Solid Wastes Provide Breeding Sites, Burrows, and Food for Biological Disease Vectors, and Urban Zoonotic Reservoirs: A Call to Action for Solutions-Based Research

Background: Infectious disease epidemiology and planetary health literature often cite solid waste and plastic pollution as risk factors for vector-borne diseases and urban zoonoses; however, no rigorous reviews of the risks to human health have been published since 1994. This paper aims to identify research gaps and outline potential solutions to interrupt the vicious cycle of solid wastes; disease vectors and reservoirs; infection and disease; and poverty. Methods: We searched peer-reviewed publications from PubMed, Google Scholar, and Stanford Searchworks, and references from relevant articles using the search terms (“disease” OR “epidemiology”) AND (“plastic pollution,” “garbage,” and “trash,” “rubbish,” “refuse,” OR “solid waste”). Abstracts and reports from meetings were included only when they related directly to previously published work. Only articles published in English, Spanish, or Portuguese through 2018 were included, with a focus on post-1994, after the last comprehensive review was published. Cancer, diabetes, and food chain-specific articles were outside the scope and excluded. After completing the literature review, we further limited the literature to “urban zoonotic and biological vector-borne diseases” or to “zoonotic and biological vector-borne diseases of the urban environment.” Results: Urban biological vector-borne diseases, especially Aedes-borne diseases, are associated with solid waste accumulation but vector preferences vary over season and region. Urban zoonosis, especially rodent and canine disease reservoirs, are associated with solid waste in urban settings, especially when garbage accumulates over time, creating burrowing sites and food for reservoirs. Although evidence suggests the link between plastic pollution/solid waste and human disease, measurements are not standardized, confounders are not rigorously controlled, and the quality of evidence varies. Here we propose a framework for solutions-based research in three areas: innovation, education, and policy. Conclusions: Disease epidemics are increasing in scope and scale with urban populations growing, climate change providing newly suitable vector climates, and immunologically naïve populations becoming newly exposed. Sustainable solid waste management is crucial to prevention, specifically in urban environments that favor urban vectors such as Aedes species. We propose that next steps should include more robust epidemiological measurements and propose a framework for solutions-based research.

The most common approach to eliminating accumulated trash in low-and middle-income countries is open burning. For example, in sub-Saharan Africa, more than 75% of waste is openly burned and worldwide an estimated 600 million tons are openly burned annually (30). Open burning of trash is dangerous for human health (6,(31)(32)(33) and the planet, as burning releases toxins into the air that pollute the environment and increase greenhouse gases which contribute to climate change (30).
Policies are slowly catching up to reduce single-use plastic supply, but these policies are only one part of a complete solution (34)(35)(36)(37) to single-use plastic production, demand, and disposal (29) and these policies often face poor enforcement, especially in LMICs (29).
At the same time, the risk of zoonosis has increased with urbanization (38) and immunologically naïve populations are newly at risk for vector-borne disease transmission due to changing geographies of suitable vector climates (39)(40)(41). Vector-borne diseases such as dengue-transmitted by container breeding Aedes spp.-threaten about half a billion people in densely populated areas (42). One very important mosquito vector, Aedes aegypti, which spreads dengue, Zika, chikungunya, and yellow fever, prefers to breed in man-made containers (43,44), such as recyclable plastic containers, tires, and trash. The 2,050 projections of over 6 billion people living in urban areas (45) suggest an impending increase in the risk of infectious disease transmission.
A holistic approach is needed to define the link between vector-borne diseases, urban zoonosis, and solid waste. Here, our objective is to identify research gaps through a review of current evidence on solid waste accumulation, in association with urban zoonosis and biological vector-borne disease risk, and to propose solutions that can interrupt the vicious cycle of solid waste accumulation and human health risks due to infectious diseases.

SYNTHESIZED FINDINGS: PUBLISHED LITERATURE ON VECTOR-BORNE DISEASES, URBAN ZOONOSIS, AND SOLID WASTE
One hundred and fifty three references were identified in the literature review, 73 of which discussed vector-borne and zoonotic diseases. We discuss vector-borne diseases and urban zoonosis in the context of solid waste and highlight major vectors, reservoirs, and diseases.
We identified 45 references related to vector-borne disease risk and solid waste. We categorized the results according to vector [Aedes species, Phlebotomus spp. (sand flies), triatominae, Anopheles species], pathogen (dengue, chikungunya, and Zika viruses, Leishmania, Trypanosoma cruzi, and Plasmodium) and type of evidence (case study, observational, intervention, policy, or review). We summarize the evidence in Table 1 and details are available in Supplementary Material 1.
We identified 16 references related to urban zoonosis and solid waste. We categorized the results according to vector (rodent and canine), pathogen (Orientia tsutsugamushi, Leptospira, Yersinia pestis, Toxoplasma gondii, and rabies virus) and type of evidence (case study, observational, intervention, policy, or review). We summarize the evidence in Table 2 and details are available in Supplementary Material 2.

Vector-Borne Diseases and Solid Waste
Vector-borne diseases, especially Aedes-borne diseases, are associated with solid waste accumulation in the urban environment, even small cups, and wrappers, but vector preferences vary over season and region. Other vectors are associated with trash as a burrow, source of food, and breeding site.
At the household-level, the evidence shows an increase of dengue risk with the presence of cans, plastic containers, tires (70), a lack of consistent garbage collection (44,71,73,74,77), and with garbage accumulation (75).
CHIKV and ZIKV have also been associated with garbage accumulation in ecological models (88,89). However, ecological models can be subject to biases and residual confounding (76). In a case study, Krystosik,Curtis (129) used spatial video and Google Street View in Cali, Colombia to create sub-neighborhood risk surfaces compared with routinely reported clinical cases of dengue, chikungunya, and Zika. Ministry of Health officials and Community Health Workers perceived proximity to unplanned urbanizations without solid waste management as a risk factor for dengue, chikungunya and Zika hotspots. Lack of sanitation can be systematic, for example, 80-90% of housing on Reunion Island was built by squatters resulting in the absence of adequate drainage systems for sewage and rainwater and the lack of properly organized garbage disposal and providing breeding grounds for vector-borne diseases, especially CHIKV (90).
Conversely, removing trash and stagnant water from around the residence is protective (78, 84-87, 94, 99), especially when the government acts with intention and the community is consistently mobilized (85,86). However, results depend on the local ecology of vector breeding (83,87).

Other Vectors
Other vectors use trash as a burrow, source of food, and breeding site. To prevent tick-borne diseases, The US Centers for Disease Control recommends removing old furniture, mattresses, or trash that may give ticks a place to hide (49); however, no other evidence of an association between trash and tick-borne disease was found. Abbasi et al. (111) identified 33 species of arthropods from a Municipal Solid Waste landfill in Urmia, Iran, including medically important species: Periplaneta americana Linnaeus (Blattodea: Blattidae) and Shelfordella lateralis Walker (Blattodea: Ectobiidae). Ahmad et al. (112) report that malaria was associated with low rates of solid waste collection system use. However, this association was based on geospatial analysis that did not control for potential confounders. Others report that Anopheles stephensi also breeds in manufactured containers (130,131).
Community members in rural India report that visceral leishmaniasis-transmitting sand flies breed in trash (105). In two studies, the risk of visceral leishmaniasis increased in the absence of regular trash collection (104,106).
In Yucatan Peninsula, Mexico, residents report triatomines, the vectors of Trypanosoma cruzi, burrow in accumulated trash, cardboard, and rocks (110). Strong entomological (109,110) and clinical (107,108) evidence supports this local perception. Dumonteil et al. (109) conducted entomological surveillance for one year in 38 randomly selected houses and created crude and adjusted models in which they observed a strong association between the practice of cleaning of trash from the peridomicile and house infestation by nondomiciliated Triatoma dimidiate (109). Fortunately, similar   Low rates of solid waste collection system use (112) KAP, Knowledge, attitude, and practice. One study found no effect (103) and one other found a negative association (93).
to Aedes interventions, environmental cleanup is associated with decreased risk of triatomine infestation (110). Clinical evidence also supports these findings. Trypanosoma cruzi infection seroprevalence in Venezuela was associated with the increase of accumulated garbage (108) and household disarray (measured as old and/or damaged artifacts accumulated, materials from construction, inadequate cleaning and free rubbish in the home) (107). Bonfante-Cabarcas et al. (107) speculate that accumulated garbage favors breeding of T. cruzi reservoirs (rats, mice, and opossum) and provides long-term refuge with immediate food sources for insects to reproduce and colonize the house for a long time, increasing the probability of intra-domiciliary vector transmission of T. cruzi.

Urban Zoonosis Associated With Solid Waste
Urban zoonoses, specifically those transmitted by rodent and canine reservoirs, are associated with solid waste, especially when garbage accumulates over time creating burrowing sites and food for reservoirs. In a review of neglected tropical diseases and their impact on global health and development (50), Hotez states of zoonoses: "Of relevance to the NTDs, the poorest favelas do not benefit from regular garbage collection or sewage treatment, thereby creating excellent niches for rats and stray dogs." Rodents and canines directly transmit disease of importance to urban zoonosis (123,125,132). Solid waste accumulation is an important factor for urban rodent and canine feeding and sheltering strategies One study found no association (119).
Frontiers in Public Health | www.frontiersin.org (126) and can be used as a proxy in the absence of reliable data on rodent distribution in the city (117,126). Presence of rubbish increased risk of scrub typhus (120); Toxoplasma infection in owners and their domiciled dogs was associated with dirty yards (126); and the bubonic plague has historically been associated with solid waste (121,122). Leptospirosis is associated with dogs (123, 125), accumulated refuse (114), garbage (113,123) and open containers and debris in the peri-domestic area (123,125). For example, leptospirosis emergence in Marseille, France is linked to garbage collection strikes that contribute to the expansion of the rat population (113). Among slum residents from Salvador, Brazil, residence <20 m from accumulated refuse was associated with increased odds of previous Leptospira infection (114). Residents of another urban slum in Salvador identified improving trash collection as necessary to control leptospirosis in their community and reported current payment for private trash collection service to avoid trash accumulation in their community or a willingness to pay for this service. Residents reported removing trash on a daily basis but identified that trash cans are >50 m from their homes (118). Leptospira interrogans and L. icterohaemorrhagiae are pathogens of severe diseases that may cluster in urban areas where trash accumulates (123) but are also found in rural households in peri-domestic open containers (debris found around the household areas including buckets, pails, jars, barrels, and old tires) (123). Evidence shows leptospirosis infection clusters at the household level (48). During a leptospirosis outbreak in Western Rio de Janeiro, Brazil, cases were associated with lower access to solid waste collection, measured as a percentage of households served by municipal solid waste collection (116), and waste accumulation was used as an indicator of probable rat presence (117).
Conversely, in Federal District Brazil, leptospirosis infection was negatively associated with population access to public services: sewage network, treated water network, and public garbage collection services (115); and in Salvador, Brazil, there was no association between leptospirosis infection and peridomiciliary trash accumulation (119).

Framework for Solutions-Based Research
Here we propose a framework for solutions-based-research in three areas: innovation, education, and policy.

Lessons Learned From Previously Proposed Frameworks
Efforts to promote circular economies in plastics are gaining international attention (29,133,134). The United Nations Environment Programme published 'Single-Use Plastics: A Roadmap for Sustainability, 2018 (29). However, it noted policies and regulations have recently been established and lack monitoring and accountability and suffer from poor implementation. Hawken discusses the short and long term costs and benefits to multiple solutions to Reverse Global Warming (133). However, the solutions require significant investment from business and government to change without a focus on upstream education and innovation. Precious Plastics (134) focuses on the community engagement aspects of reusing plastics but fails to integrate with upstream policy. Examples of successful recycling exist in the metals industry (135-137)-aluminum (135,136), and steel (137) are recycled and traded as commodities globally.
Perhaps the most common framework is "re-use, reduce, and recycle." Reusing and recycling receive ample attention given the technology involved, yet trends in the recycling industry are changing: China is no longer accepting foreign trash for recycling (138). Reusing is also challenging as few types of plastics are highly coveted and reusable. The poorer quality plastics are simply trash-unable to be reused or recycled. Therefore, while reusing/recycling/introducing plastic alternatives all have their place, reducing the consumption and sale of single-use plastics is key. Therefore, we are adapting the previously touted framework, emphasizing reduction, and encouraging a circular economy for re-use and recycle.
Building on previous frameworks (29,(133)(134)(135)(136)(137), we propose a framework (Figure 1) to reduce vector-borne disease risk and urban zoonoses from exposure to solid waste. Given the importance of intervening at the interface of solid-waste and disease-vectors-and-reservoirs, the framework creates a knowledge-to-action plan using policy and innovative plastic alternatives to decrease the upstream plastic supply, education and art to decrease the downstream global demand for plastic, and innovation to generate profitable uses for currently produced and consumed single-use plastics. The desired result is an action plan to create a circular economy of trash and reduce FIGURE 1 | Framework for solutions-based research: upstream innovation research, upstream governance and policy, and downstream education. Recognizing that the current practices and incentive structures that drive these practices are inadequate to address the volume of trash generated globally, different approaches are needed to manage the growing waste problem. Notes for the symbols in the circle. Disease vectors and reservoirs *Depends on climate suitability and duration of accumulation; Infection and Disease **Depends on vector human contact, circulation of pathogen, and susceptible individuals; Poverty is † Associated with lack of municipal waste services; Solid waste accumulation refers to † † Non-biodegradable materials which are not incentivized for recycling. the supply and demand of single-use plastics and to cultivate empowered, educated, and healthy communities that resist trash accumulation to improve health via reduced vector-borne diseases and improved air quality. The expected impact relates to the critical need to understand how the complex system that generates and discards so much trash might be tweaked, so that less trash is produced or trash is put back into either the economic or ecological cycle. As current options are insufficient, we propose solution-oriented research to either better adapt these options or to create whole new options for plastics disposal, recycling, and reuse and discover possibilities for a future without disposable plastics through policy, education, and innovation. The evidence is summarized in Figure 1 and details are available in Supplementary Material 3.

Upstream Innovation Research
Profitable upstream innovation research can decrease supply and improve the processing of solid wastes in an increasingly urbanized and market-based world. Immediate barriers are cost and scalability.
In his 2017 best-seller, Drawdown (133), Hawken discusses the possibility of converting up to 90% of current fossil-fuel based plastic production to bio-based production. However, he warns that the solution must include proper separation and processing to fulfill the goal of sustainable material. Innovation in this field is currently working to drop the price below that of current fossil-fuel-based production. According to a special report commission by the European Polysaccharide Network of Excellence and European Bioplastics, 90% of current plastics could be derived from plants (139). Zhang et al. (140) analyze sustainable materials, defined as a class of materials that are derived from renewable feedstocks and exhibit closed-loop life cycles including aliphatic polyesters and polycarbonates. They also discuss recent advancements that lower the technological barriers for developing more sustainable replacements for petroleum-based plastics including biopolymers (141)(142)(143) and agro polymers (144)(145)(146).
Two aspects of sustainable materials to consider are biodegradation (147)(148)(149) and bioremediation (150)(151)(152)(153)(154)(155). Narancic and O'Connor (150)(151)(152)156). We found bioremediation-whereby animals and bacteria can break down plastics into biodegradable products-to be particularly interesting. Narancic and O'Connor (156) review the advances and possibilities in the biotransformation and biodegradation of oil-based plastics, including bio-based and biodegradable polymers, end-of-life management of biodegradables, and a circular economy to reduce plastic waste pollution. New fungi species are biodegrading polyester polyurethane: Pestalotiopsis species (150) and Aspergillus tubingensis (151). Ideonella sakaiensis bacteria break PET (Polyethylene terephthalate) into terephthalic acid and ethylene glycol in 2 weeks (152). Mealworm larvae can digest Styrofoam in <24 h with no cost to survival over 1 month, converting 47.7% of the ingested Styrofoam into CO 2 and biodegradable residue (153,154). Wax moth Galleria mellonella caterpillars can biodegrade polyethylene bags (155). These methods are especially attractive as they require no behavior change and are sustainable and, in some cases, beneficial to the species performing the biodegradation. Yet, these pilot studies need to be studied at scale and adapted to local context to understand feasibility.
Repurposing trash for profit seems like a viable market-based solution (134,(157)(158)(159)(160)(161) but does carry some risk of exposure to contamination (162)(163)(164) for entrepreneurs and end-users depending on the type of materials and the processes used and this risk should be taken into consideration early in the process. One popular use case is waste-to-energy analyzes waste-to-energy strategies and concludes that for a net implementation cost of $36 billion, a net operational savings of $19.82 billion and 1.1 gigatons of CO 2 reduction could be gained. For example, Sweden currently converts 50% of household wastes to energy (161). Yet, Haken warns that this is only a transitional strategy, citing emissions of heavy metals and toxic compounds, even in state-of-the-art facilities. Several reviews discuss waste-toenergy regarding technological options and challenges (165)(166)(167)(168)(169), integrated solid waste management in developing countries (170,171), and the environmental impact (172,173).
These innovations must come equipped with a knowledgeto-action plan and pilots of these small-scale or theoretical solutions and engagement of external stakeholders such as existing companies, policymakers, and community groups.

Upstream Policy
Policymakers are uniquely positioned to make political and normative changes relatively quickly but struggle with enforcement, sustainability subject to elected officials, and community buy-in.
Policymakers are uniquely positioned to prevent and solve public health crises, in collaboration with public health officials and communities (84,(174)(175)(176). For example, Chen et al. (84) reported that discarded containers account for 25.4% of Aedes vector breeding sites in endemic regions of Taiwan preintervention. In 1988, the Waste Disposal Act was amended to make manufacturers, importers, and distributors responsible for the proper recovery, treatment, and recycling of packaging and containers which become an environmental menace. Noncompliance resulted in business suspension. A waste recycling system was established, and a breeding site reduction campaign was promoted for waste management. The authors reported a 98% decrease in dengue incidence reported to the Department of Health from 1988 to 1993. Several countries in Africa continue to implement bans to curb single-use plastic bags which clog drains, sewage systems, or hold rainwater, create breeding grounds for vectors (34).
Experts call for more policy solutions (177)(178)(179) and there is evidence that policy agendas can be influenced by popular norms (34,180). Others argue that informal associations such as waste-picker cooperatives (35,36,181,182) should be strengthened to improve solid waste systems. However, enforcement of such policies may be difficult, especially for nations with challenging processes or non-existent systems (37), and others call for a more community-based approach to increase participation in sustainable waste management (183)(184)(185). Businesses that use disposable packaging can also be engaged through social pressure and responsibility to adopt sustainable corporate practices (186,187) and recoup disposable packaging for recycling.

Downstream Education to Decrease Demand
Community-based education and communication have the potential to change norms and create sustainable change but require greater initial investments to tailor and iterate community-based approaches.
Eagle et al. (188) argue that social marketing principles (183,189,190) paired with education (75, 85-87, 182, 183, 189-191) and policy (section upstream policy) can intervene to change behavior to positively impact plastic pollution using a transdisciplinary approach to identify barriers to and enablers of sustained behavior change.
Creating awareness about the crisis and health and environmental risks surrounding plastic pollution will not immediately decrease supply, but information may increase social pressure and responsibility to adopt sustainable practices at household (75,85,183,192), community (75,86,87,99,183,191,(193)(194)(195)(196), and corporate levels (186,187)  Where small discarded containers presented the main problem, groups experimented with solid waste management, composting and recycling schemes. Many intervention tools were locally produced, and all tools were implemented through community partnership strategies. All sites developed socially-and culturallyappropriate health education materials. The study also mobilized and empowered women, students, and community groups and at several sites organized new volunteer groups for environmental health.
Tana et al. (86) built an innovative community-centered dengue-ecosystem management intervention in Yogyakarta city, Indonesia and assessed the process and results. The intervention results included: better community knowledge, attitude, and practices in dengue prevention; increased household and community participation; improved partnership including a variety of stakeholders with prospects for sustainability; vector control efforts refocused on environmental and health issues; increased community ownership of dengue vector management including broader community development activities such as solid waste management and recycling. Tana et al. (86) note, the community-centered approach needs a lot of effort at the beginning but has better prospects for sustainability than the vertical "top-down" approach.

Summary of Main Findings
Although evidence suggests the link between plastic pollution/solid waste and human disease, measurements are not standardized, confounders are not rigorously controlled, and the quality of evidence varies.
Here we have reviewed the available evidence for solid waste accumulation impact on biological vector-borne diseases. We hypothesized that plastic pollution, including unused plastic bottles, containers, plastic bags, and tires, is a major environmental health risk and promotes vector-borne diseases (VBD) such as dengue, chikungunya, Zika, malaria, and other VBD transmission. We conclude that solid waste accumulation is a risk factor for zoonotic and vector-borne disease transmission. However, measurements are not standardized, (107,123,197) and confounders are not rigorously controlled (106,112,123,197,198).
In the context of vicious cycles of solid waste accumulation, poor health, and poverty, policymakers use estimates of disease transmission, burden, and risk to inform the allocation of limited public health resources; thus, it is imperative epidemiological estimates control for known confounders and employ standardized measurement constructs (Table 3). Additionally, if surveillance data are used, hybrid surveillance (199,200) should be employed to correct for known surveillance biases. A framework for solutions-based research is also critical to guide research priorities.
Of note, the landscape of single-use plastics innovations and policy is developing rapidly. For example, Christensen et al. described in April 2019 a next-generation plastic to incentivize recycling in closed-loop life cycles (201,202). This new plastic can be disassembled and reassembled without loss of performance or quality, even in mixed waste streams (201). And the political trend is gaining momentum-in May 2019, 187 countries agreed to add plastics to the Basel Convention, a treaty that regulates the movement of hazardous materials from one country to another (202).

Limitations
We only included published literature and abstracts in English, Spanish, and Portuguese. We did not have access to primary data and relied on the interpretation of the publishing authors. Multiple studies included relied on surveillance data which did not correct for selection bias. Multiple studies included did not control for variables possibly associated with both exposure (trash) and outcome (disease), for example, socioeconomic status (SES), access to health care, or climate. The data needed to understand the context-specific risk factors are not yet available; particularly, the authors noted a paucity of data from sub-Saharan Africa, where policies and regulations have recently been established (29). Interestingly, although geography was not constrained in the review, most studies identified were from low-and middle-income tropical countries.
After completing our search, we constrained the scope to only urban zoonosis associated with wild mammals and domesticated animals of non-agricultural interest such as dogs and cats. This may exclude some important research related to geographical areas where cows or other domestics animals can serve as crucial reservoirs of important etiological agents.

CONCLUSIONS
Despite gaps in the research base-lack of standardized measures and residual confounding-it is clear solid wastes breed vectorborne diseases and urban zoonoses.
Future populations are at increased risk-disease epidemics are increasing in scope and scale (42) with urban populations growing (38,45), climate change providing newly suitable vector climates (39)(40)(41), and naïve populations becoming newly at risk, sustainable solid waste management is crucial to prevention, specifically in urban environments that favor urban vectors such as Aedes species and in poor urban and rural populations which lack access to municipal solid waste services.
We propose a framework for solutions-based research which includes upstream innovation research, upstream policy, and downstream education to decrease demand for singleuse plastics.

AUTHOR CONTRIBUTIONS
JF, AK, FM, and AL conceived of the initial idea and secured funding. AK drafted the initial manuscript. AK and GN conducted the literature search. LO and AL provided editing on intellectual content. All authors contributed to manuscript revision, read, and approved the submitted version.

ACKNOWLEDGMENTS
We gratefully acknowledge the assistance of the Stanford School of Medicine Lane Librarian in constructing initial literature search terms.