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.

What Cell count defines malaria?

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QUESTION

What Cell count defines malaria??

ANSWER

If you are referring to the cell count for diagnosis, then really the answer is that if ANY malaria parasites are observed in a blood film, then the slide should be considered positive for malaria. Of course, some people can have low levels of parasite in their blood, which are not easily detected under a microscope, using a blood slide. These people are also obviously positive for malaria, but have less severe symptoms or indeed may not have any symptoms at all. If they have symptoms, they may need to seek an alternative form of diagnosis, such as a rapid diagnostic test (RDT) or PCR (polymerase chain reaction).

Malaria Detection

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QUESTION

what’s the newest form of malaria detection?

ANSWER

While the traditional form of malaria detection has been through microscopy of a blood film slide, two new technologies have recently emerged. The first is the use of reagent strips, which are impregnated with molecules that bind to various other proteins present in the blood during a malaria infection. These reagent strips are usually manufactured as part of a rapid diagnostic test (RDT) kit, whereby a patient only has to provide a single drop of blood, and the result can be read within minutes, a bit like a pregnancy test. The other new method which has emerged is based on PCR (polymerase chain reaction) technology. This method looks for malaria DNA directly in the patient’s blood, using specific sequences of DNA that are unique to the malaria parasite. This method is expensive and takes several hours at minimum, but is very sensitive, and even very low levels of malaria can be detected.

Malaria with Eye Pain

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QUESTION

I am having malaria with severe eye pains. What is this?

ANSWER

Have you actually been diagnosed with malaria, or do you just think you have malaria based on the symptoms? If the latter, I would suggest you visit the doctor immediately. Eye pain is not usually associated with malaria (beyond the fact that some headaches manifest behind the eyes), whereas eye pain is a common symptom of dengue fever, which is common in many of the same parts of the world as malaria.

The other symptoms of dengue include fever and nausea and are thus similar to the general symptoms of malaria, allowing them to be mistaken for each other in some cases. If the pain worsens with eye movement, this is also characteristic of dengue fever. A key symptom is the presence of a rash, similar to that of measles.

Diagnosis is usually made based on clinical presentation, so it is crucial you see a doctor or visit a clinic. Other tests, such as a tourniquet test or a white blood cell count, can also assist diagnosis. If necessary, there are also laboratory tests, such as cell culture or PCR, which can be used to confirm the infection.

Diagnostic test for malaria?

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QUESTION:

What are the possible diagnoses tests?

ANSWER:

A blood test is usually required to diagnose malaria, although the blood can be used in a number of different ways. The most common, traditional form of diagnosis is a blood smear, observed under a microscope by a qualified technician. These can be “thick” or “thin”; the “thick” smear examines a whole drop of blood for the presence of the malaria parasites infecting the patient’s red blood cells. Because a relatively large volume of blood is examined in this way, the thick smear is useful for detecting low levels of parasites in the blood, and therefore is good for an initial “positive or negative” diagnosis. The thin smear allows for a closer look at the infected blood cells, and thus can be used to identify the species of malaria, which can be important for giving the patient appropriate treatment. The danger with blood smears is that very low intensity infections can sometimes be missed, given the a low number of parasites in the blood.

More recently, a number of antibody tests have been developed to test for malaria. These so-called “rapid diagnostic tests” (or RDTs) do not require the expertise of a blood smear and only need a tiny droplet of blood, and so can even be performed at home as part of a self-testing kit. Different tests have been developed to test between the various different species of malaria. While quick and easy, there are some concerns over the sensitivity and specificity of the various tests; trials in the field have gone some way to quantifying the effectiveness of these tests in different contexts. One potential advantage of RDTs is that in some cases they seem capable of positively diagnosing low intensity infections, that would be missed by traditional blood smear. A disadvantage for wide-spread use of these tests, especially in low resource settings, is that they are very expensive.

Finally, the advent of DNA-based techniques for identifying malaria parasites means that PCR (polymerase chain reaction) can be used on a patient’s blood for an almost fool-proof diagnosis, not only of species but also, to a certain extent, of intensity. However, this procedure takes time, is expensive and requires a fully equipped laboratory with trained personnel; as such, it is not usually used for every day diagnosis of malaria infections, and especially not in developing countries where the vast majority of malaria cases occur.

Do I have malaria?

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QUESTION:

Hi, I went to Ivory Coast August/2003 back March/2004, took some pills to help prevent Malaria on my trip but ran out and did not get more. While I was there I got many mosquito bites.

Around October/03 became very sick, got tested for malaria at the hospital in Quebec but negative. Now May/2011 still have all the same symptoms, flu like symptoms, feeling cold most of the time, chills headaches, tired.

Is there any way I got it? I’ve gone to doctors and doctors and no one can seem to find what is causing this? I am tired of taking tylenols all the time for the body ache. My wife is from there and she’s so sure that I got it from seeing how I am since she’s been around it all her life. Can you help me?

ANSWER:

There are definitely types of malaria that can cause relapses of symptoms many months or even years after an initial infection. These types are not common in the Ivory Coast but if you had many mosquito bites then it is certainly possible that you were exposed. What kind of test did you have for malaria when you returned to Canada?

Often, the test is by looking at a microscope slide of your blood under the microscope—the problem with this test is that it is not very sensitive for low levels of malaria, for example, after the worst of infection, and especially with the types of malaria that cause relapse (these types, P. ovale and P. malariae being the ones you might expect from Ivory Coast, tend to cause less severe illness than the more common type of malaria in Africa, called P. falciparum, doesn’t relapse in the same way, but results in much higher levels of the malaria parasite in the blood, which makes it easier to diagnose on blood slides). Also, since malaria is relatively rare in northern countries like Canada, laboratory technicians are not as experienced at diagnosing the parasite as they are in countries where malaria is endemic.

Having said that, there are of course lots of other illnesses which also cause symptoms similar to that of malaria – fevers, chills, etc. What I would recommend is that you re-visit the doctor, and ask for a more sophisticated test for malaria. Mention that you have had a relapse of symptoms—this should prompt them to use more sensitive tests, such as PCR or a rapid diagnostic test, and to look specifically for P. ovale or P. malariae. Not only will this answer your question about whether you have malaria, but it will allow the doctors to give you the appropriate treatment for your current symptoms (probably chloroquine) as well as treatment to prevent any further relapses (primequine).

Hope this helps!