This longitudinal follow-up study of 203 patients with serologically confirmed chikungunya (CHIK) virus infection describes the clinical features of CHIK fever during the first and tenth months of illness. During the acute stage CHIK fever presents with a wide array of symptoms. The foremost chronic symptoms at the end of a month were rheumatism (75%) and fatigue (30%). During the tenth month of follow-up the symptoms/signs observed were joint pain/swelling (46%), fatigue (13%) and neuritis (6%). The cure rate at the end of 9 months was 51%. Among the patients who had joint pain, 36% (34/94) met the American College of Rheumatology criteria to classify them as having rheumatoid arthritis. A subpopulation of the patients with joint pain (20/94) was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, and the joints were imaged by X-ray and magnetic resonance imaging (MRI). All tested negative for RF and one tested positive for anti-CCP. A radiolucent lesion in the X-ray was seen in the bones of five patients. The MRI findings were joint effusion, bony erosion, marrow oedema, synovial thickening, tendinitis and tenosynovitis. The study proves with relative certainty that CHIK arthritis is chronic inflammatory erosive arthritis, which has implications for management of the infection.
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.
STP is a versatile and reliable technique associated with low morbidity and mortality when compared with previous strategies for children with long segment tracheal stenosis. The presence of preoperative bronchomalacia is a significant risk factor for death and postoperative stenting.
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