MALARIA MENACE: Drug Recall And Matters Arising

Sodzi Sodzi-Tettey examines the malaria scourge in Ghana and the fall-outs of the decision to recall the single doses of Artesunate (200mg)-Amodiaquine (600mg)

On Saturday 17th December 2005, the Daily Graphic reported the directive of the Ministry of Health to withdraw single doses of Artesunate (200mg)-Amodiaquine (600mg) from the market.

Subsequently and understandably, members of the Ghanaian public have expressed great concern about the developing issue, posing legitimate questions as to whether health authorities conducted due diligence before the adoption of the policy in the first place.

Disturbingly, Dr Alex Dodoo and Augustina Appiah-Danquah both of the National Centre for Pharmacovigilance have faulted the Food and Drugs Board for ?not ensuring that appropriate trials and tests are carried out before products are released on the market.? This to say the least is worrying. Of course, Ben Botwe, head of drug unit of FDB is reported to have ?dismissed accusations that the FDB as a regulatory body did not scrutinise the drug well before giving approval for its use, insisting that the board did everything before the drug was put on the market.?

In this article it is my intention to deal with the specific issue of the said ban as it pertains to the aforementioned prescribers. Beyond that, I plan to examine the bigger picture of National Malaria Control, our treatment policy, preventive measures or the lack of it, and the impact of the National Health Insurance Scheme.

Mixed Signals

With all health facilities having been instructed to stop the prescription of the two single dose brands (200mg Artesunate and 600mg Amodiaquine), there has been an added call to mass action with the public being urged not to patronise them.

Suddenly, health authorities seem to be back tracking. Previous policy directives backed by massive public education notwithstanding, Artesunate-Amodiaquine is now said to be the ?preferred treatment? and no longer the ?standard recommended treatment.? Many issues are still unclear and the drug recall in itself can hardly be called a definite panacea.

It is important for example to point out that the National Malarial Control Programme has long ago issued guidelines by which the dosage of Artesunate-Amodiaquine is expected to correlate with the patient?s weight and /or age. Doses of Artesunate thus range from 25 to 200mg with the maximum dose being given to adults in excess of 70kg body weight.

When the ministry of health contends that the reported side effects are caused by the highest strengths, it is also important to establish whether by implication prescribers are prescribing the said maximum dose irrespective of a patient?s weight. In other words, are some prescribers as a matter of routine doling out maximum doses to all weight classes of patients? A random sampling of views of various clinicians gives the distinct impression that the above is not always the case. Indeed a lot of clinicians cite many examples of patients suffering intolerable side effects even though it was ensured that patients were prescribed not necessarily the maximum dose but that appropriate for their weights.

Consequently and logically, if patients are not being prescribed excessively high doses and rather the drug combination even when correctly prescribed for each weight category has been associated with deleterious side effects, then the critical question of a possible review of the whole new treatment policy is legitimate. There must thus be a scientific approach to a multifaceted issue whose solution may not simply lie in a drug recall. While we are at it, we might want to explain where the advice of the NMCP to prescribe in divided doses with food and haematinics fits in.

Drug Compliance

Simply defined, compliance refers to taking the right dose for the full duration as prescribed. With the adoption of the new drug policy, many were those who expressed apprehension about the efficacy with respect to drug compliance. This concern arose out of the observation that to be adequately treated using 50mg Artesunate and 150mg Amodiaquine formulations as is being advocated now, a 70+kg patient may be required to take a total of 24 tablets in a three day treatment programme.

It was to address this concern that local manufacturers showed initiative and went ahead to manufacture the single compressed dose with their efforts being initially lauded by the NMCP. Not surprisingly therefore some local manufacturers have had cause to complain about confusing messages from NMCP with some lamenting their initial instruction to prepare a single effective daily dose, later converted to two divided doses.

With our reversion to the possible increased number of tablets the long term effects on compliance and the longer term effects on reducing the disease burden is yet another disturbing question that cannot be glossed over.

Background

Several studies and anecdotal reports in the country were said to have thrown doubts on the efficacy of chloroquine in the management of malaria. As a response to the rising resistance to chloroquine, the NMCP established a task force of experts in various aspects of malaria control to review the evidence on efficacy of chloroquine in the treatment of malaria. This task force included Public Health physicians, epidemiologists, social scientists, clinicians, pharmacists, policy makers and Drug Regulatory Bodies.

In 1998, the NMCP in collaboration with Noguchi initiated a study on the responses of plasmodium falciparum to chloroquine in the treatment of uncomplicated malaria. Centred in 6 districts hospitals the study showed;

Treatment failure rates of 8.6% to 26%

Adequate clinical response of 75%

Parasitological failure rate of 21.7% to 49%

Based on a WHO Global Response to antimalarial drug resistance which calls for a period of drug change when treatment failure exceeds 25%, Ghana thus adopted a new anti-malaria drug policy with Artesunate-Amodiaquine being chosen as the most cost-effective drug compared to all the other alternatives.

There are those that have described the switch based on the above figures as too drastic, the wide variation in 8.5% to 26% in resistance levels considered. That may well be an issue that has to be revisited at a later date by better- qualified persons.

I shall now focus on issues of prevention and cost.

Prevention

In a communiqu? issued at the just ended 47th Annual General Conference held in Sunyani, the Ghana Medical Association had cause to note with concern ?the apparent marginalisation of preventive health, promotive and public health concepts and approaches in health care delivery??? The GMA then made a passionate appeal to the Ministry of Health to revisit and facilitate the implementation of appropriately designed public health programmes aimed at reducing the disease burden and the national cost of healthcare.

Today, in a matter of great public health concern with malaria affecting 17 million people per year, prevention seems to have lost the pride of place. Clearly, policy direction has swung full circle into the domain of curative medicine with the adoption of measures whose full costs (compliance, cost, side-effects) seem to be lost on us. Surprisingly and disappointingly or perhaps not so, some respected public health physicians have balked at providing an emphatic ?YES? in answer to the question of whether a new drug treatment that returned same patient to the mosquito will in 10 to 20 years significantly reduce the disease burden of malaria in Ghana.

Local Production

The increased cost implications of this new treatment policy could not have been lost on us. Estimated conservatively, the cost of treating malaria has shot up by more than 1000%.

Meanwhile, policy makers? continued insistence on so-called WHO approved drug formulations as perhaps the only available option has only meant one thing: import, import, import thus killing albeit softly, private local industry and initiative.

This unfortunate situation has been helped in no small part by the very confusing signals sent by authorities to the few local pharmaceutical companies who took up the challenge of preparing dose formulations prescribed by the very same bodies that are today banning their products. Of course, it must be conceded that the health of our people ought to be our paramount consideration in all our choices.

The question of whether it was not possible for Government, Ghanaian scientists and local pharmacists to partner each other in the possible production of scientifically proven, efficacious, cheaper and compliance- friendly packaging has never been adequately answered.

Alternatively, some scientists at the Centre for Tropical Research into Plant Medicine Mampong, list among their achievements, the conclusion that some local herbal preparations are efficacious in the treatment of malaria. Unfortunately, this claim seems never to have gone beyond its elementary stage into the mass production of tablets in commercial quantities to solve a pressing national need. After all, do we not know that this acclaimed Artesunate is nothing more than a Chinese plant extract which is today meeting a need?

Cost

The cost of treating malaria to the country in terms of money and time is enormous.

The monetary implications become even more alarming when viewed against the NHIS, factoring in the premium of ?72,000 coupled with our lack-lustre registration drive.

According to the Ministry of Health, 17million people report for malaria treatment each year. We can however take the argument a step further. If treating each case of malaria costs us an average of ?65,000 considering Health Insurance estimates for consultation and haematinics (to counter adverse drug effects), then assuming each of the 17 million people suffers one attack only in a year, the real cost of treatment will be in the range of ?1.1 trillion per year.

It is thus up to our leaders to analyse returns on health insurance vis-a-vis the sustainability of our treatment policy, work out worst case scenarios if people should for example suffer more than one attack per year and vigorously examine ways of introducing greater efficiency for the good of our people. Clinicians are now giving out more excuse duties to cover the period of drug administration aware as they often are of the side effects that patients complain about. The real cost in terms of man-hours lost is also yet to be quantified.

Prevention and cure must thus necessarily go hand in hand in an aggressive and thoughtful manner and we ought to act as a people with conscious awareness.

Conclusion

It must have dawned on health authorities that they have succeeded in sending down very strong confusing signals not only to the public but also to healthcare professionals. It is important therefore to communicate a clear policy to all healthcare providers and this certainly not through newspapers. Last but by no means the least, is this critical question that Ghana must answer as to whether or not the female anopheles needs to play such a dominant and destructive role in our lives. In other words, is it possible to mount a sustained, aggressive, well-coordinated non-partisan effort at community, district, regional and national levels to live lives without mosquitoes? If it is any comfort at all, be it known that in the one month that I spent at the VRA Hospital/Community in Akosombo, not one female anopheles did I encounter. And then again, this particular community has a clear policy on sanitation which is working.

Sodzi Sodzi-Tettey Asst Gen Sec Ghana Med Assoc St Anthony?s Hosp Dzodze, V/R