On June 28^th 2011, the Food and Agriculture Organization for the United Nations (FAO) has officially announced the eradication of rinderpest from the surface of the globe, 10 years after the last recorded case 1 . Thirty years had passed since the previous, and then only, global eradication of an infectious pathogen, namely the smallpox 2 . These examples are the most striking in an array of spectacular achievements of public health interventions coordinated by WHO for the last 60 years. Indeed, numerous pathogens have been eliminated in large areas, such as malaria 3 and plague 4 in Western countries, or yellow fever in Latin America 5 .

Meanwhile, in many tropical countries, infectious diseases continue to exert a major toll on human populations and directly contribute to poverty and economic instability 6 . Pathogen richness is indeed generally higher in the tropics than in temperate areas 7 and in many cases, vector biodiversity further adds to the complexity of the transmission system 8 . Emblematic examples include malaria in Africa 9 where both the parasite and its mosquito vector species have now developed high levels of resistance to the most widely used drugs and insecticides, further jeopardizing control as well as elimination efforts 10 11 . Yellow fever is another frustrating example where the pathogen remains endemic in many countries 12 despite the availability of an easily deliverable (lyophilized) and affordable vaccine 13 and because of uncontrolled sylvatic transmission cycles 14 allowing virus maintenance In turn, the current eradication campaign against poliomyelitis illustrates a tradeoff between limited available economic resources and their allocation to solve the myriad of problems that conflict or post-conflict countries have to confront without functioning governance and public administrations 15 . Moreover, in Pakistan and Afghanistan, although funding for polio eradication might not be an issue owing to substantial input from international and non governmental agencies, societal concerns about vaccination as well as the circulation of vaccine-derived polio viruses may represent the biggest roadblocks to successful eradication 16 17 . Last but not least, the HIV pandemic, as well, still defies efficient control because 80% of the infected individuals live in countries where current antiretroviral therapies remain prohibitively expensive 18 .

These issues do not concern only elimination and eradication programs, but also public health strategies aiming at reducing pathogen burden in general. Indeed, our current world is increasingly interconnected 19 20 and thus, failures to manage local epidemics may rapidly convert into global threats, as demonstrated by the SARS, Chikungunya, H5N1 and H1N1 pandemics 21 22 23 during the last decade and currently by H7N9 24 . There is thus an urgent need to explore new approaches for the development of affordable and sustainable disease control tools and strategies applicable on a global scale and particularly in low-income countries.

Ecological niche is a key concept in ecological literature, for which many different definitions can be considered 32 33 . From a very general point, we can define the niche of an organism as the position of this organism within its environment, available resources and competitors. Then, it is characterized by all the conditions required to sustain a viable population of the organism, in space and time. For instance, the “fundamental” niche of African lions contains grasslands and savannah prairies (their habitats) as well as wildebeest and zebras (their resources). However, African lions “share” their habitats and their resources with other predators such as hyenas or wild dogs, yielding a “realized” niche that is the “fundamental” one constrained by the presence of competitors.

Then, pathogens, just like any organism, may have a realized and a fundamental niche 34 . Since we aim at applying pathogens niche manipulation to propose new strategies in public health, all the potential resources and interactions have to be considered. During the last decades, the accumulation of ecological and evolutionary studies focusing on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the host immune system targeted by vaccination. More specifically, the niche of a pathogen encompasses diverse intra- and inter-host levels (Figure 1). Consequently, its boundaries and evolution will depend upon a number of biotic and abiotic interactions that go far beyond competition for the resource in susceptible hosts, the presence of pathogens in the environment or the activation of the immune system machinery in the host and/or the vector.

In many cases, human pathogens are also able to infect and develop in other vertebrate hosts and most human infectious diseases have a zoonotic transmission cycle 35 , in which the animal reservoir is fundamental to consider. In addition, vector-borne pathogens do possess a required step of development within their arthropod vector species 36 while environmentally-transmitted pathogens may persist during a significant period of time outside the host 37 . Then, a pathogen may have biotic interactions with many upper organisms and abiotic interactions with environment outside the host, including in the case of vector-borne diseases where the vector is an ectotherm arthropod.

Within-host pathogen space is not that large either. Evidences are accumulating that pathogens can compete within the same host. This competition can take several forms, through competition for resources such as red blood cells between different species of Plasmodium 38 or specialized cells within an organ like in the interaction between influenza viruses and pneumococcal bacteria in lungs 39 . Pathogens interactions are also mediated by the immune system, such as in the case of malaria and helminths 40 where each pathogen activates different and inter-dependent immune paths (Th1 and Th2). It is also the case for HIV that depresses the whole host immune system therefore fostering the development of opportunistic infections, especially to Mycobacterium tuberculosis (TB) where individuals infected by HIV are 20 to 30 times more likely to develop an infection 41 , a phenomenon enhanced by a higher fatality rate during treatment of co-infected patients. Finally, the within-host conditions also play an important role 42 , through for instance malnutrition 43 or vaccine history that alters immune system efficiency 44 .

The different layers that make up a pathogen’s niche, involving various intra- and inter-host levels, impact the infection process at two scales: host infection (colonization) and within-host invasion (within-host pathogen replication). Then, it follows that the initial and fundamental resource for a pathogen is not only the availability of susceptible hosts to infect but also the ability of hosts to sustain a sizable pathogen load.

Recent ecological and evolutionary studies of infectious diseases have shed light on examples of pathogen niche alteration with an impact on pathogen fitness, transmission and/or virulence. For example, the presence of competing pathogens is especially threatening for organism survival, such as in the case of co-infection with Plasmodium falciparum and helminths that can decrease malaria severity in humans 54 . Similarly, maternally inherited endosymbiotic bacterial Wolbachia infections were shown to directly reduce the susceptibility of insects to infection with a range of insect and human pathogens 55 , above and beyond their impact on vector’s life history traits relevant to vector capacity and transmission (e.g., blood feeding frequency, longevity, fecundity…). Niche alteration can also result from a temporary mismatch between pathogens and hosts abundance. Many pathogens reproduce at a given period of time when resources are abundant and of good quality. It is known, for instance, that apparent competition can take place between two pathogens because one removes susceptible hosts to the other one, such as in the case of measles and whooping-cough 56 . This case definitely represents two pathogens with a niche overlap.

The challenge of the niche approach implementation is double. First, it relies on the availability of several control tools with different targets that can be implemented together at the same time in the same place, or sequentially in time and space. Pathogens and vectors are known to be extremely plastic in their behavior with a high adaptive potential. Failures in implementation or incorrect planning might result in pathogen escape and niche shift with unforeseen consequences for human health and the environment. The second challenge therefore resides in the ability of public health managers to act fast and implement several control strategies together locally, within a short time-frame, but also to repeat such actions during several years in order to ensure an efficient pathogen control over the long-term. From the point of view of economic resources, the costs can be decreased quite significantly (lower level of drug use, less storage, shortening the necessity of cold chain,…), but the logistics and organization could be more complex to sort out.

These drawbacks are important and cannot be neglected. They especially highlight that the niche approach should be applied only to pathogens for which the ecological and evolutionary dimensions are sufficiently documented and achieved large scientific consensus.

We believe that the niche approach is particularly promising for countries with challenging economic constraints where traditional approaches for diseases control could not be implemented successfully and/or maintained over time mainly due to financial shortcomings. Indeed, as exemplified above, niche alteration has already been successfully applied. Nevertheless, these first successes are encouraging and clearly deserve to be continued in this specific context of economic constraints. Moreover, most of the pathogens affecting human populations are now studied through the lens of ecology and evolutionary biology, extending dramatically the possibilities on which public health strategies can rely. This new and abundant literature documenting each part of the pathogen’s niche should now be integrated into policy decisions on public health strategies.

The main benefit of such an approach is the opportunity to shift from a public health strategy working on a long time period to a public health strategy that targets specific components of the disease system during a specific period within a specific area. If we place this perspective in the case of low-income and emerging countries where disease elimination is not a priority, this approach can increase political interest because it provides opportunities to (i) decrease the cost of such public health programs and (ii) the period of time where some infrastructures have to be activated.

Thus, carefully tailoring public health interventions to the pathogen niche may provide opportunities for improving their success by enhancing control effectiveness while maintaining low cost. We believe that mathematical modeling, extensively used into the study of ecology and evolution of infectious diseases to connect theoretical mechanisms and observed patterns, is a privileged tool to design innovative strategies finely tuned to different pathogens. If such low-cost solutions, direly needed in economically constrained countries, can be identified and proved successful from both a theoretical and applied standpoint, it could be extended to other parts of the World and applied at a global scale.

In resource-poor settings, public health officers may only have access to a limited arsenal and supplies for diseases control such as curative treatment, or prophylactic measures (e.g., vaccines, antibiotics or Insecticide Treated Nets). Pursuing the goal of protecting local populations according to the protocols used in the developed world, officers may use available resources with poor efficacy and no clear assessment of the consequences. For example, inappropriately managed, vaccination against childhood diseases may be detrimental in the long term because it may postpone the mean age of infection to age classes where the disease is more severe. An example stemming from the history of malaria control is the poor management of therapy (e.g., chloroquine) and/or insecticides (e.g., DDT and pyrethroids) that yielded widespread resistance in most, if not all, major African countries.

Infectious diseases control must be applied globally, including in resource-poor countries. Ecological and evolutionary theories can inform Public Health and policy makers on which component(s) of the pathogen’s niche are the most appropriate and promising targets (Figure 3). Grand strategies of how to impact on the pathogen niche in various ways simultaneously should be investigated in the light of financial constraints and potential negative consequences for pathogen niche shifts and public health. Combining recent advances in mathematical modeling of infectious diseases, operational research and financial optimization methodologies, scientists would arm public health practitioners to prepare effective and realistic solutions.

It is worth pointing out that ecological niche theory is not the only concept from ecology and evolutionary biology that may help envision innovative public health strategies. For instance, invasion biology 66 , exploring specific traits that lead species to become invasive or pests, might provide relevant insight and foster the development of a suitable conceptual framework for devising strategies aiming at preventing novel pathogens emergence and spread, especially during this current era of emerging and re-emerging infections 67 . Despite developing such ideas is outside the scope of this paper, we believe that such translation of ecological and evolutionary concepts into public health should become a research priority.

The approach should cause a paradigm shift in public health, since we argue that a strong, but short, control program does not fit with low-income countries settings. Instead, altering the pathogen’s niche, i.e., changing significantly its environment in a permanent way, can lead to a better control in the long term. Moreover, it has been suggested that pathogen elimination in large territories are generally stable over time, i.e., a pathogen that has been eliminated does not easily re-emerge 68 . Then, while classical tools such as drugs, therapies or vaccines are definitely required to fight these pathogens, using them within a pathogen’s niche approach should allow a sustainable pathogen control in those specific areas, increasing the probability of elimination.