In dark purple, a malaria parasite migrates through a mosquito cell Photo Credit: Wikimedia Commons

Mixed Hope for the First Malaria Vaccine

Malaria is a disease that killed over 400,000 people and infected 212 million in 2015 alone, and until recently, there were no vaccines available  However, three African countries with substantial malaria presence, Ghana, Kenya, and Malawi, were recently selected for a pilot program of a promising malaria vaccine. Produced by global pharmaceutical leader GlaxoSmithKline (GSK), and distributed in collaboration with the Bill and Melinda Gates Foundation and global health non-profit PATH, the RTS,S/AS01, or Mosquirix, vaccine will be administered to more than 300,000 children beginning in 2018.

What is Malaria?

Malaria has been a major human health issue as long as other infectious diseases like polio and smallpox; descriptions of malaria cases in literature date as far back as 2700 BC. The slow discovery and development of malaria vaccines is because malaria is caused by a single-celled parasite, unlike most other infectious diseases, like polio and smallpox, which are caused by bacteria or viruses, . This is reinforced by the fact that there are currently no human vaccines licensed for commercial use against any parasite.

Parasites are microscopic organisms that live in or on a host, and whose growth comes at the expense of the host. They differ from viruses and bacteria in that the are comprised of eukaryotic cells, the same cell type as human cells. This means that they are far more complex physically and comprised of a larger variety of proteins, which can make recognition and full elimination by the immune system more difficult. Since they are able to replicate exponentially while living in a host, even a single parasitic organism escaping the body’s defense measures can produce tens of thousands of copies.

The complex lifecycle of malaria Photo Credit: CDC

Parasites also have a much more complicated life cycle that makes them harder to control via typical vaccine methodology. Malaria requires two hosts for its full life cycle, a human and a female Anopheles mosquito. Malaria can only be contracted when an individual is bit by a mosquito that has previously fed on the blood of an infected person. During its time in human body, maturation of the parasite occurs in multiple locations, the liver and then blood cells, further complicating its destruction by the immune system and targeting by vaccines. When inside the blood cells, malaria eventually causes these cells to rupture, causing symptom presentation. This is also when malaria can be taken up by a mosquito in a blood meal and spread to others. Malaria symptoms can vary widely, with severity of disease ranging from uncomplicated, with fever, chills, headache, and vomiting, to severe, with impaired consciousness, low blood counts, kidney failure, and even death. Thankfully, malaria is typically a curable disease as long as it is diagnosed and treated properly.  

 

How the vaccine works

The Mosquirix vaccine attempts to prevent the parasite from entering the liver cells. This prevents its necessary maturity in the liver and passage into the blood cells, where it causes disease symptoms and can be transmitted to other humans via mosquito. Mosquirix relies on a common vaccine mechanism; it helps the body’s own immune system develop a defense against malaria before it is exposed to the actual parasite. It accomplishes this by presenting the body with a portion of a protein commonly found on the surface of malaria cells. The body produces antibodies that recognize this protein, bind to it, and identify the attached cell as a dangerous, foreign invader that should be removed by the immune system.

Children were selected for previous Mosquirix clinical testing and this first public application since children and pregnant women account for most malaria cases. Children are also typically more susceptible to the disease’s symptoms, since their immune systems may still be developing, and it is physically more taxing for them to fight off a serious disease like malaria.  Young children also have reduced understanding for the importance of current malaria prevention measures and how best to utilize them.

The initial results have been promising; with a 39% reduction in malaria cases of children aged 5-17 months. Global health organizations, like the Centers for Disease Control (CDC) and the World Health Organization (WHO), are hopeful that this will slow the spread of the disease.

Herein lies the mixed promise of Mosquirix: it is only somewhat effective and its efficacy depends on a four-part, two-year course of administration, but it is the only malaria vaccine to clear the last phase of clinical trials showing safety and some promise. Even the partial effectiveness of Mosquirix is far from perfect, since it was dependent on receiving the fourth and final dose and similar protection was not observed in infants.

Thankfully, it’s believed that even a partial prevention in children will result in a several times larger reduction in disease spread. Mosquirix may also act as a partial stopgap before better vaccines can come to market. Several very promising, more effective malaria vaccines are entering the early stages of clinical trials. Global health experts see Mosquirix as another tool in the arsenal of methods already utilized to help control malaria, including treated bed nets, indoor insecticide spraying, and anti-malarial drugs for those suffering from the disease.

Insecticide treated bed nets used to prevent mosquito bites and minimize the associated malaria risk Photo Credit: Wikimedia Commons

Hindered by Geography and Economics

Identifying new vaccines is is a years-long process costing millions of dollars, and malaria importance and funding is low on the medical totem pole. Being a mosquito borne illness, malaria’s prevalence is concentrated near the equator, primarily affecting the developing countries found in this region; Africa accounts for around 89% of the deaths associated with the disease. This means the countries where malaria is most prevalent are least equipped economically to deal with the massive public health efforts required to contain, much less eradicate it.

The handful of cases and nonexistent outbreaks present in developed countries means that funding priority and charitable giving for malaria research and prevention are both low. Yet, more than half of the world’s population live in the areas most susceptible to malaria, so the potential for the situation to become much more dire is ever present. However, the sooner a larger portion of the population becomes immune to malaria, the sooner herd immunity, a significant turning point in public health, is established.

Infographic on the concept of herd immunity Photo Credit: Wikimedia Commons

Herd immunity is when a large enough percentage of the population has been vaccinated, driving prevalence of a disease so low that it removes the possibility that individuals without immunity to that disease will contract and further spread it. It is a form of protection for individuals whose vaccine may not mount a full immune defense or those who cannot get a vaccine for health reasons. Just like vaccinating a targeted group of children with Mosquirix in three countries is expected to yield a magnified number of cases prevented, broad scale implementation of an effective malaria vaccine would have significant global impact. Combined with the already high human toll, this makes a strong case for making malaria more of a global health priority.

More information on Malaria from the Centers for Disease Control, World Health Organization, and the Malaria Vaccine Initiative.  

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