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Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study
Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2–16) relapses prior to study enrollment, with 5 (range, 3–15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5–10) the day prior to FMT to 2 (IQR, 1–2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2–6) before transplant to 8 (IQR, 5–9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. Clinical Trials Registration. NCT01704937.
Journal Article
Prospective cohort study reveals unexpected aetiologies of livestock abortion in northern Tanzania
Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of
C. burnetii
infection in livestock; and the first report of
Neospora caninum
,
Toxoplasma gondii,
and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions.
Journal Article
Identification of Immune Traits Correlated with Dairy Cow Health, Reproduction and Productivity
Detailed biological analyses (e.g. epidemiological, genetic) of animal health and fitness in the field are limited by the lack of large-scale recording of individual animals. An alternative approach is to identify immune traits that are associated with these important functions and can be subsequently used in more detailed studies. We have used an experimental dairy herd with uniquely dense phenotypic data to identify a range of potentially useful immune traits correlated with enhanced (or depressed) health and fitness. Blood samples from 248 dairy cows were collected at two-monthly intervals over a 10-month period and analysed for a number of immune traits, including levels of serum proteins associated with the innate immune response and circulating leukocyte populations. Immune measures were matched to individual cow records related to productivity, fertility and disease. Correlations between traits were calculated using bivariate analyses based on animal repeatability and random regression models with a Bonferroni correction to account for multiple testing. A number of significant correlations were found between immune traits and other recorded traits including: CD4(+):CD8(+) T lymphocyte ratio and subclinical mastitis; % CD8(+) lymphocytes and fertility; % CD335(+) natural killer cells and lameness episodes; and serum haptoglobin levels and clinical mastitis. Importantly these traits were not associated with reduced productivity and, in the case of cellular immune traits, were highly repeatable. Moreover these immune traits displayed significant between-animal variation suggesting that they may be altered by genetic selection. This study represents the largest simultaneous analysis of multiple immune traits in dairy cattle to-date and demonstrates that a number of immune traits are associated with health events. These traits represent useful selection markers for future programmes aimed at improving animal health and fitness.
Journal Article
The Clamshell Osteotomy for Diaphyseal Malunion in Deformity Correction and Fracture Surgery
Diaphyseal malunion poses a great challenge for the orthopedic surgeon, and an inundation of morbidity for the patient. Diaphyseal malunion can cause altered gait, adjacent joint osteoarthritis and body dissatisfaction. This problem is fraught with complications without surgical intervention. There is a myriad of options for the management of a diaphyseal malunion. The clamshell osteotomy was engendered to ameliorate the difficulty in managing this issue. This technique is a viable option to correct diaphyseal malunion about the femur and tibia. Recently, the indications of a clamshell osteotomy have been expanded to function as a derotational or shortening osteotomy.
Journal Article
Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease
Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn’s disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14–29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3–92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.
Journal Article
“It’s like a connection between all of us”: Inuit social connections and caribou declines in Labrador, Canada
Many caribou populations are declining across the Circumpolar North, presenting challenges for many Indigenous Peoples who have deep and enduring relationships with this animal. In Labrador, Canada, caribou herds have recently experienced population declines, including the George River herd, which has dropped by 99% from its peak, leading to the enactment of a total hunting ban in 2013 issued by the Government of Newfoundland and Labrador. The decline and subsequent hunting ban have affected various aspects of Inuit well-being. Using Inuit-led multi-media methods, this project heard voices of Inuit across the Nunatsiavut and NunatuKavut regions in Labrador, Canada, which (1) described the importance of caribou for Inuit social connections, (2) explored the ways in which the changes in caribou populations and management strategies are influencing these social connections, and (3) discussed the meaning and value of these social connections for Inuit well-being and the sustainability of Inuit-caribou relationships into the future. Data from video interviews (Nunatsiavut region: n = 54; NunatuKavut region: n = 30) were collected and analyzed using video and photography-based methods. Results characterized how caribou are important social connectors: human-caribou relationships are core to Inuit socialization, inter-connection, and shared experience and memory regarding families, communities, and food and knowledge sharing across Labrador’s landscape. Thus, declines in caribou populations and associated social interaction have had serious implications for Inuit identity, livelihoods, emotional well-being, cultural continuity, and knowledge transfer. In order to support the broader social-ecological system and the well-being of those who are connected to caribou, increased understanding and integration of these social connections into caribou-related decision making and research is recommended.
Journal Article
Disaster waste clean-up system performance subject to time-dependent disaster waste accumulation
Disasters can produce a substantial amount of waste that can threaten the capacity of waste management systems. This paper presents a methodology for estimating waste accumulation caused by disasters considering the uncertainty of the timing and scale of disasters that can be used to estimate the return period and the reliability of the disaster waste management system. To estimate the reliability of the system, the first-order second-moment reliability assessment method, in which the reliability index (β) is used to judge the reliability of a system, is applied in this paper. In addition, two case studies illustrate how the methods can be applied to the real world. The reliability index curve of the system developed from sensitivity analysis can provide information for decision-makers in terms of disaster waste clean-up arrangements. The approach developed can be used to analyze the effects of different parameters involved in the waste clean-up system after disasters.
Journal Article
Alcelaphine Herpesvirus-1 (Malignant Catarrhal Fever Virus) in Wildebeest Placenta: Genetic Variation of ORF50 and A9.5 Alleles
Alcelaphine herpesvirus-1 (AlHV-1), a causative agent of malignant catarrhal fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta tissue for the first time. Although viral load was low, the finding of viral DNA in over 50% of 94 samples tested lends support to the possibility that placental tissue could play a role in disease transmission and that wildebeest calves are infected in utero. Two viral loci were sequenced to examine variation among virus samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic viral glycoprotein. ORF50 was well conserved with six newly discovered alleles differing at only one or two base positions. In contrast, while only three new A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level and up to 20% at the amino acid level. Structural homology searching performed with the additional A9.5 sequences determined in this study adds power to recent analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as the major homologue. The majority of MCF virus samples obtained from Tanzanian cattle and wildebeest encoded A9.5 polypeptides identical to the previously characterized A9.5 allele present in the laboratory maintained AlHV-1 C500 strain. This supports the view that AlHV-1 C500 is suitable for the development of a vaccine for wildebeest-associated MCF.
Journal Article