A mosquito bite can cause one of the world's deadliest diseases- Malaria. It kills two million people every year around the world. Malaria parasites can attack the liver, kidney and brain and kill the affected person within 48 hours.
People ill with malaria usually feel as if they have the flu, with fever, vomiting and body aches. If left untreated, malaria can cause seizures (fits), coma and death.
The World Health Organization has identified malaria as one of the three major diseases of poverty, along with HIV/AIDS and tuberculosis. Although malaria is a curable disease if promptly diagnosed & adequately treated, there are more cases of malaria today than at any time in history. About 40 per cent of the world's population is at risk. In 2001, more than 300 million new cases will occur and more than two million people will die from the disease, of whom majority will be young children. Moreover 90 per cent of malaria- related deaths will occur in Africa and South East Asia.
Malaria is a devastating disease. Biting mosquitoes pass along the parasites that cause malaria. Once inside a human, the parasites burrow into the liver, where they reproduce. The increasing army of bugs eventually leave the liver to take up residence in red blood cells, where they continue to reproduce until the burgeoning red blood cell explode and release the parasites and their related toxins into the blood stream.
Nothing so small and insignificant has perplexed scientists so much as a mosquito. Apparently fragile and frail this insect can prove deadly.
Malaria is caused by protozoan parasites of the genus Plasmodium. Four species of Plasmodium can produce the disease in its various forms:
Malaria is still an international, enormous, medical issue with 300-500 million cases annually reported. It is prevalent in rural tropical areas below elevations of 1000 meters (3282 feet). Plasmodium falciparum is found mostly in the tropics and, along with Plasmodium vivax, makes up 95 per cent of malarial infections diagnosed worldwide. Plasmodium vivax is more widely distributed than Plasmodium falciparum, but it causes less morbidity and mortality.
Internationally, there are 1.5-2.7 million deaths annually. Of these deaths, the overwhelming majority is among children aged 5 years or younger, and 90 per cent of the deaths each year occur in rural sub-Saharan Africa and South East Asia.
According to a World Health Organization report:
* 280-300 million people harbour the parasite
* 300-500 million new cases occur annually
* 1.5-2.7 million deaths occur each year
* Malaria kills 3000 children under the age of five years every day
* One child dies of malaria after every 30 seconds
These deaths are unnecessary since malaria is preventable and treatable. However, the lack of prevention and treatment due to poverty, war and other economic and social instabilities in endemic areas results in millions of deaths each year.
Plasmodium falciparum is the most dangerous of the four: untreated it can lead to fatal cerebral malaria (complication of malaria involving the brain)
Almost two decades ago malaria seemed to be eradicated from US, Europe and some parts of Asia. The next target was Africa and South America. Thanks to DDT, the widespread use of this insecticide ensured malaria- free environment in these regions at last.
Then things started to change, but not for the better.
Eradication attempts like the widespread use of DDT have not only proved futile, they even aggravated the problem by creating DDT resistant mosquitoes. The indiscriminate use, sub-effective, sub-optimal dosing of antimalarial drugs and genetic changes in the Plasmodia strain have contributed to the development of multi-drug resistant malaria, a tendency which is threatening the usefulness of current treatments and urgently calls for new antimalarial compounds.
Emergence of resistance: Malaria resistance is defined as the "ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug given in doses equal or higher than those usually recommended but within the limits of tolerance of the subject".
This definition has been modified to specify that the drug "must gain access to the parasite or the infected red blood cell for the duration of time necessary for its normal action".
In Asia, chloroquine- resistance was confined to Indo-China until the 1970s, when it extended to the West and towards the neighbouring islands to the South and East. The first case of chloroquine- resistance in India was described in 1973.
The effects of resistance: Appearance of resistance to antimalarials has increased the global cost of the disease. Therapeutic failure means consulting a health facility for further diagnosis and treatment resulting in a loss of working days for adults and absence from school for children. Studies have shown that ineffective treatment causes anaemia, which renders children's health more fragile. The appearance of chloroquine- resistance has led to an increase in hospital admissions because of severe attacks of malaria. The impact of drug resistance can also be illustrated by the modification of species composition. Plasmodium falciparum accounts for about 40 per cent of malaria cases after the advent of drug resistance.
Increasing resistance of malaria parasites to antimalarial drugs is a major contributor to the re-emergence of the disease as a major public health problem and its spread in new locations and populations.
Malaria is quickly approaching such a scenario where the malaria parasites have become increasingly resistant to well-established drugs such as Chloroquine and other antimalarials, with no other drugs ready to take their place. The number of new antimalarials is restricted due to lack of investment by the pharmaceutical industry.
Malaria control efforts include attempts to develop an effective vaccine, eradicate mosquito vectors and develop new drugs.
Development of vaccine: Development of a vaccine has proven very difficult and a highly effective vaccine will probably not be available in the near future.
Attempts to eradicate mosquito vector: Efforts to control Anopheles mosquitoes have had limited success, although the use of insecticide-impregnated bed nets does appear to reduce malaria-related death rates. In addition, methods to replace natural vector populations with mosquitoes unable to support parasite development are under study and may contribute to malaria control in the long term.
However, the current limitations of vaccine and vector control, as well as the increasing resistance of malaria parasites to existing drugs, highlight the continued need for new antimalarial agents.
Established antimalarial drugs: Antimalarial drugs have been used for centuries. Early natural products, including bark of the cinchona tree in South America and extracts of the wormwood plant in China, were among the first effective antimicrobial agents to be used. Cinchona bark was used in Europe beginning in the 17th century, and upon its isolation from bark in 1820, quinine became widely used. In the last 50 years, extensive efforts, including the screening of hundreds of thousands of compounds have led to the development of a number of effective synthetic antimalarial drugs. The most important of these, Chloroquine, has been the mainstay of antimalarial chemotherapy for the last 50 years. Chloroquine as a relatively inexpensive prophylactic drug has treated many and saved millions of lives.
The compound eradicates parasites rapidly, has minimal toxicity, is widely available at low cost throughout the world and needs to be taken only once a week for chemoprophylaxis. However, resistance to Chloroquine has been steadily increasing. Chloroquine resistance is now widespread in most Plasmodium falciparum endemic areas of the world including Pakistan. A recent article published in the Journal of College of Physicians and Surgeons of Pakistan claims that resistance to Chloroquine is to an extent of 33 per cent while resistance to Sulphadoxine/ Pyrimethamine is to an extent of 37 per cent respectively. Thus the use of Chloroquine for presumptive treatment of malaria or for chemoprophylaxis is usually no longer appropriate. Moreover, resistance to Chloroquine of Plasmodium vivax, the second most lethal human malaria parasite, is increasing in South Asia.
New antimalarial drugs: Relatively few antimalarial drugs are undergoing clinical testing. Halofantrine, identified in the 1940s has limited use because of variable oral absorption and due to cardiac toxicity.
A more effective new drug is artemisinin and its related compounds. Artemisinin was isolated in 1972 from Artemisia annua, a plant used in China for centuries to treat fever. Artemisinin derivatives (artesunate, artelinate, artemether, arteether and dihydroartemisinin) have been synthesized and these compounds, which are already widely used in some areas, are potent, rapidly acting antimalarials that are effective against Chloroquine- resistant Malaria. Because recurrence of infection after treatment are common, artemisinin and related compounds might best be used in combination with another drug.
The World Health Organiza-tion also recommends "The use of artemisinin derivatives in combination with another antimalarial as the new rationale to resistance free treatment".
The writer is professor of medicine at Dow Medical College and Civil Hospital, Karachi.
