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MALARIA: Obstacles and Opportunities 10 Epidemiologic Approaches to Malaria Control WHERE WE WANT TO BE IN THE YEAR 2010 Epidemiologists will have made great strides in elucidating the complex determinants of malaria, including the risk factors for severe and complicated disease and the role of acquired immunity. It will be clear how chemoprophylaxis and drug therapy reduce morbidity and mortality, and how malaria more severely affects pregnant women and young children. New techniques to measure the impact of various anti-malaria interventions, including strategies to control mosquito populations, will have been developed and will be used in different regions of the world. Advances in understanding local epidemiology will lead to better targeted and more effective malaria control programs. Malaria-related illness and death will decrease as a result. Drug and vaccine testing will be enhanced by epidemiologically based insights into the variations in parasite and human biology that determine the acquisition of immunity and the development of clinical disease. WHERE WE ARE TODAY Epidemiologically, malaria is extremely complex. The nature, duration, and severity of malaria infection depend not only on the species of malaria
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MALARIA: Obstacles and Opportunities parasite but also on the level of malaria-specific acquired immunity in the individual. Malaria is a focal disease whose distribution is influenced by literally dozens of factors related both to human, mosquito, and parasite populations and to the environment. Because epidemiology is a cross-disciplinary science, many of the building blocks of malaria epidemiology are discussed in greater detail elsewhere in this report (see Chapter 4, Chapter 7, Chapter 8 and Chapter 12). No attempt will be made here to provide a comprehensive review of the status of malaria epidemiology. Rather, this chapter focuses on several key issues in this evolving science and introduces a new epidemiologically-based approach to understanding malaria. Infection and Disease For many years, epidemiologic studies have focused on the prevalence of malaria infection in populations, relating levels of infection to a variety of parasitologic, climatologic, and entomologic parameters. Beginning in the late 1950s and continuing through the late 1960s, when considerable effort was directed toward the global eradication of malaria, the goal was to halt malaria transmission altogether. Therefore, it was particularly important to detect and eliminate all malaria infections. The incidence of clinical disease and an understanding of risk factors for disease were considered to be of minor significance, since it was believed that malaria would soon disappear. Indeed, little research was conducted on the clinical progression of, or risk factors for, the disease itself. This distinction between infection and disease is particularly important with respect to malaria. The vast majority of older children and adults living in some endemic areas may be infected with the parasite, but only a small proportion will suffer occasional mild or moderate illness. Knowing that someone is infected with the malaria parasite, then, is of little practical value; being able to determine which infected individuals will become ill and why would be quite useful, however. Despite the formal abandonment by the World Health Organization (WHO) in 1969 of plans to eradicate malaria in favor of strategies to control the disease, epidemiologic studies and surveillance persisted in tracking malaria infections. Even today, many malaria control programs continue to measure the magnitude of the malaria problem and the relative success of their control efforts by using the annual parasite incidence, a calculation of the number of parasite-infected individuals as a proportion of the total population at risk for becoming infected. Millions of blood films are examined under the microscope each year in malaria-endemic countries, of which less than five percent may be found to contain parasites. The resources expended on such questionably useful surveys are enormous, and given
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MALARIA: Obstacles and Opportunities the risk of transmitting the human immunodeficiency virus, hepatitis B virus, and other blood-borne pathogens through nonsterile finger-prick methods, such routine mass screening cannot be recommended. In countries where malaria is highly endemic, the epidemiology is focal, the burden of disease varies greatly, and surveys that evaluate the prevalence of malaria infection can be particularly deceptive. For example, areas of both Papua New Guinea and the Gambia are highly endemic for malaria and have similar prevalences of malaria infection, yet the levels of malaria-related mortality in the two countries appear to be quite different. On the north coast of Papua New Guinea, few deaths can be traced to malaria, even among very young children (Moir et al., 1989), while in the Gambia, a quarter of all deaths in children one to four years of age are believed to be malaria related (Greenwood et al., 1987). Some of the differences may be explained by the fact that the population around Madang, Papua New Guinea, is relatively advantaged and has better access to antimalarial drugs. Not all people in malarious areas are at the same risk of becoming sick or dying from the disease. Indeed, the risk of severe and potentially fatal infection with Plasmodium falciparum falls principally on nonimmunes, such as young children, immigrants from malaria-free areas, and pregnant women, in whom immunosuppression during pregnancy appears to be associated with a higher frequency of malaria infection and adverse pregnancy outcomes (Breman and Campbell, 1988). Despite this general pattern, and for reasons not well understood, not all individuals within these groups are at equal risk of becoming seriously ill or dying. Much of the most recent work in malaria epidemiology has thus concentrated on the identification of the variables that place certain groups at greater risk of illness and death. Central to this work has been a better understanding of the acquisition of immunity. Acquired immunity appears to be relatively short-lived and depends on repeated exposure to the parasite over time. It is directly related to the level of malaria endemicity in a given area, transmission patterns, frequency of human-vector contact, and the length of time a person resides in an endemic area. The species of parasite present, the level of endemicity, and the biologic, behavioral, and socioeconomic characteristics of the human population determine the prevalence of infection and the distribution of disease. An increasingly important issue in understanding the epidemiology of malaria disease is the availability and use of antimalarial drugs. With the spread of drug-resistant parasites, the effects of drugs on immune status and on drug resistance itself are issues of paramount concern. By looking at malaria as a disease, epidemiologists are better equipped to assess the short- and long-term impacts of various control strategies,
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MALARIA: Obstacles and Opportunities including antimosquito measures (e.g., insecticide-treated bednets) and antimalarial drugs (given as chemoprophylaxis, as therapy, or for both purposes), in reducing malaria-related morbidity and mortality. The shift from studying malaria as an infection to focusing on its importance as a disease is recent, and the questions being asked are a substantial departure from traditional routes of inquiry. The answers are far from apparent. Morbidity and Mortality In terms of its contribution to morbidity and mortality, malaria is among the world's most serious health problems. According to WHO, there are over 100 million clinical cases of malaria in the world each year (World Health Organization, 1990), and an estimated 1 to 2 million deaths. Because of the difficulty of obtaining reliable data, most of the malaria-related mortality estimates are based on extrapolations from areas and studies in which mortality has been effectively documented. One of the most widely quoted figures is that of 1 million children dying of malaria in Africa each year (Bruce-Chwatt, 1969). When one is determining levels of morbidity, for example, a clinical diagnosis of malaria in the absence of microscopic confirmation— a frequent occurrence in many parts of the world—can have an error rate of up to 50 percent. On the other hand, the prevalence of malaria parasites in peripheral blood, particularly in children living in endemic areas, can be close to 100 percent, yet most of these children have asymptomatic infections, complicating confirmation of the diagnosis by a blood film. In addition to these inherent difficulties, there is generally uneven surveillance and incomplete and irregular reporting of malaria cases at all levels of the health system in most countries where the disease is endemic. Estimates of malaria mortality are notoriously imprecise and particularly difficult to derive. Even in the most rigorously conducted studies, ascertaining the number of malaria deaths is not without pitfalls. This is in part because most people in the world die at home, not in the hospital. Therefore, studies that rely on hospital-based records consistently underestimate mortality attributable to a given disease. In a recent study conducted in the Gambia, for example, 23 of 25 children who died of malaria died at home; only 2 died in a dispensary, and none died in the hospital (Greenwood et al., 1987). A number of methodologies have been developed to better determine the causes and rates of mortality in communities that lack formalized records of births and deaths. Verbal autopsy, in which the family of the deceased is interviewed about the circumstances of the death, can be useful for identifying those diseases with characteristic clinical features. Another demographic methodology, the preceding child technique, involves asking
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MALARIA: Obstacles and Opportunities a mother about the fate of her previous child. Analysis of prospectively recorded deaths by village health workers over an extended period of time can also be helpful in determining both overall mortality and disease-specific mortality. These and other methodologies, while useful, are imperfect and often imprecise. In certain settings, however, they should be further explored in estimating the impact of malaria in childhood mortality. Approaches to Malaria Control Tactical Variants and Stratification Several approaches to thinking about malaria control have been devised over the past 20 years. Two of the best known are based on tactical variants (World Health Organization, 1979) and stratification. The resurgence of malaria in many parts of the world beginning in the mid-1960s and continuing through the mid-1970s caused a general reassessment of existing control strategies. In the most significant of these efforts, WHO proposed a way of viewing malaria control that was based on what was thought to be achievable given the epidemiologic, sociologic, managerial, logistic, and financial resources of individual malarious countries. This tactical-variant approach was adopted by the Thirty-first World Health Assembly in 1978, and the concept was further developed at the meeting of the Seventeenth WHO Expert Committee on Malaria (World Health Organization, 1979) The four variants are (1) reduction and prevention of mortality due to malaria through drug treatment; (2) reduction and prevention of mortality and morbidity, with special attention to reduction of morbidity in high-risk groups, through prompt treatment, the distribution of prophylactic drugs to special at-risk groups, and application of vector control and personal protection measures, where appropriate; (3) in addition to the features of (1) and (2) above, a reduction in malaria prevalence through the systematic application of a malaria control program; and (4) country-wide malaria control, with the ultimate objective of eradication. These tactical variants were designed to illustrate possible malaria control objectives. They were not intended to help characterize or define the malaria problem in a country. The concept of stratification, developed by WHO in the mid-1980s, characterizes epidemiologic zones of malaria in terms of their main determinants, including climate, the location of sources of water and of mountains, vector biology, anthropology, and social and economic factors. Using stratification, a country or continent could be broken down by geographic area and/or by population characteristics, and a number of epidemiologic, biologic, social, and economic factors could be identified that would govern the choice and intensity of antimalarial interventions. The scale of appli-
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MALARIA: Obstacles and Opportunities cation of stratification varied considerably, from the characterization of large homogeneous areas to that of very small epidemiologic units, such as a locality. With a few exceptions, however, stratification has not been widely adopted or implemented, in part because a large amount of detailed baseline information was required. The Epidemiologic Approach to Malaria Control The Eighteenth Expert Committee (World Health Organization, 1986) further promoted the concept of an epidemiologic approach to malaria control. The approach emphasized the local variability in the distribution of malaria problems, calling for the design of appropriate and suitable control strategies, training of staff, and monitoring and evaluation in different ecological areas within a given country. The enormous changes that have overtaken most malaria programs in the past 10 or 15 years, in their transition from eradication to control and then, in some cases, control through primary health care, often against the background of decentralization and integration of health services, were just too much for many program managers to cope with. The problem was compounded by difficulties in interpreting guidelines about what methods of control should be used, and many managers virtually suspended their programs pending a firmer identification of what was actually to be done in the field. Development of the Paradigms In an attempt to make the epidemiologic approach to malaria control more user friendly and of greater practical utility to those charged with implementing and overseeing control programs, members of WHO 's Division of Control of Tropical Diseases and representatives of the Institute of Medicine's Committee on Malaria Prevention and Control convened a two-day meeting in Montreux, Switzerland, in September 1990. The purpose of the meeting was to simplify the complex epidemiology of malaria by classifying the disease into a limited number of major types or paradigms, a model first discussed in 1989 (Najera, 1989). It was thought that this approach would enable program managers and nonspecialists to better understand the variability of malaria and if developed more fully, provide a method of matching the most appropriate control tools to specific situations. Some critics of this approach considered it to be an oversimplification. Others felt that it was nothing new, a restatement of the obvious, another name for stratification, or the first step in creating another in a long line of malaria control dicta. The paradigm concept continues to generate a good deal of controversy.
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MALARIA: Obstacles and Opportunities While the malaria paradigms may be oversimplifications, the simplicity may allow the approach to work where others have failed. Previous epidemiologic approaches to malaria control, including stratification, have been faulted for being overly complex. Even if one accepts the underlying principles, it is difficult to know how to begin to plan malaria control interventions based on these approaches. In terms of substance, the paradigms are simply a new way of examining and understanding the sound epidemiologic principles already extensively explored. They are not dicta, but a way of thinking about and systematically organizing malaria control activities. The paradigm approach is in an early stage of development. Even so, it may help program managers and others better define the malaria problem and prioritize control interventions. The approach will require refinement and field validation before we can adequately assess its usefulness in rationalizing malaria control. The paradigm approach begins with the observation that most malaria problems in the world can be categorized as one or more major types: malaria of the African savannah; forest malaria; malaria associated with irrigated agriculture; highland fringe malaria; desert fringe and oasis malaria; urban malaria; plains malaria associated with traditional agriculture; and seashore malaria. Although certain situations may not fit easily into any of these categories, such cases are of limited importance on a global scale. There may also be unique hybrids of two or more of the paradigm types which will require special consideration. Use of these easily conceptualized types, rather than more abstract epidemiologic principles, enables even nonspecialists to gain an understanding of the malaria problem. Application of the paradigm approach requires a logical progression through a series of steps in which attributes of a particular malaria problem, from the most general through the more specific, are considered (see Appendix A). The goal is to classify the situation only as narrowly as necessary, not as narrowly as possible, before choosing control tools and planning interventions. The following is a brief description of the paradigm approach. A more complete discussion of the method and its use should soon be available from the Malaria Unit of the Control of Tropical Diseases at the World Health Organization. Description of the Paradigms Malaria of the African Savannah Eighty percent of the world's malaria and 90 percent of mortality due to the disease occur in Africa south of the Sahara, mostly in the savannah regions. The principal vectors, Anopheles gambiae, An. funestus, and An. arabiensis are efficient transmitters of the malaria parasite and are found in abundance. Malaria transmission is sea-
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MALARIA: Obstacles and Opportunities sonal and correlates with relatively predictable patterns of rainfall, although transmission may continue at lower levels during the dry season. Because of the extremely high inoculation rates, virtually all of those living in these areas become infected early in life. For children, treatment (until recently, chloroquine was very effective) may prevent death long enough for acquired immunity to establish itself, which can provide protection from malaria-related death or illness later in life. Young children who do not acquire this protective immunity, and whose infections are not treated adequately or promptly, are at particular risk of dying from the disease. These areas, which can be further subdivided into wet and dry savannah, are characterized by high-intensity transmission by efficient vectors in abundance, resulting in immunity in those who survive initial infections and an eventual ability to tolerate parasitemia without symptomatic or serious illness. Forest Malaria Forest malaria, the result of human incursions into forests or jungles, occurs in several regions of the world, including the Amazon basin of South America, Southeast Asia (primarily Bangladesh, Myanmar, Thailand, and the Indochinese peninsula), Borneo, equatorial Africa, and certain of the Pacific Islands. The indigenous inhabitants of these forest and jungle areas, including Indians of the Amazon, the pygmies of central Africa, and the aborigines of the Malaysian jungle, traditionally have been relatively unaffected by malaria. Recently, however, economic pressures have brought large numbers of poor nonindigenous laborers into these regions for agriculture, timbering, gem and gold mining, and road construction. The results have been serious malaria-related morbidity and considerable mortality among the newcomers and the reintroduction or increase of malaria in indigenous populations. Typically, the mosquitoes responsible for transmitting malaria parasites in forest areas are difficult or impossible to control by traditional means. For example, An. dirus, the primary malaria vector in Southeast Asian jungles, can develop in almost any shaded collection of water (even in animal hoofprints and the bracts of commensal plants); this mosquito feeds in the early evening, and rests outdoors after taking a blood meal. Such characteristics make the application of traditional larval control measures and other tactics aimed at reducing the adult mosquito population, such as use of residual insecticides, relatively fruitless. Malaria Associated with Irrigated Agriculture Irrigation for agricultural purposes may both provide breeding sites for vector mosquitoes and allow concentrated parasite reservoirs in the form of large labor forces to become established, helping maintain a high level of malaria transmission. Examples of places where this type of malaria occurs include the cotton plantations of the Gezira in the Sudan and irrigated rice cultivation areas in Sri Lanka.
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MALARIA: Obstacles and Opportunities Sugarcane cultivation in dry areas that require irrigation has also resulted in an increase in malaria transmission where it had not been a serious problem in the past. Highland Fringe Malaria Although malaria has been transmitted at altitudes of up to 2,800 meters, the disease does not generally occur above about 1,500 meters (Bruce-Chwatt, 1985). Because of fluctuations in climate, and perhaps even global warming, vector anophelines may begin to flourish at higher and higher altitudes. The altitudes subject to this type of malaria problem may vary greatly according to the local geography. Populations, in particular settled populations, living at higher, normally malaria-free altitudes may have little acquired immunity to malaria and so may suffer devastating epidemics. Such a situation recently occurred in the highland plateaus of Madagascar, where malaria had previously been eradicated or nearly so. Because of unusual climatic conditions, or perhaps as a result of a documented gradual increase in the mean temperature, the malaria vector An. funestus recolonized the high plateau, causing many hundreds of thousands of cases of the disease and significant mortality in the nonimmune population. Similar, less devastating epidemics have been seen in Papua New Guinea, in Ethiopia, and on the mountain slopes of Kenya. Even without an expansion in the range of vector anophelines, however, economic conditions may force nonimmune highland populations to search for work in lower highland fringe areas, where they may be exposed to intense malaria transmission. Desert Fringe and Oasis Malaria This paradigm shares many characteristics with highland fringe malaria, including the occurrence of periodic and serious epidemic outbreaks of disease in nonimmune populations. Since there is normally no transmission in these arid grassland areas, the populations living in or at the edge of deserts generally do not have protective immunity against malaria. When climatic conditions change—when, for example, unusually heavy rains occur that allow vector mosquitoes to develop—nonimmune populations may be at risk of infection and of severe and often fatal malaria. Such conditions have prevailed in recent years in areas of the Sahel, along the southern edge of the Sahara, and on the fringes of the Kalahari desert, where increasingly serious epidemics have occurred in northern Namibia over the past four years. Ethiopia regularly experiences such epidemics. Both settled populations and nomadic groups may be at risk near oases that support malaria transmission, such as in the western desert of Egypt. Urban Malaria Urban malaria can be of two basic types. Malaria can be transmitted by vectors well adapted to city conditions (e.g., An. stephensi,
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MALARIA: Obstacles and Opportunities the archetypal urban vector of South Asia). This type of mosquito, which develops in domestic water sources such as wells, cisterns, and household water containers, is responsible for malaria transmission in Delhi, Karachi, Madras, and other urban centers of the Indian subcontinent. Urban malaria may also occur when sprawling urban settlements encroach on the rural habitats of malaria vectors not usually found in city environments. This occurs in semiurban African villages where the African savannah paradigm predominates. It is important to differentiate these two situations, however, as malaria control strategies will be different even if the vector is the same. Similarly, the densely populated ramshackle settlements associated with gold mines in the Amazon basin support a type of urban malaria, which is actually the result of people moving into areas of forest malaria transmission. In areas of urban malaria, larval control may be a realistic option for reducing malaria transmission, particularly if communities become actively involved. Residual spraying of houses may also be feasible in such settings. Plains Malaria Associated with Traditional Agriculture Malaria transmission in plains villages involved in subsistence agriculture is usually of low to moderate intensity and fluctuates with the seasons. Such areas are prone to epidemics, particularly in association with early and prolonged rainy seasons. The predominant parasite is often P. vivax. While devastating epidemics are seldom seen, and childhood mortality is not a significant feature as it is with African savannah malaria, this type of malaria can cause chronic debility and suboptimal agricultural productivity. Malaria of this type is widely seen in South Asia and Central America. Seashore Malaria Many seashore areas of the tropics pose a malaria threat to residents and visitors alike. Such areas are becoming more and more important economically to poor countries as tourists search out unspoiled “tropical paradises” suitable as vacation sites and large numbers of workers come to support the industry. Port areas also offer the potential for malaria transmission and may be the source of infected mosquitoes transported by ships to other regions or of malaria imported by infected seamen to other countries. Seashore malaria may be transmitted by mosquitoes that breed in brackish water such as the South China Sea. In Africa, the seashore resorts of Kenya provide another example of this type of malaria. Because there is often the potential for successful malaria control efforts, and because of the income generated by tourism, expensive interventions may be more acceptable and sustainable in these areas. Most of the world's malaria problem can be characterized according to the paradigms described above. Certain other types represent combina-
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MALARIA: Obstacles and Opportunities tions of these paradigms. Malaria on islands, for example, falls generally under one or more of the eight paradigms; many of the islands of the South Pacific have coastal and highland fringe malaria. Riverine malaria is usually an intensification of either plains malaria or African savannah malaria, associated with greater potential for vector breeding. The malaria associated with development projects is often forest malaria or irrigated agriculture malaria influenced by the specific characteristic of the development project. These characteristics will determine the feasibility of certain types of interventions to some extent irrespective of the vector mosquito or ecological setting of transmission. Principal Determinants Once the types of malaria present in a country have been identified and ranked in importance, the paradigm's principal determinants must be systematically considered. These determinants will point to specific control strategies that should be considered within any given paradigm. Eight principal determinants have been identified to date: level of endemicity; parasite species; mosquito vectors; characteristics of the human population; social, behavioral, and economic considerations; health infrastructure; availability and effectiveness of antimalarial drugs; and the influence of development projects. In many situations, existing sources provide the general knowledge and specific data necessary to assess the importance of these determinants in setting control strategies. In other cases, simple operational research projects will be needed to collect basic information. Level of Endemicity Endemicity is characterized by different patterns of malaria transmission. Levels of transmission may be high, moderate, or low, and transmission may be seasonal, perennial, or characterized by periodic epidemics. Data about transmission patterns can often be extracted from existing health facilities or records of malaria control programs. Sometimes, however, original data will need to be collected. An understanding of transmission patterns is essential to the planning of vector control operations. For example, cycles of insecticide spraying should be adjusted to anticipate increasing densities of mosquito vectors. In addition, knowledge of existing patterns of malaria transmission may provide early warning of epidemics, perhaps allowing their impact to be diminished by control efforts. Parasite Species Plasmodium falciparum is the parasite species responsible for the most serious forms of malarial illness and for essentially all fatal cases of the disease. Plasmodium vivax, the most widely distributed of the malaria parasites, is seen frequently in temperate regions and, because
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MALARIA: Obstacles and Opportunities Drug resistance is becoming a major limiting factor in the use of affordable antimalarial drugs. Chloroquine resistance in P. falciparum malaria in Africa has been followed by resistance to the sulfadoxine-pyrimethamine combination and even, in some areas, to mefloquine. It is important to note, however, that resistance is often confined to small geographic areas. In terms of controlling malaria, the likelihood that patients will comply with a recommended course of treatment—the drug regimen's feasibility—is nearly as important as the drug's antiparasite efficacy. Drug regimens requiring complex administration schedules (such as quinine-tetracycline) are unlikely to be adequately followed by outpatients, resulting in partial treatment, recrudescence, and possibly the selection of drug-resistant parasite populations. Finally, the goal of drug therapy needs to be defined. Those in charge of control efforts need to know whether it is necessary to completely eliminate malaria infection or simply to treat an episode of acute disease. In areas where infection is sporadic and work related, where patients have little or no acquired immunity, and where health services are far from the site where infection was acquired, it is essential to provide a reliably curative regimen. In situations where immunity is the most important protection against serious malaria-related morbidity or death, and where reinfection within a short period of time is certain, the aim of drug treatment may be to allow the patient to survive the current acute episode, without necessarily eradicating the parasitemia. Development Projects The local impact of development needs to be considered when antimalarial interventions are planned. Development projects may be officially sanctioned by government or undertaken by private enterprise (e.g., road building, dam construction, forestry, or agricultural projects) or they may be unofficial, uncontrolled activities, such as large-scale gem or gold mining or illegal land development. All such activities affect the epidemiologic factors relating to malaria, including population immunity, mobility, access to health services, and availability of drugs, and often represent major differences from the surrounding national or even local malaria situations. Development projects also provide a controlled setting for an effective malaria control effort specific to the labor force and their families. These settings should be exploited wherever possible and private enterprise should be enlisted to assume a major responsibility. Malaria Control Tools The control strategies adopted for any given paradigm and its principal determinants will be constrained by the control tools available and, of course, by their cost, effectiveness, and feasibility of implementation. The
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MALARIA: Obstacles and Opportunities information available in the determinants of a given paradigm should allow decisions to be made regarding affordability, efficacy, and feasibility. Antimalarial Drugs and Malaria Treatment Facilities Drugs may be used to prevent, treat, and (theoretically) stop the transmission of malaria. Prevention through drug prophylaxis is difficult in endemic populations, since the provision and administration of safe, effective drugs is often not sustainable over the longer term. However, under certain circumstances, such as in the military and organized labor camps, it is possible to provide effective prophylaxis for an extended period of time to large numbers of people exposed to malaria. Drug prophylaxis is also used by tourists visiting malarious areas. Antimalarial treatment drugs are used for oral treatment of uncomplicated illness on an outpatient basis, for parenteral treatment of patients unable to take oral medication, or for treatment of those requiring prolonged and supervised administration. Treatment is also required to eliminate persisting liver-stage parasites, which cause malaria relapse in the case of P. vivax malaria. At present, there is only one drug (primaquine) that can be used to reduce malaria transmission by adult gametocytes. However, because of the difficulty in getting adequate drug coverage in populations, and because of the drug's short half-life in the blood, this intervention has limited utility. In the case of epidemic outbreaks of malaria, mass administration of treatment doses of chloroquine and primaquine may be justified as an emergency measure to limit mortality and morbidity. In general, however, the temptation to use mass drug administration to combat malaria should be resisted, since supervision of such a program is difficult and resistant parasite strains may be selected. Other effective antimalarial drugs are less suitable for this purpose because of expense, toxicity, or both. The use of microscopy to confirm the presence of malaria parasites, and to indicate the most appropriate drugs, thereby limiting the use of sometimes expensive and toxic medications to those individuals actually requiring them, should also be considered a malaria control tool. Treatment facilities can limit the impact of malaria. The establishment and support of treatment posts throughout areas of malaria transmission, and of inpatient health care facilities capable of providing parenteral drugs and managing severe malaria and its complications, are important contributors to malaria control particularly in areas where antivector measures are not feasible. Antivector Measures Personal protection measures (e.g., mosquito nets, coils, repellents, and screens) can be used to limit or prevent human-
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MALARIA: Obstacles and Opportunities mosquito contact. Insecticide-treated mosquito nets in particular are being promoted worldwide as a relatively inexpensive, nontoxic, and culturally acceptable method of reducing human-mosquito contact. Sleeping each night under an insecticide-treated bednet is likely to reduce the individual's overall risk of infection and is a useful form of personal protection. However, the impact of community-wide use of bednets on malaria transmission, morbidity, and mortality remains to be determined. Most of the studies conducted to date, which attempted to measure, among other things, the impact of insecticide-treated bednets on overall malaria transmission, infection, and illness, reported some reduction in a key measure (Rozendaal, 1989). Unfortunately, there are difficulties in interpreting and extrapolating some of the data. For example, most studies conducted in Africa south of the Sahara had a very small sample size, making it impossible to determine the overall impact of the use of bednets on transmission, morbidity, and mortality. In some of the largest trials conducted in China (Li et al., 1989), a dramatic decline in the incidence of malaria was reported over several years; however, it is difficult to ascribe this decline to the use of insecticide-treated bednets, given the tremendous variation in the epidemiology of malaria in the study areas. Only one study to date has attempted to measure the impact of insecticide-treated bednets on child mortality (Alonso et al., 1991). This study, conducted in the Gambia, recorded substantial reductions in overall mortality and malaria-specific mortality in children one to four years of age of 63 percent and 70 percent, respectively. However, extrapolation of the results of this study to other areas is complicated by variations in infant and child mortality rates among regions, vector competence and behavior, and the acceptance and use of bednets. There is little doubt that insecticide-treated bednets are a superior form of individual protection, but as a population-based malaria control strategy, they remain experimental. Large population-based trials of insecticide-treated bednets now in progress are expected to yield valuable information on the impact of community-wide use of bednets on malaria-related mortality and morbidity. Environmental management includes such measures as draining larval development sites or clearing vegetation from such sites; reforestation in some areas and band deforestation in others; and flushing of streams where local vectors breed. Deliberately positioning domestic animals, such as horses, cattle, or buffalo, between vector sources and human dwellings (zooprophylaxis) has contributed to the reduction of transmission in some areas, including China and the Soviet Union. Larviciding may be an effective antivector method where larval development sites are accessible. Chemical agents, biological agents, or larvivorous fish have been used successfully in certain situations.
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MALARIA: Obstacles and Opportunities Residual insecticides are useful against susceptible mosquitoes that rest on sprayed surfaces. These insecticides have been the mainstay of malaria control operations in many parts of the world for decades. This approach, which continues to be effective in some areas, can also be comparatively expensive, toxic to spray personnel, and damaging to the environment when misused. It should be evaluated carefully before it is implemented. Fogging with aerosol insecticides can be extremely effective in controlling epidemics in areas of high human population density, such as refugee camps, but only when done with the correct timing, frequency, and concentration. Surveillance Techniques Malaria surveillance techniques are essential to establish priorities for control programs, target resources, and monitor program impact on morbidity and mortality. For example, monitoring of malaria morbidity, the incidence and frequency of severe disease and mortality, case-fatality rates, and the prevalence of parasitemia can delineate high-risk groups and guide control activities. Similarly, surveillance systems that detect early stages of epidemic malaria transmission can prevent the devastating effects of serious outbreaks. Monitoring of vector density, insecticide susceptibility, and vector behavior can greatly increase the cost-effectiveness of vector control efforts. It is also essential to monitor the rate at which antimalarial drug regimens fail. Measurements of the susceptibility of P. falciparum to antimalarial drugs, using in vivo techniques to guide therapy policies and in vitro techniques to define trends over time can be undertaken. When made a routine part of antimalarial activities, such monitoring can greatly increase the effectiveness of control efforts. Information, Education, and Communication The dissemination of information on how to avoid malaria infections and the importance of prompt treatment is an important tool for malaria control. Such information can be aimed at both the general public and health care personnel. Most decisions about malaria prevention and treatment are made by infected individuals and/or their families. School curricula, radio, newspapers, television, songs, theater, and films are among the media that can be used to convey information to families about malaria prevention and treatment. In many parts of the world, the local market is the primary source of antimalarial drugs. These medications are much more likely to have a therapeutic effect if patients and their families are supplied with information about correct dosage, duration of treatment, and possible toxicity. Educational campaigns that target health care providers should include information on diagnosis, correct dosage regimens, changes in the epidemiology of malaria, the characteristics of high risk-groups, the status of drug resistance, and drug toxicity.
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MALARIA: Obstacles and Opportunities Application of the Paradigm Approach Logical progression through the steps (identifying the major types of malaria occurring in a country or area, considering the impact of major determinants, and matching available tools to the requirements defined should provide a shortcut to an analysis of the malaria situation and promote a better understanding of the components of the problem. The paradigm approach can serve to orient those who plan malaria control programs, reminding them that a single control strategy applied on a countrywide basis is not likely to affect the problem throughout the country. Furthermore, the paradigm approach can help planners structure evaluations of antimalarial activities by ensuring that a consistent set of basic information is included in every consultant 's report. The paradigms may improve communication between malaria specialists and nonspecialists, and they have already been used successfully to teach nonspecialists about the complexity of the malaria problem. It is important to reiterate, however, that the paradigm approach is in an early stage of development, and considerable field testing is required to assess its utility and suggest modifications and refinements. Program Planning and Evaluation1 Insufficient attention to good management practices has probably contributed more to the failure of malaria control programs than have technical problems. Efficient management, planning, budgeting, logistics, and monitoring are often missing from malaria control programs, with the result that antimalaria measures seldom reach their full potential. The availability of new technologies will mean little in endemic areas unless there is a responsive delivery system that can successfully introduce new drugs, vaccines, or mosquito control methods into regions of the world where they are most needed. For too long, there has been unproductive debate among health planners about whether control programs should be run in a centralized, hierarchical fashion (vertical organization) or integrated into primary health care (horizontal organization). In reality, neither approach is inherently superior to the other, and the two are not mutually exclusive. Some malaria control activities, such as policy formulation, the design of intervention strategies, training, the reporting of epidemiologic data, operational (problem-solving) research, and program evaluation, are best conducted in a 1 The information and views presented in this section are drawn heavily from Liese et al., 1991.
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MALARIA: Obstacles and Opportunities centralized fashion. Other activities, such as the establishment and support of treatment facilities, implementation of vector control operations, health education, and intersectoral cooperation, are more suited to a decentralized approach. Policy Formulation Responsibility for communication between the malaria control program and other divisions of the government for formulation of policy must rest with the central administration of the malaria program, i.e., the ministry of health, as well as other concerned ministries such as those for interior, planning, social action, and agriculture. The central administration must be able both to react to changes in political and epidemiologic situations and to define strategies for disease control. Intervention Strategy The central administration of each malaria control program should be responsible for developing strategies and selecting interventions to be used in malaria control. It is of primary importance that selection of the interventions be based on an understanding of the local epidemiology of the malaria problem and of the advantages and limitations of the control technologies. A single method applied across a large area in which there are a variety of environmental and epidemiologic conditions will probably fail. Malaria control is usually constrained by the limited experience of decision makers and their tendency to apply certain interventions without careful analysis, often because they lack the training and experience to evaluate the effectiveness of current control methods. Consequently, malaria control programs frequently rely on the residual application of insecticides to reduce malaria transmission because the technique is available rather than because it is epidemiologically or biologically appropriate. Technical and human resources are not always considered when the decision to use specific control methods is made. The absence of trained personnel, for example, constrains the ability of control programs to plan effectively and, if necessary, expand. This problem is compounded by the fact that when new resources are sought or developed the efforts tend to proceed along very traditional lines because the decision makers are not prepared to think innovatively or risk new ideas. Training Training has often meant sending senior program staff to the United States or Europe for master's degrees (usually in disciplines unrelated to
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MALARIA: Obstacles and Opportunities the design or management of control programs) or for study tours or conducting low-level courses for implementing staff. The management skills of decision makers within malaria control programs have been largely ignored. Management training at this level should focus on a number of areas, including goal setting and program planning; communication and supervisory skills; personnel management techniques; budgeting, allocating, and monitoring the use of resources; and personnel training and development. The development of skills at the central level will include training in epidemiology, entomology, vector control operations, and the planning and evaluation of field research. Skill in these disciplines can often be developed through short courses (of the type offered by the Centers for Disease Control) and on-the-job training in countries that have similar malaria problems. In addition, malaria control program staff from two countries with similar problems, e.g., forest malaria in Thailand and Brazil, can often learn more from each other (if the communication is structured around focused discussions and visits, not simply through observation tours) than by attending year-long academic programs abroad. Training at the periphery of the health care system, if based on the results of local operational research, can be more effective than academic coursework. These training activities will include seminars, meetings, and panel discussions involving personnel from different institutions and levels of the health network. Training of this sort requires that supervisors and their subordinates communicate and cooperate. Training, including technical training, not only must address a review of all curricula of health personnel involved in even the smallest way with malaria control but also should initiate innovative approaches in planning, designing, and implementing courses and seminars. The development, field testing, and production of training support systems such as modules, treatment charts, and other job aids should, wherever possible, be developed. Instruction of trainers of health workers and the follow-up and evaluation of all of these activities are important components of the training programs. Reporting The ability to collect and report data on disease incidence, prevalence and severity, mortality, parasite sensitivity to antimalarial drugs, and vector behavior and susceptibility to insecticides is an essential part of any malaria control program. The practice of mass blood slide screening, originally instituted as part of efforts during the 1950s and 1960 to eradicate malaria, is no longer advised. Further, where time-limited eradication is no longer a feasible goal, preparation for identification of the last remaining
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MALARIA: Obstacles and Opportunities cases should not be the goal of surveillance and reporting. Instead, the malaria control program core staff must be able to design surveys to obtain the specific epidemiologic information required for operations management. Problem Solving (Operational Research) Operational research involves identifying a technical problem that is impeding the progress of a control program, framing an answerable question based on this problem, and designing a study that will answer the question. The questions addressed may be very straightforward: Is one drug regimen so much better than another that a change in treatment policy is justified? Does the resting behavior of the most important malaria vector warrant a program of spraying residual insecticides? Is a community likely to accept and use permethrin-impregnated bednets? A malaria control program able to make constructive changes based on the findings of operational research is more likely to be successful. Logistical Support and Transportation Logistical support and transportation are critical to the success of malaria control programs. Unfortunately, in many countries, poor or nonexistent logistical support and organization and the lack of transportation are major limiting factors in malaria control programs. Such problems consume inordinate time and are often beyond the immediate control of the malaria control program manager. Evaluation The evaluation of progress toward the stated objectives must be an integral part of every control program, and areas of success, failure, and gaps in knowledge should be identified on an ongoing basis. Any control program that receives outside support will as a matter of course periodically conduct evaluations to satisfy sponsors that progress is being made. Central Core of Expertise All of the activities identified above require the presence of a central, coordinated body of expertise. The precise membership of such a group will depend on the local malaria situation and the operational requirements of the control program. The group must be managed by someone whose responsibilities are matched by his or her capabilities and authority. Even in control programs in malaria-endemic countries that are fully integrated into the general health care system, there must be a technical focus for
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MALARIA: Obstacles and Opportunities malaria. Public health generalists do not have the level of technical expertise needed to plan and guide an effective malaria control program. Decentralized Activities Ideally, when a policy for malaria control is established, the authority for implementing necessary control activities will be decentralized. To be responsive to any number of possible changes in the malaria situation, decision making within a control program should take place at the lowest possible level, in accordance with the capabilities of the field staff. Operational decisions should be made peripherally, and decision makers should be held accountable for their decisions. RESEARCH AGENDA Infection, Immunity, and Disease The difference between malaria infection and disease is critical, since infection with the parasite does not necessarily result in disease. In the vast majority of malaria endemic countries, data on the prevalence of infection tell us very little about the incidence of clinical disease and death. Lack of immunity predisposes people to severe and complicated malaria, but very little is known about the specific factors that place certain people at greater risk than others. Further, surprisingly little is known about the acquisition of immunity among different population and age groups. RESEARCH FOCUS: Determination of epidemiologic risk factors for severe and complicated malaria. RESEARCH FOCUS: Population-based studies of parasite and human variability as they relate to the development of immunity and the evolution of clinical disease. Pregnancy and Birth Outcome Women pregnant for the first time who are in the last trimester of pregnancy are considered to be at particular risk for complications due to malaria. Maternal complications have also been linked to a number of poor birth outcomes, including intrauterine growth retardation and low birth weight. Despite their importance, the effects of malaria on maternal and fetal health and survival have received little recent attention. RESEARCH FOCUS: Measurement of the impact of malaria on pregnancy and on maternal and infant health.
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MALARIA: Obstacles and Opportunities Chemoprophylaxis and Therapy There is conflicting evidence on the role of chemoprophylaxis and therapy in reducing overall morbidity and mortality and malaria-related morbidity and mortality, and it may well be that the efficacy of measures will vary according to the intensity of malaria transmission. RESEARCH FOCUS: Assessment of the role of therapy and chemoprophylaxis in reducing overall and malaria-related morbidity and mortality in areas of varied intensity of malaria transmission. Drug Resistance The development of drug-resistant strains of P. falciparum, particularly to strains resistant to chloroquine (the preferred antimalarial drug), is widespread and increasing in all regions of the world. Within a country or region, however, drug resistance appears to be focal. The determinants of drug resistance in different regions are largely unknown. RESEARCH FOCUS: The epidemiology of drug resistance. Paradigms The paradigm approach to understanding malaria is very much in its infancy. In the coming years, it will be important to test and evaluate the strategies that evolve from the paradigm approach. RESEARCH FOCUS: Field test the paradigm approach to determine its utility in helping program managers assess the malaria situation in their areas and develop viable control strategies. Bednets Insecticide-treated bednets are increasingly being promoted around the world as a means of reducing contact with the vectors of malaria. Use of impregnated bednets will reduce an individual's risk of infection, but the impact of community-wide use of impregnated bednets on overall malaria transmission, morbidity, and mortality is unclear. RESEARCH FOCUS: Evaluation of the impact of community-wide use of insecticide-treated bednets on ma-
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Representative terms from entire chapter: