An Assessment Of The Efficacy Of Dfmo In Baboons (Papio Anubis) Infected With Trypanosma Brucei Gambiense

Infection of four baboons with Trypanosma brucei gambiense resulted in a prepatent period of 3 – 4 days. Following the first appearance of T. b. gambiense parasitaemia, the animals developed trypanosomosis characterised by elevated parasite counts in the blood, fever, increased heart and respiratory rates and increased capillary refill time. The disease was also associated with pallor of visible mucous membranes, oedema, increased reticulocyte counts, progressive decline in erythrocyte indices (RBC, Hb and PCV), consistent monocytosis, and leucopenia due to lymphopenia and neutropenia. These clinical signs and widespread pathological changes seen in the liver, kidney, lymph nodes, heart and brain were progressive with the disease. The disease also disrupted the circadian rhythmicity of sleep and wakefulness between weeks 8 and 10 when the animals were in the classical diurnal sleepiness with 8 - 10 sleep episodes and nocturnal restlessness. All the infected baboons died from the attendant disease between the 8 and 10 weeks of infection. Treatment with Berenil or DFMO at 4 weeks post infection reversed most of the clinical, haematological and pathological changes, the CSF-WBC counts and cleared the parasites from the circulation of the infected baboons. However, there was relapse parasitaemia by 18 and 20 weeks respectively post infection in the groups treated with DFMO and Berenil. The results of this study suggest that baboons manifest similar clinical and pathological lesions as man infected with T. b. gambiense and might therefore be a useful model for the study of the human disease. Furthermore, the results suggest the therapeutic usefulness of DFMO in the treatment of human and animal trypanosomosis due to T. b. gambiense

Training Non-Specialists for Craniomaxillofacial Trauma in a Warzone Setting

This study investigated a simulated craniomaxillofacial (CMF) trauma training programme for non-specialist clinicians involved in warfare environments. Many clinicians lack CMF surgical training and the course was designed as a one-day research programme to establish if non-specialists could acquire CMF trauma skills adequate for a warzone. The course consisted of six simulation skills, of which four used sheep heads to teach craniotomy, epistaxis, canthotomy and cantholysis and external pin fixation for mandibular fracture fixation. In addition, two skills utilised plaster dental models designed to enable fixation of mandibular fractures with the Erich arch bar or dental eyelet wiring. This simulation-based programme taught trauma management without the expense of cadavers or risks to patients [1]. The trainees were scored for each of the six skills by hierarchical task analysis (HTA) designed by CMF specialists [2, 3]. The trainee assessment scores improved significantly in all skills post-training, regardless of their medical or surgical deficiencies demonstrating that non-specialists can learn important surgical techniques, valuable for war environments

Use of indigenous knowledge in the management of field and storage pests around Lake Victoria basin in Tanzania

Agriculture in Lake Victoria basin (LVB) in Tanzania is predominantly subsistence and is characterised by perennial food deficits, cyclic famines and poverty prompted largely by unreliable rainfall patterns, declining soil fertility and food grains pests and diseases. The pest problem is more pronounced as farmers are yet to fully integrate synthetic pesticides into their insect pest management systems due to subsistence nature of production and high poverty levels that make them rely on indigenous knowledge (IK) systems to meet their needs. The survey was conducted to document farmers’ IK on management of key field and storage insect pests in Magu and Misungwi districts in the LVB, Tanzania. Major crops grown were maize, rice, sorghum, finger millet, bean, groundnut, cowpea, green gram, brassicas, chicken pea, cassava, sweet potato, cotton and vegetables. Crops were mainly infested by Busseola fusca (Lepidoptera: Noctuidae), Spodoptera spp (Lepidoptera: Noctuidae), Agrotis spp (Lepidoptera: Noctuidae), Maruca vitrata (Lepidoptera: Crambidae), Rhopalosiphum maidis (Homoptera: Aphididae), Aphis fabae (Hemiptera: Aphididae), and grasshoppers in field and Stophilus spp (Coleoptera: Curculionidae), Prostephanus truncates (Coleoptera: Bostrichidae), Tribolium spp (Coleoptera: Tenebrionidae), Bruchus rufimanus (Coleoptera; Bruchidae), Rhyzopertha dominica (Coleoptera: Bostrichidae) and rodents on storage. IK based control methods used by farmers ranged from animal by-products (cow’s urine and dung), plant parts (Azadirachta indica (Meliaceae),Tephrosia vogelii (Fabaceae), Tamarindus indica (Fabaceae), Aloe spp (Asphodelaceae), red pepper, Capsicum spp (Solanaceae), Nicotiana tabasum (Solanaceae) to ash (general and specific) in the field. They also used neem, Chenopodium opulifolium (Chenopodiaceae), Ocimum suave (Labiatae), Senna siamea (Fabaceae or Caesalpinioideae), tobacco and Eucalyptus spp (Myrtaceae) and plant by-products (rice husks, ash from rice husks and red maize cobs and general ash) to control storage pests. Most of these products were used together with one or two others in different formulation mixtures. However, the formulations had variable amount taken during preparation, crop/ crop product treated, preparation times, modes and rates of application. Research is needed to unveil the amount for mixing, appropriate treatment, and application rate to ensure optimum concentration for specific pest. To ensure quality and safety, biosafety and quality studies are required for quality assessment of resulting product for human health. For understanding of active compounds in the formulations, chemical composition analysis of properly prepared solutions is required. Key words: Field and storage pests, indigenous knowledge, Tanzania, botanical formulation, Lake Victoria basin

Gastric adenocarcinoma in Zambia: A case-control study of HIV, lifestyle risk factors, and biomarkers of pathogenesis

Background. Gastric cancer is a leading cause of cancer deaths worldwide but there are few data from Africa. We recently observed a trendtowards diagnosis in younger patients.Objective. To test the hypothesis that HIV might have altered risk factors for acquisition of gastric cancer, in a case-control study in theUniversity Teaching Hospital, Lusaka, Zambia.Methods. Patients (n=52) with confirmed gastric adenocarcinoma and controls (n=94) undergoing endoscopy but with no macroscopicgastric pathology. Established risk factors and HIV status were compared.Results. HIV status did not differ significantly between cases and controls (odds ratio 1.03; 95% CI 0.2 - 4.3; p=1.00) and seroprevalencein cases was similar to that of the Zambian population. Smoking, regular alcohol intake, and gastric atrophy were all associated with cancerin univariate and multivariate analysis. Helicobacter pylori serology was positive in 84% of patients studied and cytotoxin-associated gene A(cagA) serology in 66%; neither serological marker was associated with cancer. Atrophy was common in cases (57%) and controls (30%) andassociated with both smoking and alcohol use. Intestinal metaplasia was present in 17% of the controls, but was not associated with atrophy.Conclusions. HIV was not associated with gastric cancer and does not explain the apparent younger age distribution. Atrophy was commonand was not essential for the development of intestinal metaplasia, suggesting that gastric carcinogenesis in Africa does not always followthe pathway from atrophy to intestinal metaplasia to gastric carcinoma (the so-called Correa pathway)

Decoding the enigma of antiviral crisis: Does one target molecule regulate all?

Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes

Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization.

BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date. METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×105 plaque-forming units (PFU), 3×106 PFU, 2×107 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay. FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides. INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×107 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099)

Deployment of spatial attention towards locations in memory representations: an EEG study

Recalling information from visual short-term memory (VSTM) involves the same neural mechanisms as attending to an actually perceived scene. In particular, retrieval from VSTM has been associated with orienting of visual attention towards a location within a spatially-organized memory representation. However, an open question concerns whether spatial attention is also recruited during VSTM retrieval even when performing the task does not require access to spatial coordinates of items in the memorized scene. The present study combined a visual search task with a modified, delayed central probe protocol, together with EEG analysis, to answer this question. We found a temporal contralateral negativity (TCN) elicited by a centrally presented go-signal which was spatially uninformative and featurally unrelated to the search target and informed participants only about a response key that they had to press to indicate a prepared target-present vs. -absent decision. This lateralization during VSTM retrieval (TCN) provides strong evidence of a shift of attention towards the target location in the memory representation, which occurred despite the fact that the present task required no spatial (or featural) information from the search to be encoded, maintained, and retrieved to produce the correct response and that the go-signal did not itself specify any information relating to the location and defining feature of the target