A Nigerian Trio in Malaria: Over-diagnosis, the Chloroquine mystic & malaria in pregnancy

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By Prof. Wellington Oyibo, Consultant Medical Parasitologist, Lagos University Teaching Hospital, LUTH, Idi-Araba.

Background

I believe the primary reason for the veiled reality of the full import of malaria in our society is because it is so prevalent that it has become an “all-too-familiar disease”. The resultant effect of this over familiarity is an abundance of misconceptions among the general populace and even among healthcare providers about malaria diagnosis, treatment and prevention.

Over-diagnosing Malaria in Nigeria

I conducted a research (published last year) on parasite-based microscopy diagnosis done among 1211 0–12 years old children who had a fever and attended a Primary Health Centre in Lagos, Nigeria and were clinically diagnosed and treated based on symptoms with the recommended anti-malarial drugs. The Result showed that only 20.7% of those children were slide positive for malaria. 83.1% of the children under 5years of age were slide negative and had been treated with Artemisinin based combination therapies (ACTs) in line with the Integrated Management of Childhood Infectioins (IMCI) guidelines and standard practice of the Clinic. The obvious conclusion was that over-diagnosis and over-treatment of malaria in our environment was high.

Outside the healthcare setting the usual regularity of simple malaria in tropical countries like Nigeria has the effect of making self-medication commonsensical. However, an underlying fact that a non-health personnel may fail to appreciate in this case is that malaria does not have its own peculiar symptoms. Indeed a majority of the populace shows the typical commonly associated features such as fever, headache, bitter taste in mouth, loss of appetite, nausea, vomiting, joint aches, a general feeling of unwell, etc and by far the commonest is FEVER.

However, fever is a non-specific symptom because it could also be similarly present in other health conditions caused by infectious agents such as bacteria or virus; non-communicable diseases at its onset, wounds/burns etc. Ignorance of this basic fact has resulted in the over-diagnosis and subsequent overtreatment of malaria. A mere assumption of malaria based on previous experiences that is similar to a new presentation could be very wrong if a confirmatory parasite-based test diagnosis is not done. The requirement for parasite-based confirmation of suspected malaria cases now forms the best practice in malaria case management in the country. The need to conduct a test before treating malaria is so important and the increasingly widespread availability of Rapid Diagnostic Test (RDT) kits should facilitate this. Not only will reduce this practice reduce over-diagnosis and over-treatment of malaria, it will also avert the danger of glossing over other life-threatening conditions may have otherwise been missed.

This notwithstanding, children under 5 years of age presenting with fever or  with a history of fever in the past 24 hours amongst other symptoms, should be treated for malaria in addition to other treatment where diagnostic facilities cannot be accessed.

Demystifying the Chloroquine magic

First and foremost, Nigeria’s Malaria Control guideline clearly stipulates that Artemisinin Combination Therapy (ACT) is the ideal anti-malarial medication. ACTs have been shown to have the ability of clearing the blood stream of the malaria parasites. However, unlike these ACTs which only possess anti-parasitic properties, Chloroquine has an additional anti-pyretic effect -that means, chloroquine has the ability to directly reduce fever. Unfortunately, it is a proven fact that malaria parasites are now resistant to chlororquine. The implication is that individuals (sadly, including some health managers) who still use chloroquine tout about their “better” outcome because of this associated fast fever relief. These practices abound in areas where parasite-based diagnosis is not done or not accessible. In reality, the feverish symptom itself should and can be taken care of by any regular over the counter paracetamol product. Proper treatment to eradicate malaria from the blood stream has to be with the recommended ACTs, in combination with an anti-pyretic like paracetamol for symptomatic relief. Malaria treatment with chloroquine is now obsolete.

There have been rigorous therapeutic efficacy trials on our recommended ACTs with overwhelming evidence based results affirming their effectiveness. Again, the vital issue of high quality malaria testing comes into play before any arguments may be made on the efficacy of ACTs.

What is unique about Malaria in Pregnancy?

In the tropics, recurrent malaria infection helps adults to develop a form of resistance to malaria as the body system has grown to recognize the P. falciparium parasite. This “resistance” is what is referred to as an “Acquired Immunity” –acquired because no one is born with it. While this immunity DOES NOT entirely prevent a malaria attack, it helps to safely limit the infection by preventing severe complications of malaria. The natural stress of pregnancy reduces this functionality and P. falciparium additionally adopts a special attachment to the placenta… which can only be present in a pregnant woman.

Infection by the Plasmodium falciparium specie of malaria parasite can have dire consequences during pregnancy. The reason is that the infected red blood cells express a uniquely different subset of variant surface antigens within the PfEMP1 protein family, which is not found in non-pregnant individuals. It is this peculiarity that enables the infected red blood cells to selectively bind with Chondroitin Sulfate A (CSA), which is responsible for cytoadhesion at the placenta receptors. All the attendant complications of malaria to the unborn child is based on the premise of this hidden attachment and multiplication of the malaria parasite within the placenta.

However still in malaria-endemic regions, a natural protective immunity against malaria in pregnancy is also eventually acquired by women in the course of subsequent pregnancies. This special acquired immunity is as a result of developing anti-PfEMP1 antibodies which now recognize those uniquely marked placental infected red blood cells within the woman. These antibodies are female-specific (that is, not produced by males) and they are parity-dependent (that is, increases with number of pregnancies). Thus with subsequent pregnancies, especially from the third and above, the immune response against the malaria parasites increases and therefore the risk of developing severe consequences of malaria in pregnancy is minimized.

This is why EVERY pregnant woman in Nigeria should ensure that they receive the 2 routine curative doses of Fansidar in line with the recommended Intermittent Preventive Therapy (IPTp).

 

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