1.2.1 The Disease
Malaria in humans is caused by a protozoan of the genus Plasmodium, which is transmitted through bites by female mosquitoes of the genus Anopheles. Four subspecies, namely, P. falciparum, P. vivax, P. malariae, and P. ovale, are known to cause malaria in humans. The most severe malaria fevers and about 90% of malaria deaths are caused by P. falciparum, which is the predominant parasite species in Africa. It is also in Africa that the most efficient mosquito vector for malaria transmission, Anopheles gambiae, predominates.
The global malaria situation is deteriorating faster today than at any time in the past century. The number of new cases of the disease has quadrupled in the past 5 years, such that over 2 billion people, 40% of the world population, living in about 102 countries, are at risk of being infected, and half of these live in sub-Saharan Africa. The World Health Organization estimates that between 300 and 500 million new cases occur each year. In addition to causing untold suffering and disability, malaria ranks as one of the world's major killers, costing about 1 million people their lives annually. Children are especially vulnerable, as more children die from malaria than any other single disease (Figure 1.1). Pregnant women and especially primigravidae are the next highest risk group for malaria in malaria endemic areas. It is stated that malaria causes about 0.96 million deaths of children per year in Africa alone (WHO, 1999). Most malaria infections occur in Africa (see Figure 1.2). Countries in tropical Africa are estimated to account for 80% of all clinical cases and about 90% of all people who carry the parasite.
I—i Areas in which malaria has disappeared, been eradicated or never existed I I Areas with limited malaria risk □ Areas where malaria transmission occurs
FIGURE 1.2 Global malaria risk. (From 20th WHO Expert Committee Report on Malaria; WHO, 1998.)
The direct and indirect economic burden of malaria in Africa is estimated to be U.S. $2 billion annually. To the poor sub-Saharan countries of Africa, the WHO Roll Back Malaria has highlighted that:
• The cost of malaria control and treatment drains African economies. Endemic countries have to use scarce hard currency on drugs, nets, and insecticides.
• Africa's gross domestic product (GDP) today would be up to 32% greater if malaria had been eliminated 35 years ago, according to estimates from a Harvard study. Malaria endemic countries are among the world's most impoverished.
• In Thailand, malaria patients pay nine times their average daily wages for care.
• A malaria-stricken family spends an average of over one quarter of its income on malaria treatment, as well as paying prevention costs and suffering loss of income.
• Workers suffering an attack of malaria can be incapacitated for at least 5 days.
• Malaria-afflicted families on average can only harvest 40% of the crops harvested by healthy families.
1.2.3 Failure of the Worldwide Malaria Eradication and Control Program
The global malaria eradication principle was adopted in 1955 and WHO adopted a worldwide eradication program between 1957 and 1969. The eradication program was based on vector control by insecticides and chemotherapy of infected people aimed at termination of transmission and eradication of a human reservoir of infection in all malaria endemic areas in a short time. The program was initiated in all the malaria transmission areas of Africa, the Americas, Europe, and major areas of the countries in Asia. Within two decades malaria was eradicated from many parts of the countries in Europe and America and the intensity of transmission had been reduced significantly in Africa and Asia. The widespread use of DDT in India, Mauritius, and Madagascar almost eradicated malaria, whereas complete eradication was achieved in Rome and Sicily, Italy, and around the Mississippi areas in America.
This initial success in many tropical countries was interrupted mainly by the development of resistant mosquitoes and chloroquine-resistant Plasmodium falciparum, as well as, and probably most importantly, lack of strong political and financial support to the program once the problem was solved in Europe and America.
Such serious setbacks in the early 1970s caused a resurgence of the disease in areas of Asia and South America where the number of cases had been reduced to low levels.
In Africa, some pilot studies like the Pare-Taveta Scheme had produced a remarkable reduction in mortality and anemia (Bradley, 1991). However, since eradication was not achieved and this had been the goal, the scheme was abandoned and no attempts were made to replicate it elsewhere.
The malaria control strategy aimed at malaria eradication was reoriented in 1978 to focus on the reduction of malaria to a level at which it would no longer constitute a major public health problem (WHO, 1978). This strategy was based on the combined use of vector control measures and effective treatment of malaria patients.
In the interregional meeting on malaria control in Africa held in 1991 in Congo Brazzaville, analysis and ultimately revision of the malaria control strategy were made after considering that it was difficult to implement it in the majority of African countries. The new strategy consisted of three crucial elements: early diagnosis and effective treatment of malaria cases; selective vector control in areas where it is suitable and cost-effective; and early detection and rapid control of epidemics.
The present malaria control strategy, which was adopted by the Ministerial Conference on Malaria in Amsterdam in 1992, is based on the prevention of death, reduction of illness, and reduction of social and economic loss due to malaria (WHO, 1994). The practical implementation of the strategy requires two main approaches:
• Malaria chemotherapy for early and effective treatment of malaria cases, management of severe and complicated cases, and prophylaxis for the most susceptible population (particularly pregnant women and nonimmune travelers)
• Use of insecticide-treated nets for protection against mosquito bites
This strategy has, however, been increasingly confronted by serious setbacks due to the continued spread of drug-resistant P. falciparum strains, insecticide-resistant species of the mosquito vectors, and political and socioeconomic problems. The malaria situation has continued to worsen as evidenced by increased frequency of malaria epidemics and levels of parasite resistance to the most affordable drug, chloroquine (WHO, 1996).
1.2.5 Limitations of the Current Malaria Control Strategy
Currently, chemotherapy of malaria to those who need it most worldwide is based on nine key drugs: chloroquine, amodiaquine, primaquine, mefloquine, quinine, sulfadoxine/pyrimethamine, pyrimethamine/dapsone, halofantrine, and artemisinin derivatives. The availability of chloroquine, amodiaquine, sulfadoxine/pyrimethamine, and quinine in Africa has considerably improved the treatment of malaria, but unfortunately, three decades ago P. falciparum was shown to have developed some resistance to most of the cheaper antimalarials. Since then, the incidence of drug-resistant P. falciparum has been increasing at a faster rate than that of the efforts for development of new drugs (see Figure 1.3).
Reported P. Falciparum drug resistance
FIGURE 1.3 Reported P.falciparum drug resistance. (From 20th WHO Expert Committee Report on Malaria; WHO, 1998.)
Reported P. Falciparum drug resistance
□ Malaria transmission areas o Chloroquine resistance
• Sulfadoxine/pyrimethamine resistance
* Multidrug resistance
□ Malaria transmission areas o Chloroquine resistance
• Sulfadoxine/pyrimethamine resistance
* Multidrug resistance
Against this background of increasing drug resistance is the unfortunate situation whereby new effective antimalarial drugs coming into the market are completely unaffordable to the majority of the affected populations. Africa south of the Sahara has populations who are dying for lack of malaria treatment, not because there are no effective antimalarial drugs, but because these drugs are beyond their affordability.
The increasing spread of chloroquine-resistant P. falciparum malaria is a major public health problem in Africa south of the Sahara. Several countries have already abandoned chloroquine as the first-line therapy. Tanzania, Kenya, Malawi, Botswana, and South Africa have switched to sulfadoxine/pyrimethamine, while Cameroon has switched to amodiaquine. Sulfadoxine/pyrimeth-amine seems to have a short therapeutic life span, as resistant strains of P. falciparum are widespread in Southeast Asia and South America. Recent research findings from Kenya and the United Republic of Tanzania indicate a decline in parasite sensitivity to sulfadoxine/pyrimethamine in East Africa. P. falciparum is also reported to have developed resistance to mefloquine in the border areas of Thailand with Cambodia and Myanmar. Parasite resistance to quinine has already been reported in Southeast Asia and in the Amazon region. Furthermore, there is growing evidence that P. vivax has also evolved resistance to chloroquine in Indonesia (Irian Jaya), Myanmar, Papua New Guinea, and Vanuatu (WHO, 1998).
Recently, the reemergence of malaria in areas where it had been eradicated, such as Tadjikistan, the Democratic People's Republic of Korea, and the Republic of Korea, and the spread of malaria in countries where it was almost eradicated, such as northern Iraq, Azerbaijan, and Turkey, are indications of the increase in malaria risk areas in the world. The current malaria epidemics in the majority of these countries and in Africa are the result of a rapid deterioration of malaria prevention and control operations, due mainly to the lack of sufficient funds for malaria control and the paucity of effective control tools.
The search for a vaccine has been plagued by a number of shortcomings. Many of the shortcomings are related to antigenic variation, antigenic diversity, and immune evasion mechanisms exhibited in various stages of the complex life cycle of malaria parasites. In addition, malaria research and the search for vaccines require large sums of money, and it can be said that malaria research has been greatly underfunded.
While efforts are being made to overcome the hurdles for vaccine development, people are dying, and the only available effective means of reducing the number of deaths is the provision of affordable and effective medicines. Many young people are already dying of HIV/AIDS in Africa for lack of cure and affordable life-prolonging drugs. If, in addition to this, malaria is not controlled using effective drugs, Africa may see the loss of generations of youths and a huge economical setback to the extent that poverty eradication will remain but a dream for ages.
The absence of new effective and affordable antimalarials is a formidable limitation to the current malaria control strategy, and there is an urgent need to search for traditional medicines to boost the dwindling number of treatments for malaria.
1.2.6 Traditional Medicine: To Use or Not to Use
Studies of plants used in traditional medicine for the treatment of malaria in various cultures have yielded important drugs that are critical to modern medicine. Two of the most effective drugs for malaria originate from traditional medicine: quinine from bark of the Peruvian Cinchona tree, and artemisinin from the Chinese antipyretic Artemisia annua (see Chapters 2 and 3). While new efficacious antimalarial compounds and phytomedicines are being rediscovered in medicinal plants, one can only wonder about potential drugs that have not yet been discovered. Plants used in traditional medicine may hold keys to the secrets of many potent antimalarial drugs. Pharmacological investigations already carried out on crude extracts and pure compounds for antimalarial activity have shown that most plants used traditionally for the treatment of malaria are efficacious, and some of them are even more effective than some currently used antimalarials in clinical use (Gessler, 1994).
In Africa south of the Sahara and probably in many parts of the tropical world, populations use and rely on traditional medicines more than on modern medicine. This is because traditional medicines and traditional health care are easily accessible to the majority of the populations whether urban or rural. In addition, because traditional healers live within and are part of the community, they have a higher distribution and a lower patient-healer ratio in rural areas than modern medical practitioners. The fact that traditional healers live with and grow within the community makes them more understanding and understandable to the communities surrounding them. They spend more time with their clients, and knowing the background information of the clients puts them in a better position to satisfy the patient psychologically.
Modern medicine is a comparatively foreign culture and is only well known to the scholars and doctors who practice it. Because such doctors are few and are often practicing in communities within which they did not grow up and live, they have little understanding of the customs and beliefs and tend to reject these customs and practices as foolish and ignorant. They therefore tend to be rejected by the communities and are usually visited as the last resort. This fact makes modern practice difficult in rural areas because many patients are brought in too late.
The other advantage of traditional medicine is that it usually approaches diseases in a holistic manner, combining spiritual and physical care of the patient. Modern medicine is therefore viewed as a strange way of healing in many communities and appears like a mechanical garage rather than a healing process.
The spiritual needs have made mission hospitals more appealing to communities than government hospitals wherever they are, because they conduct prayers in between treatment sessions, reassuring and consoling the soul of the sick body.
In terms of cost, traditional medicine is often more expensive than modern medicine. However, this is not seen as a burden by the patient and caretaker because payment can be made in many forms, often in kind. It can also be given in installments, and through this process, the patient and the traditional healer are linked together and see each other more often and end up developing even stronger trust.
Modern medicine will only accept money for treatment, and in many rural areas in poor countries, money is hardly available to many poor households. The parents may have some property like a goat or chicken and may be willing to give it for treatment, but often at the time of sickness of the child there may be no buyer and they may have no money.
In many cases, deaths that occur in the hands of traditional healers are considered to be caused by failure of the sick or relatives to abide by the rules. This puts traditional healers in the advantageous position of always being blameless, while deaths occurring in hospitals, even though the patients are brought very late, are more likely to be blamed upon the incumbent doctors. It is therefore impossible to stop traditional medical practice, and yet the practice often lacks clear evidence for safety, efficacy, and quality control in the process of making the product (Table 1.1).
1.2.7 Introducing Scientific Approaches to Traditional Medicine
Most contemporary research concerning modernising traditional medicine is aimed at confirming the safety and effectiveness of certain traditional methods and treatments through scientific experiments designed on the basis of modern scientific theories and approaches. In the development of antimalarial drugs or phytomedicines from traditional medicine, the emphasis is on the identification of new therapeutic leads over a variety of traditional medicinal plant sources. Four basic methods are generally useful in the selection of traditional medicinal plants to be investigated for drug discovery and development: (1) random selection of traditional medicinal plants followed by mass screening; (2) selection based on ethnomedical uses; (3) leads from literature searches and review of databases; and (4) chemotaxonomic approaches. One of the most difficult tasks in the
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