Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Revisiting the antigen markers of vector-borne parasitic diseases identified by immunomics: identification and application to disease control.

INTRODUCTION: Protein microarray is a promising immunomic approach for identifying biomarkers. Based on our previous study that reviewed parasite antigens and recent parasitic omics research, this article expands to include information on vector-borne parasitic diseases (VBPDs), namely, malaria, schistosomiasis, leishmaniasis, babesiosis, trypanosomiasis, lymphatic filariasis, and onchocerciasis. AREAS COVERED: We revisit and systematically summarize antigen markers of vector-borne parasites identified by the immunomic approach and discuss the latest advances in identifying antigens for the rational development of diagnostics and vaccines. The applications and challenges of this approach for VBPD control are also discussed. EXPERT OPINION: The immunomic approach has enabled the identification and/or validation of antigen markers for vaccine development, diagnosis, disease surveillance, and treatment. However, this approach presents several challenges, including limited sample size, variability in antigen expression, false-positive results, complexity of omics data, validation and reproducibility, and heterogeneity of diseases. In addition, antigen involvement in host immune evasion and antigen sensitivity/specificity are major issues in its application. Despite these limitations, this approach remains promising for controlling VBPD. Advances in technology and data analysis methods should continue to improve candidate antigen identification, as well as the use of a multiantigen approach in diagnostic and vaccine development for VBPD control.

A versatile microfluidic platform for malaria infection screening and Plasmodium species genotyping.

BACKGROUND: Malaria, a widespread parasitic disease caused by Plasmodium species, remains a significant global health concern. Rapid and accurate detection, as well as species genotyping, are critical for effective malaria control. METHODS: We have developed a Flexible, Robust, Equipment-free Microfluidic (FREM) platform, which integrates recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)-based detection, enabling simultaneous malaria infection screening and Plasmodium species genotyping. The microfluidic chip enabled the parallel detection of multiple Plasmodium species, each amplified by universal RPA primers and genotyped by specific crRNAs. The inclusion of a sucrose solution effectively created spatial separation between the RPA and CRISPR assays within a one-pot system, effectively resolving compatibility issues. FINDINGS: Clinical assessment of DNA extracts from patients with suspected malaria demonstrates the FREM platform's superior sensitivity (98.41%) and specificity (92.86%), yielding consistent results with PCR-sequencing for malaria detection, which achieved a positive predictive agreement of 98.41% and a negative predictive agreement of 92.86%. Additionally, the accuracy of species genotyping was validated through concordance rates of 90.91% between the FREM platform and PCR-sequencing. INTERPRETATION: The FREM platform offers a promising solution for point-of-care malaria screening and Plasmodium species genotyping. It highlights the possibility of improving malaria control efforts and expanding its applicability to address other infectious diseases. FUNDING: This work was financially supported by International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion, National Natural Science Foundation of China, the Natural Science Foundation of Shanghai, Bill & Melinda Gates Foundation and National Research and Development Plan of China.

Polymorphism of Drug Resistance Genes dhfr and dhps in Plasmodium falciparum Isolates among Chinese Migrant Workers Who Returned from Ghana in 2013.

In 2013, an epidemic of falciparum malaria involving over 820 persons unexpectedly broke out in Shanglin County, Guangxi Zhuang Autonomous Region, China, after a large number of migrant workers returned from Ghana, where they worked as gold miners. Herein, we selected 146 isolates randomly collected from these patients to investigate the resistance characteristics of the parasite to sulfadoxine-pyrimethamine (SP) by screening mutations in the dhfr and dhps genes. All 146 isolates were successfully genotyped for dhps, and only 137 samples were successfully genotyped for dhfr. In the dhfr gene, point mutations occurred at three codons: 51 (83.2%, 114/137), 59 (94.9%, 130/137), and 108 (96.4%, 132/137). In the dhps gene, mutations occurred at four codons: 436 (36.3%, 53/146 for S436A, 0.7%, 1/146 for S436Y), 437 (95.2%, 139/146), 540 (3.4%, 5/146), and 613 (2.7%, 4/146). All 146 isolates had mutations in at least one codon, either within dhfr or dhps. Quadruple mutation I51R59N108/G437 (41.1%, 60/146) of partial or low resistance level was the most prevalent haplotype combination. Quintuple I51R59N108/G437E540 accounted for 2.1% (3/146). Sextuple I51R59N108/A436G437S613 was also found and accounted for 1.4% (2/146). A chronological assay incorporating two sets of resistance data from the studies of Duah and Amenga-Etego provided an overview of the resistance trend from 2003 to 2018. During this period, the results we obtained generally coincided with the total development tendency of SP resistance. It can be concluded that Plasmodium falciparum samples collected from Chinese migrant workers from Ghana presented prevalent but relatively partial or low resistance to SP. A chronological assay incorporating two sets of data around 2013 indicates that our results possibly reflect the SP resistance level of Ghana in 2013 and that the possibility of increased resistance exists. Therefore, reasonable drug use and management should be strengthened while also maintaining a continuous screening of resistance to SP. These findings also underscore the need to strengthen the prevention of malaria importation from overseas and focus on preventing its reintroduction and transmission in China.

Diagnostic Efficacy of Plasma-Based Real-Time PCR for Schistosomiasis Japonica in Mice before and after Treatment with Praziquantel.

The prevalence of schistosomiasis japonica in China is now characterized by a low epidemic rate and low-intensity infections. Some diagnostic methods with high sensitivity and specificity are urgently needed to better monitor this disease in the current situation. In this study, the detection efficacy of a real-time fluorescent quantitative PCR (qPCR) assay was assessed for schistosomiasis japonica in mice, and before and after treatment with praziquantel (PZQ). Our results showed that the sensitivity of the qPCR was 99.3% (152/153, 95% CI: 96.41-99.98%) and its specificity was 100% (77/77, 95% CI: 95.32-100%) in mice infected with different numbers of Schistosoma japonicum. After the oral administration of PZQ, mice infected with 10 cercariae or 40 cercariae were all Schistosoma japonicum-negative 6 weeks after treatment. However, the negativity rates on a soluble egg antigen (SEA)-based enzyme-linked immunosorbent assay (ELISA) were only 34.8% (8/23, 10 cercariae group) and 6.7% (1/15, 40 cercariae group) at the sixth week after PZQ treatment. These results demonstrated that the qPCR method had good sensitivity and specificity, and suggested that its sensitivity correlated with the infection intensity in mice. Moreover, this method had better potential utility for evaluating the treatment efficacy of PZQ in schistosome-infected mice than SEA-based ELISA.

Reemergence of Visceral Leishmaniasis in Henan Province, China.

Visceral leishmaniasis (VL) was widely prevalent in Henan Province in the 1950s. Through active efforts by the government, there were no local cases reported from 1984 to 2015. In 2016, local VL cases reoccurred, and there was an increasing trend of VL cases in Henan Province. To provide a scientific control of VL, an investigation was conducted in Henan Province from 2016 to 2021. The data from VL cases were obtained from the Disease Surveillance Reporting System of the Chinese Center for Disease Control and Prevention. The rK39 immunochromatographic test (ICT) and PCR assay were performed among high-risk residents and all dogs in the patients' village. ITS1 was amplified, sequenced, and subjected to phylogenetic analyses. A total of 47 VL cases were reported in Henan Province during 2016-2021. Of the cases, 35 were local, and they were distributed in Zhengzhou, Luoyang, and Anyang. The annual average incidence was 0.008/100,000, showing an upward trend year by year (χ2 = 3.987, p = 0.046). Their ages ranged from 7 months to 71 years, with 44.68% (21/47) in the age group of 0-3 years and 46.81% (22/47) in the age group ≥15 years. The cases occurred throughout the year. The high-risk populations were infants and young children (age ≤3), accounting for 51.06% (24/47), followed by farmers at 36.17% (17/47). The ratio of males to females was 2.13:1. The positive rates of rK39 ICT and PCR were 0.35% (4/1130) and 0.21% (1/468) in the residents. The positive rates of rK39 ICT and PCR were 18.79% (440/2342) and 14.92% (139/929) in the dogs. The ITS1 amplification products in the patients and positive dogs were sequenced. The homology between the target sequence and Leishmania infantum was more than 98%. The phylogenetic analysis indicated that the patients and the positive dogs were infected by the same type of Leishmania, which was consistent with the strains in the hilly endemic areas in China. This paper showed that patients and domestic dogs were infected by the same type of L. infantum and that the positive rate in dogs was relatively high in Henan Province. Because the measures of patient treatment and culling of infected dogs were not effective in reducing VL incidence in Henan Province, it is urgent to develop new approaches for the control of VL, such as wearing insecticide-impregnated collars on dogs, treating the positive dogs, spraying insecticide for sandflies control, and improving residents' self-protection awareness to prevent the further spread of VL in Henan Province.

Two Molecular Plasma-Based Diagnostic Methods to Evaluate Early Infection of Schistosoma japonicum and Schistosomiasis Japonica.

The prevalence and infectious intensity of schistosomiasis japonica has decreased significantly in China in the past few decades. However, more accurate and sensitive diagnostic methods are urgently required for the further control, surveillance, and final elimination of the disease. In this study, we assessed the diagnostic efficacy of a real-time fluorescence quantitative PCR (qPCR) method and recombinase polymerase amplification (RPA) combined with a lateral-flow dipstick (LFD) assay for detecting early infections of Schistosoma japonicum and different infection intensities. The sensitivity of the qPCR at 40 days post-infection (dpi) was 100% (8/8) in mice infected with 40 cercariae, which was higher than in mice infected with 10 cercariae (90%, 9/10) or five cercariae (77.8%, 7/9). The results of the RPA-LFD assays were similar, with sensitivities of 55.6% (5/9), 80% (8/10), and 100% (8/8) in mice infected with 5, 10, and 40 cercariae, respectively. In goats, both the qPCR and RPA-LFD assays showed 100% (8/8) sensitivity at 56 dpi. In the early detection of S. japonicum infection in mice and goats with qPCR, the first peak in positivity appeared at 3-4 dpi, when the positivity rate exceeded 40%, even in the low infection, intensity mice. In the RPA-LFD assays, positive results first peaked at 4-5 dpi in the mice, and the positivity rate was 37.5% in the goats at 1 dpi. In conclusion, neither of the molecular methods produced exceptional results for the early diagnosis of S. japonicum infection. However, they were useful methods for the regular diagnosis of schistosomiasis in mice and goats.

Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can involve persistence, sequelae, and other clinical complications that last weeks to months to evolve into long COVID-19. Exploratory studies have suggested that interleukin-6 (IL-6) is related to COVID-19; however, the correlation between IL-6 and long COVID-19 is unknown. We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19. METHODS: Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022. A total of 22 published studies were eligible for inclusion following the PRISMA guidelines. Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared (I2) statistic for heterogeneity. Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19, healthy, non-postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (non-PASC), and acute COVID-19 populations. The funnel plot and Egger's test were used to assess potential publication bias. Sensitivity analysis was used to test the stability of the results. RESULTS: An increase in IL-6 levels was observed after SARS-CoV-2 infection. The pooled estimate of IL-6 revealed a mean value of 20.92 pg/ml (95% CI = 9.30-32.54 pg/ml, I2 = 100%, P < 0.01) for long COVID-19 patients. The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls (mean difference = 9.75 pg/ml, 95% CI = 5.75-13.75 pg/ml, I2 = 100%, P < 0.00001) and PASC category (mean difference = 3.32 pg/ml, 95% CI = 0.22-6.42 pg/ml, I2 = 88%, P = 0.04). The symmetry of the funnel plots was not obvious, and Egger's test showed that there was no significant small study effect in all groups. CONCLUSIONS: This study showed that increased IL-6 correlates with long COVID-19. Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on the "early stage" of long COVID-19.

Genetic diversity and natural selection of rif gene (PF3D7_1254800) in the Plasmodium falciparum global populations.

To reveal the genetic characteristics of one member of the Plasmodium falciparum repetitive interspersed family (rif), we sequenced the rif gene (PF3D7_1254800) in 53 field isolates collected from Ghana-imported cases into China and compared them with 350 publicly available P. falciparum rif sequences from global populations. In the Ghana-imported population, the nucleotide diversities were 0.05714 and 0.06616 for the full length and variable region of rif gene, respectively. Meanwhile, 22 and 20 haplotypes were identified for the full length and variable region of rif gene (Hd = 0.843 and 0.838, respectively). Diversity of rif gene in Ghana-imported population was higher than that observed in Cambodia, Thailand, Vietnam, Myanmar, Mali, Ghana, and Senegal populations. In this analysis, we found high genetic diversity of rif gene in global P. falciparum populations and identified 158 haplotypes. Tajima's D-test shows that there are large differences in the direction of selection between the conserved and variable region of rif gene. Tajima's D value for the variable region was 0.20074, indicating that balancing selection existed in this region. We found that the variable region was the main target of selection for positive diversification, and most mutation sites were located in this region. The population structure suggested optimized cluster values of K = 6. The five groups in Ghana-imported population included a unique subpopulation. Our results reveal the dynamics of the rif gene (PF3D7_1254800) in P. falciparum populations, which can aid in the rational design of P. falciparum rif-based vaccines.

Retrospective analysis of Plasmodium vivax genomes from a pre-elimination China inland population in the 2010s.

Introduction: In malaria-free countries, imported cases are challenging because interconnections with neighboring countries with higher transmission rates increase the risk of parasite reintroduction. Establishing a genetic database for rapidly identifying malaria importation or reintroduction is crucial in addressing these challenges. This study aimed to examine genomic epidemiology during the pre-elimination stage by retrospectively reporting whole-genome sequence variation of 10 Plasmodium vivax isolates from inland China. Methods: The samples were collected during the last few inland outbreaks from 2011 to 2012 when China implemented a malaria control plan. After next-generation sequencing, we completed a genetic analysis of the population, explored the geographic specificity of the samples, and examined clustering of selection pressures. We also scanned genes for signals of positive selection. Results: China's inland populations were highly structured compared to the surrounding area, with a single potential ancestor. Additionally, we identified genes under selection and evaluated the selection pressure on drug-resistance genes. In the inland population, positive selection was detected in some critical gene families, including sera, msp3, and vir. Meanwhile, we identified selection signatures in drug resistance, such as ugt, krs1, and crt, and noticed that the ratio of wild-type dhps and dhfr-ts increased after China banned sulfadoxine-pyrimethamine (SP) for decades. Discussion: Our data provides an opportunity to investigate the molecular epidemiology of pre-elimination inland malaria populations, which exhibited lower selection pressure on invasion and immune evasion genes than neighbouring areas, but increased drug resistance in low transmission settings. Our results revealed that the inland population was severely fragmented with low relatedness among infections, despite a higher incidence of multiclonal infections, suggesting that superinfection or co-transmission events are rare in low-endemic circumstances. We identified selective signatures of resistance and found that the proportion of susceptible isolates fluctuated in response to the prohibition of specific drugs. This finding is consistent with the alterations in medication strategies during the malaria elimination campaign in inland China. Such findings could provide a genetic basis for future population studies, assessing changes in other pre-elimination countries.

Application and development of systems biology in computer-aided drug design / 中国中药杂志

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.

The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries.

BACKGROUND: Critical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. METHODS: Data comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. RESULTS: This study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89-0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27-1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25). Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

A Molecular Investigation of Malaria Infections From High-Transmission Areas of Southern Togo Reveals Different Species of Plasmodium Parasites.

Malaria particularly burdens people in poor and neglected settings across the tropics of Africa. Meanwhile, a large proportion of the Togo population have poor understanding of malaria epidemiology and parasites. This study carried out a molecular survey of malaria cases in southern Togo during 2017-2019. We estimated Plasmodium species infection rates and microscopic examination compliance with nested PCR results. Sensitivity and specificity analyses were performed in conjunction with predictive values. Also, phylogenetic characterization of species of malaria parasites was assessed. Plasmodium genus-specific nested PCR identified 565 positive cases including 536/611 (87.8%) confirmed cases from the microscopy-positive group and 29/199 (14.6%) diagnosed malaria cases from the microscopy-negative group. Our findings revealed a disease prevalence (69.8%) higher than that reported (25.5-55.1%) for the country. The diagnostic test had 94.9% sensitivity and 69.4% specificity, i.e., it missed 120 of the people who had malaria and about one-third of the people tested positive for the disease, which they did not have, respectively. In conjunction, the test showed 87.7% positive predictive value and 85.4% negative predictive value, which, from a clinical perspective, indicates the chance that a person with a positive diagnostic test truly has the disease and the probability that a person with a negative test does not have the disease, respectively. Further species-specific nested PCR followed by analysis of gene sequences confirmed species of malaria parasites and indicated infection rates for Plasmodium falciparum (Pf), 95.5% (540/565); P. ovale (Po), 0.5% (3/565); and P. malariae (Pm), 0.4% (2/565). In addition, 20 cases were coinfection cases of Pf-Po (15/565) and Pf-Pm (5/565). This study publicly reports, for the first time, a molecular survey of malaria cases in Togo and reveals the presence of other malaria parasites (Po and Pm) other than Pf. These findings might provide answers to some basic questions on the malaria scenario and, knowledge gained could help with intervention deployment for effective malaria control in Togo.

Genetic Diversity and Natural Selection of Plasmodium vivax Duffy Binding Protein-II From China-Myanmar Border of Yunnan Province, China.

Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009-2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.

Crystal Structure of Inorganic Pyrophosphatase From Schistosoma japonicum Reveals the Mechanism of Chemicals and Substrate Inhibition.

Soluble inorganic pyrophosphatases (PPases) are essential for facilitating the growth and development of organisms, making them attractive functional proteins. To provide insight into the molecular basis of PPases in Schistosoma japonicum (SjPPase), we expressed the recombinant SjPPase, analyzed the hydrolysis mechanism of inorganic pyrophosphate (PPi), and measured its activity. Moreover, we solved the crystal structure of SjPPase in complex with orthophosphate (Pi) and performed PPi and methylene diphosphonic acid (MDP) docking into the active site. Our results suggest that the SjPPase possesses PPi hydrolysis activity, and the activity declines with increased MDP or NaF concentration. However, the enzyme shows unexpected substrate inhibition properties. Through PPi metabolic pathway analysis, the physiological action of substrate inhibition might be energy saving, adaptably cytoprotective, and biosynthetic rate regulating. Furthermore, the structure of apo-SjPPase and SjPPase with Pi has been solved at 2.6 and 2.3 Å, respectively. The docking of PPi into the active site of the SjPPase-Pi complex revealed that substrate inhibition might result from blocking Pi exit due to excess PPi in the SjPPase-Pi complex of the catalytic cycle. Our results revealed the structural features of apo-SjPPase and the SjPPase-Pi complex by X-ray crystallography, providing novel insights into the physiological functions of PPase in S. japonicum without the PPi transporter and the mechanism of its substrate inhibition.

From 30 million to zero malaria cases in China: lessons learned for China-Africa collaboration in malaria elimination.

Malaria was once one of the most serious public health problems in China, with more than 30 million malaria cases annually before 1949. However, the disease burden has sharply declined and the epidemic areas has shrunken after the implementation of an integrated malaria control and elimination strategy, especially since 2000. Till now, China has successfully scaled up its efforts to become malaria-free and is currently being evaluated for malaria-free certification by the WHO. In the battle against malaria, China's efforts have spanned generations, reducing from an incidence high of 122.9/10 000 (6.97 million cases) in 1954 to 0.06/10 000 (7855 cases) in 2010. In 2017, for the first time, China reached zero indigenous case of malaria, putting the country on track to record three consecutive years of zero transmission by 2020, accoding to the National Malaria Elimination Action Plan (2010-2020). China's efforts to eliminate malaria is impressive, and the country is dedicated to sharing its lessons learned in malaria elimination-including, but not limited to, the application of novel genetics-based approaches-with other nations through new initiatives. China will promote international relationships and establish collaborative platforms on a wide range of topics in roughly 65 countries, including 20 African nations. China's experience in applying innovative genetics-based approaches and tools to characterize malaria parasite populations, including surveillance of markers related to drug resistance, categorization of cases as indigenous or imported, and objective identification of the likely sources of infections to inform efforts towards malaria control and elimination in Africa could offer game-changing results when applied to settings with ongoing transmission.

Genome-Wide Scans for Ghanaian Plasmodium falciparum Genes Under Selection From Local and Chinese Host Populations.

Initial malarial infection mostly causes symptomatic illness in humans. Infection that is not fatal induces complete protection from severe illness and death, and thus complete protection from severe illness or death is granted with sufficient exposure. However, malaria parasite immunity necessitates constant exposure. Therefore, it is important to evaluate lowered immunity and recurrent susceptibility to symptomatic disease in lower transmission areas. We aimed to investigate selection pressure based on transmission levels, antimalarial drug use, and environmental factors. We whole genome sequenced (WGS) P. falciparum clinical samples from Chinese hosts working in Ghana and compared the results with the WGS data of isolates from native Ghanaians downloaded from pf3k. The P. falciparum samples were generally clustered according to their geographic origin, and Chinese imported samples showed a clear African origin with a slightly different distribution from the native Ghanaian samples. Moreover, samples collected from two host populations showed evidence of differences in the intensity of selection. Compared with native Ghanaian samples, the China-imported isolates exhibited a higher proportion of monoclonal infections, and many genes associated with RBC invasion and immune evasion were found to be under less selection pressure. There was no significant difference in the selection of drug-resistance genes due to a similar artemisinin-based combination therapy medication profile. Local selection of malarial parasites is considered to be a result of differences in the host immunity or disparity in the transmission opportunities of the host. In China, most P. falciparum infections were imported from Africa, and under these circumstances, distinct local selective pressures may be caused by varying acquired immunity and transmission intensity. This study revealed the impact of host switching on the immune system, and it may provide a better understanding of the mechanisms that enable clinical immunity to malaria.