Chancroid

Chancroid is a highly transmissible STD STD Sexually transmitted diseases (STDs) 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) caused by  Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis”). Up to 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will develop painful inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Furthermore, of that percentage, 25% may develop complications of the suppurative lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes. Given the growth of H. ducreyi on a special medium (often not readily available), chancroid is diagnosed based upon clinical appearance and tests to rule out both 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 and herpes (the most common causes of genital ulcers). Although the disease can resolve spontaneously, antibiotics ( 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 or 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) are the treatment of choice. Treatment should involve both patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and their sexual contacts.

Last updated: Sep 29, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Chancroid (soft chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis) is a sexually transmitted disease Sexually Transmitted Disease Sexually transmitted diseases (STDs) 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) caused by a bacterium, Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus, characterized by painful genital ulcer and suppurative inguinal adenopathy.

Etiology

  • H. ducreyi:
    • Gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis
    • Nonspore forming
    • Nonmotile
    • Facultative anaerobic coccobacillus
    • Grows best in a humid atmosphere
  • Associated risk factors for STD STD Sexually transmitted diseases (STDs) 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):
    • Uncircumcised men
    • Low socioeconomic status
    • Poor hygiene
    • Risky sexual behavior (drug abuse, prostitution)

Epidemiology

  • Chancroid is an uncommon infection in most developed countries.
    • In 2011, < 20 cases were recorded in the United States.
    • In 2016, 7 cases were recorded in the United States.
  • Common in the following regions: 

Pathophysiology

  • H. ducreyi infection dependent upon:
    • Size of inoculum (100 colony-forming units carry a 90% risk of infection)
    • Host factors
  • Transmission: H. ducreyi enters via 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 microabrasions and causes mucosal breaks during sexual contact.
  • Infection process: Pathogen produces a cytolethal distending toxin → irreversible epithelial damage and death → ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers

Clinical Presentation

  • Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually develop a lesion between 4 and 10 days postexposure.
  • Lesion:
  • Affects genital areas and draining lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes:
    • In men:
      • Corona, prepuce Prepuce The double-layered skin fold that covers the glans penis, the head of the penis. Penis: Anatomy, or glans of 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
    • In women: 
      • Labia, introitus, and perianal areas
      • Can be asymptomatic, if vaginal and cervical areas are affected
    • Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy:
      • 50% will develop tender, unilateral inguinal lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy.
      • 25% will develop buboes with subsequent ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers within 2 weeks.

Diagnosis

Diagnosis is made by clinical judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment and tests to rule out the 2 most common causes of genital ulcers, herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections 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 ( 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 and 2) and 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.

  • Confirmed diagnosis is made by isolation of H. ducreyi on culture (the special media is not widely available).
  • Gram stain Gram stain Klebsiella: Organisms appear as parallel strands resembling a “railroad track” or 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.”
  • 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 tests are not readily available outside of clinical research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest.
  • Probable diagnosis:
    • ≥ 1 painful ulcer(s) are present.
    • Symptoms and signs match that of a typical chancroid lesion.
    • Negative 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) test for 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 and 2
    • No evidence of Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema (darkfield microscopy or serologic testing)
Haemophilus ducreyi bacteria

Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus 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: “ Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus 01” by CDC. License: Public Domain

Management

General principles

  • Disease course and treatment:
    • Lesion(s) can spontaneously resolve within 3 months but can be complicated by lymphadenitis Lymphadenitis Inflammation of the lymph nodes. Peritonsillar Abscess and suppurative buboes.
    • Antimicrobial therapy is the mainstay of treatment to avoid the formation of buboes.
  • Additional recommendations:
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship must be screened for other STDs.
    • Unprotected sexual intercourse should be avoided during treatment (until the ulcers have resolved).
    • Sexual partners should also be treated regardless of the symptoms.

Medical management

  • 1st-line treatment: 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 1 g orally (by mouth) as a single dose or  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 250 mg given IM as a single dose:
    • Advantage of increased compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology, as they are administered as a single-dose regimen.
    • Safe for pregnant women
  • Alternatives:
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones (3-day course)
    • 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 (7-day course)
  • Empiric treatment for 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 and 2 and 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 is also recommended (as they are more common and coinfections may exist).

Surgical management

  • Incision and drainage Incision And Drainage Chalazion of suppurative buboes
  • Needle aspiration Needle aspiration Using fine needles (finer than 22-gauge) to remove tissue or fluid specimens from the living body for examination in the pathology laboratory and for disease diagnosis. Peritonsillar Abscess can be performed, but patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may need repeat aspirations.
  • Without treatment, fistulous tracts and deep tissue destruction can occur.

Differential Diagnosis

  • Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections: common STD STD Sexually transmitted diseases (STDs) 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) caused by 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 and 2 type 1 Type 1 Spinal Muscular Atrophy or 2. Prodromal symptoms often precede clusters of painful and fluid-filled vesicles Vesicles Female Genitourinary Examination on an erythematous base. These vesicles Vesicles Female Genitourinary Examination eventually form ulcers, which can coalesce. Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), and severe neuralgia can occur. The diagnosis is generally clinical but confirmed with 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) and serologic testing. Management includes antiviral Antiviral Antivirals for Hepatitis B therapy.
  • 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: this STD STD Sexually transmitted diseases (STDs) 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) is caused by T. pallidum and has 4 clinical stages. Primary 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 begins with a solitary painless ulcer on the genitals ( chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis). Progression to secondary 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 manifests as a generalized maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever, which includes the palms and soles. The development of tertiary 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 can cause severe neurologic ( neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis), cardiovascular, and/or gummatous disease. The dormant period between secondary and tertiary 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 is the latent stage Latent Stage Benign Bone Tumors.
  • 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: rare STD STD Sexually transmitted diseases (STDs) 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) 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. The progressive, nodular genital lesions can form into painless ulcerations, which cause tissue damage. Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy is not common. The diagnosis is with microscopic findings of Donovan bodies Donovan Bodies Donovanosis from the lesion. Management involves antibiotics, such as macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides, tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines, and trimethoprim-sulfamethoxazole.
  • Lymphogranuloma venereum Lymphogranuloma venereum Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis. Chlamydial Infections: STD STD Sexually transmitted diseases (STDs) 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) caused by 3 strains of  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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have a small, self-limited genital ulcer, followed by painful inguinal and/or femoral lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Diagnosis is clinical. Although 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 help with diagnosis, the availability of this testing is limited. Management involves tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines or 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.

References

  1. Hicks, C. B. (2019). Chancroid. UpToDate. Retrieved March 01, 2021, from https://www.uptodate.com/contents/chancroid
  2. Irizarry, L., Velasquez, J., & Wray, A. A. (2020). Chancroid. StatPearls. Retrieved March 01, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK513331/
  3. Riedel, S., Morse, S. A., Mietzner, T. A., & Miller, S. (2019). Haemophilus, bordetella, brucella, and francisella. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28e. McGraw-Hill.

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