Overall, the response of the experimental infection with T. vivax in goats made it possible to demonstrate two clinical courses of the disease: the acute phase, which persisted for approximately two weeks and was characterized by increased hyperthermia and parasitemia, and the chronic phase or final stage of the disease, characterized by neurological disorders, which may be associated with the extravascular migration of the parasite.
Although T. vivax undergoes all stages of its life cycle in circulating blood, the parasite has the capacity to migrate into the tissues of a vertebrate host . Thus, the participation of the parasite in the pathogenesis of inflammatory lesions that degenerate organs, such as the heart [9, 10], testicle and epididymis  and central nervous system [4, 5], has been suggested.
CSF is a biological fluid that has an intimate relationship with the central nervous system and the meninges [6, 12]. The collection and analysis of CSF are of vital importance in African trypanosomosis, as they determine the clinical stage of the disease and guide the treatment method to be used in each case [13, 14]. Any condition capable of affecting the meninges and the encephalon can produce inflammatory changes capable of raising the values of CSF constituents above the reference levels. As a general rule, infectious agents promote meningoencephalitis with pleocytosis and increases in total protein, which in turn modifies the appearance of CSF from clear to turbid and increases the density values [12, 15]. In this study, T. vivax was not observed in the CSF of G1 animals; there were also no neurological signs or significant statistical differences in the physicochemical parameters of CSF when values were compared with G3 goats. As the disease progressed and the G2 goats showed neurological disorders, important changes in CSF were observed, such as turbidity, pleocytosis, high density and increased average total protein values, as well as hypoglycorrhachia. Thus, the alterations seen in the CSF from G2 goats reflect the violation of the state of health of the CNS by T. vivax.
Hypoglycorrhachia, the reduction of glucose values in the CSF, is generally found in hypoglycemia cases, prevention of transport through the blood-brain barrier, increases in metabolism of the brain parenchyma or infections by glycolytic organisms . The CSF evaluation revealed that G2 goats showed mean CSF glucose values below the reference range for the species in addition to a significant reduction compared to values found in G1 and G3 animals [6, 12]. The reduction of serum glucose levels is an important biochemical change in cattle experimentally infected with T. vivax and is associated with energy expenditure caused by hyperthermia and with consumption of blood glucose by trypanosomes .
The clinical course of the disease and the CSF changes seen in this study are also observed in humans and closely resemble the changes described in human African trypanosomosis caused by T. brucei [2, 3]. In human African trypanosomosis, meningoencephalitis is found when cell counts exceed 5 cells/μL of CSF . A similar observation was made in three G2 goats that had an average count of 25 cells/μL of CSF, coinciding with the diagnosis of meningoencephalitis subsequently proven in the histological exam. The occurrence of neurological signs associated with the presence of trypanosomes in the CSF of three G2 goats, as well as the inflammatory lesions characterized by meningoencephalitis, demonstrate the importance of T. vivax as the cause for clinical and pathologic manifestations of the CNS. Neurological complications associated with experimental infection by T. vivax were also observed by Whitelaw et al. , who found T. vivax in the CSF of goats that presented nervous system signs and meningoencephalitis.
The evaluation of goats experimentally infected with T. vivax isolates obtained during a cattle outbreak confirmed the tropism of T. vivax for the CNS. Cattle naturally infected in the outbreak mentioned above showed nervous signs characterized by incoordination, muscle tremors, opisthotonus, and hypermetria. In these animals, meningoencephalitis and malacia of the cerebellar white matter, thalamus and basal ganglia were observed . The locations of brain lesions described in the goats in this study, which were more severe in the brainstem, cerebellum and meninges, were remarkably similar to those described in humans infected by T. brucei gambiense . The clinical signs of ataxia and incoordination in the animals from G2 were consistent with cerebellar and brainstem lesions. In East African endemic areas, the rate development of nervous system signs in trypanosomosis caused by T. brucei rhodesiense is about 18% and generally corresponds to a diffuse meningoencephalitis with a predominance of lesions at the base of the brain .
The technique of DNA extraction for subsequent implementation of polymerase chain reaction (PCR), which is sensitive and specific in the detection of T. vivax in parasitized animals, has been refined so that not only blood , but also tissues  can be used as samples for research on the parasite. This technique has been widely employed in molecular studies because of the relative ease with which it can amplify specific in vitro regions of the genome of any organism. PCR enables the amplification of DNA sequences that are present in complex mixtures and enables a variety of studies of different natures, such as the development of highly sensitive and specific diagnosis methods, obtaining large quantities of DNA for sequencing and analyses of genetic diversity of populations.
The extravascular location of T. vivax plays an important role in the clarification of the pathogenesis of lesions in several systems. It is therefore notable that T. vivax was detected by PCR in CNS tissues for the first time, such that the parasite may be directly associated with lesions in these sites, contributing to the appearance of histopathological lesions and, consequently, to the appearance of nervous system infection signs. It is important to highlight the presence of T. vivax in the CNS parenchyma identified by the PCR technique in a goat from G1. This observation suggests early invasion of the CNS by the parasite, regardless of the physicochemical changes in CSF or manifestations of neurological disorders. In this way, CNS invasion by trypanosomes can be early in the infection process and may coincide with their presence in the circulation (hemolymphatic stage) . Positive PCR results in nervous system areas indicate that as the disease progressed, the animals showed severe histological lesions. Therefore, the relationship between the nervous system lesions and the presence of the parasite in this site is clear.
The etiopathogenic mechanisms of CNS lesions caused by several trypanosome species remain under investigation. Some authors suggest that the lesions occur due to circulatory changes caused by emboli formed by trypanosomes, leukocytes and fibrin in capillaries and venules in the brain . The immune-mediated reactions are involved in the pathogenesis of lesions, as anti-CNS antibodies are described in the CSF in infections by trypanosomes . Stiles et al.  identified and characterized a peptide derived from T. brucei that induces apoptosis of vascular endothelial cells in the brain and cerebellum. Recently, Masocha et al.  conducted an experiment on the migration of T. brucei through the blood-brain barrier of rodents and concluded that while the basal membrane composition of intracerebral vessels determines the site of parasite penetration in the brain, γ-interferon is involved in the immunological control of infection, facilitating the penetration of T. brucei through the basal membrane of the blood-brain barrier.
In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of CNS in experimentally infected goats.