Snakes and Snakebite Envenoming in Northern Tanzania: A Neglected Tropical Health Problem.

Snakebites cause considerable human and livestock injuries as well as deaths worldwide, and particularly have a high impact in sub-Saharan Africa. Generating a basic platform of information on the characteristics of snakes and snakebites in various countries is relevant for designing and implementing public health interventions. This study was performed to identify types of snakes and some of the characteristics of snakebite cases in two communities, an agricultural and a pastoralist, in Arusha region, northern Tanzania. A total of 30 field visits were carried out in areas considered by local inhabitants to be potential microhabitats for snakes. Direct observation of snake types based on morphological features and a structured questionnaire were employed for data collection. A total of 25 live and 14 dead snakes were encountered. Among the dead ones, the following species were identified: two black-necked spitting cobras (Naja nigricollis); five puff adders (Bitis arietans), one common egg-eater (Dasypeltis scabra); two rufous-beaked snakes (Ramphiophis rostratus); two brown house snakes (Lamprophis fuliginosus); one Kenyan sand boa (Eryx colubrinus), and one black mamba (Dendroaspis polylepis). The frequency of snake encounters was significantly higher (χ (2) = 4.6; p = 0.03) in the pastoral than in the agricultural area; there were more snakebite cases in the former, but the differences were not statistically significant (p = 0.7). A total of 242 snakebite victims attended at the Meserani Clinic, located in the study area, between the years 2007 to 2012. Of all cases, 146 (61.6 %) and 96 (38.4 %) were male and female patients, respectively. As for age distribution, 59.1 % of snakebite victims were from the economically active age groups between 15 and 55 years. Snakebites are a threat to rural communities and public health in general. The burden of snakebites in Tanzania presents an epidemiologically similar picture to other tropical countries. Livestock keeping and agriculture are the major economic activities associated with snakebites. Community-based public education is required to create awareness on venomous snakes and predisposing factors to snakebites. These tasks demand integration of diverse stakeholders to achieve a common goal of reducing the impact of human suffering from these envenomings in Tanzania

Group A Streptococcus pharyngitis among schoolchildren in Mbulu District, Tanzania

Streptococcal pharyngitis continues to be one of the most common childhood illnesses throughout the world. Recent evidence indicates an increased incidence of group A Streptococcal (GAS) infections, which is a significant cause of mortality and morbidity on the global scale. The objective of this study was to determine prevalence of group A Streptococcus infection among primary schoolchildren in Mbulu district, northern Tanzania. This study was carried out in five primary schools, namely Mangisha, Gunyoda, Kainam, Hyloto and Tsaayo. GAS pharyngitis was diagnosed clinically and confirmed by laboratory investigation using a rapid test. A total of 320 study participants were recruited in the study. Overall, more than half (53.8%) of the children were females.  The overall prevalence of Group a Streptococcal infection was 6.9% (95%CI [4.4-10.2]).  The highest frequency of GAS infection was observed among children at Hyloto primary school (14.3%) while, none of the children in Tsaayo had GAS infection. This study potentially indicates that group A Streptococcal infection prevalent among schoolchildren in Mbulu district calling for the need of education to create awareness of the condition in the community

Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare neurodegenerative disease associated with mutations in the human VPS13A gene. The mechanism of ChAc pathogenesis is unclear. A simple yeast model was used to investigate the function of the single yeast VSP13 orthologue, Vps13. Vps13, like human VPS13A, is involved in vesicular protein transport, actin cytoskeleton organisation and phospholipid metabolism. A newly identified phenotype of the vps13Δ mutant, sodium dodecyl sulphate (SDS) hypersensitivity, was used to screen a yeast genomic library for multicopy suppressors. A fragment of the MYO3 gene, encoding Myo3-N (the N-terminal part of myosin, a protein involved in the actin cytoskeleton and in endocytosis), was isolated. Myo3-N protein contains a motor head domain and a linker. The linker contains IQ motifs that mediate the binding of calmodulin, a negative regulator of myosin function. Amino acid substitutions that disrupt the interaction of Myo3-N with calmodulin resulted in the loss of vps13Δ suppression. Production of Myo3-N downregulated the activity of calcineurin, a protein phosphatase regulated by calmodulin, and alleviated some defects in early endocytosis events. Importantly, ethylene glycol tetraacetic acid (EGTA), which sequesters calcium and thus downregulates calmodulin and calcineurin, was a potent suppressor of vps13Δ. We propose that Myo3-N acts by sequestering calmodulin, downregulating calcineurin and increasing activity of Myo3, which is involved in endocytosis and, together with Osh2/3 proteins, functions in endoplasmic reticulum-plasma membrane contact sites. These results show that defects associated with vps13Δ could be overcome, and point to a functional connection between Vps13 and calcium signalling as a possible target for chemical intervention in ChAc. Yeast ChAc models may uncover the underlying pathological mechanisms, and may also serve as a platform for drug testing.This article has an associated First Person interview with the first author of the paper

Ca2+ homeostasis in familial Alzheimer's disease: a view from intracellular Ca2+ stores

Familial Alzheimer's disease (FAD) -linked mutations in presenilin 1 and 2 (PS1, PS2) have been causally implicated in neurodegeneration and eventually neuronal cell death by amyloid toxicity and perturbation of cellular Ca2+ homeostasis. The mechanism governing this latter phenomenon remains unclear. In the cytosol, upon stimulation, both exaggerated and reduced Ca2+ release have been reported in different cell lines and neurons expressing PS1 and PS2 mutants. Despite the contradicting data yet available, it is undisputable that FAD-linked PS mutants cause imbalances of cellular Ca2+ homeostasis. Recent independent reports have strongly suggested that the FAD-linked PS1 and PS2 mutants interact directly or indirectly with both the ER Ca2+ uptake and release machinery by modulating SERCA pump, IP3R- and RyR channel activity. In the study described here, we took advantage of two available lines of transgenic (tg) mice expressing a mutant PS2 alone or together with a mutant amyloid precursor protein (APP) - both linked to FAD - in order to investigate its effects on Ca2+ homeostasis in a physiological environment more relevant to the pathology under study. We particularly focused our attention on Ca2+ dysregulation in cortical neurons from tg mice either single homozygous for human PS2-N141I or double homozygous for human PS2-N141I and human APP swedish mutations. Ca2+ measurements were carried by the fura-2/AM technique. This study highlights the role of PS2-N141I in modulating Ca2+ homeostasis of cortical neurons. We have demonstrated that, irrespective of the presence of mutant APP, modest expression of PS2-N141I altered the Ca2+ dynamics of intracellular stores. The total Ca2+ content of intracellular stores is partially depleted, as demonstrated by reduced Ca2+ release upon ionomycin stimulation. Consequently, the tg neurons have reduced Ca2+ release in response to IP3-generating agonists. However, the PS2 mutant does not affect the protein expression levels for both SERCA pump and IP3Rs. Our results suggest that the PS2-N141I FAD mutant causes a functional defect in ER Ca2+ entry/exit pathways. We also show that both tg neurons express very low levels of the mutant protein but show Ca2+ dysregulation, similar quantitatively and qualitatively to that previously reported in cell lines upon transient over-expression of the same mutant protein. Conversely, measurements of Ca2+ release via RyRs revealed a novel and unexpected finding in PS2 mutant tg mice i.e. increased Ca2+ release in response to caffeine. In addition, RyR2 protein expression level was elevated in tg neurons. Upregulation of RyRs function and protein levels could save as an adaptation phenomenon to compensate the reduction in Ca2+ release via IP3Rs or a direct effect of mutant PS2 on RyR or a secondary effect. Furthermore, PS2-N141I causes alteration in neuronal Ca2+ excitability. The tg neurons had significantly elevated number of picrotoxin-evoked synchronous Ca2+ oscillations, which required extracellular Ca2+ influx but not Ca2+ release from intracellular stores. Interestingly, while Ca2+ dysregulation appeared to be similar qualitatively and quantitatively in both single and double tg mouse models, the total amount of brain Ab42 and Ab40 peptides (ELISA) as well as their ratios were strikingly different between the two tg lines. These results strongly suggest that in tg mice the expression of mutant APP and/or Ab levels have no primary effect on the store Ca2+ content at this early stage and provide evidence that the quite similar effects on Ca2+ dynamics observed in both tg mice are due to the mutant PS2. Finally, results presented in this work suggest that although Ca2+ dysregulation is an early event in FAD, it does not affect neuronal response and vulnerability to cytotoxic stimuli at this early stage. The second part of this study focused on the role of Ab42 oligomers in cellular Ca2+ dynamics. Synthetic Ab42 oligomers reduced Ca2+ release in response to IP3 generating agonists in wt neurons but did not affect the total Ca2+ content as monitored by ionomycin. Conversely, Ab42 oligomers increased the Ca2+ release induced by caffeine. It is likely that Ab42 oligomers exert their effect on the activation pathway from IP3 generating agonists to IP3Rs. However, the mechanisms through which Ab42 deranges intracellular Ca2+ homeostasis require further investigation. Nonetheless, it is conceivable that in addition to Ab42 oligomers, also intracellular Ca2+ stores could become likely therapeutic targets in FAD and AD in generalE stato dimostrato che mutazioni in presenilina 1 e 2 (PS1, PS2) legate alle forme familiari della malattia di Alzheimer (FAD) sono implicate nella neurodegenerazione e in ultima istanza nella morte cellulare per effetto della tossicità del peptide amiloide e della perturbazione dell'omeostasi del Ca2+ cellulare. Il meccanismo alla base di quest'ultimo fenomeno non è ancora stato chiarito. Si è visto che in linee cellulari e in neuroni esprimenti mutazioni in PS1 e PS2, il rilascio di Ca2+ nel citosol in seguito a stimolazione cellulare può essere sia aumentato che ridotto. Nonostante i dati contraddittori attualmente disponibili, è innegabile che i mutanti di PS legati a FAD provocano uno squilibrio nell'omeostasi del Ca2+ cellulare. Recentemente studi indipendenti hanno dimostrato che i mutanti FAD in PS1 o PS2 interagiscono sia con i meccanismi di rilascio che di accumulo di Ca2+ nel reticolo endoplasmatico (RE), modulando sia l'attività  della pompa SERCA che i canali di tipo IP3R e RyR. In questo studio abbiamo impiegato due linee già  disponibili di topi transgenici (tg) esprimenti una PS2 mutata, da sola o assieme alla Proteina Precursore dell'Amiloide (APP) (entrambe con mutazioni legate a FAD) al fine di investigarne gli effetti sull'omeostasi del Ca2+ in una condizione fisiologica più rilevante per la patologia oggetto dello studio. Abbiamo focalizzato in particolare la nostra attenzione sull'alterazione del Ca2+ in neuroni corticali ottenuti da topi tg omozigoti per il solo mutante PS2-N141I o doppi omozigoti per le proteine mutate PS2-N141I e APPswe. Le misure di Ca2+ sono state effettuate con la tecnica del Fura-2/AM. Questo studio mette in evidenza il ruolo della PS2-N141I nel modulare l'omeostasi del Ca2+ in neuroni corticali murini. Abbiamo dimostrato che, indipendentemente dalla presenza del mutante di APP, l'espressione della PS2-N141I, in quantità  moderata, inficia le dinamiche del Ca2+ dei depositi intracellulari. In particolare,i depositi del Ca2+ sono parzialmente svuotati, come dimostrato dal ridotto rilascio di Ca2+ in seguito a stimolazione con ionomicina. Conseguentemente i neuroni tg hanno un ridotto rilascio di Ca2+in risposta ad agonisti legati alla generazione di IP3. Occorre notare che la PS2 mutata non altera i livelli di espressione delle proteine SERCA e IP3R. I nostri risultati suggeriscono che il mutante FAD PS2-N141I causa un difetto funzionale nelle vie di entrata e di uscita del Ca2+ dal RE. Abbiamo inoltre dimostrato che i neuroni di entrambe le linee tg esprimono bassi livelli di proteina mutante ma mostrano un'alterazione del segnale Ca2+ qualitativamente e quantitativamente simile a quella precedentemente riportata per le linee cellulari sovra-esprimenti la stessa proteina. Al contrario, misure del rilascio di Ca2+ via RyR hanno rivelato un effetto inatteso, ovvero un aumentato rilascio di Ca2+ in risposta a caffeina nei neuroni tg. Inoltre, i livelli proteici di RyR2 sono aumentati nei neuroni tg. Un aumento della funzionalità  e dei livelli proteici di RyR2 potrebbero essere un fenomeno adattativo per compensare la riduzione del rilascio di Ca2+ via IP3R oppure essere un effetto diretto dei mutanti PS2 su RyR2 o ancora un effetto secondario. Infine abbiamo dimostrato che la PS2-N141I causa un'alterazione nell'eccitabilità  neuronale. I neuroni tg hanno un numero significativamente più elevato di oscillazioni di Ca2+ sincronizzate, evocate da picrotossina, che dipendono dall' ingresso di Ca2+ extracellulare e non dal rilascio di Ca2+ dai depositi. E interessante notare che, mentre l'alterazione del Ca2+ è qualitativamente e quantitativamente simile nei singoli e doppi tg, sia il livello totale di peptidi Ab42 e Ab40 nel tessuto cerebrale (misurati mediante ELISA) che il loro rapporto sono notevolmente diversi tra le due linee tg. Questi risultati suggeriscono che nei topi tg l'espressione di APP mutata o i livelli di Ab non hanno alcun effetto primario sul contenuto dei depositi di Ca2+ in questo stadio precoce, e suggeriscono che gli effetti sulle dinamiche del segnale Ca2+, così simili nelle due linee tg, siano dovuti alla PS2 mutata. Infine, i risultati qui presentati suggeriscono che nonostante l'alterazione del segnale Ca2+ sia un evento precoce nei neuroni a questo stadio, non altera la vulnerabilità  neuronale a stimoli citotossici che agiscono atrraverso i depositi del Ca2+ . La seconda parte di questo studio si è concentrata sul ruolo degli oligomeri di Ab42 sulle dinamiche del Ca2+ cellulare. Nei neuroni di topi wt, oligomeri di Ab42 sintetico riducono il rilascio di Ca2+ in risposta ad agonisti legati alla produzione di IP3, ma non riducono il contenuto totale di Ca2+ dei depositi misurato mediante applicazione di ionomicina. D'altra parte, gli oligomeri di Ab42 aumentano il rilascio di Ca2+ indotto da caffeina. E' probabile che gli oligomeri di Ab42 agiscano sulla via attivata dagli agonisti legati alla produzione di IP3 e sull' IP3R. I meccanismi attraverso cui Ab42 altera l'omeostasi intracellulare del Ca2+ richiedono tuttavia ulteriori indagini. In conclusione, oltre agli oligomeri di Ab42 anche i depositi intracellulari di Ca2+ possono diventare un importante bersaglio terapeutico per intervenire sulla patologia di Alzheimer familiare ma anche sulla forma sporadic

Scientometric mapping of veterinary research at Sokoine University of Agriculture, Tanzania

International Journal of Digital Library Services IJODLS | Geetanjali Research Publication 19 Vol. 6, July – Sept. 2016, Issue - 3A scientometric analysis was conducted to examine the research productivity of veterinary scientists at the Sokoine University of Agriculture from 1984 to 2015. Data on publications, citations and related metrics for 97 scientists were retrieved using the Publish or Perish software. A total of 2,392 publications were recorded for all veterinary scientists, giving an average of 74.75 publications per year. The whole study period recorded the mean RGR and Dt of 2.10 and 0.36 respectively. The rate of growth of publications increased while the corresponding doubling time deceased. A great majority (2304; 96.3%) of the publications were multipleauthored with over one third (891; 37.2%) of these being jointly contributed by six or more authors. The degree of collaboration among scientists was 0.96. The maximum number of citations received in a single publication was 530. The top 25 ranked veterinary researchers showed considerable variation in various metrics. Veterinary scholars at SUA published their research findings in 241 different journals during the period between 1984 and 2015

Assessment of health status, handling and management of working animals in Tanzania: A case study of Donkeys in Kilosa district

The use of donkeys as drought animal has been a tradition in various parts of Tanzania. Donkeys transport goods to markets, children to schools, sick people, women in labor and water and supplies to remote communities. Despite the importance of donkeys in the community, little is known on the common diseases affecting donkeys in Tanzania. In addition, there is no structured management systems, handling, reproduction and/or disease control programmes. According to a report by ministry of Livestock development and Fisheries, the number of donkeys is decreasing. Several measures have been undertaken to save these animals including stopping of the slaughter operations which were carried out in Dodoma municipality. However, to fulfill the demand, capacity building on proper management system, handling, disease surveillance and control systems is important. This study therefore assessed the health status of donkeys, handling and management system practiced in Kilosa. Field visits, interviews, structured questionnaire and focus group discussion were used to gather information. Clinical examination was undertaken and samples collected for disease diagnosis. Sick animals were treated. The observation showed that donkeys suffer several ailments including poor management systems (housing, feeding, and manure disposal), infectious diseases, overworking, injuries and inbreeding. Community training, empowerment and veterinary service provision is recommended to improve the health and survival of donkeys in Kilosa.Keywords: donkey, health, handling, Kilos

Ethylene bisdithiocarbamate (mancozeb®) affects the haematological parameters in domestic fowl (gallus gallus domesticus)

Mancozeb is one of the widely used fungicides in agriculture and ornamental plants. In the current study, the effects of mancozeb on haematological parameters and the morphology of blood cells were investigated in the domestic fowl. Mancozeb in sunflower oil was administered to healthy domestic fowl per os. The birds were divided into two experimental groups. In experiment one, birds were divided into five subgroups such as control (0 mg/kg), 25 mg/kg, 100 mg/kg, 400 mg/kg and 800 mg/kg body-weight to determine the minimum toxic dose of mancozeb within 48 hours. In Experiment two, a single dose of 400mg/kg bodyweight was used and blood sample was collected in spatial temporal periods to establish the time course effect of mancozeb from 5hrs to 12 days post-exposure. The result showed that in experiment one, mancozeb elevated values of monocyte at all doses. In addition, mancozeb caused significant decrease in haemoglobin concentration (Hb), total Red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC), lymphocytes and packed cell volume (PCV). In experiment two, mancozeb caused significant decrease in PCV, mean cell volume (MCV), mean cell hemoglobin (MCH) and lymphocytes from 5 hrs to 12 days post-exposure. The results of the present study suggest that mancozeb has a toxic effect on haemopoetic cells.Keywords: Mancozeb, RBC count, WBC count, PCV, Hb concentration, Domestic fow

Additional file 1: of Why has canine rabies remained endemic in the Kilosa district of Tanzania? Lessons learnt and the way forward

Multilingual abstracts in the six official working languages of the United Nations. (PDF 525 kb