Antimalarial Drug Therapeutic Life

by

QUESTION

Why do some antimalarial drugs have long therapeutic life while others have short therapeutic lives?

ANSWER

Different anti-malarial drugs target slightly different aspects of the malaria Plasmodium parasite, and so are made with different chemical structures.

The differences in therapeutic life across different malaria drugs has to do with the specific pharmacokinetic properties of the chemical compounds from which the drugs are made. Even drugs designed around the same principal chemical compound can persist for different amounts of time in the human body, depending on the other chemicals with which the active compound is bound. The length of time it takes for a chemical compound to halve in concentration, or for its pharmacological effect to reduce by half, in the human blood stream is known as its “half life.”

For example, the common anti-malarial drug chloroquine has a half life of about 10 days, and is based on a chemical compound called 4-aminoquinoline. However, another drug also based on 4-aminoquinoline, called amodioquine, has a half life of only 10 hours.

Proguanil (combined with atovaquone in the drug Malarone) is dihydrofolate reductase inhibitor with a half life of about 16 hours, while mefloquine (sold as Lariam), is made from quinoline methanol and has a half life ranging from 10-40 days. These differences in length of therapeutic action also affect the efficacy of the compounds against malaria at various stages in its progression, and can also be implicated in the propensity to resistance developing to the drug in the malaria parasite.

My Malaria Refuses to Go Away

by

QUESTION

The symptoms started about 2 months ago and I have used all kind of drugs. I have completed lumartem dose twice and I have used Coartem, I even took chloroquine injection and I am well for a few days and it comes back to the way it use to be, because of so many antibiotics I have taken I now have swellings in my body and in my leg and its making my leg ache and making walking difficult. What do I do?

ANSWER

Are you sure you have malaria? The most important thing is to get diagnosed accurately, either at a clinic or by a trained diagnostician. The most common form of diagnosis is a blood film on a slide, read under the microscope, but this can require expertise for accurate diagnosis. Another option is a rapid diagnostic test, now available in many places, which tests for the antibodies to malaria.

In my experience, in many places clinics will diagnose malaria purely on clinical symptoms, such as fever, which actually are very general to many diseases and so not necessarily mean malaria! So if you have been diagnosed without a blood test, go back to the clinic/doctor and demand a blood test.

There are no known strains of malaria that are resistant to Coartem which is why I suspect you may have something else, perhaps in addition to the initial malaria infection. Moreover, the drugs used to treat malaria are not antibiotics, and should not result in swollen legs; again, you should see a doctor or clinician before taking any further medication.

Cyclical Fever

by

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.

Malaria Symptoms, Cures, and Prevention

by

QUESTION

What is malaria cure, prevention, symptom and course?

ANSWER

I am not sure what you mean by “course” – however, links to information on malaria treatment, prevention and symptoms can be found on the main page of our website. For your convenience, I have provided them here:

As for malaria treatment, I have copied here an earlier answer in response to a question about malaria cures:

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.

 

Which Anti Malarial for South-East Asia?

by

QUESTION

We are in our 70s and will be on a cruise from Siem Reap to Ho Chi Minh. Which anti malarial would be most effective for these areas?

ANSWER

The main thing to consider when travelling to south-east Asia is that there are areas where some of the malaria is resistant to mefloquine (commonly sold as Lariam), and therefore this drug is not appropriate as an anti-malarial in these regions.

Chloroquine resistance is also rife throughout the region, although this drug is rarely used as a malaria prophylactic drug. However, apart from this, the choice of anti-malarial depends to a large extent on personal preferences.

The two main types recommended by the CDC for travel to south-east Asia are atovaquone-proguanil (marketed commonly as Malarone) and doxycycline. The former is associated with very few side effects, is taken once a day, and needs to be taken for a week after returning from the malarial area. However it is also very pricey! Doxycycline, on the other hand, is very cheap, but many people experience high sun sensitivity which can lead to severe sun burn if sufficient care is not taken. It also has to be taken for a full four weeks after returning from the malarial area.

Recurrent Malaria

by

QUESTION

Malaria has been with me since the late 1980’s after 6 years in Malawi.
During the 90’s I had it twice per year in Feb and Sept. Blood tests always came up negative. Treatment was with Chloroquine, later Halafantrin and then Co Artem. 2 or 3 treatments were required as symptoms appeared 2 weeks after completion of initial treatment.

In 2004 I treated with a bodyweight specific dose of Arinate and did not have another bout until 1 week into a Southern Mozambique visit in Aug 2008. (I was on doxycycline as a prophylactic but discontinued due to it causing diarrhoea.) Treatment was with Artecospe (unsuccessful) and CoArtem (successful.) In Nov 2010 after a visit to N Botswana another bout – treated twice with CoArtem.
Sept 18 2011 it struck again. (I have not been near a malaria area since Nov 2010). CoArtem unsuccessful 3 times with Artecospe have not worked and now on Co Arinate.

Have I some resistant strain of Malaria? Does eating during a malaria bout reduce the efficacy of treatment?

ANSWER

So far, no strains of malaria have been discovered to be resistant to Coartem. Moreover, recurrent malaria is only caused by Plasmodium vivax and Plasmodium ovale—neither of these are nearly as common in Malawi as Plasmodium falciparum, which can recrudesce (parasites re-appear in the blood) if not treated appropriately but will not relapse or reoccur months or years after the initial infection—if you have tested positive for malaria in your more recent bouts of illness, you should ask your doctor whether it could be P. vivax or P. ovale.

If it is one of these two species of malaria, you should ask about the possibility of taking primaquine to kill the dormant liver stages of the parasites and prevent future recurrence. You will need to be tested for G6DP prior to being able to take primaquine.

However, since you tested negative in Malawi initially, I suspect you did not have malaria at all at that point, and should have been tested further to determine what was causing your symptoms. Moreover, chloroquine should not have been the first treatment of choice, as resistance is rife in sub-Saharan Africa.

The symptoms of malaria are notoriously non-specific and therefore diagnosis is crucial prior to treatment, as many other infections will present with similar clinical symptoms, such as fever and nausea. Therefore, if you have any further symptoms which you suspect might be malaria, please visit a doctor or travel medicine clinic straight away for a blood test. If it is not malaria, there is no point taking further doses of Coartem or other anti-malarials and further tests might reveal another diagnosis.

Injections for Malaria Treatment?

by

QUESTION

I have a friend that just told me that she has Malaria. She said she has to go to the hospital every day for an injection for around the next 2 weeks. Is this a typical treatment. Why not just take pills? I`m just trying to wrap my head around this and understand the different treatments.

ANSWER

This is certainly not typical treatment for malaria. Uncomplicated malaria is usually treated with oral medication, and the type depends on the type of malaria you have. The most severe form of malaria, Plasmodium falciparum, is often resistant to chloroquine (still the first-line drug of choice for P. malariae, P. knowlesi and P. ovale infections, as well as for P. vivax in most parts of the world) and so first-line treatment is now usually an artemisinin-based combination therapy (ACT), such as Coartem.

As far as I am aware, it is only in cases of complicated, severe malaria that intravenous or intramuscular treatment is used (usually quinine), and in those cases, treatment would not be administered on an outpatient basis. It may be that your friend has a specific medical requirement for a non-oral form of medication, but it is definitely unusual!

Recurrent Malaria; Coartem Side Effects

by

QUESTION

I get recurrent malaria 2 to 3 times per year in Feb, March and Sept. I take Coartem which just about kills me.

I had it in early Sept this year and it was back 3 weeks later. Please can you advise how to stop it recurring. It has been a regular health problem since the 1980’s. I have had 3 Primaquine treatments to eradicate the liver parasites. The treatment did not work.

Your advice will be most appreciated.

ANSWER

Thanks for your question. First of all, is it of concern that you write that taking Coartem “nearly kills” you—do you mean you get very bad side effects? Side effects are rare with Coartem, and when they occur, they are usually mild and transient, such as headache, nausea, cough, or fever. Occasionally, patients report more significant side effects, such as tinnitus, back pain or itching. If you have more serious side effects than these, you should talk to your doctor about switching to a different formulation of malaria medication.

Given that you are based in sub-Saharan Africa, I would certainly recommend that you stick to artemisinin-based combination therapies (Coartem, for example, is a combination of artemether, which is an artemisinin-based compound, and lumefantrine), but there are different combinations, which may be more effective for you.

Second of all, in sub-Saharan Africa, Plasmodium falciparum is by far the most common form of malaria. Importantly, this parasite does NOT cause multiple episodes or recurrence, months after the initial infection, unlike Plasmodium ovale or Plasmodium vivax, both of which are found in Africa but are not nearly as common. Plasmodium falciparum infection can cause what is call “recrudescence,” which is where the number of parasites in the blood is reduced sufficiently so as not to be detectable, but then bounces back after treatment ceases, causing another bout of infection a few days or within a few weeks of the initial malarial episode—this might explain your most recent malaria experience.

Primaquine is only effective against recurring malaria when it is used to target the dormant liver stages of P. vivax and P. ovale. Therefore, in your case, it is extremely important that you are accurately diagnosed in terms of which malaria parasite you have, and each time you get infected as well. This will help determine whether you are continually being re-infected, for example with P. falciparum, or if you are indeed suffering from recurrences of P. vivax or P. ovale. If it is the latter, then primaquine is usually about 80% effective, based on global epidemiological analysis on P. vivax.

There is some evidence that strains of malaria from different regions, for example Thailand and Papua New Guinea, may be more resistant to primaquine than strains from other places. The good news about having P. vivax or P. ovale is that they are much more likely to respond to initial treatment with chloroquine, which you might tolerate better than Coartem.

So, in summary, if you have not done so already you should make sure your doctor diagnoses the species of malaria parasite that you have, either through microscopy (the different types of malaria look different under the microscope) or, preferably, through a serological blood test, which are even available as self-testing kits. At that point, alternative treatment options to Coartem can be discussed with your doctor, as well as whether it is appropriate to try primaquine again.

How is Malaria Cured?

by

QUESTION

How is malaria cured?

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.

Symptoms of Malaria

by

QUESTION

What are the main symptoms of malaria?

ANSWER

Malaria can have many different symptoms, but the initial signs are similar to a flu-like illness, with high fever, chills, headache and muscle soreness or aches. A characteristic sign of malaria is cyclical fever, with peaks of severity every two or three days. Additionally, some people will experience nausea, coughing, vomiting and/or diarrhea.

Because these symptoms are quite generic of a wide variety of illnesses, if you live in a malaria-endemic region, it is crucial to be tested when you develop such symptoms, rather than assuming it’s just the flu and soldiering on! If you have recently traveled to a malarial area and start to experience these signs of infection, similarly you should inform your doctor of your travel history, as otherwise they might not recognize your symptoms as potentially that of malaria.

If treated rapidly and with the correct medication, malaria is almost always completely treatable; it is only if treatment is delayed that it becomes more serious, with long-lasting and potentially fatal consequences. Similarly, if you take sensible precautions while living or traveling in malarial areas, such as taking prophylaxis (and taking them as per the instructions, for the full required amount of time!), avoiding being bitten by mosquitoes and sleeping under an insecticide-treated bed-net, you vastly reduce your chances of getting infected in the first place.

It’s also worth noting that different species of Plasmodium, the parasite that causes malaria, cause slightly different manifestations of the disease, and also require different forms of treatment. Plasmodium falciparum has a unique way of affecting the red blood cells it infects, which eventually can result in loss of function of internal organs. ‘Cerebral malaria’ is a particularly deadly version of this, whereby the function of the brain is affected. The cycles of fever, mentioned above, are caused by synchronous rupturing of the red blood cells in the body by the malaria parasite; P. falciparum, P. vivax and P. ovale, complete this cycle every 48 hours, resulting in fever cycles of roughly two days (though P. falciparum can be unpredictable); P. malariae, on the other hand, has a cycle lasting 72 hours, so three day cycles of fever are expected. Finally, although many types of malaria can be successfully treated with the drug chloroquine, some strains, and notably of P. falciparum, have become resistant to this treatment. In these cases, artemesinin-based treatment is recommended, usually in combination with other therapies (artemesinin-combination therapy, or ACT). P. vivax, in addition, requires an additional drug, called primaquine, which is used to treat lingering liver stages of the parasite, to prevent recurrence of the infection.