The flow of people via air travel between endemic areas may increase the risks of reemergence or resurgence in previously malaria free or low transmission areas.

Background

The worldwide air travel network has expanded at an exceptional rate over the past century. International passenger numbers are projected to rise from 1.11 billion in 2011 to 1.45 billion by 2016, with an annual growth rate of 5.3%. Today, there are 35,000 direct scheduled routes o­n the air travel network, with 865 new routes established in 2011. Malaria endemic areas are more connected to the rest of the world than at any time in history, with the disease able to travel at speeds of 600 miles per hour within infected passengers. The growth of the air travel network results in substantial concerns and challenges to the global health system, with a need to place more emphasis o­n evidence-driven surveillance and reporting that incorporates spatial and network information.

Rising rates of travel between malaria-free and -endemic countries have led to general patterns of increased rates of imported malaria over recent decades. Due to infrequent encounters, imported cases can challenge health systems in non-endemic countries, with difficulties in diagnosis, misdiagnosis and delays in treatment, as well as significant treatment expenses. Further, flights may bring infected vectors, resulting in "airport malaria", where patients who do not have a foreign travel history become infected through being bitten in the vicinity of international airports. Patterns in imported cases and airport malaria have been shown to be related to a combination of the numbers of travellers and the malaria risk at the destination, and these relationships will continue to evolve as new routes become established. The flow of people via air travel between endemic areas may increase the risks of reemergence or resurgence in previously malaria free or low transmission areas. The autochthonous malaria outbreaks in Virginia in 2002, Florida in 2003 and Greece in 2011, for example, demonstrate the continued risks of local outbreaks following reintroduction through air travel, though such occurrences are rare. Further, the examples of malaria resurgence in island nations, such as Sri Lanka, Mauritius and Madagascar, after control measures were relaxed reinforce the importance of vigilance and robust surveillance in terms of human movement in pre and post-elimination periods. Identifying the risks of malaria movement through the air travel network can provide an evidence base through which public health practitioners and strategic planners can be informed about potential malaria influxes and their origins.

Meanwhile, growing concerns have been raised about the possible spread of artemisinin resistance from the Greater Mekong subregion in Southeast Asia to other endemic areas. Recent research has highlighted increasing numbers of patients showing slow parasite clearance rates following treatment with artemisinin-based drugs in the Cambodia-Thailand border and Thailand-Myanmar border regions. Tremendous health and socioeconomic costs occurred when chloroquine-resistant parasites arrived in sub-Saharan Africa from Southeast Asia and spread across the continent. Similarly, sulphadoxine and pyrimethamine resistance emerged in Asia and spread to Africa. The WHO reports that there is already "at least o­ne study with a high treatment failure rate (>=10%) reported from six of the 23 African countries that have adopted artesunate-amodiaquine compound", and fear remains over the spread of artemisinin resistance from Southeast Asia to Africa, that could undermine current control and elimination efforts, with no alternative drugs coming in the foreseeable future. Rates of imported malaria, risks of resurgence and the spread of drug resistance are all today influenced by how the global air travel network connects up the malaria-endemic regions of the world, and the numbers of passengers moving along it. Here, recently constructed global Plasmodium falciparum and Plasmodium vivax malaria prevalence maps are combined with data o­n modelled passenger flows across the air network, to describe and quantify global malaria connectivity through air travel in 2010. Weighted network analysis statistics are derived to examine: (i) which regions show greatest connectivity to P. falciparum and P. vivax malaria-endemic zones; (ii) where the largest estimated passenger flows from endemic areas occur; (iii) which regions form 'communities', whereby malaria infection flows within them are likely to be larger than between communities, and finally, (iv) where the threat of imported artemisinin resistance is highest via air traffic, and the possible risk routes for the spread of resistance within and from Southeast Asia.

Methods

Recently constructed global P. falciparum and P.vivax malaria risk maps, along with data o­n flight schedules and modelled passenger flows across the air network, were combined to describe and quantify global malaria connectivity through air travel. Network analysis approaches were then utilized to describe and quantify the patterns that exist in passenger flows weighted by malaria prevalence. Finally, the connectivity within and to the Southeast Asia region where the threat of imported artemisinin resistance arising is highest, was examined to highlight risk routes for its spread.

Malaria distribution

Global P. falciparum and P. vivax prevalence maps were obtained from the Malaria Atlas Project and the methods behind their construction are presented in Gething et al. In brief, 22,212 community prevalence surveys were used in combination with model-based geostatistical methods to map the prevalence of P. falciparum globally in 2010 within limits of transmission defined by annual parasite incidence and satellite covariate data. Similarly, 9,970 geocoded P. vivax parasite rate (P. vivax PR) surveys collected between 1985 and 2010 were utilized in a spatiotemporal Bayesian model-based geostatistical approach to map endemicity, under the restrictions of a mask of the stable/unstable endemicity and information o­n the prevalence of the Duffy blood group. Distributions of Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi are not included here, since similar datasets o­n their distributions do not yet exist. Also, the seasonal climatic constraints that affect the transmission of P.falciparum and P.vivax are not included here, but models of each will be included in future work.

Results

The analyses demonstrate the substantial connectivity that now exists between and from malaria-endemic regions through air travel. While the air network provides connections to previously isolated malarious regions, it is clear that great variations exist, with significant regional communities of airports connected by higher rates of flow standing out. The structures of these communities are often not geographically coherent, with historical, economic and cultural ties evident, and variations between P. falciparum and P. vivax clear. Moreover, results highlight how well connected the malaria-endemic areas of Africa are now to Southeast Asia, illustrating the many possible routes that artemisinin-resistant strains could take.

Discussion

The continuing growth in air travel is playing an important role in the global epidemiology of malaria, with the endemic world becoming increasingly connected to both malaria-free areas and other endemic regions. The research presented here provides an initial effort to quantify and analyse the connectivity that exists across the malaria-endemic world through air travel, and provide a basic assessment of the risks it results in for movement of infections.

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Source: Malaria Journal 2013, 12:269 doi:10.1186/1475-2875-12-269; Zhuojie Huang (seenhzj@gmail.com); Andrew J Tatem (andy.tatem@gmail.com)

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