Pedro Alonso, at his office / Rodrigo Carrizo Couto.

“Rapid diagnostic tests are overlooked”

By AINHOA IRIBERRI. 25th APRIL 2016.

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GENEVA, SWITZERLAND — On Pedro Alonso’s (Madrid, 1959) office wall hangs a sheet with some Chinese characters. When the photographer asks permission to turn on a reading lamp to improve lighting, Alonso points at it and says: “That, that's really important.” And reads the framed motto: “Malaria is not just a task to be performed; it is a problem to be solved”.

Nothing better to achieve this goal than addressing the organism that, according to Alonso, still has a “huge burden” on issues like this, malaria itself, but also Zika, Ebola, or vaccines, among others. Since mid-2014 this physician is the head of the Global Malaria Programme of the World Health Organization. We talked with him about the rapid diagnostic tests (RDTs).

What role do RDTs play in the fight against malaria?

“We forget that one of the great revolutions has been made precisely in the diagnosis of the disease”

RDTs are the great forgotten of the past 15 years. When we talk about the great successes of malaria, we look at the insecticide impregnated mosquito nets that indeed have been key. We mention the vector control as a whole, new drugs against malaria, artemisinin derivatives - which were recognized with the Nobel prize - but we forget that one of the great revolutions has been made precisely in the diagnosis of the disease.

Was the situation very different before the appearance of these tests?

Just imagine. Before, the diagnosis was based on light microscopy. But how many people have access to a microscopist who can read microscopy, to a microscope that works, to someone who knows how to stain the sheets and read them correctly? I tell you: in Africa, a minimum percentage of the population.

And how did the idea come about?

The question is not so much that, but why this was not achieved before. In fact, the principle is the same as pregnancy tests. Although there had been many attempts to develop this kind of thing, its application to malaria, which seemed relatively clear, resisted...

What has changed?

What has modified the formula is that we now have a diagnostic test that, in less than a minute, gives a result and that can also be applied by non-specialized personnel in the most remote places in the world, even with no electricity. The tests can be done on the street itself, in what is called a point of care. Last year 200 million RDTs were distributed, this represents 200 million diagnoses (or discards) which would not had occurred otherwise.

How was malaria diagnosed before in places with no microscopes or technicians?

Until a few years ago, the main strategy was what we called presumptive treatment. If someone had a fever or was not feeling well in an endemic area, they were directly treated against the disease. RDTs have allowed us to treat only real malaria cases, so they have been one of the central tools against this disease.

Can all RDTs be trusted equally?

WHO supports those we call prequalified tests, available in a list on our website. We perform quality controls in all of them and only those who meet the criteria are selected. There are about 60 brands.

Do they all work with the same mechanism?

No. There are two. Most works by detecting an antigen called HRP II and the rest by locating the pLDH enzyme. Among the latter, we find the PMA test that detects simultaneously the two parasites - Plasmodium vivax and Plasmodium falciparum - which cause the most severe forms of the disease.

However, it seems that there may be a problem with the first...

No. We cannot talk about a problem yet. We are investigating some cases in which there have been failures in RDTs that detect HRP II. We had the first news through the Ministry of Health of Eritrea, where they began to see cases of malaria that had tested negative to RDTs but positive to optical microscopy.

What did the programme you direct do about it?

WHO led the investigation. We sent our best expert to Eritrea and she discovered that, indeed, there are areas in Eritrea where a major portion of the parasites do not have this protein or have stopped having it, which would be more worrisome. We begin to have data from other parts of Africa where something similar may be going on.

What is known for sure at this moment?

Rodrigo Carrizo Couto.

We know it has begun to be a problem. But we do not know whether these findings are casual, although the matter begins to look like a real risk. Before the publication of scientific papers on the subject, we want to get ahead. Of course, now the message is that we must maintain confidence in RDTs, not to question them and, of course, not to stop using them. From WHO we will be transparent with everything we find.

But if this finding is confirmed and generalized, is there a plan B?

Yes. Because it only affects RDTs based on the protein HRP II detection. We would have as a back up those that work with pLDH enzyme, although there are only one or two world producers of this type of RDTs that have passed quality controls, so at any given time there could be a supply problem. In any case, this is too much venturing; we send a message of calm with regard to the most used RDTs.

Despite the 200 million RDTs that have been distributed in Africa, does malaria diagnosis still remain a problem?

“We still have 200 million clinical cases of malaria each year and 438,000 deaths annually. It is technically 438,000 failures because no one should die of malaria”

Yes. It's one of our big challenges. We still have 200 million clinical cases of malaria each year and 438,000 deaths annually. It is technically 438,000 failures because no one should die of malaria. It is a reasonably preventable and perfectly curable disease when detected early. These failures are attributable to something we are not doing well in terms of prevention, but also in terms of diagnosis and treatment.

And why does diagnosis fail?

There is a clear problem of access. Although RDTs can be managed almost anywhere, there are many places in Africa where there is no direct access to minimum health services, which can be a hovel visited by a nurse once a week. And of course there is a communication problem, it is not the same to be 20 kilometers from Madrid than in an area of ​​Mozambique where, to cover the same distance, you have to cross three rivers and walk. There is also a problem of ignorance, but I would not say that is the most relevant, although it is clear that it is important to know that if your child is sick you should go first to a place where you can make a RDT and not to the local healer.

“If your child is sick you should go first to a place where you can make a RDT and not to the local healer”

Is the cost of RDTs a problem?

Most cost less than a dollar. It is a cost supported by the countries themselves and the Global Fund to Fight AIDS, Tuberculosis and Malaria, which is paid largely by public funds when countries devote resources to international cooperation.

If you had to put RDTs in a position regarding all measures to control malaria, which would that be?

In September we published a report on the global malaria situation in which we try to quantify the relative contribution of the different tools in the progress observed over the last 15 years. Actually, it is a question whose answer does not require large analysis, but we did it to stay calmer. What we found is what any student can say: prevention is more important than cure. Thus, the analysis goes on to say that more than 60% of the improvement is attributable to insecticide impregnated bed nets, but the rest is divided between better drugs and better diagnosis, where RDTs play an important role.