Why do people die of malaria?

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QUESTION:

Why is it that people die of malaria?

ANSWER:

The symptoms of malaria are caused by the malaria parasite reproducing inside the patient’s red blood cells and eventually destroying them. In this process, the malaria parasites also produce toxic waste chemicals and debris which build up in the patient’s blood stream. The body produces a strong immune response as a reaction to these toxic products and debris; most of the systemic symptoms associated with malaria, such as fever, aching muscles and joints and nausea, are related to this immune response. Infected red blood cells can also build up in internal organs, notably the spleen and the liver, causing them to swell.

Despite these nasty-sounding effects, most cases of malaria are relatively benign and don’t lead to death. However, in some cases, the manifestation of the disease can become more severe. Most commonly, this occurs when a patient is infected with Plasmodium falciparum, one of the four main kinds of malaria that infect humans, and by far the most severe. P. falciparum reproduces very rapidly in the human host, causing extremely high fever and a fast onset of symptoms. It also changes the structure of the red blood cells it infects, causing them to become “stuck” deep within tiny blood vessels and especially in major organs such as the brain, intestines, liver, heart and lungs. Stuck within these blood vessels, the infected red blood cells are effectively hidden from the immune system and are not cleared from the body via the spleen. This allows the malaria parasite’s reproduction to go unchecked, resulting in very high numbers of the parasite in the patient’s blood.

If left untreated, the build-up of infected red blood cells can result in severe anaemia, reduced local oxygen flow and the blocking of the immune reaction; the exact mechanisms are not fully understood. When these processes occur in the brain, the result is so-called “cerebral malaria”, characterised by impaired consciousness, and which can lead to convulsions, coma and death. Even if a patient recovers from the disease episode, they may be left with permanent neurological damage. Luckily, malarial comas are often rapidly reversed after treatment is administered, and in many cases, neurological damage is not permanent.

Cases of Malaria

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QUESTION:

What are reasons for the increasing number of cases of malaria?

ANSWER:

As I recently wrote in answer to another Q&A post, it is difficult to determine whether cases of malaria are indeed increasing or not. For one, a large number of cases are not reported every year, making accurate estimates difficult. Secondly, the world’s population is growing, and it is growing at the greatest rate in Africa, where the majority of malaria cases occur. As such, even if the proportion of people with malaria decreases over time, due to health initiatives such as distributing long-lasting insecticide treated bednets or free treatment, the total number of cases may still rise. Another problem we face in the fight against malaria is climate change: as the world’s patterns of rainfall and temperatures change, new areas become susceptible to malaria transmission, putting more people at risk. However, what is very encouraging is that deaths from malaria seem to be decreasing on a global scale. Malaria No More is an organisation dedicated to eliminating deaths from malaria by the year 2015; more information about their methods and some of their success stories can be found on their website.

What does malaria cause?

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QUESTION:

What does malaria cause?

ANSWER:

Malaria is a disease. It is caused by tiny single-celled parasites called Plasmodium, which are transmitted through the bite of infected Anopheles mosquitoes. There are many symptoms that occur as a result of infection with malaria, namely fever, chills, headaches and nausea, among others. Malaria can be a very serious disease, especially if not treated promptly, and so when spending time in malaria-infection areas (such as many areas of low to moderate elevation in the tropics and sub-tropics) precautions should be taken to avoid mosquito bites and thus infection. If a person finds themselves suffering from some of the above symptoms after being in a malaria transmission region, it is crucially important they get diagnosed straight away; if they do indeed have malaria, then they can be given treatment to facilitate a quick and safe recovery.

Helping Those Affected with Malaria in Africa

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QUESTION:

What are some things that might be done to make the situation better for those most affected with malaria in Africa?

ANSWER:

Currently, the emphasis on decreasing the burden of malaria on those most affected in Africa is based on a combination of prevention, education, research and treatment. In more detail:

Prevention: This is arguably one of the keys to sustainably reducing malaria burdens and even eliminating infections. Central to this goal has been the distribution of long-lasting insecticide treated bednets, which prevent people from being bitten by infected mosquitoes while they sleep at night. Unfortunately, some recent research has just been published which suggests that bednets might be contributing to insecticide resistance in mosquitoes, as well as increased rates of malaria in adults due to decreasing natural immunity. As such, it may be that more research is needed in order to determine the most effective and efficient ways of using bednets to prevent malaria infection, particularly in high-risk groups like young children and pregnant women.

Education: Through education, people living in at-risk areas for malaria transmission can learn about ways to prevent the disease, as well as what to do if they suspect they are infected. Similarly, education is important for travellers visiting malarial areas, so they know the best ways in which to avoid being infected.

Research: Understanding the distribution, factors affecting transmission and the development of new strategies for control and treatment is going to be crucial in the fight against malaria, and particularly in high-burden areas such as Africa. Similarly, scientists are busily looking for new compounds to treat malaria, as well as the ever-elusive malaria vaccine. If such a vaccine could be developed, it would be a huge step forward in the fight against malaria.

Treatment: Hand in hand with treatment comes diagnosis; if a person can have their infection easily, accurately and cheaply diagnosed, then they will be able to access effective treatment more rapidly, thus improving their chances of a swift recovery. As such, countries in Africa are working hard to provide health systems capable of local diagnosis and availability of treatment, so that people don’t have to travel far to have their infections cured.

Taken together, these four strategies are having some success even in the world’s poorest and most malaria-endemic regions, especially in decreasing the number of malaria deaths. Decreasing the overall number of infections will be yet a greater challenge, but one which the world, especially through commitment to the Millenium Development Goals, is dedicated to overcoming.

When was malaria first found in humans?

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QUESTION:

When was the first case of malaria in humans discovered? What did the name malaria originate from?

ANSWER:

Malaria has been known to humans for thousands of years; its earliest record is from around 2700 BCE in an ancient Chinese medical text. The ancient Greeks, Egyptians and Indians also recorded cases of malaria and described its symptoms. However, the parasite that causes malaria was first observed in a suffering patient in 1880; in 1897 mosquitoes were discovered to be the agents transmitting the parasite, finally allowing doctors to understand the true nature of the disease. The word “malaria” comes from “mala aria”, Italian for “bad air”, hinting at the long-held association between malaria and foul marshy regions with bad smelling air, which dates back as far as the ancient Romans. Indeed, the mosquitoes that spread malaria breed in stagnant water, so the Romans weren’t too far off!

Current Status of Malaria

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QUESTION:

What is the current status on malaria? And does P.knowlesi spp. pose a greater threat compared to the others? Does the number malaria cases increase every year globally? Is P. knowlesi spp. more dangerous than the others and why?

ANSWER:

I’ll answer your question about Plasmodium knowlesi first. So far, it is considered a relatively minor source of malaria in humans, as its natural host are macaque monkeys and so it is usually thought of as a “zoonotic” disease.Between 2000-2008, there were only been about 400 reported cases of P. knowlesi, all restricted to south-east Asia, and mainly Borneo. These figures are low compared to other forms of malaria, such as P. falciparum, which in Africa alone accounts for millions of cases a year, and close to a million fatalities. However, there are some causes for concern with regards to P. knowlesi.

First of all, it appears to be an emerging human infection; the first cases were traced back to the 1960s, with the number of cases increasing in recent years. While some of this increase is likely the result of higher accuracy diagnosis and awareness about malaria, it is also hypothesised that the increasing population density in forested areas of south-east Asia may also be leading to greater numbers of people being exposed to this parasite. Secondly, although easily treated with anti-malarial drugs, the life cycle of P. knowlesi is such that it reproduces very rapidly in the human host, causing cycles of fever every 24 hours (a so-called “quotidian fever”). This means that the infection can progress rapidly, becoming severe in a matter of days, and therefore requiring prompt treatment. Finally, although locally restricted to south-east Asia, P. knowlesi has become the dominant form of malaria in some of these areas, notably Sarawak. As such, although currently not a major source of malaria in the global human population, it is locally important to public health and moreover, more research is needed to determine why the number of cases has been on the rise.

As for your questions about the status of malaria globally, the number of cases annually is estimated to be around 250 million. The vast majority of these are in Africa. Over 700,000 people, mainly children under five, die from malaria each year. As for whether the number of cases is increasing or decreasing, this is hard to determine. For one, a large number of cases are not reported every year, making accurate estimates difficult. Secondly, the world’s population is growing, and it is growing at the greatest rate in Africa, where the majority of malaria cases occur. As such, even if the proportion of people with malaria decreases over time, due to health initiatives such as distributing long-lasting insecticide treated bednets or free treatment, the total number of cases may still rise. Another problem we face in the fight against malaria is climate change: as the world’s patterns of rainfall and temperatures change, new areas become susceptible to malaria transmission, putting more people at risk. However, what is very encouraging is that deaths from malaria seem to be decreasing on a global scale.

Malaria No More is an organisation dedicated to eliminating deaths from malaria by the year 2015; more information about their methods and some of their success stories can be found on the Malaria No More website.

Malaria After Blood Transfusion

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QUESTION:

How many days does it take to become symptomatic after a blood transfusion of malaria infected blood to patient?

ANSWER:

This depends on the strain and burden of malaria parasites in the blood being transfused. Onset of malaria symptoms can be very rapid if infected red blood cells begin to rupture immediately, say within 24-48 hours, or conversely symptoms can be very delayed (days/weeks/months) if only a few parasites are transfused. Depending on strain, the malaria parasites may need to cycle through the liver to mature before they infect the red cells (such as in the case of Plasmodium vivax or P. ovale).  Then, depending on the strain (P. vivax most commonly), the infected red cell “burden” often needs to approach 0.5 to 1% before synchronized rupture of red cells and release of the parasites is sufficient to produce acute fever and symptoms.


Malaria Schizonts

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QUESTION:

What is the difference between schizont of Plasmodium vivax and P. falciparum?

ANSWER:

P. falciparum schizonts tend to fill up to about two-thirds of the host red blood cell, and contain 8-24 merozoites (see image below for development of schizont). However, schizonts of P. falciparum are rarely seen in peripheral blood; instead, multiple, smaller rings are the usual diagnostic sign. Characteristic crescent-shaped gametocytes may also be observed, though usually later on in infection.

 

falciparum schizont CDC

The stages of maturation of a Plasmodium falciparum schizont. Image courtesy of CDC (www.dpd.cdc.gov)

P. vivax schizonts are large and fill up the entirety of the red blood cell with 12-24 merozoites, each containing visible chromatin and cytoplasm (see below). Their size and shape can differentiate them from the more compact P. ovale and P. malariae schizonts, though separating the former can sometimes be difficult.

vivax schizont CDC

The stages of maturation of a Plasmodium vivax schizont. Image courtesy of CDC (www.dpd.cdc.gov)

Malaria Vaccine

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QUESTION:

Why is a vaccine against malaria seen as the main hope for the future?

ANSWER:

This answer is courtesy of a medical doctor assisting us with answering your questions.

A vaccine is seen as the great hope for the future because the malaria parasite has an extraordinary talent for developing resistance very rapidly against each class of drug that is introduced into the arsenal against it.  This is accomplished by various mechanisms, such as concentrating and pumping the drug back outside its outer membrane, mutation of drug binding sites rendering the drug molecules incapable of attaching to or entering the cell in order to do its work and alteration of other enzymes within the cell to change the pH  (acidity), again rendering certain drugs ineffective, even if they do get in (among other mechanisms!). That said, the development of an effective vaccine has been difficult due to changing surface proteins against which these vaccines are being developed.  In order to work, the vaccine has to be developed targeting highly “conserved” outer proteins which do not undergo genetic mutation frequently…ie, not so much of a moving target.