Demythifying malaria: what exactly is it?

For people who live in a developed country like Australia, malaria seems to be a disease of the past. Many may find it difficult to relate to this “forgotten disease”, knowing very little about it. The reality is that malaria is still a very significant disease in the world despite the lack of attention of the media. It is one of the “big three” diseases of the world with the other two being HIV and tuberculosis.1 The sad thing is that when it comes to malaria, even the World Health Organisation (WHO) can be wrong, underestimating the impact of malaria by nearly 50%.1 In order to have any chance to eradicate this disease in the future, it is imperative to first raise the public awareness of this “scourge of the third world”. So let’s have a look at what exactly malaria is.

What is malaria

Malaria is a parasitic infectious disease usually transmitted by female Anopheles mosquitoes.2 Although it is no longer considered a threat in developed countries such as the United States and Australia, it is still one of the leading cause of mortality and morbidity in the developing world especially sub-Saharan Africa.2 This disparity not only exists between developed and developing nations, it also separates urban dwellers from their rural counterparts who tend to be at higher risk of contracting malaria. The reasons have been suggested to be multifaceted which include close proximity to the habitats of Anopheles mosquitos such as ponds or waterways, lack of trained health care providers, poor education and lack of proper sanitation and clean water.3

The life cycle of malaria

Malaria in humans is caused by the parasite Plasmodium which has a complicated life cycle involving both humans and mosquito hosts.2 Its life cycle has one sexual and two asexual phases. The cycle begins when an infected mosquito bites a human host and injects a large number of infectious agents known as sporozoites into the host’s bloodstream. Within three quarters of an hour, sporozoites can reach the host’s liver and begin to infect and replicate asexually within human hepatocytes.4 This stage is known as hepatic schizogony which typically lasts less than a week.4

nrmicro3111-f1
The Life Cycle of Malaria (Nature Reviews Microbiology 11, 701–712 (2013) doi:10.1038/nrmicro3111)

At the end of the replication, each sporozoite can form a cellular form known as the schizont which contains a large number of tiny motile bodies called merozoites.4 Once the mature schizonts rupture, up to 30,000 merozoites can be released into the bloodstream.2 Merozoites then invade red blood cells and self-replicate via a process known erythrocytic schizogony.4 During this process, merozoites mature into trophozoites then schizonts, which release a new generation of merozoites into the blood to infect more red blood cells.2 This cycle of cell invasion and self-replication usually repeats many times. As the result, the number of parasites within the bloodstream grows rapidly. It is also during this phase of the malaria life cycle, typical malarial symptoms such as fever, muscle pain, anaemia, vomiting and headache become apparent due to the activation of the human host’s immune response.4

At the height of the infestation, a fraction of the merozoites will differentially develop into the sexual form of gametocytes which infect mosquitoes when the host is bitten.2 The male and female gametes complete the life cycle of the parasite by maturing into sporozoites within the mosquito, which then continues another cycle of infection when it has another blood meal.2

People who is at risk

The strength of the immune system is thought to play an important role in the severity of malaria. This is evident as people who had severe malaria episodes in their early years typically acquire a degree of immunity against malaria.5 Even if they contract another episode of malaria, they either demonstrate no symptoms or only have mild episodes.5 This is why malaria usually affects children under the age of five, pregnant women and patients with comprised immune systems.1

Another significant population of malaria risk is the returned travellers. People from less-malaria-prone regions who travel to tropical or sub-tropical malaria endemic area are often the source of imported malaria.4 The fatality rate of European travellers who contracted malaria while overseas can be as high as 3 percent.4

Types of malaria and clinical manifestation

Clinically five plasmodium species have been identified so far to be responsible for human malaria which are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi.6 The first two species are responsible for the many life-threatening complications with Plasmodium falciparum being the deadliest, linked to the majority of severe malaria cases.2 Even though Plasmodium vivax appears to be less significant, it is still a major player in Asia and South America causing nearly 400 million new malaria cases each year.6

Other malaria species tend to only bring mild to no symptoms when infect a human host. This is possibly due to their more “lenient nature”. For example, a portion of Plasmodium ovale may remain dormant within hepatocytes as hypnozoites for up to five years with no symptoms to the host.4

Clinical malaria manifestation can be either uncomplicated with nonspecific flu-like symptoms or severe with rapid and fatal complications affecting central nervous system, pulmonary system, renal system and the liver.4

Treatment Options

Several drugs have been used so far to treat malaria. Drug resistance has posted a major challenge for both scientists and pharmaceutical companies.7 For example, Chloroquine used to be highly effective again malaria until the 1950s when Chloroquine-resistant Plasmodium falciparum came into the scene.8 Lack of preparation was blamed for the failure of this drug.7

The current treatment option is the artemisinin-based combination therapies.7 It has been a success so far. However, artemisinin-resistant parasites have already emerged in some parts of world, which calls for renewed effort in the development of antimalarial drugs.7

Conclusion

The information presented in this article has only just scratched the surface. Malaria is no doubt a complex disease and much more effort is needed in understanding its drug-resistant mechanism, pathogenesis and other sociological factors contributing to the perpetuation of the disease.

Bibliography

1.    Shetty P. The numbers game. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved; 2012 Apr 25;484(7395):S14–5.
2.    Gazzinelli RT, Kalantari P, Fitzgerald KA, Golenbock DT. Innate sensing of malaria parasites. Nat Rev Immunol. 2014 Nov;14(11):744–57.
3.    Noble MD, Austin KF. Rural Disadvantage and Malaria in Less‐Developed Nations: A Cross‐National Investigation of a Neglected Disease. Rural Sociology. 2016 Mar 1;81(1):99–134.
4.    Bartoloni A, Zammarchi L. Clinical aspects of uncomplicated and severe malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012026.
5.    Laishram DD, Sutton PL, Nanda N, Sharma VL, Sobti RC, Carlton JM, et al. The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar J. BioMed Central; 2012 Jan 31;11(1):29.
6.    Geleta G, Ketema T. Severe Malaria Associated with Plasmodium falciparum and P. vivax among Children in Pawe Hospital, Northwest Ethiopia. Malaria Research and Treatment. Hindawi Publishing Corporation; 2016;2016:7.
7.    Greenwood B. Treatment of Malaria — A Continuing Challenge. The New England journal of medicine. Massachusetts Medical Society; 2014 Jul 31;371(5):474–5.
8.    Wellems TE, Plowe CV. Chloroquine-Resistant Malaria. J Infect Dis. Oxford University Press; 2001 Sep 15;184(6):770–6.

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