Mayaro virus infection, the next epidemic wave after Zika?Evolutionary and structural analysis

Objective: To evaluate the evolution of the pathogen Mayaro virus, causing Mayaro fever(a mosquito-borne disease) and to perform selective pressure analysis and homology modelling.Methods: Nine different datasets were built, one for each protein(from protein C to non-structural protein 4) and the last one for the complete genome. Selective pressure and homology modelling analyses were applied. Results: Two main clades(A and B) were pointed in the maximum likelihood tree. The clade A included five Brazilian sequences sampled from 1955 to 2015. The Brazilian sequence sampled in 2014 significantly clustered with the Haitian sequence sampled in 2015. The clade B included the remaining 27 sequences sampled in the Central and Southern America from 1957 to 2013. Selective pressure analysis revealed several sites under episodic diversifying selection in envelope surface glycoprotein El, non-structural protein 1 and nonstructural protein 3 with a posterior probability P≤0.01. Homology modelling showed different sites modified by selective pressure and some protein-protein interaction sites at high interaction propensity. Conclusion: Maximum likelihood analysis confirmed the Mayaro virus previous circulation in Haiti and the successful spread to the Caribbean and USA. Selective pressure analysis revealed a strong presence of negatively selected sites, suggesting a probable purging of deleterious polymorphisms in functional genes. Homology model showed the position 31, under selective pressure, located in the edge of the ADP-ribose binding site predicting to possess a high potential of protein-protein interaction and suggesting the possible chance for a protective vaccine,thus preventing Mayaro virus urbanization as with Chikungunya virus.

Pathology and genetic connectedness of the mangrove crab (Aratus pisonii) – a foundation for understanding mangrove disease ecology

Mangrove forests are productive ecosystems,acting as a sink for CO_(2),a habitat for a diverse array of terrestrial and marine species,and as a natural barrier to coastline erosion.The species that reside within mangrove ecosystems have important roles to play,including litter decomposition and the recycling of nutrients.Crustacea are important detritivores in such ecosystems and understanding their limitations(i.e.disease)is an important endeavour when considering the larger ecological services provided.Histology and metagenomics were used to identify viral(Nudiviridae,Alphaflexiviridae),bacterial(Paracoccus sp.,'Candidatus Gracilibacteria sp.’,and Pseudoalteromonas sp.),protozoan,fungal,and metazoan diversity that compose the symbiome of the mangrove crab,Aratus pisonii.The symbiotic groups were observed at varying prevalence under histology:nudivirus(6.5%),putative gut epithelial virus(3.2%),ciliated protozoa(35.5%),gonad fungus(3.2%),gill ectoparasitic metazoan(6.5%).Metagenomic analysis of one specimen exhibiting a nudivirus infection provided the complete host mitochondrial genome(15,642 bp),nudivirus genome(108,981 bp),and the genome of a Cassava common mosaic virus isolate(6387 bp).Our phylogenetic analyses group the novel nudivirus with the Gammanudivirus and protein similarity searches indicate that Carcinus maenas nudivrius is the most similar to the new isolate.The mitochondrial genome were used to mine short fragments used in population genetic studies to gauge an idea of diversity in this host species across the USA,Caribbean,and central and southern America.This study report several new symbionts based on their pathology,taxonomy,and genomics(where available)and discuss what effect they may have on the crab population.The role of mangrove crabs from a OneHealth perspective were explored,since their pathobiome includes cassava-infecting viruses.Finally,given that this species is abundant in mangrove forests and now boasts a well-described pathogen profile,we posit that A.pisonii is a valuable model system for understanding mangrove disease ecology.

Molecular recognition of live methicillin-resistant staphylococcus aureus cells using DNA aptamers

AIM: To generate DNA-aptamers binding to Methicillinresistant Staphylococcus aureus(MRSA).METHODS: The Cell-Systematic Evolution of Ligands by Exponential Enrichment(SELEX) technology was used to run the selection against MRSA bacteria and develop target-specific aptamers. MRSA bacteria were targeted while Enterococcus faecalis bacteria were used for counter selection during that process. Binding assays to determine the right aptamer candidates as well as binding assays on clinical samples were performed through flow cytometry and analyzed using the FlowJ o software. The characterization of the aptamers was done by determination of their Kd values and determined by analysis of flow data at different aptamer concentration using Sigma Plot. Finally, the recognitionof the complex Gold-nanoparticle-aptamer to the bacteria cells was observed using transmission electron microscopy(TEM).RESULTS: During the cell-SELEX selection process, 17 rounds were necessary to generate enrichment of the pool. While the selection was run using fixed cells, it was shown that the binding of the pools with live cells was giving similar results. After sequencing and analysis of the two last pools, four sequences were identified to be aptamer candidates. The characterization of those aptamers showed that based on their Kd values, DTMRSA4 presented the best binding with a Kd value of 94.61 ± 18.82 nmol/L. A total of ten clinical samples of MRSA, S. aureus and Enterococcus faecalis were obtained to test those aptamers and determine their binding on a panel of samples. DTMRSA1 and DTMRSA3 showed the best results regarding their specificity to MRSA, DTMRSA1 being the most specific of all. Finally, those aptamers were coupled with gold-nanoparticle and their binding to MRSA cells was visualized through TEM showing that adduction of nanoparticles on the aptamers did not change their binding property.CONCLUSION: A total of four aptamers that bind to MRSA were obtained with Kd values ranking from 94 to 200 nmol/L.

The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma

This paper reviews the epidemiological status and characteristics of clonorchiasis at global level and the etiological relationship between Clonorchis sinensis infection and cholangiocarcinoma(CCA).A conservative estimation was made that 15 million people were infected in the world in 2004,of which over 85%distributed in China.The epidemiology of clonorchiasis is characterized by rising trend in its prevalence,variability among sexes and age,as well as endemicity in different regions.More data indicate that C.sinensis infection is carcinogenic to human,and it is predicted that nearly 5000 CCA cases attributed to C.sinensis infection may occur annually in the world decades later,with its overall odds ratio of 4.47.Clonorchiasis is becoming one major public health problem in east Asia,and it is worthwhile to carry out further epidemiological studies.

AJCN:过敏症来袭怎么办?新型益生菌组合疗法显神效

当进入过敏季节我们可能并不太会拿出手帕或者打喷嚏来预防过敏。日前，一项刊登在国际杂志The American Journal of Clinical Nutrition上的研究报告中。来自佛罗里达大学的研究人员通过研究发现。一种益生菌组合或许能够帮助减轻花粉症的症状。

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

The interactions of CD4^(+)T cells and B cells are fundamental for the generation of protective antibody responses,as well as for the development of harmful autoimmune diseases.Recent studies of human tissues and blood samples have established a new subset of CD4^(+)B helper T cells named peripheral helper T(Tph)cells.Unlike T follicular helper(Tfh)cells,which interact with B cells within lymphoid organs,Tph cells provide help to B cells within inflamed tissues.Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells.The differentiation mechanism is also partly shared between Tph and Tfh cells in humans,and both Tfh and Tph cells can be found within the same tissues,including cancer tissues.However,Tph cells display features distinct from those of Tfh cells,such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bd-6/Blimp1 ratio.Unlike that of Tfh cells,current evidence shows that the target of Tph cells is limited to memory B cells.In this review,we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

The Three Gorges Dam:Does it accelerate or delay the progress towards eliminating transmission of schistosomiasis in China?

The Three Gorges Dam,located in the largest endemic area of schistosomiasis in China,is one of the world’s largest hydroelectric projects to date.Some large-scale hydro projects have resulted in schistosomiasis emergence or re-emergence.Therefore,the dam’s potential impact on the transmission of Schistosoma japonicum has raised concerns from medical researchers worldwide.A systematic literature review,coupled with an analysis of data on the water level and snail density in the Yangtze River was conducted to assess the impact of the dam on schistosomiasis transmission after more than 10 years of operation.The dam has significantly altered the water levels in the Yangtze River according to different seasons.These changes directly impact the ecology of the schistosome snail host.Due to the dam,there has been a reduction in the density of Oncomelania snails and/or changes in the distribution of snails.The prevalence of infection with S.japonicum has decreased in the downstream areas of the dam,including in the Dongting and Poyang Lakes.The prevalence of infection with S.japonicum in humans has decreased from 6.80%in 2002(before the dam began operating)to 0.50%in 2012,and the number of people infected with S.japonicum have decreased from 94208 in 2002 to 59200 in 2011 in the Poyang Lake region.The presence of the dam does not seem to affect snail breeding or the prevalence of schistosomiasis in the Three Gorges Reservoir.Overall,the Three Gorges Dam has significantly contributed to changes in hydrology after more than 10 years of the dam operating.The changes caused by the dam,together with integrated control of schistosomiasis,might be accelerating the progress towards eliminating the transmission of S.japonicum in the middle and lower reaches of the Yangtze River.Despite the positive effect the dam is having in controlling S.japonicum transmission,continued surveillance is required to monitor the future ecological impacts of the dam over the long term.

Critical size limit of biodegradable nanopartides for enhanced lymph node trafficking and paracortex penetration

Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.

Integrating ecological approaches to interrupt schistosomiasis transmission:opportunities and challenges

Background:The development of agenda for global schistosomiasis elimination as a public health problem generates enthusiasms among global health communities,motivating great interests in both research and practice.Recent China-Africa schistosomiasis control initiatives,aiming to enhance collaboration on disease control in African countries,reflect in part that momentum.Yet there is a pressing need to know whether the Chinese experiences can be translated and applied in African settings.Main body:China’s remarkable achievements in schistosomiasis control programme,associated experiences and lessons,have much to offer to those combating the disease.Central to the success of China’s control programmes is a strategy termed“integrated control”-integrating environmental approaches(e.g.improved sanitation,agricultural and hydrological development and management),which target different phases of the parasite transmission system,to chemical-based drug treatment and mollusciciding.Yet,despite significant measurable public health benefits,such integration is usually based on field experience and remains largely uncharacterized in an ecological context.This has limited our knowledge on relative contributions of varying components of the integrated control programme to the suppression of disease transmission,making it challenging to generalize the strategy elsewhere.In this opinion article,we have described and discussed these challenges,along with opportunities and research needs to move forward.Conclusions:There is an urgent need to formalize an ecological framework for the integrated control programme that would allow research towards improved mechanistic understanding,quantification,and prediction of the control efforts.

Infection with severe fever with thrombocytopenia virus in healthy population:a cohort study in a high endemic region,China

Background: Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region.Methods: A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates.Results: Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334-4.461 compared to the group of < 50 years old,P = 0.004], recent contact with cats (adjustedOR = 2.195, 95%CI: 1.261-3.818,P = 0.005), and working in tea garden (adjustedOR = 1.698, 95%CI: 1.002-2.880,P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjustedOR = 2.691, 95%CI: 1.271-5.695 compared to the group of < 50 years old,P = 0.010), and recent contact with cats (OR = 2.648, 95%CI: 1.419-4.941,P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced.Conclusions: Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

Geographical variations in risk factors associated with HIV infection among drug users in a prefecture in Southwest China

Background:Previous studies have shown inconsistent or even contradictory results for some risk factors associated with HIV infection among drug users,and these may be partially explained by geographical variations.Methods:Data were collected from 11 methadone clinics in the Liangshan Yi Autonomous Prefecture from 2004 to 2012.A non-spatial logistical regression model and a geographically weighted logistic regression model were fitted to analyze the association between HIV infection and specific factors at the individual level.Results:This study enrolled 6,458 patients.The prevalence of HIV infection was 25.1%.The non-spatial model indicated that being divorced was positively associated with HIV infection.The spatial model also showed that being divorced was positively associated with HIV infection,but only for 49.4%of individuals residing in some northern counties.The non-spatial model suggested that service sector work was negatively associated with HIV infection.However,the spatial model indicated that service work was associated with HIV infection,but only for 23.0%of patients living in some western counties.The non-spatial model did not show that being married was associated with HIV infection in our study field,but the spatial model indicated that being married was negatively associated with HIV infection for 12.0%of individuals living in some western counties.For other factors,the non-spatial and spatial models showed similar results.Conclusion:The spatial model may be useful for improving understanding of geographical heterogeneity in the relationship between HIV infection and individual factors.Spatial heterogeneity may be useful for tailoring intervention strategies for local regions,which can consequently result in a more efficient allocation of limited resources toward the control of HIV transmission.

迈向人类健康和文明的新境界：星球健康

2015年7月16日，Lancet杂志发表了由洛克菲勒基金会（Rockefeller Foundation）和该杂志共同委托全球19家高校、研究所和基金会，22位公共健康、环境科学、生态学、

A primer on using mathematics to understand COVID-19 dynamics: Modeling, analysis and simulations

The novel coronavirus(COVID-19)pandemic that emerged from Wuhan city in December 2019 overwhelmed health systems and paralyzed economies around the world.It became the most important public health challenge facing mankind since the 1918 Spanish flu pandemic.Various theoretical and empirical approaches have been designed and used to gain insight into the transmission dynamics and control of the pandemic.This study presents a primer for formulating,analysing and simulating mathematical models for understanding the dynamics of COVID-19.Specifically,we introduce simple compartmental,Kermack-McKendrick-type epidemic models with homogeneously-and heterogeneously-mixed populations,an endemic model for assessing the potential population-level impact of a hypothetical COVID-19 vaccine.We illustrate how some basic non-pharmaceutical interventions against COVID-19 can be incorporated into the epidemic model.A brief overview of other kinds of models that have been used to study the dynamics of COVID-19,such as agent-based,network and statistical models,is also presented.Possible extensions of the basic model,as well as open challenges associated with the formulation and theoretical analysis of models for COVID-19 dynamics,are suggested.

Mapping the distributions of blood-sucking mites and mite-borne agents in China:a modeling study

Background:Emerging mite-borne pathogens and associated disease burdens in recent decades are raising serious public health concerns,yet their distributions and ecology remain under-investigated.We aim to describe the geographical distributions of blood-sucking mites and mite-borne agents and to assess their ecological niches in China.Methods:We mapped 549 species of blood-sucking mites belonging to 100 genera at the county level and eight mite-associated agents detected from 36 species of blood-sucking mites in China during 1978–2020.Impacts of climatic and environmental factors on the ecology of 21 predominant vector mites and a leading pathogen,Orientia tsutsugamushi,were assessed using boosted regression tree(BRT)models,and model-predicted risks were mapped.We also estimated the model-predicted number,area and population size of afected counties for each of the 21 mite species in China.Results:Laelaps echidninus is the leading mite species that potentially afects 744 million people,followed by La.jettmari(517 million)and Eulaelaps stabularis(452 million).Leptotrombidium scutellare is the mite species harboring the highest variety of mite-borne agents including four Rickettsia species and two viruses,followed by Eu.stabularis(2 agents),L.palpale(2)and La.echidninus(2).The top two agents that parasitize the largest number of mite species are O.tsutsugamushi(28 species)and hantavirus(8).Mammalian richness,annual mean temperature and precipitation of the driest quarter jointly determine the ecology of the mites,forming four clusters of major mite species with distinct geographic distributions.High-risk areas of O.tsutsugamushi are mainly distributed in southern and eastern coastal provinces where 71.5 million people live.Conclusions:Ecological niches of major mite species and mite-borne pathogens are much more extensive than what have been observed,necessitating expansion of current fled surveillance.

Addressing vulnerability,building resilience:community-based adaptation to vectorborne diseases in the context of global change

Background:The threat of a rapidly changing planet-of coupled social,environmental and climatic change-pose new conceptual and practical challenges in responding to vector-borne diseases.These include non-linear and uncertain spatial-temporal change dynamics associated with climate,animals,land,water,food,settlement,conflict,ecology and human socio-cultural,economic and political-institutional systems.To date,research efforts have been dominated by disease modeling,which has provided limited practical advice to policymakers and practitioners in developing policies and programmes on the ground.Main body:In this paper,we provide an alternative biosocial perspective grounded in social science insights,drawing upon concepts of vulnerability,resilience,participation and community-based adaptation.Our analysis was informed by a realist review(provided in the Additional file 2)focused on seven major climate-sensitive vectorborne diseases:malaria,schistosomiasis,dengue,leishmaniasis,sleeping sickness,chagas disease,and rift valley fever.Here,we situate our analysis of existing community-based interventions within the context of global change processes and the wider social science literature.We identify and discuss best practices and conceptual principles that should guide future community-based efforts to mitigate human vulnerability to vector-borne diseases.We argue that more focused attention and investments are needed in meaningful public participation,appropriate technologies,the strengthening of health systems,sustainable development,wider institutional changes and attention to the social determinants of health,including the drivers of co-infection.Conclusion:In order to respond effectively to uncertain future scenarios for vector-borne disease in a changing world,more attention needs to be given to building resilient and equitable systems in the present.

Prevalence of and risk factors associated with Cryptosporidium infection in an underdeveloped rural community of southwest China

Background:Cryptosporidium spp.is an important intestinal protozoan causing diarrhea in humans,livestock,and wild animals.Cryptosporidium infection remains a major public health issue,but its epidemiology in humans is still unclear,particularly in rural China.This study was designed to determine the prevalence of and risk factors associated with Cryptosporidium infection in a rural southwestern Chinese community.Methods:A community-based cross-sectional survey was conducted among 687 residents of a small town in a Yi autonomous prefecture of southwest China in 2014.Blood samples were examined using a broad set of quality-controlled diagnostic methods for hepatitis B virus(HBV)and human immunodeficiency virus(HIV).Stool specimens were processed using the modified acid-fast staining method,and microscopically examined for Cryptosporidium infection.Univariable and multivariable analyses were performed to determine the risk factors associated with Cryptosporidium infection.Results:The majority of the participants were Yi people with poor living conditions and unsatisfactory hygiene habits,and the study area was of very low socioeconomic status.Of the 615 individuals included in the analysis,14(2.3%)were HIV positive,51(8.3%)were infected with HBV,and 74(12.0%)had Cryptosporidium infection.The prevalences of HIV/HBV,HIV/Cryptosporidium,and HBV/Cryptosporidium co-infections were 0.3%,0.3%,and 1.8%,respectively.The prevalence of HBV infection was higher in individuals with Cryptosporidium infection(χ^(2)=5.00,P=0.03).Owning livestock or poultry was an important risk factor for Cryptosporidium infection(aOR=2.27,95%CI:1.01-5.08,P<0.05).Cryptosporidium infection was significantly associated with HBV infection(aOR=3.42,95%CI:1.47-7.92,P<0.01),but not with HIV infection(aOR=0.57,95%CI:0.07-4.39,P=0.59).Conclusions:The prevalence of Cryptosporidium infection was high in the rural area of southwestern China that was investigated,and there was a significant association between HBV infection and Cryptosporidium infection.Further investigations are needed to determine the significance of Cryptosporidium infection in patients infected with HBV.

Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020

Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases<65 years but with a lower risk(adjusted OR=0.31,95%Cl:0.18-0.51)among male cases>65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

Assessing the nonhuman primate reservoir of Schistosoma mansoni in Africa:a systematic review

Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,has led to concerns about the role of NHPs in the transmission of human schistosomiasis.We conducted a systematic review of the literature to describe the current scope of knowledge for Africa,for the NHP species implicated,their geographical distribution,infection rates with 5.mansoni,and to discuss the implications for public health and conservation.Main text:A systematic search of the literature was performed using PubMed,Web of Science,Google Scholar,the World Health Organization(WHO)library database,World Cat,and ScienceDirect without any language restriction.Studies examining 5.monsoni infeaion of any African NHP species were included.Study types,primate species,their geographical distribution,and parasite diagnostic techniques reported in the studies were qualitatively summarized.Data for species with sample sizes>10 were included in the meta-analysis.We assessed the reported infection rate,and used a random-effeas model to estimate the summary infeaion rates and 95%confidence intervals(C/s).We assessed heterogeneity among studies using the I2 statistics.Twenty-nine publications,from 1960 to 2018,were identified and included in the review.The studies examined a total of 2962 primates belonging to 22 species in 11 genera across ten countries(Cameroon,Eritrea,Ethiopia,Gabon,Kenya,Nigeria,Senegal,Tanzania,Uganda,and Zimbabwe),and 5.mansoni infeaions were found in nine species of five genera in all countries.When we excluded studies with sample sizes<10,data from 24 studies on 11 species of primates in three genera in ten countries remained in the meta-analysis.The overall pooled estimate of infection rate was 10%(95%Cl:6-16%)with high heterogeneity(I^2=9477%)across countries and species/genera.Among the three genera,Pan had the highest infection rate of 15%(95%CI:0-55%),followed by Popio at 11%(95%Cl:6-18%),and Cercopithecus at 5%(95%CI:0-14%).The association between NHP and human infections was positive,but not significant,due to low study sample matches and high variation.Conclusions:Our findings suggest that 5.mansoni infection rate is high in African NHPs,with substantial heterogeneities across spedes/genera and countries in Africa.Given the evidence for potential spillover and spillback of S.mansoni between African NHPs and humans,further research is urgently needed to understand ecology and mechanisms of transmission of the parasite between NHP and human hosts,in order to inform control strategies of this important neglected tropical disease.

Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome(SFTS)virus(SFTSV)is an emerging tick-borne virus with high fatality and an expanding endemic.Currently,effective anti-SFTSV intervention remains unavailable.Favipiravir(T-705)was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV.Here,we conducted a single-blind,randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS(Chinese Clinical Trial Registry website,number ChiCTR1900023350).From May to August 2018,laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only.Fatal outcome occurred in 9.5%(7/74)of T-705 treated patients and 18.3%(13/71)of controls(odds ratio,0.466,95%Cl,0.174-1.247).Cox regression showed a significant reduction in case fatality rate(CFR)with an adjusted hazard ratio of 0.366(95%Cl,0.142-0.944).Among the low-viral load subgroup(RT-PCR cycle threshold>26),T-705 treatment significantly reduced CFR from 11.5 to 1.6%(P=0.029),while no between-arm difference was observed in the high-viral load subgroup(RT-PCR cycle threshold<26).The T-705-treated group showed shorter viral clearance,lower incidence of hemorrhagic signs,and faster recovery of laboratory abnormities compared with the controls.The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates,particularly from two transition mutation types.The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads,further supporting the anti-SFTSV effect of T-705,especially for the low-viral loads.

Epidemiological and Clinical Features of Patients with Scrub Typhus—Guangzhou City,Guangdong Province,China,2012–2018

Summary What is already known about this topic?Scrub typhus(ST)causes public health challenges in the“tsutsugamushi triangle”in the Asia-Pacific area greater than 13 million square kilometers,affecting an estimated one million people each year.What is added by this report?A retrospective study based on 4,501 hospitalized patients with ST in Guangzhou City,China,described the epidemiological and clinical characteristics,laboratory findings of ST.