Can the PCR blood test identify hypnozoites?

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QUESTION

I have never been diagnosed with malaria but returned from Turkey in 2007 (P. Vivax endemic area; Diarbykar & Mardin areas). My symptoms were consistent with malaria and I have now had 5 relapses since then, averaging one occurrence per year. I now have impaired kidney functioning and I am uncertain if this could be because of undiagnosed malaria? Would the PCR blood test at anytime be an option to conclusively rule out malaria or would blood need to be drawn during an actual relapsing event?

ANSWER

You have certainly done your research! It’s great to hear from someone who is so well informed about the risk areas they traveled too and the diagnostic options. You’re right in thinking that PCR is only appropriate during an active relapse; while the malaria parasites are dormant in the liver (called hypnozoites, in that form), they are extremely hard to detect. One option could be to investigate the possibility of taking a test to look for antibodies to the P. vivax parasite. These tests are often referred to as ELISAs (enzyme-linked immunosorbent assays) and they can sometimes be useful for testing for malaria in between relapses because the antibodies your body produces against the malaria parasite during the relapse phase can stick around in the blood for weeks, or even months or years. Therefore these tests are not very useful for people in endemic areas (who may always have these antibodies, regardless of their current infection status) but for travelers who have been exposed a limited number of times, this test may be able to say whether you have at some stage been infected with P. vivax; together with your clinical history, this will provide strong evidence to your doctor that you might need to discuss the possibility of taking primaquine, the drug which can kill the dormant hypnozoites and prevent further relapse.

Abdominal Pain in Malaria

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QUESTION

What is the cause of abdominal pain in malaria?

ANSWER

Often, abdominal pain in malaria occurs in the early stages of malaria infection (first week or so) and can be caused by the rapid enlargement of the liver and spleen as they become inflamed. During malaria infection, and particularly that with Plasmodium falciparum, the most deadly and severe form of malaria, large numbers of red blood cell become sequestered in the liver and the spleen (as well as other major organs). A danger is that if the spleen becomes too enlarged, it may rupture, causing massive internal bleeding which can be incredibly dangerous to the patient, and  lethal without immediate medical attention.

Recurrence of Malaria

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QUESTION

If a person treated for malaria after being infected from a malaria endemic country of West Africa and cured then he travel back to his country which does not known for malaria endemic region of the world. Question is: Is there any chance of re-occurrence even he is not being exposed to malaria spreading mosquito for some time may be year?
Is it true Malaria parasites stays in liver as hibernation for a long period and attack after many months or year?
If so what treatment can prevent it?

Please advise.

ANSWER

There are several different types of malaria which are found in West Africa, and the most common and deadly form, Plasmodium falciparum, is not able to hibernate in the liver. However, two other types of malaria are able to lay dormant in the liver – these two kinds are called Plasmodium vivax and P. ovale. Both are not nearly as common as P. falciparum in West Africa, though P. ovale has been reported at prevalences of over 10% in some areas, which is double its usual prevalence elsewhere in the world. Weeks, months or even years after an initial infection with P. vivax or P. ovale, the patient may experience what is known as a relapse, which is when the dormant liver forms become active again and re-invade the blood stream, causing a renewal of malaria symptoms. These relapses can be treated with normal anti-malarial drugs (even chloroquine, in many cases), but a different drug is required to kill the dormant liver forms and prevent future relapse. This drug is called primaquine, and may not be suitable for people with certain types of G6DP deficiencies, so you should talk to your doctor about having a test for this condition before taking primaquine.

Positive RDT After Malaria Treatment

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QUESTION

I have Pv malaria repeated 2 times in two month then doctor give arthemether, lumefantrine tablet for three days twice in a day and primaquine tablet for 14 days..after this treatment malaria show positive on rapid test by a faint line….what is this?

ANSWER

It sounds like your doctor has treated you appropriately. What the line on the rapid test means depends a bit on the type of test it was. Some of these rapid tests look for parts of the malaria parasite which the body recognizes as causing disease (called antigens)—sometimes, these antigens can persist a bit in the body even after the malaria infection has been cured. Therefore, that could explain a slight positive result in a  rapid test soon after treatment. It will be important to follow this up with a second rapid test, maybe in a week, just to make sure you do not have an active infection. You should also be aware that Plasmodium vivax can remain dormant in the liver (primaquine is used to kill these dormant forms), and if primaquine treatment does not work, you will still be ay risk of relapse but you will not have any malaria parasites in the blood, and thus even a rapid test will be negative.

Recurrence of Malaria Symptoms

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QUESTION

If a person suffering from malaria is given the proper treatment and he gets well but he again develops the symptoms of malaria..? These symptoms would arise from liver or blood? Who’ll be responsible for the recurrence of the symptoms?

ANSWER

Malaria can come back in three ways: first of all, the person could have been successfully treated, but then re-infected again by being bitten by an infected mosquito. In these cases, the person should focus on improved malaria prevention, such as sleeping under a long-lasting insecticide treated bednet.

Secondly, the patient could have recrudescence: when the patient takes medication, the treatment kills most of the malaria parasites in the blood, and enough so the patient feels better again, but some parasites still remain. Then, after the treatment finished, the parasite is able to replicate again, they increase in number in the blood and the patient feels ill again. In this case, you would say the infection came back from the blood, and the patient should take another dose of anti-malarials, but of a different kind to that which they originally had, in order to kill all of the parasites.

Finally, there is what is called relapse, which only occurs with two types of malaria: Plasmodium vivax and Plasmodium ovale. These are able to form dormant stages in the liver, so even when all the parasites are killed in the blood by the malarial treatment, these dormant forms survive. Many weeks, months or even years later, these dormant liver stages can re-activate and enter the blood again, causing new malaria symptoms. In this case, the liver was the source of the parasites. Again, the active blood infection should be treated with anti-malarials, but the patient should also talk to their doctor about taking primaquine, a drug which can kill any remaining dormant liver forms and thus prevent future relapses.

Malaria: Mode of Transmission

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QUESTION

What is the mode of transmission of Malaria?

ANSWER

Malaria is transmitted normally via the bite of an infected mosquito. These mosquitoes, always female and of the genus Anopheles, carry malaria parasites in their salivary glands. The parasites, at this part of their life cycle known as sporozoites, are introduced into the host’s blood when the mosquito takes a blood meal. From there, the sporozoites travel to the liver, reproduce (this process may take several weeks), then finally re-enter the blood stream. At this point, the patient will begin to experience symptoms. Eventually, the malaria parasites change again, into gametocytes, which are picked up by another mosquito, again when it bites the infected person. In this way, the life cycle of the malaria parasite continues.

Because malaria reproduces in the blood and in the liver, in some cases malaria can be transferred via organ transplant or blood transfusion. In addition, malaria parasites can cross the placenta, and so can be transmitted from a mother to her unborn child, either in the womb or during childbirth. This is known as congenital malaria.

Malaria with Liver and Kidney Problems

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QUESTION

Can someone please tell me what kind of malaria this is. What part of the body it attacks, e.g., cerebral? Patient presenting with liver and kidney “problems”. What could these be?

ANSWER

I am not sure I fully understand your question, but the type of malaria which is associated with cerebral malaria, and also tends to have the most adverse effects on other organs (such as the kidneys) is Plasmodium falciparum. However, all species of malaria go through the liver as part of their life cycle, so all may invoke some kidney problems. The four other types of malaria which infect humans are P. vivax, P. ovale, P. malariae and P.knowlesi.

How Long Does it Take for Malaria to Affect the Body?

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QUESTION

How long does malaria take to actually affect you?

ANSWER

When you are bitten by a mosquito that is infected with the parasites that cause malaria, some of the parasites enter your blood stream in the mosquito’s saliva. After that, it will take at least one week, and usually between two and four weeks, before you start to feel the symptoms of the disease. This is because the parasite first goes to the liver, where it infects liver cells and undergoes replication. These cells mature into a form called merozoites, which then re-enter the blood stream, and start to infect red blood cells. The stage in the liver is not symptomatic for the patient, and is known as the pre-patent stage; once the merozoites start infecting and killing red blood cells, the patient will begin to feel sick, and the infection is said to have become patent.

Malaria Life Cycle

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QUESTION

What is the life cycle of malaria?

ANSWER

Malaria is caused by a single celled organism in the genus Plasmodium. Five species of Plasmodium infect humans, but all follow a very similar life cycle, including two separate cycles of asexual reproduction in the human host (one in the liver, called the exo-erythrocytic cycle, and one in the blood, and specifically inside red blood cells, known as the erythrocytic cycle) and a sexual reproductive stage inside the mosquito definitive host (usually called the “vector”). A schematic of the full life cycle is below, courtesy of the CDC (www.cdc.gov).

malaria life cycle CDC

Schematic of the malaria life cycle, courtesy of CDC (www.cdc.gov)