Zhi-Gui Xia

Research gaps for three main tropical diseases in the People's Republic of China

This scoping review analyzes the research gaps of three diseases: schistosomiasis japonica, malaria and echinococcosis. Based on available data in the P.R. China, we highlight the gaps between control capacity and prevalence levels, and between diagnostic/drug development and population need for treatment at different stages of the national control programme. After reviewing the literature from 848 original studies and consultations with experts in the field, the gaps were identified as follows. Firstly, the malaria research gaps include (i) deficiency of active testing in the public community and no appropriate technique to evaluate elimination, (ii) lack of sensitive diagnostic tools for asymptomatic patients, (iii) lack of safe drugs for mass administration. Secondly, gaps in research of schistosomiasis include (i) incongruent policy in the implementation of integrated control strategy for schistosomiasis, (ii) lack of effective tools for Oncomelania sp. snail control, (iii) lack of a more sensitive and cheaper diagnostic test for large population samples, (iv) lack of new drugs in addition to praziquantel. Thirdly, gaps in research of echinococcosis include (i) low capacity in field epidemiology studies, (ii) lack of sanitation improvement studies in epidemic areas, (iii) lack of a sensitivity test for early diagnosis, (iv) lack of more effective drugs for short-term treatment. We believe these three diseases can eventually be eliminated in mainland China if all the research gaps are abridged in a short period of time.

A single mutation in K13 predominates in Southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment

BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China. METHODS Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models. RESULTS Parasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives. CONCLUSIONS Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

Analysis of Malaria Epidemiological Characteristics in the People's Republic of China, 2004–2013

This study aims to explore and characterize the malaria-endemic situation and trends from 2004 to 2013, to provide useful evidence for subsequently more effective strategic planning of malaria elimination in China. A total of 256,179 confirmed malaria cases were recorded in this period, and 86.8% of them were reported during 2004-2008. Between 2004 and 2008, Plasmodium vivax was the major species (72.2%) of malaria parasite. Most cases (67.3%) were found in male, and mainly in the age group of 35-39 years. A total of 236 deaths resulting from malaria were reported and nearly half (45.3%) of them were in Yunnan province. In all, 204,760 local malaria (79.9%) and 51,419 imported malaria (20.1%) were observed during 2004-2013. However, afterward the proportion of imported malaria continuously increased from 2004 (16.2%) to 2013 (97.9%). Moreover, 9,285 imported malaria cases were recorded during 2011-2013 in China, of which 5,976 cases (64.4%) came back from Africa. Overall, China has made achievements in controlling malaria, the locally transmitted malaria significantly declined in the past decades, by which the incidence has achieved historically the lowest levels. On the other hand, imported malaria has increasingly become a severe threat to malaria elimination. Therefore, to prevent the reintroduction of malaria, surveillance systems need to be well planned and managed to ensure timely case detection and prompt response at the elimination stage.

Historical patterns of malaria transmission in China.

The historical patterns of malaria transmission in the Peoples Republic of China from 1949 to 2010 are presented in this chapter to illustrate the changes in epidemiological features and malaria burden during five decades. A significant reduction of malaria incidence has resulted in initiation of a national malaria elimination programme. However, challenges in malaria elimination have been identified. Foci (or hot spots) have occurred in unstable transmission areas, indicating an urgent need for strengthened surveillance and response in the transition stage from control to elimination.

A potential threat to malaria elimination: extensive deltamethrin and DDT resistance to Anopheles sinensis from the malaria-endemic areas in China

BackgroundInsecticide resistance in malaria vectors is a growing concern in many countries and requires immediate attention because of the limited chemical arsenal available for vector control. There is lack of systematic and standard monitoring data of malaria vector resistance in the endemic areas, which is essential for the ambitious goal of malaria elimination programme of China.MethodsIn 2010, eight provinces from different malaria endemic region were selected for study areas. Bioassays were performed on F1 progeny of Anopheles sinensis reared from wild-caught females using the standard WHO susceptibility test with diagnostic concentrations of 0.25% deltamethrin and 4% DDT.ResultsFor An. sinensis, the results indicated that exposure to 0.25% deltamethrin of F1 families with mortalities ranging from 5.96% to 64.54% and less than 80% mortality to DDT at the diagnostic concentration of 4% across the study areas.ConclusionsAnopheles sinensis was completely resistant to both deltamethrin and DDT, and resistance to pyrethroid has risen strikingly compared to that recorded during 1990s. The results highlight the importance of longitudinal insecticide resistance monitoring and the urgent need for a better understanding of the status of insecticide resistance in this region.

Predicting malaria vector distribution under climate change scenarios in China: Challenges for malaria elimination

Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control activities for sustaining elimination and preventing reintroduction of malaria. In China, however, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of climate change on four dominant malaria vectors (An. dirus, An. minimus, An. lesteri and An. sinensis) using species distribution models for two future decades: the 2030 s and the 2050 s. Simulation-based estimates suggest that the environmentally suitable area (ESA) for An. dirus and An. minimus would increase by an average of 49% and 16%, respectively, under all three scenarios for the 2030 s, but decrease by 11% and 16%, respectively in the 2050 s. By contrast, an increase of 36% and 11%, respectively, in ESA of An. lesteri and An. sinensis, was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios. in the 2050 s. In total, we predict a substantial net increase in the population exposed to the four dominant malaria vectors in the decades of the 2030 s and 2050 s, considering land use changes and urbanization simultaneously. Strategies to achieve and sustain malaria elimination in China will need to account for these potential changes in vector distributions and receptivity.

The Plasmodium vivax in China: decreased in local cases but increased imported cases from Southeast Asia and Africa

Currently the local P. vivax was sharply decreased while the imported vivax malaria increased in China. Despite Southeast Asia was still the main import source of vivax malaria, the trend of Africa become serious, especially for west and central Africa. Herein we have clarified the trend of P. vivax in China from 2004–2012, and made some analysis for the differences of imported vivax back from different regions. There are significantly different of P. vivax between Southeast Asia and Africa, also the difference was observed for different regions in Africa. Additionally, we have explored the possibility for the difference of the P. vivax between migrant workers back from west and central Africa and the prevalence of local population. This reminds us that surveillance and training should be strengthened by medical staffs on the imported P. vivax cases reported especially from west and central Africa, in order to reduce the risk of malaria reintroduction and, specific tools should be developed, as well as the epidemiological study to avoid the misdiagnosis such as P. ovale and P. vivax.

Amplification of pfmdr1, pfcrt, pvmdr1, and K13 Propeller Polymorphisms Associated with Plasmodium falciparum and Plasmodium vivax Isolates from the China-Myanmar Border

ABSTRACT Malaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, the pfmdr1, pfcrt, pvmdr1, and K13-propeller genotypes were determined in 26 Plasmodium falciparum and 64 Plasmodium vivax isolates from Yingjiang county of Yunnan province. The pfmdr1 (11.5%), pfcrt (34.6%), and pvmdr1 (3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% for pfmdr1 N86Y, pfcrt K76T, and pfcrt M74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes of pfmdr1 and pfcrt were Y86Y184 and M74N75T76, respectively. No pvmdr1 mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region.

Imported Malaria in China, 2012

To the Editor: Imported malaria has become a major public health challenge in China. Despite an 89.8% decrease in total cases from 2008 (26,873) through 2012 (2,729), the proportion of imported malaria cases has increased from 14.7% to 89.0% (1). We analyzed the malaria situation in China in 2012 by using data obtained from the national information reporting system of infectious diseases.

Preparedness for malaria resurgence in China: case study on imported cases in 2000-2012.

Malaria is the most important parasitic protozoan infection that has caused serious threats to human health globally. China has had success in reducing the morbidity and mortality of malaria to the lowest level through sustained and large-scale interventions. Although the total number of malaria cases declined gradually, the burden of the imported malaria cases mainly from Southeast Asian and African countries has increased substantially since 2000, posing a severe threat to public health in China. This review explores and analyses the epidemiological characteristics of the imported malaria based on data from 2000 to 2012, in order to provide theoretical bases and insights into effective prevention, avoid the resurgence of malaria in malaria-susceptible areas and develop appropriate strategies to protect peoples health in China. This review also intends to offer the useful information of innovative approaches and tools that are required for malaria elimination in various settings.