Report of the Workgroup on Parasitic Diseases

J.P. Figueroa*

The Workgroup reviewed and agreed to work with the definitions of control, elimination and eradication published in the Dahlem Workshop Report. However, it was noted that a number of resolutions of regional and international bodies, including WHO, PAHO, and the World Bank, included the expression "elimination [of a particular disease] as a public health problem".

The criteria for assessing the eradicability of diseases and conditions given in the Dahlem Workshop Report were accepted by the group. It was noted that the development of an effective strategy was part of demonstrating the feasibility of elimination. The economic impact or benefit of disease elimination/eradication may be with respect to intervention factors, including cost-effectiveness, equity (distribution issues), and the impact on the economy. The list of candidate parasitic diseases was reviewed and the group concluded that dracunculiasis was eradicable at present with current tools; separate working subgroups were designated to consider onchocerciasis, lymphatic filariasis, Chagas disease, and "other parasites".

Caution was expressed in relation to the capacity of many developing countries to engage in more than a very limited number of eradication/elimination campaigns at a given time. There is already a global eradication campaign for poliomyelitis and for candidate diseases such as measles, and there are a number of regional disease elimination campaigns. Candidate diseases for elimination will need to be ranked in order of priority on a global and regional basis. In addition, issues of certification of disease elimination and eradication need to be considered. For example, the ability of parasites to survive for long periods in humans makes the certification of elimination even more difficult.

It was agreed that onchocerciasis was a strong candidate for elimination as a public health problem, but not for eradication at the present time. As such, the subgroup endorsed the recommendations and definition used by the 1993 International Task Force for Disease Elimination, where the term "elimination as a public health problem" was used. This is a concept that encompasses both global control and elimination of infection in selected areas.

Considerable achievements have been made towards elimination of onchocerciasis in most of the Americas, all countries within the Onchocerciasis Control Programme in West Africa (OCP), and in several other African countries. Progressive increase in treatment with ivermectin has been achieved, with 500,000 doses of treatment having been distributed in 1988 and 18 million in 1997. This represents near complete coverage in the OCP and the Americas, and about 33% coverage in the APOC (African Programme for Onchocerciasis Control) countries. Extensive partnerships exist which are dedicated to the goal of sustained and complete global ivermectin treatment; the partners include Merck & Co., WHO, the World Bank, Inter-American Development Bank, nongovernmental organizations, research institutes, ministries of health, other donors, and the endemic communities.

An important constraining factor is that ivermectin is not effective in killing the adult worms (macrofilariae). Other factors are the difficulty in achieving and maintaining a sufficiently high coverage and treatment frequency to interrupt transmission, the long life span of the adult worms, and active human and vector migration.

Annual or semiannual mass ivermectin treatment must be sustained through community-based distribution programmes in endemic areas.

• Surveillance: epidemiological assessment and mapping; tools, techniques, and strategies to monitor the effectiveness of interventions; and criteria for interruption of transmission.
• Diagnosis: PCR/DNA probes for detection of Onchocerca larvae in blackflies.
• Other: development of community-level strategies to ensure programme sustainability; assessment of the effect of long-term exposure to ivermectin on longevity/fecundity in the adult worm; development of new drugs (macro- and microfilaricides); monitoring the emergence of drug resistance (especially to ivermectin); monitoring the impact of fly and human migration patterns on the programme; and assessment of the social and economic impact of the programme.

• Onchocerciasis can be eliminated as a public health problem, as has been demonstrated in the Americas and OCP.
• At present, onchocerciasis cannot be considered as a candidate for eradication. This position may need to be reconsidered in a period of 5-10 years on the basis of the data on the long-term effect of mass treatment on transmission.

• Goal I. Reduce microfilaraemia to interrupt transmission and prevent infection. (In areas of subperiodic Brugian infections (less than 5% of lymphatic filariasis cases), the goal is limited to decreasing transmission and reducing the incidence of infection. Strategies to achieve this goal included the following: mass treatment for 4-6 years of entire at-risk populations with two-drug regimens (choosing among diethylcarbamazine (DEC), ivermectin, and albendazole); use of salt fortified with DEC for 1-4 years; and vector control as an adjunctive measure.
• Goal II. Alleviate and reduce the suffering of persons with filaria-related disease. Strategies to achieve this goal include the following: community-based care and training which emphasizes hygiene and other simple measures to prevent the occurrence of acute attacks and to reverse the changes due to lymphoedema and elephantiasis; and health education.

• Transmission of the parasite is inefficient.
• The parasite does not reproduce in the vector.
• There is no animal reservoir for Wuchereria bancrofti or nocturnal Brugia infections; although animal reservoirs for subperiodic Brugia malayi (causing less than 5% of lymphatic filariasis) do exist, they are of uncertain importance for human infections.
• Simple, rapid, accurate tools exist for diagnosis; although no antigen detection assay is currently available for B. malayi, there are highly sensitive, but more labour-intensive, PCR diagnostic techniques.
• Treatment to reduce and suppress microfilarial levels in blood is effective, inexpensive, safe, simple and suitable for large-scale mass treatment (i.e. in an annual single-dose regimen). A variety of treatment options (i.e. drugs and drug combinations) are available, reducing the likelihood of the development of parasite resistance to a single drug. Treatment with these drugs provides collateral health benefits, including a reduction in the burden of intestinal helminth infections (and, with ivermectin, relief from scabies and lice infestations); this feature enhances the programme's acceptability and integration with other health programmes.
• Treatment for filaria-associated disease leading to prevention of the debilitating acute attacks and reversibility of lymphoedema and elephantiasis is simple, uses appropriate technology, can be carried out at the community level, and can provide collateral benefits for community development.
• In filariasis-endemic areas, the disease is regarded as one of high importance, in part because of its disfiguring clinical manifestations.
• Several countries already have national filariasis elimination activities underway, and others have new national plans of action.
• Partners from the private sector have already expressed a strong commitment to filariasis elimination, as exemplified by the drug donation by SmithKline Beecham.
• The type of Brugian filariasis, for which an animal reservoir may sometimes exist and for which diagnostic tools are less well developed, accounts for less than 5% of all lymphatic filariasis cases worldwide.

• Simplified diagnostic tools for B. malayi infection.
• Definition of the importance of the animal reservoir for B. malayi.
• Development of means to monitor for emergence of drug resistance.
• Development of means for integrating the twin goals of interrupting transmission through mass treatment and relieving suffering through community-based care.
• Surveillance: epidemiological assessment and mapping; means for monitoring the effectiveness of interventions in reducing and interrupting transmission; and criteria for certification of elimination of infection.
• Determination of the criteria required to initiate mass treatment, the duration of programmes, and whether there is a threshold of microfilariae prevalence below which transmission cannot be sustained.
• Assessment of the efficacy of different drugs, drug combinations, and annual sequences of drugs against the adult worm and microfilariae.
• Estimation of the costs and benefits of mass treatment with antifilarial drugs and drug combinations.
• Development of models of programme implementation, and determining the optimal approach for integrating these with primary health care and other health care services.
• Development of more effective macrofilaricidal approaches for treating the individual patient.
• Development of means for measuring, increasing, and sustaining compliance at the community level.

• W. bancrofti and periodic B. malayi infection, which cause more than 95% of lymphatic filariasis, can be eliminated and potentially are eradicable.
• Infection with B. malayi can be eliminated except in those foci where animal reservoirs exist for the "subperiodic" form of this parasite. Additional research is required to establish whether or not this infection in animals is important as a source of infections in humans.

Elimination of Triatoma infestans -- the main domestic vector of Chagas disease in the Southern Cone Region -- is an attainable goal, except in some areas of Bolivia, where sylvatic foci of this species exist. From the beginning of national programmes in Uruguay and Brazil in 1980, T. infestans has been eliminated in greater than 95% of the municipalities that were formerly infested. In the places or regions where Chagas disease (CD) programmes were well implemented (as reflected by quality and continuity), there was a dramatic decrease in human CD cases and the interruption of transmission whenever the level of house infestations decreased to 3% or less. In addition, serological surveys showed an impact on schoolchildren: for example, in Brazil (Sao Paulo State) and Uruguay, there were substantial declines in seropositivity in schoolchildren from the 1960s to 1995. Changes also occurred in other groups, including blood donors in Brazil (in 1979, 5% were seropositive versus 0.7% in 1995); pregnant women in Bambui (in 1954, greater than 45% were seropositive, compared with 18% in 1963, 1.5% in 1990, and 0% in 1997). Based on the experience in the Southern Cone countries, the subgroup concluded that domiciliary Chagas disease could probably be eliminated as a human infection in most regions.

• The primary vectors are susceptible to many insecticides and are reduced by improved housing.
• Transmission is slow and difficult.
• Effective control tools are available.
• Control programmes (especially in Brazil and Uruguay) have demonstrated the feasibility of elimination.

Constraining factors include the existence of multiple vectors, some of which are not domiciliary, and of multiple animal reservoirs; the lack of political will in some countries; the absence of an effective vaccine or drug against chronic infection; and a complex strategy requiring six complementary interventions.

• Preliminary assessment of the problem, including vector mapping, serological testing, and (in the initial stages) clinical testing which requires good laboratory support.
• Epidemiological surveillance to be conducted with the effective participation of the community.
• Health education and community mobilization.
• Insecticides for vector control.
• Housing improvement.
• Routine screening of blood bank blood should be instituted in endemic countries; blood should be treated before use if the disease incidence is greater than 10%.
• Congenital cases need to be identified and treated.

• Development of a simple, cheap, rapid blood test with high sensitivity and specificity
• KAP studies to guide health education/community mobilization interventions.
• Vector studies to a) determine to what extent and why sylvatic species infest peri-domestic environments, and b) develop methods of vector detection when vector population densities are low.
• Continued development of drugs for curing chronic infection.
• Determination of the efficacy of treatment of chronic infection with currently available drugs.
• Operational studies of housing improvement methods.
• Assessment of Trypanosoma cruzi strains responsible for human and nonhuman animal reservoir infections.

The Subgroup on Other Parasitic Diseases considered seven parasitic diseases using the criteria identified by the Dahlem Workshop ( Table 1). The diverse nature of the infectious agents (protozoa and helminths) and their modes of transmission (e.g. vectorborne, soil-transmitted, foodborne and zoonotic) makes comparison of these diseases difficult. Many of these infections, in their natural habitats, are not considered susceptible to elimination using current technologies. However, experience has revealed that they are capable of elimination from certain areas to which they have spread or been introduced.

Previous attempts to eradicate malaria were unsuccessful. However, the extreme burden imposed by this disease warrants that it continue to be considered for elimination. Further research is essential for developing a better understanding of the disease and its effective intervention.

Taenia solium taeniasis/cysticercosis was considered to be potentially eradicable. The two-host life-cycle of this cestode, including humans and domestic pigs makes it vulnerable to a variety of interventions. Historical experiences in western Europe indicate that this infection may even disappear without targeted interventions. Pigs, which rarely are allowed to survive past one year, are an excellent focal point for surveillance of the infection which may be done by local people without expensive equipment or training. There are rapid diagnostic tests for the infective stages in both humans and pigs, and effective and inexpensive drugs for mass treatment of intestinal tapeworm infections in humans. There is a need to demonstrate the cost-effectiveness and sustainability of intervention strategies in a variety of endemic situations.

The leishmaniases are difficult to eliminate because of the existence of reservoirs in domestic and wild animals. However, there are "anthropophilic" strains/species that are vulnerable to elimination by effective vector control and targeted treatment. Current epidemics of these strains are occurring in Sudan, Bangladesh and parts of India. There is a need for demonstration projects to determine the possible effectiveness of such measures.

Schistosomiasis is difficult to control under most situations. However, its public health burden makes it necessary to consider new approaches to elimination. The availability of an inexpensive and highly effective drug, praziquantel, provides a tool for greatly reducing morbidity and rates of transmission in endemic areas.

The geohelminths (ascaris, hookworms and whipworms) currently infect about one-quarter to one-third of the world's population, causing impairment of growth and cognitive development of infected children. Although refractory to elimination in most areas, mass treatment of school-age children is increasingly seen as a cost-effective intervention strategy for reducing the associated morbidity and developmental problems in affected populations. Such interventions are well accepted and form the basis for other community health interventions.

The zoonotic helminth Echinococcus granulosus, which causes human hydatid disease, is widely prevalent in populations involved in raising sheep and some other livestock animals. The disease has been effectively eliminated from island and regional situations by reduction in the number and/or by treatment of dogs, the definitive host of the tapeworm. The existence of sylvatic cycles of Echinococcus spp. precludes eradication of the agent. Similarly, with fascioliasis, the existence of animal reservoirs precludes eradication; however, improved drug therapy provides effective treatment of the disease in humans and animals.

• International agencies should review with other stakeholders the definitions and use of the terms "elimination of infection and disease" with a view to achieving a consensus.

• Funding agencies should promote research to identify an effective macrofilaricide for onchocerciasis.
• Endpoints for use in the certification of the eventual elimination/eradication of parasitic diseases need to be determined.

Thanks are due to David Addiss, Joel Breman, Dan Colley, Emanuel Miri, P.R. Narayanan, Peter Ndumbe, Eric Ottesen, Frank Richards, Peter Schantz, and Craig Withers for their special contributions to this report.

References

1. Blanks J et al. The Onchocerciasis Elimination Program for the Americas: a history of partnership. Pan American journal of public health, 1998, 3: 367-374.
2. Centres for Disease Control and Prevention. Recommendations of the International Task Force for Disease Eradication. Morbidity and mortality weekly report, recommendations and reports, 1993, 42 (RR-16).
3. Dowdle WR, Hopkins DR. eds. The eradication of infectious diseases: report of the Dahlem Workshop on the Eradication of Infections Diseases. Chichester, John Wiley & Sons, 1998.
4. Duke BOL. Onchocerciasis (river blindness) -- can it be eradicated? Parasitology today, 1990, 6: 82-84.
5. Schantz PM et al. Potential eradicability of taeniasis and cysticercosis. Bulletin of the Pan American Health Organization, 1993, 27: 397-403.
6. Control of Chagas disease. Report of a WHO Expert Committee. Geneva, World Health Organization, 1991 (WHO Technical Report Series, No. 811).
7. Four TDR diseases can be "eliminated". TDR News, 1996, 49: 7-11.
8. Lymphatic filariasis: the disease and its control. Fifth report of the WHO Expert Committee on Filariasis. Geneva, World Health Organization, 1992 (WHO Technical Report Series, No. 821).
9. Onchocerciasis and its control. Report of a WHO Expert Committee on Onchocerciasis Control. Geneva, World Health Organization, 1995 (WHO Technical Report Series, No. 852).

* Chief Medical Officer, Ministry of Health, Kingston, Jamaica.

TABLE 1. Evaluation of additional candidate diseases based on Dahlem criteria*

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