Inborn Immunity to Malaria: Sickle-Cell Anemia

Nature has devised a fascinating defense against malaria. It involves altering the very shape of the body's red blood cells (RBC). Sickle cell anemia is a disorder that changes the shape of RBC, as shown in the picture below, due to a mutation in the genetic code that is responsible for the formation of the beta-subunit portion of a hemoglobin molecule. As a result, the RBC will take a rigid sickled-shape. This leads to two important consequences: 1) malaria immunity and 2) organ damage and anemia symptoms.

Normal RBC compared with a sickle shaped one.

A mutation in the genetic code for hemoglobin causes sickle-cell anemia.
The mutation codes for a valine rather than a glutamic acid to be produced.

The Global Distribution of Anopheles Mosquito

The Anopheles mosquito is spread across the globe, and poses the threat of spreading the malaria vector worldwide. Collecting data about the mosquito type in a region provides key information about controlling populations and vector transmission.

From Kiszewksi et al., 2004. American Journal of Tropical Medicine and Hygiene 70(5):486–498

Check out the World Health Organization's world malaria report here.

Cerebral Malaria: When it Goes Too Far

Malaria is diagnosed by looking for parasites in a drop of blood smeared on a slide under a microscope.

When I woke up in the middle of the night and proceeded to throw up every thirty minutes on the the minute, developing a high-grade fever and severe dehydration, it took no more than a finger prick and a look at the blood smear under a microscope to see the parasites in my blood. The diagnosis ranges from 1-5, 5 being the most severe and meaning that there were 5 parasites seen on the slide from a single drop of blood. Within 5 hours of showing symptoms, I had a blood smear, revealing level five. Immediately, I was given an IV to administer high dose anti-malaria drugs, anti-nausea, fever reducers and pain medicine. I was in good hands, and recovered fully in less than a week.

Rise in Immunity Spurs International Concern

"Malaria is still a devastating disease, with nearly 250 million cases and more than one million deaths every year. Mosquitoes have developed resistance to existing insecticides and there is evidence of emerging resistance by the parasite to the drugs used to treat the disease.”-Professor Steve Ward, Deputy Director, of LSTM reports

RTS,S Has a Fighting Chance to Become Malaria Vaccine

Underlying Factors

 Malaria is a complex disease, and therefore poses several challenges for the development of a vaccine. It is important to note that the most prevalent species of the parasite (there are four known to cause malaria in humans), Plasmodium falciparum is the main focus of vaccine efforts at this point. The malaria parasite is a protozoan, which is more biologically complex than bacteria or viruses. It also creates a complicated array of potential vaccine targets. The three most promising vaccines and their modes of action are detailed below, including an analysis of which of the three is has the highest potential to become a widely used vaccine to prevent malaria from P. falciparum. A malaria vaccine would reduce the number of severe malaria cases and deaths, and by ensuring preventability would be an important step towards eradication of the disease. There are currently three vaccines in various stages of development, and, based on efficacy testing and other supporting evidence, it has been determined that RTS,S is the vaccine that will succeed over other candidates.

Even with vaccines that have shown efficacy, there are species that still pose a menacing line of defense against a potential cure.

NPR reports on Obama's mention of progress on the issue. Read the story here.

Staying Safe While in Danger

Before traveling to Africa for the first time, my parents were very concerned about the risks of contracting malaria and wanted to ensure our family’s safety. We asked for advice about how to prevent and treat malaria, and now I'm extending my recommendations, after years of travel experience. 

1.  Prevent mosquito bites between dusk and dawn. This is when the mosquitoes that carry malaria bite. Stay inside, wear bug repellent (DEET), and sleep under a mosquito net.
2. Take prophylactics: Doxycycline has fewer side effects than Malarone. Make sure to take the full course of the medication, starting before you travel and continuing well after your return.
3. Take medicine with you. Depending on where you are traveling, it may be in short supply. Quinine and Coartem are pretty common and will be your best bets.

I've spent time in high-risk areas where malaria is extremely rampant. So much so, in fact, that I even contracted the disease myself, despite taking certain precautions. As I learned, hyper-attention to detail makes a huge difference. I got malaria when I was volunteering for a month at the Chitokiloki hospital in rural Zambia. This is arguably the best place to get sick, as there is readily available medicine as well as medical staff who treat the disease every day. The hospital is overflowing with malaria patients during the rainy season.

Amazingly, malaria is totally curable. You have to get to medication early, however, and this is one of the major challenges in rural areas, as it is modes of transportation are slow and unreliable.

What is malaria?

Malaria is a disease that of the blood that is treatable but fatal if left untreated. Close to half the world's population is at risk of contracting the disease. There are many different malaria parasites. The most common type is called plasmodium falciparum, and it is transmitted by the female Anopheles mosquito. The mechanism of action is a parasite that requires both human and mosquito hosts to complete its life cycle. This life cycle begins when an infected mosquito bites a person, transferring the Plasmodium parasites, in the form of sporozoites, carried in the mosquito's saliva. Sporozoites then enter the human's liver cells. After a few days, the sporozoites become merozoites and penetrate the red blood cells (RBC). They then divide and, usually every 48 or 72 hours, break out of the cells, which lyses the RBC and allows some of the merozoites to infect other RBC and therefore spread throughout the body.

Not all of the merozoites infect more RBC, however. Some form gametocytes. These are critical, because they are picked up by the bite of an anopheles mosquito. The life cycle of the parasite is now continued inside of the mosquito. Gametocytes divide via meiosis to form the male and female gametes, which undergo fertilization. The zygote forms a cyst on the wall of the mosquito's gut and releases thousands of sporozoites. They migrate to the mosquito's salivary glands, ready to infect again.

Prevention a key component of combatting malaria. More to come on this topic.

Malaria deaths among children under five halved since turn of the century...

Let's keep the momentum going.

Malaria: A Huge Global Challenge. How will it be solved and how can you be involved?

 

Malaria is a very real threat to millions of people every day. One child dies per minute. The disease is completely treatable. Learn the details of the international issue.
Thousands of visitors are exposed to malaria risk factors each year. Learn how to stay safe!
Are you looking to learn about the cutting edge research currently underway to combat malaria and wondering how scientists aim to eradicate it? Vaccine development, policy programs and treatment campaigns are of critical importance.
Are you in pursuit of information regarding the toll malaria has taken in over the years, not just on those who contract the disease but on economies, governments, and the global community? Statistics and numbers can ignite conversations and provoke action.
3.2 billion individuals are at risk of malaria. In 2015, sub-Saharan Africa saw 90% of malaria deaths. Over the last 15 years, the rate of new malaria cases decreased by 37% globally, and have halved for children under the age of 5.