General Characteristics

General characteristics of Haemophilus species:

• Gram-negative pleiomorphic 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): factor V (nicotinamide adenine dinucleotide [NAD]) and factor X (heme)
  • H. influenzae requires both factors
  • May also be grown on blood agar with Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus, which provides factor NAD in excess of its own needs; heme is released from the red blood cells by the action of staphylococcal hemolysins
• The H. influenzae species is divided into typeable (encapsulated) and non-typeable (non-encapsulated), strains. In the encapsulated strains, the polysaccharide capsule 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 Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD), 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 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 in the United States (along with Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella Moraxella Moraxella is a genus of gram-negative diplococci, with M. catarrhalis being the most clinically relevant species. M. catarrhalis is part of the normal flora of the upper respiratory tract, but it can cause infection in susceptible individuals. The infection is transmitted through respiratory droplets and can lead to chronic obstructive pulmonary disease (COPD) exacerbations in adults and otitis media in children. Moraxella catarrhalis)
• Hib infection is rare in developed countries due to widespread vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination use.

Virulence factors of Haemophilus species:

• Capsular antigen (in the encapsulated strains): antiphagocytic
• Adhesin proteins (e.g., HMW1, HMW2) mediate attachment to the human epithelial cells in the airway.
• Pili and the major outer membrane P2 protein: bind sialic acid-containing moieties on epithelial cell surfaces
• IgA1 protease: cleaves immunoglobulin A at the hinge region, preventing agglutination and mechanical clearance of the pathogen
• Phase variation: The outer surface proteins are modified to adapt to changes in the host environment.
• In vivo biofilm 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. Humans are the only reservoir 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 Asplenia Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. 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, alcoholism, pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care, older age, lower socioeconomic status
• Diagnosis
  • Non-invasive respiratory infections: 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 Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)). Detection of H. influenzae in the respiratory tract does not differentiate colonization from infection.
  • Invasive infections: Culture (may lack sensitivity but necessary to understand antibiotic susceptibility; a rapid assay for beta-lactamase production is useful), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass 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 only for type b capsule strain (Hib): available since 1985
  • Polysaccharide vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. 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 (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) and inability of the child to generate sufficient antibody against the capsular antigen due to immature immune system
  • 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 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 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 of invasive Hib disease in children aged < 5 years decreased by 99%.
• Treatment:
  • Mucosal infections: amoxicillin-clavulanate
  • Meningitis or systemic disease: ceftriaxone
  • Prophylaxis 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 had invasive Hib or H. influenzae type a disease): rifampin

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

• “HaEMOPhilus causes…”
  • Epiglottitis
  • Meningitis
  • Otitis media
  • Pneumonia

Haemophilus ducreyi

• The cause 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, one of the 5 classic infectious causes of genital ulcer disease (others: Herpes simplex virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview [ HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2-1 and HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2-2], syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis [ Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema pallidum], lymphogranuloma venereum [ Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis L1-L3], granuloma inguinale [“ donovanosis Donovanosis Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. 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. Structure and Function of the Skin 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: 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 may show small gram-negative coccobacilli in chains resembling a school of fish or a railroad track, but has poor sensitivity.
• Treatment: ceftriaxone or azithromycin

Mnemonic:

Haemophilus ducreyi is so painful that you do cry.