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At least 217 records · Page 12Linked to original sources

Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology of this outbreak. METHODS: Forty-six patients from the United Kingdom treated with Gammagard (34 exposed and 12 unexposed to the batch) returned epidemiological questionnaires. RESULTS: Eighty-two percent of the exposed patients (28 of 34) became positive for HCV RNA. Eighteen percent of the patients (6 of 34) who had infusions with this batch tested negative for HCV RNA, but 2 of the patients had abnormal liver function and subsequently seroconverted to anti-HCV antibody positive. Twenty-seven percent of the patients (9 of 34) developed jaundice, and 79% (27 of 34) had abnormal liver transferase levels. Virus isolates (n=21), including an isolate from the implicated batch, were genotype 1a and virtually identical by sequence analysis of the NS5 region, consistent with transmission from a single source. CONCLUSIONS: Hepatitis C infection can be transmitted by anti-HCV-screened IV Ig. Careful documentation of IV Ig batch numbers and regular biochemical monitoring is recommended for all IV Ig recipients.

Acute Disease↗

Ostertagia ostertagi infection in the calf: effects of a trickle challenge on the hormonal control of digestive and metabolic function.

Metabolic effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day were investigated in 12 calves allocated to infected, pair-fed control or ad libitum-fed control groups. Changes in hormone levels reflecting abomasal, pituitary and pancreatic function were monitored using radioimmunoassay techniques previously validated for use in cattle. A range of metabolic profile parameters and blood metabolites was also measured. Feed intake of the infected calves began to decline as blood gastrin and pepsinogen levels reached a peak. The depression in appetite recorded in this group was responsible for significant increases in plasma urea and non-esterified fatty acid levels and associated with an increase in growth hormone/insulin ratio. No significant difference in glucagon levels was recorded between groups. A decline in blood albumin values was also shown in the infected group and associated with a drop in nitrogen digestibility. A significant depression in circulating calcium levels was related to either the hypoalbuminaemia or impaired mineral absorption in the intestine. A decrease in plasma cholesterol values in the infected group was associated with changes in digestive function.

Animals↗

Neurological disease in ex-Far-East prisoners of war.

In a group of 4684 ex-Far-East prisoners of war released in 1945, 679 had neurological disease; optic atrophy and peripheral neuropathy were the most common illnesses. However, in 89 patients neurological disease developed many years after their release; 35 of these patients had cord lesions unlike those seen in multiple sclerosis and other recognised diseases. In addition, Parkinson's disease often developed many years after release with a prevalence much higher than that in the normal population. The experiences that these patients had while in the Far East may have made them liable to develop cord disease and Parkinson's disease many years later.

Adult↗

Lack of association between type of hepatitis C virus, serum load and severity of liver disease.

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.

Adult↗

Public health, epidemiology and war.

The delivery of humanitarian aid in wartime is difficult. However, it is essential that aid is provided in the most effective manner possible, targeted on those most in need whilst minimizing waste. Furthermore the delivery of aid should be sensitive to the future needs of the communities in conflict. This requires information on the needs of the vulnerable population. There is little experience of collecting data on the impact of war on a civilian population. The war in Bosnia disrupted surveillance of communicable disease. The local authorities were assisted by the World Health Organization in re-establishing surveillance. The data generated was valuable in planning interventions to minimise the possibility of major outbreaks of infection, reduce the impact of infectious disease and in guiding the humanitarian aid effort. The experience described suggests that public health surveillance of the civilian population in wartime is possible and useful. Besides the need for planning, the public health doctor in wartime has a role as an advocate for those suffering; this function can be carried out much more effectively if it is based on objective data collection rather than hearsay.

Bosnia and Herzegovina↗

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.

Bacterial Infections↗

Genetic insights into disease mechanisms of autoimmunity.

Educating the immune system to distinguish between self and non-self is critical to ensure that an immune response is mounted against foreign antigens and not against self. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied genes and molecules are the human leukocyte antigen (HLA) region and the cytotoxic T-lymphocyte-associated 4 molecule (CTLA-4). Recently progress has been achieved in narrowing down the primary variants within both gene regions, but further work is needed to determine the function and extent of the aetiological variant(s) present. Recent exciting results also suggest a role for the newly discovered lymphoid-specific phosphatase (LYP) protein. As well as these general mechanisms, disease-specific mechanisms are beginning to be elucidated, for example the role of autoimmune regulatory element 1 (AIRE1) in autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Taken together, these data suggest that both general and disease-specific mechanisms lead to the clinical outcome of autoimmune disease and that increased understanding of these mechanisms will improve our knowledge of how autoimmune disease occurs, eventually leading to the development of novel therapeutic agents.

Antigens, CD↗

Molecular epidemiology of an outbreak of infection with hepatitis C virus in recipients of anti-D immunoglobulin.

In a retrospective investigation of possible transmission of hepatitis C virus (HCV) by anti-rhesus D immunoglobulin (anti-D) in 1977, we compared variants infecting anti-D recipients in Ireland of one of the implicated batches with those of epidemiologically unrelated HCV-infected individuals. All 100 of the recipients of the batch investigated to date were infected with a single genotype (type 1), consistent with a single-source outbreak, whereas a wider range of genotypes (1, 2, and 3) were found in anti-HCV positive individuals from Ireland infected by different routes. Nucleotide sequences from a 222 base fragment from the NS-5 region of the genome amplified from stored aliquots of the implicated batch closely matched those detected in anti-D recipients 17 years after the transmission event. This study shows the value of molecular epidemiological techniques for identifying distant sources of infection, and for the epidemiological investigation of the current distribution and transmission of HCV in different populations.

Antibodies, Anti-Idiotypic↗

Frequent infection of Hylobates pileatus (pileated gibbon) with species-associated variants of hepatitis B virus in Cambodia.

As well as being distributed widely in human populations, hepatitis B virus (HBV) infections occur frequently in chimpanzee, gibbon and other ape populations in sub-Saharan Africa and South-East Asia. To investigate the frequency and genetic relationships of HBV infecting gibbons in Cambodia, pileated gibbons (Hylobates pileatus) that were originally wild-caught were screened for surface antigen. Twelve of 26 (46 %) were positive, of which 11 were positive for HBV DNA. Phylogenetic analysis of complete genome sequences revealed two distinct genetic groups in the gibbon/orangutan clade. Three were similar to previously described variants infecting H. pileatus in Thailand and eight formed a distinct clade, potentially representing distinct strains of HBV circulating in geographically separated populations in South-East Asia. Because of the ability of HBV to cross species barriers, large reservoirs of infection in gibbons may hamper ongoing attempts at permanent eradication of HBV infection from human populations in South-East Asia through immunization.

Animals↗

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Acute Disease↗

Acute severe deterioration in cystic fibrosis associated with influenza A virus infection.

BACKGROUND: The role of non-bacterial infection in respiratory exacerbations of cystic fibrosis has been studied less than that of bacterial infection. Some non-bacterial infections, such as influenza A, may be associated with acute respiratory deterioration and may be preventable. METHODS AND RESULTS: Three patients with cystic fibrosis showed severe deterioration in lung function and general wellbeing during the influenza A virus epidemic in the winter of 1989-90. Serological confirmation of influenza A virus infection was obtained in each case. CONCLUSIONS: As immunisation against influenza A virus is safe and provokes an adequate antibody response in patients with cystic fibrosis, it is concluded that patients with cystic fibrosis should be offered immunisation at the beginning of each influenza season. Rapid diagnostic tests and the use of antiviral drugs may have a prophylactic role in minimising lung damage.

Acute Disease↗