MACROPARASITES OF GILA ORCUTTI AND PIMEPHALES PROMELAS (ACTINOPTERYGII: CYPRINIDAE) IN THE SANTA CLARA RIVER, VENTURA COUNTY, CALIFORNIA.

Freshwater fishes in the southwestern United States live in some of the most highly modified habitats in the country. As a result, the relatively small number of native fish species has been impacted in many ways, including the introduction of nonnative fishes and their parasites. Both Gila orcutti and Pimephales promelas have been introduced to the Santa Clara Drainage, the former is native to adjacent drainages in southern California, while the latter was introduced from the eastern United States. Two hundred and fourteen G. orcutti (arroyo chub) and 18 P. promelas (fathead minnow) were collected and necropsied in June through September 2017 and May through September 2018. Eight macroparasite taxa were collected from these fishes, including 6 native and 2 nonnative parasites. Four taxa of parasites were shared between G. orcutti and P. promelas: Schyzocotyle acheilognathi (Asian fish tapeworm), diplostomid metacercariae, larval acuariid cysts, and Lernaea cyprinacea (anchor worm). This study also reports the first host-association records of G. orcutti with Gyrodactylus sp., S. acheilognathi, diplostomid metacercariae, Rhabdochona sp., Contracaecum sp., and larval acuariid cysts in the Santa Clara River. Additionally, it provides the first host-association records of P. promelas with larval acuariid cysts in the Santa Clara River. This study identifies new host-parasite associations that may be useful for future conservation efforts.

N. C. Craig Sharp.

A vet whose journey took him from veterinary physiology, through pathology to sports science, a field in which he was world-renowned.

Roger Barry Clampitt.

A clinical pathologist whose outstanding contribution to the profession was to invent the first reliable clinical biochemistry analyser for use in practice.

Meningoencephalitic African trypanosomiasis: Brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology.

The relationship of neuropathology to CNS inflammatory and counter-inflammatory cytokine production in African trypanosome-infected mice was studied using an infection model with a defined disease progression. The initial phase of CNS infection by trypanosomes, where only mild neuropathology is evident, was characterised by high levels of IL-10 and IL-6. In the later phase of CNS infection and in a post-drug treatment model, moderate to severe neuropathology was associated with high levels of IFN-gamma and TNF-alpha. The relationship of these cytokines to neuropathological grade suggests that IL-10 and IL-6 protect the CNS from inflammatory pathology when parasites first enter the brain and the data reconcile previously contradictory clinical measurements of CSF cytokines in meningoencephalitic patients with post-mortem histopathology observations.

Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice.

Human African trypanosomiasis, also known as sleeping sickness, affects the CNS at the late stage of the disease. Untreated the disease is invariably fatal, and melarsoprol, the only available and effective treatment for CNS disease, is associated in up to 10% of cases with a severe post-treatment reactive encephalopathy (PTRE), which can itself cause death. We used a reproducible mouse model of the PTRE to investigate the pathogenesis and treatment of this condition. Mice infected with Trypanosoma brucei brucei and treated subcuratively with diminazene aceturate develop a severe meningoencephalitis that closely resembles PTRE. We previously reported that substance P plays an important role in PTRE. We investigated the effect of disrupting the gene encoding for the NK1 receptor in mice on the clinical and neuroinflammatory response in this model. After induction of PTRE, NK1-/- mice showed a significant reduction in clinical impairment compared with NK1+/+ mice, but the severity of the neuroinflammatory response was significantly greater in NK1-/- mice. To explore the mechanisms of this dissociated phenotype, we treated infected NK1-/- mice with antagonists to NK2 and NK3 receptors, either singly or in combination. While none of these antagonist treatments altered the clinical score, combined treatment with the NK2 and NK3 antagonists significantly reduced the neuroinflammatory grading score in the NK1-/- mice. Thus, the clinical and neuroinflammatory responses to parasite invasion can be mediated by different pathways, and, importantly, the neuroinflammatory response is altered by alternative tachykinin receptor usage. These findings could be exploited to develop novel anti-inflammatory therapies in Human African trypanosomiasis by modulating the NK1 receptor as well as the parasite.

Human African trypanosomiasis: potential therapeutic benefits of an alternative suramin and melarsoprol regimen.

Treatment of late-stage human African trypanosomiasis is complicated by the presence of trypanosomes within the central nervous system (CNS). The regimen commonly prescribed to treat CNS-stage disease involves the use of the trypanocidal drugs suramin and melarsoprol. Suramin does not cross the blood-brain barrier efficiently and therefore, at normal dosages, will not cure CNS-stage infections. An initial treatment with suramin is given to eliminate the parasites from the peripheral tissues. This is followed by a course of intravenous melarsoprol, which can enter the CNS. However, melarsoprol not only produces severe adverse reactions but also is extremely painful to administer. One possible method to help alleviate these problems is to reduce the total amount of melarsoprol in the treatment regimen. This study indicates a synergism between suramin and melarsoprol and demonstrates that experimental murine CNS-trypanosomiasis can be cured with a single intraperitoneal dose of 20 mg/kg suramin followed almost immediately by 0.05 ml (4.5 micromol) topical melarsoprol. These dosages will not cure the infection when administered as monotherapies. Moreover, the timing of the drug administration appears to be crucial to the successful outcome of the regimen. If the interval between injection of suramin and application of topical melarsoprol is extended from 15 min to 3 or 7 days, the infections are not cured. Although extended relapse times occur following these regimens when compared with monotherapy approaches. Thus, there is strong evidence that injected suramin and topical melarsoprol should be given almost simultaneously to achieve the most effective combination of the two drugs.