BACKGROUND: Neglected tropical diseases (NTDs) and malaria pose a major health challenge, especially in low- and middle-income countries. METHODS: Initially, we performed a descriptive analysis of the Global Burden of Disease (GBD) 2021 database, categorizing data by subtypes. Next, linear regression models were employed to analyze temporal trends. We then utilized four predictive models to forecast the future burden. Additionally, we explored the relationship between estimated annual percentage change (EAPCs) and age-standardized rates (ASRs), as well as Human Development Index (HDI) scores for 2021. Furthermore, decomposition analysis was applied to assess the influence of aging, population dynamics, and epidemiological changes. Lastly, frontier analysis was conducted to examine the connection between disease burden and sociodemographic development. RESULTS: In 2021, NTDs and malaria contributed significantly to the global disease burden, with considerable disparities across genders, age groups, Socio-demographic Index (SDI) regions, GBD regions, and individual countries. From 1990 to 2021, both the number of cases and the associated ASRs have shown a recent downward trend. The EAPCs are positively correlated with ASRs and HDI scores. Projections indicate a continued decline in disease burden through 2046. Additionally, our decomposition analysis highlighted the positive impact of aging and epidemiological shifts on the reduction of the disease burden. Finally, frontier analysis revealed that countries and regions with higher SDI scores have greater potential for further reducing their health burden. CONCLUSION While the global burden of NTDs and malaria has improved overall, significant disparities remain across regions and countries. Our findings highlight the importance of implementing targeted intervention strategies and maintaining sustained investments to tackle the ongoing challenges.
Malaria/epidemiology* ; Humans ; Neglected Diseases/epidemiology* ; Global Burden of Disease/trends* ; Global Health/statistics & numerical data* ; Male ; Female ; Tropical Medicine ; Adult ; Cost of Illness ; Child, Preschool ; Middle Aged ; Adolescent ; Young Adult ; Infant

Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

The most common medications for the treatment of zoonotic toxoplasmosis are pyrimethamine and sulfadiazine, which may cause serious undesirable side effects. Thus, there is an urgent need to develop novel therapeutics. Baicalein (BAI, C₁₅H₁₀O₅) has been shown to perform well against protozoan parasites including Leishmania and Cryptosporidium. In this study, the inhibition efficacy of BAI on Toxoplasma gondii was evaluated using plaque, invasion, and intracellular proliferation assays. BAI effectively inhibited T. gondii (half-maximum inhibitory concentration (IC₅₀)=6.457×10^-5 mol/L), with a reduced invasion rate (33.56%) and intracellular proliferation, and exhibited low cytotoxicity (half-maximum toxicity concentration (TC₅₀)=5.929×10^-4 mol/L). Further investigation using a mouse model shed light on the inhibitory efficacy of BAI against T. gondii, as well as the potential mechanisms underlying its anti-parasitic effects. The survival time of T. gondii-infected ICR mice treated with BAI was remarkably extended, and their parasite burdens in the liver and spleen were greatly reduced compared with those of the negative control group. Histopathological examination of live sections revealed effective therapeutic outcomes in the treatment groups, with no notable pathological alterations observed. Furthermore, alterations in cytokine levels indicated that BAI not only effectively suppressed the growth of T. gondii but also prevented excessive inflammation in mice. Collectively, these findings underscore the significant inhibitory efficacy of BAI against T. gondii, positioning it as a promising alternative therapeutic agent for toxoplasmosis.
Animals ; Toxoplasma/drug effects* ; Flavanones/therapeutic use* ; Mice ; Antiparasitic Agents/therapeutic use* ; Mice, Inbred ICR ; Toxoplasmosis/drug therapy* ; Female

Humans ; Toxoplasmosis ; Hematopoietic Stem Cell Transplantation ; Hematologic Diseases

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Child ; Adult ; Humans ; Antimalarials/pharmacology* ; Cardiovascular Diseases/drug therapy* ; Artemisinins/pharmacology* ; Quinolines ; Malaria, Cerebral/drug therapy* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy*

Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8⁺ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8⁺ and TIGIT⁺CD8⁺ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT⁺CD8⁺ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT⁺CD8⁺T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8⁺ and TIGIT⁺CD8⁺ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT⁺CD8⁺ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT⁺CD8⁺ T cells from the normal mice. The percentages of TIGIT⁺CD8⁺ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT⁺CD8⁺ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Animals ; Mice ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Interferon-gamma/metabolism* ; Interleukin-10/metabolism* ; Interleukin-17/metabolism* ; Interleukin-4/metabolism* ; Lung/metabolism* ; Malaria/metabolism* ; Plasmodium yoelii/metabolism* ; Programmed Cell Death 1 Receptor/metabolism*

In 2017, China achieved the target of zero indigenous malaria case for the first time, and has been certified as malaria free by World Health Organization in 2021. To further summarize the historical achievements and technical experiences of the elimination program, a project on the Roadmap Analysis and Verification for Malaria Elimination in China was carried out. Results of the project were compiled and published as the Atlas of Malaria Transmission in China (The Atlas). The Atlas using modern digital information technologies, has been supported by various data from 24 malaria endemic provinces of China since 1950, to assess the changes in malaria epidemic patterns from 1950 to 2019 at national and provincial levels. The Atlas is designed as two volumes, including a total of 1850 thematic maps and more than 130 charts, consisting of introductory maps, thematic maps of malaria epidemic and control at national and provincial levels. It objectively and directly shows the epidemic history, evolution process, and great achievements of the national malaria control and elimination program in China. The Atlas has important reference value for summing up historical experience in the national malaria elimination program of China, and malaria control and elimination in other endemic countries in the world.
Humans ; Malaria/prevention & control* ; China/epidemiology*

Child ; Humans ; Toxoplasmosis, Cerebral ; Hematopoietic Stem Cell Transplantation ; Thalassemia

OBJECTIVE: To analyze the RNA binding protein of Toxoplasma gondii (TgDDX39) using bioinformatics technology, and to evaluate the immunogenicity of TgDDX39, so as to provide insights into development of toxoplasmosis vaccines. METHODS: The amino acid sequences of TgDDX39 were retrieved from the ToxoDB database, and the physicochemical properties, transmembrane structure domain, signal peptide sites, post-translational modification sites, coils, secondary and tertiary structures, hydrophobicity, and antigenic epitopes of the TgDDX39 protein were predicted using online bioinformatics tools, incluiding ProtParam, TMHMM 2.0, SignalP 5.0, NetPhos 3.1, COILS, SOPMA, Phyre2, ProtScale, ABCpred, SYFPEITHI and DNA-STAR. RESULTS: TgDDX39 protein was predicted to be an unstable hydrophilic protein with the molecular formula of C₂₁₇₃H₃₄₅₈N₅₉₈O₆₆₁S₁₈, which contained 434 amino acids and had an estimated molecular weight of 49.1 kDa and a theoretical isoelectric point of 5.55. The protein was predicted to have an extremely low possibility of signal peptides, without transmembrane regions, and contain 27 phosphorylation sites. The β turn and random coils accounted for 39.63% of the secondary structure of the TgDDX39 protein, and a coiled helix tended to produce in one site. In addition, the TgDDX39 protein contained multiple B and T cell antigenic epitopes. CONCLUSIONS Bioinformatics analyses predict that TgDDX39 protein has high immunogenicity and contains multiple antigenic epitopes. TgDDX39 protein is a potential candidate antigen for vaccine development.
Humans ; Toxoplasma/metabolism* ; Toxoplasmosis/prevention & control* ; Vaccines ; Epitopes, T-Lymphocyte ; Computational Biology ; Protozoan Proteins/chemistry*

OBJECTIVE: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ² = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ² = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ²= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ² = 3.95, P < 0.05). CONCLUSIONS The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.
Humans ; Pandemics ; China/epidemiology* ; Incidence ; COVID-19/epidemiology* ; Malaria/prevention & control* ; Malaria, Falciparum/epidemiology*