Typhoid: Leukopenia, chronic carrier state and cancer (Why does typhoid fever cause leukopenia?)

I see a lot of patients with typhoid in the casualty and usually, they all have leucopenia. So I wondered - Why does the WBC count decrease in typhoid or enteric fever? Why does the WBC count become low unlike other infections?

After loads and loads of Googling, I found the answer to my question.

Intramedullary destruction of neutrophils and their precursors by non malignant histiocytes is the major cause of leukopenia and/or neutropenia in typhoid.

You see, histocytes can engulf nonapoptotic leukocytes, nonsenescent erythrocytes & platelets and thus become hemophagocytes. Humans with typhoid fever accumulate hemophagocytic histiocytes, macrophages, or dendritic cells in the spleen and bone marrow. 

Hemophagocytosis is an important mechanism in producing neutropenia, anemia and thrombocytopenia. 

PS: We do not know yet whether hemophagocytic macrophages also contain the typhoid bacteria.

In addition to hemophagocytosis - Sequestration and destruction of platelets in enlarged spleen, decreased platelet production in acute infection are also causes of thrombocytopenia in typhoid fever.

Here's something from the study group discussion, I decided to club it with this post, instead of making two separate posts:

What cancer has enteric fever been linked to?

Gallbladder cancer has been linked to chronic carriage of typhoid bacilli in the gall bladder.

Speaking of typhoid, the infamous maid Mary Mellon was found to be a chronic asymptomatic carrier of typhoid and transmitted the infection to people consuming the food she handled. This is a trivia question. What punishment was she given for this - was she sentenced to death, barred from work, or jailed?

Mary Mellon was first barred from work and jailed and then released on affidavit that she wouldn't handle food again, she changed her name to Mary Brown and started working in kitchens again, and was then quarantined for life.

Another trivia question - What did she die from?

Not typhoid, because she was an asymptomatic carrier and remained as such. She died of pneumonia and had a stroke prior to death. Typhoid bacilli were found in her gall bladder in autopsy.

What cells are typhoid bacilli suspected to inhabit in the chronic carrier state?

Macrophages are the prime suspects to harbor the typhoid bacilli in chronic carriers.

The bacteria hides inside less-aggressive macrophages associated with anti-inflammation, such as wound healing. The bacteria can then modify the macrophages into becoming more suitable for its growth, creating healthy carriers similar to Typhoid Mary.

That's all!

Bad ass are the organisms which can survive and hide in our own immune system, like typhoid.

-IkaN

Related post: Study group discussion: Typhoid