scholarly journals IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected withTrypanosoma brucei rhodesiense

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Dawn Nyawira Maranga ◽  
John Maina Kagira ◽  
Christopher Kariuki Kinyanjui ◽  
Simon Muturi Karanja ◽  
Naomi Wangari Maina ◽  
...  
Keyword(s):  
Late Stage ◽  
Vervet Monkey ◽  
Control Group ◽  
Vervet Monkeys ◽  
Trypanosoma Brucei Rhodesiense ◽  
Monkey Model ◽  
Chlorocebus Aethiops ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Novel Biomarkers

The management of human African trypanosomiasis (HAT) is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops) were experimentally infected withTrypanosoma brucei rhodesienseand treated subcuratively at 28 days after infection (dpi) to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF) and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05) elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

scholarly journals Development of a safer laboratory vervet monkey model for the study of human African trypanosomiasis

2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Maxwell Waema ◽  
Naomi Maina ◽  
Simon Karanja ◽  
Beatrice Gachie ◽  
Maina Ngotho ◽  
...  
Keyword(s):  
Late Stage ◽  
Post Infection ◽  
Human African Trypanosomiasis ◽  
Clinical Signs ◽  
Vervet Monkey ◽  
Vervet Monkeys ◽  
Monkey Model ◽  
Cell Counts ◽  
Stage Disease ◽  
Late Stage Disease

Background: There are three subspecies of Trypanosoma brucei: T. b. gambiense, T. b. rhodesiense and T. b. brucei. The first two are infectious to humans, whilst T. b. brucei is not. Identifying an animal model of T. b. brucei that mimics human African trypanosomiasis (HAT) would enable researchers to study HAT without subjecting themselves to undue risks such as accidental infection. Objectives: This study assessed the sequential clinical, parasitological and haematological changes in vervet monkeys infected with T. b. brucei.Methods: Three vervet monkeys were infected with a 104 inoculum of T. b. brucei (isolate GUTat 1). Late-stage disease was induced by subcurative treatment with diminazene aceturate 28 days post-infection. The animals were treated curatively with melarsoprol upon relapse. Parasitaemia and clinical signs were monitored daily and, at weekly intervals, the monkeys’ blood and cerebrospinal fluid (CSF) were sampled for haematology and parasitosis assessments, respectively.Results: The first-peak parasitaemia was observed between seven and nine days post-infection. Clinical signs associated with the disease included fever, dullness, pallor of mucous membranes, lymphadenopathy, splenomegaly and oedema. Late-stage signs included stiffness of joints and lethargy. The monkeys developed a disease associated with microcytic hypochromic anaemia. There was an initial decline, followed by an increase, in total white blood cell counts from early- to late-stage disease. Trypanosomes were detected in the CSF and there was a significant increase in white cell counts in the CSF during late-stage disease. Infected vervet monkeys displayed classical clinical symptoms, parasitological and haematological trends that were similar to monkeys infected withT.b. rhodesiense.Conclusion: The T. b. brucei vervet monkey model can be used for studying HAT without putting laboratory technicians and researchers at high risk of accidental infection.

scholarly journals Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense Infection in Vervet Monkeys after Oral Administration

2008 ◽  
Vol 53 (3) ◽  
pp. 953-957 ◽  
Author(s):  
R. E. Mdachi ◽  
J. K. Thuita ◽  
J. M. Kagira ◽  
J. M. Ngotho ◽  
G. A. Murilla ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Late Stage ◽  
Early Stage ◽  
Vervet Monkey ◽  
Sleeping Sickness ◽  
Vervet Monkeys ◽  
Trypanosoma Brucei Rhodesiense ◽  
Dose Rates ◽  
Group 4 ◽  
Group 5

ABSTRACT Owing to the lack of oral drugs for human African trypanosomiasis, patients have to be hospitalized for 10 to 30 days to facilitate treatment with parenterally administered medicines. The efficacy of a novel orally administered prodrug, 2,5-bis(4-amidinophenyl)-furan-bis-O-methlylamidoxime (pafuramidine, DB289), was tested in the vervet monkey (Chlorocebus [Cercopithecus] aethiops) model of sleeping sickness. Five groups of three animals each were infected intravenously with 104 Trypanosoma brucei rhodesiense KETRI 2537 cells. On the seventh day postinfection (p.i.) in an early-stage infection, animals in groups 1, 2, and 3 were treated orally with pafuramidine at dose rates of 1, 3, or 10 mg/kg of body weight, respectively, for five consecutive days. The animals in groups 4 and 5 were treated with 10 mg/kg for 10 consecutive days starting on the 14th day p.i. (group 4) or on the 28th day p.i. (group 5), when these animals were in the late stage of the disease. In the groups treated in the early stage, 10 mg/kg of pafuramidine completely cured all three monkeys, whereas lower doses of 3 mg/kg and 1 mg/kg cured only one of three and zero of three monkeys, respectively. Treatment of late-stage infections resulted in cure rates of one of three (group 4) and zero of three (group 5) monkeys. These studies demonstrated that pafuramidine was orally active in monkeys with early-stage T. brucei rhodesiense infections at dose rates above 3 mg/kg for 5 days. It was also evident that the drug attained only minimal efficacy against late-stage infections, indicating the limited ability of the molecule to cross the blood-brain barrier. This study has shown that oral diamidines have potential for the treatment of early-stage sleeping sickness.

scholarly journals Proinflammatory Cytokine Expression in the Early Phase of Trypanosoma brucei rhodesiense Infection in Vervet Monkeys (Cercopithecus aethiops)

2004 ◽  
Vol 72 (5) ◽  
pp. 3063-3065 ◽  
Author(s):  
Naomi Maina ◽  
Joseph Maina Ngotho ◽  
Tom Were ◽  
John Kibuthu Thuita ◽  
David Mumo Mwangangi ◽  
...  
Keyword(s):  
Vervet Monkey ◽  
Vervet Monkeys ◽  
Tnf Receptor ◽  
Trypanosoma Brucei Rhodesiense ◽  
Necrosis Factor Alpha ◽  
Monkey Model ◽  
Tnf Α ◽  
Factor Alpha ◽  
Soluble Tnf Receptor ◽  
Necrosis Factor

ABSTRACT A vervet monkey model of trypanosomiasis was used to study inflammatory cytokine responses in serum and cerebrospinal fuid (CSF). Gamma interferon levels were transiently up-regulated in serum between days 6 and 8 of infection, followed by a sustained up-regulation of tumor necrosis factor alpha (TNF-α) and soluble TNF receptor 1. At no time were these cytokines detectable in the CSF.

scholarly journals Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism

AIDS ◽  
2012 ◽  
Vol 26 (18) ◽  
pp. 2275-2284 ◽  
Author(s):  
José M. Marcelino ◽  
Pedro Borrego ◽  
Charlotta Nilsson ◽  
Carlos Família ◽  
Helena Barroso ◽  
...  
Keyword(s):  
Late Stage ◽  
Antibody Neutralization ◽  
Stage Disease ◽  
Late Stage Disease

Receipt of Screening Mammography by Insured Women Diagnosed With Breast Cancer and Impact on Outcomes

2021 ◽  
Author(s):  
Marissa B. Lawson ◽  
Christoph I. Lee ◽  
Daniel S. Hippe ◽  
Shasank Chennupati ◽  
Catherine R. Fedorenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Late Stage ◽  
Breast Cancer Diagnosis ◽  
Screening Mammography ◽  
Socioeconomic Deprivation ◽  
Tumor Characteristics ◽  
Stage Disease ◽  
Increased Risk ◽  
Late Stage Disease

Background: The purpose of this study was to determine factors associated with receipt of screening mammography by insured women before breast cancer diagnosis, and subsequent outcomes. Patients and Methods: Using claims data from commercial and federal payers linked to a regional SEER registry, we identified women diagnosed with breast cancer from 2007 to 2017 and determined receipt of screening mammography within 1 year before diagnosis. We obtained patient and tumor characteristics from the SEER registry and assigned each woman a socioeconomic deprivation score based on residential address. Multivariable logistic regression models were used to evaluate associations of patient and tumor characteristics with late-stage disease and nonreceipt of mammography. We used multivariable Cox proportional hazards models to identify predictors of subsequent mortality. Results: Among 7,047 women, 69% (n=4,853) received screening mammography before breast cancer diagnosis. Compared with women who received mammography, those with no mammography had a higher proportion of late-stage disease (34% vs 10%) and higher 5-year mortality (18% vs 6%). In multivariable modeling, late-stage disease was most associated with nonreceipt of mammography (odds ratio [OR], 4.35; 95% CI, 3.80–4.98). The Cox model indicated that nonreceipt of mammography predicted increased risk of mortality (hazard ratio [HR], 2.00; 95% CI, 1.64–2.43), independent of late-stage disease at diagnosis (HR, 5.00; 95% CI, 4.10–6.10), Charlson comorbidity index score ≥1 (HR, 2.75; 95% CI, 2.26–3.34), and negative estrogen receptor/progesterone receptor status (HR, 2.09; 95% CI, 1.67–2.61). Nonreceipt of mammography was associated with younger age (40–49 vs 50–59 years; OR, 1.69; 95% CI, 1.45–1.96) and increased socioeconomic deprivation (OR, 1.05 per decile increase; 95% CI, 1.03–1.07). Conclusions: In a cohort of insured women diagnosed with breast cancer, nonreceipt of screening mammography was significantly associated with late-stage disease and mortality, suggesting that interventions to further increase uptake of screening mammography may improve breast cancer outcomes.

Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

2002 ◽  
Vol 36 (6) ◽  
pp. 805-811 ◽  
Author(s):  
Sanjiv K. Jain ◽  
Philip W. Pemberton ◽  
Alexander Smith ◽  
Raymond F.T. McMahon ◽  
Peter C. Burrows ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Late Stage ◽  
Stage Disease ◽  
Late Stage Disease

scholarly journals Natural alteration of HIV-1 co-receptor tropism by contemporaneous HIV-2 infection

2018 ◽  
Author(s):  
Joakim Esbjörnsson ◽  
Fredrik Månsson ◽  
Hans Norrgren ◽  
Sarah L. Rowland-Jones
Keyword(s):  
Late Stage ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Underlying Mechanisms ◽  
Disease Understanding ◽  
Hiv 1 ◽  
The Way

In this study, we show that the pathogenic HIV-1 CXCR4-tropism is more common in HIV-1 single (79%) than in HIV-1 and HIV-2 dual-infected individuals (35%), suggesting that contemporaneous HIV-2 infection can affect HIV-1 co-receptor tropism in late-stage disease. Understanding the underlying mechanisms responsible for this natural alteration by HIV-2 could pave the way towards a deeper understanding of the AIDS pathogenesis.

scholarly journals Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

2019 ◽  
Vol 220 (7) ◽  
pp. 1172-1177 ◽  
Author(s):  
Mark J Siedner ◽  
Mwebesa Bosco Bwana ◽  
Stephen Asiimwe ◽  
Gideon Amanyire ◽  
Nicholas Musinguzi ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Late Stage ◽  
Sub Saharan Africa ◽  
Cd4 T Cell ◽  
Disease Stage ◽  
Stage Disease ◽  
Late Stage Disease ◽  
Cd4 T Cell Count

Abstract Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count <200/µL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

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