Etiology of pediatric fever in western Kenya: a case-control study of falciparum malaria, respiratory viruses, and streptococcal pharyngitis.

In Kenya, more than 10 million episodes of acute febrile illness are treated annually among children under 5 years. Most are clinically managed as malaria without parasitological confirmation. There is an unmet need to describe pathogen-specific etiologies of fever. We enrolled 370 febrile children and 184 healthy controls. We report demographic and clinical characteristics of patients with Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with undifferentiated fever. Of febrile children, 79.7% were treated for malaria. However, P. falciparum was detected infrequently in both cases and controls (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile children had a respiratory viral infection, compared with 24.8% (29/117) of controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275 (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both groups, but only influenza or parainfluenza was more likely to be associated with symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively). Malaria was overdiagnosed and overtreated. Few children presented to the hospital with GAS pharyngitis. An enhanced understanding of carriage of common pathogens, improved diagnostic capacity, and better-informed clinical algorithms for febrile illness are needed.

Aggressive venous neointimal hyperplasia in a pig model of arteriovenous graft stenosis.

BACKGROUND: Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of well over one billion dollars per annum. Venous neointimal hyperplasia characterized by stenosis and subsequent thrombosis, is the major cause of polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem, there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. We believe that this is partly due to the lack of a validated large animal model of arteriovenous stenosis that could be used to test out novel interventions. METHODS: Seven-centimeter PTFE loop grafts were placed between the femoral artery and vein of domestic pigs. The grafts were removed at 2, 4, 7, 14 and 28 days after surgery and subjected to a detailed histological and immunohistochemical examination. RESULTS: Significant neointimal hyperplasia and venous stenosis developed by 28 days at the graft-vein anastomosis. There was minimal neointimal hyperplasia at the graft-artery anastomosis. Venous neointimal hyperplasia (VNH) was characterized by (a) the presence of smooth muscle cells/myofibroblasts; (b) angiogenesis within both the neointima and adventitia; and (c) the presence of an active macrophage cell layer lining the PTFE graft material. These results are very similar to the human lesion previously described by us in dialysis patients. CONCLUSIONS: We have developed and validated a pig model of venous neointimal hyperplasia that is very similar to the human lesion. We believe that this is an ideal model in which to test out novel interventions for the prevention and treatment of clinical hemodialysis vascular access dysfunction.

External beam radiation attenuates venous neointimal hyperplasia in a pig model of arteriovenous polytetrafluoroethylene (PTFE) graft stenosis.

PURPOSE: Hemodialysis vascular access dysfunction is an enormous clinical problem that causes great morbidity and costs well over one billion dollars per annum. The vast majority of hemodialysis vascular access dysfunction occurs as a result of venous stenosis and thrombosis at the graft-vein anastomosis. At a cellular level, this venous stenosis is the result of venous neointimal hyperplasia (VNH). There are, unfortunately, no effective therapies for VNH. The purpose of this study was to assess the role of external radiation therapy in preventing VNH and venous stenosis. METHODS AND MATERIALS: Seven-centimeter polytetrafluoroethylene loop grafts were placed bilaterally between the femoral artery and vein of 12 Yorkshire Cross pigs. One side was treated with a single 16-Gy dose of external beam radiation with a linear accelerator, while the contralateral side served as an internal control. Swine were killed after 28 days, and the grafts were carefully dissected out and removed. Neointimal hyperplasia and luminal stenosis were then assessed morphometrically at the graft-vessel anastomoses. RESULTS: External beam radiation therapy significantly reduced the amount of luminal stenosis at the graft-vein anastomosis, with minimal local and systemic toxicity. CONCLUSIONS: External beam radiation therapy could be a useful and clinically relevant local treatment for venous stenosis in polytetrafluoroethylene dialysis grafts.