Recurrent Malaria

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QUESTION

can malaria represent itself after 50 years?

ANSWER

There are two types of malaria which can lay dormant for long periods of time, though I don’t personally know of more than a handful of cases where the relapse was a matter of decades after the initial infection. These two types are P. vivax and P. ovale, so if you know you were infected with one of these types a number of years ago, it is possible that you could experience a relapse many years later, though as mentioned above, it is rare for the time lapse to be as long as 50 years.

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 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.

Malaria Prevention

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QUESTION

What are the ways in which you can prevent yourself from being infected with malaria?

ANSWER

Malaria prevention consists of a combination of mosquito avoidance measures (since malaria is transmitted by infected mosquitoes) and chemoprophylaxis (medication to prevent the establishment of malaria in your body, if you do get bitten). Although very efficacious, none of the recommended interventions are 100% effective.

Mosquito Avoidance Measures

  • Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn.
  • Contact with mosquitoes can be reduced by remaining in well-screened areas, using mosquito bed nets (preferably insecticide-treated nets), using a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours, and wearing clothes that cover most of the body.
  • All travelers should use an effective mosquito repellent.
  • The most effective repellent against a wide range of vectors is DEET (N,N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children older than 2 months of age (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter). DEET should be applied to the exposed parts of the skin when mosquitoes are likely to be present.
  • In addition to using a topical insect repellent, a permethrin-containing product may be applied to bed nets and clothing for additional protection against mosquitoes.

Chemoprophylaxis

      • All currently recommended primary chemoprophylaxis regimens involve taking a medicine before travel, during travel, and for a period of time after leaving the malaria endemic area. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites.
      • Presumptive antirelapse therapy (also known as terminal prophylaxis) uses a medication towards the end of the exposure period (or immediately thereafter) to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites (dormant liver stages) of P. vivax or P. ovale. Because most malarious areas of the world (except the Caribbean) have at least one species of relapsing malaria, travelers to these areas have some risk for acquiring either P. vivax or P. ovale, although the actual risk for an individual traveler is difficult to define. Presumptive anti-relapse therapy is generally indicated only for persons who have had prolonged exposure in malaria-endemic areas (e.g., missionaries, volunteers).
      • In choosing an appropriate chemoprophylactic regimen before travel, the traveler and the health-care provider should consider several factors. The travel itinerary should be reviewed in detail and compared with the information on where malaria transmission occurs within a given country to determine whether the traveler will actually be traveling in a part of the country where malaria occurs and if significant antimalarial drug resistance has been reported in that location.
      • The resistance of P. falciparum to chloroquine has been confirmed in all areas with P. falciparum malaria except the Caribbean, Central America west of the Panama Canal, and some countries in the Middle East. In addition, resistance to sulfadoxine–pyrimethamine (e.g., Fansidar) is widespread in the Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, and in large parts of Africa. Resistance to mefloquine has been confirmed on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, in the eastern states of Burma (Myanmar), on the border between Burma and China, along the borders of Laos and Burma, and the adjacent parts of the Thailand–Cambodia border, as well as in southern Vietnam.
      • Additional factors to consider are the patient’s other medical conditions, medications being taken (to assess potential drug–drug interactions), the cost of the medicines, and the potential side effects.

The medications recommended for chemoprophylaxis of malaria may also be available at overseas destinations. However, combinations of these medications and additional drugs that are not recommended may be commonly prescribed and used in other countries. Travelers should be strongly discouraged from obtaining chemoprophylactic medications while abroad. The quality of these products is not known, and they may not be protective and may be dangerous. These medications may have been produced by substandard manufacturing practices, may be counterfeit, or may contain contaminants. Additional information on this topic can be found in an FDA document

Purchasing Medications Outside the United States.

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!

Duo-Cotecxin and Fansidar as Treatment

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QUESTION

My husband weighs and has malaria. He was told by the pharmacist to take 2 tablets stat, then 1 daily for five days followed by 3 Fansidar tablets. We live in Papua New Guinea. I see on the Duo-Cotecxin web site the dose is three tabs daily. Which is correct?

ANSWER

Fansidar is a very different drug to Duo-Cotecxin—it is made of a combination of sulfadoxine and pyrimethamine, whereas Duo-Cotecxin is an artemisisin-based combination therapy (ACT), consisting of dihydroartemisinin together with piperaquine. As such, the dosages and time courses of therapy are likely to be different. However, Fansidar is not usually recommended as treatment anymore—it appears to have low efficacy against Plasmodium vivax and in the 1980s and 1990s, the World Health Organisation and Center for Disease Control (CDC in the US) only recommended it for use against chloroquine-resistant P. falciparum.

However, nowadays, both organisations recommend ACTs (like Duo-Cotexcin) to treat all uncomplicated P. falciparum infection as well. Therefore, unless your husband has been diagnosed with P. ovale or P. malariae malaria (both of which are sometimes found in PNG), Fansidar probably should not have been the first-line treatment given to him. Keep a close watch over his recovery, and if there is any sign of reccurrence of the symptoms, go back to the doctor for another malaria test.

Repeated Malaria

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QUESTION

Since January 2011 I got three times malaria. Is it come regularly? Last week also I got maleria and I took medicine but still I have mild headache and sweating feeling tiredenes in between..

ANSWER

The timing of the repeated malaria episodes you have experienced means that it could be recrudescence (where treatment does not completely kill all the malaria parasites in your blood), relapse (where the malaria goes dormant in your liver, then comes back—this is only caused by Plasmodium vivax and Plasmodium ovale malaria) or even re-infection.

However, first of all, the most important thing is to make sure you are properly diagnosed with malaria and secondly, that you receive the right type of treatment for the kind of malaria that you have.

The symptoms of malaria are very general (fever, chills, nausea, tiredness, aches) and can also be caused by many other illnesses and diseases. As such, in order to confirm you actually have malaria, you should have a blood test (thick and thin blood smear, looked at under the microscope by a trained technician, or a rapid diagnostic test (RDT). In some places you can buy these RDTs from local pharmacies and do the test yourself at home).

Depending on where you live, there may be different types of malaria present; in this case, if you do have malaria, it is important to find out which one you have.

P. falciparum is the most common kind in sub-Saharan Africa and first-line treatment is an artemisinin-based combination therapy, such as Coartem – most areas have P. falciparum that is resistant to chloroquine, so this is not appropriate as treatment, nor are sulfadoxine and pyrimethamine combinations (such as Fansidar).

If you have P. vivax or P. ovale, chloroquine may be used, again depending on where you are and whether resistance is known from your area or not. In addition, you might also talk to your doctor about taking primaquine to prevent future relapse and recurrence of the infection.

Repeated re-infection can be prevented by protecting yourself more thoroughly against getting bitten by an infected mosquito. For example, you should sleep under a long-lasting insecticide treated bednet, screen your windows and doors and wear long-sleeved clothing at night and in the evenings. Indoor residual spraying, which coats your walls with insecticide, can also prevent mosquitoes from persisting inside your home.

Information About Malaria

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QUESTION

What is malaria?

ANSWER

Malaria is a serious and sometimes fatal disease caused by a tiny parasite that commonly infects a certain type of mosquito (of the genus Anopheles) which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Infection with P. falciparum, if not promptly treated, may lead to death. Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.

Malaria’s Scientific Name

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QUESTION

What is malaria’s scientific name?

ANSWER

The genus name for the single-celled parasite which causes malaria is Plasmodium. In the genus, there are five species which infect humans: Plasmodium falciparum (the most deadly kind), P. vivax, P. ovale, P. malariae and P. knowlesi.