Guangzhou has an ideal environment for DENV transmission; it has a subtropical climate, a population of over 10 million, presence of the vector mosquito, and frequent interaction with countries that have DENV epidemics. In total, over 10,000 DENV infection cases and 9 major outbreaks (over 200 infection cases each time) have been reported in the last 34 years in China [14, 16]. The statistical data from the Chinese Center for Disease Control and Prevention showed that from 2005 to 2010, there were 2198 reported DENV infection cases in China, and 42.63% (937 cases) of them were in Guangzhou alone, which is the highest among all cities. Given this statistic, we can say that the epidemiological and virological characteristics of DENV in Guangzhou are representative of the situation in China as a whole.
In Guangzhou, the rainy season extends from April to September, and the average temperature in Guangzhou between April and October is usually above 20°C . Our study showed that the density of Ae. albopictus and its larvae reached the highest level between June and August in Guangzhou . Those facts can explain why the DENV epidemic in Guangzhou peaks between August and October.
To determine which strains were prevalent in Guangzhou, we performed phylogenetic analysis on the full-length E gene sequenced from 90 DENV strains that had been isolated from clinical samples . DENV-1 was predominant in most of the years between 2001 and 2010 (Table 2). It was also the only serotype detected every year between 2001 and 2008, except in 2005. However, in 2009, infections caused by DENV-1, 3, and 4 serotypes occurred, and the incidence of DENV-3 prevailed over DENV-1. Then, in 2010, all 4 serotypes appeared, and again, DENV-3 predominated. The phylogenetic tree of DENV-1 showed that genotype replacement occurred during this decade. The DENV-1 strain observed in 2001 was of genotype I; however, it was replaced by genotype IV in 2002, 2003 and 2004. In 2005, the dominant strain, again, was genotype I, and it remained predominant until 2010. In 2007 and 2010, both genotype I and genotype IV co-circulated. In 2009, a new genotype, genotype V occurred. Interestingly, the strains in the phylogenetic tree of DENV-2, 3, and 4 show less diversity. The DENV-2 and 4 strains belonged to only one genotype, whereas the DENV-3 strains were divided into two genotypes. There is little evidence to support the idea that there were genotype shifts in DENV-2, 3, and 4. It could be possible that they all just appeared from 2009 (except for DENV-2 that occurred in 2005). As we have demonstrated, a lengthy longitudinal study is required to observe these shifts.
After years of investigation, we found no serotype or genotype was established in Guangzhou. Among all the DENV infection cases reported in Guangzhou, 80 (3.23%) cases were imported. Imported cases were seen every year between 2001 and 2010. The sensitivity of the population may also be another reason. No death or DHF/DSS case was found in the 2478 DENV infection cases during this decade. This incidence is quite low compared with other Southeast Asia countries. The incidence rate of DHF/DSS in Malaysia, Singapore, and Vietnam was 4.07–8.5, 10.47, and 51.01–77.65 per 1 million people from 2001 to 2010, as indicated on the WHO website . Research has shown that some human genes are associated with DENV infection severity . It could be that the people in Guangzhou are not as sensitive to DENV as the residents from other countries. Further genetic and epidemiological research would be required to determine if this is the case.
Our epidemiological investigation showed that Southeast Asian countries were the main sources (86.25%) of the imported DENV cases (Table 2). The WHO reported that the Southeast Asian region together with the Western Pacific region bears nearly 75% of the current global dengue burden. At present, from these regions, only the Democratic People’s Republic of Korea has no reports of indigenous dengue cases . Southeast Asian countries are the favored travel destination for people living in Guangzhou . Most of these Southeast Asian countries have had severe DENV epidemics and all 4 serotypes have, at some point in time, been in circulation. The increased risk of DENV infection for travelers in Southeast Asia therefore increases the risk of transmission to local people in Guangzhou. The BLAST results and the phylogenetic trees of the isolated strains support this hypothesis. For the imported cases, the phylogenetic analysis verified our epidemiological data. For the local cases, most of the strains in Guangzhou were closely related to the strains isolated in prior epidemics in Southeast Asian countries. For DENV-1, the isolates in 2002 were close to the strains in Indonesia in 1998; those in 2007 were close to the strains in Malaysia in 2004; and those in 2008 were close to the strains in Vietnam in 2003. For 2010, the DENV-2 isolates were close to the strains in Vietnam in 2006, the DENV-3 isolates were close to the strains in Indonesia in 2007, and the DENV-4 isolates were close to the strains in Indonesia in 2004. A similar outcome has been reported by Wu et al. . These results provide evidence to support the theory that Southeast Asian countries are the possible source of DENV infection in Guangzhou.
DENV-1 caused 2 major outbreaks in Guangzhou between 2001 and 2010, that is, one in 2002 (1423 cases) and another in 2006 (779 cases). Although they had the same serotype and similar impact, the strains causing the 2 outbreaks had different origins. The phylogenetic trees showed that the isolates from those two outbreaks had 2 different genotypes. The isolates in 2002 belonged to genotype IV and were close to the strain separated in Indonesia in 1998. At the beginning of the outbreak in Guangzhou in 2002 (May), a patient who came from Indonesia was found to have DENV infection. He was the first patient to be infected in 2002; however, viral isolation was unsuccessful in this case. Therefore, it cannot be concluded that the prevalent strain in 2002 came from Indonesia. Similarly, the isolates in 2006 belonged to genotype I. Cambodia was the most prevalent source of DENV infection cases in 2006. There were 8 import cases in Guangzhou that year, 4 (50%) of which came from Cambodia. They were detected in April, August, September, and October. This indicates that in 2006, DENV infection was detected in patients coming from Cambodia at the beginning and during the peak of the outbreak. This is similar to the situation that occurred in 2002, and again, no imported strain was isolated in 2006. Therefore, because of the absence of virus strains from these imported cases, and the lack of epidemiology information in Indonesia (2002) and Cambodia (2006), it’s insufficient to draw a conclusion. However, there may be some connection between the outbreaks and the imported cases.
The diversity in DENV genotypes and serotypes has increased in recent years; almost only DENV-1 was separated during 2001–2008, in contrast, the strains from 2010 included not only all 4 serotypes, but also different genotypes within the same serotype. Researchers believe that the introduction of a new serotype or genotype in an area brings with it a high possibility of a new epidemic. The high diversity of DENV in recent years indicates that there is a hidden risk of DENV epidemics occurring in Guangzhou in the near future, probably caused by the import of strains with new serotypes or genotypes.