Intracellular protozoan pathogens have to negotiate the internal environment of the host cell they find themselves in, as well as manipulate the host cell to ensure their own survival, replication, and dissemination. The transfer of key effector molecules from the pathogen to the host cell is crucial to this interaction and is technically more demanding to study as compared to an extracellular pathogen. While several effector molecules have been identified, the mechanisms and conditions underlying their transfer to the host cell remain partly or entirely unknown. Improvements in experimental systems have revealed tantalizing details of such intercellular transfer, which form the subject of this chapter.

BACKGROUND: Out of the 21 neglected tropical diseases (NTDs) listed by the World Health Organization, 15 affect the People\'s Republic of China. Despite significant achievements in controlling NTDs, comprehensive assessments of the disease burden based on actual case data and detailed information on spatial and temporal dynamics are still lacking. This study aims to assess the disease burden and spatial-temporal distribution of NTDs in China from 2005 to 2020, to provide a reference for the formulation of national health agendas in line with the global health agenda, and guide resource allocation.
METHODS: The number of cases and deaths of major NTDs in China from 2005 to 2020 were downloaded from the China Public Health Science Data Center ( https://www.phsciencedata.cn/Share/index.jsp ) of the Chinese Center for Disease Control and Prevention and relevant literatures. Simplified formulas for disability-adjusted life years (DALYs) helped estimate the years of life lost (YLLs), years lived with disability (YLDs), and total DALYs. Spatial autocorrelation analysis of the average NTDs burden data for the years 2005 to 2020 was evaluated using Moran\'s I statistic.
RESULTS: China\'s overall NTDs burden decreased significantly, from 245,444.53 DALYs in 2005 to 18,984.34 DALYs in 2020, marking a reduction of 92.27%. In 2005, the DALYs caused by schistosomiasis and rabies represent a substantial proportion of the total disease burden, accounting for 65.37% and 34.43% respectively. In 2015, Hunan and Sichuan provinces had the highest diversity of NTDs, with 9 and 8 number of different NTDs reported respectively. And the highest disease burden was observed in Sichuan (242,683.46 DALYs), Xizang Zizhiqu (178,318.99 DALYs) and Guangdong (154,228.31 DALYs). The \"high-high\" clustering areas of NTDs were mainly in China\'s central and southern regions, as identified by spatial autocorrelation analysis.
CONCLUSIONS: China has made unremitting efforts in the prevention and control of NTDs, and the disease burden of major NTDs in China has decreased significantly. Using the One Health concept to guide disease prevention and control in the field to effectively save medical resources and achieve precise intervention.

The rise of African trypanocide resistance (ATr) is influenced by various factors such as evolutionary changes in the pathogen, the presence of resistance genes in the population, poor policy decisions, limited private-public partnerships to engage local communities, and insufficient funding for the development of new drugs over the past sixty years. These challenges have been exacerbated by the inadequate implementation of drug liberalization policies in the mid 20th century, leading to poor pharmacovigilance practices for veterinary drugs in low and middle income countries (LMICs). One health (OH), a disease management framework, provides practical solutions for addressing ATr, drawing on its success in managing previous epidemics like avian influenza in 2004 and the recent COVID-19 pandemic, where institutional collaborations were rapidly established. To combat ATr, OH initiatives involving both international and local partners at the policy and grassroots levels are crucial to generate community interest. The importance of political commitment, media involvement, and nongovernmental organizations cannot be overstated, as they are essential for resource mobilization and long-term sustainability in LMICs.

Neglected and underutilized species of plants (NUS) have been identified by the Food and Agriculture Organization as valuable resources for fighting poverty, hunger and malnutrition as they can help make agricultural production systems more sustainable and resilient. Adaptation of NUS to changing environments over several millennia has rendered most of these plants resistant to pests and climate change. In this paper, we explore the potential values of some of the Mayan fruit trees justifying conservation efforts in their native habitats. Our research was primarily based on a scoping review using Google Scholar. We considered articles published in English, Spanish and Portuguese. Our review rendered two sets of articles including those focusing on the nutritional and medicinal properties of NUS and their products, and those focusing on their uses in traditional medicine. Both sets of papers strongly support arguments for conservation of NUS. Additionally, our scoping review expands and includes a case study on the conservation of NUS, highlighting the critical role of civil society on how it can spearhead rescue efforts of botanical resources through the creation of what is possibly the first arboretum of its kind in the Americas. Among the project\'s key selling points was not only the rescue of an important component of Yucatan\'s cultural heritage but its nutritional value as well as its potential medicinal properties. Our paper is not prescriptive on how to preserve or even commercially exploit NUS. It is intended as a thought-provoking piece on the potential of a One Health approach as a multisectoral platform to support conservation efforts, while stimulating greater interest in the subject and encouraging more action from the academic and pharmaceutical sectors as well as civil society.

The development of new treatments for neglected tropical diseases (NTDs) remains a major challenge in the 21st century. In most cases, the available drugs are obsolete and have limitations in terms of efficacy and safety. The situation becomes even more complex when considering the low number of new chemical entities (NCEs) currently in use in advanced clinical trials for most of these diseases. Natural products (NPs) are valuable sources of hits and lead compounds with privileged scaffolds for the discovery of new bioactive molecules. Considering the relevance of biodiversity for drug discovery, a chemoinformatics analysis was conducted on a compound dataset of NPs with anti-trypanosomatid activity reported in 497 research articles from 2019 to 2024. Structures corresponding to different metabolic classes were identified, including terpenoids, benzoic acids, benzenoids, steroids, alkaloids, phenylpropanoids, peptides, flavonoids, polyketides, lignans, cytochalasins, and naphthoquinones. This unique collection of NPs occupies regions of the chemical space with drug-like properties that are relevant to anti-trypanosomatid drug discovery. The gathered information greatly enhanced our understanding of biologically relevant chemical classes, structural features, and physicochemical properties. These results can be useful in guiding future medicinal chemistry efforts for the development of NP-inspired NCEs to treat NTDs caused by trypanosomatid parasites.

Neglected Tropical Diseases (NTDs) are a group of chronic infectious diseases of poverty affecting over one billion people globally. Intersections of NTDs, disability, and mental ill-health are increasingly evidenced but are rarely studied from a mixed-methods perspective. Here, we advance syndemic understandings by further assessing and contextualising the syndemic relationship between NTDs (particularly their associated disability) and mental distress in Liberia. Participatory qualitative methods, including body mapping (56 participants), social mapping (28 participants), and in-depth interviews (12) provided space for persons affected by NTDs to narrate their experiences. Simultaneously, 201 surveys explored experiences of common mental health conditions among persons affected by skin NTDs. An intersectionality approach was applied within the analysis for both qualitative and quantitative methods informed by Meyer\'s minority stress model, adapted for NTDs. Qualitative data was analysed thematically and gender-disaggregated, univariable and multivariable analyses were applied to survey data for the outcome measures depression (PHQ-9) and anxiety (GAD-7). Disability was associated with higher levels of depression and anxiety (p < 0.001). An interaction between disability and being a women increased incidence risk ratio of depression (p < 0.001). In alignment with qualitative findings, persons affected experienced additional generalised (financial concerns), external (experience of stigma) and internal (experience of pain and physical symptoms) minority stressors, to varying degrees, which contributed towards their mental distress, and mental health conditions. These findings were used to co-develop a syndemic-informed person-centred health system response to address the suffering associated with NTDs and mental distress, including a focus on strengthening relationships between formal and informal community health actors and the broader health system.

Infectious disorders known as Neglected Tropical Diseases (NTDs) initially affect the world\'s underprivileged citizens. They have been disregarded for many years, first as a result of a general indifference to such a developing world and, more recently, as an outcome of the intense attention on AIDS, TB, and malaria. Tropical diseases mostly affect the region where health and hygiene are sacrificed, and most of the population lacks access to sufficient food and living resources. WHO has drafted and released the directions for regulation, pre-vention, and successful eradication of NTDs as per the revised roadmap of 2021-2030. This shifts from vertical disease programs to integrated cross-cutting methods. In the current work, we have provided comprehensive information on various aspects of neglected tropical dis-eases, including the clinical management of NTDs. This encompasses the causative agent of the diseases, their symptoms, pathogenesis, diagnosis, treatment, prognosis, and epidemio-logical perspective of major NTDs. This review will shed light on several perspectives of NTDs having influential roles in proposing strategies to control and treat them around the world.

BACKGROUND: Podoconiosis is a neglected debilitating yet preventable disease. Despite its public health significance, podoconiosis is often misdiagnosed and confused with lymphatic filariasis. No appropriate diagnostic tests exist, contributing to underestimation and the absence of control interventions.
METHODS: A population-based cross-sectional survey was conducted in seven districts with suspected or reported cases of podoconiosis or an altitude of 1200 m above sea level. Conducted from 30 January to 19 March 2023, the survey employed multilevel stratified sampling to reach eligible household members.
RESULTS: Of the 10 023 participants sampled, 187 (confidence interval 1.25 to 2.78) had clinical features of podoconiosis. The highest prevalence was recorded in Nakapiripirit (7.2% [58/809]) and Sironko (2.8 [44/1564]) and the lowest in Kasese (0.3% [5/1537]), but ranged from 1.1 to 1.8% in Zombo, Rukungiri, Gomba and Hoima districts. The duration of podoconiosis was reported to range from 1 to 57 y. Factors associated with podoconiosis occurrence included advanced age, tungiasis, household cleanliness and personal hygiene. Sleeping on a bed, bathing daily, use of soap and use of footwear in at least moderate condition were protective against podoconiosis.
CONCLUSIONS: Podoconiosis occurred in all the sampled districts and was linked to personal hygiene. Long-standing cases suggest an absence of treatment. There is potential for early intervention using a holistic care model in managing this condition. Urgent action and stakeholder engagement are essential for effective podoconiosis management.

Background: Snakebite is a global environmental and occupational hazard and a significant public health threat. In rural areas, snakebite cases often go unreported and undocumented due to the lack of access to well-structured healthcare facilities/infrastructure. In some cases, the need for antisnake venom (ASV) far outstrips supply, negatively affecting treatment outcomes. This study, therefore, assessed the epidemiological characteristics of snakebite cases, their management, and how antivenoms are utilised at the selected hospital in the Jasikan District Hospital. Methods: A 6-year retrospective study using secondary data from antivenom return forms (pharmacy records), clinical records (patient folders), the District Health Information Management System-2 (DHIMS-2) database, and consulting room registers was carried out in selected hospitals in the Jasikan District, Oti, Ghana. Results: The predominant symptom of snakebite was localised pain (71.4%). The snakebite commonly occurred at home (19%) and on farms (18%). Of the 98 snakebite cases, ASV was administered to 73 (74.5%) cases. Supportive treatment applied included prophylactic antitetanus immunoglobulin (ATS) (80.6%), prophylactic antibiotics (63%), corticosteroids (80.6%), and analgesics (63%). 95% (n = 94) of complete recoveries were recorded; three were discharged against medical advice, and one was mortality. The supply and use of antivenom were erratic throughout the months of high incidence, partly due to inconsistent availability at the Regional Medical Stores. The average ASV vials and hospital stay duration were 1.23 ± 0.86 vials and 2.67 ± 1.97 days, respectively. Although the peak of snakebites occurs in April, May, and June, the demand for antivenom in April and May exceeded supply. Conclusion: The outcome of most snakebite case management was appropriate, irrespective of inadequate ASV supply in certain months. The erratic antivenom supply should be aligned with seasonal and facility-use patterns to enhance regional snakebite management.

BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco.
METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry.
RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients.
CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.