Comparative Analysis of Tick-Borne Relapsing Fever Spirochaetes from Ethiopia and Nigeria

Despite increasing reports of tick-borne diseases in Africa, remarkably, reports of tick-borne relapsing fever (TBRF) in Nigeria are lacking. Ornithodoros savignyi from Nigeria have been reported with the relapsing fever Candidatus Borrelia kalaharica. Conversely, in Ethiopia, the agent of relapsing fever is the louse-borne relapsing fever (LBRF) spirochaete Borrelia recurrentis with no TBRF reported to occur. A total of 389 Ornithodoros ticks, Ethiopia (N = 312) and Nigeria (N = 77), were sampled, together with 350 cattle, and 200 goat sera were collected from Nigeria. Samples were screened for Borrelia spp. by RT-PCR. Reactive samples were confirmed, then sequenced using flagellin B, 16S rRNA, and 16S–23S intergenic spacer region. The prevalence of Borrelia spp. in livestock was 3.8% (21/550) and 14% (3/21) after final molecular confirmation. Of 312 ticks from Ethiopia, 3.5% (11/312) were positive for Borrelia, with 36% (4/11) by conventional PCR. Sequencing revealed that the borreliae in soft ticks was C. B. kalaharica, whilst that found in animals was Borrelia theileri. Soft ticks were confirmed by sequencing 7% (22/312) and 12% (9/77) of the Ethiopian and Nigerian ticks, respectively. Phylogenetic analysis revealed that these were Ornithodoros savignyi. This is the first evidence of C. B. kalaharica in Ethiopia and demonstrates the co-existence of TBRF in a country endemic to LBRF. Important, this might cause a diagnostic challenge given that LBRF is predominantly diagnosed by microscopy, which cannot differentiate these two spirochaetes. Furthermore, we report B. theileri in ruminants in Nigeria, which may also be of veterinary and economic importance

Serospatial epidemiology of zoonotic Coxiella burnetii in a cross section of cattle and small ruminants in northern Nigeria

The persistent and highly transmissible Coxiella burnetii is a neglected infection that negatively affects reproductive parameters of livestock. It is also of zoonotic importance and has been reported to cause devastating human infections globally. Domestic ruminants represent the most frequent source of human infection. Data from Nigeria are very few and outdated. There is a significant gap in up-to-date information on the exposure, spatial distribution and risk factors of infection of this important disease. The exposure to C. burnetii was determined using sensitive serological assays in cattle and small ruminants. A total of 538 animals made up of 268 cattle and 270 small ruminants were sampled from three northern Nigerian states. The proportion of cattle sampled that were seropositive from the study locations were: Kwara 14/90 (15.6%; 95% CI: 8.8–24.7); Plateau 10/106 (9.43%; 95% CI: 4.6–16.7) and Borno 4/72 (5.56%; 95% CI: 1.5–13.6) states. Lower seroprevalence was recorded among the small ruminants sampled, with positives recorded from sheep and goat sampled from only Kwara state 6/184 (3.3%; 95% CI: 1.2–7.0); while none of the small ruminants sampled from Plateau were seropositive. The results of the bivariate analysis showed that none of the tested independent variables (village, age group, sex, breed of cattle, presence of ticks, reproductive status, and management system) were statistically significant factors associated with seropositivity of cattle for antibodies to C. burnetii. Stakeholders involved in animal husbandry should be duly educated on proper disposal of birth products as well as bodily fluids in order to reduce environmental contamination, persistence and human infection

Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease

Tau deposition in the brain is a pathological hallmark of many neurodegenerative disorders, including Alzheimer’s disease (AD). During the course of these tauopathies, tau spreads throughout the brain via synaptically-connected pathways. Such propagation of pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region (MTBR) composed of either three repeat (3R) or four repeat (4R) isoforms. The tau MTBR also forms the core of the neuropathological filaments identified in AD brain and other tauopathies. Multiple approaches are being taken to limit tau pathology, including immunotherapy with anti-tau antibodies. Given its key structural role within fibrils, specifically targetting the MTBR with a therapeutic antibody to inhibit tau seeding and aggregation may be a promising strategy to provide disease-modifying treatment for AD and other tauopathies. Therefore, a monoclonal antibody generating campaign was initiated with focus on the MTBR. Herein we describe the pre-clinical generation and characterisation of E2814, a humanised, high affinity, IgG1 antibody recognising the tau MTBR. E2814 and its murine precursor, 7G6, as revealed by epitope mapping, are antibodies bi-epitopic for 4R and mono-epitopic for 3R tau isoforms because they bind to sequence motif HVPGG. Functionally, both antibodies inhibited tau aggregation in vitro. They also immunodepleted a variety of MTBR-containing tau protein species. In an in vivo model of tau seeding and transmission, attenuation of deposition of sarkosyl-insoluble tau in brain could also be observed in response to antibody treatment. In AD brain, E2814 bound different types of tau filaments as shown by immunogold labelling and recognised pathological tau structures by immunohistochemical staining. Tau fragments containing HVPGG epitopes were also found to be elevated in AD brain compared to PSP or control. Taken together, the data reported here have led to E2814 being proposed for clinical developmen

ERS statement on chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 mu m, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.Thrombosis and Hemostasi

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Доклад ERS по хронической тромбоэмболической легочной гипертензии

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels &lt; 500 μm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/ perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions. This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH. It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.Хроническая тромбоэмболическая (ХТЭ) легочная гипертензия (ЛГ) – редкое осложнение острой тромбоэмболии легочной артерии (ТЭЛА) – как симптоматической, так и бессимптомной. При окклюзии проксимальных сегментов легочных артерий фиброзным внутрисосудистым материалом в комбинации со вторичной микроваскулопатией сосудов диаметром &lt; 500 мкм повышаются легочное сосудистое сопротивление и прогрессирующая правожелудочковая недостаточность. Механизм трансформации кровяных сгустков в остаточный фиброзный материал до сих пор не установлен. ХТЭ ЛГ у пациентов с ЛГ подозревается в случае, когда по данным вентиляционно-перфузионной сцинтиграфии легких выявляются несоответствующие картине вентиляции дефекты перфузии, которые подтверждаются при катетеризации правых отделов сердца и визуализации сосудов. В зависимости от локализации и типов повреждений, помимо пожизненного приема антикоагулянтов, на сегодняшний день доступны хирургическое лечение, ангиопластика и медикаментозное лечение. В настоящем докладе представлен обзор литературы и описана современная практика установления диагноза и ведения больных ХТЭ ЛГ. Документ охватывает области определения, диагностики, эпидемиологии, наблюдения после острой ТЭЛА, патофизиологии, лечения с помощью легочной тромбэндартерэктомии, баллонной ангиопластики легочной артерии, лекарственных препаратов и их комбинаций, реабилитации и новых направлений исследований в области ХТЭ ЛГ. Доклад представляет собой результат первого совместного проекта по ЛГ Европейского респираторного общества, Международной ассоциации хронической тромбоэмболической легочной гипертензии и Европейской сети медицинских учреждений по редким заболеваниям легких. В докладе резюмируются текущие знания, но не даются формальные рекомендации для клинической практики

Mechanism and Enantioselectivity in Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to β‑Substituted Cyclic Enones: Insights from Computation and Experiment

Enantioselective conjugate additions of arylboronic acids to β-substituted cyclic enones have been previously reported from our laboratories. Air- and moisture-tolerant conditions were achieved with a catalyst derived in situ from palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report a combined experimental and computational investigation on the mechanism, the nature of the active catalyst, the origins of the enantioselectivity, and the stereoelectronic effects of the ligand and the substrates of this transformation. Enantioselectivity is controlled primarily by steric repulsions between the t-Bu group of the chiral ligand and the α-methylene hydrogens of the enone substrate in the enantiodetermining carbopalladation step. Computations indicate that the reaction occurs via formation of a cationic arylpalladium(II) species, and subsequent carbopalladation of the enone olefin forms the key carbon–carbon bond. Studies of nonlinear effects and stoichiometric and catalytic reactions of isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium–ligand complex is the active species in the selectivity-determining step. The addition of water and ammonium hexafluorophosphate synergistically increases the rate of the reaction, corroborating the hypothesis that a cationic palladium species is involved in the reaction pathway. These additives also allow the reaction to be performed at 40 °C and facilitate an expanded substrate scope

Helminthes parasites of rodents caught around human habitats in Jos, Plateau state, Nigeria

Out of 112 rodents caught from three different locations in the University of Jos premises, 66(58.93%) were positive for helminth parasites. The prevalence rates of helminth parasites in the four species of rodents caught were 82.53% in Xerus erythropus (ground squirrel) 38.30% in Thryonomys swinderianus (cane rat) 70.00% in Rattus rattus (Black rat) and 75.00% in Cricetomys gambianus (Gambian giant rat). There was no significant difference (p>0.05) between the prevalence rates of the helminthes in the different rodent species. Four groups of helminthes, a trematode species, two species of cestodes, four species of nematodes and one species of an acanthocephalan were encountered in the rodents. The prevalence rates for the respective groups of helminthes were 11.61%, 25.00%, 33.93%, and 8.93%. The worm burdens per infected host were 1.85, 9.57, 10.47 and 8.90 for the trematode, cestodes, nematodes and acanthocephalan respectively. The prevalence rates of the different helminth parasites were 11.61, 15.18, 13.39, 18.75, 17.86, 16.96, 1.79 and 8.93% for Gastrodiscus, Hymenolepis nana, H. dimunita, Oesophagostomum, Cyathostomum, Trichuris, Ascaris and Macrocanthorhynchus respectively. Twenty (52.63%) of the 38 male rodents studied and 46(62.16%) of the 74 female rodents were infected by the helminth parasites whose prevalence rates in the male ranged from 0.00% to 15.97% and 2.70% to 22.97% in the female rodents. There was no significant difference (p>0.05) between the prevalence rates of the helminth parasites in both sexes of the rodents. The public health significance of the helminth parasites is discussed. Animal Production Research Avancees Vol. 3 (1) 2007: pp. 6-1