Agenda item 2.3 SEA/ACM/Meet.1/2.33 25 June 2008 Responding to Emerging and Re-Emerging Vector-Borne Diseases The paper outlines the growing burden of emerging and re-emerging vector-borne diseases in the South East Asia Region. To prevent the emergence of new vector-borne diseases and re-emergence of those already under control, it is essential to strengthen national vector control programmes. Regional guidelines and activities are in place to bring together to combat vector control against malaria, lymphatic filariasis, leishmaniasis, dengue, Japanese encephalitis and chikungunya etc. Most Member countries of the SEA Region have in place appropriate surveillance system for the vector borne diseases which includes monitoring of drug resistance in the case of malaria and kala-azar. The WHO regional integrated vector control strategy has been developed. Global climate changes, emerging drug resistance and development of pediatric dengue vaccine etc. are the main challenges of the future. The WHO is playing a pivotal role in capacity building, advocacy, partnerships and operational research. The views and recommendations of the Meeting of the Advisory Committee (ACM) on this agenda item will be submitted to the Sixty-first Session of the Regional Committee for its consideration. Meeting of the Advisory Committee (ACM) to review technical matters to be discussed at the Sixty-first Session of the Regional Committee WHO/SEARO, New Delhi, 30 June – 3 July 2008
SEA/ACM/Meet.1/2.3 Page 1 1. Introduction 1. In South East Asia (SEA) Region of the World Health Organization, several vector- borne diseases, especially malaria, dengue/ dengue haemorrhagic fever, lymphatic filariasis, visceral leishmaniasis (Kala azar), Japanese encephalitis, plague, rodent-borne viruses and arboviruses pose serious threats to human health with considerable health and economic impact. Considerable attention has recently been drawn at a global level to the serious threat to humans by the new, emerging and re-emerging vector borne infectious diseases. The South East Asia Region is burdened with diverse vector-borne human diseases. 2. The Region has experienced a gradual increase in outbreaks of dengue, malaria and other vector-borne diseases. These diseases are closely associated with climatic conditions, although response patterns vary between diseases. In areas with limited or deteriorating public health infrastructure, and where temperatures now or in the future are conducive of disease transmission, an increase in temperatures (along with adequate rainfall) will trigger certain vector-borne diseases (including malaria, dengue, and leishmaniasis). The strong correlation between precipitation and malaria and between temperature and dengue, documented in different studies in the Region, suggests that these and other diseases may be more prevalent in the Region as a result of global warming and climate change. Higher temperatures, in combination with conducive patterns of rainfall and surface water, will prolong transmission seasons in some endemic locations. In other locations, climate change may decrease transmission via reductions in rainfall or temperatures that are too high for transmission. In all such situations, the actual health impacts of changes in potential vector- borne diseases transmission will be strongly determined by the effectiveness of the public health system. Deforestation, poor water management, migration and life-style changes are other important factors that are related to vector-borne disease transmission. WHO will continue extending support to Member countries to strengthen their vector-borne disease control and elimination programme that will culminate in the achievement of the Millennium Development Goals related to vector-borne disease control and elimination targets through implementation of a comprehensive regional strategy. 2. The growing burden of vector-borne diseases in the SEA Region 3. An estimated 1 394 million people, or 84% of the total population of the SEA Region, are at risk of malaria. Malaria is endemic in all the Member countries of the Region except Maldives. The burden of malaria in Asia equals 38% of the number of clinical cases in the world. On an estimate, more than 100 000 deaths are reported every year in the SEA Region. The reported number of deaths due to malaria had reduced by approximately 50% in 2005 as compared to that in 1995 1 . Post 1998 Plasmodium falciparum cases had increased continuously over the years, which is mainly due to the spread of drug resistence of this species (Figure 1). There have been recent reports from the region of the Thailand- Cambodian border on the emergence of “tolerant” P falciparum to artemisinin-based SEA/ACM/Meet.1/2.3 Page 2 combination therapy (ACT) which is the most efficacious. This implies enhanced threat of malaria to the Region and globally requires urgent action to contain the spread of this particular strain of parasite. Figure 1: Malaria: Trends in number of reported cases and proportion of P. falciparum in WHO SEA Region, 1981–2006 0 500 1000 1500 2000 2500 3000 3500 4000 4500 1 98 1 198 2 198 3 1 98 4 19 85 1 98 6 198 7 198 8 1 98 9 199 0 199 1 19 92 1 99 3 1 99 4 199 5 199 6 199 7 1 99 8 199 9 200 0 2 00 1 200 2 2 00 3 200 4 200 5 2 00 6 Years N u m b er of C a se s i n t h o u sa n d s 0.0 10.0 20.0 30.0 40.0 50.0 60.0 Pf Pr o p o r t i o n s Number of Cases in 1000 Pf Proportions Source: Country reports 4. Dengue continues to pose a major public health problem in Member countries of the SEA Region. Among an estimated 2.5 billion people at risk of dengue globally, about 1.8 billion (more than 70%) reside in the countries of the Asia–Pacific region. During the last five years more than 200 000 cases were reported every year. New outbreaks have been reported at an interval of every three to four years, Showing an increasing trend. The case fatality rates in the region vary from 0.5 to 2.6 percent which is recording an overall decline as a result of improved case management (Figure 2). The main factors for the recent re- emergence of dengue in the Region are related to the increased vector population attributed to urbanization, travel, migration, climatic change and unsatisfactory water management at the household and community level. SEA/ACM/Meet.1/2.3 Page 3 Figure 2: Dengue: Trends in reported number of cases and case fatality rate in SEAR countries, 1985–2007 0 50 100 150 200 250 300 1 98 5 1 98 6 19 8 7 1 9 88 19 8 9 1 9 90 1 99 1 1 99 2 19 9 3 1 9 94 1 99 5 1 9 96 1 99 7 "1 9 9 8 " 1 999 2 00 0 2 00 1 20 0 2 2 0 03 20 0 4 2 0 05 2 00 6 2 00 7 Years N u mber of C a s es i n thous ands 0 0.5 1 1.5 2 2.5 3 C ase Fata l i t y R a t e % Number of Cases Case Fatality Rate Source: Country report 5. The epidemiological pattern and geographical distribution of Japanese Encephalitis (JE) has been changing throughout Asia. This has been possible through control efforts that integrate human vaccination, water management, immunization of amplifying animals, systematized piggery, and community awareness programs. On the other hand, the incidence of JE has shown an increasing trend in India, Nepal, Sri Lanka and Thailand. Epidemics peak every three to five years. In the SEA Region JE cases in endemic areas have been reported throughout the year though epidemics occur only immediately after the rainy season, with 90% of cases reported between mid-July and October. 6. Chikungunya fever is re-emerging in previously unaffected areas with possibly changing epidemiology and severity of the disease. Chikungunya tends to cluster geographically and overlap with Dengue because they share also some common features. This disease has not been included in the ambit of routine communicable disease surveillance in most Member countries of the South-East Asia Region. There were major outbreaks reported in India, Sri Lanka and Maldives recently and the disease has been frequently SEA/ACM/Meet.1/2.3 Page 4 reported as an outbreak phenomenon in different parts of India and other countries. Regional Strategy for Prevention and Control of Chikungunya has been developed. 7. Kala-azar, a re-emerging disease both globally and in the SEA Region, continues to be a public health concern in three countries-Bangladesh, India and Nepal. Cases of Visceral Leishmaniasis have also been identified recently in Bhutan. More than 200 million people are at risk of VL in the SEA Region. Approximately 25 000 to 40 000 cases and 200-300 deaths are reported every year, but these are believed; to be grossly underestimated (Figure 3). Recent multicentric studies identified the VL burden to be 21 cases per10 000 among the sampled population of Bangladesh, India and Nepal. The estimated figure is 420 000 VL cases 2 . The factors responsible for the upsurge of VL include poor socioeconomic status, malnutrition and insufficient spraying of insecticides in affected areas that lead to vector proliferation. Figure 3: Kala-azar: trends in reported cases and case fatality rate in endemic SEAR countries, 2001-2007 0 5 10 15 20 25 30 35 40 45 2001 2002 2003 2004 2005 2006 2007 N u m b e r of C a se s i n t housa n d 0 0.2 0.4 0.6 0.8 1 1.2 1.4 C ase F a t a l i t y R a t e % Bangladesh India Nepal* Case Fatality Rate Source: Country report 8. Lymphatic filariasis (LF) is one of the major public health problems in South-East Asia Region. Nine out of 11 countries in the Region are known to be endemic for filariasis. It is estimated that there are about 700 million people living in endemic areas, 64% of the global population is at risk and 60 million people are either harbouring microfilaraemia or suffering SEA/ACM/Meet.1/2.3 Page 5 from clinical manifestations which constitute about half of the global figure 3 . India alone has been estimated to lose US$ 1 billion per year on account of LF 4 . 3. Strategies and response 9. A substantial progress has been made in achieving the vector-borne diseases control and elimination targets for South-East Asia through the implementation of the regional strategy and strategic framework and plan for different vector-borne diseases. The Regional Office recognized the urgency to revise the Malaria Control Strategy 2006-2010. The revised strategy for the SEA Region, 2006-2010 was disseminated and shared with Member countries, development partners and donors accordingly in several forums 5 . Member countries are revising their national strategic plan accordingly and incorporating the Regional Revised Strategy for implementation. The Asia-Pacific Strategic Plan for the Prevention and Control of Dengue (2008-2015) has been developed in collaboration with the Western Pacific Region. In addition, the Asia Pacific Dengue Partnership (APDP) has been established to undertake advocacy and resource mobilization to support implementation of national and regional operational plans 6 . 10. The Regional Strategic Framework for Kala-azar Elimination from the South-East Asia Region (2005-2015) has been developed 7 . Its goal is to improve the health status of vulnerable groups and at-risk populations in kala-azar endemic areas of Bangladesh, India and Nepal by reducing the annual incidence of disease to less than one per 10 000 population at the district or sub-district level (upazila in Bangladesh, Tehsil (Sub-district) in India and district in Nepal) by 2015. The strategies proposed by WHO to achieve the goal of LF elimination have two components: interruption of transmission of filarial infection in all endemic countries through reduction of the microfilariae prevalence levels by Mass Drug Administration (MDA) through diethylcarbamazine [DEC] and albednazole and prevention and alleviation of disability and suffering in individuals already affected by LF 7 . Sri Lanka and Thailand have made significant progress with five rounds of MDA and other Member countries are progressing with the MDA of the two drugs. Coverage, however, needs to be strengthened further. 11. The proposed strategic elements for control of vector-borne diseases are healthy public policy in developmental projects and implementing a multi-sectoral approach. The emphasis is on ecological, environmental and behavioural determinants that contribute to disease transmission. Reforms aimed at programme planning and management (including monitoring and evaluation), striking a balance between treatment and control interventions, and scaling up the coverage of preventive and treatment services are essential. Vector-borne disease control supportive strategies include advocacy for mobilization of additional resources, programme planning and management, information exchange, human resources development, behavioral change communication (BCC) and development of a monitoring and evaluation framework to track the progress of programme implementation. SEA/ACM/Meet.1/2.3 Page 6 12. WHO provided technical support to Member countries in advocacy for dengue, VL, malaria, JE and LF control in the SEA Region at the political level and to partners in the communities. The Member countries are committed to achieve the MDG targets by 2015. The enhanced visibility of emerging and re-emerging vector-borne disease control and application of strategies would require sustained high level political commitment. 13. A resolution on the Revised Malaria Control Strategy was passed by the Regional Committee for SE Asia at its Sixtieth Session in Thimphu in 2007 5 . Since this resolution, the WHO SEA Regional Office has been assisting Member states in implementing the Revised Malaria Control Strategy and providing technical support to strengthen national capacity in monitoring and evaluation in Bangladesh, Bhutan, Nepal, and Sri Lanka. 14. Based on the successes of immunization for JE in the Member countries, a carefully planned programme for control of JE has been developed and attempts are in progress to incorporate JE vaccine into the Expanded Programme on Immunization (EPI) Surveillance and response systems have been included as an integral part of the programme. Case management of JE has been improved and the sequilae and mortality from the disease has been reduced. 15. A WHO mission to India’s Bihar state consisting of international and national experts reviewed the progress and identified the technical and operational challenges. Major gaps identified included the completion of treatment and information, education and communication (IEC) activities. Training guidelines and standard operating procedures have been developed and Member counties are using the same for the implementation of the programme. The procurement of drugs (Miltefosine); RDT (rk39 dipsticks); Deltamethrin (in Bangladesh), DDT (in India) and Lambda-cyhalothrin (in Nepal) has been completed. The community is suitably informed about the availability of drugs for the prevention and treatment of kala azar. Service packages available at different levels, of the health system according to the norms for the level and health facilities at different levels have the capacity to deliver effective services. Incentives regarding clients’ food, loss of compensation and housing are in place in India, and policy advocacy has been set in motion in Bangladesh and Nepal. WHO is providing technical support for all the activities, including adopting training of trainers curricula; conducting training; procuring drugs and diagnostics; updating training manuals; conducting Miltefosine Phase IV trials (in Bangladesh) and integrated vector management. 16. To support the control and elimination of the vector-borne disease initiatives, a series of national and multicentric studies in the areas of diagnosis, case detection, treatment and vector control are in implementation with the support of the Global Fund, World Bank and other funding sources. The gaps are being identified for policy and effective implementation of interventions. The experts in the Regional Office have also developed research priorities SEA/ACM/Meet.1/2.3 Page 7 in the area of vector borne diseases. The following implementation research areas have been identified: a. Identify the barriers to access care for patients and vulnerable groups (socio-economic, knowledge, cultural, gender issues, topographical). b. The scale-up proposal on “Towards More Cost-effective VL Case Detection and Case Management in Endemic Districts”. c. Explore different types of DOTS (including home-based DOTS). d. Efficacy and costs of alternative methods for VL active case finding. e. Usefulness, feasibility and cost of vector control monitoring in Kala-azar Endemic Districts. 3.1 Monitoring of drug resistance 17. Drug resistance in both P. vivax and P. falciparum malaria has been reported in many Member countries. As multi-drug resistant P. falciparum has spread in these, almost all Member countries where P. falciparum is prevalent have revised their national treatment guidelines and adopted artemisinin-based combination therapy (ACT) in line with WHO recommendations. As part of the bi-regional collaboration between the Western Pacific and South-East Asian Region, drug resistance monitoring in sentinel sites and networking continues to be strengthened and Myanmar and Thailand have been included from the SEA Region. 18. Recently miltefosine has been introduced in Member countries as a first-line drug for the treatment of kala-azar. Pharmaco vigilance guidelines have been developed to monitor the VL drug use and its resistance. 3.2 Implementing integrated vector management 19. A step-by-step approach to a regional framework for implementing integrated vector management (IVM) at the district level in the South-East Asia region was developed recently. It addresses the appropriateness of deploying an optimum mix of interventions. This framework will guide Member countries in selectively applying the various vector control tools available based on the epidemiological situation, vector bionomics and its behaviour, and the socio-behavioural characteristics of the community. 3.3 Collaboration and partnership 20. Partnership interest and engagement for the control of malaria, dengue and JE and for the elimination of VL and LF has been increasing since effective interventions and tools are available. International collaboration and partnerships are likely to influence the political commitment and help the mobilization of resources. The partners are the World Bank, Global Fund and the Bill and Melinda Gates Foundation. The Asia-Pacific Strategic Plan for SEA/ACM/Meet.1/2.3 Page 8 the prevention and Control of Dengue (2008-2015) has been developed to facilitate the development of national operational plans and undertake advocacy for resource mobilization. The APDP has been established in collaboration with the Western Pacific Region to assist Member countries to mobilize resources to support the implementation of the strategic plan. 4. Challenges and opportunities ahead 4.1 Low coverage and timely intervention 21. For the control of vector borne diseases reported coverage of insecticide-treated nets and extent of indoor spraying by the population-at-risk is low (10-20%). Though the past couple of years have seen during the past some progress in improving the coverage ITNs, the current degree of coverage is not likely to have a significant impact on arresting vector borne disease transmission transmission. The reported LF drug coverage and consumption rate of MDA in many countries is low. High coverage of MDA is very crucial to achieve elimination of LF. There has been progress in improving the timeliness, completeness and quality of data for reporting and sharing the information within and among Member countries and WHO. 4.2 Inadequate human resources and weak management 22. Vector-borne disease control programmes in most Member countries are grappling with problems of inadequate trained personnel, weak programme management and insufficient financial resources. Programmatic innovation with well-designed plans, effective surveillance, and a competent monitoring and supervision system are needs that must be urgently addressed for better prevention and control of vector-borne diseases. 4.3 Emerging drug resistance 23. The problem of multi-drug resistance P. falciparum is expanding geographically and countries of South-East Asia and the Mekong Basin are the new epicentres of such resistance. The nature of threat of P. vivax malaria has been largely ignored since the disease is non-fatal though disabling. Focal outbreak of malaria are frequently reported in almost all the countries reflecting the unstable nature of malaria transmission in the region and inadequate epidemic preparedness of the control programme. For kala-azar, monitoring of the SAG drug resistance, found to be spreading from Bihar to other parts of the continent is inadequate. It has been recommended that this is going to be discontinued in the Kala azar elimination programme .The overlapping of the VL and HIV has lead to an emergence of the new entity Leishmania HIV co-infection that is likely to worsen the problem of drug resistance. 4.4 Dengue vaccine 24. The development process of live attenuated tetravalent dengue vaccine by Mahidol University of Thailand was renewed a few years ago. These new sets of vaccine are called Mahidol set II. All dengue virus strains selected for using in attenuation attempts were recent SEA/ACM/Meet.1/2.3 Page 9 dengue viruses isolated from patients within 4-10 years. After completion of preclinical evaluation, candidate dengue vaccines for DEN-1, DEN-2, DEN-3 and DEN-4 were selected. Mahidol University intends to scale up all the DEN vaccines at industrial scale using certified continuous Vero cells. Mahidol University and Thailand Center of Excellence for Life Sciences (TCELS) have committed to build a GMP vaccine pilot plant. Clinical batches of each monovalent dengue vaccine for phase I and II clinical trials will be prepared at this GMP plant in 2009. There are several key issues and challenges on pediatric dengue vaccine development which include affordability, availability, quality and competitiveness that must be considered. Technical, economic and political commitments are also important areas to carry forward WHO endeavor in this initiative. 4.5 Climate change 25. Global warming and climate changes have taken malaria, dengue and other vector- borne diseases to new areas. Climatic factors, particularly temperature and rainfall, affect the ability of malaria parasites, viral propagation and potential mosquito vectors to coexist long enough to maintain and increase the rate of transmission. The suppression of Aedes aegypti using practical methods; strengthening of linkages between research and academic institutions; addressing issues related to unplanned poor housing, unsatisfactory living conditions, undernutrition, migration and resettlement; organization of integrated vector management (IVM), behavioral change communication strategies; and implementation of targeted interventions along with improvement and implementation of community-based- vector borne disease control programmes are other important challenges. Most of the vector- borne diseases are ecological diseases. Efforts, therefore, need to be made to adopt a community development approach and move beyond the realm of health areas. 4.6 Community participation 26. The control of vector-borne diseases is generally undertaken by disposal of potential Aedes aegypti breeding sources and containers, and use of insecticide treated nets and insecticide, and environmental management. These benefit not only those who practice these control measures but others in the community as well. A broader perspective of the disease control strategy is required for a holistic interaction between economic and political factors with the social environment to enhance community participation and promote vector-control strategies. A high motivational level in the community along with sustained and continuous collaboration among community members and stakeholders will hasten the rate of success. 5. Role of WHO 27. WHO takes a lead role in response to vector-borne diseases and is strongly committed to work with national vector-borne diseases control/elimination/eradication programmes through the scaling up of different public health interventions. The role of WHO includes: SEA/ACM/Meet.1/2.3 Page 10 • Capacity building: WHO assists in strengthening health systems that support implementation of different control, elimination and eradication programmes on emerging and re-emerging vector borne diseases. These include human resource development; service delivery; strategic information; and procurement and supply management. The training modules and standard operating procedures have been developed and intercountry, intracountry and local-level training courses have been conducted in the different areas of vector- borne diseases. • Advocacy and resource mobilization: WHO works with international development agencies and with the private sector and donors to advocate for evidence-based policies and mobilizing resources to support the implementation of national programmes. • Programme review, surveillance, monitoring/evaluation and strategic planning: WHO supports national vector-borne disease control programme review, surveillance, monitoring and evaluation. This information helps in developing national strategic plans in the Member countries. • Partnerships: It is critical to enhance the role of various sectors such as education, public works, tourism, industry, the private sector and nongovernmental organizations. WHO plays a leading role to ensure active participation of intersectoral partners in the prevention and control of vector- borne diseases. • Research: Operational/implementation research on disease transmission, epidemiology, vector management, treatment as well as socio-economic and behavioural aspects of the disease is urgently needed. The results of such studies can be used to formulate revisions in policies and strategies. 6. Issues for consideration at the national level • The development and implementation of national vector-borne control programmes that are consistent with the regional strategy for Vector-Borne Disease Control and that emphasize the improvement of the health system capacity including human resources. • Optimum coordination with ministries such as environment, education, tourism, rural development and agriculture in the implementation of vector-borne disease control programmes as a part of the corpus of healthy public policies. • The control of vector-borne diseases through multi-country activities (MCAs) within the gamut of cross border collaboration. • Strengthening surveillance to assess the burden of vector-borne diseases. • Advocacy for vector-borne diseases in national and international forums. SEA/ACM/Meet.1/2.3 Page 11 • Establishing and strengthening linkages between researchers and academic institutions. • Effective implementation of an integrated vector control plan which has been developed. 7. Issues for consideration at the regional level • Provision of technical support and advocacy for the mobilization of additional financial resources to strengthen the vector-borne disease control programme. • Promotion and implementation of evidence-based policies, standard tools for the improvement of the programme, and sharing useful information and country experiences with Member States. • Collaboration among stakeholders who include governments, development partners, NGOs, donors, academia and other relevant parties to address the issues and challenges in preventing and controlling vector-borne diseases. • Promoting and developing operational/implemention research as one of the priorities in the area of vector-borne disease control and to advocating complimentarity of research and programme implementation. 8. Issues for consideration in the case of specific vector-borne diseases • Endorsement of the Asia-Pacific Strategic Plan for Dengue 2008-2015 and recommendations to Member countries for its implementation. • Provision of technical support to facilitate and accelerate pediatric vaccine development. • Incorporation of JE immunization programme into the Expanded Programme on Immunization in disease-endemic areas along with an active inbuilt surveillance and response system. • Implementation of kala-azar and LF elimination programmes to achieve the global target. • Development of a regional strategic plan and guidelines for the management of chikungunya. 9. Conclusion 28. Vector-borne diseases are re-emerging in the WHO South-East Asia Region due to a number of natural and man-made factors. Many of these diseases, particularly dengue, japanese encephalitis and malaria are now occurring in epidemic form and causing considerable morbidity and mortality. Dengue is spreading rapidly in newer areas and with more frequent outbreaks. It requires collaboration between Member countries in the Asia- SEA/ACM/Meet.1/2.3 Page 12 Pacific to implement the Bi-regional Strategic Plan through Asia-Pacific Dengue Partnerships. Chikungunya has re-emerged in most Member countries of the SEA Region and also needs a strategic plan for its control which could be implemented together with Dengue Prevention and Control Strategy. VL and LF pose a much higher burden and are a cause for public health concern. While the morbidity for most of the vector-borne diseases has increased during the period, the case fatality rate have been reduced. To prevent the emergence of new vector-borne diseases and the re-emergence of those already under control, it is essential to have high political commitment, multisectoral collaboration and community participation. Though the health sector will continue to remain central to disease control activities, containment of VBD requires active support and commitment from many active partners to avert the factors that promote and facilitate the breeding of vectors, and the effective implementation of an integrated vector control plan that has been developed. The discovery and development of new dengue vaccine candidates needs to be accelerated in coordination with Member States. For JE a carefully planned immunization programme needs to be further incorporated into the Expanded Programme on Immunization in disease- endemic areas along with an active inbuilt surveillance and response system. SEA/ACM/Meet.1/2.3 Page 13 References 1. Kumar A, Valecha N, Jain T, Dash AP. Burden of malaria in India: retrospective and prospective view. Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):69-78. 2. A Joshi, J.P. Narain, C. Prasittisuk, R. Bhatia, Ghalib Hashim, Alvar Jorge, M. Banjara and A. Kroeger. 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