Malaria: Challenges and proposed solutions

Malaria is a leading killer in many parts of the world. The statistics on the disease are pretty scary. About 90 countries on the planet struggle with the disease, these are mostly tropical, underdeveloped nations spread across Africa, Asia and South America.

Africa undoutedly is the biggest victim and it is estimated that malaria kills a child on the continent every 30 minutes (Yeah that's pretty scary!) Some of the kids who do survive the disease unfortunately suffer from lasting mental impairment. In fact malaria makes the mortality figures of HIV/AIDS look insignificant. Most people would agree that this monster must be stopped at all costs (Yours truly included. I have taken a few blows from the disease myself over the years).

Malaria was successfully eradicated in the developed world in the 20th century using combinations of highly effective insecticides to kill off the mosquitoes and antimalarial drugs to tackle the parasite causing the disease inside the human body.

The World Health Organisation (WHO) started the Roll Back Malaria (RBM) program as a global initiative to eradicate malaria globally but the program has not been as successful as was hoped. There are a couple of reasons for the program not yielding the desired outcomes despite the enormous funds committed to the program on an annual basis. We shall explore some of these reasons and also examine some modern research findings in the battle against malaria.

It turns out that the parasite (plasmodium) and the vector (mosquito) really do enjoy hot climates, and they do not exactly fare very well in much colder parts of the world. This factor is really key to understading why the RBM program has not been very successful in Africa especially. This of course is far from being the only factor.

Other important factors include >> poor hygiene standards, inadequate health coverage especially in the rural areas, growing resistance to insecticides by the mosquitoes as well the growing resistance of the parasite to the antimalarial drugs that were once so effective in Europe and North America.

The statistics still tell a sad story despite the efforts of transnational organisations, supplying medical aids to the affected regions. I am obliged to think that a broader approach to winning the war against malaria should be employed going forward. Also the peculiarities of each country where malaria is endemic must be considered in our malaria eradication efforts. For starters, we could spend more resources on prevention measures like better education of the people in those affected areas rather than dumping millions of dollars worth of drugs into the regions and hoping for the best.

The statistics clearly show that malaria is particularly troublesome amongst the poor and uneducated folks living in largely unsanitary areas. Sometimes funds are released to government officials to provide some much needed basic instruments like mosquito nets and these funds are misappropriated. There have even been cases of corrupt individuals selling antimalarial drugs received from donor agencies around the world. The problems are numerous.

The female Anopheles mosquito

We know that the plasmodium parasite responsible for malaria is carried by the female Anopheles mosquito (the main host) and transmitted to humans when the mosquito attempts to take a sip of our blood for the primary purpose of nourishing the mosquito's eggs. (Turns out the mosquito has no malacious intent after all). All female Anopheles mosquitoes are not created equal. There are in fact hundreds of species of these bad ladies floating around. They do differ in their target unsuspecting blood donors too : some of them would rather take a blood meal from cattle while others feel human blood is the best thing sinced sliced bread or whatever the equivalent of sliced bread is in the world of mosquitoes.

This might explain some the disparities in disease prevalence even amongst the tropical countries where malaria is endemic. It has been observed that the main female Anopheles mosquito species in India has a preference for cattle and it has been suggested that cattle might perhaps be employed as pawns to divert mosquitoes away from human settlements.

A close look at Plasmodium

Plasmodium is the real culprit here, but which one exactly? There are four main speicies of the plamodium parasite that infect humans, namely : Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae It would seem that mother nature does not really fancy simplicity. By far the biggest offender is Plasmodium falciparum. Plasmodium falciparum accounts for most of the recored deaths from malaria. Let us briefly examine the life cycle of a plasmodium parasite.

Figure 1. The life cycle of plasmodium parasite. credit :: Biomedical Central

Nature and complexity once again. The life cycle of Plasmodium consists of two seperate cycles : the sexual cycle and the asexual cycle.

The sexual cycle (also known as sexual recombination) takes place within the female Anopheles mosquito while the asexual cycle takes place in the body of a person infected with the parasite. Scientists think that infected humans simply serve as factories to produce more of the parasite and to infect more mosquitoes. (I do feel a little hurt by that fact).

An infected mosquito houses the parasite in a form known as sporozoites in its salivary gland. The sporozoites easily gain entry into the circulation of a human when the mosquito takes a sip of blood. These sporozoites usually make their way to the liver within 30 minutes and infect liver parenchymal cells, forming schizonts. Eventually the liver cells rupture and release loads of the parasite (in a form known as merozoites into the blood stream to commence the erythrocytic cycle. Recall that red blood cells (RBCs) are known as erythrocytes. These merozoites then bind to some receptors on the surface RBCs and gain entry into the RBCs.

The merozoites present within the RBCs form motile intracellular parasites known as trophozoites which multiply rapidly using haemoglobin as their source of amino acids. The parasite at this stage inserts some of its proteins into the membranes of RBCs allowing metabolic wastes to be moved out of the cell. It is worth noting that the haem in haemoglobin would normally be toxic to the parasite, but of course there is a mechanism to detoxify haem (some antimalarial drugs like chloroquine, quinine, lumefantrine interfere with the detoxification of haem).

Trophozoites develop into schizonts and just like what happened to the liver cells, the RBCs rupture and release millions of merozoites, most of which infect more RBCs and start the erythrocytic cycle over again. As you would have rightly guessed, this continual invasion of red blood cells by Plasmodium is pretty disastrous and so many kids suffering from malaria succumb to anaemia. Also the red blood cells become sticky and can not freely flow through blood vessels, depriving vital organs of adequate blood supply.

Some merozoites develop into male and female gametocytes which are crucial in the sexual cycle to form zygotes once taken up by the female Anopheles mosquitoes and later developing into oocysts (or sporocysts). The oocyst undergoes multiplication within the gut of the mosquito leading to the release of sporozoites into the salivary gland of the mosquito, waiting to start another asexual cycle in humans who get bitten by the infected mosquito.

Some preventive approaches

Having just examined the complexity involved in the malaria puzzle, it is clear that a multi-faceted approach to dealing with both the vector and the parasite would need to be adopted. Prevention is usually better and cheaper than cure so we might have to concentrate more on ensuring people do not get infected with malaria in the first place. We shall explore some preventive measures below.

• Sanitation : This is certainly one of the cheapest ways -- at least in the long run -- to keep malaria infection and mortality rates low. By simply limiting the breeding grounds of the mosquitoes to areas far from human habitation, we essentially minimize the risk of mosquito bites and malaria prevalence in those areas. One of the major issues in Africa, especially in less-developed areas is a clear lack of proper drainage systems to keep water flowing along when it rains, much to the delight of mosquitoes which use the availability of stagnant water to complete their life cycle.

• Mass provision and adoption of mosquito nets : The introduction of mosquito nets has been shown to decrease malaria prevalence and mortality rates in parts where malaria is endemic.

• Mosquitio repellent lotions : Some companies are producing mosquito-repellent lotions which scramble the mosquito's ability to sense their human targets thereby decreasing the sheer number of mosquito bites.

Some pharmacological approaches

We have made giant strides in public health. We have been able to eradicate polio, small pox and other infectious diseases from most parts of the world using a special weapon : Vaccine

Developing an effective vaccine to solve the malaria problem once and for all has unfortunately proved ellusive thus far. The difficulty in producing an effective vaccine is primarily due to the complex life cycle of the Plasmodium parasite. Refer to figure 1 above. Drugs have been our major partners in combating malaria, although the parasite has evolved several defensive mechanisms over the years, making alot of the antimalarial drugs all but useless in some parts of the world.

Drugs such as chloroquine, quinine and dapsone have seen their potencies wane significantly due to resistance. One mechanism of resistance by the parasite is to increase efflux (pumping out) of the drugs, thereby preventing them from reaching their intracellular targets within the parasite. It is worth noting that resistance usually develops much faster when these drugs are used alone. Nowadays a multi-drug approach to treatment is widely used. Some of the more popular combinations are Artemether and Lumenfantrine, Pyrimethamine and Sulfadoxine, Atavoquone and Proguanile

Conclusion

• Malaria remains a major killer around the globe despite our efforts to eradicate the disease globally.

• Millions of people, mostly children die from malaria each year in parts of Africa, Asia and South America.

• An effective vaccine against malaria has not made it past clinical trials unto the market mainly due to the complex life cycle of the parasite.

• Mosquitoes are rapidly developing resistance to the commonly used insecticides and Plasmodium is developing resistance to alot of the commonly used antimalarials.

• Research into new antimalarial drugs and an effective vaccine is on-going but the process is painfully slow.

• Preventing the disease (through proper sanitation, better nutrition, use of mosquito nets and even mosquito-repellent lotions) remains the best option.

We will explore some of the new findings from malaria research in the future. Stay tuned.