Integrated disease management: arboviral infections and waterborne diarrhoea

Abstract Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems. We believe that these two disease groups share common risk factors, namely inadequate household water management, poor sanitation and solid waste management. Where water provision is inadequate, water storage is essential. Aedes mosquitoes commonly breed in household water storage containers, which can hold water contaminated with enteric disease-causing organisms. Microbiological contamination of water between source and point-of-use is a major cause of reduced drinking-water quality. Inadequate sanitation and solid waste management increase not only risk of water contamination, but also the availability of mosquito larval habitats. In this article we discuss integrated interventions that interrupt mosquito breeding while also providing sanitary environments and clean water. Specific interventions include improving storage container design, placement and maintenance and scaling up access to piped water. Vector control can be integrated into sanitation projects that target sewers and drains to avoid accumulation of stagnant water. Better management of garbage and solid waste can reduce the availability of mosquito habitats while improving human living conditions. Our proposed integration of disease interventions is consistent with strategies promoted in several global health frameworks, such as the sustainable development goals, the global vector control response, behavioural change, and water, sanitation and hygiene initiatives. Future research should address how interventions targeting water, sanitation, hygiene and community waste disposal also benefit Aedes-borne disease control. The projected effects of climate change mean that integrated management and control strategies will become increasingly important.


Introduction
Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems (Box 1; Table 1). The effects of water on disease are determined by multiple factors including the water source, pathogen abundance and diversity, and human water management practices. For waterborne diarrhoeal diseases, these determinants relate to faecal contamination at the water source, in transit and during storage, while for diseases borne by Aedes spp. mosquitoes, such as dengue fever, Zika virus disease and chikungunya, the determinants relate to water storage functioning as mosquito larval habitats.
Storage of water for human consumption and water management practices in both the domestic and public domains are shared risk factors for the transmission of the dengue virus (representative of Aedes-borne arboviral diseases in this article) and diarrhoea (here representing a multitude of gastrointestinal diseases). Other potential shared risk factors are inadequate sanitation and waste disposal. 4,19 Targeting such risk factors allows for integrated disease control and risk management. Co-occurrence and coinfection of both diarrhoeal diseases and dengue may explain the shared epidemiology of the diseases and can guide the design of integrated management strategies. In this article, we propose options for integrated interventions and how they fit into established health and development frameworks. We discuss considerations around sustainability of interventions and identify priorities for future research.

Common factors
Knowing the geographical co-occurrence of diseases is important for allocating scarce resources. Globally, the burden of diarrhoeal diseases is highest in Africa, 8 whereas dengue is highest in Asia. 13 However, recent research on dengue in Africa has shown that it is more prevalent than previously thought. 20 Some regions, notably the Caribbean (such as Haiti and Suriname) and Asia (such as India, Indonesia, Lao People's Democratic Republic and the Philippines), have a high incidence of both dengue and diarrhoeal diseases. 8,13 Spatial overlap may be more evident at smaller scales, because more detailed spatial and temporal variation in disease prevalence is not fully reflected in national-level statistics. Diarrhoeal diseases are more widespread and their burden is orders of magnitude higher than dengue. The more geographically constrained distribution of dengue could therefore provide a starting point for identifying locations suitable for integrating management strategies within areas where the two diseases overlap.
Understanding the shared risk factors between dengue and diarrhoeal diseases can help identify suitable integrated management and control strategies. We conducted a problem analysis as part of a logical framework approach showing cause and effect relationships between dengue and diarrhoeal diseases (Fig. 1). We identified water storage containers, sanitation and waste disposal as the main shared risk factors. These factors vary by location and time.
Factors related to water management include the source of water and how the water is collected, stored, used and Abstract Water-related diseases such as diarrhoeal diseases from viral, bacterial and parasitic organisms and Aedes-borne arboviral diseases are major global health problems. We believe that these two disease groups share common risk factors, namely inadequate household water management, poor sanitation and solid waste management. Where water provision is inadequate, water storage is essential. Aedes mosquitoes commonly breed in household water storage containers, which can hold water contaminated with enteric disease-causing organisms. Microbiological contamination of water between source and point-of-use is a major cause of reduced drinking-water quality. Inadequate sanitation and solid waste management increase not only risk of water contamination, but also the availability of mosquito larval habitats. In this article we discuss integrated interventions that interrupt mosquito breeding while also providing sanitary environments and clean water. Specific interventions include improving storage container design, placement and maintenance and scaling up access to piped water. Vector control can be integrated into sanitation projects that target sewers and drains to avoid accumulation of stagnant water. Better management of garbage and solid waste can reduce the availability of mosquito habitats while improving human living conditions. Our proposed integration of disease interventions is consistent with strategies promoted in several global health frameworks, such as the sustainable development goals, the global vector control response, behavioural change, and water, sanitation and hygiene initiatives. Future research should address how interventions targeting water, sanitation, hygiene and community waste disposal also benefit Aedes-borne disease control. The projected effects of climate change mean that integrated management and control strategies will become increasingly important.
treated, all of which can also affect water quality. Contamination may occur at any of these points, but also through poor sanitation and sewage systems. Poor water management is clearly related to diarrhoeal diseases, but can also contribute to propagation of the vectors of dengue. The nutritional quality of the larval environment affects the size and survival of mosquitoes, which may also impact vector-borne disease transmission. 21 As such, general contamination or accumulation of organic matter in water can favour larval development. We have previously shown that there are more Ae. aegypti pupae in containers that are contaminated with Escherichia coli compared with uncontaminated containers. 22 Inadequate sanitation and solid waste management also affect both diseases as these factors increase the risk of water contamination and the availability of potential mosquito larval habitats. 4

International frameworks
As we discuss in the next section, our proposed integrated interventions are closely aligned with the sustainable development goals (SDGs), particularly: strengthening good health and well-being (SDG 3), improving quality education to promote sustainable development (SDG 4), providing clean water and sanitation (SDG 6), making cities and communities safe, resilient and sustainable (SDG 11), reducing the effect of climate change (SDG 13) and supporting global partnerships (SDG 17).
The World Health Organization's (WHO) Handbook for integrated vector management aims to break the traditional top-down, insecticide-based, single-intervention approaches in favour of more evidence-based, integrated and participatory strategies. 7 Integrated vector management is defined as a rational decision-making process to optimize the use of resources for vector control. Vector control methods should preferably target the vectors of multiple diseases and be implemented through intersectoral collaboration and community participation. Integrated vector management is at the centre of the WHO global vector control response adopted in 2017, which aims to reduce vector-borne disease mortality and incidence in 2030 by at least 75% and 60%, respectively. 6 This target will be achieved by strengthening intersectoral collaboration, engaging communities, enhancing vector surveillance and scaling up and integrating vector control methods, supported by enhanced capacity and increased research and innovation. The global vector control response recommends comprehensive vector control through integrated action using effective existing and novel vector control approaches. A complementary framework for addressing behavioural change in dengue control is the Communication for Behavioural Impact approach, 23 which is a planning tool with a mixture of theory and practice. The approach uses communication theory and marketing practices to achieve behaviour change through a broad integration of mobilization, communication, strategic planning and evaluation of specific behaviours.
Waterborne disease control frameworks include interventions related to water, sanitation and hygiene (known as WASH). WHO and others promote household water treatment and safe storage. 24 Some scientists argue, however, that the evidence for scaling up household water treatment to reduce diarrhoeal diseases is not strong enough and that greater emphasis should be placed on water access and water quantity, rather than water quality. 25 Nonetheless, household water treatment and safe storage does substantially improve the microbiological quality of water. More than an estimated 60% (risk ratio: 0.39; 95% confidence interval: 0.32-0.48) of diarrhoeal diseases prevalence could be reduced by filtering and safe storage of water. 26 Water safety plans are international preventive risk management systems developed by WHO to manage, monitor and evaluate drinking-water quality. 27 The guidelines apply to all kinds of water supply systems from large piped drinking-water supplies to small community and household supply systems. Other researchers have proposed the Integrated Behavioural Model for water, sanitation and hygiene to address behavioural change. 28 Based on a comprehensive framework, the model includes contextual, psychosocial and technology factors that operate on five different levels: societal (broad organizational, institutional or cultural factors); community (physical and social environment); interpersonal or household (interactions between closely related individuals); individual (sociodemographic factors, such as age and sex); and habits (opportunities and necessities affecting behaviours nested within the individual). The model provides conceptual and practical tools for improving knowledge about and evaluation of factors that influence water, sanitation and hygiene practices to sustain behaviour change in areas with limited infrastructure. The theoretical behavioural frameworks mentioned above are only a small sample of the available evidence-based behavioural theories demonstrated to be suitable and useful in waterborne disease control in general. Finally, these and other related frameworks must be understood in relation to climate resilience, 29 and community vulnerability and adaptability. 30

Box 1. Risk factors and burden of dengue and diarrhoeal diseases
Water-related diseases may be classified into waterborne, such as diarrhoeal diseases; waterbased, such as schistosomiasis; and water-related vector-borne, such as dengue. 1 Dengue, Zika virus and chikungunya arboviral diseases are major global causes of morbidity and mortality sharing the same water-related risk factors and vector species (Table 1). 2 The main vector, Aedes aegypti, commonly breeds in clean water in household water containers in urban areas and is highly anthropophagic, endophilic and diurnal. The larval habitats of Ae. aegypti proliferate in areas where water supply is unreliable or where conventional water storage habits persist. 3 Solid waste production (garbage) and inadequate disposal also result in the accumulation of larval habitats. 4 A lack of clear evidence of the effectiveness of existing vector control methods indicates that innovative vector control strategies, socioecological approaches and controlled experimental studies are needed. 5 Determining the disease burden from dengue is impeded by diagnostic difficulties, poor surveillance, low fatality rates and a general lack of intersectoral coordination. 6,7 Diarrhoeal diseases are responsible for some of the highest mortality rates worldwide, particularly in young children and people who are malnourished or have impaired immunity (Table 1). 8 In locations where water provision is inadequate, communities must rely on water harvesting, transport and storage in or near houses for domestic purposes. Microbial contamination between source and point-of-use is often an important cause of reduced quality of household drinking water. 9 The fraction of diarrhoeal diseases attributable to inadequate water, sanitation and hygiene practices in low-and middle-income countries is about 60% (an estimated 829 000 deaths out of 1.4 million total deaths in 2016). 10 Both future contraction and expansion of areas at risk for dengue have been projected. 16 Most predictions expect negative impacts of climate change on dengue. An increase in the ability of mosquitoes to transmit dengue and more people being exposed to climates suitable for dengue create greater potential for epidemics of dengue. 17

Integrated disease management
The frameworks we outline provide a foundation for evaluating the suitability of specific interventions for integrated disease control and management. Here we propose the integrated management of diarrhoeal diseases and dengue based on identified shared risk factors (Fig. 1). Integrated management should interrupt mosquito breeding while providing a clean sanitary environment along with clean water. Generally, the household is targeted for integrated disease management, but interventions that focus on non-domestic sites -such as schools, workplaces, hospitals and industrial sites -must also be considered. 6 In this context, urban spaces need to be classified by their physical accessibility and legal accountability, which may impede access to and failure of assigning responsibility for vector control actions. 31 Such interventions in society can be helpful in identifying integrated strategies that are suitable for specific locations, employing bottom-up community action as well as government-driven top-down approaches.
Another consideration is the impact of climate change on these diseases. Increases in temperature and increases or decreases in rainfall, flooding and humidity will likely intensify the epidemic potential and expand areas suitable for transmission of both arboviral and waterborne diarrhoeal diseases. 17,18 These changes involve complex causal pathways, including the prevalence of breeding sites; increased survival or prevalence of pathogens and vectors; contamination of drinking-water resources; overwhelmed infrastructures; and population displacements. 17,18 The effects of climate change on the seasonality of disease outbreaks may also be important, involving complexities beyond the scope of this article. However, future increases in the occurrence of these diseases would increase the need for integrated management strategies. 30,32 To mitigate the effects of climate-related events, early warning systems could be useful for both dengue and diarrhoeal disease surveillance and control. 33

Water management
Water management relates to the quantity, quality and accessibility of water, its collection, transport and storage practices, as well as its consumption and treatment patterns. The source of the water can influence its quality, which can affect both its suitability for human consumption and the risk of Aedes mosquitoes breeding. A study in southern Lao People's Democratic Republic found that household containers filled with borehole water were almost four times more likely to be infested with Ae. aegypti pupae than containers with rain-fed or purchased bottled water. 34 Containers with borehole water had higher levels of Escherichia coli than other containers. 35 A relationship between Ae. aegypti productivity and E. coli-contaminated domestic water Fig. 1. Problem analysis of  Nutrients for mosquito larvae Note: The figure shows a problem tree done using a logical framework approach indicating cause and effect relationships between dengue (representing Aedesborne arboviral diseases) and waterborne diarrhoeal diseases.
Integrated management of dengue and diarrhoea Hans J Overgaard et al.
containers has been found, 22 although any consequent disease outcomes remain unknown. Water quality is a risk factor for diarrhoeal diseases and potentially also for dengue, since the nutritional quality of larval habitats affect mosquito size and survival, which in turn affect vector capacity. 21,36 India has implemented groundwater recharge programmes to manage water crises through a variety of rainwater harvesting structures, such as percolation pits and structures connected to wells (in use or disused). Defective rainwater harvesting structures were found to be key breeding habitats for Aedes mosquitoes. 37 These findings highlight that integrated control interventions targeting the water source should include water quality improvements as well as infrastructure management and repair.
Insufficient supply of water requires the need to store water. Improving the supply and storage of water in domestic and public domains is an obvious target for integrated control of dengue and diarrhoeal diseases. An unreliable drinking-water supply has been associated with higher Ae. aegypti indices, such as the presence and proportion of positive containers (container index). 3 Rural areas with a lack of piped water supply in Viet Nam had a higher risk of dengue than urban areas with an adequate water supply. 38 However, domestic household water storage is common even in areas with reliable access to piped water, and immature vectors of dengue are still found in such containers. 22 Simply improving water connections into houses may not necessarily prevent people from storing water.
Interventions targeting water storage containers for integrated control in households should focus on the type, quality and cleanliness of the container. Improving container design is needed, including covers that prevent mosquitoes from breeding and other types of contamination from occurring. Improved design and placement of containers may prevent contamination during flooding and heavy rainfall events that are expected to become more frequent with climate change. If drinking-water containers contribute substantially to the number of mosquitoes produced in an area, then an integrated dengue-diarrhoea control project could have a major impact. The WHO global assessments of household water treatment technologies show that several meet the established microbiological performance criteria in terms of pathogen removal. 24 Such technologies are based, for example, on various filtration methods using membrane, ceramic or flocculation techniques and disinfection methods using ultraviolet, solar or chemical (chlorine) techniques. However, the effect of these methods on mosquito breeding is not well characterized. Differences in designs of these technologies determine their importance for integrated control. Indeed, inclusion of vector control effects as an additional criterion would enhance the value of these household water treatment assessments. Chlorine has been used to clean containers for vector control but, although effective against bacteria and protozoa, chlorine is less effective against viruses. 24 Scrubbing the inside walls of washbasins and water storage drums with a mixture of bleach and detergent in households in Honduras showed high mortality rates of Ae. aegypti eggs, larvae and pupae. 39 It is unclear, however, whether maintaining container cleanliness for vector control would also reduce pathogens through chlorine residuals. These findings underscore the importance of appropriate site-specific dosing based on the chlorine demand of the water to be treated. Regular monitoring is also needed to ensure that free residual chlorine concentrations of 0.2-0.5 mg/L are maintained and that these interventions reduce vector breeding.
The physical location of water storage tanks can also provide an opportunity for integrated control. Studies have reported that Ae. aegypti pupae are not found in elevated water storage tanks which are located, for example, on a roof or otherwise above the ground, potentially due to heating from direct sun exposure. 40 Keeping water storage containers out of reach of people or, preferably, installing closed systems that avoid contamination should be considered for integrated dengue and diarrhoeal diseases control. Such interventions will become even more important during climate change when flooding and extreme weather events are likely to become more frequent.

Sanitation and waste management
A sanitation system includes the capture, storage, transport, treatment and disposal or reuse of human excreta and wastewater. Targeting the sanitation system to reduce water contamination is well known to reduce diarrhoeal diseases, but less is known about its impact on dengue. Ae. aegypti can lay eggs in raw sewage, with normal egg hatching and larvae development. 41 Aedes mosquitoes have also been found breeding in subterranean septic tanks and subsurface catch basins, which can contribute substantially to productivity. 42 As sanitation projects often target sewers and drains, vector control could be incorporated into such projects by avoiding the accumulation of stagnant water and ensuring that vectors are unable to enter physical structures.
Poor solid waste disposal is another potential risk factor for transmission of vector-borne and diarrhoeal diseases. Improperly managed waste such as motor vehicle tyres -implicated in the global spread of Ae. albopictus 43 -provide suitable larval habitats for mosquito vectors as well as increased risk for enteric diseases, particularly for children. 44 Stockpiles of tyres should be properly stored in ways that avoid water accumulation and reduce mosquito breeding. Deficiencies in public services, such as water supply, waste collection and excreta disposal, can be responsible for high indices of Ae. aegypti infestation. 45 Provision of solid waste management, recycling and repurposing of plastics and tyres, reliable piped water supplies and improved housing design are all key long-term steps towards reducing vector populations and improving environmental health.

Discussion
Water management, sanitation and waste management are key targets for integrated dengue and diarrhoeal diseases control. Specific water management interventions targeting the water source should include water quality improvements and infrastructure management and repair. Household water treatment and storage interventions should consider improved container design to prevent mosquito breeding and water contamination as well as container cleanliness using disinfection methods, such as chlorine. Awareness of vector control opportunities while planning improvements of sanitation systems, such as physical and organizational structures and facilities, could lead to improved sanitation as well as reduced vector densities. An effective The lack of research on integrated dengue and diarrhoeal disease interventions prevents us from drawing conclusions about their benefits. We have found only one trial that assessed an integrated strategy, assessed by a factorial, cluster, randomized controlled design in rural primary schools in Colombia during 2012-2014. 46 The trial implemented sets of physical and educational interventions targeting dengue and diarrhoeal diseases. Interventions were effective in reducing mosquito larval habitats in schools and in providing clean water; however, students' absence from school and adult mosquito density in schools were not affected. The study concluded that integrated approaches should not be limited to schools but also implemented simultaneously in communities. Two years after the trial ended the researchers assessed the sustainability of the interventions and institutional adoption in terms of stakeholder empowerment, financial support, participation and leadership, adaptive flexibility and capacity. 47 These categories were measured using a mixture of knowledge, attitude and practices questionnaires assigned to students and teachers, semi-structured interviews with teachers, as well as observations of the maintenance of the interventions. Both the educational and the physical interventions were considered moderately sustainable, but the institutional and human adoption were considered unsustainable. A lack of adoption of initiatives is not uncommon, where the short-term nature of projects often conflicts with the longterm needs of the community. The researchers further explained the failure of institutional commitment by a lack of integration of the interventions into the activities of schools and municipalities. Integration is a process that requires time and respectful dialogue between project innovators and the educational institutions to generate engagement, enthusiasm and a sense of ownership. From a teaching standpoint, schools should focus on place-based education that promotes learning rooted in local habitats. 48 Such teaching methods, combined with adapted Communication for Behavioural Impact activities, 23 can contribute to diffusion of knowledge from schools to communities and can lead to community empowerment and long-term impact. 49 Integrated interventions targeting schools or other non-residential sites, such as hospitals, religious sites or markets, require comprehensive planning and action. Such action needs appropriate combinations of interventions that are site-specific, effective, acceptable and affordable. Implementing integrated interventions requires collaboration among different sectors, capacity-building and leadership training of implementers to mobilize resources, form networks, and engage in participatory decision-making to ensure sustainability.
In addition to the issues discussed above, some underlying factors (Fig. 1) need to be in place for integrated interventions to be effective, such as political will, funding, knowledge, capacity and empowered communities. Political will and funding largely depend on external factors, whereas facilitation of education and training and community engagement are technical aspects that can be adapted to the context of local communities. Community ownership of interventions to care for common environments and individual well-being must be based on bottom-up approaches, justified by social and behavioural theories. 50 Fundamental factors in sustaining good integrated strategies would be strengthened by well-educated, confident, responsible and environmentally aware citizens who understand the holistic interrelationships between environment and disease and keeping neighbourhoods clean and healthy. On the other hand, physical accessibility and legal accountability criteria are important to select spaces that are suitable for integrated strategies where bottom-up community approaches or governmentdriven top-down approaches or both can be employed. Finally, and as a recommendation for future research, we have identified some gaps in knowledge that need to be addressed to strengthen the evidence base for best practices in management strategies for the integration of dengue and waterborne diarrhoeal diseases (Box 2). ■