Spontaneous tumour regression

Complete tumour regression is the optimal outcome of cancer therapies. There are however types of tumours that naturally regress. Most of these are benign, dermatological and have an early onset in life. This literature study aims to elucidate the mechanisms behind spontaneous tumour regression. In Libechov Melanoblastoma-Bearing minipigs, an animal-model specifically bred to develop malignant melanoma, the tumours usually involute within three months. This has been proven to be the effect of a lymphocytic infiltrate, predominated by cytotoxic T-cells. An epidermotropic myeloid tumour of Langerhans cell origin, frequently seen in young dogs, is called histiocytoma and is known to have a very brief proliferation followed by a quick remission. The involuting process is due to extensive lymphoid infiltrate. In hemangioma, rapid growth of the tumour is followed by a regressing stage that has been linked to apoptosis, possibly induced by mast cells. As in the case of hemangioma, infantile mastocytomas are known to regress before the child reaches puberty. The series of events behind the remission remains poorly investigated, but is thought to be connected to increased apoptosis of tumour cells. Another self-involuting tumour of the skin is the virus-induced papilloma, which self-keratinizes to oblivion. The infected cells become terminally differentiated and thus lose their ability of mitosis. There appears to be no overall explanation as to why and how spontaneous tumour regression occurs, but different types of tumours seem be unique from one another.Målet med cancerbehandling är en total tillbakagång av den maligna tumören. Det finns dock dokumenterade cancerfall där hela tumören gått i regress utan att behandling satts in. På den benigna sidan finns tumörtyper där spontan tumörregression är ett välkänt faktum. Gemensamt för de flesta av dessa är att de är lokaliserade till huden samt att de ofta bildas tidigt i livet. Denna litteraturstudie syftar till att utreda bakomliggande mekanismer till spontan tumörregression. Melanoblastom-bärande Libechov-minigrisar är en försöksdjursmodell speciellt framtagen för att studera patogenes och regression av malignt melanom. Djuren utvecklar maligna tumörer inom tre månader post partus, vilka sedan går i regress inom kort. Man har i studier visat att detta beror på att tumörcellerna stöts bort av grisarnas immunförsvar. En liknande mekanism har påvisats i kutant histiocytom, vilket ofta drabbar unga hundar. I båda fallen drivs tumörregressionen av ett T-cellsdominerat immunsvar huvudsakligen bestående av cytotoxiska T-celler. Infantilt hemangiom är en annan tumör som går tillbaka spontant. I studier har detta visats bero på en ökad apoptos av tumörcellerna och en del resultat indikerar att mastceller är den inducerande faktorn. Precis som i hemangiom tros apoptos vara en förklaring till att infantila mastocytom går i regress. Terminal differentiering är den bakomliggande orsaken till varför virus-inducerade papillom så småningom tillbakabildas. När cellerna blir slutgiltigt differentierade förlorar de sin förmåga att dela sig och blir tillslut keratiniserade och dör. Det verkar inte gå att hitta en generell förklaring till varför en del tumörer går i spontan regression. De fall som finns skildrade i litteraturen uppvisar vitt skilda mekanismer

Dog bite incidence and associated risk factors

Dog bites pose a threat to public health globally and can lead to infection, disfigurement, incapacity, post-traumatic stress syndrome and even death. In geographical areas where rabies is endemic, bites from infected dogs account for over 90% of the human rabies cases. Children have been proven to be at a greater risk of being bitten by dogs and subsequently contracting rabies than adults. In this cross-sectional study, a school survey was undertaken in association with a rabies awareness campaign in India, to investigate the dog bite incidence and various risk factors associated with dog bites as well as assessing the knowledge of safe interaction with dogs among children in the age group 10-18 years. A total of 1295 questionnaires were collected. 43.2 % (n=556) out of the respondents were boys and 56.8 % (n=731) were girls with a mean age of 14 years. Of the children asked, 73.5 % (n=945) did not own a dog, whereas 26.6 % (n=338) reported they did own a dog. Out of the respondents, 23.3% (n=279) reported having been bitten by a dog. More children were bitten by family dogs than stray dogs, and the most common location for dog bites was in a domestic environment. The gender distribution among the children who reported to have been dog bitten was 39.7% (n=110) girls and 60.3% (n=167) boys. The gender difference was found to be statistically significant (p<0.05). There was a significant correlation between owning a dog and being bitten by a dog as well as displaying unsafe behaviour when engaging with dogs. Boys were more likely to display unsafe behaviour than girls. Children who had taken part of an informational lecture on rabies and dog bite prevention gave more correct answers when asked about safe interaction with dogs, but showed no difference in the risk perception compared to children who had not taken part of a lecture. It is suggested that educational efforts targeting children are implemented to raise the level of awareness of rabies, proper wound management, dog population control and safe dog behaviour to reduce the dog bite incidence as well as contributing to the eradication of rabies from India.Hundbett utgör ett globalt hot mot folkhälsan och kan, förutom att leda till döden, även orsaka infektioner , missbildningar , handikapp och även posttraumatiskt stressyndrom. I geografiska områden där rabies är endemiskt står bett från infekterade hundar för över 90 % av de humana rabiesfallen. Barn löper större risk att bli hundbitna än vuxna, och därmed även ökad risk för att smittas av rabies. I denna tvärsnittsstudie genomfördes en skolundersökning i samband med en rabiesinformationskampanj i Indien, för att undersöka hundbettsincidensen och olika riskfaktorer relaterade till hundbett samt en uppskattning av kunskapen om säkert beteende vid interaktion med hundar bland barn i åldersgruppen 10-18 år. Totalt 1295 enkäter samlades in. Av de tillfrågade var 43,2 % (n = 556) pojkar och 56,8 % (n = 731) flickor med en medelålder på 14 år. Av de tillfrågade barnen ägde 73.5 % (n = 945) ingen hund, medan 26,6 % (n = 338) var hundägare. Andelen hundbitna bland barnen var 23.3 % (n = 279). Fler barn hade blivit bitna av familjehundar än gatuhundar och den vanligaste platsen för hundbett var i en hemmiljö. Könsfördelningen bland de hundbitna barnen 39.7 % (n = 110) flickor och 60.3 % (n = 167) pojkar. Könsskillnaden visade sig vara statistiskt signifikant (p < 0,05). Det fanns ett signifikant samband mellan att äga en hund och att bli biten av en hund samt att uppvisa riskbeteende vid interaktion med hundar. Pojkar var mer benägna att visa riskbeteende än flickor. Barn som fått delta i en informativ föreläsning om rabies och förebyggande åtgärder mot hundbett svarade signifikant bättre på frågor om säker interaktion med hundar, men visade ingen skillnad i riskuppfattning jämfört med barn som inte fått någon föreläsning. Det föreslås att utbildningsinsatser riktade till barn genomförs för att höja medvetenheten om rabies, korrekt sårbehandling, hundpopulationskontroll och säkert hundbeteende för att minska hundbettsincidensen och som en del i att utrota rabies i Indien

Detection of subclinical mastitis in camels (Camelus dromedarius) using somatic cell count, N-acetyl-beta-D-glucosaminidase and lactate dehydrogenase activity

Clinical and subclinical mastitis (SCM), mostly related to intramammary infection (IMI), is prevalent in pastoralist camel herds. An IMI has implications for public and animal health as well as for household economy. As bacterial culturing is expensive, time consuming and impractical in a pastoralist setting, other early detection methods for SCM in camels need to be investigated. Somatic cell count (SCC) is the standard for detecting SCM in cattle. The udder health indicators of N-acetyl-beta-D-glucosaminidase (NAGase) and lactate dehydrogenase (LDH) activity are useful as diagnostic markers in cow, sheep and goat milk; they could be of potential use in camel milk production. The aim of this study was to improve the understanding of SCM in camels, and specifically to assess SCC, and NAGase- and LDH activity in camel milk. In addition, potential associations between SCM (defined by a California Mastitis Test (CMT) score >= 3 and no signs of clinical mastitis) and SCC, NAGase- and LDH activity were investigated.In total, 40 healthy camels without clinical mastitis were sampled in four herds in Kenya. Quarter milk samples were collected aseptically and screened using CMT. SCC was analysed using a direct cell counter (DCC, DeLaval), and NAGase and LDH activity was analysed using kinetic fluorometric measures.In total, 116 milk samples were tested with CMT and analysed for SCC. Of these, 88 were analysed further for NAGase and LDH. The median SCC was 151,000 cells/mL (IQR: 49,500-709,000 cells/mL), and median NAGase and LDH were 18.5 U/l (IQR:14.8-24.0 U/l) and 12.0 U/l (IQR: 8.5-16.2 U/l) respectively. All inflammatory markers (SCC, NAGase, LDH) were significantly associated with SCM (P < 0.001). In conclusion, SCC, NAGase and LDH are potential inflammatory indicators in camel milk that can be used for detection of udder quarters with SCM

Investigation of extramammary sources of Group B Streptococcus reveals its unusual ecology and epidemiology in camels

Camels are vital to food production in the drylands of the Horn of Africa, with milk as their main contribution to food security. A major constraint to camel milk production is mastitis, inflammation of the mammary gland. The condition negatively impacts milk yield and quality as well as household income. A leading cause of mastitis in dairy camels is Streptococcus agalactiae, or group B Streptococcus (GBS), which is also a commensal and pathogen of humans and cattle. It has been suggested that extramammary reservoirs for this pathogen may contribute to the occurrence of mastitis in camels. We explored the molecular epidemiology of GBS in camels using a cross-sectional study design for sample collection and phenotypic, genomic and phylogenetic analysis of isolates. Among 88 adult camels and 93 calves from six herds in Laikipia County, Kenya, GBS was detected in 20% of 50 milk samples, 25% of 152 nasal swabs, 8% of 90 oral swabs and 3% of 90 rectal swabs, but not in vaginal swabs. Per camel herd, two to four sequence types (ST) were identified using Multi Locus Sequence Typing (MLST). More than half of the isolates belonged to ST617 or its single-locus variant, ST1652, with these STs found across all sample types. Capsular serotype VI was detected in 30 of 58 isolates. In three herds, identical STs were detected in milk and swab samples, suggesting that extramammary sources of GBS may contribute to the maintenance and spread of GBS within camel herds. This needs to be considered when developing prevention and control strategies for GBS mastitis. The high nasal carriage rate, low recto-vaginal carriage rate, and high prevalence of serotype VI for GBS in camels are in stark contrast to the distribution of GBS in humans and in cattle and reveal hitherto unknown ecological and molecular features of this bacterial species

Investigation of extramammary sources of Group B Streptococcus reveals its unusual ecology and epidemiology in camels

Camels are vital to food production in the drylands of the Horn of Africa, with milk as their main contribution to food security. A major constraint to camel milk production is mastitis, inflammation of the mammary gland. The condition negatively impacts milk yield and quality as well as household income. A leading cause of mastitis in dairy camels is Streptococcus agalactiae, or group B Streptococcus (GBS), which is also a commensal and pathogen of humans and cattle. It has been suggested that extramammary reservoirs for this pathogen may contribute to the occurrence of mastitis in camels. We explored the molecular epidemiology of GBS in camels using a cross-sectional study design for sample collection and phenotypic, genomic and phylogenetic analysis of isolates. Among 88 adult camels and 93 calves from six herds in Laikipia County, Kenya, GBS was detected in 20% of 50 milk samples, 25% of 152 nasal swabs, 8% of 90 oral swabs and 3% of 90 rectal swabs, but not in vaginal swabs. Per camel herd, two to four sequence types (ST) were identified using Multi Locus Sequence Typing (MLST). More than half of the isolates belonged to ST617 or its single-locus variant, ST1652, with these STs found across all sample types. Capsular serotype VI was detected in 30 of 58 isolates. In three herds, identical STs were detected in milk and swab samples, suggesting that extramammary sources of GBS may contribute to the maintenance and spread of GBS within camel herds. This needs to be considered when developing prevention and control strategies for GBS mastitis. The high nasal carriage rate, low recto-vaginal carriage rate, and high prevalence of serotype VI for GBS in camels are in stark contrast to the distribution of GBS in humans and in cattle and reveal hitherto unknown ecological and molecular features of this bacterial species

Pure white gold : Subclinical mastitis in dairy camels in Kenya with a special focus on Streptococcus agalactiae

In the drylands of the Horn of Africa, camels are fundamental for food and nutritional security due to their ability to produce milk despite limited access to feed and water. Subclinical mastitis (SCM) is common in the region and has a negative impact on food security and household income. In this thesis project, we investigated the prevalence, aetiology and potential biomarkers of SCM. Antibiotic susceptibility was assessed and the molecular epidemiology of Streptococcus agalactiae (SRA) investigated through genomic and phylogenetic analysis. In total, 804 udder quarters in 206 lactating camels were screened using the California Mastitis Test and milk was sampled for bacteriological culture. Whole-genome sequencing was carried out on 122 SRA genomes collected from camel milk and extramammary sources. The prevalence of SCM at quarter, camel and herd level was 26%, 46% and 100% respectively and SCM was associated with a higher age, later stage in lactation and lesions on the udder or teats. The most common udder pathogen was SRA, followed by non-aureus staphylococci and Staphylococcus aureus. Tetracycline resistance was widespread among SRA isolates. Most SRA isolates from milk belonged to sequence type (ST) 616 and showed signs of adaptation to the mammary gland. However, there was a high nasal prevalence in healthy camels and the same STs were found in milk and extramammary isolates, suggesting a more complex epidemiology than previously assumed. Udder health in camels could be improved with the development of informed control strategies adapted to the local context

Genomic analysis of group B Streptococcus from milk demonstrates the need for improved biosecurity: a cross-sectional study of pastoralist camels in Kenya

Background Streptococcus agalactiae (Group B Streptococcus, (GBS)) is the leading cause of mastitis (inflammation of the mammary gland) among dairy camels in Sub-Saharan Africa, with negative implications for milk production and quality and animal welfare. Camel milk is often consumed raw and presence of GBS in milk may pose a public health threat. Little is known about the population structure or virulence factors of camel GBS. We investigated the molecular epidemiology of camel GBS and its implications for mastitis control and public health. Results Using whole genome sequencing, we analysed 65 camel milk GBS isolates from 19 herds in Isiolo, Kenya. Six sequence types (STs) were identified, mostly belonging to previously described camel-specific STs. One isolate belonged to ST1, a predominantly human-associated lineage, possibly as a result of interspecies transmission. Most (54/65) isolates belonged to ST616, indicative of contagious transmission. Phylogenetic analysis of GBS core genomes showed similar levels of heterogeneity within- and between herds, suggesting ongoing between-herd transmission. The lactose operon, a marker of GBS adaptation to the mammary niche, was found in 75 % of the isolates, and tetracycline resistance gene tet(M) in all but two isolates. Only the ST1 isolate harboured virulence genes scpB and lmb, which are associated with human host adaptation. Conclusions GBS in milk from Kenyan camel herds largely belongs to ST616 and shows signatures of adaptation to the udder. The finding of similar levels of within- and between herd heterogeneity of GBS in camel herds, as well as potential human-camel transmission highlights the need for improved internal as well as external biosecurity to curb disease transmission and increase milk production

How GBS got its hump: genomic analysis of Group B Streptococcus from camels identifies host restriction as well as mobile genetic elements shared across hosts and pathogens

Group B Streptococcus (GBS) literature largely focuses on humans and neonatal disease, but GBS also affects numerous animals, with significant impacts on health and productivity. Spill-over events occur between humans and animals and may be followed by amplification and evolutionary adaptation in the new niche, including changes in the core or accessory genome content. Here, we describe GBS from one-humped camels (Camelus dromedarius), a relatively poorly studied GBS host of increasing importance for food security in arid regions. Genomic analysis shows that virtually all GBS from camels in East Africa belong to a monophyletic clade, sublineage (SL)609. Capsular types IV and VI, including a new variant of type IV, were over-represented compared to other host species. Two genomic islands with signatures of mobile elements contained most camel-associated genes, including genes for metal and carbohydrate utilisation. Lactose fermentation genes were associated with milk isolates, albeit at lower prevalence in camel than bovine GBS. The presence of a phage with high identity to Streptococcus pneumoniae and Streptococcus suis suggests lateral gene transfer between GBS and bacterial species that have not been described in camels. The evolution of camel GBS appears to combine host restriction with the sharing of accessory genome content across pathogen and host species