The Global Approach to Malaria Control and Eradication

 

The world continues to be plagued by a disease that has confronted her arguably since the emergence of prehistoric man (Bruce-Chwatt,1980). The global spread of malaria, although rarely publicized, continues to be the primary health and economic concern for over one-third of the world's population. In 1982, one million children under the age of five died as a direct result of malaria in tropical Africa alone (Bailey,1982). In the same year, the World Health Assembly reported that 150 million people fell victim to a malaria parasite, resulting in 2 million deaths (Bailey, 1982). Now, two decades later, those numbers are even higher.  300 cases of malaria are reported and, unfortunately, more people die from malaria today than 30 years ago.  Estimates indicate that 1.5 to 2.7 million people die from malaria yearly, 70-90% of which are children under the age of 5.(Phillips, 2001; Bloland, 2001)  The victims of malaria, however, need not be counted only among those who die. For those who survived their infection, the debilitating nature of this disease presents a bleak outlook for their survival of future sicknesses and reduces their life expectancy (Krier, 1980).  Malaria accounts for 25-50% of all hospital admissions in Africa (Krishna, 1997)

 

Malaria is clearly a global problem, presenting a serious infection risk to 2.7 billion people. The parasite has made its way into 52 of 58 countries in Africa, 11 of 18 countries in southwest Asia, all countries of Oceania, and 9 of 24 countries in south central and southeastern Asia (Bogitish,1990). In the Americas, there were an estimated 2.1 million cases of malaria in 1984 (Clyde, 1987). The parasite is constrained only by the expanse of its Anopheles vector and the social and climatological conditions of the area it finds itself. The tropical band in which the parasite is found contains countries that present very little defense against the spread of malaria, consisting predominately of Third World countries who lack surplus economic resources to enact legitimate and effective antimalarial programmes. Conditions of poverty, low standards of living in which health and educational services are underdeveloped and poorly funded, malnutrition, illiteracy and ignorance all serve to create an environment that enables Plasmodium to thrive (Prothero, 1965).

 

Not only do the majority of affected countries lack significant educational or monetary resources to combat the spread of malaria, but many of them exacerbate the problem. Poorly fed irrigation systems and unmonitored borrow-pits for housing construction encourage the growth of Anopheles populations (Bruce-Chwatt, 1980). The nomadic pastoral culture of North and Northeastern Africa and Mesopotamian regions encourages the spread of the parasite through infected individual into uninfected areas (Prothero, 1965). A great number of human factors contribute to the already volatile natural state of malarial transmission and frustrate what efforts are made today to control the disease (Prothero, 1965).

 

Plasmodium Morphology and Life Cycle

A complete understanding of the life cycle of Plasmodium is necessary in understanding the methods used in controlling the epidemic nature of the parasite. The malaria parasite is a one-celled organism that belongs to the phylum Apicomplexa, named because it possesses an apical complex.  All Plasmodium species feed on the hemoglobin in the red blood cells (erythrocytes) of their host by taking up cell cytoplasm through the micro pores and forming a food vacuole. Heme, a toxic metabolic byproduct of the hemoglobin digestion, is polymerized by heme polymerase into harmless hemozoin pigment and is deposited into the erythrocytic cytoplasm (Slater, 1992).

 

The life cycle of the human-infecting Plasmodium species can be broken down into two different stages -the vector (mosquito) stage and the host (human) stage. The sexual stage of the parasite is found in the female mosquito of the genus Anopheles and the asexual stage is found in humans for P. falciparum, P. vivax, P. malariae, and P. ovale. Transmission of the parasite occurs when a female mosquito takes a blood meal from an infected host. The male- and female-equivalent parasite forms capable of sexual reproduction (macrogametocytes, or gametes), both inactive in the host, are taken up in the blood meal. Here the red blood cell material surrounding them is broken down by the digestive juices of the mosquito, and the gametes are released into the lumen of the stomach. .The microgamete undergoes a maturation process at this stage by a process called exflagellation. During exflagellation, the nucleus undergoes three divisions. The nuclei formed from these divisions migrate to the cell edges and attach to portions of the cell structural components (centrioles). From this center an axoneme arises and the nucleo-axonemic complex detaches as a flagellate microgamete. The microgamete approaches the macrogametes formed by the macrogametocyte and penetrates the membrane-derived fertilization cone.

 

The fertilized macrogamete elongates after 12 to 24 hours to become a mobile form of the parasite called the ookinete, which passes through the stomach lining of the mosquito and embeds itself . Here the ookinete enlarges to 4 or 5 times its original size and develops into an cyst-like form, visible on the side of the mosquito gut (Bogitsh, 1990). Within the oocyst, storage pockets form that enlarge and segment the oocyst into smaller segments called sporoblasts. Repeated division within the sporoblast produces long, spindle -shaped structures called sporozoites (Bruce-Chwatt, 1980). When the engorged oocyte ruptures, these sporozoites are released into the mosquito and make their way into the salivary gland. At this point the mosquito becomes infective.

 

Whenever the mosquito takes another blood meal, the sporozoites are injected into the blood stream of the person via the saliva. Inside the host, the sporozoites that are not killed by the immune system  travel to the cells of the liver, marking the beginning of the  exo-erythrocytic phase of the parasite. .Inside the liver the parasites change forms again, into something called a trophozoite  and begin the pre-erythrocytic stage (Krier, 1980). The trophozoite duplicates non-sexually, producing thousands of forms called merozoites that fill the tissue of the trophozoite cell that ruptures when fully developed. These merozoites flood the surrounding tissue and enter the blood stream under most common circumstances; however, with some variants, the merozoites reenter the liver cells for what is called a secondary pre-erythrocytic stage (Bruce-Chwatt, 1980; Garnham, 1966). It is not currently known whether late relapses of the disease are caused by a dormant primary pre-erythrocytic parasite or a clinically undetectable secondary pre-erythrocytic system (Bruce- Chwatt, 1980). It is difficult to correlate the later hypothesis with the clinical course of the infection, as rupturing of tissue parasites is commonly associated with the first course of fever. Individuals often go decades without any signs of infection, i.e. fever, between the time of primary infection, their first exposure to the parasite, and their relapse, but the cycle for the pre-erythrocytic stage is two weeks at most.

 

The release of merozoites into the bloodstream begins the last stage in the life cycle of the parasite called the erythrocytic stage.  Although multiple parasitism is highly common, the simplest model is that single merozoites actively invade the cytoplasm of the erythrocytes, a process that requires the presence of surface Duffy antigens. According to Burton Bogitish at Vanderbilt University, parts of the parasite secrete substances that cause the erythrocytic membrane to stretch and fold in on itself, creating a storage chamber (vacuole) that surrounds the parasite. At this point the parasite begins to feed on the hemoglobin molecules within the red blood cell and convert the byproducts into a non-toxic pigment called hemozoin, as mentioned above. Young parasite forms in the cytoplasm of red blood cells posses a large food vacuole that pushes parasitic cytoplasm to the periphery.

 

When viewed under light microscopy, this stage resembles a ring, a phenomenon that gives this morphology the name "signet ring stage". The immature ring stage continues to feed on host cytoplasm and develops into a mature trophozoite whose food vacuole is responsible for little of the cell's volume. The nucleus then undergoes multiple fission (asexual reproduction), followed by a process of cell substance division producing a variable number of merozoites, depending on the species of malaria. After rupture of the red blood cell, merozoites can either reenter a naive erythrocyte and begin the erythrocytic cycle anew, or, in some models of malaria development, become a gametocyte if it is the product of a cycle late in the erythrocytic stage of infection. These gametocytes remain inactive in the bloodstream of the host, but begin to differentiate morphologically if taken up by a mosquito, starting the whole cycle again.

 

Epidemiology

The successful eradication of malaria in a region is dependant not only on an adequate knowledge of the malaria lifecycle, but in the epidemiology of the parasite as well.  In its most basic form, epidemiology is the study of the nature and spread of a disease founded from a concern for the health of a population or a group (Knox, 1979). Its application to malaria is an example of a complex biological system that involves the interaction between the mosquito and the human within an intricate environment in which climate, social conditions, and economic conditions all contribute influence (Krier, 1980). The epidemiology of malaria is interested in understanding the interaction between four factors involved in the transmission of the disease -the parasite, the host, thevector, and the environment.

 

The Parasite. Intense observation and experimentation over the last 150 years have yielded an immense amount of knowledge about the life cycle and transmission of the Plasmodium parasites. Integral to the epidemiologic study of the parasite is the knowledge of how various species exert dominance or acquire advantage through life cycles. P. malariae exhibits extreme longevity in the host, surviving for up to 50 years. This characteristic, in combination with its slow bloodstage cycle and lower metabolic rate, enables it to be more resistant to anti-malarial drugs and, with recent human technology, be likely to be transmitted through blood transfusion (Clyde, 1987). P. ovale  and P. vivax both persist in the liver of their host, releasing parasites periodically to enter the erythrocytic stage. These strains are thought to possess two types of sporozoites -one that demonstrates normal activity through exo-erythrocytic and erythrocytic stages within a normal time period, and an abnormal sporozoite termed a hypnozoite that remains dormant in the hepatocyte indefinitely, released by physiologic changes in the host (Bogitish,1990). Relapse, therefore, is common in P. ovale and P. vivax, which ensures an increased availability of gametocytes for Anopheline ingestion. P. falciparum, responsible for a high percentage of the malaria fatalities, possesses a rapid reproduction rate and is not preferential for what age erythrocyte  it infects, giving it marked advantage in mixed infections (Clyde, 1987). 

 

Many parasitic subspecies possess specific adaptations to increase transmission probability and to prolong host life. Krier proposes that P. malariae is most adapted to man because it seldom kills its host and demonstrates "almost commensalistic features," whereas P. falciparum may be the least adapted, as evidenced by its high mortality rate (Krier, 1980). Many parasites "observe" long incubation periods to align their highest level of clinical parasitemia with periods of increased  Anophelene feeding activity (Clyde, 1987;Krier, 1980). 

 

The Human host. Human factors affecting the epidemiology of malaria are both physiological and behavioral. In western Africa, most individuals lack theDuffy surface antigens that are necessary for P. vivax penetration of the erythrocytic plasma membrane (Bogitsh, 1990). People carrying the gene for haemoglobin S, which is phenotypically expressed as sickle-cell anemia, are unable to support  P. falciparum growth (Bruce-Chwatt, 1980). There is also recent evidence, although denied by studies done by S.K. Martin, that a deficiency in glucose-6-phosphate dehydrogenase gives some amount of protective action against malaria (Clyde,1987). Immunological factors also affect the susceptibility of individuals to infection. Although a limited and short-lived passive immunity is given to children by their mothers transplacentally, the lack of adequate immune response to infection is the explanation given to the high mortality rates among infected children (Clyde, 1987). Because of repeated exposure, most individuals in infectious areas develop an acquired immunity "strong enough to mitigate the symptoms of further attacks and to restrain parasitemia" (Clyde, 1987). Behaviorally, men in malarious areas often work at times of high vector activity an, as a result, display a higher degree of infection than women of the area. Other individuals fail to take necessary precautions, like the use of an insect repellant or protective netting at night, that help prevent a mosquito bite. Mass migrations as a result of war, famine or political distress are also major factors in the epidemiology of malaria.

 

The Anopheles Vector. .Critical density, a common statistic used to represent the influence of vectors on the endemic status of malaria in a population, is a measure of the number of bites per person per night. This measure is a good indication of the vector influence because it includes climactic changes and the preference of local Anopheles species for humans. Of 400 species of Anopheles, only 60 are proven vectors of human malaria (Bruce-Chwatt, 1980). Many species prefer animals, rather than humans, for blood meals, a characteristic that limits the spread of malaria in certain areas (Clyde, 1987). The longevity of the mosquito is another variable that affects the spread of malaria. While some species live long enough to allow several generations of sporozoites to develop, obviously a favorable condition for the parasite, other species have life spans of less than 10 days, which is not enough time for any of the species of Plaslnodium to complete their vector phase of sporozoite production (Clyde, 1987; Krier, 1980). Mosquitoes also demonstrate a seasonal fluctuation in population and, in a smaller time frame, specific times of feeding. The seasonal fluctuations are a function primarily of climate, which restrains the mosquito not only to specific seasons of transmission, but also to geographic regions. According to a study done by Wernsdorfer and Wemsdorfer in 1967, humidity has a major effect on the survival of certain species of Anopheles (Krier, 1980).  Anopheles vary in the parasites that they will support. While the European strain of P. falciparum readily develops in A. atroparvus, the African and Indian strains fail to be carried by the mosquito (Bruce-Chwatt,1980), and similarly a Kenyan strain of P. falciparum failed to infect several species of European mosquitoes. Other characteristics influencing the spread of malaria via the Anophelene vector include certain mosquito's preference for indoor (endophilic) or outdoor (exophilic) feeding and the differential feeding rates of different species of mosquitos.

 

The environment. The primary influence of environment of the transmission of malaria is meteorologic. Climatic conditions play a central role in determining the range of the vector, the work and social habits of the host, and certain cycle length constraints on the parasite. Malaria is restricted to regions between latitudes 65o N and 40o S and altitudes less than about 3000 meters because of climatic boundaries of the vector. Within the given boundaries, temperature and weather conditions continue to affect the transmission and development abilities of the parasite. Colder temperatures slow down the natural cycles of the parasite, sometimes extending them beyond the longevity of the mosquito, and cease the metabolic activity of the parasite if temperature dips below 16o C (Bailey, 1982; Bruce-Chwatt,1980).  Rainfall is an important factor in the environmental influence, but it is complex in its effects. Although rainfall increases the amount of water available for the female Anopheles to breed, often large amounts of rain disrupt standing bodies of water, transforming them into moving streams or rivers that will not support larval development. On the converse, the absence of rain for long periods of time may increase the chances of a body of water being stagnant, but the total surface area of water is reduced. Other sources of stagnant water surface irrigation ditches, have dangerous effects on malarial transmission rates because they raise water tables and humidity in addition to providing a favorable breeding ground for Anopheles (Krier, 1980). Humidity, as mentioned before, has a marked effect on the survival rates of mosquitos, and provides another boundary for the vector (Bruce-Chwatt, 1980; Clyde, 1987). When humidity levels begin to drop below 60%, the mortality rate for Anopheles begins to rise (Krier, 1980). 

 

Strong winds have also been given credit for reducing the life expectancy of mosquitoes and preventing them from ovipositioning. Gentle winds, however, broaden the flight range of the vector and therefore broaden the range of Plasmodium transmission (Krier, 1980). The presence of water-bearing plants that cup small amounts of water, in which the mosquitos breed, also has a positive effect on the rate of malarial transmission (Clyde, 1987). 

 

Malaria Eradication

The burden of malaria control in the Twentieth Century had been largely taken up by World Health Organization, which adopted a formal policy on the control and eradication of the parasite in 1955. At the same time the WHO also created the Division of Malaria Eradication and established an account to fund the project called the Malaria Eradication Special Account (Prothero, 1965). This program no longer exists, but has been replaced by the Roll Back Malaria program.  The universally accepted concept for the eradication of malaria is to reduce the mosquito population to levels that cannot support the spread of the malaria parasite and to eliminate all other sources of infection over a long enough period of time so that the parasite will naturally die out (Prothero, 1965). To achieve this comprehensive control of the parasite, most eradication programmes are implemented in four phases - preparatory, attack, consolidation and maintenance (Prothero, 1965).

 

The preparatory phase consists predominantly of the establishment of the organizational, political and educational framework from which the enacted programmes will operate. It includes training of workers, building adequate operational facilities, area research and census, and assessment of the epidemiological problem. The attack phase involves the enactment of eradication programmes and feedback on the effectiveness of procedures. It is in the attack phase where anti-larval, insecticidal, and anti-malarial measures are enacted. The third phase, consolidation, consists of close surveillance of the population and the use of machinery that responds to and deals with fresh cases of infection effectively and rapidly. The final phase, maintenance, is enacted when no intrinsic transmission has occurred in three years, and serves to watch against parasite reintroduction.(Krier, 1980;Prothero, 1965).

 

Malaria Epidemic Control

Because of the exponentially growing nature of malaria and the ease by which it can be transferred from one host to another, like many other infectious diseases that have plagued the globe, this disease must be vigorously attacked through each of the factors that affects it. Without adequate control, the disease advances to epidemic proportions and becomes an economic and sociologic concern in addition to its health risk. Recognizing this fact, as mentioned before, the World Health Organization has taken primary leadership in controlling the spread of malaria by enacting significant eradication policy in affected areas. In attempting to eradicate Plasmodium infections from a given population, the WHO has established four primary objectives.

 

First, programmes are intended to reduce the rate of infection transmission in areas where the disease has reached epidemic proportions (Clyde, 1987). In order to reduce transmission, effective programs employ two basic ideas: decrease the population of mosquitos and prevent the mosquitos from reaching humans.  To decrease mosquito populations, programs will spray insecticides using many different devices to kill mosquitos, eliminate standing, stagnant bodies of water where mosquitos breed, and use biological methods of larval control such a larvae-eating fish and molds and bacteria that destroy mosquitoes as well.  In order to prevent mosquitos from reaching humans, communities may discourage citizens from being out at dusk when mosquitos are most likely to bite, and employ widespread use of insecticide impregnated bed nets.  Other successful strategies have been to improve housing by repairing window screens and encouraging the use of applied insecticides.  India serves as an example of the use of these programs.  In 1953-4, the spread of malaria in India had reached 75 of 360 million people of the nation's population. The disease was responsible for 10 percent of the hospitalizations and large economic losses both in agriculture and in industry. In response, the National Malaria Control Programme, established just that year, enacted major efforts to control the Anopheles vector through the use of large-scale residual insecticides (Knox, 1979). Unfortunately, the effort failed, primarily due to cost and the emergence of an insecticide resistance in the vector; however, this situation serves to illustrate the primary objective of eradication programmes of reducing the spread of the disease through vector control.

 

A second objective in malaria eradication programmes is to reduce the morbidity and mortality of the parasitic infections. The bulk of chemotherapy and chemoprophylaxis techniques are established in epidemic and pre-epidemic areas to accomplish this objective. Specifically included in this objective is the distribution of drugs to all available treatment services and clinics, the enactment of prophylactic services using anti-malarial drugs to specific population groups like children, pregnant women, and various labor groups, and the establishment of certain oversight organizations to monitor the epidemiologic effects of existing programmes (Cyde, 1987).

 

The third objective is to prevent the spread of malaria to non-infected areas of the globe (Clyde, 1987). This objective is ill-defined in specific programming and often comes as a result of vector control, chemotherapy, and chemoprophylaxis. Problems arise in areas of increased mobility where a nomadic existence is the way of life. In European colonial areas of Africa, political power has been used in the past to end the fluid nature of populations and offer social stability (Prothero, 1965). Here, political stability often has indirect affects on the ability of malaria control and eradication policies to effectively accomplish their objectives. Such events as civil war, famine or political upheaval and subsequent migrations often serve to spread infected individuals into "naive" areas, where malaria has not yet been observed.

 

The final objective in malarial eradication in a population is to assist in social and economic growth in the particular area. Without adequate funding and social structure to uphold eradication policy, programme services fail to be effectively carried out and fail to make lasting effect on parasitic transmission trends. In the example of the India problem in the Fifties, the primary concern of programmes was cost, which not only slowed the enactment of policy to some degree, but also dictated policy and created a paradigm shift in the goals of proposed programmes. Specifically, when costs rose to an unacceptable levels, policy shifted from transmission control to transmission eradication, a more expensive solution, but one whose cost projections were finite (Knox, 1979). Cost, though, is not the only non-scientific concern of epidemiology. In respect to the importance of social and economic advancement in the eradication of malaria, Leonard Jan Bruce-Chwatt states, “The close relationship between disease and socio-economic advance of developing tropical countries has been abundantly proved. It is now clear that the successful implementation of malaria eradication requires a certain minimum level of basic health services," (Bruce-Chwatt, 1980). Often intense political pressure forces the enactment of massive malaria programmes onto local, or peripheral, health care establishments, decentralizing eradication efforts that require immense coordination to be effective. Where adequate health services exist, little cooperation exists between the public and the private sectors for the enactment of eradication programmes, and the cooperation that does exist is primarily at the ministerial or health directorate level, rather that at the field operational level where coordination is crucial to effectiveness (Clyde, 1987).

 

Chemotherapy, Chemoprophylaxis and Vector Control

Chemotherapy and prophylaxis. In attempting to control the spread of malaria in a given area and reduce the transmission of the parasite to level at which the parasite population will die out naturally, a major part of programming and funding goes to the acquisition and distribution of antimalarial drugs to eliminate the parasite from the human host. These drugs are used for three different purposes, with different drugs existing for each purpose.

 

First, antimalarial drugs are used to prevent infection from occurring in an individual (Bruce-Chwatt, 1980). Drugs used for this purpose are termed schizonticidal because they attack the pre-erythrocytic stages of parasites. The goal of causal prophylactic drugs is not to prevent sporozoites from reaching the liver of the inoculated individual, but, rather, to attack the early stages of the parasite while it is still confined to the liver parenchymal cells and to prevent these parasites from releasing merozoites into the bloodstream. An example of this type of antimalarial is proguanil which, although it has slow schizonticidal action on erythrocytic forms of the parasite, is highly effective on tissue schizonts (Clyde, 1987). Proguanil, or primethamine, a close relative of proguanil, is preferred in endemic areas because of their safety and absence of side-effects. Proguanil is rapidly absorbed by the upper gastrointestinal tract and is eliminated slowly through urine and feces, leaving little in the host to accumulate in the tissues. Another type of prophylaxis exists where schizogony is not prevented, but parasites are kept at a subpatent level so that no clinical symptoms are observed. This condition is known as suppressive, or clinical, prophylaxis. When the administration of drugs of this nature is ceased, system parasitemia is expected, as is the appearance of clinical symptoms. Blood schizonticides are effective as clinical prophylactic drugs (Bruce-Chwatt, 1980).

 

Secondly, antimalarial drugs are used for curative purposes to act on existing infections. The action of drugs used for therapeutic purposes is primarily on blood schizonts, preventing the erythrocytic cycle to continue. Therapeutic drugs can either result in temporary cure with a temporary suppression of symptoms or temporary cure in which the parasite is completely removed from the host system.  Drug treatment for malaria species that often result in relapse or recrudescence is usually followed by an anti-relapse drug like primaquine or pyrimethamine (Bruce-Chwatt, 1980). All eight of the common antimalarial compounds - quinine, mepacrine, chloroquine, amodiaquine, primaquine, proguanil, pyrimethamine, and the sulphones/sulphoamines -have blood schizonticidal activity, although some have greater effects than others.

 

For over three centuries quinine has been the only available effective drug against malaria. A derivative of cinchona, quinine has fast action on asexual erythrocytic parasites and is active against the gametocytes of all species of malaria except P. falciparum. Severe side-effects including giddiness, temporary blindness, deafness, and ringing in the ears result if quinine is used over a long period of time. It has been replaced recently by synthetic compounds that are less toxic and produce less side-effects (Bruce-Chwatt, 1980). The most widespread replacement of quinine is chloroquine, a 4-aminoquinoline that is excellent in the attack of malaria and in its suppression. Chloroquine, when given at normal dosages, has no significant side-effects, although it can be responsible for pruritus, headache, nausea, severe retinitis and blurring of vision if given in large doses over extended periods of time (Krier, 1980). Unfortunately, chloroquine-resistant strains of Plasmodium have begun to show up in alarming numbers throughout the globe, resulting in a resurgence in the numbers of malaria cases. In most endemic areas, in which chloroquine resistance is highest, countries are beginning to mover toward sulfadoxine/pyrimethamine combination as first line treatment for infections.  In areas where multi-drug resistance is common, the treatment strategies have moved to using combinations such as mefloquine/quinine or mefloquine/artesunate as the first line of therapy.(Bloland, 2001)

 

The final use of anti-malarial drugs is in the prevention of the transmission of malarial infection. This is accomplished by drugs that act on the gametocytes in the blood of the host or by interrupting the development of oocysts in the mosquito when it takes a blood meal from an individual who has taken a sporontocidal drug (Bruce-Chwatt,1980). Primaquine, chloroquine, mepacrine and quinine are all active against sexual forms of parasites in the erythrocytic phase, whereas pyrimethamine, proguanil and primaquine all disrupt the development of gametocytes in the mosquito.

 

Vector control. The other main thrust in programmes for the eradication of malaria is the attempt to remove the Anophelene vector from the endemic area.  Complete action against the mosquito includes larval control and the use of insecticides to reduce adult populations. 

 

There are three main classes of larval reduction techniques - civil, structural, biological, and insecticidal. The major cause of massive mosquito breeding in a given area is the existence of large, stagnant bodies of water. Drainage ditches, irrigation ditches, borrow pits, and swamp lands all offer unlimited breeding spaces for mosquito populations. First priority in most eradication operations is the elimination of such bodies of water by either filling them in or restructuring the drainage systems to facilitate the movement of water. When free-standing bodies of water are necessary, as in the case of a reservoir or a water well, other methods of larval control are necessary. Often species of larivivorous fish are introduced into water systems as an efficient method of larval control. In a small town in India, the introduction of 20 Gambusia into the area wells effectively eliminated the breeding of the major vector in the area (Clyde, 1987). Other natural pathogens that are used in attacking mosquito larvae include viruses, bacteria (Bacillus thuringiensis ), protozoa (Nosema ), fungi (Coelomomyces ), and nematodes. Communities can also use chemical larvicides applied to the surface of the water to control breeding. The most common insecticides applied in conjunction with larval eradication programmes include petroleum oils, constituent compounds of Pyrethrum, chlorinated hydrocarbons, organophosphorus insecticides, and carbamates (Bruce-Chwatt, 1980).

 

Vector control efforts also include the periodic insecticidal spraying of homes and free spaces of known mosquito density, a practice known as space spraying, in order to control adult vector populations. Residual pesticides like pyrethrum and DDT are among the most common because of their low cost and high degree of vector mortality (Clyde, 1987). Unfortunately, several species of Anopheles have become resistant to the successor pyrethroid insecticides and threaten to make mass spraying and insecticide-impregnated nets ineffective against the control and spread of the malaria-bearing mosquito.  As a result of the emerging resistance, spraying programs have relied more and more on household DDT spraying (Whitty, 2002).  In conjunction with mass-applied insecticides, personal barriers are employed to reduce the amount of bites by female mosquitoes.  The two most common barriers are mosquito netting, which is used to cover the beds of individuals at night, and removable curtains impregnated with various insecticides to block entrances of hon1es (Clyde, 1987). The cost effectiveness of residual spraying is steadily decreasing as resistant Anopheles strains begin to emerge, creating the need for different, more expensive chemical compounds to attack adult populations of mosquitoes (Bruce-Chwatt, 1980).

 

Vaccine Development

The development of a vaccine against the many species of malaria has always been held as the ultimate goal in controlling and potentially eradicating the parasites from human disease.  Because of the many forms the parasite takes on once inside the host body, vaccine development has been an intensely challenging goal, with only recent developments showing much promise for success.  In general, vaccines are targeted against one of three stages in the malaria lifecycle – pre-erythrocytic, erythrocytic or sexual.

 

In the pre-erythrocytic stage, the vaccine is directed against the trophozoites or sporozoites.  This stage offers the most hope in vaccine development and has been the target of most trials conducted thus far.  One trial of a vaccine targeted at this stage achieved 71% initial protection at 2 months.  Unfortunately, this protection quickly waned and fell to near zero by fifteen weeks (Whitty. 2002).  If a vaccine of this type were successfully developed, it would be beneficial to both residents of endemic areas and travellors alike.  Erythrocytic phase vaccines are directed towards the merozoite that are released from red blood cells.  Vaccines of this type are more difficult to develop and test due to the mortality associated with circulating parasites.  Volunteers would become quite ill before the traditional methods of parasite detection would show the presence of organisms.  Polymerase chain reaction techniques, although, have allowed researchers to detect parasites at much lower levels, and may be the key to successful and safe vaccine testing of erythrocytic-targeted vaccines.  Finally, vaccines targeted at the sexual stage of the malaria lifecycle attempt to stop the spread of the gametocyte from the human host to the vector.  This type of vaccine would be ineffective in preventing individuals from being infected by novel malaria infections but would be effective at the population level to eliminate the spread of malaria and would, over time, be potentially effective in eradicating malaria. 

 

One exciting area of interest in vaccine development is the area of DNA vaccines.  With a DNA vaccine, the genomic code of a parasitic antigen is revealed to the host using a carrier vector like a pox virus or alpha virus.  Once inside the host, a limited amount of the antigenic protein is produced, which triggers an intense host response.(Poland, 2002)  Recent trials of DNA vaccines have shown promise in inducing an immune response to malarial antigens.(Wang, 1998)  Another hopeful area of vaccine development is the concept of a multivalent, multistage vaccine in which more than one antigen is targeted at more than one stage of the parasite lifecycle.  With the realization that complete sterile immunity may not be achieved, a vaccine of this type might be able to reduce the burden of disease and decrease the incidence of first infection both by reducing susceptibility to infection and by reducing infectiveness or disease transmission.   Like the DNA vaccines, several trials of multivalent vaccines are underway; unfortunately, however, success thus far has been limited. (Holder, 1999)

 

Roll Back Malaria

Origin and Objectives.  In 1998 the World Health Organization, under the leadership of Dr. Gro Harlem Brundtland, began the Global Roll Back Malaria Initiative (RBM) against malaria to combat the growing malarial burden on developing countries, seeing the health issue as an issue of poverty.  The WHO was joined in partnership in this effort by UNICEF, UNDP and the World Bank initially, and then later by multilateral and bilateral national aid organizations like USAID, DFID and ECHO, various non-governmental organizations like Medicines Sans Frontiers and International Federation of Red Cross, various governments and private sector companies like Eni, ExxonMobil, GlaxoSmithKline and Proctor & Gamble.  The primary objective of RBM was to reduce malaria related mortality by one half by the year 2010 and reduce mortality even further in successive years.  This objective was to be accomplished by meeting several short term and eventual long term goals.  Short term goals include strengthening of national capacity for malaria control programs, inter-country resource networking and cooperation , and grass roots support of RBM initiatives to gain community involvement and support.   The long term goals are to reduce the burden of malaria in individual contries using locally directed interventions and to ensure universal access to malaria treatment and interventions, seeing such access and health equity as a basic right of individuals in malaria endemic areas.  RBM, in comparison to its predecessor program, the Malaria Eradication Programme, has at the core of its establishment the desire to invest in health sector development, essentially empowering and enabling countries and regions who might not otherwise have the resources to combat malaria.  RBM is clear in its desire to invest in the health infrastructure of countries with a desire to benefit those countries’ efforts against other communicable diseases (WHO, 2000)

 

Philosophy.  According to the WHO website, Roll Back Malaria “is not a project or program.  It is a social movement that is part of broader societal action for health and human development.” (WHO, 2000)  This concept of societal action for health development in addressing the global problem of malaria stems from the view of malaria as a developmental and poverty issue.  Malaria in these terms can be seen as part of a vicious cycle in economic depression both at the family and the community level.  Within a household, illness from malaria can lead to as much as a 25% loss in earnings. Continued bouts of malaria are known to slow children’s cognitive and social development, and in school age children will slow their educational progress.  Families affected by malaria are less likely to plant and harvest crops, and when they do they are more likely to plant less labor-intensive crops, rather than crops that generate greater revenue but require more energy.  At the national level, malaria can cost a country upwards of 6% of its Gross Domestic Product, taking away resources that might otherwise be invested in infrastructure, preventative health care or social programs that would benefit the population. 

 

Strategy.  As stated earlier, the basic strategy of Roll Back Malaria is to empower individual countries to enact malaria programs that they might not otherwise be able to afford by mobilizing cooperative expertise and outside monetary support.  The WHO advocates four basic approaches to accomplish the overarching reduction goal of 50% by 2010:  prompt access to treatment, prevention and control in pregnant women, vector control, and prediction and containment of epidemics.  (WHO, 2003)  In this respect, each country is encourage to devise a Country Specific Plan (CSP) to address its unique problems.  As a continent, Africa set personal goals to assure that 60% of its population would have access to treatment of acute disease within 24 hours, 60% of at risk populations including children under 5 and pregnant women would have access to preventive measures such as impregnated mosquito nets, and 60% of pregnant women would have access to intermittent preventive treatment.  To encourage investment in malaria programs, tariffs and taxes on necessary supplies are waived and debt relief is provided.  The RBM program has established the following strategic directions to lead the work being done in individual countries:  to have an integrated approach addressing issues common to primary prevention measures and major communicable diseases, to promote equity by focusing on disadvantaged populations and establishing basic standards of health care, to incorporate primary prevention in the initiatives, to increase media involvement through partnership, to strengthen advocacy at the political and professional levels, to enhance the role of health professionals, to support communities and families in basic prevention, to mainstream the concepts of RBM, and to continue to forge new partnerships in the RBM initiatives. (WHO, 2001)

 

Timetable. Roll Back Malaria was established with an embedded timetable to guide progress.  The preparatory phase was planned to go from June, 1999 to December, 1999.  The piloting phase as designed to be a two-year trial and pilot phase in selected areas from January, 2000 to December, 2000.  The operational phase is scheduled to run from 2002 to 2006.  So far, many countries have become involved and begun to see impressive gains in their individual fights against the malaria burden in their regions.  An 18 month trial in Sri Lanka using treated bed nets saw an 80% decrease in malaria infections and a similar trial in Vietnam saw malaria infection drop 95%.  Plans are underway in sub-Saharan Africa to distribute high-tech bed nets over the next 5 years to more than 60 million homes.  This program is a good example of outside subsidy and local health programs working together as the price of the nets are expected to drop by 50% from US$ 4 to US$2, and will be distributed free of charge from health facilities for those who cannot afford them.(WHO, 2000)

 

Conclusion

Malaria is a tremendous global problem in the new millennium   As resistance of both mosquitos and the parasites to the currently used insecticides and treatments emerge and expand, the world faces the possibility of seeing a rise in the incidence of malaria.  The control and decrease of malaria will be attainable only through the commitment of communities to address the problem.

 

Within the communities, success can be attainable through the methodical application of the basic tenents of the global eradication scheme of preparation, attack, consolidation and maintenance.  Local programs must plan ahead assuring commitment and adequate infrastructure prior to beginning the process.  When initiating the attack phase, programs must address all aspects of the disease addressing mosquito populations, mosquito access to humans, and rapid and adequate treatment of infected individuals.  During the consolidation phase, communities must be diligent to monitor for new infection and address issues that might have led to cracks in the system like decreased adherence to the use of bed nets or allowing water to become stagnant.  Finally, programs must not abandon the gains accomplished during the previous three phases when they finally reach the maintenance phase.  They must continue to monitor on a periodic basis and adhere to the basic practices that allowed them to achieve success.  With sound fundamentals, an enduring commitment to eradication and adequate resources the global problem of malaria can be addressed and the world can see the end a deadly and costly disease.

 

 

Useful Resources

Burton Bogitish and Thomas Cheng, Human Parasitology, (Saunders College Pub: Philadelphia, 1990)

http://www.rbm.who.int

 http://www.whosea.org/malaria

http://www.malariasite.com/malaria/ControlOfMalaria.htm

 

References

 

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Bloland, Peter B., Drug Resistance in Malaria, (WHO: Geneva, 2001)

 

 Burton Bogitish and Thomas Cheng, Human Parasitology, (Saunders College Pub: Philadelphia, 1990)

 

Bruce-Chwatt, Leonard Jan,  Essential malariology (Heinemann Medical Books: London, 1980)

 

Clyde, David F. 1987. Recent Trends in the Epidemiology and Control of Malaria. Epidemiologic Reviews, Vol.

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Krishna, Sanjeev, “Science, Medicine and the Future:  Malaria”, BMJ 1997;315:730-732 (20 September)

 

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WHO Technical Report Series 805, Practical Chemotherapy of Malaria, (WHO: Geneva, 1990).

 

World Health Organization, Rollback Malaria: A Global Partnership, http://www.rbm.who.int (WHO, 2003)

 

World Health Organization, Rollback Malaria, http://www.whosea.org/malaria, (WHO, 2000)