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Haemophilus ducreyi (Chancroid)

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Haemophilus ducreyi (Chancroid)

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A 28-year-old man comes to a primary care clinic with fever, generalized muscle aches, and inguinal ulcers. Three months ago, he was diagnosed with acute urethritis and treated with a course of oral antibiotics. He is sexually active and began a monogamous relationship with a new partner three months ago. They use condoms inconsistently. Temperature is 37.0°C (98.6°F), pulse is 90/min, respirations are 20/min, and blood pressure is 120/75 mmHg. The abdomen is soft and nontender. External genital examination reveals multiple purulent, tender ulcers on the penile shaft. Tender inguinal lymphadenopathy is noted along with overlying ulcerative lesions. Histological analysis of one of these ulcers reveals an organism organized in parallel strands. Which of the following is the most likely organism responsible for this patient’s symptoms?

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Viviana Popa, MD

Haemophilus ducreyi is a Gram-negative coccobacillus, which means that shape-wise, it’s somewhere between a spherical coccus and a rod-like bacillus.

Haemophilus ducreyi is an obligate human pathogen and causes a sexually transmitted disease, called chancroid.

Now, Haemophilus ducreyi has a thin peptidoglycan layer, so it doesn’t retain the crystal violet dye used during Gram staining.

Instead, like any other Gram-negative bacteria, it stains pink with safranin dye.

So, under the microscope, the bacteria look like short or relatively long pink rods with rounded ends, that usually grow in chains, so they’re sometimes compared to a “school of fish”.

Now, Haemophilus ducreyi is: non-motile, so it doesn’t move / facultatively anaerobic, which means it can survive in both aerobic and anaerobic environments / oxidase positive which means it produces an enzyme called oxidase / and catalase negative, which means it doesn’t produce an enzyme called catalase.

Finally, Haemophilus ducreyi can be cultivated on chocolate agar, because this medium contains essential nutrients that Haemophilus ducreyi need to grow, like factor X, also called hemin.

They’re fastidious bacteria that only grow in a CO2 environment, at a temperature between 33 and 35 degrees Celsius, and it forms small, grey or translucent colonies.

Now, Haemophilus ducreyi enters the body through mucosal and skin breaks and has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.

Now, Haemophilus ducreyi is encapsulated, so it has a polysaccharide layer called a capsule, that acts like a shield, protecting the bacteria against phagocytic cells like macrophages and neutrophils.

On the capsule there are fimbria-like proteins, such as Flp1, Flp2 and Flp3 and uses them to attach to subcutaneous epithelial cells and fibroblasts.

Underneath the capsule there’s an outer membrane which consist of lipo-oligo-saccharide, or LOS, which is also involved in cell adhesion.

After attachment, Haemophilus ducreyi makes epithelial cells secrete proinflammatory cytokines like IL-6 and IL-8.

These molecules signal for white blood cell reinforcements - specifically, IL-6 makes CD4 T-cells accumulate in the epidermis and dermis, while IL-8 leads to accumulation of poly-morpho-nuclear leukocytes and macrophages.

Now, neutrophils and macrophages try to kill invading bacteria by generating a bunch of toxic oxygen radicals, such as superoxide, which results from oxidative metabolic burst.

Unfortunately, Haemophilus ducreyi produces an enzyme called copper-zinc superoxide dismutase, which converts superoxide radicals to oxygen and hydrogen peroxide, so it survives the attack.

Furthermore, Haemophilus ducreyi makes two toxins.

One of them, called cyto-lethal distending toxin, or HdCTD, causes G2/M cell cycle arrest, which means that it stops the cell cycle right when the cell is at its largest, in preparation for mitosis, or cell division.

So basically, the cell can’t divide to restore its normal size.

Eventually, this causes cell death.

The other one is a cytotoxic hemolysin, which can lyse foreskin epithelial cells and immune system cells such as macrophages, T cells and B cells.

So, this leads to tissue destruction and avoidance of immune system.

Finally, Haemophilus ducreyi needs zinc to thrive and replicate, so it has a zinc-binding protein that snatches zinc from the host cells.

Summary

Haemophilus ducreyi (Chancroid) is a gram-negative, facultatively anaerobic, nonmotile coccobacillus. It is known to cause a sexually transmitted disease called chancroid, which is characterized by one or more painful genital ulcers associated with tender inguinal adenopathy.