Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans

Cytokine expression in malaria-infected non-human primate placentas

Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis)-Plasmodium knowlesi (P. knowlesi) H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA). Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-{\alpha}) and interleukin 12 (IL-12). Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-{\gamma}) levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.Comment: Open Veterinary Journal 1st June 2012. Seven pages, Three Figures. arXiv admin note: text overlap with arXiv:1201.323

Expanding whole exome resequencing into non-human primates

Background: Complete exome resequencing has the power to greatly expand our understanding of non-human primate genomes. This includes both a better appreciation of the variation that exists in non-human primate model species, but also an improved annotation of their genomes. By developing an understanding of the variation between individuals, non-human primate models of human disease can be better developed. This effort is hindered largely by the lack of comprehensive information on specific non-human primate genetic variation and the costs of generating these data. If the tools that have been developed in humans for complete exome resequencing can be applied to closely related non-human primate species, then these difficulties can be circumvented. Results: Using a human whole exome enrichment technique, chimpanzee and rhesus macaque samples were captured alongside a human sample and sequenced using standard next-generation methodologies. The results from the three species were then compared for efficacy. The chimpanzee sample showed similar coverage levels and distributions following exome capture based on the human genome as the human sample. The rhesus macaque sample showed significant coverage in protein-coding sequence but significantly less in untranslated regions. Both chimpanzee and rhesus macaque showed significant numbers of frameshift mutations compared to self-genomes and suggest a need for further annotation. Conclusions: Current whole exome resequencing technologies can successfully be used to identify coding-region variation in non-human primates extending into old world monkeys. In addition to identifying variation, whole exome resequencing can aid in better annotation of non-human primate genomes

Meta-Analysis on Zoonotic Infectious Diseases Between Humans and Non-Human Primates

Due to genetic similarity, non-human primates are often the focus of zoonotic infectious disease research. The objective of zoonotic disease research can vary depending upon whether the study is focusing on human health or the health of wild non-human primate populations. Research with non-human primates is often associated with their use in medical laboratories for the benefit of human health. However, other studies focus on both the health of wild non-human primate populations and human interactions. This study reviews zoonotic disease research published in three main primatology journals: American Journal of Primatology, International Journal of Primatology, and Primates. Reviewing journals from within the field of Primatology establishes common trends and sets a baseline for further research to work off of. To find these common trends each article was categorized based off of the research\u27s primary objective in question. Furthermore, this study looks at how zoonotic disease impacts primate conservation and whether or not current research is looking into this. As anthropogenic habitat destruction increases, humans and non-human primates interact more, which leads to an increase in disease transmission. Zoonotic disease negatively impacts both human and non-human primate populations. Many non-human primate populations are endangered and disease transmission further affects conservation efforts

Multisensory Integration in Self Motion Perception

Self motion perception involves the integration of visual, vestibular, somatosensory and motor signals. This article reviews the findings from single unit electrophysiology, functional and structural magnetic resonance imaging and psychophysics to present an update on how the human and non-human primate brain integrates multisensory information to estimate one's position and motion in space. The results indicate that there is a network of regions in the non-human primate and human brain that processes self motion cues from the different sense modalities

An Open Resource for Non-human Primate Imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets

Non-Human Primate Models in Neuroscience Research

Neuroscience is progressively increasing its comprehension of the normal functioning of the central and  peripheral nervous system. Such understanding is essential to challenge important neurodegenerative disorders  and clinical conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, etc. The  aim of neuroscience research is to improve understanding of normal and pathological functions and to  develop therapeutic strategies and tools. Fundamental neuroscience utilizes a variety of techniques which  include: electrophysiology, imaging, and computational modelling and entails interactions with clinical  studies. Non-human primates are the closest species to humans in terms of biological, physiological, immunological  and neurological characteristics; their closeness has been, and is still, an important reason for  using them in biomedical studies. These animals have a vertebrate brain that is most like that of humans  in terms of neural circuitry and this, together with similarities with human physiological and behavioural  characteristics, makes them more valuable and accurate models of neurological and psychiatric diseases  than other animals. This article provides an overview of the contribution of non-human primate models in  fundamental neuroscience research and in generating clinically relevant findings and therapeutic developments.

Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow