暂无摘要。

UNASSIGNED: Systematic infrastructure and regulatory weaknesses over many decades, in communities struggling with animal African trypanosomiasis (AAT) would be expected to create an environment that would promote drug misuse and risk development of drug resistance. Here, we explore rural community practices of livestock keepers, livestock extension officers and drug shop attendants to determine whether appropriate practice was being followed in administration of trypanocides and other drugs.
UNASSIGNED: A questionnaire-based survey was undertaken in southwestern Uganda in 2022 involving 451 farmers who kept cattle, sheep or goats and 79 \"professionals\" who were either livestock extension officers or drug shop attendants.
UNASSIGNED: Respondents reported using one or more type of trypanocidal drug on 80.1% of the 451 farms in the last 30 days. Diminazene aceturate was used on around three-quarters of farms, while isometamidium chloride was used on around one-fifth. Homidium bromide was used on less than 1% of farms. Cattle were significantly more likely to be treated with trypanocides than sheep or goats. On around two-thirds of farms, trypanocides were prepared and injected by farmers, with extension officers administering these drugs on most of the other third, especially on cattle farms. Almost all drugs were obtained from privately-owned drug shops. For treatment of AAT with trypanocides, prescription-only medicines were routinely used by farmers without professional supervision and in the absence of a definitive diagnosis. While a far greater proportion of professionals had a better education and had received training on the use of trypanocides than farmers, there was relatively little difference in their ability to use these drugs correctly. Farmers were more likely than professionals to use only DA to treat trypanosomiasis and were more likely to use antibiotics as well as trypanocidal drugs to treat the animal. Furthermore, they estimated, on average, that twice the recommended dose of either diminazene aceturate or isometamidium chloride was needed to treat a hypothetical 400 kg bovine. A minority of both farmers and professionals reported that they observed the recommended withdrawal times following injection of trypanocidal drugs and very few of either group knew the recommended withdrawal times for milk or meat. Only one in six farmers reported using the sanative pair (alternating use of diminazene aceturate and isometamidium chloride), to reduce the risk of drug resistant trypanosome strains emerging, while this approach was more widely used by professionals. Farmers reported using antibiotics more commonly than the professionals, especially in sheep and goats, raising concerns as to overuse and misuse of this critical class of drugs. In addition to using trypanocides, most farmers also reported using a topical veterinary pesticide for the control of ticks and tsetse. On average, farmers spent 12.2% of their income from livestock sales on trypanocides.
UNASSIGNED: This study highlights the complexity of issues involved in the fight against AAT using drug treatment. A multistakeholder campaign to increase awareness among farmers, drug shop attendants, and extension workers of the importance of adherence to recommended drug dosing, using the sanative pair and following recommended drug withdrawal guidance would promote best practice, reduce the risk of emergence of resistant strains of trypanosomes, and support enhanced food safety.

BACKGROUND: People in China and the countries in the Association of Southeast Asian Nations (ASEAN) are affected by neglected tropical diseases and malaria (NTDM). In this study, we aimed to assess the current status and trends of NTDM burden from 1990 to 2019 in China and ASEAN countries, and also explore the association of NTDM burden with socio-demographic index (SDI).
METHODS: The data from the Global Burden of Diseases Study 2019 (GBD 2019) results were used. Absolute incidence and death number, and age-standardized incidence and mortality rate (ASIR and ASMR) of NTDM in China and ASEAN were extracted. The estimated annual percentage change (EAPC) and join-point regression in the rates quantified the trends. Nonlinear regression (second order polynomial) was used to explore the association between SDI and ASRs.
RESULTS: The ASIR of NTDM increased in China, Philippines, Singapore and Brunei, at a speed of an average 4.15% (95% CI 3.83-4.47%), 2.15% (1.68-2.63%), 1.03% (0.63-1.43%), and 0.88% (0.60-1.17%) per year. Uptrends of ASIR of NTDM in recent years were found in China (2014-2017, APC = 10.4%), Laos (2005-2013, APC = 3.9%), Malaysia (2010-2015, APC = 4.3%), Philippines (2015-2019, APC = 4.2%), Thailand (2015-2019, APC = 2.4%), and Vietnam (2014-2017, APC = 3.2%, all P < 0.05). Children < 5 had relatively low incidences but unexpectedly high mortality rates of NTDM in most ASEAN countries. Both incidence and mortality rates of NTDM were higher in older people. ASIR and ASMR of NTDM had a U-shaped association with SDI.
CONCLUSIONS: The burden of NTDM in China and ASEAN countries was still huge and affects vulnerable and impoverished populations\' livelihoods, including children under the age of 5 and people aged 60 and older. Facing with the large burden and complex situation of NTDM in China and ASEAN countries, regional cooperating strategies are needed to reduce the burden of NTDM, so as to achieve the goal of elimination in the world.

This study sought to investigate the parasitic diseases of neglected tropical diseases defined by the World Health Organization based on the Global Burden of Disease Study (GBD) database. Importantly, we analyzed the prevalence and burden of these diseases in China from 1990 to 2019 to provide valuable information to formulate more effective measures for their management and prevention.
Data on the prevalence and burden of neglected parasitic diseases in China from 1990 to 2019 were extracted from the global health data exchange (GHDx) database, including the absolute number of prevalence, age-standardized prevalence rate, disability-adjusted life year (DALY) and age-standardized DALY rate. Descriptive analysis was used to analyze the prevalence and burden changes, sex and age distribution of various parasitic diseases from 1990 to 2019. A time series model [Auto-Regressive Integrated Moving Average (ARIMA)] was used to predict the DALYs of neglected parasitic diseases in China from 2020 to 2030.
In 2019, the number of neglected parasitic diseases in China was 152518062, the age-standardized prevalence was 11614.1 (95% uncertainty interval (UI) 8758.5-15244.5), the DALYs were 955722, and the age-standardized DALY rate was 54.9 (95% UI 26.0-101.8). Among these, the age-standardized prevalence of soil-derived helminthiasis was the highest (9370.2/100,000), followed by food-borne trematodiases (1502.3/100,000) and schistosomiasis (707.1/100,000). The highest age-standardized DALY rate was for food-borne trematodiases (36.0/100,000), followed by cysticercosis (7.9/100,000) and soil-derived helminthiasis (5.6/100,000). Higher prevalence and disease burden were observed in men and the upper age group. From 1990 to 2019, the number of neglected parasitic diseases in China decreased by 30.4%, resulting in a decline in DALYs of 27.3%. The age-standardized DALY rates of most diseases were decreased, especially for soil-derived helminthiasis, schistosomiasis and food-borne trematodiases. The ARIMA prediction model showed that the disease burden of echinococcosis and cysticercosis exhibited an increasing trend, highlighting the need for further prevention and control.
Although the prevalence and disease burden of neglected parasitic diseases in China have decreased, many issues remain to be addressed. More efforts should be undertaken to improve the prevention and control strategies for different parasitic diseases. The government should prioritize multisectoral integrated control and surveillance measures to prioritize the prevention and control of diseases with a high burden of disease. In addition, the older adult population and men need to pay more attention.

A global plan has been set to end human deaths from dog-mediated rabies by 2030 (\"Zero-by-30\"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China.
Based on data from China\'s national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM.
The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the \"One Health\" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results.
The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the \"One Health\" rabies-control strategy most cost-effective.

Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0−91.6); I2 = 96.99% (95% CI: 94.6−98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94−59.09) and 6.56% (3.06−11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.

Leishmaniasis is a neglected tropical disease that seriously influences global public health. Among all the parasitic diseases, leishmaniasis is the third most common cause of morbidity after malaria and schistosomiasis. Circular RNAs (circRNAs) are a new type of noncoding RNAs that are involved in the regulation of biological and developmental processes. However, there is no published research on the function of circRNAs in leishmaniasis. This is the first study to explore the expression profiles of circRNAs in leishmaniasis. GO and KEGG analyses were performed to determine the potential function of the host genes of differentially expressed circRNAs. CircRNA-miRNA-mRNA (ceRNA) regulatory network analysis and protein-protein interaction (PPI) networks were analyzed by R software and the STRING database, respectively. A total of 4664 significant differentially expressed circRNAs were identified and compared to those in control groups; a total of 1931 were up-regulated and 2733 were down-regulated. The host genes of differentially expressed circRNAs were enriched in ubiquitin-mediated proteolysis, endocytosis, the MAPK signaling pathway, renal cell carcinoma, autophagy and the ErbB signaling pathway. Then, five hub genes (BRCA1, CREBBP, EP300, PIK3R1, and CRK) were identified. This study provides new evidence of the change of differentially expressed circRNAs and its potential function in leishmaniasis. These results may provide novel insights and evidence for the diagnosis and treatment of leishmaniasis.

The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda-a \'living\' document hosted on the IDDO website-and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.

暂无摘要。

An updated analysis of neglected tropical diseases (NTDs) from a global perspective is missing from the literature. We aimed to assess the global burden and trends of NTDs from 1990 to 2019.
Yearly incident case, mortality and disability-adjusted life years (DALYs) data for NTDs were extracted from the Global Burden of Disease Study 2019 (GBD 2019) based on global, regional, country, social development index (SDI), age and sex categories. The age-standardized rate (ASR) and number of incident cases, mortality and DALYs were computed from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASR was calculated to quantify the changing trend.
Globally, the age-standardized incidence rate (ASIR) and the number of incident cases of total NTDs increased between 1990 and 2019, whereas the age-standardized mortality rate (ASMR), mortality, age-standardized DALY rate and DALYs of total NTDs decreased. Although tropical Latin America, South Asia, Southeast Asia and Oceania had the highest ASIR for total NTDs in 2019, tropical Latin America was the only region to experience a decreasing trend in ASIR from 1673.5 per 100 000 in 2010 to 1059.2 per 100 000 in 2019. The middle, high-middle and high SDI regions experienced increasing ASIR trends between 1990 and 2019, whereas the low-middle SDI region remained stable, and the low SDI region presented a decreasing trend. Children and older adults were vulnerable to dengue, rabies and leishmaniasis (cutaneous and mucocutaneous). Females had a higher ASIR but a lower ASMR and age-standardized DALY rate than males.
NTDs still represent a serious problem for public health, and the increasing ASIR and incident cases globally may require more targeted strategies for prevention, control and surveillance, especially among specific populations and endemic areas.