Haemophilus

General Characteristics

General characteristics of Haemophilus species:

• Gram-negative pleomorphic Pleomorphic Bacteroides coccobacilli
• All 24 members of Haemophilus are usually cultured on chocolate agar plates, as all species require at least 1 of 2 growth factors (provided by chocolate agar but not blood agar Blood agar Nocardia/Nocardiosis): factor V Factor V Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Hemostasis ( nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway [ NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway]) and factor X Factor X Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called stuart-prower factor deficiency, may lead to a systemic coagulation disorder. Hemostasis (heme)
  • H. influenzae requires both factors
  • May also be grown on blood agar Blood agar Nocardia/Nocardiosis with Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess, which provides factor NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway in excess of its own needs; heme is released from the red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology by the action of staphylococcal hemolysins Hemolysins Proteins from bacteria and fungi that are soluble enough to be secreted to target erythrocytes and insert into the membrane to form beta-barrel pores. Biosynthesis may be regulated by hemolysin factors. Leptospira/Leptospirosis
• The H. influenzae species is divided into typeable ( encapsulated Encapsulated Klebsiella) and non-typeable (non-encapsulated), strains. In the encapsulated Encapsulated Klebsiella strains, the 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 is used to serotype them into 6 types, a to f, with type b (Hib) being the most virulent and clinically important one.
• The non-typeable H. influenzae (NTHi) strains also cause disease, especially mucosal diseases of the upper respiratory tract such as otitis media, acute rhinosinusitis, acute bronchitis Acute Bronchitis Acute bronchitis is an infection of the mucous membrane of the bronchi without evidence of pneumonia. Due to its pathogenesis, acute bronchitis is frequently accompanied by an upper respiratory tract infection. Cases in which the trachea is also involved are referred to as tracheobronchitis. Acute Bronchitis, acute exacerbations of chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis, and non-bacteremic 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, and are usually non-invasive. H. influenzae is also one of the 4 most common causes of bacterial conjunctivitis Bacterial Conjunctivitis Conjunctivitis in the United States (along with Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess, Streptococcus pneumoniae, and Moraxella catarrhalis Moraxella catarrhalis Gram-negative aerobic cocci of low virulence that colonize the nasopharynx and occasionally cause meningitis; bacteremia; empyema; pericarditis; and pneumonia. Moraxella)
• Hib infection is rare in developed countries due to widespread 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 use.

Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus factors of Haemophilus species:

• Capsular antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (in the encapsulated Encapsulated Klebsiella strains): antiphagocytic
• Adhesin 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 (e.g., HMW1, HMW2) mediate attachment to the human epithelial cells in the airway Airway ABCDE Assessment.
• 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 and the major outer membrane P2 protein: bind BIND Hyperbilirubinemia of the Newborn sialic acid-containing moieties on epithelial cell surfaces
• IgA1 protease IgA1 protease Neisseria: cleaves immunoglobulin A at the hinge region, preventing agglutination and mechanical clearance of the pathogen
• Phase variation: The outer surface proteins Outer surface proteins Borrelia are modified to adapt to changes in the host environment.
• In vivo biofilm Biofilm Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an extracellular polymeric substance matrix that is secreted by the microbes. They occur on body surfaces such as teeth (dental deposits); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with dentifrices; disinfectants; anti-infective agents; and anti-fouling agents. Staphylococcus production is especially important in the pathogenesis of acute otitis media Acute Otitis Media Acute otitis media is an infection in the middle ear characterized by mucosal inflammation and retention of fluid. The most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The condition can present with fever, otalgia, and diminished hearing. Acute Otitis Media (AOM). (AOM is the most common pediatric bacterial infection, affecting up to 75% of children at some point before the age of 5 years. S. pneumoniae and H. influenzae, especially NTHi, are responsible for up to 80% of bacterial AOM.)

Haemophilus influenzae

• Transmission: respiratory droplets Droplets Varicella-Zoster Virus/Chickenpox. Humans are the only reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli for H. influenzae.
• Despite the name, H. influenzae does NOT cause influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza, which is exclusively viral.
• Risk factors
  • Age < 5 years and absent or incomplete Hib immunization
  • Functional or anatomic asplenia Anatomic Asplenia Asplenia, including sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease
  • Any underlying medical conditions that interfere with immune function
  • Structural lung disease, smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome, 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, older age, lower socioeconomic status
• Diagnosis
  • Non-invasive respiratory 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: Use clinical signs and symptoms (AOM, 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, exacerbation of chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis). Detection of H. influenzae in the respiratory tract does not differentiate colonization Colonization Bacteriology from infection.
  • Invasive 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: Culture (may lack sensitivity but necessary to understand antibiotic susceptibility; a rapid assay for beta-lactamase Beta-Lactamase Penicillins production is useful), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast spectrometry, polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR))-based assays
• 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 only for type b 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 strain (Hib): available since 1985
  • Polysaccharide 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 conjugated to the diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria toxoid Toxoid Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are tropanes found in cyanobacteria. Vaccination (to get a better response)
  • Administered to infants aged 2–6 months (2 or 3 doses) with a booster dose at age 12 through 15 months. 
  • Even 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, infection still possible, with a peak occurrence at 6 months to 1 year, corresponding to a decline in maternal protective immunoglobulin G ( IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis) and inability of the child to generate sufficient antibody against the capsular antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination due to immature 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
  • Before 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, H. influenzae was the leading cause of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis and other serious invasive diseases in children aged < 5 years in the United States; after the introduction of conjugate Hib vaccines in 1987 and 1989, the 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 invasive Hib disease in children aged < 5 years decreased by 99%.
• Treatment:
  • Mucosal 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: amoxicillin-clavulanate
  • 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 systemic disease: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
  • Prophylaxis Prophylaxis Cephalosporins 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 for close contacts (if index case Index case Basic Terms of Genetics had invasive Hib or H. influenzae type a disease): rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis

To help remember the common clinical manifestations of H. influenzae, use the following mnemonic:

• “ Ha HA Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic AnemiaEMOP hilus Hilus Lungs: Anatomy causes…”
  • Epiglottitis
  • Meningitis
  • Otitis media
  • Pneumonia

Haemophilus ducreyi

• The cause of chancroid, one of the 5 classic infectious causes of genital ulcer disease (others: Herpes simplex virus [HSV-1 and HSV-2], syphilis [Treponema pallidum], lymphogranuloma venereum [Chlamydia trachomatis L1-L3], granuloma inguinale [“donovanosis,” caused by Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella granulomatis])
• Also one of the causes of non-genital chronic 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 ulcers in tropical climates
• Clinical presentation of chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid:
  • Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus: 3 to 10 days
  • Ulcers: painful, sharply circumscribed or irregular with ragged undermined edges
  • Inguinal adenopathy in 50% of cases
  • Males more often symptomatic than females
• Transmission: direct contact
• Diagnosis: Difficult, so clinical criteria often used while excluding other more likely causes to arrive at “probable diagnosis”
  • Culture or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing can be used for diagnosis, but not always available.
  • Gram stain Gram stain Klebsiella may show small gram-negative coccobacilli in chains resembling a school of fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing or a railroad track, but has poor sensitivity.
• Treatment: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins or azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides

Mnemonic:

Haemophilus ducreyi is so painful that you do cry.