Malaria Recurrence

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QUESTION

I had malaria 5 months back it has again reoccurred. this time there has been increase in the size of the spleen. As of now it is being treated but I fear of getting it again. Is it true the malaria which i am down with reoccurs every 6- 8 months ??? Local people call it as registered malaria.. .

ANSWER

There certainly are types of malaria that can reoccur relatively regularly, at various intervals. This malaria is caused by one of two species, either Plasmodium vivax or Plasmodium ovale.

With both, it is important to get it diagnosed via a blood test with a doctor before getting treated again, to make sure it is indeed a relapse of the same malaria, and not a new infection with a different kind, or indeed some other disease (the symptoms of malaria can often be confused with other infections).

There is also medication that can be taken to prevent future relapses and re-occurrences—it is called primaquine, so you should talk to your doctor about the possibility of taking this medication. Please note it is not suitable for people who have G6DP deficiency, so you should be tested for that before taking it.

Repeated Malaria Cases, New Guinea

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QUESTION

Hello, I live in Papua New Guinea. Myself, my wife and my 2 kids (both under 4 years old), get diagnosed with malaria approximately 3-4 times a year, usually vivax or falciparum. Our GP uses a prick of blood and examines under a microscope. Is it that easy/obvious to diagnose under this method and is it common to get this many attacks in a year? I also fear the affects of taking malaria tabs (eg Fansidar, Primaquin, Artemeter, Amodiaquine) this many times, especially for my young kids. Please help!

ANSWER

In high transmission areas, particularly in rural areas in sub-Saharan Africa, it certainly isn’t unusual for children to get as many a 5 or 6 malaria attacks in a year; adults tend to present with fewer clinical episodes, usually because they were heavily exposed as children and thus developed a significant level of immunity against malaria.

If you and your wife didn’t grow up in a malarial area, then you would not have that acquired immunity, and so you would be expected to get sick almost as often as your young children. Papua New Guinea certainly is a high transmission zone, and I think one thing which might help your family is to focus more on malaria prevention. Since malaria is transmitted by mosquitoes, the best way to avoid getting malaria is to avoid getting bitten by mosquitoes. You should all be sleeping under log-lasting insecticide-treated bednets, which kill and/or repel mosquitoes that try to bite you while you sleep (the mosquitoes that transmit malaria, of the genus Anopheles, are most active at dusk, at night, and at dawn—during the heat of the day they usually don’t feed, but may be found in cooler, heavily shaded areas).

You could also try spraying the walls of your house with a long-lasting insecticide like permethrin, which will also kill adult mosquitoes. Making sure your house is well-screened will also prevent mosquitoes from getting in and biting you at night and in the evenings, and if you are going out during these times, you and your family should wear long-sleeved clothing, and exposed skin should be covered with insect repellent. A DEET-based insect repellent is best, but you may not be comfortable using these regularly on young children, since it can have some potentially dangerous long-term effects, particularly on the liver.

In terms of your other questions, looking at your blood under the microscope is the normal way to diagnose malaria in many places, so it sounds like your GP is doing a good job. There is no indication of adverse effects from taking multiple, repeated doses of anti-malarials, but as I mention above, taking additional preventive measures may further help in reducing your family’s malaria incidence.

One thing you might want to talk to your doctor about is the fact that in some cases, Plasmodium vivax can cause relapses of infection weeks or even months after the initial infection. The reason is that P. vivax can form dormant life stages, which can hide out in the liver, and cannot be killed by the normal anti-malarial treatment. However, there is a medication, called primaquine, which can kill these liver forms, and prevent future relapse. People with a deficiency in a particular enzyme, called G6DP, may not be able to take this medication, as it may cause severe anaemia, so prior to taking the drug you might have to be tested for this deficiency. However, it is definitely something you should talk to your GP about.

Please take a moment to complete our Malaria Survey, as it will help us better understand the effects of malaria medications.

P.vivax Malaria Treatment

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QUESTION

Which drug should be given to a p.vivax malaria patient with deficient glucose 6-phosphate for prevention of relapse?

ANSWER

Unfortunately, primaquine is the only drug that is known to kill the latent liver stages of P. vivax and P. ovale. Since it can induce haemolysis in people with G6DP deficiency, this drug is usually not recommended for people with this deficiency. However, there are actually gradations of severity of G6DP deficiency, and so in some cases, primaquine at therapeutic doses may be tolerated by people with only mild G6DP deficiency, if they are carefully monitored for anaemia throughout the process. This may be preferable to no treatment, since no other known medication can prevent relapse.

Malaria Treatments

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QUESTION

What are the of different types of antimalaria drugs?

ANSWER

Most drugs used in treatment are active against the parasite forms in the blood (the form that causes disease) and include:

  • chloroquine
  • atovaquone-proguanil (Malarone®)
  • artemether-lumefantrine (Coartem®)
  • artesunate-pyronaridine (Pyramax®)
  • dihydroartemisinin-piperaquine (Duo-Cotecxin®)
  • mefloquine (Lariam®)
  • quinine (given intravenously, this is recommended first-line treatment for severe, complicated malaria)
  • quinidine
  • doxycycline (used in combination with quinine)
  • clindamycin (used in combination with quinine)

All of the treatments above which combine an artemisinin-derivative (such as artemether, artesunate or dihydroartemisinin) in combination with another anti-malarial are called the artemisinin-based combination therapies (ACTs) and are collectively recommended by the World Health Organisation as the first line medication against uncomplicated malaria.

In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency.

Treatment and Management of Malaria Parasite

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QUESTION

What are the treatments and management of malaria?

ANSWER

Treatment is actually part of the strategy for managing malaria, so I will come back to that later. The other main ways in which malaria is controlled is through prevention, diagnosis (followed by treatment if necessary) and education.

1) Prevention:

There are a number of ways to prevent malaria. These can be placed into two categories: medication and vector protection.

For medication, there are drugs you can take to prevent the malaria parasite from developing after someone is bitten by an infected mosquito. These drugs are known as “chemoprophylaxis.”

There are several different kinds, such as doxycycline, mefloquine (marketed as Lariam), atovaquone-proguanil (marketed as Malarone) and chloroquine—the type you use depends on the type of malaria present in the area. For example, in much of Africa and India, malaria is resistant to chloroquine, so this cannot be used as a prophylactic. In parts of Thailand, resistance to mefloquine has emerged. However, if the appropriate type of prophylaxis is used, it is very effective against malaria.

The problem is that these drugs have not been tested for long-term use, can be expensive and may have side-effects. Therefore they are of limited use for people who live in areas where malaria is endemic, and are more appropriate for travelers who are in malarial areas for short amounts of time. However, anti-malarial medication may be used in a very specific way for people at particularly high-risk for malaria, such as pregnant women and young children. In these cases, the high-risk individuals receive a dose or series of doses of malaria medication in order to prevent malaria. This form of prevention is known as intermittent preventive therapy (IPT).

Vector prevention involves protecting oneself against getting bitten by mosquitoes. This can involve wearing long-sleeved clothing in the evenings and at night, when malaria mosquitoes are most active, or wearing insect repellent on exposed skin. Indoor residual spraying, whereby repellent and insecticides are sprayed inside the house, can also be used to bring down the number of mosquitoes.

Another very effective technique for preventing malaria is to sleep under a long-lasting insecticide-treated bednet. The mesh acts as a barrier against the mosquitoes, and the insecticide impregnated in the mesh further repels the mosquitoes and prevents them from biting through the mesh.

2) Diagnosis

Diagnosis is considered a crucial step in controlling malaria, since it ensures that people are receiving correct medication, whether for malaria or for another condition which is causing their symptoms. Currently, the most commonly observed form of diagnosis is through microscopy of thick and thin blood films, which can be stained if necessary. These should be read by a qualified technician to determine both the species of malaria infection and the intensity of parasitaemia (number of parasites in the blood).

More recently, other methods for diagnosis have emerged. These include the use of rapid diagnostic tests (RDTs) which utilize a drop of blood applied to a reagent strip which very quickly reacts to show whether the patient is infected with malaria. While considered generally more sensitive than blood films, some RDTs don’t test for all types of malaria parasite, and many require that the reagents be kept cold in order for the test to be effective, which can be a problem in some developing countries.

Perhaps the most sensitive test for malaria is through PCR, which can theoretically detect a single malaria parasite in a drop of blood, and also determine the species. However, measures of infection intensity require an alternative form of PCR, called real-time PCR, which can be technologically challenging. All forms of PCR require a lot of expensive equipment and reagents, trained technicians and take several hours to run.

3) Treatment

Malaria treatment can be determined based on the diagnostic results, as well as other factors, such as:

  • The area where the infection was acquired and its drug-resistance status
  • The clinical status of the patient
  • Any accompanying illness or condition
  • Pregnancy
  • Drug allergies, or other medications taken by the patient

Most uncomplicated (i.e. not severe) cases of P. falciparum can be treated with oral medication, such as artemisinin-based combination therapies (ACTs). Artemisinin is given in combination with another anti-malarial drug in order to prevent resistance from developing in the parasite. Patients who have complicated (severe) P. falciparum malaria or who cannot take oral medications should be given the treatment by continuous intravenous infusion, with quinine recommended by WHO as the first-line treatment.

Other drugs, which are used in some settings, are considered second-line or alternative forms of treatment. These include:

  • chloroquine (very rarely used for P. falciparum, due to widespread resistance)
  • atovaquone-proguanil (Malarone®)
  • mefloquine (Lariam®)
  • quinine
  • quinidine
  • doxycycline (used in combination with quinine)
  • clindamycin (used in combination with quinine)

In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses, for patients with P. vivax or P. ovale malaria. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency.

4) Education

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

Malaria Prophylaxis in Ghana, Africa

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QUESTION

My husband will be traveling to Ghana soon. We have Mefloquine and Primaquine. Which one do you think is best for prophylaxis in Ghana? He also has Fansidar, but we understand it’s best not to use this for prophylaxis. Thank you for your help!

ANSWER

There are positives and negatives associated with both of these medications. Mefloquine is recommended for travelers in Ghana (whereas the Centers for Disease Control does not explicitly recommend primaquine for this area, since primaquine is particularly effective against Plasmodium vivax malaria, which is almost completely absent from West Africa), and only has to be taken once a week (primaquine must be taken daily).

A disadvantage with mefloquine is that you must start taking it 2 weeks before your trip, whereas primaquine can be started as little as 1-2 days before travel; mefloquine is also not recommended for people with a history of psychiatric or mental problems, as it can cause severe side effects. Even healthy individuals often report disturbing dreams or increased agression/anxiety while taking mefloquine. However, one major disadvantage to primaquine is that you must be tested for G6DP deficiency prior to taking it – your husband may have already done this, prior to being prescribed the drug. People with G6DP deficiency should not take primaquine.

Overall, the decision comes down to personal preference, though from a disease perspective, mefloquine would probably be the better choice for travel to Ghana, given the higher prevalence of P. falciparum malaria in this region, as opposed to P. vivax. Other options to consider would be atovaquone-proguanil (Malarone – expensive, taken daily, but very effective and very well tolerated by most people, with very low side effects) or doxycycline (very cheap, taken daily, is an antibiotic so can prevent some other infections but often results in sun sensitivity, which can be a problem in the tropics). Both of these can be started 1-2 days before arriving in the malarial area.

After you come back, I would be very grateful if you could take our malaria medication side effects survey, as we are very interested in hearing from our readers what their experiences with malaria prophylaxis and treatment have been.

Malaria Effects on the Body

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QUESTION

What are the effects of malaria on the body?

ANSWER

Malaria has a number of effects on the body. The parasite passes from the blood (where it enters via the bite of an infected mosquito) into the liver, where it reproduces and changes form. After a period of 1-4 weeks (usually – it can be longer) in the liver, the malaria parasite re-enters the blood and begins to infect red blood cells, undoing more reproduction inside the cells and then, in synchrony, bursting out once the cycle is complete. This process of reproduction and destroying red blood cells results in a build-up of toxins and debris in the blood; the resultant immune reaction produces side effects which are the common observable symptoms of malaria, such as fever, chills, nausea and aches.

One particular type of malaria, Plasmodium falciparum, is also able to modify the surface of red blood cells it infects. It causes these cells to become “sticky”, so they lodge in the small blood vessels leading up to major organs. This build-up is called sequestration, and results in reduced blood flow and oxygen deprivation in the organs. When sequestration occurs in the blood vessels in the brain, the patient may experience impaired consciousness, psychological disruption, coma and even death – this manifestation is called “cerebral malaria”.

If diagnosed and treated promptly, the malaria parasites in the blood can usually be killed rapidly and the patient will soon enjoy a complete recovery. With two forms of malaria, P. vivax and P. ovale, the parasite can remain dormant in the liver for months or even years, resulting in relapse of disease at a later date. To prevent this from occurring, patients with these types of malaria can sometimes take primaquine, a drug which kills the liver stages of the malaria parasite as well.

Reoccurring Malaria

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QUESTION

Can malaria reoccur year after year from a single infection? I have been told that it comes back every year by many people. I have had malaria once and it never came back after successful treatment. My thinking is that once the parasite has been eliminated from the system it is gone unless you get bitten again.

ANSWER

There are several different types of malaria that infect humans, and two of these species (Plasmodium ovale and Plasmodium vivax) can recur from year to year after a single infection.

The way it happens is that these types of malaria are able to form dormant life stages which hide in the liver. Most malaria medication only targets the blood stage form of malaria, and so these liver stages escape being killed by the medication, and can survive for long periods of time without the patient knowing about them. Then, at some point later (no one knows exactly what triggers the relapse—there is evidence that infection with other forms of malaria can instigate relapse, or being bitten by mosquitoes, or even just the climate), the liver stages activate again and re-enter the blood stream, which causes a renewal of symptoms.

It is possible to prevent these relapses—there is one type of medication, called primaquine, which is able to kill the dormant liver stages and thus completely clear the patient of malaria. However, it is important to talk to your doctor before taking primaquine, as it is not suitable for some people (especially those with G6DP deficiency).

Apart from these two types of malaria, the other three forms that infect people (P. falciparum, P. malariae and P. knowlesi) cannot reoccur in the same way as described above – if you have been infected with one of these, and then been successfully treated, you cannot get the disease again unless you are bitten by another infected mosquito.

Treatment of Chronic Vivax Malaria

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QUESTION

What is the treatment of chronic Vivax malaria?

ANSWER

Blood stage infection with Plasmodium vivax can usually be treated successfully with chloroquine, though resistance is spreading in some areas (notably the Pacific Islands, Papua New Guinea, parts of south-east Asia and especially Indonesia, and Peru). P. vivax is also sensitive to artemisinin-based combination therapies (ACTs) and as no resistance to artemisinin has been reported, these are widely recommended (though combinations which include sulfadoxine-pyrimethamine should be avoided as many strains of P. vivax appear to be resistant to pyrimethamine).

Liver stage (i.e. relapsing) P. vivax can only be treated with one drug: primaquine. Instances of liver stage treatment failure are relatively commonplace, and may be strain or dosage dependent. Primaquine is not recommended for people with G6DP deficiency, so potential patients, and particularly those from locations or ethnic groups known to have high levels of G6DP deficiency, should be tested prior to treatment.

Malaria Testing

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QUESTION

My daughter is in Kigoma, Tanzania and has the symptoms of Malaria. She was given Duo Cotecxin and it seems to have started making her feel better. But after reading up on all the different types of Malaria parasites I am wondering if a blood test reading at a clinic would be recommended or is it too late for an accurate reading now that she is on meds?

ANSWER

I am always very nervous about people given malaria medication without a proper blood test-based diagnosis. The symptoms of malaria can sometimes be very general, and I have recently seen some data from elsewhere in Tanzania whereby clinics are giving virtually everyone who comes in with a fever malaria medication, even if the blood tests are negative! This is a sure way to develop resistance to malaria drugs, plus exposes people to the potential side effects of medication that they may not need, while also failing to diagnose or treat them for whatever other condition they may also have.

In your daughter’s case, since she is feeling better, it may be that she did indeed have malaria. Regardless, now that she is taking the treatment, she should make sure to finish the full dose of pills. It still could also be worth going in for a blood test. In any case it will put your mind at rest, and if there are still traces of the parasite in her blood, then you will know for sure that she had malaria. Moreover, it might tell you which type of malaria she had. While P. falciparum is the most common form of malaria in sub-Saharan Africa, cases of other types, such as P. vivax and P. ovale, are being reported more and more frequently.

These two types can form liver stages (called hypnozoites) which can stay dormant for weeks, months or even years after the initial infection. During this period, the patient will experience no symptoms; then, when the hypnozoites activate and re-enter the blood again, the patient will get a “relapse” of the malaria symptoms. The only drug available to kill these liver stages is primaquine; as such, if your daughter is positively diagnosed with P. vivax or P. ovale malaria, she should be aware of the possibility of a relapse, and perhaps discuss with a doctor the possibility of taking primaquine.

I hope she recovers fully and enjoys her stay in Kigoma—I spent almost a month out there last year!