Soil-transmitted helminths are highly prevalent in the Asia-Pacific region. We report a 96.5% prevalence of zoonotic soil-transmitted helminths in dogs in Kiribati. We advocate for urgent implementation of treatment and prevention programs for these zoonotic pathogens, in line with the Kiribati-World Health Organization Cooperation Strategy 2018-2022.

Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of αβ-tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well-characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of process outgrowth both in vivo and in vitro With single-cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze process outgrowth and show that four tubulins (tba-1, tba-2, tbb-1, and tbb-2) function partially or fully redundantly, while two others (mec-7 and mec-12) perform specialized, context-dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts.

Allogenic hematopoietic stem cell transplant (allo-HSCT) can lead to sinusoidal obstruction syndrome (SOS) and graft-versus-host disease (GvHD) in some individuals. GvHD is characterised by an immune triggered response that arises due to donor T cells recognizing the recipient tissue as "foreign". SOS results in impaired liver function due to microvascular thrombosis and consequent obstruction of liver sinusoids. Endothelial damage occurs following chemotherapy and allo-HSCT and is strongly associated with GvHD onset as well as hepatic SOS. Animal models of GvHD are rarely clinically relevant, and endothelial dysfunction remains uncharacterised. Here we established and characterised a clinically relevant model of GvHD wherein Balb/C mice were subjected to myeloablative chemotherapy followed by transplantation of bone marrow (BM) cells± splenic T-cells from C57Bl6 mice, resulting in a mismatch of major histocompatibility complexes (MHC). Onset of disease indicated by weight loss and apoptosis in the liver and intestine was discovered at day 6 post-transplant in mice receiving BM+T-cells, with established GvHD detectable by histology of the liver within 3 weeks. Together with significant increases in pro-inflammatory cytokine gene expression in the liver and intestine, histopathological signs of GvHD and a significant increase in CD4+ and CD8+ effector and memory T-cells were seen. Endothelial activation including upregulation of vascular cell adhesion molecule (VCAM)- 1 and downregulation of endothelial nitric oxide synthase (eNOS) as well as thrombosis in the liver indicated concomitant hepatic SOS. Our findings confirm that endothelial activation is an early sign of acute GvHD and SOS in a clinically relevant mouse model of GvHD based on myeloablative chemotherapy. Preventing endothelial activation may be a viable therapeutic strategy to prevent GvHD.

Remote and rural communities in low- and middle-income countries (LMICs) are disproportionately affected by infectious animal diseases due to their close contact with livestock and limited access to animal health personnel). However, animal disease surveillance and diagnosis in LMICs is often challenging, and turnaround times between sample submission and diagnosis can take days to weeks. This diagnostic gap and subsequent disease under-reporting can allow emerging and transboundary animal pathogens to spread, with potentially serious and far-reaching consequences. Point-of-care tests (POCTs), which allow for rapid diagnosis of infectious diseases in non-laboratory settings, have the potential to significantly disrupt traditional animal health surveillance paradigms in LMICs. This literature review sought to identify POCTs currently available for diagnosing infectious animal diseases and to determine facilitators and barriers to their use and uptake in LMICs. Results indicated that some veterinary POCTs have been used for field-based animal disease diagnosis in LMICs with good results. However, many POCTs target a small number of key agricultural and zoonotic animal diseases, while few exist for other important animal diseases. POCT evaluation is rarely taken beyond the laboratory and into the field where they are predicted to have the greatest impact, and where conditions can greatly affect test performance. A lack of mandated test validation regulations for veterinary POCTs has allowed tests of varying quality to enter the market, presenting challenges for potential customers. The use of substandard, improperly validated or unsuitable POCTs in LMICs can greatly undermine their true potential and can have far-reaching negative impacts on disease control. To successfully implement novel rapid diagnostic pathways for animal disease in LMICs, technical, regulatory, socio-political and economic challenges must be overcome, and further research is urgently needed before the potential of animal disease POCTs can be fully realized.

BACKGROUND: Taenia solium is a neglected zoonotic parasite. The performances of existing tools for the diagnosis of porcine cysticercosis need further assessment, and their shortcomings call for alternatives. The objective of this study was to evaluate the performance of tongue palpation and circulating antigen detection for the detection of porcine cysticercosis in naturally infected pigs of slaughter age compared to full carcass dissections (considered the gold standard). Additionally, alternative postmortem dissection procedures were investigated. A total of 68 rural pigs of slaughter age randomly selected in the Eastern Province of Zambia were dissected. Dissections were conducted on full carcasses (or half carcass in case cysticerci were already detected in the first half), including all the organs. Total cysticercus counts, location and stages were recorded and collected cysticerci were identified morphologically and molecularly. All sera were analysed with the B158/B60 antigen detecting ELISA (Ag-ELISA). RESULTS: Key findings were the high occurrence of T. solium infected pigs (56%) and the presence of T. solium cysticerci in the livers of 26% of infected animals. More than half of the infected carcasses contained viable cysticerci. Seven carcasses had T. hydatigena cysticerci (10%), out of which five carcasses were co-infected with T. hydatigena and T. solium; two carcasses (3%) had only T. hydatigena cysticerci. Compared to full carcass dissection, the specificity of the Ag-ELISA to detect infected carcasses was estimated at 67%, the sensitivity at 68%, increasing to 90% and 100% for the detection of carcasses with one or more viable cysticerci, and more than 10 viable cysts, respectively. Tongue palpation only detected 10% of the cases, half carcass dissection 84%. Selective dissection of the diaphragm, tongue and heart or masseters can be considered, with an estimated sensitivity of 71%, increasing to 86% in carcasses with more than 10 cysticerci. CONCLUSIONS: Depending on the aim of the diagnosis, a combination of Ag-ELISA and selective dissection, including investigating the presence of T. hydatigena, can be considered. Full carcass dissection should include the dissection of the liver, kidneys, spleen and lungs, and results should be interpreted carefully, as small cysticerci can easily be overlooked.

The current COVID-19 global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of probable bat origin, has highlighted the ongoing need for a One Health response to emerging zoonotic disease events. Understanding the human-animal interface and its relevance to disease transmission remains a critical control point for many emerging zoonoses. Determination of the susceptibility of various animal species to infection with SARS-CoV-2 and the role of animals in the epidemiology of the disease will be critical to informing appropriate human and veterinary public health responses to this pandemic. A scoping literature review was conducted to collect, evaluate and present the available research evidence regarding SARS-CoV-2 infections in animals. Experimental studies have successfully demonstrated SARS-CoV-2 infection and transmission in cats, ferrets, hamsters, bats and non-human primates under experimental settings. Dogs appear to have limited susceptibility to SARS-CoV-2, while other domestic species including pigs and poultry do not appear susceptible. Naturally occurring SARS-CoV-2 infections in animals appear uncommon, with 14 pets, 8 captive big cats and an unreported number of farmed mink testing positive at the time of writing (early July 2020). Infections typically appear asymptomatic in dogs, while clinical signs of respiratory and/or gastrointestinal disease tend to be mild to moderate in felines, and severe to fatal in mink. Most animals are presumed to have been infected by close contact with COVID-19 patients. In domestic settings, viral transmission is self-limiting; however in high-density animal environments, there can be sustained between-animal transmission. To date, two potential cases of animal-to-human transmission are being investigated, on infected mink farms. Given the millions of COVID-19 cases worldwide and ongoing potential for further zoonotic and anthroponotic viral transmission, further research and surveillance activities are needed to definitively determine the role of animals in community transmission of SARS-CoV-2.

OBJECTIVE: The zoonotic helminth Taenia solium is endemic in Zambia, causing human (taeniasis and (neuro)cysticercosis) and pig (porcine cysticercosis) diseases with high health, social and economic burdens. We aimed to evaluate the impact of a health educational program intended to lead to powerful and cumulative improvements in knowledge, attitudes and practices that decrease parasite transmission and disease occurrence. METHODS: Half-day health education workshops were conducted in three primary schools in the highly endemic Eastern Province of Zambia, using the computer-based T. solium educational program 'The Vicious Worm'. Questionnaires were administered before and after the educational component to determine the program's impact on knowledge uptake in primary school students. RESULTS: In total, 99 students participated: 38 males and 61 females, with a median age of 14 years (range 10-18 years). Baseline general knowledge of T. solium, including awareness of the different human and pig disease states, and disease diagnosis, treatment and prevention, was quite high (average score 62%) and consistent across all three study areas. Participants' knowledge had significantly increased after the educational component, particularly regarding parasite transmission and disease prevention. CONCLUSION: Preliminary assessment of 'The Vicious Worm' indicates it is an effective tool for the short-term T. solium education of primary school students in Zambia. Follow-up studies are planned to assess the longer term impact of the program on knowledge uptake in the study neighbourhoods. Inclusion of tailored 'The Vicious Worm' educational workshops should be considered in integrated cysticercosis control programs in endemic areas of sub-Saharan Africa.

BACKGROUND: The Taenia solium cysticercosis-taeniasis complex is a Neglected Tropical Disease of significant public health importance in many impoverished communities worldwide. The parasite is suspected to be endemic in Lao PDR as a result of widespread risk factors including open human defecation, free ranging pigs and weak systems for meat inspection and carcass condemnation. Reported prevalences of human taeniasis throughout the country have ranged from 0-14%, although few of these have definitively diagnosed T. solium, grossly indistinguishable from Taenia saginata (beef tapeworm) and Taenia asiatica. This short communication details the suspicion of a hyper endemic "hotspot" of T. solium in a remote Tai Dam village in northern Lao PDR. FINDINGS: Initial antibody serosurveillance of four provinces in Lao PDR in 2011 indicated human taeniasis and cysticercosis prevalences of 46.7% and 66.7% respectively, in the village of Om Phalong in the north of the country. Subsequent copro-antigen ELISA on 92 human faecal samples from this same village, representing a total 27.9% of the target community, indicated a taeniasis prevalence of 26.1% (95% CI?=?18.2-35.9). Subsequent PCR and sequencing of samples (n?=?5) all identified as T. solium; the other human tapeworms T. saginata and T. asiatica were not detected in any of the samples genotyped. CONCLUSION: This is potentially one of the highest documented prevalences of T. solium taeniasis to date in Lao PDR, if not the Southeast Asia region. This result raises suspicion that other "hotspots" of T. solium hyper endemicity may exist in the region, particularly in communities where the consumption of raw pork is commonplace as a result of cultural practices.

BACKGROUND: Taenia solium is a neglected zoonotic parasite endemic throughout many low-income countries worldwide, including Zambia, where it causes human and pig diseases with high health and socioeconomic burdens. Lack of knowledge is a recognized risk factor, and consequently targeted health educational programs can decrease parasite transmission and disease occurrence in endemic areas. Preliminary assessment of the computer-based education program 'The Vicious Worm' in rural areas of eastern Zambia indicated that it was effective at increasing knowledge of T. solium in primary school students. The aim of this study was to evaluate the impact of 'The Vicious Worm' on knowledge retention by re-assessing the same primary school students one year after the initial education workshops. METHODOLOGY/PRINCIPAL FINDINGS: Follow-up questionnaires were administered in the original three primary schools in eastern Zambia in 2017, 12 months after the original workshops. In total, 86 pupils participated in the follow-up sessions, representing 87% of the initial workshop respondents. Knowledge of T. solium at 'follow-up' was significantly higher than at the initial 'pre' questionnaire administered during the Vicious Worm workshop that took place one year earlier. While some specifics of the parasite's life cycle were not completely understood, the key messages for disease prevention, such as the importance of hand washing and properly cooking pork, remained well understood by the students, even one year later. CONCLUSIONS/SIGNIFICANCE: Results of this study indicate that 'The Vicious Worm' may be an effective tool for both short- and long-term T. solium education of rural primary school students in Zambia. Inclusion of educational workshops using 'The Vicious Worm' could be recommended for integrated cysticercosis control/elimination programs in sub-Saharan Africa, particularly if the content is simplified to focus on the key messages for prevention of disease transmission.

Infections with Taenia solium cause significant public health and economic losses worldwide. Despite effective control tools, long-term sustained control/elimination of the parasite has not been demonstrated to date. Success of intervention programs is dependent on their acceptability to local communities. Focus group discussions (FGDs) and questionnaires (QS) were conducted in two study communities in eastern Zambia to assess local perceptions and acceptance of two piloted intervention strategies: one targeting pigs only ('control' study arm), and one integrated human- and pig-based ('elimination') strategy. QS (n = 227) captured data regarding participation in project activities, knowledge and perceptions of T. solium and of the interventional drugs used in the study. FGDs (n = 18) discussed perceived advantages and disadvantages of the interventions and of the project's delivery and value. QS data revealed 67% of respondents participated in at least one educational activity, and 80% correctly identified at least one disease targeted by the education. All elimination study arm respondents (n = 113) had taken the human treatment, and 98% intended to do so next time. Most (70%) indicated willingness to pay for future treatments (median 0.20 USD per dose). Of pig-owning respondents, 11/12 (92%) had allowed their pigs to be treated/vaccinated and all intended to do so again next time. Four pig owners indicated willingness to pay 0.10-0.50 USD per dose of treatment or vaccine. FGD feedback revealed positive perceptions of interventions; people reported improved health in themselves and their pigs, and fewer cysticerci in pork. Latrine use, hand washing, meat inspection and proper cooking of pork had reportedly increased since the program's inception. Preliminary assessment indicates that the piloted intervention methods are generally acceptable to the communities. The reported willingness of many respondents to pay for the medications would contribute to the feasibility of long-term, government-led T. solium intervention programs in future.

Soil-transmitted helminths, such as roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and hookworms (Necator americanus and Ancylostoma spp.), are gastrointestinal parasites that occur predominantly in low- to middle-income countries worldwide and disproportionally impact children. Depending on the STH species, health status of the host and infection intensity, direct impacts of these parasites include malnutrition, anaemia, diarrhoea and physical and cognitive stunting. The indirect consequences of these infections are less well understood. Specifically, gastrointestinal infections may exert acute or chronic impacts on the natural gut microfauna, leading to increased risk of post-infectious gastrointestinal disorders, and reduced gut and overall health through immunomodulating mechanisms. To date a small number of preliminary studies have assessed the impact of helminths on the gut microbiome, but these studies are conflicting. Here, we assessed STH burden in 273 pre-school and school-aged children in Tha Song Yang district, Tak province, Thailand receiving annual oral mebendazole treatment. Ascaris lumbricoides (107/273) and Trichuris trichiura (100/273) were the most prevalent species and often occurred as co-infections (66/273). Ancylostoma ceylanicum was detected in a small number of children as well (n = 3). All of these infections were of low intensity (<4,999 or 999 eggs per gram for Ascaris and Trichuris respectively). Using this information, we characterised the baseline gut microbiome profile and investigated acute STH-induced alterations, comparing infected with uninfected children at the time of sampling. We found no difference between these groups in bacterial alpha-diversity, but did observe differences in beta-diversity and specific differentially abundant OTUs, including increased Akkermansia muciniphila and Bacteroides coprophilus, and reduced Bifidobacterium adolescentis, each of which have been previously implicated in STH-associated changes in the gut microfauna.

Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans. Using these techniques, we uncover surprising tissue-specific differences in mitochondrial morphology when fusion or fission proteins are absent. From ultrastructural analysis, we reveal a novel role for the fusion protein FZO-1/mitofusin 2 in regulating the structure of the inner mitochondrial membrane. Moreover, we have determined the influence of the individual mitochondrial fission (DRP-1/DRP1) and fusion (FZO-1/mitofusin 1,2; EAT-3/OPA1) proteins on animal behaviour and lifespan. We show that loss of these mitochondrial fusion or fission regulators induced age-dependent and progressive deficits in animal movement, as well as in muscle and neuronal function. Our results reveal that disruption of fusion induces more profound defects than lack of fission on animal behaviour and tissue function, and imply that while fusion is required throughout life, fission is more important later in life likely to combat ageing-associated stressors. Furthermore, our data demonstrate that mitochondrial function is not strictly dependent on morphology, with no correlation found between morphological changes and behavioural defects. Surprisingly, we find that disruption of either mitochondrial fission or fusion significantly reduces median lifespan, but maximal lifespan is unchanged, demonstrating that mitochondrial dynamics play an important role in limiting variance in longevity across isogenic populations. Overall, our study provides important new insights into the central role of mitochondrial dynamics in maintaining organismal health.