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Neisseria

Neisseria

Neisseria is a genus of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. These pathogens have many virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus, including fimbriae Fimbriae Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins. Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of 'pili'. Escherichia coli, lipooligosaccharide envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, a polysaccharide capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides (unique to N. meningitidis), and IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS. Gonococcal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are sexually or perinatally transmitted and include gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea, pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease, septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, and neonatal conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis. Meningococcal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are transmitted via respiratory and oral secretions. They most commonly cause meningococcemia Meningococcemia Terminal Complement Pathway Deficiency with petechial hemorrhages Petechial Hemorrhages Brown-SĂ©quard Syndrome and meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis.

Last updated: 25 Feb, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be classified according to a lab procedure called Gram staining Gram staining Bacteriology.
Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology with cell walls that have a thin layer of peptidoglycan Peptidoglycan Penicillins do not retain the crystal violet stain utilized in Gram staining Gram staining Bacteriology. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be further classified according to morphology (diplococci, curved rods, bacilli Bacilli Shigella, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be more narrowly identified by growing them on specific media ( triple sugar iron Triple sugar iron Shigella ( TSI TSI Shigella) agar) where their enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes can be identified ( urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain Gram stain Klebsiella
** Pleomorphic Pleomorphic Bacteroides rod/coccobacillus
*** Require special transport media

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General Characteristics

  • Many Neisseria species are normal inhabitants of the mucosal surfaces of many animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic.
  • Of the 10+ species that infect humans, only 2 are strictly human pathogens: N. gonorrhoeae (gonococcus) and N. meningitidis (meningococcus).
  • Gram-negative diplococci (paired cocci Cocci Bacteriology)
  • Facultative intracellular Facultative intracellular Yersinia spp./Yersiniosis organisms
  • Non-motile
  • Oxidase and catalase Catalase An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. Nocardia/Nocardiosis positive
  • Sugar fermentation:
    • N. meningitidis uses maltose and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance.
    • N. gonorrhoeae uses glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance only.
  • Contain lipooligosaccharides (LOS) with strong endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus activity
  • Require special culture media to grow:
    • N. meningitidis is less fastidious Fastidious Bordetella and grows on sheep agar.
    • N. gonorrhoeae requires modified Thayer-Martin agar (MTM) for optimal growth: enriched chocolate agar Chocolate agar Haemophilus with antimicrobial agents that selectively favor growth of Neisseria by inhibiting growth of other bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology and fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology.
N. meningitidis N. gonorrhoeae
Encapsulated Encapsulated Klebsiella (polysaccharide capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides) Not capsulated
Ferments maltose and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance Ferments glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance only
Colonizes nasopharynx Nasopharynx The top portion of the pharynx situated posterior to the nose and superior to the soft palate. The nasopharynx is the posterior extension of the nasal cavities and has a respiratory function. Pharynx: Anatomy Colonizes genital mucosa
Rarely has plasmids Plasmids Extrachromosomal, usually circular DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in genetic engineering as cloning vectors. DNA Types and Structure Most have plasmids Plasmids Extrachromosomal, usually circular DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in genetic engineering as cloning vectors. DNA Types and Structure

Neisseria Gonorrhoeae

Epidemiology

  • Worldwide distribution
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of 583,405 cases in the United States in 2018, with a 5% increase from the year before and a higher rate in males than females (212.8:145.8 per 100,000 people)
  • A nationally notifiable disease

Transmission

  • Sexual contact with the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy, vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy, mouth, or anus of an infected individual
  • Perinatal transmission Perinatal transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections (during vaginal delivery)

Pathogenesis

  • Exclusively pathogenic for humans

General virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus: 

  • Pili Pili Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. This preferred use of ‘pili’ refers to the sexual appendage, to be distinguished from bacterial fimbriae, also known as common pili, which are usually concerned with adhesion. Salmonella ( fimbriae Fimbriae Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins. Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of ‘pili’. Escherichia coli): 
    • Enhance attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology to host cells
    • Furnish resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation
    • Provide antigenic variation among different strains 
  • Por proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis in cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane: 
    • Components of the proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis of the outer membrane vesicles Vesicles Female Genitourinary Examination (OMVs)
    • May prevent intracellular killing by neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation by interfering with phagosome-lysosome fusion
  • Opacity Opacity Imaging of the Lungs and Pleura-associated (Opa) proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (outer membrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis): aid in attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology to host cell receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Lipooligosaccharide (LOS, endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus) envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology protein:
    • LOS is an oligosaccharide with a lipid A component. 
    • Responsible for most of the toxicity Toxicity Dosage Calculation in gonococcal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., causes fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, ciliary loss, and mucosal cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death in the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy)
    • Not to be confused with the capsular polysaccharide of meningococci
  • IgA1 protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS: inactivates IgA1 immunoglobulin and reduces host’s defense

Mechanisms to evade immune recognition Immune Recognition Yaws, Bejel, and Pinta:

  • LOS mimics human cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane glycosphingolipids and can be sialylated, which renders them resistant to serum killing.
  • Can rapidly switch from one antigenic form of LOS, pilin, and Opa to another

Mechanisms of antimicrobial resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:

  • Plasmids Plasmids Extrachromosomal, usually circular DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in genetic engineering as cloning vectors. DNA Types and Structure code for:
    • Penicillinase (similar to Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus spp. and other gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology)
    • Resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-induced Liver Injury (from the conjugative streptococcal plasmid)
  • Most gonococci have plasmids Plasmids Extrachromosomal, usually circular DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in genetic engineering as cloning vectors. DNA Types and Structure, but meningococci rarely have them.
Neisseria gonorrhoeae pathogenesis

Pathogenesis of N. gonorrhoeae.
The bacterium adheres to the mucosal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology (1) where it competes with microbiota and colonizes to invade the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology (2). Peptidoglycans, LOS, and OMVs are released (3), activating TLR and NOD signaling in epithelial cells, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions (4). This leads to the production of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity (5) which brings about a neutrophil-rich purulent exudate Exudate Exudates are fluids, cells, or other cellular substances that are slowly discharged from blood vessels usually from inflamed tissues. Pleural Effusion and phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation of the harmful bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology (6). Since N. gonorrhoeae has defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual’s subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms that resist being killed, the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology-laden neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation can also act as agents of transmission to another host (7).

Selected abbreviation key:
LOS: lipooligosaccharide
OMV: outer membrane vesicles Vesicles Female Genitourinary Examination
TLR: toll-like receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
NOD: nucleotide-binding oligomerization domain-containing protein

Image by Lecturio.

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • The incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period ranges from 1–14 days (usually < 7).
  • The clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor can vary greatly depending on the age and immunologic state of the host, as well as the mode of transmission. 
  • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can present asymptomatically.
    • More common in young women
    • Higher risk of spreading the infection and developing long-term complications
Type of presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal LaborClinical features
Gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea (acute gonococcal infection; commonly referred to as “the clap”)
  • Sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) ( STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs))
  • Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor varies depending on the mode of transmission:
    • Can be asymptomatic, especially in women
    • Urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs): purulent, yellow-green discharge through urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy with painful urination
    • Cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea: purulent, yellow-green (or blood-tinged) with foul smell Smell The sense of smell, or olfaction, begins in a small area on the roof of the nasal cavity, which is covered in specialized mucosa. From there, the olfactory nerve transmits the sensory perception of smell via the olfactory pathway. This pathway is composed of the olfactory cells and bulb, the tractus and striae olfactoriae, and the primary olfactory cortex and amygdala. Olfaction: Anatomy, abdominal pain Abdominal Pain Acute Abdomen, or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways during pelvic exam
    • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis: sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis, difficulty swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility, swollen lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and purulent exudante
    • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and mucosal swelling Swelling Inflammation of the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy with purulent, yellow-green discharge
    • Prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis: fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, painful and difficult urination and ejaculation, with foul-smelling urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat
    • Orchitis Orchitis Inflammation of a testis. It has many features of epididymitis, such as swollen scrotum; pain; pyuria; and fever. It is usually related to infections in the urinary tract, which likely spread to the epididymis and then the testis through either the vas deferens or the lymphatics of the spermatic cord. Epididymitis and Orchitis and epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis: unilateral pain Unilateral Pain Cluster Headaches and swelling Swelling Inflammation of the scrotum Scrotum A cutaneous pouch of skin containing the testicles and spermatic cords. Testicles: Anatomy
Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease ( PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease)
  • Infection of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy, fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy (salpingitis), and/or ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy that began as an asymptomatic case, urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs), or cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea
  • Presents as:
    • White, purulent discharge Purulent Discharge Dacryocystitis
    • Cervical motion tenderness
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Abdominal/pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/ dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency
    • Abnormal menstrual bleeding
  • Complications:
    • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
    • Ectopic pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Chronic pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Fitz-Hugh-Curtis syndrome: spreads to the upper peritoneal cavity Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of winslow, or epiploic foramen. Peritoneum: Anatomy with infection of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides and characteristic “violin string” peritoneal adhesions
    • Ovarian or cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer
Neonatal conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis (gonococcal ophthalmia neonatorum Ophthalmia Neonatorum Acute conjunctival inflammation in the newborn, usually caused by maternal gonococcal infection. The causative agent is Neisseria gonorrhoeae. The baby’s eyes are contaminated during passage through the birth canal. Gonorrhea)
  • Presents as purulent conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis 2–5 days after birth
  • Due to perinatal transmission Perinatal transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections during vaginal delivery
  • Can be prevented by the local application of 0.5% erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides or 1% tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-induced Liver Injury to the conjunctivae of newborns (mandatory in the United States)
Disseminated gonococcal infection
  • More common in women (ratio, 4:1)
  • Presents as a mixture or any of the following:
    • Septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: swelling Swelling Inflammation of multiple joints (up to 4)
    • Dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)– arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis syndrome: vesicular, pustular, or maculopapular Maculopapular Dermatologic Examination lesions on the trunk and extremities with necrotic or hemorrhagic centers
    • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
    • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis

Diagnosis

  • Specimens used: 
    • Pus/secretions from various sites 
    • First-catch urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat, without pre-cleansing, for genitourinary tract lesions
    • Blood and joint fluid for culture (only 30% sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques) needs a special transport medium.
    • Smears: Sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques and specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays vary among sites.
      • > 90% in urethral exudates from men
      • 50% sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques for endocervical exudates 
      • < 10% for joint fluid
      • Gram stain Gram stain Klebsiella is not helpful for throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy or rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy samples because non-pathogenic Neisseria often colonize these sites. 
  • Culture on modified Thayer-Martin medium Thayer-Martin Medium Brucella/Brucellosis:
    • Not routinely used because nucleic acid amplification Nucleic acid amplification Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template. Septic Arthritis test (NAAT) is much faster and reliable
    • Used to determine antibiotic resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing if patient failed initial therapy
    • Identification Identification Defense Mechanisms by:
      • Positive oxidase test, only glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance is oxidized
      • Immunologic (coagulation) testing
      • MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast spectrometry for same-day identification Identification Defense Mechanisms
Histopathology in an acute case of gonococcal urethritis using g

N. gonorrhoeae are gram-negative diplococci that provoke a marked neutrophilic response, as seen in this image, with several neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation containing many phagocytized bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.

Image: “ Gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea Neisseria gonorrhoeae” by Joe Miller. License: CC0

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Neisseria Meningitidis

Epidemiology

  • Meningococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis occurs in 2 settings:
    • Epidemic waves, associated with crowding
      • Military bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance/encampments
      • School dormitories
      • Religious pilgrims
      • Sub-Saharan Africa (the “ meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis belt,” from Senegal to Ethiopia)
    • Sporadic Sporadic Selective IgA Deficiency “interepidemic” cases
      • Older infants, children, and adolescents have the highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in developed countries.
  • In the United States, the annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is approximately 1/100,000.

Transmission

Pathogenesis

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus:

  • Capsular polysaccharides Polysaccharides Basics of Carbohydrates are antigenic and form 6 important serogroups, responsible for most invasive meningococcal disease (IMD): 
    • A, B, C, X, Y, W (formerly W-135)
    • Serogroup A causes most meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis in sub-Saharan Africa.
    • Serogroup B causes most sporadic Sporadic Selective IgA Deficiency meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis.
  • Other virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus are similar to those of N. gonorrhoeae.
    • Lipooligosaccharide (LOS, endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus) envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology protein
      • LOS mimics human cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane glycosphingolipids.
      • Can be sialylated→ resistant to serum killing
      • Lipid A disaccharide ( endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus) component causes much of the toxicity Toxicity Dosage Calculation.
    • IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS: inactivates IgA1 immunoglobulin and reduces host’s defense
    • Can rapidly switch antigenic forms of LOS, pilin, Opa
Neisseria meningitidis pathogenesis

Neisseria meningitidis pathogenesis
The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology enters the respiratory system to invade mucous membranes, entering the bloodstream. In the blood, proliferation occurs and the pathogen releases endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus which causes fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, increased vascular permeability, shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock, and petechiae Petechiae Primary Skin Lesions. The antiphagocytic capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides enables the pathogen to evade destruction by the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs.

Image by Lecturio.

Pathogenesis:

  • The nasopharynx Nasopharynx The top portion of the pharynx situated posterior to the nose and superior to the soft palate. The nasopharynx is the posterior extension of the nasal cavities and has a respiratory function. Pharynx: Anatomy is the portal of entry, attaching to mucosal cells with the aid of pili Pili Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. This preferred use of ‘pili’ refers to the sexual appendage, to be distinguished from bacterial fimbriae, also known as common pili, which are usually concerned with adhesion. Salmonella.
  • Organisms reach the bloodstream → IMD, which has a rapid course and manifests as sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock ( meningococcemia Meningococcemia Terminal Complement Pathway Deficiency) and meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis.
  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology may also reach the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy from nearby infected structures or through a congenital Congenital Chorioretinitis or acquired defect in the skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy or spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy. 
  • Much of the neurologic injury is caused by the immune response to the endotoxin Endotoxin Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Proteus and other bacterial components rather than direct bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology-induced tissue injury.
    • Inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity → intense acute inflammatory response, vasogenic edema Vasogenic Edema Increased Intracranial Pressure (ICP), and purulent exudate Exudate Exudates are fluids, cells, or other cellular substances that are slowly discharged from blood vessels usually from inflamed tissues. Pleural Effusion (visible on the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification surface)
    • Interstitial and cytotoxic Cytotoxic Parvovirus B19 edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus, and thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus → ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, infarction, and cerebral herniation Herniation Omphalocele

Clinical presentations

Type of presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal LaborClinical features
Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • N. meningitidis is the most common cause of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis in children from 1 month to 18 years of age.
  • The classic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis triad may not always be present:
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Nuchal rigidity Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Megacolon or “stiff neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess”
  • Other signs and symptoms include:
    • Decreased level of consciousness
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures (usually focal)
    • Elevated ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) that can lead to cerebral herniation Herniation Omphalocele and death
Meningococcemia Meningococcemia Terminal Complement Pathway Deficiency (meningococcal septicemia) Acute meningococcemia Meningococcemia Terminal Complement Pathway Deficiency:
  • Septicemia with or without meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Presents as:
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Septic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Generalized hemorrhagic state that leads to a diffuse erythematous maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever that becomes petechiae Petechiae Primary Skin Lesions and/or purpura
  • Progresses rapidly and is highly fatal without treatment

Chronic meningococcemia Meningococcemia Terminal Complement Pathway Deficiency:
  • Milder disease
  • Presents as:
    • Persistent bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides (for weeks)
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
    • Petechial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
    • Can progress to acute meningococcemia Meningococcemia Terminal Complement Pathway Deficiency
Waterhouse-Friderichse syndrome
  • A complication of meningococcemia Meningococcemia Terminal Complement Pathway Deficiency
  • Presents as:
    • DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
    • Bilateral hemorrhagic adrenal infarctions
    • Septic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
Other presentations
  • Rare, usually as a result of meningococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis or septicemia that disseminates:
    • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
    • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Urethritis Urethritis Inflammation involving the urethra. Similar to cystitis, clinical symptoms range from vague discomfort to painful urination (dysuria), urethral discharge, or both. Urinary tract infections (UTIs)
ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP): intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension
DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation: disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation

Identification Identification Defense Mechanisms

  • Specimens used:
  • Lumbar puncture Lumbar Puncture Febrile Infant: if no contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation (elevated ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP), coagulation disorders, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, uncorrected shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock)
  • Culture: N. meningitidis is less fastidious Fastidious Bordetella than N. gonorrhoeae but special transport media should still be used, as well as culture on modified Thayer-Martin medium Thayer-Martin Medium Brucella/Brucellosis.

Prevention

Prevention is done by quadrivalent meningococcal polysaccharide conjugate vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination:

  • Contains A, C, Y, and W 
  • Recommended for individuals 11–18 years, with a booster dose 3 years later
  • A single dose only if > 16 years of age
  • Vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination at 2 months and older for at-risk groups of people
  • Efficacy: 82% first year after vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination, waning to 59% at 3–6 years

Related videos

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Neisseria Meningitidis
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Neisseria Meningitidis (Meningococcus): Signs & Symptoms

References

  1. Riedel, S., Hobden, J.A. (2019). In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed, pp. 295–305).
  2. Textor, S. (2018). In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 1, pp. 1114–1129). 
  3. Secondhand smoke linked to childhood meningitis. (2018, October 3). Nhs. Uk. https://www.nhs.uk/news/pregnancy-and-child/secondhand-smoke-linked-to-childhood-meningitis/
  4. Apicella, M. (2020). Treatment and prevention of meningococcal infection. UpToDate. Retrieved November, 1, 2020, from https://www.uptodate.com/contents/treatment-and-prevention-of-meningococcal-infection?search=Meningococcal%20meningitis&source=search_result&selectedTitle=1~45&usage_type=default&display_rank=1#H2603449448
  5. Rosenthal, K.S. & Tan, M.J. (2010). Rapid Review Microbiology and Immunology (Goljan, E.F.) (3rd ed.). Mosby/Elsevier.
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