Travel, Migration and Emerging Infectious Diseases.

Emerging infectious diseases (EID) threaten public health and are sustained by increasing global commerce, travel and disruption of ecological systems. Travelers could play a role in importing EIDs and could be a sentinel of major epidemics. In connection with the extension of poverty, urbanization, extensive livestock rearing and globalization, we could be exposed to a third epidemiological transition characterized by zoonotic diseases and infections with multidrug-resistant bacteria. The risk appears low for emerging infectious diseases, or very low for high-risk emerging infectious diseases, but higher for multidrug-resistant enterobacteriaceae carriage with possibly limited consequences. The role played by migrants is weaker than imagined. Immigrants don't play the role of sentinel epidemic so far. They could play a role in importing multidrug-resistant enterobacteriaceae, but it is poorly evaluated.

Emerging infectious diseases (EIDs) have led to cooperation between countries, the first international epidemic response conference in 1851 and the establishment of WHO in 1948.

EIDs are diseases that have appeared recently or that have recently increased in frequency, geographical distribution or both (1). Since the end of the 20th century, there has been a constant stream of newly identified pathogens and an increasing occurrence of pandemic threats to global health (2).

These infections are due to new agents (HIV-1, Severe Acute Respiratory Syndrome CoronaVirus-SARS-CoV- (2003), avian influenza virus H5N1 (2005), H1N1 (2009)), geographical area in extension (West Nile, Dengue, Chikungunya, and Zika viruses), increased incidence of infectious disease (HIV, tuberculosis, plague), modification of virulence (Neisseria meningitidis) or acquisition of resistance (Extended-spectrum betalactamases -ESBL- or carbapenemase producing enterobacteriaceae and multidrug-resistant -MDR- tuberculosis).

We can also compare the re-emerging infections (polio virus (2014), Ebola virus (2014), etc.) (3, 4).

EIDs threaten public health and are sustained by increasing global commerce, travel and disruption of ecological systems and in particular urbanization. Urbanization is characterized by rapid intensification of agriculture, socioeconomic change, and ecological fragmentation, which can have profound impacts on the epidemiology of infectious disease (5). However, their interactions with travel and migrations are less well known.

Travelers could play a role in importing EIDs and could be a sentinel of major epidemics.

In France, there are more than 20 million travelers every year, 4.5 million of which are destined for areas at high risk for health. There are several modes of travel: tourist, business or visiting friends and relatives. Trips can be very short or extended in time.

Infectious diseases are rare health events, with the exception of common infectious diseases such as traveler’s diarrhea and are a single cause of death, far behind accidents and cardiovascular disease (6).

The risk of emerging infections such as dengue in a risk zone was estimated at 1% for one month of travel (7).

We have seen (re-)emergence of diseases imported by travellers in Europe, such as chikungunya and dengue in France and Itay, and malaria in Greece (8-10). Apart from these examples, these are rare situations. However, with global travel growth, the risk could become more tangible (11).

A particular concern is that of Multidrug Resistant Enterobacteriaceae (MRE) carriage. MRE acquisition is very frequent among travellers to tropical regions (12). The acquisition was higher in Asia (72%) than in sub-Saharan Africa (48%) or Latin America (31%). However, the same study showed that MRE carriage was limited in time and disappeared after a few months.

Migration is a global phenomenon that influences the health of individuals and populations over the course of their lives (13). Migrants are special travellers who, in most case, do not migrate by choice. Migrants are considered at higher risk for a range of health problems including infectious diseases as HIV, hepatitis B, tuberculosis, schistosomiasis and malaria (14, 15). This higher risk is partly due to poor socioeconomic conditions and, in some countries, is due to the lack of rights to health coverage for undocumented migrants (16-19).

Existing evidence from different European countries highlights the difficulties to access health services that migrants are facing (20-23). These infectious diseases unequally expose the majority population, from none at all (e.g., malaria) to a little (e.g., tuberculosis).

One can take the examples of epidemics of Middle East Respiratory Syndrome Coronavirus -MersCov- and Ebola, for which no secondary case has been reported in France.

Among the published studies on migrants and infectious diseases, the majority were non-emergent diseases with the exception of MDR tuberculosis and multidrug-resistant bacteria (24, 25).

In connection with the increased use of antibiotics in low-resource countries, there is a worrying increase in the prevalence of multidrug-resistant bacteria (26, 27). This increase could lead to an increased risk for migrants and their relatives, but there are few data on this point (28). The risk seems particularly increased when they return home to visit friends and relatives (29). While antimicrobial resistance is of concern, the prospects for pandemic spread of a bacterial or fungal emerging pathogen by migrants seem less likely (30).

Endemic disease, as tuberculosis, impose a far higher public health burden than epidemic disease (31). Denmark experienced an increase in the incidence of tuberculosis in the 1990s in relation to the increase in the number of cases among migrants (32). The rate of tuberculosis in France is 10 times higher among immigrants than in the majority population. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes but the data remains poor (33).

Thus, there is little evidence to support the theories by which migrants would expose the host population to significant infectious risk. However, human diseases acquire a social status based on their perceived risk that determines their acceptability (31).

In a study that we conducted with a number of 347 doctors in France (infectious diseases and general practitioners), they were asked if first-time migrant people represent a vector of infectious diseases different from the majority population: 8% answered no, 13% yes but weakly, 44% yes but moderately, 27% yes significantly and 9% did not know.

Thereby, apart from infections such as tuberculosis and multidrug-resistant bacteria, the introduction of EIDs into human populations seems to be more often a consequence of economic development that brings zoonotic reservoirs in closer proximity to people.

Indeed, most pandemic threats are caused by viruses from either zoonotic sources or vector-borne sources (30). There is a need for rapid diagnosis of EIDs. Systems biology approaches can lead to a greater understanding of EIDs pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner (30, 34).

Close collaboration is therefore needed between specialists in tropical medicine, in public health, immunologists and biologists to anticipate the risk of EIDs in order to achieve the Sustainable Development Goals established by the United Nations in 2015(35).

The WHO established a Department of Pandemic and Epidemic Diseases in 2011 to better prepare for and respond to EIDs.

In conclusion, in connection with the extension of poverty, urbanization, extensive livestock rearing and globalization, we could be exposed to a third epidemiological transition characterized by zoonotic diseases and infections with multidrug-resistant bacteria (36).

The risk appears low for EIDs, or very low for high-risk EIDs, but higher for MRE carriage with possibly limited consequences. The role played by migrants is weaker than imagined (except for tuberculosis). Immigrants don’t play the role of sentinel epidemic so far. They could play a role in importing MRE, but it is poorly evaluated.