Interventions and Their Effectiveness
Malaria will be conquered only by full coverage, access to, and use of antimalarial services by priority groups; rapid, accurate diagnosis; prompt and effective patient management (diagnosis, treatment, counseling and education, referral); judicious use of insecticides to kill and repel the mosquito vector, including the use of ITNs; and control of epidemics. Eliminating malaria from most endemic areas remains a distant, huge, but surmountable challenge because of the widespread Anopheles breeding sites; the large number of infected people; the use of ineffective antimalarial drugs; and the inadequacies of resources, infrastructure, and control programs. The Roll Back Malaria Partnership, which began in 1998, aims to halve the burden of malaria by 2010 and has developed strategies and targets for 2005 (box 21.1). While ambitious, the initiative is making substantial progress by means of effective and efficient deployment of currently available interventions (WHO 2003, 2005). Indeed, Brazil, Eritrea, India, and Vietnam are reporting recent successes in reducing the malaria burden (Barat 2005). Despite the enormous investment in developing a malaria vaccine administered by means of a simple schedule and recent promising results in the laboratory and in field trials in Africa, no effective, long-lasting vaccine is likely to be available for general use in the near future (Alonso and others 2004; Ballou and others 2004).
[Box 21.1]
Drug Use
Proper use of drugs is essential. Early diagnosis and effective treatment of patients lends credibility to the malaria program, strengthens confidence in the health care system by families and communities, and raises the esprit of clinicians and public health workers.
Early Diagnosis and Treatment
Early diagnosis and effective treatment can cure infection, prevent further morbidity and progression to severe disease and death, and arrest transmission. This intervention requires timely and accurate diagnosis; use of efficacious drugs; education of patients and their families about the disease, home management, and prevention; and referral to higher levels of the health system. The following are critical to the effectiveness of this intervention:
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Timeliness. A febrile malaria attack warrants early treatment. If left untreated, a proportion of P. falciparum malaria infections, perhaps 1 in 250 (and to a far lesser extent infections with other malaria species) will progress to severe disease within a few hours to a few days (Greenwood and others 2005). The globally agreed goal is that diagnosis and effective treatment should be provided within 24 hours of the onset of symptoms and signs.
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Diagnosis and effective drug treatment. An accurate diagnosis of malaria is based on detection of the parasite and, if laboratory diagnosis is not feasible, on clinical grounds. Health workers must monitor the therapeutic efficacy of drugs closely and change treatment policies when parasite resistance to chloroquine (figure 21.2), SP, and other drugs emerges (Baird 2005; Laxminarayan and others 2006; WHO 2002a). Concerns include unreliable and inaccurate microscopy and the disadvantages of alternative tests plus the widespread distribution and use of substandard and counterfeit drugs. The recommended treatments for malaria in areas with resistance to single drugs are combination treatments, preferably artemisinin combination therapy (ACT) (WHO 2001a, 2001b, 2003a, 2005). While ACT is a welcome, life-saving approach, more information on the cost-effectiveness of this new strategy is needed (Arrow, Panosian, and Gellband 2004; Yeung and others 2004). Baird (2005) reports that ACT costs range from US$2.00 (artesunate-amodiaquine, three doses in 48 hours) to US$9.12 (artemether-lumefantrine, six doses in 48 hours) per adult treatment; WHO has obtained the latter drug for US$2.40 per adult treatment for qualified purchasers, meaning those from low-income malarious countries.
[Figure 21.2] -
Location of clinical management. Effective management of patients requires skilled and well-equipped personnel at all levels of the health system. The two strategies for delivering antimalarials effectively are through health facilities and in or near the home when access to health facilities is limited. Given the pervasiveness of malaria infections, more information on the most effective and efficient ways to promote home treatment is urgently needed.
Evidence for the effectiveness of early diagnosis and treatment is available from two different epidemiological conditions and health systems. In areas of low to moderate transmission, for example, southern Africa, the Americas, and Southeast Asia, where health care systems are relatively effective, the two major consequences of prompt and effective intervention are reduction of the period of infectivity of infected persons, and thus reduced transmission and incidence, and a lowered case-fatality rate and overall mortality. In Vietnam and the KwaZulu-Natal province of South Africa, P. falciparum malaria incidence and mortality rates fell when effective treatment policies (artesunate and ACT) replaced failing monotherapies (Hung and others 2002). The effective drug policies were implemented in conjunction with enhanced vector control; thus, effective treatment alone does not account for the fall in malaria incidence and mortality.
In areas with stable, high transmission of P. falciparum malaria—for instance, Papua New Guinea and Sub-Saharan Africa—where access to treatment is poor, little is known about the impact of early and effective treatment on malaria transmission. With a high EIR (10 to 1,000), a reduction in transmission intensity is unlikely to affect the incidence of disease until low EIRs (less than 10) are reached.
IPT in Pregnancy and Infancy
IPT is recommended in pregnancy in areas with high and stable transmission of P. falciparum malaria; IPT usually consists of two curative doses of antimalarial treatment. The recommended drug is SP given during the second and third trimesters of pregnancy during prenatal care visits. IPT in infancy involves giving infants treatment doses during vaccination or well-baby visits to health clinics.
In primigravid and secundigravid women, the incidence of severe maternal anemia, the incidence and density of placental parasitemia, and the incidence of low birthweight were 25 to 95 percent lower when mothers were given IPT than when they were not (Kayentao and others 2005; Steketee and others 2001). While initial studies indicate that IPT in infancy reduces anemia and febrile episodes, more research is needed. SP is becoming ineffective for IPT, and health experts are suggesting ACT as a replacement (White 2005).
Chemoprophylaxis
Chemoprophylaxis is advised by travel medicine specialists for nonresidents of endemic areas who are exposed to malaria for short periods. WHO does not recommend chemoprophylaxis for permanent residents of endemic areas because of low feasibility and compliance and high costs relative to the public health benefits (WHO 1996, 2000a, 2000b). The choice of chemoprophylaxis will depend on the drug-sensitivity profile, tolerance, side effects, costs, regimen, and compliance by patients (Baird 2005; Kain, Shanks, and Keystone 2001; White and Breman 2005). The effectiveness of chemoprophylaxis will depend mainly on patient compliance and parasite susceptibility.
Supervision and Policy Change
In relation to drug use, all control activities must be supervised and evaluated rigorously to ensure high-quality care for patients and program effectiveness and efficiency (Bryce and others 1994; Jha, Bangoura, and Ranson 1998). Studies in 37 countries indicate the need for a treatment policy change to ACT (WHO 2002a). Several countries in Africa, Asia, and South America are now implementing ACT as the first-line treatment for uncomplicated malaria (WHO 2005). Many countries are also trying to improve the time lag before treatment. More than 83 percent of the population in the three malarious provinces in South Africa is within 10 kilometers of a health facility (Sharp and le Sueur 1996). In Burkina Faso, Ethiopia, and Uganda, where access to clinics was poor and difficult, mothers and community health workers were empowered to dispense treatment, which resulted in major reductions in mortality and morbidity in children (Kidane and Morrow 2000; Pagnoni and others 1997; Sirima and others 2003).
Insecticide-treated Nets
The use of ITNs (bednets, curtains, and other materials) to provide personal protection by killing or repelling mosquitoes is one of the major strategies of malaria control (RBM 2002). Pyrethroids are recommended for the periodic treatment or retreatment of the protective materials.
The effectiveness of ITNs depends on their acceptability by the population at risk and their affordability. It is contingent on the habits, biology, and susceptibility of the mosquito vector; the compliance of the human population; and the concentration of insecticide on or in the fiber, which has to be maintained by regular re-treatment or by incorporating the insecticide in the fiber for long duration.
Over 20 studies in Africa and Asia have demonstrated more than 50 percent protective efficacy for individual users of ITNs in reducing malaria episodes, 29 percent protection against severe malarial disease, and substantial protection against anemia (Lengeler 2004). Most importantly, the use of ITNs reduced child mortality by 18 percent in five sites in Sub-Saharan Africa (Lengeler 2004).
Lengeler's (2004) review demonstrates the efficacy of ITNs in both stable and unstable transmission areas. Widespread use of ITNs resulted in an overall reduction in mortality of 19 percent, protected against anemia, and had a substantial impact on mild disease episodes. One large-scale rural study in Tanzania found that ITNs and untreated nets reduced mortality of children one month to four years, with protective efficacies of 27 and 19 percent, respectively (Armstrong-Schellenberg and others 2001). Re-treating ITNs semiannually or just before the annual peak in transmission is essential for effective vector control and is proving a major logistical and financial challenge. Fortunately, new types of nets with a long-lasting insecticidal property are now available, and retreatment will soon cease to be an issue. The salutary impact of large-scale ITN programs has been demonstrated in China (Tang 2000), Tanzania (Abdulla and others 2001; Armstrong-Schellenberg and others 2001; WHO 2005), and Vietnam (Hung and others 2002). More operational experience is required to inform national initiatives to scale up ITN use (Lengeler and Sharp 2003); yet, recent encouraging reports show that Eritrea, Malawi, Togo, Zambia, and other countries in Africa are already scaling up nationally with high coverage.
Vector Control
The reduction of Anopheles breeding and biting of humans involves different methods of insecticide and repellent application, environmental management, and behavioral change of populations at risk.
Indoor Residual Spraying of Dwellings with Insecticide
Indoor residual spraying (IRS) is the application of long-lasting insecticides (up to six months) on the walls of dwellings. Insecticides repel mosquitoes from entering houses or impart a lethal dose of the insecticide on the female mosquito when it rests on a sprayed surface, thereby preventing subsequent transmission. IRS is most effective against indoor-biting (endophilic) mosquito vectors. Vector susceptibility and post-feeding behavior are the main criteria to be considered when choosing an insecticide: organophosphates, carbamates, and pyrethroids are the main compounds used although some countries still rely on organochlorines (dichlorodiphenyl-trichloroethane, or DDT).
The effectiveness of this intervention depends on cost, toxicity, acceptability of the insecticide, its residual effects, and local political and international partnership commitment. Malaria incidence decreased sharply following the use of IRS in large-scale programs in many parts of Africa, the Americas, Asia, and Europe (Lengeler and Sharp 2003).
In southern Africa, more than 13 million people in six countries are protected from malaria (WHO 2002c). Control was initiated through the use of IRS and supported by engineering approaches, larviciding, prompt diagnosis, and effective treatment. Examples of successful and sustained malaria elimination using IRS with effective drug treatment are available from Cyprus, Greece, Portugal, Spain, and the former Yugoslavia and its successor states (Curtis and Mnzava 2000). The most successful malaria control efforts were linked closely to research and took place in many parts of Asia, where the notable example is the near eradication of malaria from Sri Lanka in the early 1960s, and in Central and South America from the late 1950s to early 1970s (Alilio, Bygbjerg, and Breman 2004; Carter and Mendis 2002; Gilles 2002).
Larviciding and Fogging
Larviciding is the application of chemical insecticides, including those of biological origin and insect growth regulators, to breeding sites. These may be applied to all mosquito breeding sites or targeted to the breeding sites of specific vectors. Recommended compounds, formulations, and dosages for larviciding are available through the WHO Pesticides Evaluation Scheme. Fogging or space spraying with insecticides requires specialized equipment, because the particle size of the insecticide determines its suspension qualities in the air, the number of droplets, and the penetration of space. The insecticide is not effective for as long as with IRS or ITNs, and application must occur during periods of peak target mosquito activity, generally at night.
Larviciding is not generally indicated for large-scale vector control in rural endemic areas because of the difficulty of locating all breeding sites, their often temporary nature, and the required frequency of application. Thus, larviciding is usually limited to urban areas, refugee camps, and industrial and development projects. Despite its impact on mosquito density and its contribution to reducing transmission, larviciding is not as effective as IRS and ITNs in reducing mosquito longevity (Najera and Zaim 2002).
Civil Engineering
Draining and filling larval breeding sites is one of the oldest methods of mosquito control and must be targeted to the breeding sites of locally important malaria vectors. Civil engineering strategies can require costly heavy equipment and materials and are useful for eliminating permanent breeding sites in urban areas, which are increasing globally, and at development project sites where earth removal has occurred.
Home Repellents and Insecticide Use
Commercially available mosquito repellents are applied directly on the skin or clothing as aerosols, lotions, or creams and contain active ingredients that protect the individual from mosquito bites. Commercially available mosquito coils containing pyrethroids can be burnt to repel mosquitoes, and electrically heated dispensers serve a similar function. Some communities in endemic regions use smoke, burning herbs, or plants to deter mosquitoes from entering the home.
N,N-diethyl-meta-toluamide (DEET) is the most widely used and effective ingredient in commercially available repellents (Curtis and others 1991). While several studies have shown that mosquito coils are effective at repelling mosquitoes, they are not as effective as ITNs (Charlwood and Jolly 1984).
Health Education and Counseling
Health education is the provision of information via newspapers, radio, or television, and health counseling is interactive, is individual, and involves the transfer of skills. The provision of information to households on ways to prevent malaria is needed in all endemic communities. It should cover the importance of early treatment and where to access it, the use of referral services, and the significance of full compliance with treatment and other interventions. The necessary information can be provided by community and voluntary health workers. These persons are an extension of the health system and work under the direct supervision of health facility staff or nongovernmental organizations and in conformity with standards and norms established by the national government (Gilles 2002). Such information can help to increase the standard of patient care and prevention programs by promoting citizen and community advocacy and demand for control.
