Malaria, Mozzies and Mzungu: Part 4

This is the 4th article in our series on malaria, if you want to read the others go on The Eye website and you will find the full or even expanded articles. We have covered the life cycle, the disease, the effect of immunity, and diagnosis. We asked the question, why is a Pakwatch schoolboy who is bitten 5 times a night completely well most of the time, yet a Mzungu bitten once on a weekend in Murchison is very ill in 10 days and without treatment dead in another week? More importantly, why are so many travelers told they have malaria even when they are taking prophylaxis and don’t even have a fever, or have only been in the country for 4 days?

We looked at the reality of malaria diagnosis, the difficulty of relying on a blood slide, and the results of some research highlighting the very real problem of overdiagnosis.
One about to be published article shows some research in Tanzania where in one area 98% of people diagnosed and treated for malaria did not have malaria. So how do you know if you have malaria and not another cause of fever, a virus, or meningitis, or a hangover?

If you are on holiday, away from home, or sitting worrying in your house at midnight with a hot cross 2 years old and desperate for a good night’s sleep, what do you do? Your friends confidently tell you the child has malaria, but you really don’t think so. Is the child going to go unconscious before morning? Is it safe to carry on our trip? Is it safe to be pregnant in Uganda, won’t malaria cause a miscarriage, and the treatment harm the baby?

Article 3 finished asking, “What is the answer?” Read On!

First common sense! Ask the 3 questions looked at in detail in the last article: where were you 10 days ago, am I taking prophylaxis, do the symptoms fit. Common sense can take you a long way in medicine!

The next best answer is the malaria rapid test. They have a sensitivity of finding malaria if there is 1 parasite in 25,000 cells. In theory, The Gold Standard lucky expert could find one parasite in 50,000 if he looked for long enough. However as the number increases by about 10 every 2 days, then the worst that can happen is that 2 days later there is 1 parasite in 2,500 cells. Not a big deal. You need to wait another 4 days, i.e. a total of 6 days, to get the potentially fatal 5% parasite, count. So a good malaria rapid test, repeated the next day if negative is going to find your malaria long before you get seriously sick. It will pick up as a faint positive while you still have a slight headache and a fever that you hardly know is there.

Magic
So what is the problem?
First. There are some very poor tests on the market. We found one that missed malaria even with one in 2,000 parasites. It will find them before the fatal amount, but still far too insensitive to be of any use in the field. We wrote to the importer requesting them to take it off the market. We cannot name it! But the following we can recommend. Becton Dickinson, ACT, and MR were made in Cape Town and distributed by The Surgery. Those are genuinely sensitive to one in 25,000.

Next problem. They go out of date. If in doubt trade it in for a new one.
Next. Too much heat ruins them. They may give a false positive, telling you that you have malaria when you don’t or miss it when you do. If it has been cooked, chuck it.
Next. The reagent evaporates. It does not happen if the top is screwed down properly! We have tried it, we kept them upside down for weeks and they do not leak if properly tight! If your bottle is empty, get it refilled. It is only buffered water, and we have liter bottles of it.

Next. They will miss vivax and p. malaria. It doesn’t matter, as neither can cause severe malaria, but can be a big nuisance. So if you get a 2-day or 3-day recurrent fever with a persistently negative rapid, think of other species. One good clue: urobilinogen in the urine. It makes it very dark even if you are drinking plenty. There are vivax rapid tests, even some that pick up all 3. They cost a bit more but if you live in a vivax area, i.e. a bit cooler, get the kit that tests for both.

Next. They stay positive for a very long time after cure. It picks up a protein called the F protein that is released by the parasites. It carries on circulating in the blood for weeks after the parasite is dead and gone; until it is removed by enzymes that cut it up and metabolize it. So in a semi-immune with a stimulated and efficient enzyme pathway, it goes negative in a few days after treatment. In a traveler, it takes up to 6 weeks. So a positive rapid 3 weeks after treatment does not mean you have another bout of malaria. It might! Or it might still be fading. All you can do is repeat the next day. If it is an even stronger positive that means you have new malaria. If it is fainter then it is the old one still showing positive.

However, this is not only a problem; it is also one of the good things about the rapid tests. It means we can tell if someone really did have malaria after treatment. So if someone has “malaria” and is treated and doesn’t get better, we can see if they really did have malaria or we need to look for another disease causing the symptoms. Every day we see people who have been treated for “malaria” with very unlikely symptoms. In about 9 out of 10 cases we find the rapid is negative.

Summary. Diagnosis of malaria is not as straightforward as you may think. The symptoms are not specific, very many different diseases can be wrongly diagnosed as malaria, and blood slides are easily misinterpreted.
If the diagnosis is missed for too long it can be fatal. However, treating every disease like malaria can also be fatal.
A really expert microscopist with new slides, clean stains, and a properly serviced microscope, with negatives, repeated a day later, is the best method of diagnosing malaria, as they can tell if it is falciparum vivax or p. malaria, how many parasites there are and if the number is close to being dangerous.

In practice in most places, the most reliable method is the do-it-yourself malaria rapid test. It can be done at home, on the road, or on holiday back in Europe. It can save a lot of lives as well as lots of hassle. It will pick up malaria at very low densities of 1 in 25,000, including the time when they are “sequestrated” in the deep organs and therefore not seen in a slide. They also need to repeat negatives in 24 hours. They will miss the other species unless it is a multi-species test, and give false positives for up to 6 weeks after treatment. They can also be spoilt; out of date and done wrongly, they are not the perfect answer.

The absolute best is both! A rapid and a slide. If in doubt, remember common sense. And the most important piece of health equipment you can have with you is your mobile phone. In the next eye, we look at treatment