Secret Benefits to Thalassemia, Round 2: Email Inquiry

I get emails from people asking for me to diagnose them based on images of maggots that they found on their skin, a peculiar rash they've had for years, or something they found in their poop. I have to say, I love these emails. If anyone is worried about the NSA spying on their email activity, it should probably be me, because my inbox is full of stuff that could be considered private medical information, and I am not an MD.

But sometimes I get legitimate questions, like this one that I featured on my blog forever ago (don't worry, I always ask if they mind if I post their questions). Recently, I got a really interesting and smart question from an anonymous reader. The email said:

Dear Doc,  is there an immunity of reduction of Ebola with people who have beta-thalassemia? Or is it just the opposite, a more susceptible case for those with beta-thalassemia?

If you don't remember what beta-thalassemia is, or why it might be "beneficial" (I say this loosely, as it's not necessarily a good thing to have), feel free to brush up by reading this old post about it and it's relationship with malaria.

Image from the American Society of Hematology

To recap, thalassemia is a disease associated with globin gene mutations (both α- and β-globin genes can be mutated, yet α-globin mutations are most common). Since your α- or β-globin gene is recessively mutated if you have active Thalassemia, your red blood cells develop into malformed, or "sickled", cells, thus inhibiting their affinity to bind and transport oxygen (see image above for a great example). This lower affinity can cause extreme cases of anemia. In major cases, treatments such as chronic blood transfusion therapy, splenectomy, transplantation and iron supplementation are used. Thalassemia would make a great potential candidate for genome editing therapies that are still in the research stage (yes, I know that article is about hemophilia, but it's a good example).

So, why is this anonymous question a great one? Simply put, it doesn't really have an answer. There isn't any research being done to look into populations that aren't as affected by Ebola right now, as far as my searches have illustrated. This might be because most research that's being done is to either understand the physiology of the virus, to identify all possible vectors (yes, most evidence point to bats as the vector, but I'm still not convinced), or to come up with therapies/treatments and vaccines.

But the submitted question addresses an important point: thalassemia, specifically β-thalassemia is really prevalent in Nigeria (25% of the population are carriers for Sickle Cell Disease, while another 25% is hemizygous for the G6PD gene), and other parts of Africa. So, why isn't this being looked into? I can't answer that. I don't know. All I can say is maybe it isn't yet. I'm sure now that Ebola is in the spotlight, there will be a new emphasis on funding down the line for exploratory research.

In my fervent literature search to find an answer for the anonymous email, I did find that similar research has been done to look at the effects of thalassemia on hemorrhagic fevers (specifically Dengue Hemorrhagic Fever), mostly in Thailand and Southeast Asian countries. It turns out that patients with thalassemia don't necessarily have any higher risk, or even less of a risk (as seen with malaria), of getting hemorrhagic fevers, as my anonymous email inquiry asked. But, they do present differently, meaning their symptoms may seem different than infected people without thalassemia. Most normal (non-thalassemia) patients show signs of hemoconcentration (or an increase of solids in the blood), but patients with thalassemia present anemia (which is the opposite). This is the main symptom that presents differently, but its a really important one. Other symptoms also reference changes in AST and ALT levels, which illustrate the concentration of enzyme in the liver, heart and muscle cells, and can indicate liver function.

Hemoconcentration is really important during the diagnostic phase, and to track how the infection is progressing. So, if, instead, your patient is presenting with the exact opposite, it might lead to misdiagnosis. Also, if a patient with thalassemia, who is also infected with dengue hemorrhagic fever, is showing anemia, it needs to be watched. The three papers I linked to above talk about new suggested courses of action for patients with thalassemia, like frequent blood transfusions.

So, anonymous emailer, the answer is probably not. The biggest risk that thalassemia would give you is misrepresenting symptoms, which can lead to improper care. Yes, that can be really dangerous, especially with hemorrhagic fevers. But, luckily, if you have a high fever and other viral (standard) infection symptoms, your doctor will usually run other diagnostic tests (like an ELISA or PCR, etc.). That's why they always ask you questions about where you've been, what you've been in contact with, and other patient history questions.

This is definitely research that should be done, even if it starts with a retroactive epidemiology study.

Thanks for your question!

If any of you have other questions, feel free to email me at microscopic.blog@gmail.com!

Secret Benefits of Thalassemia

I didn’t think it would happen, but I actually had a request for my next blog entry!

I can’t exactly tie this one into any overly religious, candy-laden holiday, but it happens to be one of my more favored parasites that are often mistaken for a virus… any guesses?

Malaria!

I’m not sure why, but I’ve heard many people refer to malaria as a viral infection, when it is actually a hemolytic parasite. Maybe it’s the fact that early malaria was associated with the air content of the prevalent environments (often murky or musty), which gave rise to the naming of malaria-- meaning “bad air”. This can be drawn to some viruses and their airborne, or aerosolized, transmission technique. Yet, we (as in…scientists, duh.) quickly discovered that malarial transmission was not through aerosolization of a virus, or from any direct contact. The only other similarity that the parasite genus Plasmodium has to common viral infections is the series of flu-like symptoms, such as fever and chills. In initial diagnosis trials, malaria was often misdiagnosed as an ongoing influenza with rhythmic symptom cycles. Seasonal influenza causes anywhere between 250,000 and 500,000 deaths annually, whereas Malaria causes approximately 1 million deaths annually. Needless to say, there are major differences.

So, now that we know Malaria is, in fact, a parasite, the details of its lifecycle can help answer many further questions (also, one specifically that has been requested).

Malaria is actually, roughly, an umbrella term that can be used to describe the disease in humans that is caused by four parasites: Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale.

Plasmodium ovale is regionally specific to West/sub-Saharan Africa, with a much lower prevalence (~5%) in places like the Philippines, Papua New Guinea and Cambodia. P. ovale is very specific in region and may seem to have a stippled appearance. P. ovale is also the only form of malaria that is fibronated.

Plasmodium ovale: trophozoite after "ring stage"

Plasmodium vivax is the most common form of malaria that causes reoccurring symptoms, or is tertiant in its cycle. P. vivax is found widely spread over Asia, Latin America and some parts of African, and causes debilitating, reoccurring symptoms that are mostly non-fatal. It can also cause splenomegaly, or enlargement of the spleen, which is highly fatal.

Plasmodium vivax: immature schizonts in human blood smear

Plasmodium malariae is very similar to P. ovale, in that it causes “milder”, or less fatal symptoms in very specific areas. P. malariae is thought to be the oldest form of Malaria causing parasites, and is relatively non-commensal. P. malariae undergoes a quartant cycle, replicating every 72 hours. Sometimes, the meroxoites form in a rosette fashion. My parasitology professor always used to say “if you have to choose which type of malaria to be infected with, choose Plasmodium malariae.”

…right. It’s so convenient how those Anopheles are giving you a choice, these days.

 Plasmodium malariae: trophozoite illustrating the "ring stage" in human blood smear

Now, my favorite, Plasmodium falciparum is the most deadly of the four. To illustrate its fatal nature, it is shaped like a banana. Yea, a deadly banana. Aren’t you scared?

P. falciparum is often termed as the “newest” of the four because it is so dangerous and deadly. In recent years, it has accounted for more than 95% of all malarial infections, and over 90% of all the deaths caused by malarial infections. P. falciparum has the unique ability to infect one cell with multiple merozoites. Essentially, P. falciparum is like a sniper version of malaria: it gets the job done. Like I said, deadly banana.

Plasmodium falciparum: banana shaped gametocytes in human blood smear

The lifecycle of malaria occurs in two parts: the sexual cycle that occurs within the vector’s gut, and the asexual cycle that occurs within the human host’s tissues and circulatory system.

Within the human, the Plasmodium sporozoites infect the liver cells and release merozoites. These merozoites infect red blood cells, replicate, and cause the red blood cells to literally rupture and explode in order to infect other red blood cells nearby. Eventually, this causes chaos in your liver tissues and circulatory system. 

Credit: NIAID

Yet, interestingly enough, if you already have Thalassemia, you have the added bonus of an evolutionary “immunity” to malaria diseases. Thalassemia is a disease associated with globin gene mutations (both α- and β-globin genes can be mutated, yet α-globin mutations are most common). Since your α- or β-globin gene is recessively mutated if you have active Thalassemia, your red blood cells develop into malformed, or sickled, cells, thus inhibiting their affinity to bind and transport oxygen. This lower affinity can cause extreme cases of anemia. In major cases, treatments such as chronic blood transfusion therapy, splenectomy, transplantation and iron supplementation are used.

Many immunologists believe that this immunity to malaria diseases that is associated with Thalassemia is a result of Darwinian genetics. A good example of this is Africa, which has some of the highest rates of malaria in the world, as well as a Thalassemia diagnosis of approximately 40% of the entire population. Those with the recessive mutation survive malaria more effectively, and have a higher likelihood of handing such mutations down through to following generations.

On a semi-related note, a friend turned me on to this Animal Planet show called Monsters Inside Me, which is all about parasites and other fun things! Here is a short video about malaria with some neat animations of the active infection:








I’m sure I will go into more specifics about malaria in future posts, but I wanted to address the question and request that I received in a timely manner. With that being said, if you have a topic that you are dying to read about, please feel free to send me an email, and I’ll get to it!