Lassa viral dynamics in non-human primates treated with favipiravir or ribavirin

Lassa fever is an haemorrhagic fever caused by Lassa virus (LASV). There is no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, the nucleotide analogue favipiravir showed a high antiviral efficacy, with 100% survival obtained in an otherwise fully lethal non-human primate (NHP) model of Lassa fever. However the mechanism of action of the drug is not known and the absence of pharmacokinetic data limits the translation of these results to the human setting. Here we aimed to better understand the antiviral effect of favipiravir by developping the first mathematical model recapitulating Lassa viral dynamics and treatment. We analyzed the viral dynamics in 24 NHPs left untreated or treated with ribavirin or favipiravir, and we put the results in perspective with those obtained with the same drugs in the context of Ebola infection. Our model estimates favipiravir EC₅₀ in vivo to 2.89 μg.mL^-1, which is much lower than what was found against Ebola virus. The main mechanism of action of favipiravir was to decrease virus infectivity, with an efficacy of 91% at the highest dose. Based on our knowledge acquired on the drug pharmacokinetics in humans, our model predicts that favipiravir doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus and provide a milestone towards a future use in humans.     

Tissue distribution of SARS-CoV-2 in non-human primates after combined intratracheal and intranasal inoculation

正Dear Editor,As of 5 July, 2020, approximately 20,162,000 confirmed cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), have been reported globally, including an estimated 740,000 deaths. Although the clinical manifestations of COVID-19 are heterogeneous, viral infection and pathological changes in the respiratory system, especially the lungs, still represent common characteristics of COVID-19.     

Myeloablative irradiation in non-human primates

Purpose  We used total body irradiation (TBI) as conditioning for cord blood transplantation studies in pigtailed macaques. In these studies, different doses of TBI were explored to obtain optimal myelosuppression with acceptable radiation-related side effects.
Methods  Four macaques received TBI ranging from 800 to 1320 cGy, followed by standard post-transplant care. Hematopoietic recovery was monitored by CBC and donor contribution by variable number of tandem repeats analysis.
Results  Animals receiving 800 or 1020 cGy TBI tolerated the irradiation well with autologous recovery of neutrophils within 24 days. At a dose of 1200 cGy, neither autologous recovery nor extramedullary toxicity was observed. A fourth animal received 1320 cGy of TBI and suffered significant toxicity necessitating termination of the study.
Conclusions  We conclude that previously considered myeloablative doses of TBI allowed for autologous recovery in the pigtailed macaque, and that a dose of 1200 cGy may be most appropriate, providing both myeloablation and acceptable non-hematopoietic toxicities.     

Hepatitis viruses in non-human primates

BACKGROUND: Previous epidemiological studies of rural human populations in Gabon reveal a high prevalence of human hepatitis A, B, C and D viruses. In order to investigate the prevalence of the blood-born hepatitis viruses in apes and monkeys living in the same area, we performed an epidemiological survey of HBV, HCV and HDV in wild-born non-human primates. METHODS: We tested 441 wild-born non-human primates from Gabon and Congo and 132 imported monkeys for the presence of serological markers of HBV, HCV and HDV infections. RESULTS: None of Cercopithecidae monkeys were reactive against HBV/HDV and HCV. In contrast, 29.2% of wild-born great apes (154 chimpanzees and 14 gorillas) were positive for HBV serological markers. Nine chimpanzees were in the replicative phase of HBV infection. None of these HBV infected chimpanzees exhibited symptoms or significant changes in serum clinical chemistry related to HBV infection. CONCLUSIONS: The negativity to HCV-related viruses and the negativity of the Cercopithecidae species tested against HBV/HDV do not allow us to definitively rule out the presence of an animal counterpart of human hepatitis viruses in non-human primates.     

非人灵长类性打搅行为研究进展

性打搅行为是指非人灵长类社群内非交配个体对正在发生性行为个体的干扰行为,该行为在非人灵长类中普遍存在,通过综述目前已知的36种非灵长类的性打搅行为的报道,探讨性打搅行为的功能和意义。性打搅行为具有更高度的种间和种内差异,种间的性打搅的方式不同、同时受到社会结构和婚配制度的影响;在种内受到性别、年龄、等级等因素的影响。结合川金丝猴性打搅的研究结果,从性打搅的类型、被打搅的反应、性打搅的功能以及相关假说等方面入手,对非人灵长类性打搅行为进行系统总结,旨在为我国相关领域的研究提供参考,为生殖行为学研究者启发思路,推动本领域的发展。     

Melioidosis in imported non-human primates

In 1969, five cases of melioidosis in three separate outbreaks were diagnosed in nonhuman primates in the United States. In the first outbreak, two stump-tailed macaque monkeys (Macaca arctoides) developed signs of the disease approximately 6 months after purchase. A third animal, a chimpanzee (Pan troglodytes), probably acquired its infection from one of these monkeys. Two other unrelated cases involving a pig-tailed monkey (Macaca nemestrina) and a rhesus monkey (Macaca mulatta) were diagnosed. These monkeys had been imported 3 years and 6 months, respectively, prior to the recognized onset of their disease. These cases represent the first known occurrences of spontaneous melioidosis in nonhuman primates in the United States.     

Use of florfenicol in non-human primates

Studies were undertaken to determine if florfenicol, an antimicrobial agent structurally similar to chloramphenicol, could be used as an effective broad spectrum antibiotic for the treatment of bacterial infections in primates. Florfenicol was developed as an injectable antibiotic for use in cattle on an every other day dosing schedule. Its broad spectrum activity, long duration of action following i.m. administration, and its safety as compared with chloramphenicol made it an attractive antibiotic for use in non-human primates. Previous studies had shown that florfenicol is effective against common primate pathogens such as Salmonella, Klebsiella, Escherichia coli, Bordetella bronchiseptica, Streptococcus pneumoniae, Staphylococcus spp., and Yersinia pseudotuberculosis. We performed experiments on a total of 15 macaques. The animals were given florfenicol at 50 mg/kg i.m. and blood samples taken at various time points. Serum was evaluated for florfenicol absorption. Necropsies were also performed to determine if major organs were affected and to determine the effects of i.m. injection of florfenicol. We determined that florfenicol given every 48 hours in rhesus macaques results in blood levels that were acceptable for therapeutic use. The effect on muscle tissue of i.m. injection was similar to ketamine and normal saline. There were no gross lesions observed and no changes with tissues submitted for histology. Our work shows that with further studies, florfenicol may be useful when injectable antibiotic therapy is required in non-human primates.     

旅游干扰对非人灵长类动物的影响

随着经济发展及生活水平的提高,以亲近自然为主要目的的生态旅游正成为公众的主要休闲方式.作为人类的近亲,非人灵长类动物在吸引游客方面具有天然的亲和力,因此很多保护区及旅游景区正逐渐把“猴园”、“猴谷”及“猴岛”等作为招揽游客的平台.野外观猴能够提高公众的野生动物保护意识,但同时也给动物带来了负面影响.该文综述旅游活动对动物行为模式、繁殖和健康状况等的影响,并对减少不利影响的措施进行归纳总结,为开展非人灵长类动物观赏旅游提供参考.     

Economic behaviours among non-human primates

Do we have any valid reasons to affirm that non-human primates display economic behaviour in a sufficiently rich and precise sense of the phrase? To address this question, we have to develop a set of criteria to assess the vast array of experimental studies and field observations on individual cognitive and behavioural competences as well as the collective organization of non-human primates. We review a sample of these studies and assess how they answer to the following four main challenges. (i) Do we see any economic organization or institutions emerge among groups of non-human primates? (ii) Are the cognitive abilities, and often biases, that have been evidenced as underlying typical economic decision-making among humans, also present among non-human primates? (iii) Can we draw positive lessons from performance comparisons among primate species, humans and non-humans but also across non-human primate species, as elicited by canonical game-theoretical experimental paradigms, especially as far as economic cooperation and coordination are concerned? And (iv) in which way should we improve models and paradigms to obtain more ecological data and conclusions? Articles discussed in this paper most often bring about positive answers and promising perspectives to support the existence and prevalence of economic behaviours among non-human primates.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

Attention to elders' voice in non-human primates

The observed respect and attention to elders'' speech in traditional cultures appears to have a ‘universal’ component which questions its possible biological bases. Animals present differential attention to the vocalizations of other individuals according to their characteristics but little is known about the potential propensity to pay more attention to vocalizations of elders. On the basis of several hundreds of vocal exchanges recorded, here we show that aged female Campbell''s monkeys (Cercopithecus campbelli), despite being significantly less ‘loquacious’ than their younger adult counterparts, elicit many more responses when calling. These findings show that attention to elders'' vocal production appears in non-human primates, leading to new lines of questioning on human culture and language evolution.     

Voice processing in human and non-human primates

Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be--unlike those involved in speech perception--directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs 'special', i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations?     

Yersinia enterocolitica infections in non-human primates.

Yersinia enterocolitica was isolated from ten non-human primates in the Netherlands. The following species were represented: Potto, Senegalgalago, wooly monkey, black spider monkey, common marmoset, cottonhead tamarin, pigtailed macaque and lesser whitenosed guenon.     

Suffixation influences receivers' behaviour in non-human primates

Compared to humans, non-human primates have very little control over their vocal production. Nonetheless, some primates produce various call combinations, which may partially offset their lack of acoustic flexibility. A relevant example is male Campbell''s monkeys (Cercopithecus campbelli), which give one call type (‘Krak’) to leopards, while the suffixed version of the same call stem (‘Krak-oo’) is given to unspecific danger. To test whether recipients attend to this suffixation pattern, we carried out a playback experiment in which we broadcast naturally and artificially modified suffixed and unsuffixed ‘Krak’ calls of male Campbell''s monkeys to 42 wild groups of Diana monkeys (Cercopithecus diana diana). The two species form mixed-species groups and respond to each other''s vocalizations. We analysed the vocal response of male and female Diana monkeys and overall found significantly stronger vocal responses to unsuffixed (leopard) than suffixed (unspecific danger) calls. Although the acoustic structure of the ‘Krak’ stem of the calls has some additional effects, subject responses were mainly determined by the presence or the absence of the suffix. This study indicates that suffixation is an evolved function in primate communication in contexts where adaptive responses are particularly important.     

Chromobacterium violaceum infections in 13 non-human primates

Background Recently, an Indian‐origin macaque was found dead and Chromobacterium violaceum was isolated from the skin wound, and hepatic and pulmonary abscesses. Methods By searching the database, a total of thirteen cases of C. violaceum infection in pigtail macaques (n = 8), rhesus macaques (n = 4), and one baboon were identified from 2001 to 2010 at Tulane National Primate Research Center. Medical records were reviewed for breed, sex, age, clinical findings, treatment, outcome, bacteriology, and gross and histological findings. Results Seven pigtail macaques and one Indian‐origin rhesus macaque died of chromobacterial septicemia. All chromobacterial septicemic pigtail macaques were adult with higher incidence in female. Hepatic abscess and thrombosis were typical findings along with pulmonary abscess and thrombosis, renal venous thromboembolism, and necrosuppurative pleuritis, peritonitis, splenitis, myocarditis, pericarditis, and meningoencephalitis. Skin wound, uterine infection, and oral and respiratory exposure were considered the points of entry for these animals. Conclusions This represents the first report of chromobacteriosis in pigtail, rhesus macaque, and baboon. Our experience suggests that chromobacterial infections may be more common in non‐human primates than previously recognized.