Interventional magnetic resonance imaging guided carotid embolectomy using a novel resonant marker catheter: demonstration of preclinical feasibility.

To assess the visualization and efficacy of a wireless resonant circuit (wRC) catheter system for carotid artery occlusion and embolectomy under real-time MRI guidance in vivo, and to compare MR imaging modality with x-ray for analysis of qualitative physiological measures of blood flow at baseline and after embolectomy. The wRC catheter system was constructed using a MR compatible PEEK fiber braided catheter (Penumbra, Inc, Alameda, CA) with a single insulated longitudinal copper loop soldered to a printed circuit board embedded within the catheter wall. In concordance with IACUC protocol (AN103047), in vivo carotid artery navigation and embolectomy were performed in four farm pigs (40-45 kg) under real-time MRI at 1.5T. Industry standard clots were introduced in incremental amounts until adequate arterial occlusion was noted in a total of n=13 arteries. Baseline vasculature and restoration of blood flow were confirmed via MR and x-ray imaging, and graded by the Thrombolysis in Cerebral Infarction (TICI) scale. Wilcoxon signed-rank tests were used to analyze differences in recanalization status between DSA and MRA imaging. Successful recanalizations (TICI 2b/3) were compared to clinical rates reported in literature via binomial tests. The wRC catheter system was visible both on 5° sagittal bSSFP and coronal GRE sequence. Successful recanalization was demonstrated in 11 of 13 occluded arteries by DSA analysis and 8 of 13 by MRA. Recanalization rates based on DSA (0.85) and MRA (0.62) were not significantly different from the clinical rate of mechanical aspiration thrombectomy reported in literature. Lastly, a Wilcoxon signed rank test indicated no significant difference between TICI scores analyzed by DSA and MRA. With demonstrated compatibility and visualization under MRI, the wRC catheter system is effective for in vivo endovascular embolectomy, suggesting progress towards clinical endovascular interventional MRI.

Comparative clinico-pathological observations in young Zebu (Bos indicus) cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse areas of Northwest Ethiopia.

BACKGROUND: The Northwest region of Ethiopia is affected by both tsetse and non-tsetse transmitted trypanosomosis with a huge impact on livestock productivity. The objective of this experimental study was to determine clinical and pathological findings in young Zebu cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia. A total of 18 cattle (Bos indicus) aged between 6 and 12 months, purchased from a trypanosome-free and confirmed to be trypanosome negative divided into three groups of six animals were used. Animals in the first two groups (Group TT: tsetse infested isolate infected and Group NT: non-tsetse infested isolate infected) received 2 mL of infected blood from donor animals at 10(6) trypanosomes/mL, and the remaining group was non-infected control (NIC). Each group was observed for a period of eight consecutive weeks, daily for clinical signs and once per week for parasitaemia. Postmortem examinations were done on euthanized animals, and tissue samples were taken for histopathological analysis. RESULTS: The prepatent period of the disease was earlier in the NT group 6 days post infection (dpi) than TT group 12 dpi. The infection was characterized by reduced feed intake, intermittent pyrexia and parasitaemia, enlarged lymph nodes, lacrimation, reduced feed intake and emaciation. Less frequently diarrhea, oedema and nervous signs were observed in both groups of infected animals. At necropsy, infected animals showed enlarged spleen, enlarged lymph nodes, pneumonic and emphysematous lung, enlarged liver, and haemorrhages on the brain and intestine. Histopathological analysis revealed lymphoid hyperplasia of the spleen, necrosis of the liver, encephalitis and hyperplasia of lymph nodes. CONCLUSION: Trpanosoma vivax isolates from both tsetse infested and non-tsetse areas showed a variety of virulence factors leading to the development of acute clinical signs, gross and histopathological lesions. However, the parasitaemia and clinical signs appeared earlier in the NT compared to TT infected groups.

Prevalence of bovine trypanosomosis and assessment of trypanocidal drug resistance in tsetse infested and non-tsetse infested areas of Northwest Ethiopia.

The Northwestern region of Ethiopia is affected by both tsetse and non-tsetse transmitted trypanosomosis with a significant impact on livestock productivity. The control of trypanosomosis in Ethiopia relies on either curative or prophylactic treatment of animals with diminazene aceturate (DA) or isometamidium chloride (ISM). In the present work; questionnaire survey, cross-sectional and experimental studies were carried out to; a) assess the utilization of trypanocidal drugs; b) determine the prevalence of bovine trypanosomosis and; c) assess the drug resistant problems respectively in Tsetse and non-tsetse infested areas on NW Ethiopia. A total of 100 respondents were included for the survey and the questionnaires focused on the drug utilization practices for the control of Trypanosomosis. Blood from cattle 640 (324 cattle tested in 2011, 316 cattle tested in 2012) and 795 (390 cattle tested in 2011, 405 cattle tested in 2012) were examined from tsetse infested and non-tsetse infested areas respectively using the buffy coat technique and thin blood smear for the detection of trypanosomes and measurement of packed cell volume (PCV). For the assessment of trypanocidal drug resistance three isolates, one from tsetse (TT) and two from non-tsetse (NT) areas were used on thirty six trypanosome naïve calves. The experimental animals were divided randomly into six groups of six animals (TT-ETBS2-DA, TT-ETBS2-ISM, NT-ETBD2-DA, NT-ETBD2-ISM, NT-ETBD3-DA and NT-ETBD3-ISM), which were infected with T. vivax isolated from a tsetse-infested or non-tsetse infested area with 2 × 106 trypanosomes from donor animals, and in each case treated with higher dose of DA or ISM. The results of the questionnaire survey showed trypanosomosis was a significant animal health constraint for 84% and 100% of the farmers questioned in non-tsetse and tsetse infested areas of Northwest Ethiopia respectively. Responses on trypanocidal drug utilization practices indicated that risk factors for the development of drug resistance are common and treatment failures are frequently seen. Accordingly, the majority of farmers in tsetse infested area get trypanocides from drug stores and unauthorized sources whereas those from non-tsetse area get from veterinary clinics. Moreover, treatment administration is mainly by animal health personnel and treatment frequency is a maximum of three times/year/animal in non-tsetse area whereas it is administered mainly by the farmers more than seven times/year/animal in tsetse infested area. The prevalence of trypanosomosis varied from 17.59% in 2011 to 25.0% in 2012 in tsetse infested areas with a significant (P = 0.023) difference. Similarly, in non-tsetse infested area the prevalence was varied from 3.85% in 2011 to 5.93% in 2012 without significant rise. Trypanosoma congolense (75%) was the most prevalent followed by T. vivax (20.58%) and mixed infections (4.41%) in tsetse infested area while in non-tsetse infested area only T. vivax was detected. The overall mean PCV in parasitaemic animals (20 ± 2.3 SD) was significantly (P < 0.001) lower than that of aparasitaemic animals (27 ± 4.3 SD). The assessment of trypanocidal drug resistance tests revealed one isolate of non-tsetse infested area against DA in group NT-ETBD2-DA is resistant to the higher dose used with 3 relapsing animals (50% relapses) in the group. Another two relapses were detected one against ISM for the isolate from tsetse infested area (TT-ETBS2-ISM) and one against DA for another isolate (NT-ETBD3-DA) from the non-tsetse area. In conclusion, trypanosomosis is widely prevalent in both study areas causing significant reduction in the mean PCV values. Farmers' trypanocidal utilization practices appear to pose risks of drug resistance problems. The in vivo drug resistance tests indicated the presence of resistant parasites with the higher dose against DA for NT-ETBD2 isolate and suspected resistance problems were detected against ISM and DA for TT-ETBS2 and NT-ETBD3 isolates respectively. Therefore, trypanosomosis is a major constraint in Northwest Ethiopia and drug resistance is a threat in the control of trypanosomosis in both study areas.

In vivo experimental drug resistance study in Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia.

Ethiopia, particularly in the Northwest region, is affected by both tsetse fly and non-tsetse fly transmitted trypanosomosis with a significant impact on livestock productivity. The control of trypanosomosis in Ethiopia relies on either curative or prophylactic treatment of animals with diminazene aceturate (DA) or isometamidium chloride (ISM), respectively. However, since these two trypanocides have been on the market for more than 40 years, this may have resulted in drug-resistance. Therefore, in vivo drug resistance tests on two Ethiopian isolates of Trypanosoma vivax were completed, one from an area where tsetse flies are present and one from an area where tsetse flies are not present. Twenty four cattle (Bos indicus) aged between 6 and 12 months, purchased from a trypanosome-free area (Debre Brehan: Northcentral Ethiopia) and confirmed to be trypanosome-negative, were randomly assigned into four groups of six animals, which were infected with T. vivax isolated from a tsetse-infested or non-tsetse infested area, and in each case treated with curative doses of DA or ISM. Each animal were inoculated intravenously 3×10(6) trypanosomes from donor animals. Parasitaemia became patent earlier in infections with non-tsetse T. vivax (∼7 days post-infection) than tsetse (∼14 days post-infection). Both groups were treated at the highest peak parasitaemia with DA or ISM and nine cattle, four with non-tsetse T. vivax (two ISM- and two DA-treated) and five with tsetse T. vivax (three ISM- and two DA-treated) showed relapses of parasitaemia. Moreover, treatment did not improve diagnostic host markers of trypanosome infections in these animals. In conclusion, in vivo drug tests indicated the presence of resistant parasites (>20% of treated animals in each group relapsed) against recommended doses of both available trypanocidal drugs.

Comparative biochemical changes in young Zebu cattle experimentally infected with Trypanosoma vivax from tsetse infested and non-tsetse infested areas of northwest Ethiopia.

Trypanosomosis is a vector-borne protozoan disease of animals and humans in sub-Saharan Africa. In Ethiopia, particularly the northwest region is affected by both tsetse and non-tsetse transmitted trypanosomosis. The aim of the present study was to determine the effects and compare differences in virulence of Trypanosoma vivax infection between tsetse and non-tsetse infested areas of northwest Ethiopia on the basis of serum biochemical values in Zebu cattle. Eighteen cattles purchased from trypanosome free area and aged between 9 and 12 months were assigned into three groups of six animals (Group TT=infected with T. vivax from tsetse infested area, Group NT=infected with T. vivax from non-tsetse infested area and Group C=non-infected control). For each experimental animal 3 ml of blood from naturally infected cattle was inoculated intravenously at 10(6) trypanosomes/ml except the control. Blood sample was collected once a week for 8 consecutive weeks for analyzing serum biochemical values (glucose, total cholesterol, total protein, albumin, and enzymes including GOT, GPT and ALP) using a Humastar 80 clinical chemistry analyzer. Both T. vivax parasites caused an acute infection with parasites appearing in circulation on 6 and 12 days post-infection for NT and TT cattle, respectively. A significant reduction (P<0.001) in glucose levels was observed in infected groups compared with the control with mean values of 33.8 ± 3.6 mg/dl for TT, 34.3 ± 3.6 mg/dl for NT and 70.9 ± 3.0 mg/dl for control groups. A similar reduction was also seen in total cholesterol values (P=0.001) with 70.4 ± 10.6 mg/dl for TT and 78.0 ± 10.6 mg/dl for NT groups compared to 139.5 ± 8.7 mg/dl for the control group. No difference was observed for total serum protein between the three groups (P=0.260) whereas the mean albumin level was significantly (P<0.001) decreased (3.5 ± 0.1g/dl and 2.9 ± 0.1g/dl in TT and NT groups respectively) compared to that for control cattle (4.5 ± 0.1g/dl). On the other hand, infected groups had higher ALP values compared to the control (P=0.007), with a mean value of 538. 4 ± 64.4 IU/L, 564.9 ± 64.4 IU/L and 273.2 ± 52.6 IU/L for TT, NT and control cattle, respectively. In conclusion, the two T. vivax parasites caused significant biochemical changes indicative of pathological responses. However, there was no significant variation between the two parasites in initiating these changes despite the difference in the onset of parasitaemia.