Malaria outbreaks in China (1990–2013): a systematic review

Malaria was highly endemic in China (estimated 30 million annual cases) before the foundation of the People’s Republic in 1949 [1]. Tremendous efforts have been put into reducing the malaria burden since the launch of the National Malaria Control Programme in 1955. Despite two major outbreaks in the 1960s and 1970s, respectively, the country showed a steady decrease of its malaria burden [2]. By the end of 1990, there were 117,000 malaria cases reported from China [2]. Over the last two decades, China has further reduced the malaria burden, now with a goal of elimination by 2020 [3, 4]. However, sporadic outbreaks have consistently been reported during the last two decades [5‐7].

Plasmodium falciparum and Plasmodium vivax are the two main malaria species in China. Falciparum malaria was already restricted to only two provinces (Yunnan, Hainan) by 1998, and vivax malaria accounted for 95% of the indigenous malaria cases in 2012 [8, 9]. Plasmodium vivax is less responsive to control interventions and much more difficult to eliminate than P. falciparum[10]. On the other side, imported falciparum malaria is increasingly seen in many provinces [8, 11].

Malaria outbreaks are a clear threat to maintain achievements and to the final goal of elimination in China [12]. They can have various reasons, ranging from environmental causes over parasite/vector characteristics to health system factors and human behaviour aspects [13]. Increasing development in China, which is associated with increased mobility, led to malaria outbreaks in areas where local malaria transmission had previously been interrupted. A strengthened surveillance system contributed largely to active investigation and better reporting of these outbreaks. Therefore, a thorough analysis of the specific reasons for these outbreaks will be helpful to improve the effectiveness of the national malaria programme.

A systematic literature review on causes of published malaria outbreaks in China from 1990 until 2013 has thus been conducted.

The initial search yielded 1,564 records, of which 1,222 remained after removing duplicates (Figure 1). Among them, 154 articles appeared to describe or allude to malaria outbreaks so the full texts were assessed for eligibility. Of these 154 articles, 59 were excluded because the information in the paper was repeated in more detail in other papers; 29/154 articles describing 17 epidemic events were excluded because they do not meet the outbreak definition. For example, the majority (13/17) of the reported epidemics were based on imported malaria cases with no secondary cases. A few of these epidemics were small family clusters (2/17) or caused by parasite transmission through blood donations (2/17). Nine of the 154 articles were excluded because of insufficient information provided; nine were excluded because the reported events occurred before 1990; two articles were excluded because the reported events occurred outside Mainland China. Thus, a total of 46 articles describing 36 outbreaks over the period 1990–2013 were included in the final analysis (see Additional files 1 and 2).

This is the first systematic review to characterize recent malaria outbreaks in China, based on both Chinese and English publications. The study has analysed the main causes of 36 malaria outbreaks reported since 1990 in China. Malaria outbreaks occurred frequently during this time period in about half of all Chinese provinces, but there was no outbreak in the past five years. This supports the promising development of malaria burden reduction in China in recent years [3, 4]. Moreover, a clear shift towards a predominance of P. vivax malaria was observed, which supports the assumption of P. vivax elimination being more difficult than P. falciparum elimination [34]. Population migration was the most frequently identified outbreak cause, followed by operational problems of the health services, environmental factors and changes of vector and host-related factors.

Population migration clearly is of major importance for malaria outbreaks [13]. The causal pathway can either be that populations move from an endemic to a non- or low-endemic area, leading to new or increased malaria transmission, or from a non- or low-endemic area to an endemic area, increasing the pool of susceptible individuals [35]. The findings from this study show that both pathways play an important role in China. Interestingly and in contrast to the situation in the USA and in European countries, where citizens with migration background often import malaria after having visited friends or relatives in their country of origin [36, 37], malaria outbreaks associated with population movements in China were mainly caused by returning export labourers from endemic provinces. These are usually low social class labourers often working under conditions at increased risk of malaria (e g, mining, construction sites, forest work), who are not well protected at night due to poor accommodation, have a low education level and thus lack awareness of malaria risks, have no specific immunity, and often have limited access to health services [38]. Malaria associated with population movements is thus an important threat for elimination, but also for trying to ‘hold the line’ after having already successfully eliminated malaria [12, 39]. This needs to be addressed by national programmes, e g, through active screening of returning workers especially in areas at high risk of outbreaks [12]. Early diagnosis and effective treatment would not only avoid unnecessary deaths but also secondary infections.

Operational problems of the health services were identified as another important cause of outbreaks. Here, aspects related to malaria case management were most frequently mentioned, and this concerns mainly P. vivax. Chloroquine in combination with primaquine has been used for more than 60 years as radical treatment for vivax malaria and is shown to still be effective in central China [40]. However, compliance and safety aspects with prolonged treatment regimens for P. vivax malaria remain a major challenge [41]. Minority populations in China have a high prevalence of G6PD deficiency and are thus at increased risk for haemolysis associated with primaquine treatment [42]. Innovative interventions are thus needed to address this challenge in China if the country wants to achieve the goal of malaria elimination by 2020.

Many formerly endemic areas successfully reduced the malaria burden or even achieved malaria elimination, which was sometimes followed by loosening of vigilance and consequently surveillance by the responsible health services [43]. However, in China surveillance systems have been largely strengthened in recent years and especially after the SARS epidemic [44]. For example, a web-based reporting system of infectious diseases has been implemented since the year 2003 [45]. In order to achieve malaria elimination, a robust surveillance system has been established in China that combines passive and active case detection methods with rapid response measures, including radical treatment and targeted vector control. Moreover and since 2010, China has implemented a ‵1-3-7′ surveillance strategy: one day to report a case, three days to confirm and classify the case, and seven days to conduct a local response and prevent any onward transmission [46]. Since that time, no malaria outbreaks have occurred in China.

Environmental changes such as irrigation or dam projects were also associated with malaria outbreaks in China [47]. However, whether such projects will cause malaria outbreaks depends on various factors. Malaria epidemics are less likely to derive from irrigation projects in high-transmission areas where inhabitants have natural immunity [48]; in contrast, in unstable transmission areas there is high potential for epidemics [49]. In China, most malaria-endemic areas belong to low-transmission areas. Thus, it is important to strengthen intersectoral cooperation and to establish appropriate health services, including early warning systems together with development projects [50]. Extended rainy seasons and natural disasters such as flooding and earthquakes can also contribute to malaria outbreaks [51]. A particularly interesting outbreak, which is described in this review, was attributed to a major fire disaster, where the reduction of cattle that functioned as a biological barrier largely increased human vector contact [24]. Therefore, outbreak awareness and prevention needs to accompany early responses to such disasters.

The considerable re-emergence of malaria at the beginning of 21st Century, which was mainly observed in central China, was associated with changes in vector capacity of An. sinensis for P. vivax[28, 52]. In contrast to An. anthropophagus, which has been the main vector in this area in the past, An. sinensis is considered of low epidemiological significance as it usually shows exophilic and non-anthropophilic behaviour [53, 54]. Malaria endemicity was sustained in areas where An. sinensis remained the single vector, which has been explained by a significant increase in the transmission capacity of An. sinensis for P. vivax[55, 56]. These observations point to the importance of entomological surveys in areas at risk for malaria outbreaks.

This review has some limitations. As these data are from published malaria reports only, it is possible that some outbreaks not documented in the literature have been missed. Another limitation is the fact that clear reasons for outbreaks were frequently not reported in existing publications, and these were consequently not included in the analysis. The findings may also be subject to reporting bias, as report authors may be influenced by their research interests or perhaps by their affiliations (e g, with regional control programmes).

The findings of this review point to the importance of sustaining quality surveillance for population movements associated with malaria transmission for preventing malaria outbreaks in China. Moreover, further strengthening of environmental and entomological surveillance as well as early case management (e g, radical treatment of vivax cases) will pave the way to achieving the final goal of malaria elimination in China.