Virology Past Paper PDF - Our Lady of Fatima University

VIROLOGY Our Lady of Fatima University – College of Pharmacy  Virus Virus is an infectious agent with both living and nonliving characteristics. Living Characteristics of Viruses a. Reproduce at an extensive rate (only in living host cells) b. Has the ability to mutate ...

VIROLOGY Our Lady of Fatima University – College of Pharmacy  Virus Virus is an infectious agent with both living and nonliving characteristics. Living Characteristics of Viruses a. Reproduce at an extensive rate (only in living host cells) b. Has the ability to mutate  Virus Nonliving Characteristics of Viruses a. Acellular (no cytoplasm, cell membrane, nor cellular organelles) b. Cannot metabolize on their own c. Possess DNA or RNA but never both  Viral Structure Since viruses are not cells, they are structurally much simpler than bacteria. An intact infectious viral particle is called a virion and consists of: 1. Genome 2. Capsid 3. Envelope  Viral Structure 1. Genome Molecule of nucleic acid functioning as the genetic material of the virus. Codes for the synthesis of viral components and viral enzymes for replication. Single or segmented Circular or linear Single-stranded or double-stranded DNA or RNA (but never both)  Viral Structure 2. Capsid A.k.a. protein coat, core A protein shell surrounding the genome and is usually composed of protein subunits called capsomeres. The capsid serves to protect and introduce the genome into host cells.  Viral Structure Some viruses consist of no more than a genome surrounded by a capsid and are called nucleocapsid or naked viruses. Attachment proteins (spikes) project out from the capsid and bind the virus to susceptible host cells.  Viral Structure 3. Envelope Viruses with an envelope surrounding a polyhedral or helical nucleocapsid are called enveloped viruses. The envelope is composed of phospholipids and glycoprotein and for most viruses, is derived from host cell membranes by a process called budding.  Viral Structure The envelope may come from the host cell's nuclear membrane, vacuolar membranes (packaged by the Golgi apparatus), or outer cytoplasmic membrane.  Host range Refers to the spectrum of host cells in which a virus can multiply. Most viruses infect only specific types of cells in one host species. Host range is determined by the specific attachment site on the host cell’s surface and the availability of host cellular factors.  Size Viral size is ascertained by electron microscopy. Viruses range from 20 to 14,000 nm in length.  Classification of Viruses Viruses are often classified by the following characteristics: A. The type of nucleic acid they have for their genome B. The shape of their capsid (helical or polyhedral) C. Whether they are enveloped or naked (lack an envelope)  Classification of Viruses Helical viruses resemble long rods, and their capsids are hollow cylinders surrounding the nucleic acid. Polyhedral viruses are many sided. Usually the capsid is an icosahedron. Enveloped viruses are covered by an envelope and are roughly spherical but highly pleomorphic.  Polyhedral (icosahedral) Helical  Classification of Viruses Complex viruses have complex structures. For example, many bacteriophages have a polyhedral capsid with a helical tail attached. HELICAL POLYHEDRA L ICOSAHEDRAL  Classification of Viruses Viruses can store their genetic information in six different types of nucleic acid which are named based on how that nucleic acid eventually forms the viral mRNA able to bind to host cell ribosomes and be translated into viral proteins.  Classification of Viruses These types of nucleic acid are: 1. (+/-) double-stranded DNA. The (-) DNA strand is directly transcribed into viral mRNA e.g. bacteriophages, Papovaviruses, Adenoviruses, Herpesviruses. 2. (+) DNA or (-) DNA. Once inside the host cell, its converted into dsDNA and the (-) DNA strand is transcribed into viral mRNA. Phage M13, Parvoviruses.  Classification of Viruses 3. (+) RNA. Functions as mRNA after entry into the cell. Picornaviruses, Togaviruses, Coronaviruses. 4. (-) RNA. The (-) RNA is copied into a (+) RNA which functions as viral mRNA. Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses.  Classification of Viruses 5. (+/-) double-stranded RNA. The (+) of the (+/-) RNA functions as viral mRNA. Reoviruses. 6. (+) RNA in retrovirus. The (+) RNA is reverse transcribed into (-) DNA that makes a complementary copy to become (+/-) DNA. The (-) DNA is transcribed into viral mRNA. Retroviruses.  Stages of Viral Replication 1. Adsorption or attachment The process in which the virus adheres to the host cell surface This process is selective, in which the virus will adhere only to selected host cells it can infect (permissive cells) depending on the receptors found on the host cell (receptor) and on the viral surface (anti-receptor).  Stages of Viral Replication 2. Penetration Also called viral entry This process follows attachment and happens almost instantaneous the moment the virus attaches to the cell. Three (3) types: Viral translocation across the plasma membrane; endocytosis; membrane fusion  Stages of Viral Replication 3. Uncoating Happens after viral entry wherein the capsid protecting the viral genome is removed. Removed by degradation by enzymes, whether viral or host or by simple dissociation. This results in the release of the viral nucleic acid.  Stages of Viral Replication 4. Synthesis After the genome is liberated, viral parts are now synthesized from the genome. The first usual step is the replication of the mRNA (except for (+)RNA viruses). Then the viral mRNA are used to synthesize different proteins needed by the virus.  Stages of Viral Replication 5. Assembly Step after the synthesis of viral parts. All the viral parts needed to complete a virion are assembled.  Stages of Viral Replication 6. Release Viruses are then released form the cell by lysis of the cell (lytic cycle) or if the virus is enveloped, by budding. Stages of Viral Replication Some viruses undergo a lysogenic cycle where the viral genome would be integrated in the host cell’s chromosome and becomes a provirus, or a prophage if in bacteria. When the cell replicates, it replicates along with it, the viral genome. Until such time that the genome would synthesize the virus, the cell would now be lysed.  Stages of Viral Replication Isolation, Cultivation, and Identification of Viruses Viruses must be grown in living cells. The easiest viruses to grow are bacteriophages.  General Information Taxonomy of Viruses Classification of viruses is based on type of nucleic acid, morphological class, and presence or absence of an envelope. Virus family names end in –viridae; genus end in –virus. A viral species is a group of viruses sharing the same genetic information and ecological niche.  General Information Nucleic acid of all DNA viruses are double- stranded, except Parvovirus While all RNA are single-stranded, except Reovirus Most viruses have linear genome, except Papovavirus which have supercoiled, circular genomes  General Information Most viruses with icosahedral symmetry are naked, except Toga, Herpes, Retro and Flavi, Bunya, Hepadna virus. Smallest: Parvovirus, Picornavirus Largest: Poxvirus  Virus Families RNA viruses Picornaviridae Reoviridae Astroviridae Arenaviridae Flaviviridae Filoviridae Orthomyxoviridae  Naked RNA viruses Picornaviridae (icosahedral) Astroviridae (icosahedral) Calicivirus (icosaheral) Reoviridae (icosahedral – outer and inner capsid) (dsRNA)  Enveloped RNA viruses Flaviviridae (icosahedral) Togaviridae (icosahedral) Coronoviridae (pleomorphic) Retroviridae (icosahedral) Bunyaviridae (icosahedral) Orthomyxoviridae (pleomorphic)  Enveloped RNA viruses Arenaviridae (pleomorphic) Filoviridae (helical) Rhabdoviridae (helical, rod-shaped) Paramyxoviridae (helical, pleomorphic)  Virus Families DNA viruses Hepadnaviridae Herpesviridae Adenoviridae Poxviridae Papovaviridae Parvoviridae  Naked DNA viruses Parvoviridae (icosahedral, ssDNA) Papovaviridae (circular DNA) Adenoviridae (icosahedral)  Enveloped DNA viruses Hepadnaviridae (icosahedral) Herpesviridae (icosahedral) Poxviridae (oval, large) (complex structure) Medically Important DNA Viruses  Herpesviridae Herpes simplex virus 1 and 2 (HSV-1 and HSV- 2) 1 = face, 2 = genitals Varicella zoster virus (VZV) – chicken pox , shingles (reactivated chicken pox) HERPES SIMPLEX VIRUS 1 HERPES SIMPLEX VIRUS 2  Herpesviridae Epstein-Barr virus – one of the most common viruses in humans; causes infectious mononucleosis; associated with cancers Human cytomegalovirus (HCMV or CMV) VARICELLA ZOSTER EPSTEIN-BARR VIRUS VIRUS CYTOMEGALOVIRUS  Papovaviridae Human papilloma virus (HPV) – warts  Poxviridae Vaccinia virus and variola virus – smallpox First human disease to be successfully eradicated by science  Hepadnaviridae Hepatitis B virus (HBV) Medically Important RNA Viruses  Picornaviridae Rhinovirus – common colds Hepatitis A virus (HAV)  Togaviridae Rubella virus – German measles  Paramyxoviridae Measles virus or rubeola Mumps virus MMR vaccine  Flaviviridae Hepatitis C virus (HCV) Dengue virus Yellow fever virus – also hemorrhagic and transmitted by Aedes aegypti  Reoviridae Rotavirus – most common cause of severe diarrhea in infants and children; known for stomach flu  Orthomyxoviridae Influenza virus – flu  Rhabdoviridae Rabies virus  Coronaviridae Corona virus – common colds; SARS; The coronavirus disease (COVID-19) is an infectious disease caused by a new strain of coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019.  Retroviridae Human immunodeficiency virus (HIV) – AIDS  Filoviridae Marburg virus (MARV) Ebola virus Both viruses can cause viral hemorrhagic fever and are categorized as possible agents for bioterrorism. Antiviral Drugs  Antiviral Drugs Nucleoside Reverse Transcriptase Inhibitor Zidovudine Lamivudine Didanosine Zalcitabine Stavudine  Antiviral Drugs Protease Inhibitors Saquinavir Indinavir Ritonavir Amprenavir  Antiviral Drugs DNA Polymerase Inhibitor Aciclovir Ganciclovir Ribavirin Foscarnet  Antiviral Drugs Interferons Palivisumab  END OF DISCUSSION.  Pharmaceutical Microbiology and Parasitology (PHMP 211) Virology Our Lady of Fatima University College of Pharmacy After the discussion, the students should be able to: ☐Understand the basic structures and growth of virus ☐Learn the pathogenesis of the organisms ☐Identify the different types of fungal infection based on their affectation and pathogenesis ☐Identify the different laboratory tests and diagnostic procedures for viral infection ☐Learn the different Pharmacologic therapies against viral infections. Virus ☐The smallest infectious agents (ranging from about 20 to 300 nm in diameter) and contain only one kind of nucleic acid (RNA or DNA) as their genome. ☐ The entire infectious unit is termed a virion. ☐ Replicates only in living cells and are inert in the extracellular environment Terms Capsid: ☐ The protein shell, or coat, that encloses the nucleic acid genome. Capsomeres: ☐ Morphologic units seen in the electron microscope on the surface of icosahedral virus particles. ☐ Capsomeres represent clusters of polypeptides, but the morphologic units do not necessarily correspond to the chemically defined structural units. Defective virus: ☐ A virus particle that is functionally deficient in some aspect of replication. Envelope: Enveloped virus with ☐ A lipid-containing membrane that surrounds some icosahedral symmetry. Not all virus particles. It is acquired during viral maturation icosahedral viruses have envelopes by a budding process through a cellular membrane ☐ Virus-encoded glycoproteins are exposed on the surface of the envelope. ☐ These projections are called peplomers. Nucleocapsid: ☐ The protein–nucleic acid complex representing the packaged form of the viral genome. The term is commonly used in cases in which the nucleocapsid is a substructure of a more complex virus particle. Structural units: ☐ The basic protein building blocks of the coat. They are usually a collection of more than one nonidentical protein subunit. The structural unit is often referred to as a protomer. Subunit: Virus with helical symmetry ☐ A single folded viral polypeptide chain. Virion: ☐ The complete virus particle. Nucleic Acid ☐DNA viruses – Usually double stranded (ds) but may be single stranded (ss) – Circular or linear ☐RNA viruses – Usually single stranded, may be double stranded, may be segmented into separate RNA pieces – ☐ssRNA genomes ready for immediate translation are positive-sense ☐Positive-sense RNA contain the message for translation ☐ssRNA genomes that must be converted into proper form are negative-sense RNA ☐Negative-sense RNA must be converted into positive-sense message Basis of Classification ☐Virion morphology, including size, shape, type of symmetry, presence or absence of peplomers, and presence or absence of membranes ☐Virus genome properties, including type of nucleic acid (DNA or RNA), size of the genome, strandedness (single or double), whether linear or circular, sense (positive,negative, ambisense), segments (number, size), nucleotide sequence, percent GC content, and presence of special features (repetitive elements, isomerization, 5′-terminal cap, 5′-terminal covalently linked protein, 3′-terminal poly(A) tract). ☐Genome organization and replication, including gene order, number and position of open reading frames, strategy of replication (patterns of transcription, translation), and cellular sites (accumulation of proteins, virion assembly virion release) Basis of Classification ☐Virus protein properties, including number, size, amino acid sequence, modifications (glycosylation, phosphorylation, myristoylation), and functional activities of structural and nonstructural proteins (transcriptase, reverse transcriptase, neuraminidase, fusion activities). ☐ Antigenic properties, particularly reactions to various antisera. Basis of Classification ☐Physicochemical properties of the virion, including molecular mass, buoyant density, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially solubilizing agents and detergents. ☐Biologic properties, including natural host range, mode of transmission, vector relationships, pathogenicity, tissue tropisms, and pathology Taxonomy of Viruses ☐Classification of viruses is based on type of nucleic acid, morphological class, and presence or absence of an envelope. ☐Virus family names end in –viridae; genus end in –virus. ☐A viral species is a group of viruses sharing the same genetic information and ecological niche. DNA Viruses HHAAPPPPy RNA Viruses: (PRAyFOR PRC)TBB Nucleic acid of all DNA viruses are double-stranded, except Parvovirus While all RNA are single-stranded, except Reovirus Most viruses have linear genome, except Papovavirus which have supercoiled, circular genomes Most viruses with icosahedral symmetry are naked, except Toga, Herpes, Retro and Flavi, Bunya, Hepadna virus. Smallest: Parvovirus, Picornavirus Largest: Poxvirus Stages of Viral Replication Adsorption or attachment The process in which the virus adheres to the host cell surface This process is selective, in which the virus will adhere only to selected host cells it can infect (permissive cells) depending on the receptors found on the host cell (receptor) and on the viral surface (anti-receptor). Penetration ☐Also called viral entry ☐This process follows attachment and happens almost instantaneous the moment the virus attaches to the cell. Three (3) types: ☐Viral translocation across the plasma membrane; endocytosis; membrane fusion ☐Naked viruses only undergoes the first two. Uncoating Happens after viral entry wherein the capsid protecting the viral genome is removed. Removed by degradation by enzymes, whether viral or host or by simple dissociation. This results in the release of the viral nucleic acid. ☐Endocytosis – entire virus is engulfed and enclosed in a vacuole or vesicle ☐Fusion – envelope merges directly with membrane resulting in nucleocapsid’s entry into cytoplasm Synthesis ☐After the genome is liberated, viral parts are now synthesized from the genome. ☐The first usual step is the replication of the mRNA (except for (+)RNA viruses). ☐Then the viral mRNA are used to synthesize different proteins needed by the virus. Assembly ☐Step after the synthesis of viral parts. ☐All the viral parts needed to complete a virion are assembled. Release ☐Viruses are then released form the cell by lysis of the cell (lytic cycle) ☐ Lysis – nonenveloped and complex viruses released when cell dies and ruptures ☐ if the virus is enveloped, by budding. ☐Budding – exocytosis; nucleocapsid binds to membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed Medically Important Viral DNA VIRUS infections Parvoviridae ☐Non enveloped ☐Parvoviruses (from Latin parvus meaning small) ☐Smallest DNA animal virus ☐ Replication occurs only in actively dividing cells ☐capsid assembly takes place in the nucleus of the infected Erythema infectiosum cell ☐Human parvovirus B19 replicates in immature erythroid cells and causes several adverse consequences, including aplastic crisis, fifth disease, and fetal death  Parvoviridae ☐Transmission is through respiratory route blood transfusion or vertical transmission ☐Fifth disease and transient aplastic crisis ☐There is no vaccine against human are treated parvovirus, although prospects are symptomatically. good that a vaccine can be developed. Severe anemia due to ☐There are effective vaccines against the latter may require animal parvoviruses for use in cats, transfusion therapy dogs, and pigs. There is no antiviral drug therapy Polyomaviridae ☐ Nonenveloped, heat-stable, solubilization-resistant viruses ☐from Greek poly-(many) and –oma (tumor) and refers to the ability of some of these viruses to produce tumors in infected hosts ☐These agents have a slow growth cycle, stimulate cell DNA synthesis, and replicate within the nucleus ☐The most well-known human polyomaviruses are ☐JC virus, the causative agent of progressive multifocal leukoencephalopathy; ☐BK virus, associated with nephropathy in transplant recipients ☐Merkel cell virus, found associated with the majority of Merkel cell skin carcinomas Papillomaviridae ☐Latin papilla (nipple) and Greek –oma (tumor) and describes wart-like lesions produced by these viral infections. ☐causative agents of genital and cervical cancers in humans ( genital warts) ☐Transmission of viral infections occurs by close contact ☐HPV ( Human Papillomavirus) type 16 and 18 are the most common and highest cancer risk Vaccines ☐Gardasil® ☐Recombinant vaccine prepared from L1 protein of HPV type 6, 11, 16 and 18 ☐Gardasil® 9 ☐Recombinant vaccine that targets 9 HPV subtypes, 6,11, 16, 18, 31,33,45,52,58 ☐Cervarix® ☐Recombinant vaccine prepared from L1 protein of HV type 16 and 18 Adenoviridae ☐ from Latin adenos meaning gland) are medium-sized (70–90 nm), ☐ non enveloped viruses exhibiting cubic symmetry, with fiber spikes protruding from capsomers that aid in host attachment ☐At least 67 types infect humans, especially in mucous membranes, and some types can persist in lymphoid tissue. ☐Adenoviruses can cause acute respiratory diseases, conjunctivitis, and gastroenteritis. ☐There is no specific treatment for adenovirus infections Hepadnaviridae ☐ from Latin hepa meaning liver ☐Replication involves repair of the single-stranded gap in the DNA, transcription of RNA, and reverse transcription of the RNA to make genomic DNA ☐Acid sensitive, causes acute and chronic disease ☐The surface protein is characteristically overproduced during replication of the virus, which takes place in the liver, and is shed into the bloodstream ☐Hepadnaviruses such as Hepatitis B virus can cause acute and chronic hepatitis; persistent infections are associated with a high risk of developing liver cancer (hepatocellular carcinoma) Vaccines ❑Engerix B ( 1mL(20mcg)), Recombivax HB (1mL(10mcg)) ❑3 doses 1 mL (20 mcg) ❑0,1 and 6 months interval for adults ❑For newborn with HBsAg –negative mothers: 0.5mL within 24 hrs ❑For newborn with HBsAg- positive mothers: 0.5mL within 12 hrs plus HBIG ❑Heplisav- B ❑2 doses ( for 18 years old and above) ❑0.5mL IM at 0 and 1 month interval Herpesviridae ☐Herpesviruses are family of large viruses 150–200 nm in diameter. ☐The name refers to Latin herpes (creep), describing the spreading nature of skin lesions caused by these viruses. ☐Human herpesviruses include ☐Herpes simplex types 1 and 2 (oral and genital lesions), ☐Varicella-zoster virus (chickenpox and shingles), ☐Cytomegalovirus ☐Epstein-Barr virus (infectious mononucleosis and association with human neoplasms), ☐Human herpesviruses 6 and 7 (T cell lymphotropic, Roseola infantum, Sixth disease), ☐human herpesvirus 8 (associated with Kaposi sarcoma). Classification of Herpes virus Herpesviridae ☐HSV-1 and HSV-2 infect epithelial cells and establish latent infections in neurons. ☐ Type 1 is classically associated with oropharyngeal lesions and causes recurrent attacks of “fever blisters.” ☐ Type 2 primarily infects the genital mucosa and is mainly responsible for genital herpes, though the anatomical specificity of these viruses is diminishing. ☐Both viruses can also cause neurologic disease. HSV-1 is the leading viral cause of sporadic encephalitis in the United States. ☐Both types 1 and 2 can cause neonatal infections that are often severe. Herpesviridae ☐VZV causes chickenpox (varicella) on primary infection and establishes latent infection in neurons. ☐Upon reactivation, the virus causes herpes zoster (shingles). ☐Adults who are infected for the first time with varicella-zoster virus can develop serious viral pneumonia Herpesviridae ☐CMV replicates in epithelial cells of the respiratory tract, salivary glands, and kidneys and persists in lymphocytes ☐It causes an infectious mononucleosis (heterophile antibody-negative). ☐In newborns, disseminated cytomegalic inclusion disease may occur. ☐CMV is an important cause of congenital defects, neonatal hearing loss, and mental retardation. Herpesviridae ☐EBV replicates in epithelial cells of the oropharynx and parotid gland and establishes latent infections in lymphocytes. ☐It causes infectious mononucleosis and can induce human lymphoproliferative disorders, especially in immunocompromised patients. Herpesviridae ☐HHV-6 infects T lymphocytes. It is typically acquired in early infancy and causes exanthem subitum (roseola infantum) as well as infections in immunocompromised patients. ☐HHV-7, also a T-lymphotropic virus, has not yet been definitively linked to any specific disease. ☐HHV-8 is associated with the development of Kaposi sarcoma, a vascular tumor that is common in patients with AIDS Poxviridae ☐large brick-shaped or ovoid viruses ☐The particle structure is complex, with a lipid- containing envelope ☐from Anglo-Saxon pokkes meaning pouch, referring to their characteristic vesicular skin lesions. ☐Replication occurs entirely within the cell cytoplasm. Some are pathogenic for humans (smallpox, vaccinia, molluscum contagiosum); ☐others that are pathogenic for animals can infect humans (cowpox, monkeypox) Poxviridae ☐Most of the poxviruses that can cause disease in humans are contained in the genera Orthopoxvirus and Parapoxvirus ☐The orthopoxviruses have a broad host range affecting several vertebrates. ☐They include ectromelia (mousepox), camelpox, cowpox, monkeypox, vaccinia, and variola (smallpox) viruses. (can infect humans) ☐Vaccinia virus, the agent used for smallpox vaccination, is a distinct species of Orthopoxvirus ☐ The genome of vaccinia virus are distinctly different from those of cowpox virus, which was believed to be its ancestor ☐ At some time after Jenner’s original use of “cowpox” virus, the vaccine virus became known as “vaccinia virus.” ☐ Vaccinia virus may be the product of genetic recombination, a new species derived from cowpox virus or variola virus by serial passage, or the descendant of a now extinct viral genus Poxviridae ☐Variola has a narrow host range (only humans and monkeys) ☐Methisazone is a chemotherapeutic agent historically evaluated against poxviruses. It is effective as prophylaxis but is not useful in treatment of established disease. ☐Cidofovir, a nucleotide analog, shows activity against poxviruses in vitro and in vivo. ☐ It has been used to treat molluscum contagiosum and orf virus infections. Medically RNA VIRUS Important Viral infections Picornaviridae ☐Picornaviruses are small (28–30 nm), ether-resistant viruses exhibiting cubic symmetry ☐The groups infecting humans are enteroviruses (polioviruses, coxsackieviruses, echoviruses, parechoviruses, and rhinoviruses [more than 100 serotypes causing common colds]) and hepatovirus (hepatitis A) ☐Rhinoviruses are acid labile and have a high density; other enteroviruses are generally acid stable and have a lower density. ☐Picornaviruses infecting animals include foot-and- mouth disease of cattle and encephalomyocarditis of rodents Picornaviridae Poliovirus (Wild poliovirus type 1-3) ☐ Mouth is the portal of entry ☐ Multiplies in the intestine and oropharynx (tonsils, lymph nodes of the neck, payer's patches, small intestine) ☐ The CNS may then be invaded by way of the circulating blood ☐ Spread to the axon of the peripheral nerves to the CNS ☐ where it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain. ☐ Poliovirus invades certain types of nerve cells, and in the process of its intracellular multiplication, it may damage or completely destroy these cells ☐ The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells. Some cells that lose their function may recover completely. Inflammation occurs secondary to the attack on the nerve cells. Picornaviridae A. Mild disease ☐ Most common form of disease ☐Minor illness, Recovery within days ☐S/S: Headache, nausea, vomiting, constipation, sore throat B. Non- paralytic Poliomyelitis ( aseptic meningitis) ☐Symptoms of mild disease plus stiffness and pain in the back and neck. ( 2-10 days) ☐Rapid recovery Picornaviridae C. Paralytic poliomyelitis: ☐ flaccid paralysis resulting from lower motor neuron damage ☐ The virus spreads from person to person and can infect a person's spinal cord, causing paralysis ☐ incoordination secondary to brain stem invasion and painful spasms of nonparalyzed muscles may also occur ☐ Maximal recovery usually occurs within 6 months, with residual paralysis lasting much longer. D. Progressive Postpoliomyelitis Muscle Atrophy ☐ recurrence of paralysis and muscle wasting has been observed in individuals decades after their experience with paralytic poliomyelitis ☐ result of physiologic and aging changes in paralytic patients already burdened by loss of neuromuscular functions  Picornaviridae ☐The oral polio vaccine is being used in the global eradication program ☐There are no antiviral drugs for treatment of poliovirus infection, and treatment is symptomatic Picornaviridae COXSACKIEVIRUSES ☐Divided into groups A and B ☐ Group A: ☐Herpangina (vesicular pharyngitis), ☐hand-foot-and-mouth disease ☐ acute hemorrhagic conjunctivitis ☐Group B: ☐Pleurodynia (epidemic myalgia), ☐ myocarditis, ☐pericarditis, ☐severe generalized disease of infants Picornaviridae The incubation period of coxsackievirus infection ranges from 2 to 9 days Aseptic meningitis: ☐ Fever, malaise, headache, nausea, and abdominal pain are common early symptoms. The disease sometimes progresses to mild muscle weakness suggestive of paralytic poliomyelitis. Patients almost always recover completely from nonpoliovirus paresis. Herpangina ☐is a severe febrile pharyngitis that is caused by certain group A viruses Hand-foot-and-mouth disease ☐oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs Pleurodynia ☐(also known as epidemic myalgia) and stabbing chest pain are usually abrupt in onset but are sometimes preceded by malaise, headache, and anorexia. ☐The illness is self-limited and recovery is complete, although relapses are common Myocarditis ☐ a serious disease. It is an acute inflammation of the heart or its covering membranes (pericarditis) Generalized disease of infants ☐ an extremely serious disease in which the infant is overwhelmed by simultaneous viral infections of multiple organs, including the heart, liver, and brain ☐May be acquired transplacentally FOOT-AND-MOUTH DISEASE (APHTHOVIRUS OF CATTLE) ☐This highly infectious disease of cloven-hoofed animals such as cattle, sheep, pigs, and goats is rare in the United States but endemic in other countries. ☐It may be transmitted to humans by contact or ingestion. In humans, the disease is characterized by fever, salivation, and vesiculation of the mucous membranes of the oropharynx and of the skin of the feet. Astroviridae ☐ Astroviruses are similar in size to picornaviruses (28–30 nm), but particles display a distinctive star-shaped outline on their surfaces ☐These agents are associated with gastroenteritis in humans and neurological disease in some animals ☐The family Astroviridae contains two genera; all human viruses are classified in the Mamastrovirus genus ☐Astroviruses cause diarrheal illness and may be shed in extraordinarily large quantities in feces. The viruses are transmitted by the fecal–oral route through contaminated food or water, person-to-person contact, or contaminated surfaces. Caliciviridae Caliciviruses are similar to picornaviruses but slightly larger (27–40 nm). The particles appear to have cup-shaped depressions on their surfaces Important human pathogens are the ☐ noroviruses (eg, Norwalk virus), ☐ the cause of epidemic acute gastroenteritis, ☐Sapovirus, which includes the Sapporo-like viruses; ☐Initially discovered in an outbreak of gastroenteritis in an orphanage in Sapporo, Japan, in 1977 Arboviruses and Rodent-Borne Viruses ☐Arthropod-borne viruses (arboviruses) and rodentborne viruses represent ecologic groupings of viruses with complex transmission cycles involving arthropods or rodents. Classified under: ☐Arenaviridae, ☐Bunyaviridae, ☐Flaviviridae, ☐Reoviridae, ☐Togaviridae Arenaviridae Arenavirus ☐pleomorphic, enveloped viruses ranging in size from 60 to 300 nm (mean, 110–130 nm). The genome is segmented ☐Most members of this family are unique to tropical America ☐Rodentborne ☐Lassa fever virus ☐Transmitted by “multimammate rat” (Mastomys natalensis) ☐Non specific symptoms ☐Most common complication is deafness ☐Ribavirin, an antiviral drug, has been used with success in Lassa fever patients Bunyaviridae Bunyaviruses are spherical or pleomorphic, 80- to 120-nm enveloped particles. The majority of these viruses are transmitted to vertebrates by arthropods ☐Hantavirus: ☐“New World” hantaviruses are found in america, and may cause hantavirus pulmonary syndrome (HPS). ☐ “Old World” hantaviruses, are found mostly in Europe and Asia and may cause hemorrhagic fever with renal syndrome (HFRS). Filoviridae ☐ Enveloped, pleomorphic viruses that may appear very long and threadlike ☐Marburg and Ebola viruses cause severe hemorrhagic fever in Africa. These viruses require maximum containment conditions ☐The incubation period is 3–9 days for Marburg disease and 2–21 days for Ebola ☐They cause similar acute diseases characterized by fever, headache, sore throat, andmuscle pain followed by abdominal pain, vomiting, diarrhea, and rash, with both internal and external bleeding, often leading to shock and death. Filoviridae ☐Ebola virus was discovered in 1976 when two severe epidemics of hemorrhagic fever occurred in Sudan and Zaire (now the Democratic Republic of the Congo). ☐The outbreaks involved more than 500 cases and at least 400 deaths caused by clinical hemorrhagic fever. ☐ In each outbreak, hospital staff became infected through close and prolonged contact with patients, their blood, or their excreta. ☐These subtypes of Ebola virus (Zaire, Sudan) are highly virulent. The mean time to death from the onset of symptoms is 7–8 days. Filoviridae ☐The U.S. Food and Drug Administration (FDA) has approved the Ebola vaccine, ERVEBO®, for the prevention of EVD. ☐ ERVEBO vaccine has been found to be safe and protective against only the Zaire ebolavirus species of ebolavirus. Flaviviridae Flaviviruses are enveloped viruses ☐Mature virions accumulate within cisternae of the endoplasmic reticulum ☐Most members are transmitted by blood-sucking arthropods. Japanese B encephalitis, Zika, Dengue, West nile, yellow fever ☐Hepatitis C virus is a flavivirus with no known vector Flaviviridae ☐Yellow fever virus is the prototype member of the Flaviviridae family. It causes yellow fever, an acute, febrile, mosquitoborne illness that occurs in the tropics and subtropics of Africa and South America ☐The incubation period is 3–6 days. At the abrupt onset, the patient has fever, chills, headache, dizziness, myalgia, and backache followed by nausea, vomiting, and bradycardia. ☐The disease progresses to a more severe form, with fever, jaundice, renal failure, and hemorrhagic manifestations. The vomitus may be black with altered blood ☐When the disease progresses to the severe stage (hepatorenal failure), the mortality rate is high (20% or higher), especially among young children and elderly adults. ☐Death occurs on day 7–10 of illness. ☐Vaccination is the best preventive measure (YF-VAX) Flaviviridae ☐Dengue virus ( breakbone fever) ☐ mosquito-borne infection caused by a flavivirus that is characterized by fever, severe headache, muscle and joint pain, nausea and vomiting, eye pain, and rash. Severe forms of the disease, dengue hemorrhagic fever and dengue shock syndrome, principally affect children. ☐ A severe syndrome—dengue hemorrhagic fever or dengue shock syndrome—may occur in individuals (usually children) with passively acquired (as maternal antibody) or preexisting nonneutralizing heterologous dengue antibody caused by a previous infection with a different serotype of virus. ☐ Four serotypes (DENV 1-4), Aedes aegypti and Aedes albopictus are the vectors ☐ Vaccine development is difficult because a vaccine must provide protection against all four serotypes of virus ☐ Dengvaxia contains attenuated (weakened) yellow fever viruses that have been modified so that they contain proteins from dengue virus Flaviviridae Hepatitis C (hepacivirus) ☐Most new infections with HCV are subclinical. The majority (70–90%) of HCV patients develops chronic hepatitis, and many are at risk of progressing to chronic active hepatitis and cirrhosis (10–20%). In 1–5% of infected individuals, ☐HCV leads to hepatocellular carcinoma, which is the fifth most common cause of cancer worldwide. ☐Commonly transmitted parenteral through blood transfusion, and sharing of used needles ☐Present in blood, saliva and semen, no known vector ☐No vaccine, Pegylated interferon combined with ribavirin has been the standard treatment for chronic hepatitis C. Caliciviridae Noroviruses are the most common cause of nonbacterial gastroenteritis in the United States, causing an estimated 21 million cases annually. ☐Known as the stomach flu or stomach bug ☐ This is associated with epidemic outbreaks of waterborne, foodborne, and shellfish-associated gastroenteritis low infectious dose (as few as 10 virus particles), relative stability in the environment, and multiple modes of transmission. It sur vives 10 ppm chlorine and heating to 60°C; it can maintain viability in steamed oysters. ☐Treatment is symptomatic, no vaccine available Reoviridae ☐Reoviruses are medium-sized (60–80 nm), ether- resistant, nonenveloped viruses having icosahedral symmetry. ☐Reoviruses of humans include rotaviruses, which have a distinctive wheel-shaped appearance and cause Gastroenteritis ☐Rotaviruses are a major cause of diarrheal illness in human infants and young animals, including calves and piglets. Infections in adult humans and animals are also common. Antigenically similar reoviruses infect many animals. Reoviridae Coltiviruses form another species within the Reoviridae ☐Colorado tick fever virus, transmitted by ticks, is able to infect humans can cause fever, rash, and systemic symptoms in infected patients ☐spread by the bite of an infected Rocky Mountain wood tick, Dermacentor andersoni Reoviridae Orbiviruses are a genus within the reovirus family. ☐They commonly infect insects, and many are transmitted by insects to vertebrates ☐Serious animal pathogens include bluetongue virus of sheep and African horse sickness virus ☐in cattle, constant changing of position of the feet gives bluetongue the nickname the dancing disease Togaviridae They have a lipid-containing envelope and are ether sensitive, and their genome is single-stranded, positive-sense RNA, An example is eastern equine encephalitis Virus, Chikungunya and Rubella virus (has no arthropod vector) ☐Chikungunya ☐Transmitted via mosquito (same as dengue vector) ☐Infection resembles dengue ☐Characterized by high fever and severe joint pain ☐Treatment: non-aspirin NSAIDS, paracetamol and fluids ☐in those who have more than two weeks of arthritis, Ribavirin may be useful ☐No vaccine available Rubella ☐Sole member of the genus rubivirus from togaviridae ☐Known as the German measles and 3-day measles ☐Characterized by rash and lymphadenopathy ☐transmitted by respiratory secretions rather than arthropods. ☐It is the mildest of the common viral exanthems ☐infection during early pregnancy may result in serious abnormalities of the fetus, including congenital malformations and mental retardation. ☐The consequences of rubella in utero are referred to as the congenital rubella syndrome ☐With vaccine (MMR, MMRV), no specific treatment, self limiting Hepeviridae Hepeviruses are similar to caliciviruses. ☐The particles are small (32–34 nm) and ether resistant. The genome is single-stranded, positive-sense RNA, 7.2 kb in size. ☐ It lacks a genome-linked protein (VPg). ☐Human hepatitis E virus belongs to this group Hepeviridae ☐HEV is transmitted enterically and occurs in epidemic form in developing countries, where water or food supplies are sometimes fecally contaminated ☐It was first documented in samples collected during the New Delhi outbreak of 1955, when 29,000 cases of icteric hepatitis occurred after sewage contamination of the city’s drinking water supply. ☐Pregnant women may have a high (20%) mortality rate if fulminant hepatitis or acute liver failure develops. ☐No chronic disease, non carcinogenic, non enveloped Orthomyxoviridae Influenza Viruses Three immunologic types of influenza viruses are known, designated A, B, and C. ☐Influenza A ☐HA: hemagglutinin ☐binds virus particles to susceptible cells and is the major antigen against which neutralizing (protective) antibodies are directed ☐NA:Neuraminidase ☐functions at the end of the viral replication cycle. It is a sialidase enzyme that removes sialic acid from glycoconjugates ☐Minor antigenic changes in HA and NA, termed ANTIGENIC DRIFT, occur independently and are caused by accumulation of point mutations. ☐Major antigenic change in HA or NA, called ANTIGENIC SHIFT, results in a new influenza virus subtype and is caused by genetic reassortment of genome segments between human and animal viruses. Significant influenzavirus A in history: ☐H1N1, which caused Spanish Flu in 1918, and Swine Flu in 2009 ☐H2N2, which caused Asian Flu in 1957 ☐H3N2, which caused Hong Kong Flu in 1968 ☐H5N1, which caused Bird Flu in 2004 Treatment ☐Vaccines are available for common flu ( given yearly) ☐Treatment: Oseltamivir and Zanamivir ☐Neuraminidase inhibitors Coronaviridae Coronaviruses are enveloped 120- to 160- nm particles containing an unsegmented genome of positive-sense, singlestranded RNA resemble orthomyxoviruses but have petal-shaped surface projections arranged in a fringe, similar to a solar corona ☐Classically, human coronaviruses cause mild acute upper respiratory tract illnesses—“colds”—but more recently discovered coronaviruses cause severe acute respiratory syndrome (SARS, SARS-Cov2) and Middle East respiratory syndrome (MERS). Coronaviruses tend to be highly species specific. Most of the known animal coronaviruses display a tropism for epithelial cells of the respiratory or gastrointestinal tract ☐Viral tropism is the ability of different viruses to infect different cellular types ultimately to produce a successful infection ☐SARS- CoV: 2002, Guandong province, China ☐ Bats ☐MERS-CoV: 2012, Middle east ☐Camel ☐SARS-CoV2: covid19: 2019, Wuhan, China ☐Under investigation ☐Virions bind to specific receptor glycoproteins or glycans via the spike protein. SARS-CoV2 ( COVID-19) ☐ transmitted via short- range aerosol, direct contact with eyes, nose and mouth (droplet transmission) ☐infected people appear to be most infectious just before they develop symptoms (namely 2 days before they develop symptoms) and early in their illness. ☐Symptoms may appear 2-14 days after exposure to the virus Signs and Symptoms ☐Fever or chills ☐Cough ☐Shortness of breath or difficulty breathing ☐Fatigue ☐Muscle or body aches ☐Headache ☐New loss of taste or smell ☐Sore throat ☐Congestion or runny nose ☐Nausea or vomiting ☐Diarrhea Paramyxoviridae ☐linear, singlestranded, ☐nonsegmented, negative-sense RNA ☐Particles are pleomorphic ☐Viruses: ☐mumps, measles, parainfluenza, metapneumovirus, and respiratory syncytial viruses. Paramyxoviridae Mumps ☐an acute contagious disease characterized by nonsuppurative enlargement of one or both salivary glands. ☐Involvement of the parotid gland is not an obligatory step in the infectious process. ☐May cause Orchitis in men (20-50%) and oophoritis in women (5%) ☐Because of the lack of elasticity of the tunica albuginea, which does not allow the inflamed testis to swell, the complication is extremely painful ☐May cause sterility due to atrophy of the testes as a result of pressure necrosis ☐ The virus is transmitted by direct contact, airborne droplets, or fomites contaminated with saliva or urine ☐With Vaccine (MMRV, MMR) no specific treatment Paramyxoviridae MEASLES (RUBEOLA) ☐acute, highly infectious disease characterized by fever, respiratory symptoms, and a maculopapular rash ☐Humans are the only natural hosts for measles virus, ☐Respiratory tract-> multiply locally-> spread to regional lymmph nodes-> Primary viremia-> replication in the reticuloendothelial system-> secondary viremia-> seeds the epithelial surfaces of the body, including the skin, respiratory tract, and conjunctiva, where focal replication occurs ☐The described events occur during the incubation period, which typically lasts 8–15 days but may last up to 3 weeks in adults. Paramyxoviridae ☐Involvement of the central nervous system is common in measles ☐Symptomatic encephalitis develops in about one in 1000 casesA rare late complication of measles is subacute sclerosing panencephalitis (SSPE) ☐Transmission occurs predominantly via the respiratory route (by inhalation of large droplets of infected secretions). ☐Fomites do not appear to play a significant role in transmission. ☐Hematogenous transplacental transmission can occur when measles occurs during pregnancy. ☐Vitamin A treatment in developing countries has decreased mortality and morbidity. MMRV, MMR Paramyxoviridae ☐Parainfluenza virus replication in the immunocompetent host appears to be limited to respiratory epithelia ☐major cause of lower respiratory tract disease in young children infections with types 1 and 2 occur at a lower rate, reaching prevalences of about 75% and 60%, by 5 years of age. ☐Type 3 is endemic, with some increase during the spring; types 1 and 2 tend to cause epidemics during the fall or winter, frequently on a 2-year cycle. ☐transmitted by direct person- to- person contact or by large-droplet aerosols ☐ No vaccine  Rhabdoviridae ☐ Rabies is an acute infection of the central nervous system that is almost always fatal ☐ belong to the genus Lyssavirus ☐ Bullet-shaped ☐ Rabies virus produces a specific eosinophilic cytoplasmic inclusion, the Negri body, in infected nerve cells. ☐ There are no tests to diagnose rabies infections in humans before the onset of clinical symptoms ☐ The virus is widely distributed in infected animals, especially in the nervous system, saliva, urine, lymph, milk, and blood, but ☐ rabies virus has not been isolated from the blood of infected persons Rhabdoviridae ☐Multiply in the site of inoculation ( muscle, connective tissue)-> Enters peripheral nerves and neuromuscular junction-> spreads to the nervous system-> It multiplies in the central nervous system and progressive encephalitis develops ☐The virus then spreads through peripheral nerves to the salivary glands and other tissues-> The organ with the highest titers of virus is the submaxillary salivary glands ☐Other organs where rabies virus has been found include pancreas, kidney, heart, retina, and cornea. ☐Rabies virus has not been isolated from the blood of infected persons. Rhabdoviridae 1. Prodromal phase: ☐ Fever, malaise, Anorexia, irritability, melancholia ☐Hyperesthesia ☐Sensitivity to light and loud noise ☐Excessive salivation ☐Abnormal sensation in the inoculating site including pruritus and tingling Rhabdoviridae 2. Excitation phase - the excitation phase begins gradually and may persist to death ☐ Strabismus: failure of the eyes to follow one another in any movement ☐ Nystagmus ☐ Tachy/ bradycardia ☐ Hydrophobia and Aerophobia 3. Paralytic phase ☐ hydrophobia disappears, painful swallowing ☐ Urinary incontinence ☐ Flaccid paralysis ☐ Peripheral vascular colapse Rhabdoviridae ☐ No treatment for for clinical rabies Immunity: All vaccines for human use contain only inactivated rabies virus. ☐ Human diploid cell vaccine (HDCV) ☐ rabies virus is grown in the MRC-5 human diploid cell line. ☐ Purified chick embryo cell vaccine (PCEC) ☐ prepared from the fixed rabies virus strain Flury LEP grown in chicken fibroblasts. Immunoglobulin: ☐ Rabies immune globulin, human (HRIG) ☐ γ-globulin prepared by cold ethanol fractionation from the plasma of hyperimmunized humans. ☐ Equine Anti-rabies serum ☐ Concentrated serum from horses hyperimmunized with rabies virus Retroviridae ☐Spherical, enveloped viruses (80–110 nm in diameter) whose genome contains two copies of linear, positive- sense, single-stranded RNA ☐Replication is unique; the virion contains a reverse transcriptase enzyme that produces a DNA copy of the RNA genome. ☐This DNA becomes circularized and integrated into host chromosomal DNA. ☐The virus is then replicated from the integrated “provirus” DNA copy. ☐Hosts remain chronically infected. ☐Significant disease: HIV-> AIDS There are two distinct types of human AIDS viruses: HIV-1 and HIV-2. HUMAN IMMUNODEFICIENCY VIRUS Blood borne disease that is typically transmitted via ☐Sexual route ☐Mother to child transmission* ☐Shared intravenous paraphernalia Immune deficiency is due to the depletion of helper T lymphocytes (CD4+). Loss of CD4+ cells results in the development of opportunistic infection and neoplastic processes. ` Diagnosis ☐ELISA test ( preliminary test) ☐Western Blot assay ( confirmatory test) Prophylaxis for opportunistic infection Gancioclovir ☐Cytomegalovirus ☐Reserved for patients with CD4 below 50/uL Fluconazole ☐CD4 below 100/uL ☐Histoplasmosis, coccidiodomycosis, candida Azithromycin/ clarithromycin ☐CD4 below 50/uL ☐Mycobacterium avium Cotri moxazole ☐PCP ( Pneumocystis jiroveci) ☐Toxoplasmosis and if CD4 count is below 100/uL ☐DAPSONE for patients with G6PD HAART guidelines ☐Therapy should involve combinations of drugs ☐Two nucleoside-analogue reverse transcriptase inhibitors combined with either protease inhibitor or a non nucleoside- analogue- reverse transcriptase inhibitor ☐ART should be given to patients with CD4 below 350/uL ☐ART should be given to pregnant , patients with HIV associated nephropathy, Hep B, regardless of the CD4 count ☐Philippines: ☐LTE: Lamivudine, Tenofovir disoproxil fumarate, Efavirenz ☐Preexposure prophylaxis: Truvada: Emtricitabine and tenofovir ☐GOAL: UNDETECTED VIRAL LOAD= UNTRANSMISSIBLE MICROBIAL DISEASE OF THE SKIN AND EYES Our Lady of Fatima University – College of Pharmacy  Unit Outcomes 1. Describe the structure of the skin and mucous membranes and the ways pathogens can invade the skin. 2. Differentiate staphylococci from streptococci, and name several skin infections caused by each. 3. List the causative agent, mode of transmission, and clinical symptoms of Pseudomonas dermatitis, otitis externa, acne, and Buruli ulcer. 4. Provide examples of normal skin microbiota, and state the general locations and ecological roles of its members.  Unit Outcomes 5. List causative agents, modes of transmission, and symptoms of warts, smallpox, monkeypox, chickenpox, shingles, cold sores, measles, rubella, fifth disease, hand- foot-and-mouth disease, and roseola. 6. Differentiate cutaneous from subcutaneous mycoses, and provide an example of each. 7. List the causative agent and predisposing factors for candidiasis. 8. List the causative agent, mode of transmission, clinical symptoms, and treatment for scabies and pediculosis.  Unit Outcomes 9. Define conjunctivitis. 10. List the causative agent, mode of transmission, and clinical symptoms of these eye infections: ophthalmia neonatorum, inclusion conjunctivitis, trachoma. 11. List the causative agent, mode of transmission, and clinical symptoms of these eye infections: herpetic keratitis, Acanthamoeba keratitis.  Unit Outline 1. Structure and Function of the Skin 2. Normal Microbiota of the Skin 3. Microbial Disease of the Skin a. Bacterial Diseases of the Skin b. Viral Diseases of the Skin c. Fungal Diseases of the Skin and Nails d. Parasitic Infestation of the Skin 4. Structure of the Eyes 5. Microbial Disease of the Eyes  Checklist ☐ Read course outcomes and unit objectives ☐ Read required readings prior to class attendance ☐ Proactively participate in discussions ☐ Watch videos related to the topic ☐ Participate in discussion board (Canvas) ☐ Answer and submit course unit tasks  Required Readings Before attending our class, please read Chapter 21: Skin and Eye infections on the open-sourced Microbiology book using the following link: https://openstax.org/books/microbiology/page s/21-introduction Microbial Disease of the Skin  Structure and Function of the Skin The skin is a physical barrier against microorganisms. Moist areas of the skin support larger populations of bacteria than dry areas. Structure and Function of the Skin 1. Epidermis 2. Dermis Components: Keratin Sebum Perspiration  Structure and Function of the Skin Epidermis The outer portion of the skin Composed of several layer of epithelial cells The outermost layer, the stratum corneum, consists of many rows of dead cells that contains a waterproofing protein called keratin Effective physical barrier against mo  Structure and Function of the Skin Dermis The inner, relatively thick portion of skin Composed mainly of connective tissue The hair follicles, sweat gland ducts, and oil gland ducts in the dermis provide passage- ways through which microorganisms can enter the skin and penetrate deeper tissues.  Structure and Function of the Skin Perspiration Provides moisture and some nutrients for microbial growth Also contains salt which inhibits many micro- organisms Contains the enzyme lysozyme, which is capable of breaking down the cell walls of certain bacteria; and antimicrobial peptides.  Structure and Function of the Skin Sebum Secreted by oil glands A mixture of lipids (unsaturated fatty acids), proteins, and salts Prevents skin and hair from drying out  Structure and Function of the Skin Mucous membrane a.k.a. mucosa Lines the body cavities that open to the exterior, i.e. gastrointestinal, respiratory, urinary, and genital tracts Consists of sheets of tightly packed epithelial cells attached at their bases to a layer of extracellular material called basement membrane  Structure and Function of the Skin Many secretes mucus Other mucosal cells have cilia, i.e. respiratory system Often acidic Membranes of the eyes are mechanically washed by tears, and the lysozymes in tears destroys the cell walls of certain bacteria  Normal Microbiota of the Skin Microorganisms that live on skin are resistant to desiccation and high concentrations of salt. Gram-positive cocci predominate on the skin. Washing does not completely remove the normal skin microbiota.  Normal Microbiota of the Skin Members of the genus Cutibacterium metabolize oil from the oil glands and colonize hair follicles. Malassezia furfur yeast grows on oily secretions and may be the cause of dandruff.  Normal Microbiota of the Skin The majority (90%) of skin microbiota consist of coagulase-negative Staphylococcus epidermidis.  Microbial Diseases of the Skin Different Terms for Rashes and Lesions Vesicles are small fluid-filled lesions Bullae are vesicles larger than 1 cm Macules are flat, reddened lesions Papules are raised lesions Pustules are raised lesions containing pus  Papules Bullae Vesicle Pustules Macules  Bacterial Diseases of the Skin  Staphylococcus Staphylococci are spherical gram-positive bacteria that form irregular grape-like clusters Divided into those that produce coagulase, and those that do not Coagulase-positive S. aureus Coagulase-negative S. epidermidis  Staphylococcus Staphylococcus epidermidis Coagulase-negative Very common on the skin Generally pathogenic only when the skin barrier is broken or is invaded by medical procedures, e.g. insertion and removal of catheters into veins  Staphylococcus Staphylococcus aureus Resident microbiota of the nasal passage Forms golden-yellow colonies Almost all pathogenic strains of S. aureus produce coagulase Some strains have impressive array of virulence factors and means of evading host defenses  S. aureus infects the skin Blocks Resistant to chemotaxis of opsonization neutrophils It stimulates vigorous Produce toxins Survive well inflammatory response that kills within the phagocytic cells phagosome Macrophages and Neutralize the Cell wall is neutrophils are attracted to peptide defensin lysozyme the site of infection on skin resistant However, S. aureus evade host defense  Staphylococcus Localized infections (sties, pimples, and boils) result from entry of S. aureus through openings in the skin.  Staphylococcus Carbuncle is a furuncle which extensively damages neighboring tissues Produce a hard, round deep inflammation of tissue under the skin Patient can exhibit general illness with fever  Staphylococcus Impetigo is highly contagious skin infection caused by Staphylococci. Characterized by isolated yellow pustules that become crusted.  Staphylococcus Toxemia occurs when toxins enter the bloodstream; staphylococcal toxemias include scalded skin syndrome and toxic shock syndrome.  Staphylococcus S. aureus produces exfoliative toxins: Exfoliatin A – causes localized, bullous impetigo Exfoliatin B – causes the systemic infection of scalded skin syndrome  Staphylococcus Scalded skin syndrome is also characteristic of the late stages of toxic shock syndrome (TSS). Potential life-threatening condition, fever, vomiting, and a sunburn-like rash Followed by shock and sometimes organ failure (especially kidney failure) Caused by a staphylococcal toxin called TSST-1  Streptococcus Streptococci are gram-positive spherical bacteria usually grows in chains. Prior to division, the individual cocci elongate on the axis of the chain, and then the cells divide. Cause a wide range of disease conditions including meningitis, pneumonia, sore throat, otitis media, endocarditis, puerperal fever, and even dental caries.  Streptococcus Streptococci are classified according to their hemolytic enzymes (hemolysin) and cell wall antigens. Hemolytic activity Alpha, beta, gamma Cell wall antigen Group A to T  Streptococcus Streptococcus pyogenes Group A beta-hemolytic streptococci (GAS) produce a number of virulence factors: M protein, deoxyribonuclease, streptokinases, and hyaluronidase. Cause severe and rapid tissue destruction.  Streptococcus Erysipelas Skin erupts into reddish patches with raised margins Can progress to local tissue destruction and even enter the bloodstream causing sepsis Usually appears first on the face High fever is common  Streptococcus Necrotizing fasciitis Invasive group A streptococcal infection that destroys tissue and initially resembles TSS “Flesh-eating bacteria” Causes by pyrogenic toxins, streptococcal M- protein types (act as superantigens) Associated with streptococcal TSS  Pseudomonas Pseudomonas aeruginosa Aerobic gram-negative rod Resistant to many antibiotic and disinfectant Can survive in any moist environment, traces of unusual organic matter such as soap films, cap liner adhesives  Pseudomonas Diseases caused by P. aeruginosa include otitis externa, respiratory infections, burn infections, and dermatitis Produces an endotoxin and several exotoxins  Other Bacteria Mycobacterium ulcerans Causes deep-tissue ulceration or Buruli ulcer  Other Bacteria Cutibacterium acnes Formerly known as Propionibacterium acnes Its metabolic products (fatty acids) cause inflammatory acne Comedonal (mild) acne Inflammatory (moderate) acne Nodular cystic (severe) acne  Viral Diseases of the Skin  Warts Papillomaviruses cause skin cells to proliferate and produce a benign growth called a wart or papilloma. Warts are transmitted from one person to another by direct contact, even sexually. After infection, there is an incubation period of several weeks before the warts appear.  Warts Warts may regress spontaneously or be removed chemically or physically. Nonpharmacologic Treatment Cryotherapy Electrodessication Acid treatment Laser  Warts Pharmacologic Treatment Salicylic acid Podofilox Imiquimod Bleomycin  Variola Variola, also known as smallpox, is caused by an orthopoxvirus known as smallpox (variola) virus. Variola virus causes two types of skin infections: variola major and variola minor.  Variola Smallpox is transmitted by the respiratory route, and the virus is moved to the skin via the bloodstream. The growth of the virus in the epidermal layers of the skin causes lesions that becomes pustular after 10 days or so.  Variola Smallpox has been eradicated as a result of a vaccination effort by the World Health Organization.  Varicella-Zoster Chickenpox (varicella) is a relatively mild disease when contracted, as it usually is, in childhood. It is the initial infection of a herpesvirus Varicellovirus. The species is varicella-zoster, or officially, human herpesvirus (HHV-3).  Varicella-Zoster HHV-3 is transmitted by the respiratory route and is localized in skin cells after about 2 weeks. The infected skin is vesicular for 3 to 4 days. Complications of chickenpox include encephalitis and Reye’s syndrome.  Varicella-Zoster Shingles Characterized by a vesicular rash along the affected cutaneous sensory nerves. After chickenpox, the virus can remain latent in nerve cells and subsequently activate as shingles.  Varicella-Zoster Treatment HHV-3 can be treated with acyclovir. An attenuated live vaccine is available.  Herpes Simplex Herpes simplex viruses (HSV) can be separated into two identifiable groups: HSV-1 (or human herpesvirus 1) HSV-2 (or human herpesvirus 2)  Herpes Simplex Cold sores Herpes simplex (HSV-1) infection of mucosal cells Painful, short-lived vesicles that occur near the outer red margin of the lips https://www.verywellhealth.com/stages-of-a-cold-sore-outbreak-4173005  Herpes Simplex HSV-1 is transmitted primarily by skin contact, oral and respiratory routes. The virus remains latent in nerve cells, and cold sores can recur when the virus is activated.  Herpes Simplex Herpes encephalitis occurs when herpes simplex viruses (HSV-1 and HSV-2) infect the brain. Treatment Acyclovir has proven successful in treating herpes encephalitis.  Measles Measles (Rubeola) Caused by measles virus An extremely contagious viral disease transmitted by the respiratory route Vaccination (MMR vaccine) against measles provides effective long-term immunity  Measles After the measles virus has incubated (10-12 days) in the upper respiratory tract, the following signs and symptoms appear. Symptoms (like fever) similar to common cold. Macular lesions appear on the skin. Koplik’s spots appear on the oral mucosa. https://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba /6111_lores.jpg  Measles Complications of measles include middle ear infections, pneumonia, encephalitis, and secondary bacterial infections.  Rubella Rubella (German measles) The rubella virus is transmitted by the respiratory route and causes a red rash and light fever. Congenital rubella syndrome can affect a fetus when a woman contracts rubella during the first trimester of her pregnancy.  Rubella Vaccination with live, attenuated rubella virus provides immunity of unknown duration.  Other Viral Diseases Fifth disease Also known as erythema infectiosum Causes by human parvovirus B19 Characterized by symptoms similar to mild influenza and a slapped-cheek facial rash that slowly fades Roseola Mild, very common childhood disease caused by HHV-6 and HHV-7  Other Viral Diseases Hand-foot-and-mouth disease An infection in young children in day care, preschool, and kindergarten Caused by several enteroviruses Spread by contact with mucous or saliva of an infected person Characterized by sore throat, then rashes appearing on hands, feet, mouth, tongue, and interior cheeks  Fungal Diseases of the Skin and Nails  Fungal Infection Fungal infections or mycoses cause a wide range of diseases in humans. 1. Superficial Infection 2. Cutaneous Infection 3. Subcutaneous Infection 4. Deep mycosis  Superficial Fungal Infection Pityriasis versicolor Common superficial mycosis, which is characterized by hypopigmentation or hyperpigmentation of skin of the neck, shoulders, chest, and back Due to Malassezia furfur which involves only the superficial keratin layer  Superficial Fungal Infection Black Piedra A superficial mycosis due to Piedraia hortae which is manifested by a small firm black nodule involving the hair shaft  Superficial Fungal Infection White Piedra Due to Trichosporon beigelii is characterized by a soft, friable, beige nodule of the distal ends of hair shafts  Superficial Fungal Infection Tinea Nigra Most typically presents as a brown to black silver nitrate-like stain on the palm of the hand or sole of the foot and and is caused by Phaeoannellomyces werneckii  Cutaneous Fungal Infection Dermatophytoses Caused by fungi (Microsporum, Trichophyton, and Epidermophyton) that colonize the outer layer of the epidermis cause dermatomycoses Also known as ringworm, or tinea These fungi grow on keratin-containing epidermis, such as hair, skin, and nails  Name Common Name Location Tinea pedis Athlete’s foot Feet Tinea unguium Onchomycosis Nails Tinea corporis Ringworm Arm, legs, and trunk Tinea cruris Jock itch Groin area Tinea manuum Hands and palm area Tinea capitis Scalp Tinea barbae Barber’s itch Facial hair Tinea faciei Face fungus Face  Athletes’ foot Onychomycosis (Tinea unguium) Ring worm (Tinea corporis) Tinea cruris (jock itch) Tinea capitis Tinea barbae Tinea faciei  Cutaneous Fungal Infection Diagnosis is based on the microscopic examination of skin scrapings or fungal culture.  Cutaneous Fungal Infection Dermatomycoses Cutaneous infections due to other fungi, the most common of which are Candida albicans. C. albicans causes infections of mucous membranes and is a common cause of oral thrush and vaginitis. Subcutaneous Fungal Infection Sporotrichosis Results from a soil fungus (Sporothrix schenckii) that penetrates the skin through a wound Common among gardeners or people working with soil Subcutaneous Fungal Infection Chromoblastomycosis Subcutaneous mycosis characterized by verrucoid lesions of the skin Most common causes are: Fonsecaea pedrosoi (Pedroso’s disease) Fonsecaea compacta (Fonseca’s disease) Cladosporium carionii (Cladosporiosis) Phialophora verrucosa Subcutaneous Fungal Infection Madura foot (mycetoma) Chronic infection of the skin and underlying tissues by both bacteria (actinomycetoma) and fungi (eumycetoma). Suppurative and granulomatous subcutaneous mycosis Occur most often in farmers, hunter-gatherers, and field laborer  Parasitic Infestation of the Skin  Scabies Scabies Involves intense local itching Caused by a tiny mite Sarcoptes scabiei burrowing and laying eggs in the skin The mite is transmitted by intimate contact https://www.nhs.uk/conditions/scabies/  Scabies Mite lives ~25 days, but by that time eggs have been laid and hatched Diagnosis Microscopic examination of skin scrapings Treatment Topical permethrin Oral ivermectin  Pediculosis Pediculosis Infestation by the head lice Pediculus humanus capitis Lice are easily transferred by head- to-head contact https://www.skin-disorders.net/diseases/pediculosis-capitis.html © Gilles San Martin (2010) Microbial Disease of the Eyes  Structure of the Eyes Conjunctiva The mucous membrane, made of epithelial cells, lining the eyelid and covering the eyeball A transparent layer of living cells replacing the skin Image from https://www.humpath.com/spip.php?article20751  Structure of the Eyes Conjunctivitis Inflammation of the eye membranes (conjunctiva) Conjunctivitis is caused by several bacteria and can be transmitted by improperly disinfected contact lenses  Structure of the Eyes Cornea The transparent convex portion of the anterior eye. https://my.clevelandclinic.org/health/treatments/17714-cornea-transplant/when-to- call-the-doctor  Structure of the Eyes Keratitis Inflammation of the cornea https://www.nvisioncenters.com/conditions/keratitis/  Bacterial Infection Bacterial microbiota of the eye usually originate from the skin and upper respiratory tract.  Bacterial Infection Ophthalmia neonatorum Caused by the transmission of Neisseria gonorrheae from an infected mother to an infant during its passage through the birth canal.  Bacterial Infection Causes suppurative conjunctivitis that results to corneal ulceration (may also lead to blindness) if not treated. Treatment Silver nitrate solution (1%) Erythromycin Dilute povidone-iodine solution  Bacterial Infection Inclusion conjunctivitis An infection caused by Chlamydia trachomatis to the conjunctiva Transmitted to infants during birth and is transmitted in unchlorinated swimming water  Bacterial Infection Resolve spontaneously in a few weeks or months, but in rare cases it can lead to scarring of the cornea Treatment Tetracycline ophthalmic ointment  Bacterial Infection Trachoma A serious eye infection, one of the major cause of preventable blindness Caused by a certain serotype of C. trachomatis Conjunctivitis transmitted by hands, fomites, and perhaps flies  Bacterial Infection Repeated infections cause inflammation leading to trichiasis. Can be corrected surgically. Secondary infections by other bacterial pathogens are also a factor in the disease.  Bacterial Infection Treatment Oral azithromycin Improve sanitary practices and health education  Fungal Infection Fusarium, Candida, and Aspergillus fungi can infect the eye especially in Africa and Asia.  Viral Infection Herpetic keratitis Caused by the same herpes simplex type 1 virus (HSV-1) that causes cold sore and trigeminal neuralgia An infection of the cornea, causes deep ulcers One of the cause of infectious blindness  Parasitic Infection Acanthamoeba keratitis Painful corneal infection caused by Acanthamoeba protozoa Can cause a serious form of keratitis as to require a corneal transplant or even removal of the eye  Parasitic Infection Can be transmitted via water Contributing factors include inadequate disinfecting procedures of contact lenses Using homemade saline solutions Wearing contact lenses overnight Wearing contact lenses while swimming  Parasitic Infection Diagnosis is confirmed by the presence of trophozoites and cysts in stained scrapings if the cornea Treatment Chlorhexidine 2% solution Propamidine isethionate eye drops Topical neomycin  Summary 1. Structure and Function of the Skin 2. Normal Microbiota of the Skin 3. Microbial Disease of the Skin a. Bacterial Diseases of the Skin b. Viral Diseases of the Skin c. Fungal Diseases of the Skin and Nails d. Parasitic Infestation of the Skin 4. Structure of the Eyes 5. Microbial Disease of the Eyes  END OF DISCUSSION  References Tortora, G.J., Funke, B.R., & Case, C.L. (2019). Microbiology: an introduction 13th edition. Boston, MA: Pearson. Jindal, A., Patel, L. M., Singh, A., & Dutta, R. (2018). Clinical Picture: Madura Foot. Indian Journal of Surgery, 80(6), 627–628. https://doi.org/10.1007/s12262-018-1789-1 Parker, N., Schneegurt, M., Tu, A. -H. T., Lister, P., & Forster, B.M. (2016). Microbiology. Houston, Texas: OpenStax. https://openstax.org/books/ microbiology/pages/21-introduction MICROBIAL DISEASE OF THE RESPIRATORY SYSTEM Our Lady of Fatima University – College of Pharmacy  Unit Outcomes 1. Describe how microorganisms are prevented from entering the respiratory system. 2. Characterize the normal microbiota of the upper and lower respiratory systems. 3. Differentiate pharyngitis, laryngitis, tonsillitis, sinusitis, and epiglottitis. 4. List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for streptococcal pharyngitis, scarlet fever, diphtheria, cutaneous diphtheria, and otitis media.  Unit Outcomes 5. List the causative agents and treatments for the common cold. 6. List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for pertussis and tuberculosis. 7. Compare and contrast the seven bacterial pneumonias discussed in this chapter. 8. List the etiology, method of transmission, and symptoms of melioidosis.  Unit Outcomes 9. List the causative agent, symptoms, prevention, and preferred treatment for viral pneumonia, RSV, and influenza. 10. List the causative agent, mode of transmission, preferred treatment, and laboratory identification tests for four fungal diseases of the respiratory system.  Unit Outline 1. Structure and Function of the Respiratory System 2. Normal Microbiota of the Respiratory System 3. Microbial Disease of the Upper Respiratory System a. Bacterial Infections b. Viral Infections 4. Microbial Disease of the Lower Respiratory System a. Bacterial Infections b. Viral Infections c. Fungal Infections 5. COVID-19 RESPIRATORY SYSTEM  Structure and Function of the Respiratory System Infections of the upper respiratory system are the most common type of infection. Pathogens that enter the respiratory system can infect other parts of the body.  Structure and Function of the Respiratory System The Upper Respiratory System The upper respiratory system consists of the nose, pharynx, and associated structures, such as the middle ear and auditory tubes.  Structure and Function of the Respiratory System Coarse hairs in the nose filter large particles from air entering the respiratory tract. The ciliated mucous membranes of the nose and throat trap airborne particles and remove them from the body.  Structure and Function of the Respiratory System Lymphoid tissue, tonsils, and adenoids provide immunity to certain infections.  Structure and Function of the Respiratory System The Lower Respiratory System The lower respiratory system consists of the larynx, trachea, bronchial tubes, and alveoli.  Structure and Function of the Respiratory System The ciliary escalator of the lower respiratory system helps prevent microorganisms from reaching the lungs. Microbes in the lungs can be phagocytized by alveolar macrophages. Respiratory mucus contains IgA antibodies.  Normal Microbiota of the Respiratory System The normal microbiota of the nasal cavity and throat can include pathogenic microorganisms. Microbial Disease of the UPPER RESPIRATORY SYSTEM  Microbial Diseases of the Upper Respiratory System Specific areas of the upper respiratory system can become infected to produce pharyngitis, laryngitis, tonsillitis, sinusitis, and epiglottitis. https://www.cdc.gov/antibiotic-use/community/for-patients/common-illnesses/sinus-infection.html  https://upload.wikimedia.org/wikipedia/commons/thumb/b/b1/Pharyngitis.j pg/300px-Pharyngitis.jpg https://upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Pos_s trep.JPG/300px-Pos_strep.JPG https://coreem.net/core/epiglottitis/ Microbial Diseases of the Upper Respiratory System These infections may be caused by several bacteria and viruses, often in combination. Most respiratory tract infections are self- limiting. Haemophilus influenzae type b can cause epiglottitis.  Bacterial Diseases of the Upper Respiratory System  Streptococcal Pharyngitis Also known as strep throat This infection is caused by group A beta- hemolytic streptococci, the group that consists of Streptococcus pyogenes.  Streptococcal Pharyngitis Symptoms of this infection are inflammation of the mucous membrane and fever; tonsillitis and otitis media may also occur. Rapid diagnosis is made by enzyme immunoassays. Immunity to streptococcal infections is type- specific.  Scarlet Fever Strep throat, caused by an erythrogenic toxin- producing S. pyogenes, results in scarlet fever. S. pyogenes produces erythrogenic toxin when lysogenized by a phage. Symptoms include a red rash, high fever, and a red, enlarged tongue. https://www.gponline.com/infectious-diseases-scarlet- fever/infections-and-infestations/nfeictions-and- infestations/article/1324924 https://www.nhs.uk/conditions/scarlet-fever/  Diphtheria Diphtheria Caused by exotoxin-producing Corynebacterium diphtheriae. Exotoxin is produced when the bacteria are lysogenized by a phage.  Diphtheria A membrane, containing fibrin and dead human and bacterial cells, forms in the throat and can block the passage of air. https://upload.wikimedia.org/wikipedia/commons/thumb/4/47/Dirty_white_pseudomembrane_classically_seen_in_diphtheria_2013-07-06_11- 07.jpg/290px-Dirty_white_pseudomembrane_classically_seen_in_diphtheria_2013-07-06_11-07.jpg  Diphtheria The exotoxin inhibits protein synthesis, and heart, kidney, or nerve damage may result. Laboratory diagnosis is based on isolation of the bacteria and the appearance of growth on differential media. Routine immunization in the United States includes diphtheria toxoid in the DTaP vaccine.  Diphtheria Slow-healing skin ulcerations are characteristic of cutaneous diphtheria. There is minimal dissemination of the exotoxin in the bloodstream.  Otitis Media Earache, or otitis media, can occur as a complication of nose and throat infections. Pus accumulation causes pressure on the eardrum. Bacterial causes include Streptococcus pneumoniae, non- encapsulated Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes.  Viral Diseases of the Upper Respiratory System  The Common Cold Any one of approximately 200 different viruses, including rhinoviruses, coronaviruses, and EV-D68, can cause the common cold. We tend to accumulate immunities against these viruses during our lifetime.  The Common Cold The symptoms include sneezing, excessive nasal secretion, and congestion. The incidence of colds increases during cold weather, possibly because of increased interpersonal indoor contact or physiological changes. Microbial Disease of the LOWER RESPIRATORY SYSTEM Microbial Diseases of the Lower Respiratory System Many of the same microorganisms that infect the upper respiratory system also infect the lower respiratory system. Diseases of the lower respiratory system include bronchitis and pneumonia. https://www.medicalnewstoday.com/articles/327431  Bacterial Diseases of the Lower Respiratory System  Pertussis Also known as whooping cough. Pertussis is caused by Bordetella pertussis. The initial stage of pertussis resembles a cold and is called the catarrhal stage. The accumulation of mucus in the trachea and bronchi causes deep coughs characteristic of the paroxysmal (second) stage.  Pertussis The convalescence (third) stage can last for months. Regular immunization for children has decreased the incidence of pertussis.  Tuberculosis Tuberculosis is caused by Mycobacterium tuberculosis. Mycobacterium bovis causes bovine tuberculosis and can be transmitted to humans by unpasteurized milk. M. avium-intracellulare complex infects patients in the late stages of HIV infection.  Tuberculosis Tuberculosis An infectious disease caused by the bacterium M. tuberculosis, a thin rod and an obligate aerobe. https://publichealth.yale.edu/research_practice/departments/emd/diseases/tuberculosis/  Tuberculosis The rods grow slowly (20-hour or longer generation time), sometimes form filaments, and tend to grow in clumps.  Tuberculosis Mycobacteria stained with carbol fuchsin dye cannot be decolorized with acid-alcohol and are therefore classified as acid-fast. This is due to their high lipid cell wall containing mycolic acid. It is responsible for the resilient characteristic of the bacterium, i.e., resistant to drying, antiseptics and disinfectants.  Tuberculosis M. tuberculosis may be ingested by alveolar macrophages; if not killed, the bacteria reproduce in the macrophages.  Tuberculosis Lesions formed by M. tuberculosis are called tubercles; macrophages and bacteria form the caseous lesion that might calcify and appear in an X-ray image as a Ghon’s complex.  Tuberculosis Liquefaction of the caseous lesion results in a tuberculous cavity in which M. tuberculosis can grow.  Tuberculosis Clinical Disease a. Primary infection involves the mid or lower lung field, and the focus is usually single. b. Active tuberculosis may develop as a progression of primary infection or as a reactivation of a quiescent infection.  Tuberculosis c. Miliary (disseminated) tuberculosis involves new foci of infection which can develop when a caseous lesion ruptures and releases bacteria into blood or lymph vessels.  Tuberculosis Diagnosis A positive tuberculin skin test can indicate either an active case of TB, prior infection, or vaccination and immunity to the disease. Active infections can be diagnosed by detection of IFN-γ or rapid PCR test for M. tuberculosis. https://www.theurgentcare.com/tb-skin-tests/ https://www.cdc.gov/tb/topic/testing/tbtesttypes.htm  Tuberculosis Treatment Chemotherapy usually involves three or four drugs taken for at least 6 months; multidrug- resistant M. tuberculosis is becoming prevalent. BCG vaccine for tuberculosis consists of a live, avirulent culture of M. bovis.  Bacterial Pneumonias Pneumonia An infection that inflames your lungs' air sacs (alveoli). The alveoli may fill up with fluid or pus, causing symptoms such as a cough, fever, chills and trouble breathing. Pneumonia, caused by bacteria. Figure A shows pneumonia affecting part of the left lung. Figure B shows healthy alveoli (air sacs). Figure C shows alveoli filled with mucus. https://www.nhlbi.nih.gov/health-topics/pneumonia  Bacterial Pneumonias Typical pneumonia (two-thirds of cases) is caused by pneumococci. Atypical pneumonias are caused by other microorganisms. Pneumococcal pneumonia Caused by encapsulated Streptococcus pneumoniae. S. pneumoniae is a gram-positive, ovoid bacterium that usually appears in pair.  Bacterial Pneumonias Symptoms Pneumococcal pneumonia involves both the bronchi and the alveoli. Symptoms include high fever, breathing difficulty, and chest pain. The sputum is often rust colored from blood coughed up from the lungs.  Bacterial Pneumonias Diagnosis Optochin test Bile solubility test Latex indirect agglutination test Treatment Antibiotic Vaccine (conjugated pneumococcal, pneumococcal polysaccharide)  Bacterial Pneumonias Children under 5 and adults over 65 are most susceptible to Haemophilus influenzae pneumonia. H. influenzae is a gram-negative coccobacillus. Treatment 3rd generation cephalosphorins Hib vaccine  Bacterial Pneumonias Mycoplasma pneumoniae causes mycoplasmal pneumonia; it is an endemic disease. M. pneumoniae lacks cell wall. The symptoms, which persist for 3 weeks or longer, are low-grade fever, cough, and headache. Other terms for the disease are primary atypical and walking pneumonia.  Bacterial Pneumonias Legionellosis Also known as Legionnaire’s disease, is caused by the aerobic gram-negative rod Legionella pneumophila. Unknown until an outbreak in 1976 during American Legion Convention in Philadelphia. Characterized by a high fever of 40.5°C, cough, and general symptoms of pneumonia.  Bacterial Pneumonias L. pneumophila is also responsible for Pontiac fever, which is essentially another form of legionellosis. Its symptoms include fever, muscular aches, and usually a cough. The condition is mild and self-limiting. During outbreaks of legionellosis, both forms may occur.  Bacterial Pneumonias Diagnosis Culture on Charcoal-Yeast extract medium Serological test Treatment Azithromycin Macrolide antibiotics  Bacterial Pneumonias Chlamydophila psittaci, the bacterium that causes psittacosis (ornithosis), is transmitted by contact with contaminated droppings and exudates of fowl. C. psittaci, is a gram-negative, obligate intracellular bacterium.  Bacterial Pneumonias Chlamydophila pneumoniae causes pneumonia; it is transmitted from person to person.  Bacterial Pneumonias Q fever Caused by the obligate intracellular parasitic bacteria Coxiella burnetii. This bacteria naturally infects some animals, such as goats, sheep, and cattle. People can get infected by breathing dust contaminated with secretions from these animals. Bacterial Pneumonia  Melioidosis Melioidosis Infection caused by Burkholderia pseudomallei Transmitted by inhalation, ingestion, or through puncture wounds Symptoms include pneumonia, sepsis, and encephalitis.  Viral Diseases of the Lower Respiratory System  Viral Pneumonia Several viruses can cause pneumonia as a complication of infections such as influenza. The etiologies are not usually identified in a clinical laboratory because of the difficulty in isolating and identifying viruses.  Respiratory Syncytial Virus Respiratory Syncytial Virus (RSV) A common respiratory virus that usually causes mild, cold-like symptoms. The most common cause of bronchiolitis and pneumonia in infants.  Influenza Influenza (Flu) Caused by Influenzavirus and is characterized by chills, fever, headache, and general muscular aches. Hemagglutinin (HA) and neuraminidase (NA) spikes project from the outer lipid bilayer of the virus. https://micro.magnet.fsu.edu/cells/viruses/influenzavirus.html  Influenza Viral strains are identified by antigenic differences in their protein coats (A, B, and C); influenza A is further subdivided by differences in the HA and NA spikes. Antigenic shifts and antigenic drift enable the virus to evade natural immunity.  Influenza Multivalent vaccines are available. Zanamivir and oseltamivir are effective drugs against influenza A virus.  Fungal Diseases of the Lower Respiratory System  Fungal Diseases of the Lower Respiratory System Fungal spores are easily inhaled; they may germinate in the lower respiratory tract. https://www.technologynetworks.com/diagnostics/news/marker-indicates-those-more-at-risk-from-lethal-fungal-spores-309768  Fungal Diseases of the Lower Respiratory System The incidence of fungal diseases has been increasing in recent years. The mycoses in the following sections can be treated with itraconazole.  Histoplasmosis Histoplasmosis Histoplasma capsulatum causes a subclinical respiratory infection that only occasionally progresses to a severe, generalized disease. May be associated with a chronic inflammatory process known as fibrosing mediastinitis.  Histoplasmosis The disease is acquired by inhaling airborne conidia. Isolating or identifying the fungus in tissue samples is necessary for diagnosis.  Coccidioidomycosis Coccidioidomycosis Results from inhaling the airborne arthroconidia of Coccidioides immitis. Most cases of are clinically occult or mild infections. But some patients have progressive pulmonary infection and may suffer dissemination to the brain, bone, and other sites.  Pneumocystis Pneumonia Pneumocystis pneumonia Pneumocystis jirovecii is found in healthy human lungs. However, it causes disease in AIDS patients and other immunosuppressed patients.  Blastomycosis Blastomycosis Also known as North American Blastomycosis Blastomyces dermatitidis is the causative agent of blastomycosis The infection begins in the lungs and can spread to cause extensive abscesses  Other Fungi Involved in Respiratory Disease Opportunistic fungi can cause respiratory disease in immunosuppressed hosts, especially when large numbers of spores are inhaled. Among these fungi are Aspergillus, Rhizopus, and Mucor.  COVID-19 SARS-CoV-2 Infection  COVID-19 Coronavirus Disease 2019 Defined as illness caused by SARS-CoV-2 (formerly called 2019-nCoV) https://emedicine.medscape.com/article/2500114-overview  COVID-19 Timeline First identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China (Dec 31, 2019). Global health emergency (Jan 30, 2020) Global pandemic (March 11, 2020)  COVID-19 Patient 1: First confirmed COVID-19 case in the Philippines (January 30, 2020). Patient 2: Second confirmed case and first COVID-19 deaths outside of China (February 1, 2020). Edrada, E.M., Lopez, E.B., Villarama, J.B. et al. First COVID-19 infections in the Philippines: a case report. Trop Med Health 48, 21 (2020). https://doi.org/10.1186/s41182-020-00203-0  COVID-19 President Rodrigo Duterte’s declaration placing Metro Manila (March 15, 2020) under community quarantine and the rest of Luzon two days later (March 17, 2020). In Philippines, from 3 January 2020 to 4:14pm CET, 29 December 2021, there have been 2,839,111 confirmed cases of COVID-19 with 51,213 deaths, reported to WHO. As of 15 December 2021, a total of 100,019,137 vaccine doses have been administered.  COVID-19 Comorbidities DM Significant association Heart conditions with risk of severe Immunocompromised state from solid organ COVID-19: transplant CA Obesity Cerebrovascular Pregnancy disease Smoking, current or CKD former COPD  COVID-19 Signs and Symptoms Headache May develop 2 days – New loss of taste or smell 2 weeks after exposure Sore throat Fever or chills Congestion or runny Cough nose Shortness of breath or Nausea or vomiting difficulty breathing Diarrhea Fatigue Muscle or body aches  COVID-19 Diagnosis RT–PCR is a variation of PCR, or polymerase chain reaction. The two techniques use the same process except that RT– PCR has an added step of reverse transcription of RNA to DNA, or RT, to allow for amplification. https://www.iaea.org/newscenter/news/how-is-the-covid-19-virus-detected-using-real-time-rt- pcrhttps://www.sigmaaldrich.com/PH/en/applications/genomics/pcr  COVID-19 Management Vaccination Monoclonal-directed antibodies Convalescent plasma Remdesivir – viral RNA polymerase inhibitor Baricitinib – a Janus kinase inhibitor Tocilizumab – an interleukin-6 inhibitor  END OF DISCUSSION  References Background photo by Polina Tankilevitch from Pexels Tortora, G.J., Funke, B.R., & Case, C.L. (2019). Microbiology: an introduction 13th edition. Boston, MA: Pearson Parker, N., Schneegurt, M., Tu, A. -H. T., Lister, P., & Forster, B.M. (2016). Microbiology. Houston, Texas: OpenStax. https://openstax.org/books/ microbiology/pages/22-introduction Centers for Disease Control and Prevention. (2018, June 26). Respiratory syncytial virus (RSV). Retrieved December 16, 2020, from https://www.cdc.gov/rsv/ Centers for Disease Control and Prevention. (2019, January 15). Q fever. Retrieved December 16, 2020, from https://www.cdc.gov/qfever/index.html  References Edrada, E.M., Lopez, E.B., Villarama, J.B. et al. First COVID-19 infections in the Philippines: a case report. Trop Med Health 48, 21 (2020). https://doi.org/10.1186/s41182-020-00203-0 Cennimo, D., Bronze, M., Boyd, D., Wolf, S., & Miller, M. (2021). Coronavirus Disease 2019 (COVID-19): Practice Essentials, Background, Route of Transmission. Retrieved 3 January 2022, from https://emedicine.medscape.com/article/2500114-overview MICROBIAL DISEASE OF THE DIGESTIVE SYSTEM Our Lady of Fatima University – College of Pharmacy  Unit Outcomes 1. Describe the major anatomical features of the human digestive system 2. Describe the normal microbiota of various regions in the human digestive system 3. Explain how microorganisms overcome the defenses of the digestive tract to cause infection or intoxication 4. Describe general signs and symptoms associated with infections