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.

Malaria Recovery Time

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QUESTION

How long does it take to recover from malaria?

ANSWER

A number of different factors affect recovery time from malaria. These include the type of malaria, how quickly treatment is administered and the immune status of the patient. For example, children and pregnant women tend to get much more severe cases of malaria, due to their reduced natural immunity. 

The type of malaria will impact on the severity and length of the infection as well—P. falciparum is the most severe kind, and can result quickly in death if not treated promptly, whereas less rapidly progressing forms of malaria, such as P. malariae, may persist for longer but not cause severe disease. For most cases of uncomplicated malaria, once the appropriate form of treatment is started, the patient will start to recover within a couple of days.

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.

Headache and Chills with Malaria

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QUESTION

Could a person be infected by malaria without symptoms of headache and chills?

ANSWER

Malaria symptoms vary considerably, depending on the type of malaria, the severity of the infection and the patient’s natural immunity. It is certainly possible for a patient to have malaria without experiencing headache and chills; some people infected with certain forms of malaria, such as Plasmodium malariae, may not even experience severe fever and barely realise they are infected. However, most cases of malaria, especially in sub-Saharan Africa, are caused by Plasmodium falciparum, which is a faster-acting, more severe form of malaria and usually results in fever and chills, often accompanied by headache and nausea.

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.

Who Discovered Malaria?

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QUESTION

Who discovered malaria?

ANSWER

People have known about malaria for thousands of years—the first record of it comes from 2700 BCE, in an ancient Chinese medical text. Other ancient peoples, such as the Egyptians, Greeks and Romans, also knew the symptoms associated with malaria. But it wasn’t until the 19th century that the causes of malaria were understood. In 1880, a French physician named Charles Louis Alphonse Laveran first saw the parasites that cause malaria in the blood of a patient. By 1886, Camillo Golgi, an Italian physiologist, had observed that there were at least two separate types of malaria, which produced different length cycles of fever during the clinical presentation. These two forms were later called Plasmodium vivax and Plasmodium malariae. It wasn’t until more than a decade later, in 1897/1898, that the method of transmission of malaria was first understood – Ronald Ross, a British army doctor, showed that malaria could be passed from a human patient to a mosquito vector, and also between infected hosts using mosquitoes. He won the Nobel Prize for medicine for his work in 1902.

Since then, research on malaria has expanded exponentially, with particular attention giving to understanding ways in which the parasite can be therapeutically halted, thus leading to the discovery of new malaria medications.

Post Malaria Auto-Immune Disease

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QUESTION

I contracted P. Malariae while on a Humanitarian trip in El Salvador in 1996, despite taking the Doxycycline prophylaxis. The diagnosis was difficult, as my fever never broke 100 deg F. A sample of my blood was eventually sent to the CDC to confirm the suspicions of my Dr, who just couldn’t prove the dx by smear. The titer came back positive 1. Now to my question. Have you come across any cases of post-malarial auto-immune disorders or cluster-type syndromes?

About a year and a half. After my initial infection, I developed severe hand joint pain that progressed to much of the rest of my body. At the time, RNP/anti-RNP tests were positive, with elevated sed rates, but negative ANA & RF tests. Now those tests are all “wnl,” but I have some form of “agressive osteoarthritis,” DDD, Spinal stenosis/osteophytes/spinalolisthesis w/nerve damage, and the catch all “Fibromyalgia” along with it’s cluster symptoms.

I would be so very, very grateful if you could point me in the right direction of a study, more information, a Dr who has experience with tropical diseases, or any other information that might net me some answers. I am so tired of being tired and in pain. I shouldn’t need knee replacements and 2 discectomies with a double lumbar fusion at 44. Sadly, I’ve already had one in my neck & may need more. I feel like my life was stolen by a mosquito—the deadliest creature on Earth.

ANSWER

I do not believe there is any relationship between the malaria and these symptoms or with any autoimmune diseases.  Although it sounds like your P. malariae infection was a bit difficult to diagnose it is very easy to treat.  There is no known drug resistance and so any of the recommended treatment courses should have cured you of the infection.  If you subsequently developed an autoimmune disease, it is most likely just a coincidence.  Untreated P. malariae infections can become chronic and result in late complications such as renal failure but that is not the case here.

Malaria Cure

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QUESTION

What is the cure for malaria?

ANSWER

Malaria can be cured with a number of different medications, depending on then type of malaria and how far the disease has been progressed.

For standard, non-complicated Plasmodium falciparum malaria, the World Health Organisation recommends use of artemisinin-based combination therapies (ACTs), such as Coartem. This is due to increasing levels of resistance to chloroquine in many parts of the world. Indeed, even though chloroquine is still used in many places as first-line treatment against P. vivax, P. malariae, P. ovale and P. knowlesi uncomplicated malaria, there is some evidence that resistance to this treatment is also emerging, for example in P. vivax in parts of south-east Asia.

In cases where malaria infection has progressed to a stage where oral administration of medication is not possible, or where cerebral symptoms are suspected, the usual treatment option is intravenous quinine.

In addition, P. vivax and P. ovale malaria parasites are able to produce forms (called hypnozoites) which can become dormant in liver hepatocyte cells after the blood stages of the infection have been cleared. These dormant forms can become reactivated weeks or even months or years after the initial infection, which is called a “relapse” of the infection. One drug, called primaquine, is able to kill these liver stages, and so patients with either of these types of malaria should also discuss the possibility of taking primaquine.

Apart from these first-line treatments, there are other medications which are used against malaria, both prophylactically as well as for treatment. These include orally-administered quinine, pyrimethamine, mefloquine, proguanil, atovaquone and sulfonamides.

For more information, see the WHO recommendations for malaria treatment.


Cyclical Fever

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QUESTION

My husband has been suffering from recurring fever every 3rd or 4th day for the past 7 months. All blood tests are normal, esr ,crp, cultures of urine and blood all normal, chest ct full body pet heart echo all normal. Tested positive for montoux and quantiferon gold, with no symptom other than fever, was put on ATT on 4th JULY 2011 fever persists with no other symptoms. Has been on ATT for more than 4 months with no respite and as per doctor TB is ruled out but 6 month course mandatory. Please help. Fever comes with mild chills and head ache at times.

ANSWER

Cyclical fever every few days is one of the characteristic signs of malaria, and the length of the cycles can help identify the type of malaria. Specifically a fever every three days is indicative of Plasmodium malariae infection, which also fits with the long, chronic persistence of the illness.

This parasite can be hard to diagnose as it is often present in low concentrations in the blood. If you haven’t had a blood film done already, ask your doctor to make a thin and thick blood film to look for the presence of Plasmodium malariae in your husband’s blood.

If the first films are negative, continue with daily films for a further 2 or 3 days. Another diagnostic option is a rapid diagnostic test, which can detect antibodies to the malaria parasites in the blood. P. malariae is easily treated with chloroquine.

Unfortunately, without further information and a more complete medical history it will be impossible to make a further diagnosis of your husband’s condition, but certainly checking for Plasmodium through a blood test would be a good first step.