Admission Characteristics, Diagnoses And Outcomes Of HIV-Infected Patients Registered In An Ambulatory HIV-Care Programme In Western Kenya

Objective: To determine admissions diagnosis and outcomes of HIV-infected patients attending AMPATH ambulatory HIV-care clinics. Design: Prospective cohort study. Setting: Academic Model for Prevention and Treatment of HIV/ AIDS (AMPATH) ambulatory HIV-care clinic in western Kenya. Results: Between January 2005 and December 2006, 495 HIV-infected patients enrolled in AMPATH were admitted. Median age at admission was 38 years (range: 19 - 74), 62% females, 375 (76%) initiated cART a median 56 days (range: 1- 1288) before admission. Majority (53%) had pre-admission CD4 counts 200 cells/ml. Common admissions diagnoses were: tuberculosis (27%); pneumonia (15%); meningitis (11%); diarrhoea (11%); malaria (6%); severe anaemia (4%); and toxoplasmosis (3%). Deaths occurred in 147 (30%) patients who enrolled at AMPATH a median 44 days (range: 1 - 711) before admission and died a median 41 days (range: 1 -713) after initiating cART. Tuberculosis (27%) and meningitis (14%) were the most common diagnoses in the deceased. Median admission duration was six days (range: 1 - 30) for deceased patients and eight days (range: I - 44) for survivors (P=0.0024). Deceased patients enrolled in AMPATH or initiated cART more recently, had lower CD4 counts and were more frequently lost to follow-up than survivors (

Risk factors for death in HIV-infected adult african patients recieving anti-retroviral therapy

Objective: To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART).Design: Retrospective Case-control study.Setting: The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya.Results: Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p<0.0148). Mediantime from enrollment at AMPATH to initiation of ART was two weeks for both groups while median time on ART was eight weeks for the deceased and fourty two weeks for the living (p<0.0001). Patients with CD4 cell counts <100/mm3 were more likely to die than those with counts >100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p<0.003). Patientsattending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p<0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level <10 grams% were associated with time to death while age, marital status, educational level, employment status andweight were not.Conclusion: Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation

Induction of lymphomas by inoculation of Marek's disease virus-derived lymphoblastoid cell lines: prevention by CVI988 vaccination.

Lymphoblastoid cell lines 265(L) and 990(O) are monoclonal lymphomas, derived respectively from liver and ovarian tumours, generated in inbred P-line (MHC B(19)/B(19)) chickens infected with RB-1B strain of Marek's disease virus (MDV) and pRB-1B5 BAC clone respectively. These were inoculated into inbred, MDV-susceptible, P-line chickens by intra-venous or intra-abdominal routes. Additional groups of birds were vaccinated using 1000 plaque-forming units of CVI988 vaccine 8 days prior to inoculation of the cell lines. Non-vaccinated birds developed visceral Marek's disease tumours with an increased rate 30 to 60 days post inoculation. Vaccination prevented tumour and disease development in challenged birds. TCRβ repertoire analysis by spectratyping and sequencing of the inoculum was used to track tumour identity in primary tumours and tumour cell lines derived from inoculated birds. These data revealed that the tumours were a consequence of de novo virus infection and not metastasis and expansion of the inoculated tumour cells. Moreover, the data showed that the two MDV-derived cell lines were not transplantable even in syngeneic P-line birds. The data also demonstrated the application of spectratyping as a tool to track tumour identity in lymphoma transplantation studies

Bespoke adaptation in rural Africa? An asset-based approach from Southern Ethiopia

Debates on adaptation in rural Africa rarely consider how responses to climate variability vary by wealth group. This study examines differences across wealth groups based on principal component analysis and cluster analysis triangulated with participatory methods. Results indicate that perceptions of weather variability and extreme events are detected by most households regardless of wealth status. The most common responses—using drought-resistant crops and changing planting dates—are also similar across groups. However, there are significant differences in the type of adaptation options adopted by wealthier and poorer farmers: the former intensify agriculture through improved seed varieties, fertiliser and manure; the latter depend on craft activities, seasonal migration and support from relatives and neighbours. Overall, our findings suggest that measuring asset holdings could allow a differentiated approach to supporting adaptation across socio-economic groups in rural regions in Ethiopia and Africa more broadly