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MALARIA IN SOUTHERN AFRICA - a community pharmacists perspective
Peter Rollason, Zimbabwe
 I would wish you to see malaria through the eyes of one who deals with the disease every day of the week. This situation of a community pharmacist in a malarious area is very different from that of a researcher, or even a medical practitioner/prescriber. The disease presents itself to a community pharmacist as patients in a "scare" situation, bedevilled by confused utterances. Scared because 1000 people died from it in Zimbabwe last year; confused by so much differing advice on offer by everyone from the Professor to the next door neighbour. Let me
clarify the existing situation of the disease as seen in Southern Africa.
Firstly, vector control. Urban areas in Zimbabwe, in some cases cities of a million or more people, are generally controlled at the start of the season by residual insecticide spraying undertaken by the local authority, and concentrated on standing water and puddles. Most of these major urban areas are situated on the high veld, above 1000 metres above sea level, which means, in this part of Africa, a very low incidence of malaria. It is acknowledged that the altitude parameter of anophelene breeding varies as one moves nearer the equator. In rural areas, and especially those below 1000 metres, residual insecticide spraying is normally undertake by central government. Even in days past, when DDT was used, this presented no environmental hazard as the spraying was confined to dwellings, both inside and outside. As a measure of its success, when the government runs outs of money (far too frequently), and spraying at the beginning of the rainy season is reduced, morbidity and distressingly, mortality more than doubles. There has been encouragement for the greater use of bed-nets, preferably pre-treated with residual insecticide such as pyrethrins, and this is now becoming very acceptable and successful.
It is general policy in Zimbabwe and surrounding countries not to supply any form of chemoprophylaxis to constant dwellers in rural malarious areas. These people, who are daily challenged with infected vectors, are regarded as being partial immunes, probably with a similar degree of success as would be achieved by most preventive drug regimes. Of course, urban high veld dwellers, going to visit in low veld malarious areas need a preventive drug. And this is where a problem immediately arises.
Take this situation as an example: The peasant family lives in a low veld malarious area.
Tjolotjo, the father works at a factory on the high veld, in Bulawayo, more than 100 Kms. away. The family are partial immunes, but he is not. When he goes to visit them once in three or four months, he is advised to take his malaria tablets. But he says: "Why? I do not need
medicine, I am not sick. My wife and children do not take anything, so why must I?" So.. he takes nothing, and gets malaria! Add to that the confused story of prophylaxis and the various regimes on offer, and it makes for a very difficult situation. There is also another point that should mentioned here - that of communication and knowledge of language and local customs.
We are experiencing more and more "commuter malaria". Where I live, on the high veld in what is regarded as a non-malarious area, no chemoprophylaxis is advocated and generally not used. However there are more and more cases of malaria being contracted in these areas, contrary to expectations. These are mosquitoes that go "walk-about". They travel in from malarious to non-malarious areas on buses, trains and bicycles, and do their damage on arrival. We had a fatal case of cerebral falciparum a few years ago in
Bulawayo. The mosquito had hitched a ride in a boat trailer of some people who had been having a holiday on Lake Kariba, in the Zambesi Valley. The trailer was parked on arrival home; the mossie escaped and bit the lady who lived next door. She had not been out of the city for over two years, and yet she died from cerebral malaria, because it had neither been suspected, nor had it been thought of geographically for diagnosis. Another lady, who collapsed from general malaise and possible mal-nutrition was given routine blood tests, and surprisingly, malaria was found. She was treated with chloroquin and fully recovered. The offending mosquito seemingly came into town wrapped in the blankets of one or her employees returning to work after spending the Christmas holidays in a malarious area.
Probably of prime importance however, is malaria treatment per se. I, of course, can only relate to my own region's circumstances. Up as far as the Zambesi River, resistance to chloroquin, although known and documented, is generally fairly isolated and not too significant. In fact, chloroquin resistance is greatly over-estimated. Why should this be so? The answer to this vexed question (and I am sure this applies in many other parts of the world) is inaccurate diagnosis. Chloroquin is, as we know, the drug of choice, and is still remarkably effective. It is widely used, easily available and cheap. Some years ago in Zimbabwe, it was decided to make chloroquin freely available to people, especially in rural areas, through local general stores, so that when they felt that they were succumbing to malaria, they could easily buy treatment very close to home. The normally recommended dose was well publicised and encouraged. It all went wrong .The people bought the chloroquin all right, but usually
took two tablets only, to cure a headache or a hangover, or, conversely, a massive quantity to produce an abortion! The amount used for the legitimate treatment of malaria was negligible. This problem has been partly overcome by making the product only saleable in original packs of ten tablets, but obviously this is not the complete answer.
The only place where accurate diagnosis of malaria can normally occur is in the towns, where there is a laboratory with a good microscope and above all a well-trained technologist to read and interpret the blood slides. In most parts of the country this just doesn't happen. There was a W.H.O. plan a few years ago to obtain some 2000 microscopes, and to send them out to the rural areas, in order to increase diagnostic efficiency.
However, there was no one to read the slides and even if they could have been prepared, there was no electricity for illumination, and finally, no microscopes working - they were either broken, stolen or sold!.
All of this leads to the system that is prevalent throughout - presumptive diagnosis. In essence, this means that when a person feels unwell, even with minor symptoms, and is, or has been, in a malarious area, chloroquin is given in a full dose regime. If he recovers, that's fine. So often he does not respond. Is the inference to be that the chloroquin has failed? Not at all. He has probably not had malaria, but rather influenza, diarrhoea, dysentery or particularly, tick fever. Fortunately chloroquin seems to have little in the way of adverse effects in an otherwise uncompromised person. Even skin itching, although known, is nothing like as severe in my part of Africa as has been reported in parts of West
Africa. So, we have a system of basic mis-diagnosis, and this is so often classified as an example of chloroquin-resistant malaria. In fact, the figures quoted by so many publications for such "resistance" are so false that, in my estimation, they are up to 50% wrong. I have heard quotations from other highly professional and responsible sources
that are as high as 60% wrong! There is also another reason for confusion. Very few medical practitioner and even epidemiologists know what chloroquin resistance really means. They are not aware of R1, R2, and R3 resistance, let alone the more recent W.H.O. parameters for resistance estimation.
Diagnosis therefore, is the kingpin of malaria containment. There is much hope
in this direction. The incidence of different malaria strains in Zimbabwe and Southern Africa generally is estimated roughly as
P. Falciparum 98%, P. Malariae 1.5%, P. Ovale 0.5%a and
P. Vivax virtually nil (although more of the latter is now being found). The diagnostic system that measures the histidine-rich protein of
Falciparum invasion by means of a "dip-stick" procedure is therefore most valuable. I introduced this into Zimbabwe a few years ago. The original manufacturers donated a set of 100 tests for trial. In the city of Bulawayo, I worked with G.P. doctors, and when they had a suspected malaria case, they telephoned me and I went immediately to their surgery and did the test with them on the spot. An unusual role for a community pharmacist! Every diagnosis was deliberately confirmed by blood slide, which could require a day or more to produce a result, but every single case was confirmed. The point here is that every positive case was commenced on treatment immediately, and results were 100% good. Negative diagnosis required the doctor to think again, and in every such case, another disease syndrome was found, and then adequately treated. After a number of tests done in this way, I gave the balance of tests to the local laboratory who conducted them for the G.P.'s at no cost. They then purchased more and the service is now standard procedure. There are now variations of this original test, and the price is coming down. Furthermore, these tests are being produced for multi-valent recognition of all the types of malaria likely to be present. These are just what we need. In my opinion, there should be just such a diagnostic system installed at every health clinic, every mobile health centre, and even with village health workers. Malaria would then be likely to be much more accurately and efficiently dealt with and a lot of unnecessary treatment and drug use avoided. Incidentally, the tests are so simple that they can be done by someone who is even illiterate, and they take less than ten minutes each.
Coming now to the classic situation of P. Falciparum malaria. What treatment policy is followed in Southern Africa? Chloroquin is still our number one drug. The drug of second choice, and beloved by travellers from overseas, to carry as a "stand-by" is pyrimethamine/sulphadoxine combination, sometimes with chloroquin added. Third line - mefloquin or halofantrine. The former is so far inclined to be used sparingly, the latter generally successfully, but now less popular because of its erratic absorption and its known cardiac side effects. Quinine is still high on the list and is used quite extensively. More recently, the artemesenins, in the form of injection or tablets are being used by some doctors, generally with excellent results. They are sometimes combined with other drugs. Any course of an artemesenin drug must be carried through to its completion, otherwise recrudescence of the disease almost always occurs.
So what problems do we have? With chloroquin, very few. We do know of resistance, we know where it occurs in isolated pockets, but as yet, these do not seem to be too significant. We have found nausea and vomiting a problem with chloroquin, especially when the initial dose of
600mg base is taken, but almost always, this can be overcome if it is administered with a glucose drink. Pyrimethamine/Sulphadoxine is unquestionably an effective drug, but it has a complicating factor. After administration of the usual three- tablet dose, the patient's symptoms usually improve quite soon
within 36 hours or less. But when blood slides are taken parasitaemia remains rather higher than expected.
Many practitioners are not aware that in the case of this drug the parasite load is reduced rather slowly, so they panic and rush to quinine for the patients, with all its nasty side effects and basically unnecessary treatment.
Mefloquin is now more often used for treatment, but it is expensive. When one is so ill with malaria, the likely psychotic side effects don't seem to matter too much! Artemesenins are very useful, especially in recalcitrant cases, a heavy parasite load, and in the distressing escalation of cerebral malaria. Resistances to quinine and these other drugs have not been recorded to any extent. Incidentally, very few doctors, and even fewer patients are aware that cerebral malaria is usually as a result of either un-diagnosed or inadequately treated
P. Falciparum malaria, and are inclined to regard it as a special, different fatal disease.
Malaria is not a notifiable disease in terms of the law, and therefore incidences and geographical disposition can only be assessed by positive visits and voluntary reports. The Zimbabwe Government has a research laboratory in Harare that concerns itself, among other things, with malaria, and there is a malaria unit within the Ministry of Health and Child Welfare. They both work in conjunction with the W.H.O. regional and sub-regional officers in the same city.
In 1994, I was awarded by the International Pharmaceutical Federation, a travelling scholarship to research malaria incidence, treatment and prevention in parts of Southern Africa. I concentrated on four countries - South Africa, Namibia, Zimbabwe and Botswana, South Africa is well involved in malaria work, which includes research at Universities. There is a special unit under the Medical Research Council based in Durban which employs more than twenty people who, when I visited them, were mainly concerned with researching chloroquin resistance. They are also constructing malaria maps for the whole region, and I was able to supply them with the Zimbabwe component. Namibia and Botswana have no research, but generally follow W.H.O. guidelines. Zimbabwe does more, although it does not have a specific biological research laboratory.
Where treatment is concerned, there is little difference within the four countries, drug availability being the main limiting factor. By contrast, where prophylaxis and particularly advice on prophylaxis is concerned, there is the utmost confusion. I must here mention South Africa's policy of recommending mefloquin as the main preventive drug to be used, and registering it only for that purpose. If tolerated, it is an excellent preventive drug. A doctor's prescription is required, costs are extremely high, and the incidence of unacceptable side effects, especially in the first few weeks, is very high. What is more, this has led to a bad reputation for the drug among both practitioners and the lay public. More importantly this has resulted in poor compliance and thus increased risk. The side effects usually slowly decrease over a period of three to four weeks - just in time to return home from your trip, having felt miserable all the time you were away!
We in Zimbabwe, have used Pyrimethamine/Dapsone for over twenty years as a main preventative, with excellent results and no known single case of agranulocytosis or resistance recorded. It affords about a 70% protection. I was highly delighted to see acknowledgement of our use of this combination in the March 1995 edition of the British National Formulary.
Proguanil/chloroquin combination is still used extensively, world-wide, as a prophylactic, giving a similar protection picture, but, usually, this is only used by us if a patient has a sulphonamide allergy to dapsone. Side effects from this combination are much higher than is generally acknowledged and include general malaise, headaches, stomach upsets and, above all, mouth ulcers. This all leads to poor compliance, or even abandoning the drug, which has never
been adequately documented! Furthermore, having to take sixteen tablets a week and then feel poorly, when one has been physically fit, is not likely to lead to good compliance, especially if you are a visitor on holiday. Whatever protection drugs are used, W.H.O. advises (and we follow suit) on continuation of medication for four weeks after leaving a malarious area. If there should be a risk of
P. Vivax, then six weeks is advised. On my travels, I found that Botswana, at that time, was only indicating two weeks, but I believe that that has now changed. The new combination drug, atovaquone/proguanil (“Malarone”) is not yet available to us here, but from extensive trials in East Africa, there have been excellent reports of its value, with, as yet, little or no evidence of resistance.
Titrating the dose of any drug for children is always somewhat hazardous Age is usually the measurement, but children vary tremendously in size and weight for age. Thus there is a tendency to marginally overdose. In one part of my country, where the population is concentrated under one employer, pyrimethamine/dapsone is administered every Monday. On that day, quite a number of children go blue from a slight dapsone overdosage, but it doesn't matter, and simply acts as proof that the dose has been taken. The origin of “Blue Monday”? We have records from the hospital that administers the whole area that even during the last four or more bad seasons, not one employee who had been given this prophylaxis had malaria.
There is little doubt in practice that the success of malaria chemoprophylaxis with medication depends on compliance with the medication dosage provided. The same applied to treatment. Many people, especially travellers, carry “stand-by” medication when visiting malarious areas. On feeling unwell, malaria is suspected, so the medication is
taken, so often incorrectly. For example, a course of three tablets of pyrimetyhamine/sulphadoxine will be carried for just such an eventuality. The person feels only a little bit ill, suspects malaria, so takes one tablet – just in case. Expense plays an important part in the choice of drug by the lay public. In Zimbabwe, pyrimethamine/dapsone is reasonably cheap. Proguanil/chloroquin works out at about ten times the price, and mefloquin (requiring a prescription) up to 60 times as expensive.
I have not mentioned the possibility of a vaccine. Obviously this will come in
time – another 10 years or more? – but with all respect, it will have very little impact on those of us who live here in Africa. It will, I am sure, be fine for the itinerant traveller from overseas, who needs protection for about three months or so, but I doubt whether it will come within our ambit of practicality or price.
In summary, Southern Africa has a bad malaria situation, and the control of the disease is not getting any better. However, there is at last more inter-action between neighbouring countries, and the W.H.O. “Roll back malaria” campaign will certainly help to increase awareness and, hopefully, action.
We always tell our visitors to beware of the anophelene mosquito, and especially the female, She does not buzz, only bites between sundown and sunrise, and sticks her backside in the air when she does it, and is transparent with spots or stripes. So – they are advised that if they are sitting around a camp fire out in the bush at sundown time, and they come across a spotted, transparent beastie with her backside in the air, which they cannot see or hear then – they can kill it! It gives one something else to think about! And while on the subject of sundowners, remember the best malaria preventative of all – Gin and Tonic. The tonic, originally made for the British Raj in India so many years ago still contains quinine, and was made for the purpose. Of course, you need a lot of it, and it goes without saying that you will have to have a lot of gin to make it
palatable. And that, in turn, is likely to produce a somewhat alcoholic mosquito who doesn't know what she is doing anyway; so you are well protected. Food (and drink) for thought.
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