Recurrent Malaria; Coartem Side Effects

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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.

Diagnostic Advice

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QUESTION

Healthy 30 year  old male, arrived in West Africa 2 weeks ago, using doxycycline as prophyaltic but not systematically—I know I missed a day or two, and had not taken it before arriving; lots of mosquito bites. Also believe my doxy to be expired—how long is it good for in capsule form? Doesn’t have expiry on my prescription. Symptoms showed up around day 7 in Mali: sore neck, headache, nausea, slight fever. Then left me for several days but returned strongly 5 or 6 days later at which time I went to pharmacy and began Artequin 600/750 (Artesunate + Mefloquine) – three day treatment. Felt better immediately after taking first dose. After second dose went to clinic for blood work for some reassurance but test came neg for Pl. falciparum; doc had warned that neg result is likely due to medication. The blood work showed my Lym # to be higher than normal range 74% vs range of 20-40%, however the clinician provided no comment and I only realized this after. Just took day three dose and don’t feel any worse but have some diareah, general discomfort. Not as intense as two previous waves of sore neck and nausea. Now resting but its awkward having no reassurance I have malaria. I read high lym (presuming this means lymphocyte—french blood result printout) count is generally due to viral infection.

Could I have a virus that may require a different form of treatment? Should I stay put at hotel hoping the malaise will pass or seek further medical assistance? (any consensus on what time frame for symptoms to pass?) Thank-you.

ANSWER

I have passed your question on to our advising medical doctors at malaria.com, and once they get back to me I’ll post it here. In the meantime, it might be worth knowing that although elevated monocyte levels can be associated with malaria infection, lymphocyte/general white blood cell counts tend to be decreased in malaria patients (I find it unusual that your value was given as a percentage rather than a number). As such, it suggests you might have some other infection, though it doesn’t have to be viral—there are other causes of elevated lymphocyte counts, such as bacterial infections, which can be tested for in a hospital.

Depending how long you are going to be in Mali for, you can either try to see a physician there who might be able to give you further tests (you should also have another malaria test a few days after you have finished the course of medication, especially if you still feel ill), or if you are feeling better, you could perhaps wait til you get home and talk to your primary care doctor there about other possible causes for elevated lymphocytes.

UPDATE: I’ve just heard back from one of our medical advisor. He suggests that it is quite unlikely you could have had malaria only 7 days after arriving in West Africa, since the incubation period is usually more like 2-3 weeks (and is often extended when people take anti-malarials). As such, it may be worth seeing a doctor to check whether you might have another infection, which is contributing to your illness and also might account for the high white blood cell count.

How to Control Malaria

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QUESTION

Suggestions to control malaria?

ANSWER

This answer is copied from an earlier question asking about strategies for controlling malaria in Africa. The methods below are being used by many health ministries, international agencies and non-governmental organisations to combat malaria all over the world (and not just in Africa).

Currently, malaria control 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. Another arm of prevention is reducing the number of mosquitoes in an area (called vector control), and thus preventing transmission from occurring at all – this can be achieved through insecticide spraying but also filling in the stagnant pools of water that mosquitoes lay their eggs in. Vector control was highly successful in reducing malaria transmission in the United States and Mediterranean in the years after World War II.

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; recently, a study was published which reported the results of the first Phase 3 clinical trial of a malaria vaccine, in African children. The vaccine appeared to confer approximately a 50% level of protection against malaria; while this is a start, it perhaps did not live up to many people’s hopes of a new method for controlling 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.

 

 

Passing Malaria to Baby

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QUESTION

I contracted Malaria 3.5 years ago (either in Uganda or Rwanda). I believe it was the Plasmodium falciparum strain. Upon my diagnosis, I was treated and have been healthy since.

In regards to pregnancy, is it safe for me to have a baby? What are the chances of passing the malaria virus to the baby?

ANSWER

First of all, malaria is caused by a single-celled parasite, not a virus.  Secondly, you probably don’t have to worry—malaria is only very rarely transmitted directly between a mother and her unborn baby, via infected red blood cells passing through the placenta. When I say rare, I mean very rare, especially in developed countries without endemic transmission. There are only 48 cases of this occurring in the United States in the last 60 years, for example. Moreover, this can only occur if you actually have malaria during the pregnancy; if you were successfully treated when you had malaria 3.5 years ago, the parasite should no longer be present at all in your body.

P. falciparum does not lay dormant in the body, unlike some other types of malaria. The only thing to consider is if you plan to travel to malarial areas while you are pregnant – pregnancy makes women more vulnerable to malaria infection, and many forms of malaria preventative medication and treatment have not been thoroughly tested for safety in pregnant women. If you are planning on travelling to malarial areas while pregnant, it would be wise to consult with a specialist travel doctor for the most up-to-date recommendations of malaria prevention when pregnant.

Three Attacks of Malaria

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QUESTION

I am right now recuperating from a third attack in less than one year’s time. What could have gone wrong ?

I am awaiting to hear your advice.

ANSWER

There are a number of reasons for multiple malaria attacks. One is that although malaria can be easily treated, these treatments often don’t prevent re-infection. There are separate drugs which can be used to prevent malaria (known as malaria prophylactics), but these must be taken all the time to be effective (usually either once a week, once a day or twice a day, depending on the specific drug), and so usually aren’t appropriate (due to the unknown health risks of taking the drugs for that long, plus the prohibitive cost) for people living in areas where malaria occurs.

For people living in malarial areas, other means of prevention are required, of which avoiding being bitten by mosquitoes is paramount. For this, it is recommended to sleep under a long-lasting insecticide treated bednet at night, when many malarial mosquitoes are active. Similarly, wearing long sleeved clothing, especially if it is impregnated with an insecticide such as permethrin, can help avoid the bite of infected mosquitoes.

Second of all, there are some types of malaria which cause repeat episodes of illness, even after only a single infection. Specifically, Plasmodium vivax and Plasmodium ovale (the former is common in many parts of Asia in particular) can form life stages called hypnozoites which rest dormant in liver cells, even after the parasites in the blood have been cleared.

During this time, the patient will have no trace of malaria if they take a blood test, and they will feel fine. However, if these hypnozoites become active again, they will re-invade the blood, and the symptoms of disease will reoccur – at this stage, the parasite will once again be observable in the blood, and so the patient will be diagnosed as positive for malaria. As such, it is very important to find out what type of malaria you have, and if it is one of the above two species, then you can talk to your doctor about taking another type of medication, in addition to that which cures the blood infection, called primaquine—primaquine kills the hypnozoite liver stages of malaria and thus prevent recurrence of the disease.

Thanks for your question—since we think other people may benefit from the questions in this forum, I have removed your name and contact information to preserve your anonymity.

Medicines to Prevent Malaria?

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QUESTION

Which medicines are used to prevent malaria?

ANSWER

There are a number of drugs used to prevent malaria infection, known as malaria prophylactic medication. These vary in terms of how they are taken, how long they are taken for, how much they cost and the typical side effects people experience while they are taking them. In addition, some are recommended more highly for certain types of malaria or certain regions of the world, due primarily to the emergence of resistance in certain areas.

The most common forms of malaria prophylaxis used are doxycycline, atovaquone/proguanil (sold under the brand name Malarone), chloroquine (sold as Aralen) and mefloquine (sold as Lariam). More information on these, on other types of prophylaxis and malaria prevention in general can be found on our Malaria Prevention page.

How is Malaria Cured?

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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.

Do Sporozoites in blood signal the end of prepatent period?

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QUESTION

Will the appearance of sporozoites in blood mark the end of prepatent period in malaria?

ANSWER

Actually, no. The presence of sporozoites indicates the start of the infection. Sporozoites are introduced into the bloodstream via the bite of an infected mosquit0. The sporozoites then have to make their way to the liver and infect hepatocyte cells, where they undergo pre-erythrocytic schizogony. This is where the malaria parasites produce multiple copies of their nucleus without dividing the cytoplasm of the cell; new copies of the cell are produced by budding. These new cells are called merozoites, and they are released back into the blood, where they search for erythrocytes (red blood cells) to infect.

This is the end of the pre-patent period in malaria, as the symptoms of disease will start once the merozoites infect and rupture the host’s red blood cells, and parasitaemia may also be detected at this stage through observation of peripheral blood samples.

Dietary Values in West Africa

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QUESTION

In many West African countries where malaria attacks the general population of the people what is their dietary intake like? What are their foods or nutritional values?

ANSWER

In most West African countries, the diet is dominated by starchy tubers or grains, such as cassava, rice, sorghum and millet. This base foodstuff is often served alongside a vegetable or meat-based stew or soup, often thickened with leafy greens or vegetables such as okra. Meat has gained in popularity in recent years, and there has also been a shift from the use of traditional oils (palm oil near the coast and shea nut oil further inland) to processed and hydrogenated vegetable oils.

While the traditional diet is fairly balanced, the emphasis on high amounts of starch can lead to mild malnourishment (particularly through lack of protein) and micronutrient deficiencies. Increasing the proportion of meats and oils in the diet, as is becoming more common, tends to reverse malnutrition into obesity, while not solving the micronutrient deficiencies.

Having said all that, there is little evidence that diet can specifically protect against malaria infection, although good overall health, which can be assisted by a healthy, balanced diet, may provide some protection against progression of the disease and the ability to fight the infection.

How did it get the name “malaria”?

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QUESTION

How did malaria get its name?

ANSWER

The word “malaria” comes from Italian, “mala aria” which literally translates to “bad air”. This came from the ancient association, traced back as far as the ancient Greeks and Romans, that the disease was associated with swampy, marshy areas where the air smelled bad.

The mechanism of transmission was not known back then, nor did they know anything about infectious disease agents like bacteria, viruses or the single-celled protozoa like what causes malaria. So they believed it was the air itself that caused the infection, hence giving malaria its name. The protozoan which causes malaria was not discovered until 1880 when Charles Louis Alphonse Laveran observed the parasites in a patient; it was a few years later, in 1897/1898, that Ronald Ross discovered that mosquitoes transmitted malaria between human hosts. He won a Nobel Prize for this discovery in 1902.