Malaria Drug Binding Site

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QUESTION

What is malaria, and drug binding site?

ANSWER

Malaria is caused by a single-celled protozoan parasite of the genus Plasmodium. Five kinds of Plasmodium are known to infect people: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

There is no one drug binding site with respect to malaria: different anti-malarial drugs have different modes of action, and not all are well described. I will briefly outline the proposed mechanism of action of two of the most common types of anti-malarials: artemisinin (and derivatives) and chloroquine (quinine is thought to act similarly to chloroquine).

Artemisinin is thought to have anti-malarial properties by virtue of possessing an endoperoxide moiety, or double oxygen bridge (-Carbon-Oxygen-Oxygen-Carbon). In the presence of intracellular free ion, this moiety is converted by a chemical reaction to “free radicals”, atoms with unpaired electrons which are highly reactive. The free radicals act as alkylating agents and induce cell death, but only those that are already pathologically crippled, for example due to malaria infection. Another hypothesis is that the free radicals directly damage the malaria parasite.

Chloroquine is thought to act by causing buildup of the toxic by-product of hemoglobin metabolism, heme – the malaria parasite usually converts heme to hemozoin, a non-toxic crystal, and stores it in the digestive vacuole. When chloroquine diffuses into an infected red blood cell, it reacts with heme to “cap” it, preventing further conversion into hemozoin. Moreover, chloroquine also converts hemozoin into a highly toxic substance called the FP-Chloroquine complex. This build-up of toxicity leads to breakdown of the cell membrane, and eventual cell death and autodigestion.

Recurring Malaria

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QUESTION

I had malaria twice when I was 4 and 8 years old. I am 50 years old now but I have severe chills at least once or twice a month, muscle aches, fatigue severe head aches for the past 10-15 years with no apparent cause and my I take head ache medication for migraine (maxalt and excedrim) and my chills and fatigue is getting more frequent. I had no other history of any diseases. Is this symptoms a possible recurrent malaria.

ANSWER

Thanks for your question. One of the most common symptoms of malaria is high fever, which comes in cycles with chills in between. Without fever, it is unlikely that you are suffering from malaria.

However, there are some forms of malaria which can cause relapses. Specifically, Plasmodium vivax and P. ovale can form dormant liver stages which can then re-enter the blood causing a relapse of malaria infection and a recurrence of symptoms. To diagnose malaria in your case, next time you have an episode of chills, go to your doctor and ask for a blood test to check for malaria. S/he will either look at your blood under the microscope or perform a rapid diagnostic test, which tests for malaria-specific proteins, called antigens, in your blood.

In either case, it will tell you whether you have malaria, and which kind. If you have one of the relapsing kinds (P. vivax  or P. ovale) then you may be able to take a course of a drug called primaquine which kills the dormant liver forms of the malaria parasite and thus prevents future relapses. However, people with G6DP deficiency should not take primaquine, so you should be tested for this deficiency prior to taking the drug.

Malaria Relapse

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QUESTION

Why do I suffer from constant malaria attack? The doctor has prescribed different prescriptions every time I get an attack but its still coming back. What could be the problem?

ANSWER

There are a number of possible answers to your question. First of all, your doctor might not be prescribing the right type of treatment for the type of malaria that you have. The World Health Organisation now recommends that all uncomplicated cases of malaria should be treated with artemisinin-based combination therapies (ACTs), such a Coartem. However, in some places, doctors still prescribe other drugs, such as Fansidar or chloroquine. This can be a problem, as in many areas, the local kinds of malaria have become resistant to these earlier drugs, and so you may not be cleared of the infection. This is called recrudescence—when a malaria infection is not cleared completely from the blood and so symptoms come back once the treatment has stopped.

Alternatively, if there is a longer time interval between your episodes of illness, you may be suffering from relapses. This occurs with two particular types of malaria: Plasmodium vivax and P. ovale. These types of malaria can form liver stages which remain dormant even after the treatment you take kills all the malaria in your blood. Therefore it will appear like you have been cured, but really you still have an infection in the liver.

These liver stages can re-activate and re-enter the blood, causing another episode of malaria symptoms months or even years after the initial infection. If your doctor finds that you are positive for one of these two types of malaria, you should talk to him/her about the possibility of taking primaquine. This drug kills the liver stages of the parasite, but is not appropriate for people with G6DP deficiency, so you should be tested for that first.

Finally, there is the possibility that you are continually being re-infected with malaria. In this case, you should take more preventative precautions. For example, sleep under a long-lasting insecticide-treated bednet, wear long-sleeved clothing (especially at night) and cover exposed skin with insect repellent. All of these measures will help prevent mosquito bites, which transmit malaria. In addition, you could consider indoor residual spraying, which coats the walls inside your house with insecticide to further eliminate the presence of mosquitoes.

Symptoms and Causes of Malaria

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QUESTION

What are the symptoms and causes of malaria?

ANSWER

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. Usually, people get malaria by being bitten by an infective female Anopheles mosquito. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito’s saliva and are injected into the person being bitten.

Because the malaria parasite is found in red blood cells of an infected person, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her unborn infant before or during delivery (“congenital” malaria).

There are five kinds of malaria known to infect humans: Plasmodium falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. The symptoms of malaria differ depending on the type of malaria; P. falciparum  is the most deadly and severe form of the disease. General symptoms of malaria include  include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells.

Symptoms usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs.

What are the causes of malaria?

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QUESTION

What are the causes of malaria?

ANSWER

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. Usually, people get malaria by being bitten by an infective female Anopheles mosquito. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito’s saliva and are injected into the person being bitten.

Because the malaria parasite is found in red blood cells of an infected person, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her unborn infant before or during delivery (“congenital” malaria).

There are five kinds of malaria known to infect humans: Plasmodium falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

Is malaria possible years after bite?

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QUESTION

My child had a fever for 40 days after returning from a cruise 3 years ago. I begged the pediatrician to test for malaria because she got bit by something in Mexico but they laughed at me. She has had swollen lymph nodes on both sides of her neck for 3 years and all the docs tell me you can have swollen lymph nodes forever but now she has them in her groin and under arm on left side. She is pale and tired all the time. I took her back to the pediatrician and her cbc was normal so the dr is blowing it off. Malaria and Lymphoma are on my mind. My question is, Can malaria live in the body that long without it killing you?

ANSWER

Malaria can certainly survive in the body for a long time, but usually would present as recurring episodes of fever rather than enlarged lymph nodes (the malaria parasites reside dormant in the liver). There are two types of malaria that can reside in the body for extended periods: Plasmodium vivax and P. ovale. The former is found in parts Mexico, but cases of malaria are rare, especially in coastal areas. Unfortunately, malaria can only be detected when it enters the blood again – this occurs during the fever episodes. So, if your daughter does have a fever again, it might be worth asking for a malaria test, and specifically to look for P. vivax. If positive, there is a drug, primaquine, which can be taken to kill the remaining liver stages of malaria and prevent further relapses. However, overall, your daughter’s case doesn’t sound like malaria. What was your daughter’s Hb level? Anemia could explain the pallor and lethargy, though your pediatrician should have spotted that on the blood tests.

How long do I need to carry a Malaria Risk Card

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QUESTION

Hello, 13 months ago I worked in Nigeria, Africa for a period of 6 weeks. During which time I took Malarone tables daily. I think I was only bitten once or twice when there – but have never had Malaria. I currently carry a Malaria Risk Card in my wallet. At the time I was told I could potentially contract Malaria up to a period of 2 years after exposure – is this correct, or can I now remove the Risk Cards from my wallet?

ANSWER

If you never had malaria while you were in Nigeria, then you certainly would not still be at risk from it now. The only case in which you might still be at risk is if you had been diagnosed with either Plasmdodium ovale or P. vivax (two of the five forms of malaria that infect humans) – these can cause relapses months or even years after initial infection.

However, as I said above, since you did not have malaria at all, this does not apply to you. It is true that malaria has a latent phase, and so can sometimes only start to cause symptoms after someone returns home from a malarial area, but this period is usually one or two weeks, and certainly not months or years!

How many types of malaria are there?

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QUESTION

How many types of malaria are there?

ANSWER

There are four species of malaria parasite that commonly infect humans. These are: Plasmodium falciparum, P. vivax, P. ovale and P. malariae. In addition, a fifth species, P. knowlesi, is starting to draw public health attention as an infection in humans in south-east Asia, and particularly Borneo – previously, it was thought to only infect macaque monkeys.

Apart from these five species, there are many other species of Plasmodium, which infect other primates (including gorillas, chimpanzees and orangutans), rodents, birds and reptiles. A closely related group of parasites, called Hepatocystis, infects monkeys, squirrels, hippopotamus and bats.

Long term health effects of malaria when young?

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QUESTION

I’m trying to find out if having malaria at a young age can have long term effects on health.

Around 25 years ago when I was 4 years old I contracted malaria when living in central Africa. Unfortunately I do not know the type of malaria, only that I received medication and recovered without complications.

Over the last few years I’ve had a general feeling of poor health and fatigue. Blood tests indicate I have some level of liver damage but I’m at a loss for the cause.

Is there any chance of having picked up liver damage (or other long term effects) from contracting malaria at a young age?

ANSWER

There is little evidence for any long term complications associated with uncomplicated malaria infection. One thing to investigate might be the type of malaria you had as a child; Plasmodium vivax and Plasmodium ovale, while not as common as Plasmodium falciparum in Central Africa, both occur in this region, and differ from P. falciparum in that they can have a dormant liver stage.

While I still have not heard of liver problems being associated with dormant malaria parasites, it is conceivable that if you had one of these two types of malaria and did not have the liver stages treated, you might later feel some ill effects; relapse from P. vivax has been known to occur decades after the initial infection. The good news is that there is a drug available, called primaquine, which can kill these liver stages (known as hypnozoites). So, if you know you had P. vivax or P. ovale, you could mention this possibility to your doctor—prior to taking primaquine you should have a test for G6DP deficiency, as such as deficiency makes it dangerous to take this medication.

If you have ever taken anti-malaria medication, please take Malaria.com’s brief Malaria Medication Side-effects Survey: Treatment and Prophylaxis.

What are the Symptoms of Malaria?

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QUESTION

What are malaria symptoms?

ANSWER

Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells.

Symptoms usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death. In many parts of the world, the parasites have developed resistance to a number of malaria medicines.

For most people, symptoms begin 10 days to 4 weeks after infection, although a person may feel ill as early as 7 days or as late as 1 year later. Two kinds of malaria, P. vivax and P. ovale, can occur again (relapsing malaria). In P. vivax and P. ovale infections, some parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation and begin invading red blood cells (“relapse”), the person will become sick.

Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria disease can be categorized as uncomplicated or severe (complicated) . In general, malaria is a curable disease if diagnosed and treated promptly and correctly.