Jun-Hu Chen

Surveillance-response systems: the key to elimination of tropical diseases

Tropical diseases remain a major cause of morbidity and mortality in developing countries. Although combined health efforts brought about significant improvements over the past 20 years, communities in resource-constrained settings lack the means of strengthening their environment in directions that would provide less favourable conditions for pathogens. Still, the impact of infectious diseases is declining worldwide along with progress made regarding responses to basic health problems and improving health services delivery to the most vulnerable populations. The London Declaration on Neglected Tropical Diseases (NTDs), initiated by the World Health Organization’s NTD roadmap, set out the path towards control and eventual elimination of several tropical diseases by 2020, providing an impetus for local and regional disease elimination programmes. Tropical diseases are often patchy and erratic, and there are differing priorities in resources-limited and endemic countries at various levels of their public health systems. In order to identify and prioritize strategic research on elimination of tropical diseases, the ‘First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination’ was convened in Shanghai in June 2012. Current strategies and the NTD roadmap were reviewed, followed by discussions on how to identify and critically examine prevailing challenges and opportunities, including inter-sectoral collaboration and approaches for elimination of several infectious, tropical diseases. A priority research agenda within a ‘One Health-One World’ frame of global health was developed, including (i) the establishment of a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis, malaria and schistosomiasis; (ii) development of new strategies, tools and approaches, such as improved diagnostics and antimalarial therapies; (iii) rigorous validation of surveillance-response systems; and (iv) designing pilot studies to transfer Chinese experiences of successful surveillance-response systems to endemic countries with limited resources.

A Diagnostics Platform for the Integrated Mapping, Monitoring, and Surveillance of Neglected Tropical Diseases: Rationale and Target Product Profiles

JX; Chen, JH; Churcher, TS; Drakeley, CJ; Edwards, T; Fenwick, A; French, M; Gabrielli, AF; Grassly, NC; Harding-Esch, EM; Holland, MJ; Koukounari, A; Lammie, PJ; Leslie, J; Mabey, DC; Rhajaoui, M; Secor, WE; Stothard, JR; Wei, H; Willingham, AL; Zhou, XN; Peeling, RW (2012) A diagnostics platform for the integrated mapping, monitoring, and surveillance of neglected tropical diseases: rationale and target product profiles. PLoS neglected tropical diseases, 6 (7). e1746. ISSN 1935-2727

Co-infections with Babesia microti and Plasmodium parasites along the China-Myanmar border

BackgroundBabesiosis is an emerging health risk in several parts of the world. However, little is known about the prevalence of Babesia in malaria-endemic countries. The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R. China, however, human infection with Babesia microti (B. microti) is not recognized in this region, and its profile of co-infection is not yet clear.MethodsTo understand its profile of co-infections with B. microti, our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013. Four parasite species, including B. microti, Plasmodium falciparum (P. falciparum), P. vivax, and P. malariae, were identified among 449 suspected febrile persons detected by nested polymerase chain reaction (PCR) assay based on small subunit ribosomal ribonucleic acid (RNA) genes of B. microti and Plasmodium spp.ResultsOf all the collected samples from febrile patients, mono-infection with B. microti, P. vivax, P. falciparum, and P. malariae accounted for 1.8% (8/449), 9.8% (44/449), 2.9% (13/449), and 0.2% (1/449), respectively. The rate of mixed infections of B. microti with P. falciparum or P. vivax are both 0.2% (1/449), and mixed infections of P. falciparum and P. vivax accounted for 1.1% (5/449).ConclusionsThis report supports the hypothesis that babesiosis caused by B. microti is emerging along the China-Myanmar border in the Yunnan province, P.R. China, but it was ignored because of low parasitemia or mixed infection with Plasmodium spp. More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.

Rapid identification and differentiation of Fasciola hepatica and Fasciola gigantica by a loop-mediated isothermal amplification (LAMP) assay

The present study developed and validated a species-specific loop-mediated isothermal amplification (LAMP) assay for the rapid detection and discrimination of Fasciola hepatica and Fasciola gigantica. The LAMP assay is inexpensive, easy to perform and shows rapid reaction, wherein the amplification can be obtained in 45 min under isothermal conditions of 61 °C or 62 °C by employing a set of four species-specific primer mixtures and results can be checked through naked-eye visualization. The optimal assay conditions with no cross-reaction with other closely related trematodes (Clonorchis sinensis, Opisthorchis viverrini, Orientobilharzia turkestanicum and Schistosoma japonicum) as well as within the two Fasciola species were established. The assay was validated by examining F. gigantica DNA in the intermediate host snails and in faecal samples. The results indicated that the LAMP assay is approximately 10(4) times more sensitive than the conventional specific PCR assays. These findings indicate that this Fasciola species-specific LAMP assay may have a potential clinical application for detection and differentiation of Fasciola species, especially in endemic countries.

Characterization of microRNAs in Taenia saginata of zoonotic significance by Solexa deep sequencing and bioinformatics analysis

The beef tapeworm Taenia saginata infects human beings with symptoms ranging from nausea, abdominal discomfort to digestive disturbances and intestinal blockage. In the present study, microRNA (miRNA) expressing profile in adult T. saginata was analyzed using Solexa deep sequencing and bioinformatics analysis. A total of 15.8 million reads was obtained by Solexa sequencing, and 13.3 million clean reads (1.73 million unique sequences) was obtained after removing reads smaller than 18 nt. Ten conserved miRNAs corresponding to 607,382 reads were found when matching the reads against known miRNAs of Schistosoma japonicum in miRBase database. The miR-71 had the most abundant expression in T. saginata, followed by miR-219-5p, but some other common miRNAs such as let-7, miR-40, and miR-103 were not identified in T. saginata. Nucleotide bias analysis found that the known miRNAs showed high bias and the uracil was the dominant nucleotide, particularly at the first and 11th positions which were almost at the beginning and middle of conserved miRNAs. One novel miRNA (Tsa-miR-001) corresponding to ten precursors was identified and confirmed by stem-loop RT-PCR. To our knowledge, this is the first report of miRNA profiles in T. saginata, which will contribute to better understanding of the complex biology of this zoonotic trematode. The reported data of T. saginata miRNAs should provide valuable references for miRNA studies of closed related zoonotic Taenia cestodes such as Taenia solium and Taenia asiatica.

Scaling up impact of malaria control programmes: a tale of events in Sub-Saharan Africa and People’s Republic of China

This review aims at providing synthetic information with scientific evidence on the trends in the malaria events from 1960 to 2011, with the hope that it will help policy makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in both Sub-Sahara Africa and in the People’s Republic of China by highlighting the achievements, progress and challenges in research on moving malaria from epidemic status towards elimination. Our findings showed that since 1960, malaria control programmes in most countries have been disjointed and not harmonized. Interestingly, during the last decade, the causal factors of the unprecedented and substantial decline in malaria morbidity and mortality rates in most vulnerable groups in these endemic areas are multifaceted, including not only the spread of malaria and its related effects but also political and financial willingness, commitment and funding by governments and international donors. The benefits of scaling up the impact of malaria coverage interventions, improvement of health system approaches and sustained commitment of stakeholders are highlighted, although considerable efforts are still necessary in Sub-Sahara Africa. Furthermore, novel integrated control strategies aiming at moving malaria from epidemic status to control towards elimination, require solid research priorities both for sustainability of the most efficient existing tools and intervention coverage, and in gaining more insights in the understanding of the epidemiology, pathogenesis, vector dynamics, and socioeconomic aspects of the disease. In conclusion, political commitment and financial investment of stakeholders in sustaining the scaling up impact of malaria control interventions, networking between African and Chinese scientists, and their Western partners are urgently needed in upholding the recent gains, and in translating lessons learnt from the Chinese malaria control achievements and successes into practical interventions in malaria endemic countries in Africa and elsewhere.

Frontiers of parasitology research in the People's Republic of China: infection, diagnosis, protection and surveillance

Control and eventual elimination of human parasitic diseases in the Peoples Republic of China (P.R. China) requires novel approaches, particularly in the areas of diagnostics, mathematical modelling, monitoring, evaluation, surveillance and public health response. A comprehensive effort, involving the collaboration of 188 scientists (>85% from P.R. China) from 48 different institutions and universities (80% from P.R. China), covers this collection of 29 articles published in Parasites & Vectors. The research mainly stems from a research project entitled “Surveillance and diagnostic tools for major parasitic diseases in P.R. China” (grant no. 2008ZX10004-011) and highlights the frontiers of research in parasitology. The majority of articles in this thematic series deals with the most important parasitic diseases in P.R. China, emphasizing Schistosoma japonicum, Plasmodium vivax and Clonorchis sinensis plus some parasites of emerging importance such as Angiostrongylus cantonensis. Significant achievements have been made through the collaborative research programme in the following three fields: (i) development of strategies for the national control programme; (ii) updating the surveillance data of parasitic infections both in human and animals; and (iii) improvement of existing, and development of novel, diagnostic tools to detect parasitic infections. The progress is considerable and warrants broad validation efforts. Combined with the development of improved tools for diagnosis and surveillance, integrated and multi-pronged control strategies should now pave the way for elimination of parasitic diseases in P.R. China. Experiences and lessons learned can stimulate control and elimination efforts of parasitic diseases in other parts of the world.

Prevalence of coccidial infection in sheep and goats in northeastern China

The prevalence of coccidial infection in sheep and goats was examined in Heilongjiang Province, northeastern China between January 2007 and June 2009. A total of 508 faecal samples (309 from sheep and 199 from goats) were collected from eight sheep and goat rearing administrative regions. Oocysts in faecal samples were detected using a flotation technique, sporulated and identified to species based on morphological features of the sporulated oocysts. The overall prevalence of coccidial infection was 90.9% (462/508), with prevalence of 92.9% (287/309) for sheep and 87.9% (175/199) for goats. 13 species of Eimeria were identified, namely, E. bakuensis, E. faurei, E. parva, E. ahsata, E. crandallis, E. granulosa, E. intricata, E. pallida, E. christenseni, E. caprina, E. alijevi, E. apsheronica and E. arloingi. In sheep, the most common Eimeria species were E. ahsata (67.2%), E. parva (59.9%) and E. bakuensis (44.3%). In goats, the more prevalent species were E. christenseni (78.3%), E. alijevi (73.7%), E. caprina (62.3%) and E. arloingi (44.6%). Concurrent infection with two to eight species was common. However, no clinical symptoms were observed in the examined sheep and goats. The results of the present investigation have implications for the control of coccidial infections in sheep and goats in northeastern China.

An integrated immunoproteomics and bioinformatics approach for the analysis of Schistosoma japonicum tegument proteins.

UNLABELLED Schistosomiasis remains one of the major neglected tropical diseases (NTDs) causing morbidity of humans residing in the tropical countries. Much effort has been devoted to the development of vaccines, since it is recognized that vaccines can be served as an important supplementary component alongside chemotherapy for the future control and elimination of schistosomiasis. To accelerate digging new potential target antigens, it is essential to extensively and intensively search immunogenic proteins in a high-throughput manner using proteomics-microarray techniques. In the present study, an integrated immunoproteomics and bioinformatics approach was used to profile the tegument of the human blood fluke Schistosoma japonicum. Results showed that the full-length tegument proteins were high-throughput cloned and expressed and screened with sera from S. japonicum-infected patients and normal subjects using protein arrays. Here, thirty highly immunoreactive tegument proteins and 10 antigens with an AUC value greater than 0.90 were identified at first time. In particularly, STIP1, the highest immunoreactive tegument protein has been shown good antigenicity and immunogenicity, and thus makes it to be a potential target for designing anti-parasite drug or vaccine. BIOLOGICAL SIGNIFICANCE The schistosome tegument plays a crucial role in host-parasite interactions and there are several tegument proteins that proved to be potential vaccine candidates. However, vaccines are not yet available, thus it is important to identify new target antigens from schistosome tegument proteome. Herein, we demonstrate that the S. japonicum tegument proteins were analyzed by an integrated immunoproteomics and bioinformatics approach. We found that thirty highly immunoreactive tegument proteins and 10 antigens with an AUC value greater than 0.90 were identified for the first time. In particularly, we found 17 of tegument immunoproteomes having putative interaction networks with other proteins of S. japonicum. The results will provide clues of potential target molecules for vaccine development and biomarkers for diagnostics of schistosomiasis.

Nobel prize for the artemisinin and ivermectin discoveries: a great boost towards elimination of the global infectious diseases of poverty

The Millennium Development Goals (MDGs) made a marked transformation for neglected and vulnerable communities in the developing countries from the start, but infectious diseases of poverty (IDoPs) continue to inflict a disproportionate global public health burden with associated consequences, thereby contributing to the vicious cycle of poverty and inequity. However, the effectiveness and large-scale coverage of artemisinin combination therapy (ACT) have revolutionized malaria treatment just as the control of lymphatic filariasis (LF) and onchocerciasis have benefitted from harnessing the broad-spectrum effect of avermectin-based derivatives. The paradigm shift in therapeutic approach, effected by these two drugs and their impact on community-based interventions of parasitic diseases plaguing the endemic low- and middle-income countries (LIMCs), led to the Nobel Prize in Physiology or Medicine in 2015. However, the story would not be complete without mentioning praziquantel. The huge contribution of this drug in modernizing the control of schistosomiasis and also some intestinal helminth infections had already shifted the focus from control to potential elimination of this disease. Together, these new drugs have provided humankind with powerful new tools for the alleviation of infectious diseases that humans have lived with since time immemorial. These drugs all have broad-spectrum effects, yet they are very safe and can even be packaged together in various combinations. The strong effect on so many of the great infectious scourges in the developing countries has not only had a remarkable influence on many endemic diseases, but also contributed to improving the cost structure of healthcare. Significant benefits include improved quality of preventive and curative medicine, promotion of community-based interventions, universal health coverage and the fostering of global partnerships. The laudable progress and benefits achieved are indispensable in championing, strengthening and moving forward elimination of the IDoPs. However, there is an urgent need for further innovative, contextual and integrated approaches along with the advent of the Sustainable Development Goals (SDGs), replacing the MDGs in ensuring global health security, well-being and economic prosperity for all.