Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented. An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models. From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973–1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976–1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973–1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000–2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events. In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.

While great success in malaria control has been achieved in China, imported malaria has become a major challenge in the context of malaria elimination. This retrospective study describes the epidemiological profile of imported malaria and identifies the at-risk population during the period of 2001–2011 in Jiangsu Province. Data on imported malaria cases in Jiangsu Province from 2001 to 2011 were collected from the infectious disease surveillance system and case investigation reports. Epidemiological trends were described and correlations between trends in exported labour and malaria imported from other countries were explored. From 2001 to 2011, 918 malaria cases and six malaria deaths were due to malaria imported from other countries, accounting for 12.4% of all malaria cases and 100% of all malaria deaths. During this time period the annual number of indigenous cases decreased from 1,163 to 13 while the number of imported cases increased from 86 to 366. The relative proportion of cases imported from other countries versus other provinces also increased from 0.0% (0/86) to 97.0% (350/361). The most affected demographic groups were males (897 cases, 97.7%) and adults (20–50 years old: 857 cases, 93.4%). All 918 cases had a recent travel history to malaria-endemic areas and the main purpose for travel was overseas labour (848 cases, 92.4%). The cases were mainly acquired from African countries (855 cases, 93.1%). Plasmodium falciparum was the most common species (733 cases, 79.8%). The increase in malaria cases imported from other countries was associated with the growth of investment to Africa from Jiangsu (R² = 0.8057) and the increasing number of exported labourers to Africa from Jiangsu (R² = 0.8863). From 2001 to 2011 in Jiangsu Province, there was a consistent increase in the number of malaria cases imported from other countries while the number of locally acquired cases sharply declined. This trend may be ascribed to the increasing investment from China to Africa and the rising number of Chinese labourers working in Africa. Preventative efforts should be targeted to this high-risk group and the surveillance and response system should be strengthened to prevent local resurgence in Jiangsu.

In Central China the declining incidence of Plasmodium vivax has been interrupted by epidemic expansions and imported cases. The impact of these changes on the local parasite population, and concurrent risks of future resurgence, was assessed. Plasmodium vivax isolates collected from Anhui and Jiangsu provinces, Central China between 2007 and 2010 were genotyped using capillary electrophoresis at seven polymorphic short tandem repeat markers. Spatial and temporal analyses of within-host and population diversity, population structure, and relatedness were conducted on these isolates. Polyclonal infections were infrequent in the 94 isolates from Anhui (4%) and 25 from Jiangsu (12%), with a trend for increasing frequency from 2008 to 2010 (2 to 19%) when combined. Population diversity was high in both provinces and across the years tested (H_E = 0.8 – 0.85). Differentiation between Anhui and Jiangsu was modest (F’ _ST = 0.1). Several clusters of isolates with identical multi-locus haplotypes were observed across both Anhui and Jiangsu. Linkage disequilibrium was strong in both populations and in each year tested (I_A^S = 0.2 – 0.4), but declined two- to four-fold when identical haplotypes were accounted for, indicative of occasional epidemic transmission dynamics. None of five imported isolates shared identical haplotypes to any of the central Chinese isolates. The population genetic structure of P. vivax in Central China highlights unstable transmission, with limited barriers to gene flow between the central provinces. Despite low endemicity, population diversity remained high, but the reservoirs sustaining this diversity remain unclear. The challenge of imported cases and risks of resurgence emphasize the need for continued surveillance to detect early warning signals. Although parasite genotyping has potential to inform the management of outbreaks, further studies are required to identify suitable marker panels for resolving local from imported P. vivax isolates.

Following initiation of China’s National Malaria Elimination Action Plan in 2010, indigenous malaria infections in Jiangsu Province decreased significantly. Meanwhile imported Plasmodium infections have increased substantially, particularly Plasmodium ovale and Plasmodium malariae. Given the risk for malaria resurgence, there is an urgent need to understand the increase in imported P. ovale and P. malariae infections as China works to achieve national malaria elimination. An observational study of imported malaria cases in Jiangsu Province, China was carried out for the period of 2011–2014. A total of 1268 malaria cases were reported in Jiangsu Province from 2011 to 2014. Although imported Plasmodium falciparum cases (n = 1058) accounted for 83.4 % of all reported cases in Jiangsu, P. ovale cases (14, 19, 30, and 46) and their proportion (3.7, 9.6, 8.8, and 13.0 %) of all malaria cases increased over the 4 years. Similarly, P. malariae cases (seven, two, nine, and 10) and proportion (1.9, 1.0, 2.6, and 2.8 %) of all malaria cases increased slightly during this time. A total of 98 cases of Plasmodium ovale curtisi (47/98, 48 %) and Plasmodium ovale wallikeri (51/98, 52 %) were identified as well. Latency periods were significant among these Plasmodium infections (p = 0.00). Also, this study found that the latency periods of P. ovale sp., P. malariae and Plasmodium vivax were significantly longer than P. falciparum. However, for both P. ovale curtisi and P. ovale wallikeri infections, the latency period analysis was not significant (p = 0.81). Misdiagnosis of both P. ovale and P. malariae was greater than 71.5 and 71.4 %, respectively. The P. ovale cases were misdiagnosed as P. falciparum (35 cases, 32.1 %), P. vivax (43 cases, 39.4 %) by lower levels of CDCs or hospitals. And, the P. malariae cases were misdiagnosed as P. falciparum (ten cases, 35.7 %), P. vivax (nine cases, 32.1 %) and P. ovale sp. (one case, 3.6 %). Geographic distribution of imported P. ovale sp. and P. malariae cases in Jiangsu Province mainly originated from sub-Saharan Africa such as Equatorial Guinea, Nigeria, and Angola. Although the vast majority of imported malaria cases were due to P. falciparum, the increase in other rare Plasmodium species originating from sub-Saharan Africa and Southeast Asia should be closely monitored at all levels of health providers focusing on diagnosis and treatment of malaria. In addition to a receptive vector environment, long latency periods and misdiagnosis of P. malariae and P. ovale sp. increase the risk of re-introduction of malaria in China.

China has made great progress in malaria control over the last century and now aims to eliminate malaria by 2020. In 2012, the country launched its 1-3-7 surveillance and response strategy for malaria elimination. The strategy involves to case reporting within 1 day, case investigation within 3 days, and focus investigation and public health actions within 7 days. The aim of this study was to evaluate the challenges in and lessons learned during the implementation of the 1-3-7 strategy in China so far. This qualitative study was conducted in two provinces in China: Gansu province (northwestern China) and Jiangsu province (southeastern China) in 2014. Key informant interviews (n = 6) and in-depth interviews (n = 36) about the implementation aspects of the 1-3-7 strategy were conducted with malaria experts, health staff, laboratory practitioners, and village doctors at the provincial, city, county, township, and village levels. Broad themes related to the challenges in and lessons learned during the implementation of the 1-3-7 strategy were identified according to: case reporting within 1 day, case investigation within 3 days, focus investigation within 7 days, and the overall strategy. The major challenges outlined were related to respecting the timeline of surveillance procedures, the absence of or difficulties in following guidelines on conducting focus investigations, diagnostics, and the increasing number of returning migrant workers from malaria-endemic countries. Important lessons learned revolve around the importance of continuous capacity building, supervision and motivation, quality control, information technology support, applied research, governmental commitment, and intersectoral collaboration. Surveillance is a key intervention in malaria elimination programs. The Chinese 1-3-7 strategy has already proven to be successful but still needs to be improved. In particular, dealing appropriately with imported malaria cases through the screening of migrant workers from malaria-endemic countries is essential for achieving and sustaining malaria elimination in China. China has perfect preconditions for successful malaria elimination provided political commitment and financial investment are guaranteed. The 1-3-7 strategy may also be considered as a model for other countries.

Chloroquine (CQ) was the cornerstone of anti-malarial treatment in Africa for almost 50 years, but has been widely withdrawn due to the emergence and spread of resistance. Recent reports have suggested that CQ-susceptibility may return following the cessation of CQ usage. Here, we monitor CQ sensitivity and determine the prevalence of genetic polymorphisms in the CQ resistance transporter gene (pfcrt) of Plasmodium falciparum isolates recently imported from Africa to China. Blood samples were collected from falciparum malaria patients returning to China from various countries in Africa. Isolates were tested for their sensitivity to CQ using the SYBR Green I test ex vivo, and for a subset of samples, in vitro following culture adaptation. Mutations at positions 72–76 and codon 220 of the pfcrt gene were analyzed by sequencing and confirmed by PCR-RFLP. Correlations between drug sensitivity and pfcrt polymorphisms were investigated. Of 32 culture adapted isolates assayed, 17 (53.1%), 6 (18.8%) and 9 (28.1%) were classified as sensitive, moderately resistant, and highly resistant, respectively. In vitro CQ susceptibility was related to point mutations in the pfcrt gene, the results indicating a strong association between pfcrt genotype and drug sensitivity. A total of 292 isolates were typed at the pfcrt locus, and the prevalence of the wild type (CQ sensitive) haplotype CVMNK in isolates from East, South, North, West and Central Africa were 91.4%, 80.0%, 73.3%, 53.3% and 51.7%, respectively. The only mutant haplotype observed was CVIET, and this was almost always linked to an additional mutation at A220S. Our results suggest that a reduction in drug pressure following withdrawal of CQ as a first-line drug may lead to a resurgence in CQ sensitive parasites. The prevalence of wild-type pfcrt CQ sensitive parasites from East, South and North Africa was higher than from the West and Central areas, but this varied greatly between countries. Further surveillance is required to assess whether the prevalence of CQ resistant parasites will continue to decrease in the absence of widespread CQ usage.