African schistosomiasis in mainland China: risk of transmission and countermeasures to tackle the risk

Schistosomiasis is a major disease of public health importance in humans occurring in 76 countries of the tropics and sub-tropics. In China, schistosomiasis japonica is one of the highest priorities in communicable disease control defined by the central government. Since 1970s, the habitats of Biomphalaria straminea, an intermediate host of Schistosoma mansoni in South America, have been identified in Hong Kong Special Administrative Region and Shenzhen city, Guangdong province of China. With the sharp growth in the China-aided projects in Africa and labor services export to Africa, a gradual rise in the cases infected with S. haematobium or S. mansoni is reported in those returning from Africa to China. The existence of intermediate snail hosts and import of infectious source of schistosomiasis results in concern about the transmission of African schistosomiasis in mainland China in the context of global climate change. This paper evaluates the risk of transmission of African schistosomiasis in China, and proposes countermeasures and research priorities to tackle the risk.

Schistosomiasis is a snail-borne parasitic disease caused by trematodes of the genus Schistosoma, which affects more than 207 million people in 76 countries of the tropical and subtropical regions [1]. Six species of the blood fluke are reported to infect humans causing schistosomiasis, including S. haematobium, S. japonicum, S. mansoni, S. intercalatum, S. mekongi and S. malayensis; S. mansoni, S. japonicum and S. haematobium are the most significant species for human disease but vary in geographical distribution. The transmission of this neglected tropical disease is determined by the existence and geographic distribution of the intermediate host snails (Table 1). It has been proved that Schistosoma is endemic in regions where intermediate host snails are identified, while the transmission does not occur in areas in absence of host snails, although imported schistosomiasis cases are detected [2].
In China, only S. japonicum is endemic. Since the 1970s, the snail intermediate hosts of S. mansoni have been found in the natural environments of Hong Kong Special Administrative Region (SAR) and Shenzhen city, Guangdong province in China [3,4], and high-density Biomphalaria straminea habitats have been identified in many rivers of Shenzhen city recently [5]. With a quickening pace of integration of the global economy, the deepening collaboration between China and African countries and Chinese rapid economic development, there has been a sharp growth in China-aided projects in Africa and labor services export to Africa, and a gradual increase in the cases infected with S. haematobium or S. mansoni is reported in those returning to China [6][7][8]. Once these infected cases, as sources of infection of schistosomiasis, are imported to regions where the snail intermediate hosts of African schistosomes are present, there is a high possibility of transmission of African schistosomiasis in China. This has received much attention. Hereby, we evaluated the risk of transmission of African schistosomiasis in China and proposed some countermeasures and research priorities to tackle the risk.

Existence of snail intermediate hosts of African schistosomes in mainland China
The emergence and transmission of a snail-transmitted parasitic disease is governed by the geographic distribution of the snail hosts [2].  [9]. To compare the development of S. mansoni in B. tenagophila, B. straminea and B.glabrata, 200 snails of each species were individually exposed to 50 miracidia of the S. mansoni AL line, and it was found that the infection rates of the snails and the average numbers of cercariae shed per day were 32.6% and 79 ± 90 for B. tenagophila, 11.3% and 112 ± 100 for B. straminea, and 75.3% and 432 ± 436 for B. glabrata, respectively. The lower levels of infection and average numbers of cercariae shed by B. tenagophila and B. straminea are considered to be related to their more potent internal defense systems [10]. It was found that B. tenagophila was poorly compatible with the LE strain of S. mansoni (Frandsen's total cercariae production index class II) and compatible with the SJ and AL strains (class III), and B. straminea was not very compatible with the SJ strain (class I) and poorly compatible with the LE and AL strains (class II), while B. glabrata was extremely compatible (class VI) with all the three lines of S. mansoni [11]. In addition, B. straminea and B. tenagophila from different Argentine localities displayed different susceptibility and compatibility to S. mansoni EC strain (class 0-II), whereas B. orbigny and B. oligoza were incompatible [12]. These studies indicate that different species of Biomphalaria vary in the susceptibility to various strains of S. mansoni.
In 1974, a snail intermediate host B. straminea of S. mansoni in South America, as an invasive snail species, was first discovered in a stream in Hong Kong [3]. This snail species was first found in some ponds, ditches and rivers of Shenzhen city, mainland China in 1981 [4], and a further survey in 1983 showed the wide distribution of B. straminea in Shenzhen river systems and demonstrated that the snails were spread into Shenzhen from Hong Kong via water [13], which proves that B. straminea is able to survive, reproduce, and form new populations naturally in southern China such as Hong Kong and Shenzhen, and it can spread along the river systems. A recent epidemiology survey revealed that B. straminea as a predominant snail population has widely spread in Shenzhen city, and many snail habitats had been observed [5]. The introduction of the intermediate host snails and their survival, reproduction, spread and formation of new habitats in natural environments of southern China constitutes the prerequisite for the transmission of schistosomiasis mansoni in China.

Continuous import of source of infection of schistosomiasis into mainland China
It is estimated that 85% of the world's cases of schistosomiasis are in Africa, and at least 90% of those requiring treatment for schistosomiasis live in Africa [14]. Since 1970s when China started the program to aid African infrastructure construction and sent engineering technicians and workers to African countries, imported cases with S. mansoni or S. haematobium infections have been continuously detected in returners from Africa [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Table 2 demonstrates the imported cases with African schistosomiasis detected among returners from Africa in China. Although there is currently lack of knowledge on comprehensive epidemiological surveys of schistosome infections among laborers working in African countries, the available case reports prove the real existence of imported African schistosomiasis cases returning from Africa in China, which constitutes the necessary condition for the transmission of African schistosomiasis in mainland China. We summarized the characteristics of imported cases with African schistosomiasis according to the available data (see the following List of Saints). The uncertainty, mobility, and likelihood of development of praziquantel resistance in the imported cases with African schistosomiasis increase the complexity and difficulty of control of the imported infectious sources. It is therefore considered that there is a gradually increasing risk of transmission of African schistosomiasis in mainland China.
1. High schistosome infection rate in field workers and underestimation of actual cases. It has been shown that most of the subjects infected with African schistosomes are identified in field workers during physical examinations, due to high frequency of contact with the infested water. Since the cases

Global climate change
The lifecycle of schistosomes includes two hosts: a definitive host where the parasite undergoes sexual reproduction, and a single intermediate snail host where there are a number of asexual reproductive stages [2]. The geographic distribution of intermediate host snails and the development of schistosome larvae within snails are closely associated with environmental temperature. The snail species has been shown to exhibit a high adaptability to humidity and temperature, however, various species of snails and the schistosomes parasitizing snail hosts have their respective optimum temperatures for survival and reproduction. B. straminea lives naturally in freshwater at tropical regions, with the optimum water temperature of 20-30°C for growth [29]. It is found that juvenile B. straminea snails grows quickly at 24°C, while a large number of snails start to die at 16-17°C during the daytime and at 7-8°C during the night [30], indicating that B. straminea survives in a temperature-dependent manner. Habitats are found to form 30 years after the first discovery of B. straminea snails in Shenzhen, southern China, demonstrating that the natural environment in Shenzhen is suitable for the survival and reproduction of this snail species. In addition, the environmental temperature is reported to directly affect snail egg hatching, juvenile snail growth, adult snail survival and matching, invasion of miracidia into snails, development of schistosome larvae within snails, and the release of cercariae from snails, which plays a crucial role in the transmission of schistosomiasis [31].
There is burgeoning consensus that global warming is real. According to the report of the Intergovernmental Panel on Climate Change, the Earth's surface temperature is likely to increase, on average, by 1.4°C to 5.8°C over the period 1990 to 2100. This increase is about two to tenfold higher than the average temperature increase already observed during the 20th century [32]. It has been predicted, based on recent meteorological models using the mean annual temperature for the whole of China, that the mean temperature will continue to rise, indeed at an accelerated pace with predicted increases by 1.7°C in 2030 and by 2.2°C in 2050, respectively [33]. The continuous rise in the Earth's surface temperature would certainly create an appropriate condition for the survival and reproduction of the intermediate host snails, as well as the development, parasitizing and transmission of schistosomes, and affect the original landscape of schistosomiasis, thereby increasing the risk of transmission of schistosomiasis.
Countermeasures and research priorities to tackle the risk    [34][35][36][37][38], the detection and monitoring of praziquantel resistance has to be enhanced in imported cases of African schistosomiasis to timely identify those infected with nonsusceptible or resistant schistosome isolates. Once reduced sensitivity to praziquantel or resistance is detected, other antischistosomal drugs as alternatives of praziquantel, are employed for treatment of human infections, which can effectively cure cases timely. On other hand, such a replacement could rapidly remove the resistant strains from the schistosome populations in a certain area, which would effectively control the spread of drug resistance-associated genes in the endemic foci [39].

Conclusions
With a quickening pace of integration of global economy and Chinese rapid development of international trade, more and more China-aided projects in Africa and the continuous growth in labor service export would necessarily increase the probability of import of subjects infected with African schistosomes, as sources of infection, into China. In the context of global climate warming, the likelihood of introduction of the snail intermediate hosts into China and the subsequent spreading and expansion increases continuously, thereby breaking through the limitation of the original geographic distribution of the snail hosts. It is considered that the continuous growth in imported schistosomiasis cases will certainly increase the risk of transmission of African schistosomiasis in China in the presence of snail intermediate hosts. Based on epidemiological survey and basic and operational studies, assessment of the risk of transmission of African schistosomiasis and establishment of a surveillance-response system is critical to prevent the transmission.