The effects of urbanization on global Plasmodium vivax malaria transmission

The world population has undergone unprecedented growth along with rapid urbanization. Slightly more than 50% of the population (3.6 billion) is now living in urban areas compared to only 30% (0.7 billion) in 1950[1]. By 2050, it is projected that urban dwellers will account for approximately 67% (6.3 billion) of the world total population, while most of the estimated growth will be concentrated in less developed regions, particularly in Asia and Africa[1]. These substantial transitions have significant public health implications associated with changes in the social and physical environment and access to public health services[2‐6].

Although large heterogeneity exists, it is commonly accepted that the process of urbanization reduces malaria transmission, primarily because urban environments (e.g. the lack of suitable breeding sites, the pollution of existing larval habitats, etc.) are generally unsuitable for malaria vectors[7‐9]. Other explanations include better access to health care services and an increased ratio of humans to mosquitoes[7, 10, 11]. However, there is concern regarding urban malaria in less developed regions, typically those undergoing rapid and unprecedented urbanization[12, 13].

Between the two dominant parasite species of human malaria, Plasmodium falciparum has attracted the focus of most research because of its high mortality and intensive transmission in Africa[14]. Plasmodium vivax malaria, in contrast, is commonly considered as a “benign” infection and largely overlooked by researchers, government, and funding agencies. Increasing evidence has shown that P. vivax is neither rare nor benign, however. It is estimated that 2.85 billion people were at risk of P. vivax infection in 2009, with 91% (2.59 billion) of them living in Central and South East Asia[15], and that P. vivax is the most widely distributed (geographically) malaria species of humans. Furthermore, although the infection with P. vivax malaria is rarely directly fatal, it can cause severe clinical syndromes[16, 17].

Recent studies have examined the impact of urbanization on P. falciparum malaria endemicity and disease burden estimation[7‐9, 13, 18]. Various urban extent maps have been used to compare the differences in P. falciparum malaria endemicity between urban settlements and rural areas[18]; exclude the urban extents of cities identified as malaria free in the mapping of malaria transmission limits[19, 20]; downgrade endemic classes in estimates of malaria burden[9, 21]; and predict P. falciparum malaria endemicity based on geo-statistical models[22, 23]. However, according to our best knowledge, no known research has examined the effect of urbanization on P. vivax malaria over similarly large scales. In addition, the regions of highest P. vivax transmission in Asia are composed of a considerably greater range of vector species and species complexes than seen in Africa, where P. falciparum transmission is princi-pally concentrated[24‐27], and urbanization may impact each of these vector species differently, dependent on their preferences and bionomics. For example, Anopheles culicifacies was reported to be the vector responsible for 60-65% malaria cases in urban environments of India[28] and shows significant environment tolerance and adaptability[29, 30], while larvae of Anopheles stephensi were found in various domestic containers and collections of water related to construction and industrial sites in cities[31, 32]. Therefore, there is a need to examine the effects of urbanization on P. vivax transmission by dominant vector species to discern whether differential impacts are evident.

Here geo-referenced P. vivax parasite rate (Pv PR) surveys and urban extent maps are integrated to examine the impact of urbanization on P. vivax malaria transmission at various spatial scales (global, regional, national and at the city level). Furthermore, distribution maps of dominant Anopheles vectors are used to explore the relationships between urbanization, Anopheles vectors and P. vivax malaria transmission.

The rapid urban transformation of the developing world[47] has and will continue to have a profound influence on the malaria landscape. The need for accurate and contemporary descriptions of populations at risk (PAR) has lead to several attempts to quantify the impact of urbanization on P. falciparum malaria transmission[9, 13, 18]. Knowledge is lacking however regarding the relationship between urbanization and P. vivax malaria transmission. In this study, the most contemporary and comprehensive database of Pv PR surveys was used to explore the differences in P. vivax transmission between urban and rural areas.

Lower P. vivax malaria transmission in urban areas than surrounding rural areas was found globally, and in the Africa+ and Asia+ regions (Table 2), which corroborates previous findings that the urban environment is typically not suitable for malaria mosquito vectors[7‐9]. The consistent patterns of significantly lower urban Pv PR values found at the national scale in most of the countries in Africa+ and Asia+ further supports these findings (Table 2). However, the urban–rural survey pairs for each region are dominated by a few countries (e.g., Indonesia accounts for 65% of the Asia pairs and Sudan accounts for 45% of the Africa pairs), which make the patterns found at regional scale less informative. Distinct and inconsistent results were found in the Americas, with higher Pv PR values in urban areas at the continental scale and for one particular country (Brazil) at the national scale. This result is probably due to the lack of Pv PR surveys in this region, as surveys from the region only account for 4.1% of the Pv PR global database. Getting extreme results is more likely when the numbers of surveys are small and only the rural Pv PR surveys were averaged. There is also evidence suggesting that higher malaria transmission in some areas of Brazil was actually a result of rapid urbanization, during which settlements were built close to forest boundaries or along riversides and thus resulting in greater exposure to the malaria parasite for residents[48].

Figure 2 indicates that considerable heterogeneity exists when examining individual cities, with two cities (out of twenty) showing significantly lower Pv PR in their surrounding rural areas, and seven cities showing significantly lower prevalence in urban areas. Thus, only nine of the twenty cities examined showed significant differences in transmission between urban and rural areas, and three showed zero prevalence both within and around the urban areas. Compared to P. falciparum[18], therefore, the patterns of Pv PR between urban and rural areas exhibit a higher level of heterogeneity. Several possible reasons include: 1) the wider transmission limits of P. vivax[15], but lower transmission intensity with many zero Pv PR values in the database; 2) the wide distribution in Asia and high prevalence of Duffy negativity in Africa[49, 50]; 3) relatively fewer Pv PR surveys available in the MAP database compared with a total of 22,212 P. falciparum parasite rate (Pf PR) surveys in 2010[23].

The Pv PR differences between urban and rural settings within the ranges of the dominant Anopheles vectors generally follows the patterns found in each region. This is partly because vector species that had sufficient urban–rural Pv PR pairs within their extents usually cover a large portion of the region. An issue raised here is that the distributions of most of the vector species overlap substantially with each other. Thus, drawing conclusions about the patterns of individual vector species is difficult without considering such overlap. However, according to expert-opinion distribution maps of global DVS[25‐27], the spatial relationships among those vector species are extremely complex and the interaction effects of them are beyond the scope of this analysis.

The GRUMP-UE was used to define urban areas here, though several alternative global urban maps exist[42]. Every global map suffers from different errors and uncertainties[42], and the GRUMP-UE map exhibits overestimation of large urban area extents, due to the blooming effect of NTL imagery[42, 51]. This suggests that the Pv PR urban values that were significantly higher than nearby rural ones found in the Americas and several other individual cities could actually be located in surrounding lower population density areas, as significantly higher malaria prevalence and entomologic inoculation rates in peri-urban areas compared to urban centers have been found in a number of studies[9, 13, 18]. To assess briefly this potential bias in the GRUMP-UE map, urban extents mapped using Moderate Resolution Imaging Spectroradiometer (MODIS) satellite sensor imagery[40, 41] were utilized to derive an alternative, more conservative, urban assignment for the Pv PR surveys. Again, sets of spatially and temporally associated urban–rural pairs of Pv PR values were extracted and tested. The results show that, due to the more conservative nature of the classification, and the fact that only intensely urban areas were mapped[40, 41], far fewer Pv PR surveys were identified as urban and the differences in Pv PR between urban and rural areas were generally not significant (see Additional file2). Such results highlight the differing outcomes that can occur through using differing definitions of urban, and that the effects of urbanization on P. vivax transmission may extend beyond the borders of intensely urban areas for most of the regions as a general trend of decreased Pv PR was found in urban areas. Another issue is that the GRUMP-UE map was produced in 2004 and some Pv PR surveys may be misclassified as the urban extent changes through time. However, global urban maps that are updated regularly or that quantify urban extent change do not currently exist. Furthermore, the majority of the Pv PR surveys were conducted between 2000 and 2010 (Table 1). Thus, it is reasonable to use the single time-point GRUMP-UE map in this analysis.

A range of human-induced environmental changes (e.g., deforestation, urbanization, water control projects and climate change) have been identified as drivers of ‘emerging’ and ‘reemerging’ diseases and the transmission of vector-borne and other infectious diseases[52‐55]. Urbanization is usually recognized as one of the primary factors affecting vector-borne diseases[56] as it can not only provide residents with better access to healthcare and interventions[4, 5], and an environment generally less favorable for many disease vectors[7, 8], but can also modify land uses to expose humans to new pathogens and vectors[57]. While global and regional-scale results here show a general trend of decreased P. vivax transmission in urban areas, the heterogeneous impacts of urbanization on P. vivax malaria transmission at the city scale found in these analyses support increasing concerns of urban malaria problems in developing countries. Urbanization in these regions is often associated with poverty, poor water supplies and sanitation in peri-urban areas, providing breading sites for certain vectors[12]. Although malaria vectors are generally not favoured by urban environments, there is evidence highlighting the potential of malaria vectors in adapting to urban environments[58‐60]. For example, Anopheles gambiae s.s. was found breeding in polluted water bodies in Lagos, Nigeria[59]. Furthermore, many studies suggested that urban agriculture is another important source for providing favourable breeding sites for malaria vectors in cities[61‐64]. Increased malaria prevalence is often found in communities within a distance of 1 km from irrigated urban agriculture in Accra, Ghana[64], for example. Thus, malaria transmission in urban areas exhibits considerable spatial heterogeneity both between and within cities, depending on factors such as proximity to possible vector breeding habitats, urbanization level and socio-economic status[7, 65]. Future work should aim to elucidate these drivers through examination of the disparity of P. vivax malaria transmission between and within cities using detailed household prevalence surveys and higher resolution urban maps.

In general, the results here highlight a consistent relationship at large scales between urban areas and lower P. vivax transmission, mirroring results found for P. falciparum, and pointing towards global declines in P. vivax transmission as urbanization permanently alters the receptivity of many areas. The findings suggest that these trends will likely continue to catalyze malaria declines on the path to a malaria free future.