Search

An experimental infection using Babesia (B.) rossi was performed in healthy male Beagle dogs to assess the changes in endocrine variables during disease. Two dogs were infected with a low dose (LD) of parasite inoculum (10 4 parasites) and three dogs were infected with a high dose (HD) (10 8 parasites). Basal serum cortisol, thyroxine (T4), and thyrotropin (TSH) concentrations were measured every second day. Samples were analyzed using a solid- phase, competitive chemiluminescent enzyme immunoassay (Immulyte® 2000, Siemens). Variables were compared between groups and timepoints using linear mixed models. In both groups, the median cortisol concentration increased, whilst the median T4 concentration decreased after infection, with a return towards baseline concentration post treatment. The highest cortisol and the lowest T4 concentrations were reached at 96 h and 108 h post infection, respectively, in the HD group and slightly later at 108 and 144 h post-infection, respectively, in the LD group. A higher cortisol concentration with a more rapid increase, and a lower T4 concentration with a more rapid decline, were associated with disease severity and a higher dose of parasite inoculum. The TSH concentration remained within the reference interval throughout the study period. This study illustrated the temporal changes in endocrine parameters during experimental B. rossi infection and demonstrated that cortisol and T4 tracked the severity of disease, albeit in opposite directions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier GmbH.)

Babesia rossi causes severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimental B. rossi study we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Six healthy male beagle dogs formed the study population, one was used to raise the infectious inoculum, three were administered a high B. rossi infectious dose (HD group) and two a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated and treatment administered when predetermined experimental or humane endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD and LD groups respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease in B. rossi infection and infectious dose influences the onset of the inflammatory response. Treatment enhances the inflammatory response in the immediate post-treatment period which may contribute to disease associated complications. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dogs with babesiosis can present with multiple complications, including acute kidney injury (AKI). The objective of this study was to characterize AKI in dogs with babesiosis caused by Babesia rossi at presentation and after treatment. Thirty-five client-owned dogs with B. rossi infection and 10 control dogs were included in this prospective observational study. Blood and urine were collected in Babesia-infected dogs at presentation (T 0 , n = 35), after 24 h (T 24h , n = 11), and after 1 month (T 1m , n = 9). The following urinary kidney injury biomarkers were assessed: urinary protein to creatinine ratio (UPC), urinary glomerular injury biomarkers (immunoglobulin G (uIgG) and C-reactive protein (uCRP)), and urinary tubular injury biomarkers (retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL)). Serum functional renal biomarkers were creatinine (sCr) and symmetric dimethylarginine (sSDMA). Post-mortem kidney biopsies were analyzed by light and transmission electron microscopy. At T 0 , all kidney injury biomarkers were significantly higher in Babesia-infected dogs compared to healthy controls (P < 0.001), while functional renal biomarkers were not significantly different (P > 0.05). At T 24h , all urinary tubular injury biomarkers and UPC decreased significantly (P < 0.01), while glomerular injury biomarkers did not (P = 0.084). At T 1m , all urinary kidney injury biomarkers decreased to values not significantly different from healthy controls (P > 0.5). Significant changes in functional renal biomarkers were not seen after treatment (P > 0.05). Dogs with complicated babesiosis had significantly higher glomerular injury biomarkers, UPC, and sSDMA compared to uncomplicated cases (P < 0.05), while all tubular injury biomarkers and sCr were not significantly different (P > 0.1). Dogs with babesiosis caused by B. rossi showed transient kidney injury, which was detected by all kidney injury biomarkers, but remained undetected by functional biomarkers. All infected dogs, irrespective of disease severity, suffered comparable kidney injury based on tubular injury biomarker concentrations, while loss of function was seen more often in dogs with complicated babesiosis based on sSDMA results., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The efficacy of alphacypermethrin-treated high density polyethylene (HDPE) mesh applied to jet stalls against Culicoides biting midges (Diptera: Ceratopogonidae) was determined by mechanical aspiration of midges from horses and using Onderstepoort 220 V downdraught black light traps in four blocks of a 3 × 2 randomised design under South African field conditions. The alphacypermethrin-treated HDPE mesh applied to the stall significantly (P = 0.008) reduced the number of Culicoides midges, predominantly Culicoides (Avaritia) imicola Kieffer, mechanically aspirated from horses housed in the stall. The mesh reduced the Culicoides midge attack rate in the treated stall compared to the untreated stall and a sentinel horse by 6 times and 14 times, respectively. The number of Culicoides midges and C. imicola collected in light traps from the untreated and alphacypermethrin HDPE mesh-treated stalls did not differ significantly (P = 0.82). Alphacypermethrin-treated HDPE mesh could be used to reduce exposure of horses in jet stalls to Culicoides midges, specifically C. imicola, and the risk of midge-borne Orbivirus transmission., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The efficacy of untreated and alphacypermethrin-treated high density polyethylene (HDPE) mesh against Culicoides biting midges (Diptera: Ceratopogonidae) was determined using Onderstepoort downdraught black light traps and a contact bioassay. Three traps were operated overnight in four replicates of a 3×3 randomised Latin square design near horses under South African field conditions. Both the untreated and alphacypermethrin-treated HDPE mesh significantly (P<0.05) reduced the numbers of Culicoides midges, predominantly Culicoides (Avaritia) imicola Kieffer, collected in the light traps by 4.2 and 7.2 times, respectively. A repellent effect of the alphacypermethrin-treated mesh was not confirmed because the number of midges collected in the light traps with untreated and alphacypermethrin-treated HDPE mesh was not significantly different (P=0.656). Bioassay of the insecticidal contact efficacy indicated median C. imicola mortality of 100% from 30 and 10 min following exposure to the alphacypermethrin-treated HDPE mesh for 1 or 3 min, respectively. In the bioassay, mortality was significantly higher (P=0.016) at 5 min post exposure in the midges exposed to the alphacypermethrin-treated mesh for 3 min (74.8%) compared to the 1 min exposure group (59.5%). The HDPE mesh could be used to reduce exposure of housed animals to Culicoides midges, specifically C. imicola, and viruses transmitted by these midges. Mesh treated with alphacypermethrin had the additional benefit of a rapid insecticidal effect on C. imicola., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Tuberculous (TB) meningitis is common in resource-poor communities but also occurs in developed countries where the diagnosis is frequently delayed because of unfamiliarity with the disease. TB meningitis develops whenever a small intracranial tuberculoma (Rich focus) ruptures causing predominantly basal meningitis. This results in hydrocephalus, cranial nerve palsies, and ischemic brain injury secondary to tuberculous vasculitis. The primary source of TB is usually the lung. Early diagnosis is difficult because patients tend to present subacutely with nonspecific symptoms such as fever, cough, vomiting, listlessness, and failure to thrive. Lumbar puncture typically shows clear and colorless CSF with a low, predominantly lymphocytic, leukocytosis and raised protein and low glucose levels. Decision to treat is mostly clinical because of difficulty in demonstrating TB bacilli on routine smear and time needed for culture. A positive TB contact, Mantoux skin test, chest radiograph, CT/MRI brain scan, PCR for tuberculosis on CSF, and demonstration of TB bacilli from extraneural sources are invaluable in supporting a diagnosis of TB meningitis. Current World Health Organization guidelines recommend treatment with a four-drug regimen for 2 months, followed by a two-drug regimen for 10 months, the total duration of treatment being 12 months. Corticosteroids reduce mortality without changing neurological morbidity. Outcome relates closely to age and stage of disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Renal damage is deemed a common, yet poorly documented, complication in canine babesiosis. Serum urea and creatinine are insensitive and non-specific markers of early renal dysfunction and their measurements are influenced by hemolysis caused by babesiosis. Therefore, the aim of this study was to use urinary markers to assess the localization and degree of renal dysfunction in dogs with Babesia rossi infection. Urinary immunoglobulin G (uIgG) and urinary C-reactive protein (uCRP) were measured as markers for glomerular dysfunction, while urinary retinol-binding protein (uRBP) was used as a marker for tubular dysfunction. Eighteen dogs presenting with uncomplicated babesiosis were included and compared with eight clinically healthy dogs. Previously validated commercial ELISA kits were used for the measurement of uIgG, uCRP, and uRBP. Results were related to urinary creatinine concentrations (c). Dogs with babesiosis had significantly higher concentrations of all three measured urinary markers compared to healthy dogs. Except for urinary protein/c ratio (UPC), routine urinary and serum markers for renal function (urine specific gravity (USG), serum urea and creatinine (sCr)) were not significantly different between dogs with babesiosis and healthy dogs. All three urinary markers were positively correlated with each other and with UPC. The data supports the presence of both glomerular and tubular dysfunction in dogs suffering from uncomplicated B. rossi infection. Urinary markers were superior to USG, serum urea and creatinine concentrations for the early detection of renal dysfunction in dogs with babesiosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The nematode Spirocerca lupi (S. lupi) induces sarcoma in the dog oesophagus in about 25% of cases. The aim of this study was to compare the differences in the cytokine milieu between dogs with neoplastic (n=29) and non-neoplastic disease (n=49) and age- and gender-matched healthy controls (n=25). We measured IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, GM-CSF and MCP-1 in a specific canine multiplex immunoassay kit. Cytokine concentrations were compared between the different groups using the Kruskal-Wallis test followed by Dunn's test. Only IL-8 and IL-18 showed significant differences in their plasma concentration among the three groups. Kruskal-Wallis test revealed a significant (p=0.001) difference in IL-8 concentration between the neoplastic group (634pg/ml), the non-neoplastic (429 pg/ml) and the control groups (150 pg/ml). Post-test analysis revealed a significance difference between the two S. lupi groups and the control group (p<0.01). The highest IL-18 concentration was found in the non-neoplastic group (53 pg/ml), followed by the control group (46 pg/ml) and finally the neoplastic group (33 pg/ml). IL-18 concentrations were significantly higher in the non-neoplastic group than in the neoplastic group (p=0.05). The increased IL-8 in the spirocercosis groups is consistent with the neutrophilic infiltrate in spirocercosis lesions and in those of other inflammatory-induced neoplasias such as Barret's oesophagus and Helicobacter gastritis. IL-18 showed negative regulatory effect in several worm infections and it is possible that it plays the same role in spirocercosis, allowing the worm to evade the host response and to induce neoplastic transformation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Hypoglycaemia has been identified as a life-threatening metabolic complication in almost 20% of severely ill dogs suffering from babesiosis due to Babesia canis rossi infection, and has been correlated with mortality. Hyperinsulinaemia as a result of inappropriate insulin secretion may precipitate hypoglycaemia, and has been suggested as a possible cause of hypoglycaemia in human and murine malaria. This prospective, cross-sectional, observational study, including 94 dogs with naturally occurring virulent babesiosis, sought to identify the presence of inappropriate insulin secretion in hypoglycaemic canine babesiosis. Pre-treatment jugular blood samples were collected for simultaneous determination of plasma glucose and insulin concentrations. Animals were retrospectively divided into three groups: hypoglycaemic (BG<3.3 mmol/L; n=16), normoglycaemic (BG 3.3-5.5 mmol/L; n=62), and hyperglycaemic (BG>5.5 mmol/L; n=16). The median insulin concentrations for the hypoglycaemic, normoglycaemic, and hyperglycaemic groups were 10.7 pmol/L, 10.7 pmol/L, and 21.7 pmol/L, respectively. Statistical analysis revealed no significant difference in insulin concentration between the three groups. Additionally, the median insulin concentration in the hypoglycaemic and normoglycaemic groups was below the detection limit of the assay, suggesting that insulin secretion was appropriately low (i.e. undetectable) in these cases. Only two dogs had inappropriately elevated insulin concentrations. One of these dogs was hypoglycaemic. We conclude that hyperinsulinaemia is an infrequent cause of hypoglycaemia in virulent canine babesiosis. Other causes of hypoglycaemia, such as increased glucose consumption, depletion of hepatic glycogen stores, and hepatic dysfunction with impaired gluconeogenesis, are speculated to play more important roles in the pathophysiology of hypoglycaemia in canine babesiosis.

Background: Tuberculosis is a major public-health problem in South Africa, made worse by poor adherence to and frequent interruption of treatment. Direct observation (DO) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome. We compared DO with self-supervision, in which patients on the same drug regimen are not observed taking their pills, to assess the effect of each on the success of tuberculosis treatment., Methods: We undertook an unblinded randomised controlled trial in two communities with large tuberculosis caseloads. The trial included 216 adults who started pulmonary tuberculosis treatment for the first time, or who had a second course of treatment (retreatment patients). No changes to existing treatment delivery were made other than randomisation. Analysis was by intention to treat. Individual patient data from the two communities were combined., Findings: Treatment for tuberculosis was more successful among self-supervised patients (60% of patients) than among those on DO (54% of patients, difference between groups 6% [90% CI -5.1 to 17.0]). Retreatment patients had significantly more successful treatment outcomes if self-supervised (74% of patients) than on DO (42% of patients, difference between groups 32% [11%-52%])., Interpretation: At high rates of treatment interruption, self-supervision achieved equivalent outcomes to clinic DO at lower cost. Self-supervision achieved better outcomes for retreatment patients. Supportive patient-carer relations, rather than the authoritarian surveillance implicit in DO, may improve treatment outcomes and help to control tuberculosis.

The value of cerebrospinal fluid C-reactive protein (CSF CRP) determination as a diagnostic aid in infective meningitis has been investigated in four groups of children. In a "no meningitis" group of 10 children, a median CSF CRP value of 0.08 micrograms/ml was obtained (range 0 to 0.31 micrograms/ml); in a viral meningitis group of 21 children a median value of 0.01 micrograms/ml (range 0 to 3.06 micrograms/ml); in a bacterial meningitis group of 27 children a median value of 9.6 micrograms/ml (range 0 to 31.5 micrograms/ml); and in a tuberculous meningitis group of 18 children a median value of 0.29 micrograms/ml (range 0 to 4.9 micrograms/ml). CSF CRP values in the bacterial meningitis group differed significantly from those of each of the other groups (P less than 0.01), but considerable overlap between the groups detracted from the diagnostic value of the test. In six patients with bacterial meningitis with ambiguous conventional CSF chemistry results, normal CSF CRP values were found. Simultaneous serum CRP was determined in nine patients with tuberculous meningitis and 11 with bacterial meningitis, and the CRP response in both the serum and CSF appears subdued in tuberculous meningitis in comparison with bacterial meningitis. CSF CRP and total protein values were determined intermittently during a 24-hour period in ventricular CSF from two children with tuberculous meningitis who underwent temporary direct ventricular drainage. A considerable and apparently parallel diurnal variation in both values was seen. CSF CRP values have limited application in the etiologic diagnosis of meningitis.