Progress towards dog-mediated rabies elimination in PR China: a scoping review

Abstract Background Rabies continues to be a serious threat to global public health endangering people’s health and public health safety. In the People’s Republic of China, multi-sectoral and comprehensive prevention and control strategies have aimed to extensively curb human rabies transmission. Here, we examine the current state of rabies infection in China, explore strategic interventions put in place in response to WHO’s ambition of “Zero rabies deaths by 2030” and critically assess the constraints and feasibility of dog-mediated rabies elimination in China. Methods This study analyzed and evaluated the process towards dog-mediated rabies elimination in China from five perspectives: namely, human, dog, policy, challenge, and prospects. Evidence-based data on progress of dog-mediated rabies elimination in China was derived from a number of sources; a literature search was undertaken using PubMed, Web of Science and CNKI databases, distribution data for human rabies cases as derived from the Data-center of the China Public Health Science and policy and document data were obtained from official websites of the relevant China ministries and commissions. Results The incidence of human rabies cases in China have shown a downward trend year-on-year since 2007. Implementation of a government-led, multi-sectoral “One Health” approach to combating rabies has driven down the total number of rabies deaths nationwide to around 200 in 2020. The number of provincial-level administrative divisions (PLADs) reporting human cases of rabies has also decreased to 21 in 2020, 13 of which reported less than 10 cases. Furthermore, the number of outpatient visits seeking rabies post-exposure prophylaxis has risen dramatically over the past two decades, with demand being 15 times higher than it was initially. There remain however, significant gaps in rabies elimination outcomes across the different regions of China. To date the target of achieving a canine rabies vaccination rate of > 75% has not been met. The challenges of rabies immunization of dogs and dog management in underdeveloped cities and rural areas need to be addressed together with more effective animal surveillance and rabies risk from and too wildlife and livestock. Conclusions The Chinese government-led, multi-sectoral “One Health” approach to combating rabies and has made significant progress over the past decade. Development and adoption of more cost-effective One Health strategies can achieve more nationally beneficial rabies elimination outcomes. The ambitious target of “Zero rabies deaths by 2030” can be met through establishment of long-lasting herd immunity in dogs by means of dog mass vaccination campaigns, dog population management, epidemiological surveillance and the application of large-scale oral rabies vaccine to eliminate rabies in wild animals coupled with deployment of cost-effective human post-exposure prophylaxis, and community education. Graphical Abstrac

<i>MiR-26a</i> Promotes Ovarian Cancer Proliferation and Tumorigenesis

<div><p>MicroRNAs (miRNAs) important for posttranscriptional gene expression are involved in the initiation and progression of human cancer. In this study, we reported that <i>miR-26a</i> was over-expressed in human EOC specimens and the expression level of extracellular <i>miR-26a</i> in plasma can distinguish patients from healthy controls in EOC. Ectopic expression of <i>miR-26a</i> in ovarian cancer (OC) cells increased cell proliferation and clonal formation. This growth promoting effect of OC cell growth was mediated by <i>miR-26a</i> inhibition of the posttranscription of ER-α. Furthermore, inhibition of <i>miR-26a</i> suppressed the tumor formation generated by injecting OC cells in nude mice. Our results suggest that aberrantly expressed <i>miR-26a</i> may contribute to OC development.</p></div

ERα was a target of <i>miR-26a</i>.

<p>(A) Stable 1 cells (S1) were transfected with pGL3-ERα-WT (WT) reporter vector or pGL3-ERα-Mut (MUT). Data were mean±s.e. of three independent experiments. **P<0.01 vs control cells (Ctrl). (B) Quantitative analysis of the expression levels of ERα in Stable1 (S1), Stable2 (S2) and control (Ctrl) cells were determined and normalized to GAPDH mRNA levels. *p<0.05,**P<0.01 vs Ctrl. (C) Western-blot analysis of total cell lysates extracted from indicated stable cells using the indicated antibodies. Data was representative of three independent experiments and quantitation normalized with the Ctrl. Tubulin served as a loading control. (D) The growth curves of S1, S2 and Ctrl cells. Data were mean±s.e. of three independent experiments in triplicate. *p<0.05, **P<0.01 vs Ctrl. (E) Over-expression of ERα decreased the growth of S1 cells after transfection. Cell numbers were normalized to Ctrl cells. Data were mean±s.e. of three independent experiments in triplicate.</p

The expression of <i>miR-26a</i> was increased in EOC patients.

<p>(A)Quantitative analysis of the expression levels of <i>miR-26a</i> in EOC samples normalized to those of 18s rRNA by qRT-PCR. Data for each dot were mean value of one sample repeated in three independent experiments (normal, n = 19; tumor, n = 26). **P<0.01 vs Normal. (B)Quantitative analysis of the expression levels of plasma <i>miR-26a</i> by qRT-PCR. Data for each dot were mean value of one sample repeated in three independent experiments (normal, n = 13; tumor, n = 17).</p

<i>MiR-26a</i> promoted EOC cell growth.

<p>Growth curves of SKOV3 (A) or ES2 (B) cells transfected with <i>miR-26a</i> (left panel) or anti-miR-26a (right panel). Cell numbers were normalized to those in 0 hr. Data were mean±s.e. of three independent experiments in triplicate. *p<0.05, **p<0.01 vs empty vector (Ctrl) or negative control (NC). (C) Cell proliferation transfected with <i>miR-26a</i> was measured by a WST-1 assay. Data were mean±s.e. of three independent experiments in triplicate. **p<0.01 vs empty vector (Ctrl) (D) Quantification of the colonies formed by Ctrl or <i>miR-26a</i> transfected cells. Data were mean±s.e. of three independent experiments. **P<0.01 vs Ctrl.</p

<i>MiR-26a</i> promoted the development of tumor in nude mice.

<p>Tumor formation generated by the SKOV3 cells. (A) transfected with <i>miR-26a</i> or anti-miR-26a(B) Nude mice were subcutaneously injected with 2×10⁶ transfected cells. Representative images, measurement of the final volume and weight of the tumors formed. The tumor sizes were measured and calculated in Materials and methods. Data were mean±s.d. of 4–6 mice. **P<0.01 vs empty vector or nonsense.</p

Epidemiology of Trypanosomiasis in Wildlife—Implications for Humans at the Wildlife Interface in Africa

While both human and animal trypanosomiasis continue to present as major human and animal public health constraints globally, detailed analyses of trypanosome wildlife reservoir hosts remain sparse. African animal trypanosomiasis (AAT) affects both livestock and wildlife carrying a significant risk of spillover and cross-transmission of species and strains between populations. Increased human activity together with pressure on land resources is increasing wildlife–livestock–human infections. Increasing proximity between human settlements and grazing lands to wildlife reserves and game parks only serves to exacerbate zoonotic risk. Communities living and maintaining livestock on the fringes of wildlife-rich ecosystems require to have in place methods of vector control for prevention of AAT transmission and for the treatment of their livestock. Major Trypanosoma spp. include Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma cruzi, pathogenic for humans, and Trypanosoma vivax, Trypanosoma congolense, Trypanosoma evansi, Trypanosoma brucei brucei, Trypanosoma dionisii, Trypanosoma thomasbancrofti, Trypanosma elephantis, Trypanosoma vegrandis, Trypanosoma copemani, Trypanosoma irwini, Trypanosoma copemani, Trypanosoma gilletti, Trypanosoma theileri, Trypanosoma godfreyi, Trypansoma simiae, and Trypanosoma (Megatrypanum) pestanai. Wildlife hosts for the trypansomatidae include subfamilies of Bovinae, Suidae, Pantherinae, Equidae, Alcephinae, Cercopithecinae, Crocodilinae, Pteropodidae, Peramelidae, Sigmodontidae, and Meliphagidae. Wildlife species are generally considered tolerant to trypanosome infection following centuries of coexistence of vectors and wildlife hosts. Tolerance is influenced by age, sex, species, and physiological condition and parasite challenge. Cyclic transmission through Glossina species occurs for T. congolense, T. simiae, T. vivax, T. brucei, and T. b. rhodesiense, T. b. gambiense, and within Reduviid bugs for T. cruzi. T. evansi is mechanically transmitted, and T. vixax is also commonly transmitted by biting flies including tsetse. Wildlife animal species serve as long-term reservoirs of infection, but the delicate acquired balance between trypanotolerance and trypanosome challenge can be disrupted by an increase in challenge and/or the introduction of new more virulent species into the ecosystem. There is a need to protect wildlife, animal, and human populations from the infectious consequences of encroachment to preserve and protect these populations. In this review, we explore the ecology and epidemiology of Trypanosoma spp. in wildlife