Non-specific induction of increased resistance in mice toTrypanosoma congolenseandTrypanosoma bruceiby immunostimulants

Parasitology ◽  
1979 ◽  
Vol 79 (3) ◽  
pp. 349-366 ◽  
Author(s):  
Max Murray ◽  
W. I. Morrison

SUMMARYAdministration of the immunostimulantsCorynebacterium parvum, Bacillus Calmette-Guérin(BCG) orBordetella pertussisprior to, or at the same time as, challenge withTrypanosoma congolensesignificantly increased survival times in mice, both of trypano-susceptible (A/J) and trypano-resistant (C57Bl) strains. The increased survival time was associated with significant alterations in parasitaemia, which included lengthening of the pre-patent period, a delay in the time taken to reach the first peak of parasitaemia and a reduction in the level of parasitaemia. Similar results were obtained when these strains of mice were challenged withTrypanosoma bruceifollowing pre-treatment withC. parvum. Thus, by the use of immunostimulants it was possible to reduce the susceptibility of mice to trypanosomiasis and the hope is that this can also be achieved with domestic livestock.

Parasitology ◽  
1982 ◽  
Vol 85 (1) ◽  
pp. 127-148 ◽  
Author(s):  
R. J. Gilbert ◽  
B. A. Newton

SUMMARY[14C[ethidium bromide has been used to determine drug levels in tissues and body fluids of rabbits and calves following intramuscular injection. Uninfected and Trypanosoma brucei- or Trypanosoma congolense-infected animals were studied. Blood and tissue fluid levels reached a maximum within 1 h and then fell rapidly; after 96 h 80–90% of the radioactivity injected had been excreted, approximately one third in urine and two thirds in faeces. By 1 h after injection of 1 mg [14C]ethidium/kg into a T. congolense-infected calf, 70–80% of the radioactivity in blood was found to be bound to trypanosomes. Doses of 1 or 10 mg/kg were found not to be curative for T. congolense or T. brucei infections in rabbits; drug treatment resulted in a period of sub-patent parasitaemia which was always followed by a relapse. Examination of the prophylactic action of ethidium in rabbits showed that the drug extended the pre-patent period following trypanosome inoculation but provided no absolute protection. A period of ‘apparent’ prophylaxis observed after drug treatment of infected rabbits has been correlated with the presence of anti-trypanosome IgG in the serum.


2009 ◽  
Vol 77 (9) ◽  
pp. 3948-3957 ◽  
Author(s):  
Birgit Rathkolb ◽  
Harry A. Noyes ◽  
Andy Brass ◽  
Paul Dark ◽  
Helmut Fuchs ◽  
...  

ABSTRACT Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia, and degree of liver damage are not associated with each other, despite the correlation in the parental lines. These data suggest that the congenic loci affect survival but do not affect control of parasite number. They may therefore act by limiting the pathological consequences of T. congolense infection.


Author(s):  
Purity K. Gitonga ◽  
Kariuki Ndung’u ◽  
Grace A. Murilla ◽  
Paul C. Thande ◽  
Florence N. Wamwiri ◽  
...  

African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.). In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6). We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates. Results showed that the overall pre-patent (PP) periods were 8.4 ± 0.9 (range, 4–11) and 4.5 ± 0.2 (range, 4–6) for T. congolense and T. brucei isolates, respectively (p < 0.01). Despite the longer mean PP, T. congolense–infected mice exhibited a significantly (p < 0.05) shorter survival time than T. brucei–infected mice, indicating greater virulence. Differences were also noted among the individual isolates with T. congolense KETRI 2909 causing the most acute infection of the entire group with a mean ± standard error survival time of 9 ± 2.1 days. Survival time of infected tsetse flies and the proportion with mature infections at 30 days post-exposure to the infective blood meals varied among isolates, with subacute infection–causing T. congolense EATRO 1829 and chronic infection–causing T. brucei EATRO 2267 isolates showing the highest mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study provides further evidence of occurrence of differences in virulence and transmissibility of eastern African trypanosome strains and has identified two, T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse infectivity and transmissibility experiments.


1977 ◽  
Vol 47 (1) ◽  
pp. 35-43 ◽  
Author(s):  
M. Stephen Mahaley ◽  
Robert E. Gentry ◽  
Darell D. Bigner

✓ The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Guérin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon survival times. The most consistent prolongation of survival time was produced by triple therapy: BCG + intraperitoneally administered sarcoma cells + intravenously administered BCNU.


2019 ◽  
Vol 3 (s1) ◽  
pp. 37-37
Author(s):  
Jo Ellen Wilson ◽  
Sarasota Mihalko ◽  
Stephan Heckers ◽  
Pratik P. Pandharipande ◽  
Timothy D. Girard ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.


2014 ◽  
Vol 203 (3-4) ◽  
pp. 270-275 ◽  
Author(s):  
Annelise Sahin ◽  
Corinne Asencio ◽  
Julien Izotte ◽  
Davita Pillay ◽  
Virginie Coustou ◽  
...  

Parasitology ◽  
1998 ◽  
Vol 116 (S1) ◽  
pp. S23-S28 ◽  
Author(s):  
I. Maudlin ◽  
S. C. Welburn ◽  
P. J. M. Milligan

SummaryThe effect of trypanosome infection on vector survival was observed in a line of Glossina morsitans morsitans selected for susceptibility to trypanosome infection. The differential effects of midgut and salivary gland infections on survival were examined by exposing flies to infection with either Trypanosoma congolense which colonizes midgut and mouthparts or Trypanosoma brucei rhodesiense which colonizes midgut and salivary glands. A comparison of the survival distributions of uninfected flies with those exposed to infection showed that salivary gland infection significantly reduces tsetse survival; midgut infection had little or no effect on the survival of tsetse. The significance of these findings is discussed in relation to the vectorial capacity of wild flies.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Harriet Lane-Serff ◽  
Paula MacGregor ◽  
Lori Peacock ◽  
Olivia JS Macleod ◽  
Christopher Kay ◽  
...  

The haptoglobin-haemoglobin receptor of the African trypanosome species, Trypanosoma brucei, is expressed when the parasite is in the bloodstream of the mammalian host, allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes. Here we show that in Trypanosoma congolense this receptor is instead expressed in the epimastigote developmental stage that occurs in the tsetse fly, where it acts as a haemoglobin receptor. We also present the structure of the T. congolense receptor in complex with haemoglobin. This allows us to propose an evolutionary history for this receptor, charting the structural and cellular changes that took place as it adapted from a role in the insect to a new role in the mammalian host.


1981 ◽  
Vol 54 (4) ◽  
pp. 461-467 ◽  
Author(s):  
Alexander M. Spence ◽  
Joseph P. Geraci

✓ The combination of cyclotron fast-neutron radiotherapy with BCNU chemotherapy was compared to 137Cs gamma photon radiotherapy combined with BCNU in the 36B-10, F-344 rat-transplanted glioma model. Radiation and drug treatments were administered 7 to 8 days after intracerebral tumor implantation. Increase in animal survival time was used as the measure of the effectiveness of various treatment schedules. Single-dose neutron or gamma radiotherapy was tested on Day 7 over the ranges 0 to 900 rads and 0 to 2000 rads, respectively. This therapy produced increases in mean survival times up to 70% at the highest radiation doses. When BCNU (10 mg/kg body weight) was administered intravenously on Day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35% to 50%, irrespective of the dose or type of irradiation. In contrast, by using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 hour before either neutron or gamma irradiation on Day 7, there was enhancement of the radiation effect by BCNU. Under these conditions, the maximum enhancement of the mean survival time was 70% to 75% in neutron-treated animals and 120% to 150% in gamma-treated animals. Treatment with BCNU 1 hour before or 1 day after neutron irradiation proved to be no more effective in improving the survival time of tumor-bearing animals than the drug similarly combined with conventional gamma irradiation.


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