August 2022 - Volumes

The Economics of Resistance

It would be extremely difficult to calculate, with any high degree of accuracy, the global economic impact of insecticide resistance. For starters, we must consider that insect management plays a pivotal role in a variety of sectors – agriculture, home and garden, forestry, structural applications, and vector control. Analysis of the totality of economic impacts arising from resistance in any one of these sectors quickly becomes a complicated interplay of variables that interact within that given system.

To account for the full economic impact, one must layer in the amount being spent on insect management and how much of that investment is lost to resistance, but also the economic impact of losses to the overarching objectives of a given program.

To calculate the impact, you must first calculate what is at risk.

Let us focus on vector control for a moment. According to the World Health Organization (WHO), vector borne diseases account for 17% of all infectious disease and more than 700,000 deaths annually. In this context; we research, analyze, and report on outbreak events and may consider the impact of resistance through that lens. To do so, we must also account for variability between local and regional infrastructures, strategic and operational approaches to vector control, available technologies, the social and political climate of the areas affected, as well as surveillance activities and the quality of data coming from reporting systems, if any.

Extend this view to cross all geographies and vector borne diseases, and the complexity of calculations quickly becomes mind numbing. However, there is a simpler way to think about resistance that is even more pressing. What is the cost of resistance when faced with a future (or imminent) epidemiological event? What is the incremental cost of having to rely on tools that are somewhat, but not entirely ineffective? Costs that manifest not only as dollars but also quality of life? Since the overarching objective of vector control is reducing the incidence of vector-borne disease, then any impacts of insecticide resistance on disease burden must be considered.

Insecticide Resistance in Vector Control

Statistical analysis of the economic impact of resistance is hard to come by. Researchers at North Carolina State University suggest the cost of pesticide resistance to US agriculture is in the neighborhood of $10 billion per year.1 But when the costs include human capital, calculations must include direct costs such as medical costs and the cost of vector control, but also loss of productivity, compensation for businesses losses, and the research and public health programs aimed at mitigating the risk.

As we start to unpack the impact of resistance in vector control, not all target insects and disease are alike. According to the Centers for Disease Control and Prevention (CDC), ticks, for example, may account for up to 77% of all the vector borne disease incidence in the US.2 However, insecticide resistance is not considered a major challenge in that space because wide-area applications for tick control are not the norm. Instead, interventions for tick-borne disease focus more on community awareness campaigns and the application of insect repellants onto clothing.

Other diseases, such as Sleeping Sickness (Tsetse Fly) and Chagas disease (Kissing Bug), provide similar challenges for wide area control. Found mainly in poverty-stricken areas, these diseases depend on localized pesticide applications and drug therapies for the afflicted. WHO estimates the global burden of Chagas disease to be $7 billion per year.

Leishmaniasis is a debilitating disease of the tropics caused by infection with Leishmania parasites, spread by the bite of female sandflies, to which WHO estimates as many as 310 million people at risk. Like malaria, interventions for this disease are heavily dependent upon insecticide-treated nets and indoor residual sprays (IRS). Significant advancements were made against Onchocerciasis (see Public Health Landscape, October 2020) using vector control of blackflies combined with the drug therapy, ivermectin.

While insecticide resistance plays some role in management of these important diseases, economic impact becomes even harder to gauge. Our best insights on the impact of insecticide resistance in public health might rather come from mosquito-borne illnesses, where insecticide interventions play a direct and pivotal role.

Major Insect-Vectored Diseases by Region

MAJOR-INSECT-VECTORED-DISEASES-BY-REGION
Insect vectors and diseases listed among the top-five in importance, by geographic region. Source: CMETE. Graphics adapted from World Health Organization.

Global Risk Map: Aedes-Vectored Diseases

08 Global Risk Map Aedes Vectored Diseases
Global, country-level occurrences of selected arboviral diseases vectored by Aedes mosquitoes (2018).
Source: https://www.sciencedirect.com/science/article/pii/S1201971217303089

Chikungunya (CHIKV) is a mosquito-borne, neglected tropical disease transmitted by Aedes mosquitoes in a viral transmission cycle that includes rodents and small mammals. According to the WHO, it is the second most widely distributed arboviral disease after dengue. It was first identified in 1952 in Africa but has grown in importance over the last two decades. While other viral diseases can be mild, Chikungunya is rarely asymptomatic. The disease Chikungunya is known for its large resource burden and decreased quality of life.3 With the disease, comes fever and pain to the joints, which can be severe. The susceptible will have inflammation and be subject to chronic arthritis and long-term pain, with a significant diminution in quality of life. Approximately 14% of CHIKV patients develop chronic arthritis.4 

No treatment is available.

Endemic in many African and Asian countries, Chikungunya has been reported in 106 countries and made its way to the Americas in the 2000s. About 200 travel-related cases of Chikungunya were recorded in the US between 2006 and 2013. It wasn’t until July of 2014 that the first U.S. local transmission of the disease was confirmed in Florida. An outbreak across the Americas began with a confirmed case in December 2013. This led to an estimated two million cases of Chikungunya, suspected or confirmed, by April of 2016, spanning 45 countries or territories in Central, South, and North America.  

One interesting study on the economics of Chikungunya centered around an outbreak on the U.S. Virgin Islands. It began with the first local transmission in June 2014. By February of 2015, almost 2,000 suspected cases emerged from a population of just 103,574, or about 1/50 of the island’s residents. 

As with many other vector-borne disease events, underreporting likely plagued the statistical analysis. Since a public awareness campaign raised during the event made residents aware there was no treatment available, researchers speculate that many of the afflicted may not have sought medical attention. Of the laboratory confirmed cases, 89% missed work for as many as six days, 33% had to make multiple visits for health care, and 9% were hospitalized.

Researchers placed the total cost of the US Virgin Islands outbreak somewhere between $14.8 million and $33.4 million depending on the actual percentage of symptomatic infections, the degree of underreporting, and the employment rate among reported cases. This amounted to approximately 1% of the territory’s GDP. Indirect costs (lost wages, lost productivity, and costs resulting from the need for home and childcare that would otherwise not be incurred) were thought to be between four and six times higher than the direct cost of medical care and mosquito control from the event.

Since there is no treatment available, mosquito control is listed as the primary prevention for Chikungunya. This brings the implications of insecticide resistance quickly to light. Larvicides are often employed to breeding sites to keep mosquito populations down, but adulticides are indispensable when outbreaks occur. Pronounced resistance to pyrethroid-based and organophosphate interventions is a well-known challenge to mosquito abatement on a global scale.

Dealing with Dengue

Dengue is the most prevalent viral mosquito-borne illness in the world, with more than 3.9 billion people at risk across 129 tropical and sub-tropical countries and territories in Asia-Pacific, the Americas, the Middle East, and Africa. One estimate places the number of global dengue infections at 390 million cases per year.5  According to WHO, dengue incidence has increased by a factor of 30 over the last five decades – an effect of rapid urbanization. In 2013, estimates of the total cost of dengue burden ranged from $1 billion to $8.9 billion globally. The disease is vectored primarily by Aedes mosquitoes, which lay their eggs in containers and are closely associated with human dwellings.

Among 32 countries with dengue deaths reported, the mortality rate is in the neighborhood of 1/6000. While this rate is relatively low compared to other vector-borne diseases, dengue is known to have a tremendous impact on quality of life. The long-term joint and muscle pain associated with chronic dengue infections brings economic stress to the social fabric of affected areas, their health care systems, and within households of the afflicted. 

WHO estimates the cost of dengue to the Super Region Asia Oceania at $4.8 billion, and at $1.7 billion within Latin America and the Caribbean. Globally, WHO estimates that the average Disability-adjusted Life Years (DALYs) lost to dengue rose from 1.14 million globally in 2013 to 2.92 million in 2017.6

How does resistance figure into this equation? The answer begins with WHO guidelines for dengue control, which prominently include “vector control strategies comprising environmental management, source reduction, and chemical interventions (adulticide and/or larvicide).” Whenever the effectiveness of these recommended interventions is compromised, there is an unavoidable impact on cost to society.

Need for a Global Vector Control Response

In 2017, the World Health Organization (WHO) published its Global Vector Control Response 2017–2030 to help in addressing the growing challenges of global vector-borne disease. The document established clear objectives based on the need for vector control in mitigating the effects of vector-borne disease:

  • Transmission and risk of vector-borne diseases are rapidly changing due to unplanned urbanization, increased movement of people and goods, environmental changes, and biological challenges – such as vectors resistant to insecticides and evolving strains of pathogens. 
  • Never has the need for a comprehensive approach to vector control to counter the impact of vector-borne diseases been more urgent.
  • Large population areas are at risk of emergence and expansion of arboviral diseases spread by mosquitoes.
  • Many countries are unprepared to address these challenges. 
  • The strong influence of social and environmental factors on vector-borne pathogen transmission underscores the critical importance of flexible vector control delivery and monitoring and evaluation systems that support locally tailored approaches.
  • Re-alignment of national programmes is required to optimize implementation of interventions against multiple vectors and diseases, and to maximize the impact of available resources.
  • Response require not only the availability of effective, evidence-based control interventions, but also well-trained government staff who can build sustainable systems for their delivery.
  • Multiple approaches that are implemented by different sectors will be required.

Dengue Incidence and Cost

Dengue-Incidence-and-Cost
Dengue incidence per 100,000 population (A) and cost per head of symptomatic dengue infections (2013 US$; B). Source: http://dx.doi.org/10.1016/S1473-3099(16)00146-8

Economic Burden of Zika Virus

In 2016, much of the Americas mobilized in response to a Zika virus outbreak. The arbovirus is vectored by Ae. aegypti and Ae. albopictus, the same mosquitoes that vector dengue and Chikungunya. Zika was characterized by its particular threat to pregnant mothers and unborn children, along with the fact that the disease could be sexually transmitted. One highlight from the response was that Zika transmission was interrupted for the first time in history – in the U.S. – thanks to preparedness and a full-scale mosquito control program that included wide-area aerial treatments of a biological larvicide in combination with adulticides.

According to estimates by the World Bank, estimates of the short-term economic impact of Zika in the Latin America and Caribbean region totaled $3.5 billion.7 The study assumed four million infected within the region with as many as 750,000 people losing at least one week of work.

2016 Zika Outbreak: Estimated Economic Impact 

Carribean and South America

3 Zika Costs
Source: World Bank Group

While the disease is considered largely asymptomatic (only about 20% of cases result in sickness), stark images of infants born with microcephaly dominated the media for much of late 2016. While relatively rare, images of the birth defect had a dramatic impact on tourism in and around the region. The estimate lifetime medical cost to care for a child with microcephaly is $10 million.8 The total commercial and governmental economic cost was between $7 and $18 billion, according to a report by the United Nations Development Programme.

As with previously mentioned diseases, much of the direct cost of the Zika outbreak was spent on mosquito control. Biological larviciding was shown to impact the transmission cycle in the U.S., but adulticides were also critical in all affected areas. Since adulticide resistance is population-specific, it remains difficult to calculate the exact impact from loss of effectiveness and/or increased expenditure on materials. If even one pregnant woman were bitten by an infected, resistant mosquito; the cost would be in the millions.

Americas West Nile Outbreak

West Nile Virus represents another arboviral disease cycled between birds and mosquitoes, which infect humans. Discovered in Uganda in 1937, the disease expanded slowly over the next several decades through the Middle East, Eastern Europe, and Russia. In the 1990s, a new strain emerged and was detected in Romania, parts of Europe, Russia, and Israel.9 Then in August of 1999, New York City hospitals were struck by an unusual number of encephalitis cases. At the same time, captive exotic birds and crows began to die of encephalitis in and around the Bronx Zoo. West Nile was eventually identified as the culprit, its first-ever appearance in the Western Hemisphere.

Unlike the Aedes-vectored diseases, WNV is vectored by Culex mosquito species, which made northern regions susceptible. By 2003, 45 states reported WNV approaching 10,000 cases nationally. By 2012, all 48 continental United States and the District of Columbia had experienced local transmission of WNV. To date, more than 30,000 cases in the U.S. have been reported with more than 1000 deaths. In 2002 alone, healthcare costs attributed to West Nile virus in the U.S. totaled $200 million.

Economic impact studies were conducted surrounding two local outbreaks: St. Tammany and Tangipahoa Parishes of Louisiana in 2002 (329 confirmed cases), and Sacramento County, California (163 confirmed cases) in 2005. In Louisiana, estimated direct and indirect costs of the outbreak from June 2002 to February 2003 totaled $20.1 million.8  The cost of healthcare and emergency sprays in Sacramento County in 2005 totaled about $3 million. 9  In all, a total economic impact of WNV infections in the U.S. between 1999 and 2012 has been placed at $778 million for medical costs and productivity losses. Despite this impact, research and funding into WNV have recently declined.

Estimated total cost of West Nile Virus in the United States

7-West-Nile-Numbers
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945683/

Resistance and Malaria

Malaria is widely known as the most prolific killer among vector-borne diseases and accounts for the vast majority of vector-borne disease deaths each year. Of the more 700,000+ vector-borne disease deaths in 2020, WHO estimates that 627,000 people died from malaria. Malaria is vectored by the Anopheles mosquitoes. Nearly half of the world’s population lives in areas at risk of malaria transmission.

Malaria’s pronounced impact and the fact that the majority of malaria deaths are children aged 5 or younger has brought about a significant amount of collaboration and public-private partnerships. Interventions stemming from these efforts have cut malaria mortality by approximately 36% between 2010 and 2020, but the decline has slowed in the past 10 years. WHO reports that scarce resources and socio-economic instability have hindered control activities.10  Today, direct costs from the illness, treatment, and premature death are estimated at about $12 billion per year. 

Insecticide-treated nets (ITNs) are the mainstay intervention against malaria in Africa. Over the past 10 years, the global public health community has distributed more than one billion ITNs into Sub-Saharan Africa, the vast majority of which are treated with pyrethroids.11 . Given the wealth of evidence surrounding the onset of pyrethroid resistance among global mosquito populations, there is mounting concern regarding the potential impact of resistance upon future malaria interventions.

Managing Resistance into the Future

When considering insecticide resistance, it is important to remember it is only one factor in an Integrated Vector Management (IVM) system. Studies have shown an undeniable association between vector control and disease occurrence, and in its Global Vector Control Response 2017-2030 document, WHO leaves little doubt as to the role of IVM in curtailing vector-borne disease. The document lists several opportunities to improve the impact of vector control interventions, among them:

  • Capacity building and the institutionalization and routinization of vector control activities
  • Better data to support the impact of IVM
  • Improved collaboration across ministries, sectors, partners, and networks
  • Adaptation of flexible vector control delivery, monitoring, and evaluation systems that support locally tailored approaches that can be adapted to specific opportunities or challenges. 
  • Development of novel tools, technologies, and approaches such as new insecticides to reduce the burden or eliminate certain vector-borne diseases – especially important in the context of emerging biological challenges, such as vector resistance to public health insecticides.

Footnotes:

  1. Gould F, Brown Z, Kuzma J, “Wicked evolution: Can we address the sociobiological dilemma of pesticide resistance?,” Science, 18 May 2018, Vol 360, Issue 6390, pp. 728-732. https://www.science.org/doi/10.1126/science.aar3780
  2. Rosenberg R, Lindsey NP, Fischer M, et al. Vital Signs: Trends in Reported Vectorborne Disease Cases — United States and Territories, 2004–2016. MMWR Morb Mortal Wkly Rep 2018;67:496–501. DOI: http://dx.doi.org/10.15585/mmwr.mm6717e1
  3. Leora R. Feldstein, Esther M. Ellis, Ali Rowhani-Rahbar, Morgan J. Hennessey, J. Erin Staples, M. Elizabeth Halloran, Marcia R. Weaver, “Estimating the cost of illness and burden of disease associated with the 2014–2015 chikungunya outbreak in the U.S. Virgin Islands,” PLoS Neglected Tropical Diseases, July 2019, DOI 10.1371/journal.pntd.0007563
  4. Pathak H, Mohan MC, Ravindran V. “Chikungunya arthritis.” Clin Med (Lond). 2019 Sep;19(5):381-385. doi: 10.7861/clinmed.2019-0035. PMID: 31530685; PMCID: PMC6771335.
  5. Bhatt, S., Gething, P., Brady, O. et al. “The global distribution and burden of dengue.” Nature 496, 504–507 (2013). https://doi.org/10.1038/nature12060
  6. Knerer G, Currie CSM, Brailsford SC (2020) “The economic impact and cost-effectiveness of combined vector-control and dengue vaccination strategies in Thailand: results from a dynamic transmission model.” PLoS Negl Trop Dis 14(10): e0008805. https://doi.org/10.1371/journal.pntd.0008805
  7. Economic Impact of Zika Virus, Chapter 11, Editor(s): Adnan I. Qureshi. Zika Virus Disease, Academic Press, 2018, pp. 137-142, https://doi.org/10.1016/B978-0-12-812365-2.00012-3.
  8. Zohrabian A, Meltzer MI, Ratard R, et al. West Nile Virus Economic Impact, Louisiana, 2002. Emerging Infectious Diseases. 2004;10(10):1736-1744. doi:10.3201/eid1010.030925.
  9. Barber LM, Schleier JJ, Peterson RK. “Economic Cost Analysis of West Nile Virus Outbreak, Sacramento County, California, USA, 2005.” Emerging Infectious Diseases. 2010;16(3):480-486. doi:10.3201/eid1603.090667.
  10. https://www.cdc.gov/malaria/malaria_worldwide/impact.html
  11. Glunt KD, Coetzee M, Huijben S, Koffi AA, Lynch PA, N’Guessan R, Oumbouke WA, Sternberg ED, Thomas MB. “Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.” Evol Appl. 2017 Dec 4;11(4):431-441. doi: 10.1111/eva.12574. PMID: 29636797; PMCID: PMC5891045.