The heterogeneity and complexity of malaria involves the political and natural environments, socioeconomic development, transportation and cross-border movement, access to health care services, and vector biology, factors that cannot be changed in a short time [1–7]. This study aimed to assess the impact of 2 facets, economic growth and cross-border movement, in moving toward malaria elimination in the remaining highly endemic areas along the China–Myanmar border, in the border areas of Yunnan Province during its pre-elimination phase.

Several studies have noted that it is important to fully understand the complex pathways between poverty and malaria so as to develop effective strategies for sustainable malaria control [8–11]. One study on malaria and poverty suggested a potential bidirectional relationship: poverty as a cause of malaria and malaria as a cause of poverty. Poverty sustains the conditions in which malaria thrives, and malaria impedes economic growth and keeps communities in poverty [9]. Another study reviewing the published and grey literature on malaria and poverty reported that the quality of the literature examining this issue is highly variable, with many different measures of socioeconomic status [11]. In assessing the economic burden of malaria, 2 different approaches have typically been followed. i.e., the perspectives of microeconomics and macroeconomics. Microeconomics studies assess the direct costs of malaria prevention and treatment at individual, household, and health service levels, with or without the estimated indirect cost of lost work time. Macroeconomics studies assess the long-term economic growth and development of malaria at larger scale (e.g., provincial, country level) [9].

Studies at country level examining the gross domestic product (GDP) of poor countries have revealed that malaria impedes economic growth in these countries. The loss of GDP owing to malaria in Uganda during 2003 was equivalent to USD 11 million (about USD 0.43 per capita) whereas almost 1.1% of GDP (about USD 2.2 per capita) is devoted to dealing with malaria in Tanzania [9]. In China, Yunnan Province lags behind other provinces in social and economic development. Its GDP per capita ranks 29th of 31 provinces [12]. One study in Yunnan noted that poverty and malaria appear to have a clear inverse relationship, with residents living along the border experiencing greater degrees of poverty and malaria infection than those in other regions of this province [10].

The challenge of countries nearing malaria elimination is often owing to international borders with countries that have not yet achieved substantial reductions in malaria transmission [12]. Cross-border movement of infected individuals from endemic areas to neighboring countries has been recognized as a contributor to the spread of malaria in Asia and Africa [1,13–15]. Cross-border malaria transmission and reintroduction is the main challenge for China as it shares 4,060 km of porous international borders with Greater Mekong Subregion (GMS) countries. The China–Myanmar border is particularly challenging owing to ongoing conflict on the Myanmar side of the border, resulting in uninterrupted disease transmission [16–22]. Yunnan faces a problem similar to most GMS countries in that border malaria is a major source of disease transmission, and malaria parasites are introduced via porous borders by highly mobile human populations [13,23–25]. In 2011–2013, imported malaria infections accounted for more than 70% of all cases of malaria in Yunnan [26–29]. Another threat of malaria introduction is owing to internally displaced persons (IDPs) from neighboring Myanmar, where the malaria situation is far worse than that in Yunnan [30,31]. The Technical Scheme of China Malaria Elimination defined malaria cases as “indigenous case” or “imported case”. An imported case is a patient who diagnosed with malaria with a history of travelling to overseas malaria-endemic areas during the malaria-transmission season, and the onset of malaria symptoms was less than 1 month after returning. An indigenous case is a patient whose malaria infection was acquired from local transmission by Anopheles mosquitoes within China, including malaria cases with no clear evidence of being imported from outside the country.

As malaria is considered to be related to poverty and economic inequality, and poverty is often an underlying factor for migration, the specific objectives of the present study were to examine the spatial and temporal trends of indigenous and imported cases of malaria in relation to economic growth (per capita GDP) in the 18 border counties of Yunnan Province during the malaria pre-elimination phase and rapid economic development in China during 2011–2016. In addition, the spatiotemporal patterns of malaria at hotspots in adjacent areas between Yingjiang County of China and the Kachin Special Region II (KSR II) of Myanmar was analysed to examine changes in the persistently high incidence of border malaria during the same period.

The heterogeneity and complexity of malaria epidemiology presents a challenge to the interruption of local malaria transmission. This study had assessed the spatiotemporal trends of malaria cases in relation to economic growth and cross-border movement over 6 years during the pre-elimination phase along the Yunnan border.

China has been successfully reducing gaps in socioeconomic development between urban and rural areas, especially remote mountainous regions, and between eastern and western regions of Yunnan [1]. A previous study suggested that malaria incidence in Yunnan during 2011–2016 had been significantly reduced, but transmission persists along the border and in poorer areas [37]. It was noted in another study that poverty may be a driver of malaria transmission in Yunnan, based on maps showing a spatial convergence of poverty and malaria incidence at county level [10]. The results of the present study confirmed the previous observation that the temporal distribution of malaria cases and economic growth showed an inverse trend: as per capita GDP increases, malaria cases decreased over the years. In contrast to that finding, when examining spatial patterns of the average annual GDP per capita at county level in Yunnan during 2011–2016, the results suggest an uneven distribution of economic status across the 18 border counties. When overlaying the spatial trends of malaria cases on GDP by county, no obvious pattern is visible; counties with a high number of malaria cases had neither very high nor very low GDP indices. Thus, caution must be used in drawing conclusions about the inverse relationship between malaria transmission and indices of economic development.

Since the launch of the National Malaria Elimination Program in 2010, through integrated strategies and activities, indigenous cases of malaria have declined dramatically in Yunnan, particularly in the border area, with only 1 case reported in 2016 [36,38]. According to the national surveillance system, there have been no indigenous malaria cases reported in Yunnan since 2017, after the study period. The province thus declared the first zero report since the fight against malaria in China began [39]. About 85% of malaria cases in the study area were imported, similar to the proportion of imported cases reported in China during the past decade, at about 89% [30]. When mapping either indigenous or imported malaria cases together with GDP at county level, there again appeared to be no direct relationship between the 2 variables. More cases of malaria tended to be clustered in the middle part of the 18 counties, with GDP somewhat in the midrange between high and low GDP levels.

It is important to note that it may be difficult to determine whether an infected cases is indigenous or imported, since the incubation period varies depending on the strain of Plasmodium vivax. Individual immune status, prevention of medication, mixed infection, etc., can also affect the incubation period. Due to the climatic conditions and the history of local malaria epidemics in Yunnan, it is sometimes very difficult to determine the place of infection when a vivax malarian case occurs over 1 month after return from a malaria-endemic area outside the country. However, a previous study of malaria status from 2005 to 2012 showed meteorological factors--temperature, humidity, rainfall, and sunshine--did not show significant differences with malaria incidence per year, which also explained the conclusion that most malaria cases were imported [40]. I routine work in Yunnan Province, for cases of vivax malaria that occurred over 1 month after return, comprehensive investigation, analysis and judgment will be made in combination with histories of movement in/through malaria-endemic areas, preventive medication, malaria infection, malaria epidemic(s) in the patient’s place of residence, and an investigation of Anopheles mosquitoes. Thus, vivax malaria cases that occur over 1 month after return, and with insufficient evidence to prove they are imported, will be treated as local infections. According to the WHO, in China, cases of vivax malaria will be followed for 3 years. The criteria are as follows: no indigenous case at any administration level for a consecutive period of 3 years if the county, municipality, or even the whole country, aim to achieve malaria elimination.

Economic growth may have an indirect effect on the distribution of malaria cases, as poverty and cross-border movement could be interrelated. With the development of China in recent years, increased economic prosperity and job opportunities may attract local people to work inside the country rather than abroad, thereby avoiding malaria infection while improving their income. On the other hand, those unable to find work locally may be compelled to become migrant workers seeking work such as logging, mining, planting, and road construction, by which could increase their income, but by working in high-risk areas of Myanmar, for example, where they work unprotected from malaria infection and are unable to access healthcare services. However, in the present study, most imported cases did not occur among laborers in very high GDP counties; most cases tended to occur in counties in the middle part of study areas during the 6-year study period. Imported cases of malaria are attributed to mass movement of mobile populations across international borders [29,41–43]. A study in Tengchong, a county in Yunnan with a high number of malaria cases, reported that migrant workers returning from Myanmar were the main contributor of imported malaria [44].

According to other surveys on imported malaria in the region, the distinctive characteristics of imported cases include adults, male sex, mainly engaged in agriculture, and labor-related travel history to other countries [9,10,31,45]. An analysis of the malaria epidemic situation in Tengchong, between 2010–2015, found that imported cases were mainly migrant workers who had returned from Myanmar. Malaria cases were reported in all towns and were clearly clustered with large numbers of migrant workers. The numbers of cases in April-June were higher than other periods, and the peak was inconsistent with the malaria-transmission season in Tengchong; instead, it was related to the return and number of migrants [46]. Tengchong County is adjacent to the Special Region of Kachin State in Myanmar, where degrees of malaria epidemic vary. Without natural barriers in most areas, there are many channels for entry and exit, and bilateral population flows are frequent. Such a setting makes this region a major source of malaria infection among migrant workers. The cross-border movement of imported cases into the central part of the 18 counties of Yunnan with high-to-midrange economic growth, rather than areas with the highest economic growth, might be based on workforce flows and the convenient adjoining border in that part of the province.

Political conflict is another underlying factor in cross-border movement and malaria cases. Specific spatial and temporal patterns of the malaria distribution in this study were illustrated at the village/IDP camp level in Yingjiang County in Yunnan and in part of the KSR II in Myanmar along the border. Owing to the internal military conflicts on the Myanmar side of this region, residents have been evacuated from the inner part of the KSR II to villages and IDP camps situated very close to the border [33,47]. A previous study showed that the number of malaria cases and incidence rates in the villages and IDP camps on the Myanmar side were at least 8-fold higher than those in villages of neighboring Yingjiang County in China [17]. In this study, the average annual malaria incidence rates in local villages on the Myanmar side during 2014–2016 decreased to about 5-fold higher than those in IDP camps. The ongoing conflict not only undermines the public health infrastructure in Myanmar but also leads refugees from endemic areas with higher malaria rates to relocate to border areas [17,48]. The inevitable introduction of a large number of people with malaria infection, coupled with poor living conditions and a lack of malaria prevention efforts, undoubtedly increases the burden of malaria along these bilateral areas [12,18,31,49]. This finding also reflects a common challenge in that these 2 countries share a border and also share common malaria ecologies but are different in stages of the control-to-elimination pathway [50–52].

It is important to measure and quantify the relationship between poverty, cross-border movement, and the malaria burden at individual, community, county, country, and regional levels. Poverty or economic prosperity can be defined in many ways. Studies at individual or community level often define poverty indicators using a combination of household assets (housing type and ownership, education and sex of the head of household, and crowding in the household) or evidence-based indicators of socioeconomic status (occupation, transportation tools, income, expenditure or asset ownership, and rural location) [8,11,49]. For example, a study in Ghana found that social and economic factors are directly related to malaria morbidity, such that income levels for heads of household below the poverty line of USD 1 per day are a significant determinant of malaria morbidity [53]. A community-based study in Uganda reported that housing improvements and agricultural development to reduce poverty could be effective interventions against malaria [8]. At country level, a study in Saudi Arabia reported that increasing GDP had an impact on quality of life through urbanization, provision of higher education, and improved health care systems in the country; however, whereas low malaria incidence occurred during the period of rapid economic development, it was also coupled with aggressive local elimination strategies and cross-border collaboration [50]. This may be similar to the setting in Yunnan. As GDP increased in all counties together with more intensive efforts in reaching malaria elimination targets, the number of indigenous cases reached zero and imported cases were reduced. It is therefore difficult to quantify the impact of any single contributing factor among multi-faceted interventions. In moving toward elimination, consideration should not only be given to macroeconomic contributors but also to microeconomic development, as the distribution at larger scale may not be thoroughly covered at individual level, especially among the poor and the labor workforce at risk of malaria infection.

This study has a number of limitations. First, this study used data from government databases, which may be incomplete, and the variables were limited to what had been mandated for data collection. However, the research team compared data in the national databases against those from data sources at the local level, to ensure data quality. Second, the analysis was based on secondary data and some were aggregate data; thus, caution is needed in interpreting the results owing to the possibility of ecological fallacy. An inverse relationship might be observed at macro level but not at individual level. Third, the conceptual framework of the study was based on observation and an ecological study design; thus, it was unable to identify causal pathways linking economic development and cross-border movement with malaria cases in the study area. Fourth, GDP might be an imperfect index to represent poverty reduction over the years. Despite the aforementioned limitations, the spatiotemporal trend analyses in this study reflected changes in the patterns of indigenous and imported malaria cases in relation to changes in economic development in areas with persistence of endemic malaria along the Yunnan border. The findings will be useful in planning a framework for elimination.

In this study, over 90% of imported malaria cases were from Myanmar. Since there are no natural barriers along the China-Myanmar border, both people and mosquitoes easily cross the border. In many border communities, some households are Chinese and others Burmese, and they share the same mosquito breeding sites and mosquito species. For the reasons outlined above, it may be conjectured that the major malaria-infecting species in the area are very similar (i.e., P. vivax and P. falciparum) and the proportion of people living on both sides of the border are infected similarly with both species of parasites. This hypothesis regarding the high similarity of malaria-infecting species along these border areas requires further investigation and validation.

It has been anticipated that Yunnan, particularly the border counties of the province, would be the final location in China of malaria elimination. However, the results of the present study showed that malaria has substantially decreasing during the pre-elimination phase (2011–2016). A remaining threat is imported cases in a number of counties adjacent to porous borders. The spatial and temporal trends shown in this study suggested that economic development may have an indirect effect on the reduction of malaria when observed from a macro-level perspective; however, malaria still persists owing to complex, multi-faceted factors including poverty at individual level and cross-border movement of the workforce. In moving toward malaria elimination, despite economic growth, cooperative efforts with neighboring countries are critical to not only interrupt local transmission but also to prevent reintroduction of malaria via imported cases. Cross-border workers should be educated in preventive measures through effective behavior change communication, and investment is needed in active surveillance systems and novel diagnostic and treatment services during the elimination phase.