Zoonotic respiratory infections and great ape conservation - an emerging challenge

The conservation of great apes faces many challenges, one of which is the threat of infectious disease outbreaks. Zoonotic transmission of respiratory diseases from humans to wild great apes has recently been confirmed. Since respiratory disease is one of the major causes of death in both gorillas and chimpanzees, this gives reason for major concern. Little is known about the risks of disease transmission from humans to great apes in natural environments, and there is a need for systematic risk evaluation. Researchers, conservation staff and tourists spend time in very close proximity of wild great apes, sometimes during long time periods, which poses a potential risk of disease spillover. However, the presence of researchers and tourists has been shown to decrease the risk of poaching, making the matter increasingly complex. The risk of respiratory diseases of human origin affecting great apes can be minimized by hygienic rules and visitor regulations. Preventive measures can also be aimed directly at the apes through hands-on veterinary medicine. Direct intervention in wild populations through preventive or curative treatment is however a very controversial matter, since it risks interfering with evolutionary processes. Conservation medicine is a multidisciplinary science that cannot be isolated from ecology, ethology, human medicine or social sciences. Neither can the health and disease of wild great apes be separated from the health and disease of humans in the same area. A scientific, interdisciplinary approach is necessary in the aim for a standardized, systematic strategy to disease prevention and surveillance in endangered great ape populations.Bevarandet av människoapor möter många utmaningar, bland annat risken för utbrott av infektiösa sjukdomar. Zoonotisk överföring av respiratoriska sjukdomar från människa till andra människoapor har nyligen bekräftats och är en anledning till oro, eftersom respiratorisk sjukdom är en av de främsta dödsorsakerna hos både gorillor och schimpanser i det vilda. Idag är kunskapen om riskerna för överföring av infektiösa sjukdomar från människor till människoapor i naturliga miljöer bristfällig och det finns ett behov av systematisk riskbedömning. Turister, forskare och parkpersonal spenderar ibland lång tid i människoapornas habitat, vilket utgör en risk för zoonotisk smittoöverföring. Samtidigt har närvaro av turister och forskare visat sig verka skyddande mot tjuvjakt – vilket gör detta till en komplex fråga. Risken för att humana respiratoriska sjukdomar ska drabba människoapor kan minimeras genom hygienbestämmelser och restriktioner som omfattar alla personer som vistas i deras habitat. Förebyggande åtgärder kan även riktas direkt mot människoaporna genom veterinära åtgärder, såsom vaccinationer eller annan medicinsk behandling. Direkta interventioner i vilda populationer är dock mycket kontroversiella, då de riskerar att inverka på evolutionära processer. Bevarandemedicin är en multidisciplinär vetenskap som inte kan särskiljas från studier inom ekologi, etologi, humanmedicin eller samhällsvetenskap. På samma sätt kan inte människoapornas hälsa särskiljas från hälsan hos de människor som lever och rör sig i samma områden. Ett vetenskapligt, interdisciplinärt angreppssätt är nödvändigt i strävan efter en standardiserad, systematisk strategi kring förebyggande arbete, hälsoövervakning och sjukdomsbekämpning i populationer av utrotningshotade människoapor

Enteric pathogens of zoonotic concern in selected non-human primates in Sri Lanka

In order to understand the dynamics of zoonotic disease transmission in the animal-human interface, a One Health approach is imperative. This study investigated the occurrence of the zoonotic pathogens Campylobacter spp., Salmonella spp. and rotavirus in fecal samples from free-ranging endangered toque macaques (Macaca sinica) and near threatened tufted gray langurs (Semnopithecus priam) in Sri Lanka. During March through May of 2015 samples were opportunistically collected at five sites in Sri Lanka where these primates come into close contact with humans. Standard culturing methods were used to screen for the bacteria and an ELISA-based quick-test was used to detect presence of type A human rotavirus. Bacterial sensitivity to selected antibiotics was analysed using VetMICTM broth microdilution panels. From the five sites, 98 samples were obtained. All samples tested negative for human type A rotavirus. All 40 samples from gray langurs were negative for Campylobacter spp. and Salmonella spp. Fifty-eight samples were collected from toque macaques, of which ten were positive for C. jejuni, four for C. coli and two for Salmonella Virchow. In vitro resistance to ampicillin, ciprofloxacin, nalidixic acid and tetracycline was detected in C. jejuni samples. All C. coli were in vitro resistant to ampicillin. The detected Salmonella Virchow were sensitive to all the antibiotics tested for. This study has detected C. jejuni, C. coli and Salmonella Virchow in fecal samples from endangered toque macaques in Sri Lanka with close human contact. The bacteria showed varying sensitivity to antibiotics and several C. jejuni were multidrug resistant. The presence of these bacteria in free-ranging animals could have implications both for non-human primate conservation and public health in Sri Lanka.Ett One Health perspektiv är viktigt när epidemiologi hos zoonotiska sjukdomar undersöks – både för bevarande av hotade arter och för folkhälsan. Denna studie undersökte förekomsten av de zoonotiska patogenerna Campylobacter spp., Salmonella spp. och rotavirus i träckprover från den utrotningshotade ceylonmakaken (Macaca sinica) och den nära hotade grå hulmanen (Semnopithecus priam) i Sri Lanka. Prover samlades in opportunistiskt under mars-maj 2015 från fem platser i Sri Lanka där människor och dessa primater kommer i nära kontakt med varandra. Konventionella odlingsmetoder användes för att odla fram bakterier och ett ELISA-baserat snabbtest användes för att detektera humant rotavirus typ A. Bakteriernas känslighet för utvalda antibiotika testades med VetMICTM testpaneler. Från de fem platserna samlades totalt 98 prover in. Alla prov var negativa för humant rotavirus typ A. Alla 40 prover från grå hulmaner var negativa för Campylobacter spp. och Salmonella spp. Totalt samlades 58 prover in från ceylonmakaker och av dessa var tio positiva för C. jejuni, fyra för C. coli och två för Salmonella Virchow. In vitro resistens mot ampicillin, ciprofloxacin, nalidixinsyra och tetracyklin påvisades hos C. jejuni. Alla C. coli var in vitro resistenta mot ampicillin. De två detekterade Salmonella Virchow var känsliga mot alla undersökta antibiotika. Denna studie har detekterat C. jejuni, C. coli och Salmonella Virchow i träckprover från utrotningshotade ceylonmakaker i Sri Lanka med nära kontakt med människor. Bakterierna uppvisade varierande känslighet mot antibiotika och flera C. jejuni var multidrogresistenta. Detektionen av dessa bakterier hos vilda djur kan ha konsekvenser både för bevarande av icke-mänskliga primater och folkhälsan i Sri Lanka

Alpha-chloralose poisoning in 25 cats: clinical picture and evaluation of treatment with intravenous lipid emulsion

Objectives The aims of this study were to describe the clinical picture and progression in cats with alpha-chloralose (AC) intoxication and to determine if treatment with intravenous (IV) lipid emulsion (ILE) influenced either the serum concentration of AC or the clinical signs. Methods Cats with suspected AC poisoning admitted to a university small animal hospital were included. The cats were randomised into two groups: one receiving 20% ILE at a dose of 300 mg/kg as a 2 min bolus, followed by a 1500 mg/kg continuous rate infusion over 30 mins (IL+ group) and the other receiving IV fluid therapy with Ringer's acetate (IL- group). Serum samples were drawn at 0, 2, 12 and 24 h after admission. Samples were tested for AC with a novel validated, quantitative, ultra-high-performance liquid chromatography-tandem mass spectrometry method. Vital and predefined clinical signs were noted at the times of sampling and patients were scored using a previously described intoxication severity score. Telephone interviews were conducted after discharge to assess outcome. Results A total of 25 cats were enrolled: 13 cats in the IL+ group and 12 in the IL- group. The most common clinical signs at presentation were tremor (n = 22, 88.0%), cranial nerve deficits (n = 20, 80.0%) and bradycardia (n = 19, 76.0%). No significant difference in AC concentration or change in intoxication score over time was found between the IL+ and IL- groups at any time point (P >0.05). All cats recovered within 72 h. Conclusions and relevance ILE did not have any effect on the AC serum concentration or clinical signs in AC-poisoned cats. All cats survived until follow-up. In cats with an acute onset of the described neurological signs, AC intoxication is an important differential diagnosis with an excellent prognosis

Nitrofurantoin plasma- and urine exposure in eight healthy beagle dogs following standard nitrofurantoin dosing regimen

Bacterial cystitis is common in dogs and is usually treated with antibiotics. Nitrofurantoin is used for treatment of bacterial cystitis in humans and might provide a feasible treatment option in dogs. The aim of this study was to investigate the nitrofurantoin plasma concentration-time course and potential adverse effects in dogs. Nitro-furantoin (4.4-5.0 mg/kg) was administered orally to eight healthy beagles every 8 h for five days before repeated plasma and urine samples were collected. An additional four beagles served as untreated controls. The nitrofurantoin plasma and urine concentrations were measured using ultra high precision liquid chromatography coupled to tandem mass-spectrometry and further analysed using a non-compartmental pharmacokinetic model. In plasma, the median C-max was 2.1 mu g/mL, t(max) was 2 h, the terminal rate constant was 0.9 per h and the terminal half-life was 0.8 h. In urine, median C-max was 56 mu g/mL, t(max) was 1 h and the terminal half-life was 4.3 h. No adverse effects were observed clinically or in haematology or biochemistry. The data presented in this study combined with in vitro sensitivity data from common urine pathogens and the lack of observed adverse effects suggest that nitrofurantoin in a standard dosing regimen could be effective in sporadic bacterial cystitis treatment in dogs. Further clinical studies are highly warranted to verify the effectiveness in clinical cases

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia

Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats

Plasma Cholesterol-Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (&gt;= 80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-)Apob(100/100)Mttp(flox/flox)Mx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. Author Summary The main underlying cause of heart attacks and strokes is atherosclerosis. One strategy to prevent these often deadly clinical events is therefore either to slow atherosclerosis progression or better, induce regression of atherosclerotic plaques making them more stable. Plasma cholesterol lowering (PCL) is the most efficient way to induce atherosclerosis regression but sometimes fails to do so. In our study, we used a mouse model with elevated LDL cholesterol levels, similar to humans who develop early atherosclerosis, and a genetic switch to lower plasma cholesterol at any time during atherosclerosis progression. In this model, we examined atherosclerosis gene expression and regression in response to PCL at three different stages of atherosclerosis progression. PCL led to complete regression in mice with early lesions but was incomplete in mice with mature and advanced lesions, indicating that early prevention with PCL in individuals with increased risk for heart attack or stroke would be particularly useful. In addition, by inferring PCL-responsive gene networks in early, mature and advanced atherosclerotic lesions, we identified key drivers specific for regression of early (PPARG), mature (MLL5) and advanced (SRSF10/XRN2) atherosclerosis. These key drivers should be interesting therapeutic targets to enhance PCL-mediated regression of atherosclerosis

Behavioral patterns in a population of Samango monkeys (Cercopithecus albogularis erythrarcus)

The understanding of behavioral patterns in different species is an important part of the proper management and conservation of wild populations of animals. This study aims to contribute to the understanding of behavioral patterns in the samango monkey (Cercopithecus albogularis erythrarcus) of northern South Africa. Using the scan- sampling procedure, the behaviors of an isolated population of free-ranging samango monkeys in the Soutpansberg, Limpopo Province, were recorded during 16 days in the summer of 2010. The day was divided into the intervals: morning, midday and afternoon, and the behaviors social, resting, movement, and feeding were recorded and analyzed. The results showed a behavioral pattern in which the relative frequency of occurrence of social behaviors and movement were significantly different depending of the time of day, whereas the behaviors resting and feeding were not. During midday, social behaviors increased, while movement decreased. The groups’ degree of arboreality was also recorded and analyzed. The group spent significantly more time on the ground during midday compared to morning and afternoon. The amount of time this group spent on the ground is not entirely consistent with what has been described in the literature, where the samango has been described as strictly arboreal. A longer study including more environmental parameters, and using focal animal sampling together with the scan sampling method would be valuable for the further understanding of the behavior of the samango monkey.

Behavioral patterns in a population of Samango monkeys (Cercopithecus albogularis erythrarcus)

The understanding of behavioral patterns in different species is an important part of the proper management and conservation of wild populations of animals. This study aims to contribute to the understanding of behavioral patterns in the samango monkey (Cercopithecus albogularis erythrarcus) of northern South Africa. Using the scan- sampling procedure, the behaviors of an isolated population of free-ranging samango monkeys in the Soutpansberg, Limpopo Province, were recorded during 16 days in the summer of 2010. The day was divided into the intervals: morning, midday and afternoon, and the behaviors social, resting, movement, and feeding were recorded and analyzed. The results showed a behavioral pattern in which the relative frequency of occurrence of social behaviors and movement were significantly different depending of the time of day, whereas the behaviors resting and feeding were not. During midday, social behaviors increased, while movement decreased. The groups’ degree of arboreality was also recorded and analyzed. The group spent significantly more time on the ground during midday compared to morning and afternoon. The amount of time this group spent on the ground is not entirely consistent with what has been described in the literature, where the samango has been described as strictly arboreal. A longer study including more environmental parameters, and using focal animal sampling together with the scan sampling method would be valuable for the further understanding of the behavior of the samango monkey.

Alpha-chloralose poisoning in cats : clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time &lt;48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia