssRNA genome and a protein capsid RNA genome (7500 nucleotides long) Icosahedral symmetry; 30 nm in diameter Composition Icosahedral, 28–30 nm in diameter, contains 60 subunits Single-stranded RNA, linear, positive sense, 7.2–8.4 kb in size, molecular weight 2.5 million, infectious, contains genome linked protein (VPg) Proteins Four major polypeptides cleaved from a large precursor polyprotein. Surface capsid proteins VP1, VP2 and VP3 are major antibody-binding sites. VP4 is an internal protein. Envelope None Outstanding characteristic END RESULT: Atrophy due to disuse, loss of stimulation/ innervation CLINICAL MANIFESTATIONS & COMPLICATIONS About 25% are (+) for FLU-LIKE symptoms: Sore throat Fever Tiredness Nausea Headache Stomach pain (GIT related) Less than 1% are (+) for symptoms that affect the brain and spinal cord ○ Paresthesia ("pins and needles” sensation) ○ Meningitis ○ Paralysis RNA (30%), protein (70%) Genome Replication “Type 1 is the most virulent and common” IMPORTANT PROPERTIES OF PICORNAVIRUSES Virion PATHOGENESIS Entry through MOUTH Replication in oropharynx & GIT Cytoplasm Family is made up of many enterovirus and rhinovirus types that infect humans and lower animals, causing various illnesses ranging from poliomyelitis to aseptic meningitis to the common cold. [A] Child with a deformity of her right leg caused by poliovirus; [B] Child in Nigeria with a leg paralyzed from Polio; [C] A patient with arm paralysis caused by poliovirus infection (Rare) Copy for: HAW, SPENCER O. | 1 Specimen: Throat, Feces/ stool and CSF CDC laboratories conduct testing for poliovirus, including: ○ Culture ○ Intratypic Differentiation To differentiate the serotypes ○ Genome Sequencing ○ Serology Greatest viral yield is from viral culture of stool Detection of poliovirus in CSF or blood is rare – TIMING is of essence; when the patient is showing signs and symptoms TREATMENT, PREVENTION & CONTROL Vaccine Types: 1. Inactivated Poliovirus Vaccine (IPV) a. Salk Vaccine (TuSALK = Tusok) b. Contains killed virus (injected) 2. Oral Poliovirus Vaccine (OPV) a. Sabin Vaccine (Sabin = Sa BABA) b. Contains live attenuated/ weakened virus COXSACKIE CLASSIFICATION AND STRUCTURE LARGEST enteroviral group; Enterovirus genus of Picornaviridea family Named after the Coxsackie Village, NY state Icosahedral capsid ○ Spherical protein shell ○ d/t 20 equilateral triangular faces (looks like a volleyball) Naked Positive-sense ssRNA virus PATHOGENESIS Virus distribution is similar to enterovirus (INGESTION) Early stage of infection; no particular tropism; easily isolate virus from different specimen ○ Blood ○ Throat All available for 5-6 weeks ○ Stool Incubation Period ○ 2-9 days CLINICAL MANIFESTATIONS & COMPLICATIONS GROUP A COXSACKIE Aseptic meningitis (A7, A9) Herpangina (severe febrile pharyngitis) ○ Infection observed in the mouth Hand-foot-mouth disease ○ Associated with A6, A16, B1 & enterovirus 71 ○ More common in CHILDREN ○ Rashes may appear inside the mouth, around the lips, Palmar region, Dorsal surface & Plantar surface; But does not go lower than the wrist ○ Ulcers may grow and cause pain ○ Vesicles heal without crusting ○ Acute hemorrhagic conjunctivitis – Bacterial Vs. Viral Bacterial – RED EYES + MORNING DUST (muta) Viral – LESS RED EYES + BLEPHARITIS (Inflamed eyelids) GROUP B COXSACKIE May cause more SERIOUS and FATAL infections Aseptic meningitis (all types) Pleurodynia (epidemic myalgia) ○ Fever, stabbing chest pain – malaise, headache & anorexia Myocarditis ○ Fatal in neonates ○ Permanent heart damage Hepatitis Pancreatitis & Pneumonia Generalized disease of infants LABORATORY DIAGNOSIS & IDENTIFICATION SPECIMEN: Throat washing (first few days) Stool (first few weeks) Nasal secretions Feces, Conjunctival, Throat swabs CSF → Signs of aseptic meningitis Cytopathic effect (tissue culture) ○ 5-14 days NUCLEIC ACID DETECTION Reverse transcription PCR Real-time PCR Assays Copy for: HAW, SPENCER O. | 2 SEROLOGY (Screening) Difficult to evaluate (this is the reason why serology is not good for diagnosis) ○ Multiplicity of virus types Immunofluorescence (Serum Abs) CLINICAL MANIFESTATIONS & COMPLICATION TREATMENT, PREVENTION & CONTROL SORE THROAT – The cold virus irritates your nasal lining, triggering extra mucus production. Normally, tiny hairs (cilia) sweep mucus away, but the cold can slow them down. This excess mucus then drips down the back of your throat causing soreness. No vaccines or antiviral drugs Analgesic intake Adequate fluid intake Rest RHINOVIRUS CLASSIFICATION & STRUCTURE Common Cold Virus – Most of the common colds are caused by rhinovirus Enterovirus Positive-sense, non-enveloped, ssRNA Icosahedral in structure 4 capsid proteins VP1, VP2, VP3 & VP4 Acid-labile >150 serotypes are known Receptor: Intercellular Adhesion Protein Molecule-1 (ICAM-1) PATHOGENESIS Gain entry through respiratory tract It can be passed through an airborne droplet or passage in fomites Tropism: epithelial cells of the nose Interacts with ICAM-1 receptor Virus exits the cell through cell lysis and exits the body through mucous secretions or droplets COMPLICATIONS: Otitis media – eustachian tube related Sinusitis Asthma COPD Cystic fibrosis – problems in the electrolyte channels OTITIS MEDIA – The common cold can cause inflammation in the Eustachian tube (connects middle ear to throat). This swelling can trap fluid and create a breeding ground for bacteria, leading to an ear infection. CYSTIC FIBROSIS – Excessive mucus build up caused by blockage of electrolyte channels; mucus is not expelled that well LABORATORY, DIAGNOSIS & IDENTIFICATION SPECIMEN: Nasal secretions Confirmation of rhinovirus infection is rarely required ○ Because it is very common RT-PCR Cell culture (MRC-5) using PLAQUE ASSAY TREATMENT, PREVENTION & CONTROL No specific prevention or treatment No available vaccines OTC medicines help ease symptoms Rest and Drink plenty of fluids Copy for: HAW, SPENCER O. | 3 To reduce the risk of getting colds: Wash your hands with soap and water Avoid touching your eyes, nose and mouth with unwashed hands Stay away from people who are sick Disinfect frequently touched surfaces and objects ROTAVIRUS CLASSIFICATION & STRUCTURE Family Reoviridae Wheel-like appearance Nonenveloped, dsRNA viruses Three concentric shells (protein capsid) Structural protein: VP1-VP4, VP6, VP7 7 distinct groups: A to G groups (Most important are A,B & C) Stable at 50 deg C; pH 3.0 - 9.0 and to lipid solvents ○ Basically unaffected by ACIDS or ALKALI Size (nm) Group A Group B Group C Epidemiology Important as a cause of hospitalization 60-80 Single most important cause (viral or bacterial) of endemic severe diarrheal disease in infants and young children worldwide (in cooler months in temperate climates) YES 60-80 Outbreaks of diarrheal illness in adults and children in China and Southeast Asia NO 60-80 Sporadic cases and occasional outbreaks of diarrheal illness in children NO Group A – in the Philippines, it is common regardless of the climate because of unclean food products or unhygienic attitudes. PATHOGENESIS 1 2 Virus Enters The Body Virus Reaches The Small Intestine Replicate In The Cytoplasm Of Enterocytes Once inside the enterocytes, the virus hijacks the cell's machinery to make copies of itself. This replication process disrupts the normal function of the enterocyte. 4 NSP4 Induce Secretion By Triggering Ca-Independent Signal Transduction Pathway A non-structural protein produced by the virus, called NSP4, plays a key role in causing diarrhea. NSP4 activates a signaling pathway within the cell that doesn't involve calcium (Ca-independent). This pathway leads to the secretion of fluids and electrolytes into the intestine. Damage Cells Slough Off Into The Lumen Of The Intestine 5 ROTAVIRUS Virus 3 Rotavirus is typically spread through contaminated hands, surfaces, or close contact with an infected person. The virus enters the mouth and travels through the digestive system. It specifically targets the mature enterocytes, which are the cells lining the villi in the small intestine responsible for nutrient absorption. Viral replication and NSP4 activity damage the enterocytes. The damaged cells detach from the lining of the small intestine and are shed into the lumen (the hollow center). NECROSIS OF THE VILLI (DAMAGED) Damaged mitochondria → No ATP → Calcium levels will INCREASE → Affecting electrolytes → K, Na will extravasate → Water follows Na → Causing now WATERY STOOL 2 FORMS: Complete – double-shelled (LARGE) Incomplete - single shelled (SMALL) CLINICAL MANIFESTATIONS & COMPLICATIONS Diarrheal illness ○ Mostly in infants and children but not in adults ○ Avoid dehydration; drink plenty of fluids Fever – normal response of the body to eliminate the virus Abdominal pain Vomiting LABORATORY DIAGNOSIS & IDENTIFICATION SPECIMEN: Stool specimen Rotavirus can be diagnosed through: ○ EIAs ○ IEM – Add antisera to agglutinate virus; easy visualization ○ PCR – screening ○ ELISA – screening Copy for: HAW, SPENCER O. | 4 TREATMENT, PREVENTION & CONTROL No specific treatment Drink plenty of liquids Oral rehydration solutions – Orisol Severe dehydration may require hospitalization Waste water treatment and sanitation are significant control measures 3 proteins → Participate in viral envelope formation ○ (M) Matrix protein ○ (HN) Hemagglutinin-neuraminidase ○ (F) Fusion protein CLASSIFICATION PARAMYXOVIRIDAE Includes the: ○ Mumps and Measles ○ Respiratory Syncytial Virus Common in infants & young children ○ Parainfluenza virus Mumps and measles is disseminated throughout the body and cause generalized disease Initiate infection via the respiratory tract Limited to the respiratory epithelia (replication site) ○ From there it could spread through your LYMPH and BLOOD VESSELS; Cause infection all throughout the body STRUCTURE & COMPOSITION MORPHOLOGY Spherical Pleomorphic Size: 150 nm or more in diameter (up to 700 nm) ENVELOPE Fragile Labile to storage conditions Prone to distortion in electron micrographs VIRAL GENOME Linear Negative-sense Single-stranded Non-segmented RNA Size: 15kb PROTEINS: 6 structural proteins 3 proteins → complexed w/ viral RNA ○ (N) nucleocapsid ○ (L) large polymerase ○ (P) Phosphoprotein RUBULAVIRUS 2 other parainfluenza viruses Mumps virus MORBILLIVIRUSES Rubeola virus (Measles) Canine distemper virus Aquatic morbilliviruses SYNCYTIUM – Single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei (HALLMARK) NOTICE: Syncytial formation – induced by paramyxoviruses Copy for: HAW, SPENCER O. | 5 RUBULAVIRUS (Mumps Virus) Acute Contagious Disease Characterized by: ○ Non-suppurative enlargement of one or both salivary glands Mostly causes a mild childhood disease Adult complication are fairly common ○ E.g. meningitis and orchitis 5. Generalized spread to salivary and other glands and to other body sites: The virus in the bloodstream has a particular affinity for salivary glands, especially the parotid glands (located near your cheeks and ears). Infection of these glands causes swelling, the characteristic symptom of mumps. In some cases, the virus can also infect other glands like the (1) testicles (orchitis) or (2) ovaries (oophoritis), causing inflammation and pain. Less commonly, the virus can reach other body sites like the (3)brain (leading to meningitis) or the testicles (leading to orchitis). CLINICAL MANIFESTATIONS AND COMPLICATIONS PATHOGENESIS & PATHOLOGY Incubation Period: 2-4 weeks (~14-18 days) Virus is shed on the saliva around 3-9 days after the onset of salivary gland swelling There is a difficulty in controlling its transmission because its incubation period is variable 1. Silent entry into respiratory tract: The virus enters your body through inhaled respiratory droplets from an infected person (coughing, sneezing). Unlike some viruses, rubulavirus doesn't cause immediate symptoms at this stage. 2. Spread to local lymph nodes: The virus first infects cells in the lining of your respiratory tract (like the throat). It replicates inside these cells, producing new viruses. The newly formed viruses then spread to nearby lymph nodes, which are part of your immune system. 3. Spread to distant lymph nodes and spleen: Within the lymph nodes, the virus infects immune cells, further multiplying its numbers. From these initial lymph nodes, the virus can travel through the lymphatic system to reach distant lymph nodes and even the spleen (another immune organ). 4. Viraemia: After replicating in the lymph nodes, some viruses enter your bloodstream, a stage called viraemia. This allows the virus to spread throughout your body. At lease ⅓ of all mumps infections are subclinical; If it manifests, it is usually in the prodromal stage SWOLLEN SALIVARY GLANDS ○ Most characteristic feature of symptomatic cases (about 50%) COMPLICATIONS COULD BE: (MOMPS) Meningitis (aseptic) Orchitis/ oophoritis (5% of women) Meningoencephalitis (Occurs 5-7 days after the inflammation of salivary glands Parotitis/ Pancreatitis (4% of cases) Self-Limited (Usually) LABORATORY DIAGNOSIS AND IDENTIFICATION SEROLOGY – detect antibody rise ELISA - Mumps specific IgM/ IgG Hemagglutination Inhibition Test Copy for: HAW, SPENCER O. | 6 NUCLEIC ACID DETECTION RT-PCR Most sensitive; for epidemiologic studies VIRUS ISOLATION & IDENTIFICATION Immunofluorescence – Detect antigens as early as 2-3 days Culture – CSF, Saliva or Urine (inoculate immediately because the virus is THERMO-LABILE) ○ Will show syncytia Hemadsorption test TREATMENT, PREVENTION & CONTROL No specific therapy Immunization - MMR Vaccine (Measles-Mumps-Rubella); Can be given to 1 yr olds; 3 doses + 1 booster MORBILLIVIRUS (Rubeola (Measles) Virus) HARD MEASLES (Pain measles) – Acute; highly infectious; characterized by: (1) Fever, (2) Respiratory symptoms, (3) Maculopapular rash Currently low cases because the vaccine is effective 7 Reticuloendothelial system The bloodstream carries the virus to various organs, particularly those rich in the reticuloendothelial system (RES). This system includes organs like the spleen, liver, and bone marrow, which play a role in filtering blood and harboring immune cells. 8 Secondary viremia Within the RES organs, the virus replicates again. This burst of viral production leads to a secondary viremia, a much larger release of virus particles back into the bloodstream. 9 Epithelial Surfaces of the body The secondary viremia allows the virus to reach and infect epithelial surfaces throughout your body. These are thin layers of cells lining various organs and systems, including: The respiratory tract (where the infection began) - This can cause coughing, sneezing, and a runny nose. The skin - This leads to the characteristic measles rash. The eyes (conjunctivitis) - Causing redness and irritation. The gastrointestinal tract (diarrhea) The events during incubation period usually lasts around 8-5 days but can reach 3 weeks in adults The virus can replicate in certain lymphocytes that would be responsible for its spread throughout the body PATHOGENESIS 1 Measles Virus This stage simply identifies the culprit - a type of virus called a morbillivirus, with measles being the most common example. 2 Respiratory tract The virus enters your body through inhaled droplets from an infected person's cough or sneeze. These droplets land in your respiratory tract, like the nose or throat. 3 Multiplies locally The virus infects cells lining your respiratory tract. Once inside, it hijacks the cell's machinery to make copies of itself, multiplying its numbers. 4 Regional lymphoid Tissues The newly formed viruses escape the infected cells and travel to nearby lymph nodes, which are part of your immune system. 5 Further multiplies Within the lymph nodes, the virus infects immune cells, creating a viral breeding ground and further amplifying its numbers. 6 Primary viremia After replicating extensively in the lymph nodes, some viruses enter your bloodstream, a stage called primary viremia. This allows the virus to spread throughout your body. Warthin-Finkeldey – multinucleated giant cell w/ intranuclear inclusion; seen in lymphoid tissues of infected individuals MACULOPAPULAR RASH Patients are highly contagious during: ○ Prodromal phase (2-4 days) ○ First 2-5 days of rash Day 14 ○ Maculopapular rash appearance (after the settles) ○ Detectable circulating antibodies ○ Viremia disappears ○ Fever fades fever Copy for: HAW, SPENCER O. | 7 CLINICAL MANIFESTATIONS & COMPLICATIONS In non-immune hosts: Infection is almost always SYMPTOMATIC Incubation period: 8-15 days PRODROMAL PHASE: (Last few hours of the Log phase) Fever Sneezing Coryza (runny nose) & cough Redness of the eyes Conjunctivitis w/ photophobia Koplik spots Lymphopenia Rash Otitis Media – most common complication in measles Pneumonia ○ Caused by secondary bacterial infection (life threatening) ○ Giant cell pneumonia (Common in children and adults) Encephalitis ○ Primary Measles Encephalitis – Usually occur in 1-3 patients in about 1000 children contracting measles ○ Acute Postinfectious Measles Encephalomyelitis (APME) ; 1 in 1000 children w/ measles ○ Measles Inclusion Body Encephalitis (MIBE) Immunosuppressed patients; generally after 6 months of measles virus infxn ○ Subacute sclerosing panencephalitis (SSPE) Occurs in ~10 years in previously healthy patient Together with MIBE occur after the acute phase of the infection SUBACUTE SCLEROSING PANENCEPHALITIS (SSPE) Aka Dawson Disease; 1 in 5,500 children under 1 year of age Rare late complication Begins insidiously 5-15 years after measles; immunocompromised Characterized by progressive (1) Mental retardation, (2) Involuntary movements, (3) Muscular rigidity, and (4) Coma KOPLIK SPOTS (Characteristic of Measles) – These spots resemble grains of salt on a red base FEVER & 3C (Cough, Conjunctivitis & Coryza)– Persist until the rash appears RASH – Starts on the head then spread progressively down to limbs ; ○ Hairline → face → Torso → Limbs ○ Appears as light pink, discrete maculopapules that coalesce to form blotches, becoming brownish in 5-10 days COMPLICATIONS (MEASLES COMP): Myocarditis Encephalitis Appendicitis Subacute Sclerosing Panencephalitis Laryngitis Early Death Severe Diarrhea Corneal ulcer Otitis media Mesenteric Lymphadenitis Pneumonia LABORATORY DIAGNOSIS & IDENTIFICATION Antigen and Nucleic Acid Detection Via RT-PCR Isolation of identification of virus Collection: Febrile period Nasopharyngeal and conjunctival swabs, blood samples, respiratory secretions, and urine For culture: Human kidney cells or Lymphoblastoid cell lines ○ We can also use Shell-vial culture – Virus samples are added to cells growing on a cover slip in a small vial. Serology (Depends on a 4 fold rise in the antibody titer) ELISA HAI Neutralization test TREATMENT, PREVENTION & CONTROL Vaccination – attenuated live measles Vitamin A treatment HIGH RISK POPULATION: Unvaccinated child, Missed Booster Shots, Unvaccinated due to medical reasons Copy for: HAW, SPENCER O. | 8 TOGAVIRIDAE German Measles (Rubella Virus) Member of the Togaviridae The only member of the Genus Rubivirus The only known host is humans Postnatal Rubella & Congenital Rubella ○ Congenital Rubella is often seen in pregnant moms) PATHOGENESIS & PATHOLOGY POSTNATAL RUBELLA Infects NEONATES, CHILDREN and ADULTS Mucosa of the upper respiratory tract Incubation period: 12 Days or more Viremia: Develop after 7-9 days and lasts until antibodies will appear ○ Rise of antibody will coincide with the appearance of the rashes 1 Rubella Virus The culprit: The rubella virus, a single-stranded RNA virus. 2 Transmitted via respiratory droplets The virus enters your body when you inhale droplets from an infected person coughing or sneezing. 3 Infects cells in the upper respiratory tract The droplets land in your upper respiratory tract (like the nose or throat). The virus infects cells lining this area. 4 Virus multiplies Once inside the cells, the virus hijacks their machinery to make copies of itself, rapidly increasing its numbers. 5 Extends in the regional lymph node New virus particles escape the infected cells and travel to nearby lymph nodes, which are part of your immune system. 6 Virus replicates in the nasopharynx While some viruses travel to lymph nodes, some may stay and continue replicating in the nasopharynx (upper part of the throat behind the nose). This extended replication in the original infection site can contribute to the contagious nature of the illness. 7 8 Infection is established in the skin The virus spreads through the bloodstream, reaching and infecting skin cells throughout your body. Forchherimer’s spot may develop In some cases, tiny red spots (rose pink) called Forchheimer's spots may appear on the soft palate (roof of the mouth) before the main rash. 9 Rashes develop Infection of skin cells disrupts their normal function, leading to the characteristic red, maculopapular rash associated with rubella. This rash typically starts on the face and spreads down the body. 10 Virus can be found in the skin, blood and respiratory tract During active infection, the virus can be present not only in the skin causing the rash, but also in the blood (viremia) and the respiratory tract (where it can be transmitted to others). CLINICAL MANIFESTATIONS & COMPLICATIONS Malaise, low-grade fever and a morbilliform rash RASH: Face → Trunk and extremities (3 days) Rubella antibodies appear in the serum of patients as the rash fades and the antibody titer rises rapidly over the next 1-3 weeks LABORATORY DIAGNOSIS & IDENTIFICATION SEROLOGY Hemagglutination Inhibition ELISA Culture PCR PATHOGENESIS & PATHOLOGY CONGENITAL RUBELLA SYNDROME – The baby is still inside the womb 1 Rubella Virus infection in the early weeks of pregnancy Maternal infection with rubella virus, especially during the first trimester (first 12 weeks), poses the highest risk for CRS in the developing fetus. 2 Accumulation of Vitamin A in the liver Rubella infection disrupts liver function, potentially affecting vitamin A metabolism. This would now cause LIVER DAMAGE The liver normally stores vitamin A and converts it into various forms, including retinoic acid, which plays a crucial role in fetal development. 3 Acute liver damage and cholestasis Cholestasis is the stalling of bile flow through our biliary system 4 Spillage of retinoic acids in the bile and leakage of retinyl esters into the This would not be good for surrounding tissues and would cause the next step to happen Copy for: HAW, SPENCER O. | 9 circulation from damaged hepatocytes 5 Mitochondrial damage, apoptosis and alterations in the DNA Rubella infection can directly damage fetal cells through various mechanisms, including mitochondrial dysfunction, programmed cell death (apoptosis), and alterations in DNA. This cellular damage likely plays a significant role in causing birth defects. 6 Congenital Rubella Syndrome The various factors mentioned above, including potential vitamin A disruption and direct cellular damage, likely contribute to the development of CRS birth defects. These defects can affect multiple organ systems, leading to the characteristic features of CRS. CLINICAL MANIFESTATIONS & COMPLICATIONS CLASSIC TRIADS Cataracts Deafness Cardiac Abnormalities TRANSIENT SYMPTOMS Growth retardation Rash Hepatosplenomegaly Jaundice Meningoencephalitis TREATMENT, PREVENTION & CONTROL No specific treatment MMR = 3 doses with booster Copy for: HAW, SPENCER O. | 10 Mycology and Virology | MLS-415 F4: Influenza Virus Professor: Thynee Tago, MSMT Date: May 6, 2024 INFLUENZA Part of Orthomyxoviridae Enveloped RNA Virus; tendency to be pleomorphic ○ Its envelope changes yet the internal structure is always spherical Causes contagious respiratory illness (FLU/ INFLUENZA) that infect the nose, throat and lungs ○ They are around us all year long Occurs as: Sporadic, Epidemic & Pandemic HISTORY Influenza Pandemics of the 20th Century 1918: Pandemic (H1N1 Virus); The Spanish Flu ○ This strain of flu virus which is common in humans 1957: Asian Influenza (H2N2) ○ The very first recorded H2N2 pandemic 1968: Hong Kong Influenza (H3N2) 1977: Russian Flu, A Juvenile, Age-restricted Pandemic (People