Musa Simon Reef
16 March 2008
Resistance to anti- malarial drugs in patients is becoming a worrisome phenomenon in Nigeria. It has posed serious challenge of combating malaria in most parts of the world.
Since the early 60's there has been marked resistance by malaria parasites to chloroquine, the best and most widely used drug for treating malaria, has been less efficacious. Newer anti-malarial drugs were discovered later, but all these drugs are either expensive or have undesirable side effects. Moreover after a variable length of time, the parasites, especially the falciparum species, have started showing resistance to these drugs also. Drug resistance, by definition, is the ability of the parasite species to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within the limit of tolerance.
Resistance to chloroquine: Discovery of chloroquine revolutionalised the treatment of malaria, pushing quinine to the sidelines. Resistance began from two epicentres - Columbia (South America) and Thailand (South East Asia) in early 1960s. Since then, resistance has been spreading world wide and reached the Indian state of Assam in 1973. Resistance is conferred by a stable mutation which is transferred to the progeny. It involves multiple mutations which means that resistance need not be complete - it may be partial also.
Resistance to quinine: Chloroquine resistance has brought this drug back to the limelight. Quinine remains quite effective even after extensive use. Reports of resistance to quinine are rare, but cases have been reported from Thailand and East Africa. High degree of resistance to quinine is not common. For reasons not known clearly, it has been difficult to induce quinine resistance in experimental conditions. Efficacy of quinine can be increased by adding tetracycline group of drugs. Poor compliance is a major drawback of this drug.
Resistance to mefloquine: Sporadic cases of mefloquine resistance have been reported from Thailand and Kenya. Structurally it is close to quinine and hence cross resistance with quinine is common. Resistance develops when the parasite is able to efflux the drug. Initially it was given at dose of 15mg/kg and was combined with sulfadoxine/pyrimethamine to reduce emergence of resistance. This approach did not succeed in Thailand probably due to the already existing high grade resistance to sulfa/pyrimethamine. Later the dose was increased to 25 mg/kg. Even at this dose efficacy of mefloquine is only 50 per cent in Thailand. Since it is easy to induce resistance for mefloquine due to its prolonged half life, its use should be limited, especially since it has cross resistance to quinine. To prevent development of resistance to this valuable drug, it has been suggested that mefloquine should always be used in combination with another antimalarial, like pyrimethamine/ sulphadoxine.
Resistantace test: Four basic methods are involved in testing malaria for drug resistance: in vivo tests, in vitro tests, molecular characterization, and animal models. Of these, only the first three are routinely done.
In vivo tests, patients with clinical malaria are administered a dose of an anti-malarial drug under observation and monitored over time for either failure to clear parasites or for reappearance of parasites. In vitro tests, blood samples from malaria patients are obtained and malaria parasites are exposed to different concentrations of anti-malarial drugs in the laboratory. Some methods call for adaptation of parasites to culture first, while others put blood directly from patients into the test system. Molecular characterization: For some drugs (chloroquine, SP and similar drugs, atovaquone), molecular markers have been identified that confer resistance. Molecular techniques, such as polymerase chain reaction (PCR) or gene sequencing can identify these markers in blood taken from malaria-infected patients.
Dr. Lawal Abdulrahman, who works in private hospital in Abuja, explained that several factors are responsible for the increased resistance of malaria to drugs. One factor he identified is the presence of fake drugs in the country. He noted that despite the aggressive campaign against fake drugs, several drugs, especially malaria drugs still find their ways into the markets. Abdulrahman advocates strict adherence to the genuine drugs to avoid patients being administered with fake drugs.
Another medical practitioner, Solomon Agbese, said the prevalence of resistance of malaria to certain drugs may be attributed to the abuse of drugs by patients. It is based on this abuse of the malaria drugs on the part of patients, that hospitals have adopted the task of ensuring that patients suffering from malaria are adequately treated.
According to the PLoS Medicine study, "most of the fakes examined as part of Operation Jupiter contained no artesunate, and some contained a wide range of potentially toxic active ingredients. Also of grave concern was the fact that counterfeiters sometimes included dangerously small amounts of artesunate in the tablets. This may be done to foil screening tests of drug quality, but these doses are too low to be efficacious, yet high enough to contribute to malaria parasites becoming resistant to this class of drugs."
It is this small amount of artesunate found in fake drugs, according to Dr. Paul Newton of the University of New York, that has led to increased resistant of the disease to the malaria parasite
"Artesunate, as part of artemisinin-based combination therapy, is vital for malaria treatment and is one of the most effective weapons we have against this terrible scourge. "Those who make fake anti-malaria drugs have killed with impunity, directly through the criminal production of a medicine lacking active ingredients and by encouraging drug resistance to spread. If malaria becomes resistant to artesunate, the effect on public health in the tropics will be catastrophic."
Causes of resistance: Several factors have been identified as being responsible for the resistance of malaria against drugs. One of the factors is the faking of drugs by pharmaceutical companies of the world. In April 2004, a team of investigators from the International Criminal Police Organisation, INTERPOL, with the cooperation of the World Health Organisation's Western Pacific Regional Office, and the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme, in collaboration with the Chinese authorities uncovered A MEGA fake anti-malaria drugs syndicate in China.
The discovery, according to PLoS Medicine journal, represents a defining moment in the world's attempt to uncover the forces behind the manufacturing of fake drugs which insiders believe is worth $40 billion (N5 trillion). The world's companies have always been accused of not making any deliberate attempt to unravel the forces behind the fake drugs manufacturing which has led to several deaths in the world. The China arrest, according to public health workers bring to fore the threat posed by faked pharmaceuticals and the dilemma of tracking down the perpetrators.
Even before the arrest, the National Agency for Food Drugs Administration and Control, NEAFDAC, has been up in arms against the activities of drugs faking. Informed analysts are of the opinion that the cumulative effects of drug counterfeiting has led to several deaths and officials of government are now harping on the need to attack sources through which these drugs are being produced.
WHO estimates that 200,000 of the one million malaria deaths every year would have been avoided if the patents patronised genuine drugs. The high cost of drugs coupled with the poverty level of the people are said to be major factors encouraging counterfeit peddlers to boost sale of fake drugs. Sources from NAFDAC reveal that in 2001, about 68 per cent of medicines in circulation in Nigeria were unregistered, and as much as 41 per cent were believed to be fake. But latest report from NAFDAC says incidence of fake drugs in Nigeria has gone down to below 15 per cent. The Director-General of NAFDAC, Prof. Dora Akunyili, sees counterfeiting as "mass murder".
Akunyili said, "The fake drug racket and the silence associated with it have led to the resurgence of malaria... The companies kept quiet. The regulators were paid off and everybody was helpless. Drug counterfeiters operated in this country and in most developing countries for almost three decades, unchallenged. If the companies had risen up to their responsibilities early enough, the issue of the preponderance of fake drugs would not have got to the level it got to in Nigeria. It is this silence that is actually largely encouraging drug counterfeiting."
There is no doubt that drug resisting malaria ailment is not a Nigerian phenomenon; it cuts across several countries and continents. While it may not be for the nation's best interest to ban monotherapy artemisinin, adequate measures must be focused towards fighting drugs counterfeiting and finding out what best treatment for sufferers of the malaria disease.
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