In 1897, Ronald Ross conclusively demonstrated that mosquitoes were not just a “nuisance”, but vectors transmitting the deadly malaria parasite. Walter Reed’s discovery that another feared disease, yellow fever, was vectored by mosquitoes quickly followed. In the nineteenth century, the incidence of these two diseases and other mosquito-borne pathogens in Europe and North America was comparable to that of many tropical regions [
1]; by mid-twentieth century, both were eradicated as public health concerns. While mosquito-borne diseases remain largely suppressed, tick-borne diseases are rampant, comprising over 90% of all vector transmitted pathogens in the US and Europe [
2‐
4], with Lyme disease becoming a common infection with estimated 240,000–444,000 annual infections tripling between 2004 and 2016 [
3,
5,
6] with much higher most recent estimates [
7] The spirochete responsible for Lyme disease was described in 1982 [
8]. Almost 40 years post-discovery, its incidence continues to increase, along with other tick-borne diseases such as ehrlichiosis, babesiosis, and anaplasmosis [
3].
Why did malaria and other mosquito-borne diseases elicit effective interventions while Lyme and the other tick-borne diseases have not? We examine this question to draw lessons needed to ensure future success against one of the most challenging contemporary public health problems.
Success and failure in vector-borne disease control
The decline of the disease in the human population is the most significant indicator of a public health program’s success. The US anti-malaria campaign was thus tremendously successful, while anti-Lyme efforts are failing (Fig.
2a, b). Malaria consistently declined in 1920–1948 with 50% morbidity reduction every 5 years excepting the Great Depression [
17,
28] led by the hyperendemic areas (Fig.
1), where the number of high mortality counties declined from 96 to 14 between 1935 and 1942 [
31]. In contrast, the Healthy People 2010 modest goal of 50% reduction in Lyme diseases incidence from 17.4 to 9.7 per 100,000 [
65,
89] was not met; instead the incidence had increased threefold.
The underlying biological, technical, and societal causes for these two very different outcomes are complex. Epidemiologically, human to human transmission is more easily interrupted because both the hosts and the vector populations can be targeted to drive the basic reproductive rate (R
0) below the rate of replacement. For malaria, vector control reduced the number of the pathogen carriers; at the same time, sanitary measures lessened the susceptible human population [
90]. Targeting wildlife hosts is much more difficult proposition, which explains why pathogens with wildlife reservoirs continue to persist. This challenge is shared between all zoonotic diseases regardless of vector identity. One of the more well-known examples is West Nile virus, a mosquito-borne zoonotic disease, which remains difficult to control because its wildlife hosts are widely distributed in the environment, and virus amplification is governed by many stochastic processes [
33,
34].
Biologically, the difference between mosquitoes and ticks as vectors is important [
91]. Daily survival probability is very low for mosquitoes and is high for ticks translating into low population stability but higher transmission potential for mosquitoes compared to an enduring reservoir for infection but lower transmission for ticks [
91]. Consequently, tick-borne diseases tend to have lower incidence rates compared to mosquito-borne diseases (Fig.
2). Adult mosquito mobility and intense feeding by immature mosquitoes make them more susceptible to dispersed or ingested insecticides. Aggregated aquatic mosquito stages are easier to target. Ticks inhabit much more cryptic environments, are spread over the suitable habitat, and have only one bloodmeal per each life stage [
39,
91]. Tick exposure is mostly peridomestic rather than recreational in the endemic areas of the United States [
92,
93]. While recreational exposure on mostly public lands can be more easily mitigated by landscape modification, application of pesticides, and host management [
73], residential exposure is more difficult to alleviate due to lack of access, required permissions, highly fragmented habitat, and regulatory impediments.
From the technical perspective, mosquito control was a mature science-based approach with effective techniques and products by the 1930s. Mosquito control personnel could apply chemical larvicides, use predatory killifish for biological control, or make the habitat inhospitable by drainage. No comparably effective tick products or techniques exist and the current methods of targeting the host species and habitat modification have much less impact on the tick populations.
Nevertheless, these challenges cannot fully explain the failure of public health programs since there are historical examples of successful tick-borne disease control. The most instructive cases of tick-borne encephalitis (TBE) and tularemia come from the former Soviet Union (Fig.
2c, d). The anti-TBE campaign focused chiefly on its vector
, Ixodes persulcatus using DDT applications [
58,
94]. The peak of the campaign in 1965–1971 was accompanied by sharp declines in TBE incidence [
57] (Fig.
2c). With the cessation of DDT applications in the early 1970s, the incidence of TBE steadily increased remarkably similar to the DDT impact on mosquito populations in North America [
95]. The manifold increase in TBE cases in the former Soviet Union and Europe occurred despite existence of highly effective TBE vaccines [
96,
97]. Austria, where 85% of the population was vaccinated, was the only country experiencing TBE incidence decline [
97]. However, relying solely on a vaccine does not work well in multi-pathogen multi-vector systems [
58], and Austria has one of the highest Lyme disease burdens in the world [
2,
4].
Arguably, the only long-term success story against a tick-borne disease is tularemia (Fig.
2d) [
59,
60]. The enzootic cycle was suppressed by host removal, tick vectors were targeted by DDT applications over vast areas, strict sanitary procedures were implemented, and human protection was conferred by an effective vaccine administered on a mass-scale [
60]. As a result of this integrated pest management (IPM) approach tularemia cases fell from a high of approximately 150,000 annually [
98] to a few hundred in 1945–1959 stabilizing at < 0.5/100,000 in 1965 (compared to ~ 5.5. in 1950) and maintained by minimal vaccination in the disease hotspots [
59]. The effect of DDT was strong in reducing disease incidence, but the resilience of the system seemed to depend on other factors, such as vaccination rate and host removal. More widespread distribution of Lyme disease may present more substantial challenges for these methods.
These examples bring us to the most crucial aspect of vector-borne disease control - the societal dimension - political, administrative, financial, and legal. The importance of socioeconomic changes for the fight against malaria is well documented [
99,
100]. In 1943, the National Malaria Society presidential address stated “there is much to learn about malaria, we already have more information than we are using to control the disease…the main obstacles in the way of malaria control today are not so much technical, as they are social” [
101], i.e. absence of educated public opinion, inadequate administrative principles, and minimal transfer of knowledge between research and applied control, all of which are valid today.
In the realm of public opinion, Lyme advocacy groups continue to drive public attention toward clinical aspects of the disease and the chronic Lyme controversies [
102]. The general public would be hard pressed to find any information on vector control or other real long-term solutions to this problem. Very often novel proposals of dubious nature (such as transgenic mice or ticks) take the front stage, while very little attention is paid to developing public support for the large-scale interventions that will eventually be required to lessen the burden of tick-borne illness.
The same despondent attitude seems to prevail in public health professional organizations. The CDC, a federal agency that was created to fight malaria, doesn’t even have a dedicated tick-borne disease branch despite the fact that the Lyme epidemic is becoming comparable to malaria, at least in the geographic extent if not intensity (Fig.
1). It is hard to envision the public health authorities in the 1930s promoting personal protection as the only way of eliminating malaria. Yet, the organizations tasked with public health protection nowadays do not hesitate to shift the burden to individuals and homeowners. The outcomes are clear when the long-term epidemiological data are compared: while malaria disappeared completely within two decades of vigorous efforts, Lyme disease has been on the rise over the last 40 years (Fig.
2a, b).
The repeatedly heard argument about the lack of resources for tick-borne diseases is refuted by The National Academy reporting funding levels comparable to those during the malaria eradication program (Table
1) [
13]. However, 95% out of approximately $100 million annual appropriations are spent on fundamental molecular and clinical research. This imbalance greatly impedes the efforts to find effective control options for tick-borne diseases [
87]. These major investments have failed to produce a single useful product for tick control, host management, or a marketable vaccine. The only significant advancement in tick control of the past 40 years, the 4-poster system, was entirely supported by USDA grant [
103], and not by the agencies with direct responsibility to protect public health. Contrast this with malaria, where the federal government was directing anti-malaria efforts, providing professional support, labor, development, and eventually delivering a new synthetic insecticide (DDT) to finish the job, with main resources directed toward actual vector control.
Collaboration between the federal government, academia, and local public health agencies on Lyme disease control is very limited in stark contrast to anti-malaria operations staffed, funded, and trained by the US Public Health Service and Rockefeller Foundation [
12,
14,
17,
24,
104]. US Public Health scientists were not only conducting surveillance and research studies, but spent a considerable amount of their time supervising fieldwork [
14]. Three federal public health stations engaging in applied research and surveillance were established in the hardest hit areas [
105]. None of this federal infrastructure has been put in place during the 40 years of the current tick-borne disease epidemic.
In the early part of the twentieth century, environmental protection was not of political concern. Modern tick control methods must not only work, but be environmentally compatible. Tick control has a strong relationship with wildlife management and a new level of interactions with agencies and stakeholders unfamiliar to health authorities. The Lyme disease epidemic is so closely tied to deer overpopulation that control measures will require actively managing and reducing deer populations, at least in heavily populated areas [
74].
Realization that control of the vector was essential to anti-malaria efforts engendered the political will and public policies enabling an integrated program of environmental management aimed at that vector to proceed. To emulate this success, the public health agencies, the political system and the public must come to a similar evolution in public policy. First, there must be a realization that tick-borne diseases cannot be controlled without reductions in vector populations. The relationship between ticks and deer must be recognized as the key factor in designing control efforts. At that point, all the involved agencies and stakeholders must come to accept that deer overpopulation must be part of an integrated solution. This becomes even more important as exotic tick species that feed on deer, such as the Asian longhorned tick, are introduced in the US [
106]. Research and development (R&D) efforts can then most profitably be directed at innovative methods for reducing deer populations and controlling ticks on deer, where they are most concentrated and vulnerable. This change in paradigm to allow effective control of tick-borne diseases will require strong leadership, especially on the Federal and State levels. Potential steps to improve the coordination among the different levels of government have been outlined [
37], with the key component of increasing resources and capacities at the local level where practical vector control is carried out. While changing attitudes and policies with respect to the management of tick and deer populations will take considerable time, it will never happen if not attempted. Meanwhile, R&D funds for tick control need to be greatly increased to reflect the level of threat that exists. The most important change, however, will have to be in the “hearts and minds” of our public health and environmental managers that Lyme and other tick-borne diseases are a problem that demands serious, rationally designed large-scale control measures based on cooperation of all involved parties and significant support by the federal government.