Interventions and Their Effectiveness
For each of the four diseases in this chapter, effective interventions are available.
Chagas Disease
The primary approaches to control of Chagas disease are halting transmission and providing adequate treatment for those infected. The two most important routes of transmission are insect vectors and blood transfusion from infected donors; thus, control programs focus on eliminating domestic vector populations and improving the serological screening of blood donors.
Vector Control
Triatoma infestans lives only inside houses and in the peridomestic area. Work during the late 1940s suggested that spraying houses with residual insecticides could eliminate vectors' domestic populations. The effect and sustainability of such vector control programs can be enhanced when they are combined with improved housing and when communities are well informed and closely involved in vector surveillance activities.
Argentina and Brazil initiated programs for nationwide vector control in the 1960s, and Chile and Uruguay did so in the 1970s. These programs were strengthened in 1991 by the Southern Cone Initiative, a multinational effort to eliminate infestation by T. infestans launched by the ministries of health of Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay and coordinated by the WHO Regional Office for the Americas. Similar regional initiatives for Central America and the Andean Pact regions, targeted primarily against Rhodnius prolixus, followed in 1997.
The results in the Southern Cone region have been impressive, with vast areas now free of domestic infestation with T. infestans and other vector species. In Argentina, seroprevalence rates among men age 18 to 20 drafted for military service decreased from 5.8 percent in 1981 to 1.2 percent in 1993. The number of cases of Chagasic cardiomyopathy, when compared with the number expected in the absence of control, indicates a decrease of 81 percent in the population up to 18 years of age. In 2001, a WHO commission certified that 4 of the 18 endemic provinces were free of vectorial transmission. In Brazil, domestic infestation rates decreased by 98.3 percent between 1991 and 2000. Of the 11 Brazilian states that were originally endemic for T. infestans, 9 have been certified as free of vectorial transmission. In Chile, house infestation rates decreased from 28.80 percent in 1982 to less than 0.01 percent in 1999, when the country was certified free of vectorial transmission. Uruguay also achieved a dramatic reduction in house infestation rates, from 5.7 percent in 1983 to 0.3 percent in 1997, when it too was certified as free of vectorial transmission. Bolivia and Paraguay have not yet eliminated transmission, but thousands of houses have been sprayed since 1991.
Blood Transfusion Control
The purpose of screening for T. cruzi in blood banks is to eliminate all units of potentially infected blood. Argentina and Brazil require screening to be done using two serological tests to reduce the risk of false negatives; however, the cost-benefit ratio of the two-test approach may be questionable in countries where prevalence is low and the reagents used for diagnosis are highly sensitive.
In 1993, the national coverage of blood donor screening was analyzed in four Central American and six South American countries (Schmunis and others 1998). At that time, only Honduras, Uruguay, and Republica Bolivariana de Venezuela screened 100 percent of donors, and even in those countries infected transfusions were possible because of the lack of sensitivity of the reagents used. Since then, the sensitivity and specificity of serological tests have improved, and more countries have passed legislation requiring the screening of all blood donors. By 2001, seven endemic countries were screening 100 percent of blood donors for T. cruzi, four were screening more than 99 percent of donors, 0and two were screening about 90 percent; but four countries were still screening fewer than 25 percent of donors. In countries with a high number of immigrants from Latin America, such as Spain and the United States, thousands of individuals are potentially infected, and screening of blood donors for T. cruzi infection may be indicated in these countries.
Treatment
If untreated, most individuals infected with T. cruzi will remain infected for life. Spontaneous cure is rare. Only two drugs, nifurtimox and benznidazole, are effective for treating T. cruzi. Both are highly effective for acute infections and can be used in cases of congenital Chagas disease. Their effectiveness for treating chronic cases remains unclear, but increasing evidence indicates that they are effective in clearing parasitemia when administered to young cases, which may impede the development of chronic lesions. Both drugs may cause serious side effects and should be administered under medical supervision.
Lymphatic Filariasis
In recent years, new control tools and strategies have become available for LF (Ottesen and others 1997), and the World Health Assembly has adopted a resolution on the global elimination of LF. The Global Programme for the Elimination of Lymphatic Filariasis was launched in 2000 with the primary goals of interrupting transmission and preventing suffering and disability caused by the disease (Ottesen 2000).
The core strategy for interrupting transmission is annual mass drug administration (MDA) to treat the entire at-risk population for a period long enough to ensure that levels of blood microfilariae remain below those necessary to sustain transmission. Two annual, single-dose, two-drug regimens are recommended for MDA: ivermectin plus albendazole in African countries that are coendemic for onchocerciasis, and diethylcarbamazine plus albendazole for all other endemic countries. Where feasible, diethylcarbamazine-fortified salt as the only source of domestic salt for a period of at least six months would be an alternative strategy to MDA.
The principal strategy for alleviating suffering and decreasing the disability caused by LF focuses on decreasing secondary bacterial and fungal infection of limbs or genitals whose lymphatic function has already been compromised by filarial infection. Operationally, a regimen of meticulous local hygiene of affected areas and the creation of hope and understanding among patients and their communities are the principal strategic approaches (Dreyer, Dreyer, and Noroes 2002).
Mass Treatment
It is not yet known how many years of MDA are needed to eliminate LF transmission, but empirical evidence on the effect of MDA on transmission is progressively becoming available. In Anopheles-transmitted W. bancrofti in Papua New Guinea, four rounds of MDA with diethylcarbamazine or diethylcarbamazine plus ivermectin that reached about 88 percent of the target population reduced the annual transmission potential (the estimated number of infective-stage larvae inoculated per person per year) by 97 percent and 84 percent in low- and high-transmission areas, respectively. In India, where W. bancrofti is transmitted by C. quinquefasciatus, six rounds of MDA that reached 54 to 75 percent of the target population reduced the annual transmission potential by 95 and 80 percent in diethylcarbamazine- and ivermectin-treated villages, respectively (Ramaiah and others 2003). Modeling studies indicate that the required duration of treatment will depend largely on the treatment coverage achieved and the extent of systematic noncompliance to treatment—that is, noncompliance by the same individuals during successive treatment rounds (Stolk and others 2003). The physiology of the vectors also plays a role, because with Culex-transmitted LF, the critical microfilariae density required to interrupt transmission is thought to be lower than in areas where Anopheles is the vector.
The addition of albendazole to the two established anti-filarial drugs—diethylcarbamazine and ivermectin—is based on clinical trials indicating that the combination therapy is as good as or better than single-drug therapy and that albendazole may enhance the macrofilaricidal action of diethylcarbamazine. Albendazole is also effective and safe against intestinal helminth infections, and its inclusion may enhance compliance with MDA. However, clinical trials have not yet been conclusive, and more robust evidence on the advantages of combination therapy is needed (Addiss and others 2004; Gyapong and others 2005). Community trials are ongoing in India and Africa, and preliminary results of a trial in south India suggest that the combination of diethylcarbamazine and albendazole may indeed achieve greater reduction in the prevalence of antigenemia than diethylcarbamazine alone (Rajendran and others 2002). A study in Nigeria showed that the addition of albendazole to ivermectin had an additive effect on reducing LF mosquito infection rates. (Richards and others 2005).
Vector Control
Vector control has sometimes been extremely effective against LF. In the Solomon Islands, 9 to 10 years of vector control virtually eliminated LF. In India, five years of integrated vector control in an urban area reduced the overall prevalence of microfilariae by 28 percent and the prevalence in children by 92 percent. Studies suggest that 11 to 12 years of effective vector control may eliminate LF (Ramaiah, Das, and Dhanda 1994). Vector control combined with chemotherapy produced the best results. The introduction of polystyrene beads in vector breeding habitats and treatment with diethyl-carbamazine reduced the annual infective biting rate in Tanzania by 99.7 percent (Maxwell and others 1990). In India, vector control combined with single-dose treatment with diethylcarbamazine plus ivermectin reduced the annual transmission potential by 96 percent, compared with 60 percent using chemotherapy alone (Reuben and others 2001).
Such results, along with the limitations of MDA for completely eliminating microfilariae in some situations, have reactivated the debate on the role of vector control in LF elimination (Burkot and Ichimori 2002). However, few endemic countries have an adequate vector control infrastructure.
In some African countries, the same vector species transmit both LF and malaria. In such situations, the effect of malaria control measures, particularly insecticide-treated bednets, on LF vector densities and transmission needs further evaluation. A review of the role and feasibility of community-based vector control strategies and large-scale application of biological control agents is also needed.
Morbidity Management
The second objective of the Global Programme for the Elimination of Lymphatic Filariasis is to decrease the disability caused by LF. Simple and cheap methods have been developed for managing lymphedema, using water and soap occasionally supplemented with antibiotics. Studies in India, Africa, and the Americas have shown that such methods can significantly improve the quality of life of those affected, but implementation of this strategy has greatly lagged behind the MDA campaigns.
Onchocerciasis
Onchocerciasis control is based on vector control and large-scale ivermectin treatment.
Vector Control
Vector control used to be the only feasible intervention when available drugs were too toxic for large-scale use. Following success with vector control in Kenya, where the application of larvicides resulted in local elimination of the vector S. neavei, and in selected locations in West Africa, where the application of larvicides effectively stopped local vector breeding but could not prevent reinvasion of infective vectors from elsewhere, vector control was considered feasible in the West African savanna if carried out on a large scale. In 1975, the OCP started large-scale vector control operations using helicopters for weekly spraying of larvicides over the vector breeding sites in river rapids (Molyneux 1995). The operation ultimately covered some 50,000 kilometers of rivers over a geographic area of 1,235,000 square kilometers. The OCP's strategy was to maintain vector control for at least 14 years to interrupt transmission and eliminate the parasite reservoir. Despite initial problems with reinvasion by infective flies, the strategy proved effective, eliminating onchocerciasis as a public health problem throughout the OCP area. The OCP was successfully concluded in 2002, but concerns remain about the possible recrudescence of onchocerciasis through reinvasion by infected blackflies or migration of infected persons into OCP areas. The OCP countries, therefore, need to maintain effective surveillance to identify any recurrences of infection (Richards and others 2001).
Treatment with Ivermectin
In 1987, Merck & Co., the manufacturer of ivermectin, agreed to donate the drug for onchocerciasis control for as long as needed (Peters and Phillips 2004). Clinical and community trials involving more than 70,000 people showed that annual ivermectin treatment was safe, prevented ocular and dermal morbidity, and significantly reduced transmission; however, ivermectin is a microfilaricide and does not kill the adult worms, and long-term treatment is needed to sustain suppression of the microfilarial load (Remme 2004b). Additional research is needed to determine the extent to which repeated treatments reduce the reproductive capacity of the adult worm population over time.
The introduction of ivermectin allowed the OCP to achieve its objective in 12 years instead of 14 by combining vector control with ivermectin treatment, but most important, it also provided an opportunity to control onchocerciasis in endemic areas outside the OCP where vector control was not feasible. This ability led to the creation of two other regional programs for controlling onchocerciasis in endemic areas of Africa and the Americas: APOC (Remme 1995) and the Onchocerciasis Elimination Program for the Americas (OEPA) (Richards and others 2001).
The World Bank and WHO launched APOC in 1995 to serve 19 onchocerciasis-endemic countries outside the OCP. APOC's principal strategy is to establish annual ivermectin distribution in highly endemic areas to prevent eye and skin morbidity. In partnership with ministries of health and nongovernmental organizations, APOC currently provides more than 35 million ivermectin treatments per year and aims to reach 65 million treatments per year before its scheduled termination in 2010. APOC uses an approach referred to as community-directed treatment with ivermectin, whereby local communities rather than health services direct the treatment process (Amazigo and others 2002). A community decides collectively whether it wants ivermectin treatment, how it will collect ivermectin tablets from the medical supply entity, when and how the tablets will be distributed, who will be responsible for distribution and recordkeeping, and how the community will monitor the process. Health workers provide only the necessary training and supervision. To date, communities have responded enthusiastically to this approach (Seketeli and others 2002), and interest is now growing in exploring this strategy for interventions against other diseases (Homeida and others 2002).
In the Americas, O. volvulus transmission occurs only in a few small areas in six endemic countries. Accordingly, OEPA's strategy is based on intense ivermectin treatment twice a year that should allow eventual cessation of ivermectin delivery without the risk of recrudescence (Richards and others 2001). OEPA was launched in 1992 and is currently reaching more than 85 percent of its intended target population.
Leprosy
The objectives of leprosy control are to interrupt transmission, to cure patients, to prevent the development of associated deformities, and to rehabilitate those patients already afflicted with deformities. The strategy involves early case detection and the provision of adequate chemotherapy and comprehensive patient care (ILA 2002).
Multidrug Therapy
Dapsone therapy for leprosy was introduced in the late 1940s and successfully used as monotherapy for two decades. In the 1970s, resistance to dapsone emerged, and WHO introduced multidrug therapy (MDT) in 1982. Paucibacillary patients were to be given a six-month regimen of daily dapsone and supervised monthly rifampicin. Multibacillary patients were to be treated with a three-drug regimen for two years or, where feasible, until the skin smear had become negative. This regimen followed the paucibacillary regimen, adding a smaller daily dose of clofazimine and a larger supervised dose once a month.
These regimens have had good results, with a relapse incidence of less than 0.1 percent per year (ILA 2002). No multidrug-resistant leprosy has been reported so far, and reports of rifampicin-resistant M. leprae have been few. In 1998, the standard multibacillary MDT regimen was shortened to 12 months. Long-term relapse rates for the 12-month regimen are not yet available.
Public health specialists expected that wide application of MDT together with earlier diagnosis resulting from the upgrading of leprosy services would have a considerable effect on transmission; however, by 2002, clear evidence of a reduction in transmission had not been seen.
Immunoprophylaxis and Chemoprophylaxis
Several randomized trials have shown that vaccination with the bacillus Calmette-Guerin (BCG) vaccine reduces the risk of developing leprosy (Fine and Smith 1996), with the level of protection varying from 20 to 80 percent. Chemoprophylaxis based on dapsone or intramuscular acedapsone conferred overall protection against leprosy of about 60 percent (Smith and Smith 2000). Two large trials are currently under way in Bangladesh and Indonesia to investigate the efficacy of one or two doses of rifampicin in preventing leprosy, with preliminary results from the Indonesian trial indicating a significant protective effect.
Prevention of Disabilities
As concerns primary prevention, leprosy-related disability is preventable, but when peripheral neuropathy has become established, it is irreversible and leads to lifelong morbidity and disability (Bekri and others 1998; Meima and others 1999). Early case detection and treatment are therefore likely to be the most effective interventions in relation to preventing disability. When detected and treated in time with corticosteroids, primary impairments may be reversible, but because many patients present late, some 11 to 51 percent do not recover or get worse.
In relation to secondary prevention, the main strategy is self-care to prevent worsening of impairments in people who already have irreversible neural impairment or secondary impairments such as wounds and contractures. The role of health care workers is to educate patients so that they can be responsible for the daily management of the effects of nerve function impairment. An essential part of secondary prevention is the use of protective footwear by people with anesthetic feet. Several studies have shown that the use of locally acceptable, appropriate footwear is a cost-effective intervention for those with a loss of plantar sensation (ILA 2002). Reconstructive surgery, protective footwear for people with insensitive feet, and assistive devices to correct or prevent activity limitations are also used in secondary prevention.
As concerns tertiary prevention, the stigma attached to leprosy often prevents patients from participating in normal community activities. Strategies include counseling of those affected and their families, neighbors, and communities; vocational training; and advocacy work.
Rehabilitation
Impairments often lead to activity limitations and restrictions on social participation, which can be prevented by correcting the underlying impairment if it is not yet irreversible. After impairment is established, activity limitations can still be minimized with the help of reconstructive surgery or appropriate assistive devices, such as orthoses, grip aids, calipers, or prostheses. A large but unknown percentage of people succeed in overcoming activity limitations by themselves. Some require rehabilitation interventions, such as physical or occupational therapy, reconstructive surgery, or temporary socioeconomic assistance.
Intervention Effectiveness
For all four diseases covered in this chapter, interventions are available that are effective under routine control conditions. The feasibility of eliminating these diseases as public health problems from most endemic areas is therefore not in doubt; however, questions remain about the effectiveness and sustainability of control under specific conditions and about the feasibility of eliminating the parasites and transmission. The vector control strategy for Chagas disease worked well in the Southern Cone countries, but the sylvatic reservoir of T. cruzi remains unaffected, and continued surveillance will be essential. Vector control is more challenging in the Andean and Central American countries, where some of the vectors are not domiciliated. For LF, the number of years of MDA and the treatment coverage required to interrupt transmission remain unknown, just as the epidemiological conditions and the number of rounds of ivermectin treatment required to achieve the same for onchocerciasis are not yet known. For leprosy, the key questions remain how much effect MDT has on transmission and when the incidence of new cases can be expected to decline significantly. Hence, the sustainability of control remains a critical issue.
The control programs for three of the diseases depend on drug donations. To date, the pharmaceutical companies donating the drugs and the donors supporting drug distribution have shown impressive commitment to the programs, but if their commitment were to lapse, the control programs would collapse and the diseases would return as public health problems. Another risk is drug resistance. The control programs rely on just a few drugs, and even though drug resistance is not currently apparent, if it were to emerge, the essential tools for control would be lost. Hence, although elimination is in sight, the battle has not yet been won, and research to develop new and improved interventions and strategies for these tropical diseases remains important.
