Distance to treatment as a factor for loss to follow up of hepatitis C patients in North East England.

BACKGROUND: A large proportion of the 200 000 HCV-infected individuals in the UK are undiagnosed or lost to follow-up. Engaging known infected individuals in treatment is essential for elimination. METHODS: Using PHE surveillance data and HCV treatment registers from North East of England (NE) treatment centres for 1997-2016, we estimated the number of HCV cases not linked to treatment and the proportion with active infection. We compared distances of treated and untreated cases to treatment services, and assessed the effect of expanding HCV treatment into existing drug and alcohol treatment centres in the NEE on treatment accessibility. RESULTS: The odds of being treated was associated with distance to treatment services. Confirmatory results for ~50% were not reported to PHE NE. Overall, 3385 patients reported to PHE NE had no record of treatment; we estimated 1621 of these may have been lost to follow-up after confirmation of active infection. CONCLUSIONS: Poor access to healthcare services may contribute to under-diagnosis or loss to follow-up. Expanding HCV treatment delivery into NEE drug and alcohol treatment centres would improve the accessibility of treatment services to people infected with/at risk of HCV. This may increase the proportion receiving treatment and support progress towards elimination.

Treatment outcome and cost-effectiveness of different highly active antiretroviral therapy regimens in the UK (1996-2002).

The aim of this study was to estimate the outcome and cost-effectiveness per life-year-gained (LYG) of first-, second- and third-line non-nucleoside reverse transcriptase inhibitors (NNRTI) versus protease inhibitor (PI) containing highly active antiretroviral therapy regimens. Hospital care costs (2002 US dollars discounted 3.5% per annum) were linked to treatment failure times. Results show that the median time-to-treatment failure for first-line (nucleoside reverse transcriptase inhibitors) 2NRTIs + NNRTI was substantially longer than that for 2NRTIs + PI(boosted), 2NRTIs + PI and 2NRTIs + 2PIs, whereas for second- and third-line they were similar. Comparing first-line 2NRTIs + NNRTI with 2NRTIs + PI(boosted) cost per LYG was US$ 12,375; US$ 12,139 per LYG when compared with 2NRTIs + PI and US$ 2948 per LYG when compared with 2NRTIs + 2PIs. For second-line cost per LYG comparing 2NRTIs + NNRTI with 2NRTIs + PI(boosted) was US$ 19,501; US$ 18,364 per LYG when compared with 2NRTIs + PI and cost-saving when compared with 2NRTIs + 2PIs. For third-line cost per LYG comparing 2NRTIs + NNRTI with 2NRTIs + PI(boosted) was US$ 2708; US$ 11,559 per LYG when compared with 2NRTIs + PI and cost-saving when compared with 2NRTIs + 2PIs. In conclusion, first-line 2NRTIs + NNRTI was cost-effective or cost-saving when compared with PI-containing regimens for all lines of therapy. Such information is required by clinicians and managers of HIV services to make appropriate treatment decisions based on clinical and financial grounds, and given the increasing number of people living with HIV, such information will become more important over time.

Acute rheumatic fever mimicking an acute coronary syndrome.

An elevated troponin measurement does not always reflect myocardial ischaemia secondary to obstructive coronary artery disease. Troponin levels can also be elevated in other disease states including pulmonary emboli, myo-pericarditis, acute rheumatic fever, and in the critically ill. Thus, patients presenting with chest pain and electrocardiological and biochemical evidence of myocardial necrosis are not always suffering from an acute coronary syndrome.

Immunisation of babies of women who screen positive for hepatitis B.

Pregnant women from countries with high prevalence rates of hepatitis B virus (HBV) infection may have significant HBV DNA levels despite being hepatitis B e antigen (HBeAg) negative and having antibody to HBeAg (anti-HBe positive). It is suggested that their babies, following delivery, should be given hepatitis B specific immunoglobulin (HBIG) in addition to hepatitis B vaccine in order to ensure their protection against infection.

Reactivity of soluble fibrin assays with plasmic degradation products of fibrin and in patients receiving fibrinolytic therapy.

The ability to identify the products of thrombin and plasmin action on fibrinogen is important in patients with thrombotic and fibrinolytic disorders. New assays have been developed for "soluble fibrin" which represents soluble derivatives other than fibrinopeptides formed from fibrinogen by thrombin. These assays are either immunological, using antibodies for fibrin-specific neoepitopes, or functional and based on the cofactor activity of soluble fibrin in the tissue plasminogen activator (t-PA)-mediated conversion of plasminogen to plasmin. As plasmic derivations of fibrin share structural features with soluble fibrin, they may be reactive with assays for soluble fibrin. Therefore, we prepared plasmic digests of fibrin and determined the degree of reactivity with four soluble fibrin assays. Three assays used Mabs directed toward the fibrin-specific neoepitopes at alpha17-23 (A), gamma312-324 (B) and alpha17-78 (D). A fourth (C) was based on t-PA co-factor activity. Tests A and C demonstrated marked crossreactivity with fibrin degradation products, and digests containing the largest derivatives showed greatest reactivity. Plasmic derivatives of crosslinked fibrin had greater reactivity than those of non-crosslinked fibrin. Tests B and D demonstrated minimal reactivity with plasmic derivatives of crosslinked or of non-crosslinked fibrin. Samples from patients with lower limb peripheral arterial occlusion were assayed for soluble fibrin, D-dimer and fibrinogen at presentation and eight hours after thrombolytic therapy. Variable results were seen at presentation with elevations in 13, 1, 0 and 4 of 19 patients using Tests A, B, C and D, respectively. After fibrinolytic therapy, marked increases in soluble fibrin levels were observed up to 600-fold above normal. A strong correlation between baseline levels was observed with Test B and Test D, which showed the least cross-reactivity with plasmic derivations. After thrombolytic therapy there were either weak or no correlations among the different assays. The results demonstrate that assays for soluble fibrin may react with plasmic derivatives of fibrin and this must be considered in interpreting clinical results.

Detection of antibodies against hepatitis C virus in saliva: a marker of viral replication.

Hepatitis C surveillance has been restricted owing to the lack of a sensitive antibody assay for saliva. The aim of our study was to develop and evaluate a screening assay for hepatitis C antibody in saliva specimens. Serum/saliva pairs were collected from 115 hepatitis C-positive patients. A modified hepatitis C antibody assay for saliva was developed and linked to testing carried out in the diagnostic laboratory. Correlation between the presence of antibody in serum and in saliva was poor (100% vs 85%). However, of 98 patients who were saliva antibody positive, 96 (98%) were also serum hepatitis C RNA positive and two (2%) were serum hepatitis C RNA negative. Hence, the correlation between a positive salivary antibody test and the serum hepatitis C RNA status of intravenous drug users suggests that this test could be used as a surrogate marker for hepatitis C viraemia in epidemiological studies.

Hepatitis C antibody detection in dried blood spots.

In the UK, there have been few studies of the seroprevalence of antibodies to hepatitis C virus (anti-HCV). As part of an ongoing prevalence study of HCV in injecting drug users, we have developed a technique for detecting anti-HCV in blood spots dried on filter paper using a commercially available assay. Subjects with and without serum anti-HCV were studied. The manufacturer's recommended cut-off (CO) for a positive anti-HCV result is kit-dependent, and therefore a ratio of test result (T) to kit CO was used to standardize results. T/CO values greater than 0.99 had a sensitivity of 100% and a specificity of 87.5% for anti-HCV detection. T/CO values greater than 1.99 had a sensitivity of 97.2% and a specificity of 100%. Hence, testing dried blood spots may be useful for detecting anti-HCV in epidemiological studies and as a diagnostic test in patients with poor peripheral venous access.

The effect of saliva specimen collection, handling and storage protocols on hepatitis C virus (HCV) RNA detection by PCR.

OBJECTIVES: Commercial assays can now be adapted to detect salivary anti-hepatitis C virus (HCV) antibodies, increasing the potential of saliva as a non-invasive diagnostic specimen suited to surveillance and epidemiological studies. However, current diagnostic algorithms involve confirmation of HCV infection by RT-PCR. Manipulation and storage conditions of serum can influence the stability of viral RNA. This study examined whether varying specimen collection, handling and storage protocols also affected subsequent HCV RNA detection by RT-PCR applied to saliva specimens. METHODS: Whole unstimulated saliva, together with saliva samples collected in two commercially available devices (Salivette and Omnisal) were obtained from 50 HCV seropositive intravenous drug users. The specimens were subjected to a number of handling and storage conditions, including heat treatment and prolonged storage, then examined for HCV RNA by RT-PCR using primers derived from the 5' non-coding region (5'NCR). RESULTS: HCV RNA was detected in saliva samples from 25 (50%) of the patients. No single collection device or handling procedure identified all the subjects with HCV RNA positive saliva though whole saliva yielded the greatest number of positive results. CONCLUSIONS: Collection and processing of saliva specimens for RT-PCR analysis is complex. At present, detection of salivary HCV RNA by PCR is not sufficiently sensitive for use as a diagnostic tool in epidemiological studies.

A soluble fibrin standard: comparable dose-response with immunologic and functional assays.

A soluble fibrin (SF) preparation has been developed as a potential standard by the Scientific and Standardization Committee for use in assays evaluating in vitro preparations and patient plasma samples. The SF standard was prepared by reaction of factor XIII-free fibrinogen with thrombin, followed by neutralization with hirudin and solubilization of the fibrin in acetic acid. As characterized by SDS-PAGE, the polypeptide chain structure shows the anticipated loss of fibrinopeptides and lack of gamma or alpha chain crosslinking. The standard was added to pooled normal plasma at concentrations from 12.5 microg/ml to 340 microg/ml and tested with four commercially available assays based on immunologic reactions using ELISA or latex agglutination or on t-PA cofactor activity for plasminogen to plasmin conversion. Absolute "soluble fibrin" concentrations were calculated using the manufacturers' calibrators and showed distinct dose-response relationships for each assay. Expression of the results following log-transformation produced a series of parallel lines, indicating that this SF preparation can serve as a standard, effectively normalizing the disparate proprietary internal calibrators currently used for each assay.

Treatment of chronic viral hepatitis.

Interferon-alpha therapy has proved effective for up to 40% of patients with adult-acquired chronic hepatitis B virus (HBV) infection and for 20-25% of those with chronic hepatitis C virus (HCV) infection. Nucleoside analogues, such as lamivudine and famciclovir, are showing promise as antiviral agents for chronic HBV and the combination of interferon-alpha and ribavirin is proving to be successful therapy for 40-50% of patients with chronic HCV. In this article we review current therapy and discuss future strategies of the therapy of chronic viral hepatitis.

A 3-year retrospective review of 132 patients with Salmonella enterocolitis admitted to a regional infectious diseases unit.

Over a 3-year-period, 132 patients were admitted to the Infectious Diseases Unit, Ruchill Hospital, Glasgow, with non-typhoidal salmonellae enterocolitis. Salmonella enteritidis and typhimurium were isolated from 67% of admissions. Of all patients, 11% had recently travelled overseas, 12% were hypochlorhydric and 3.8% were bacteraemic. Salmonella typhimurium infection was associated with a younger age group, a more pronounced leucocytosis and an earlier and less marked summer peak than S. enteritidis.

Visual loss in a returning traveller with tick typhus.

Rickettsial diseases are increasingly found world-wide and should be considered in febrile patients returning from abroad. This case report describes the vasculitic complications of a patient returning from the Republic of South Africa with tick typhus.

Predominance of HCV type 2a in saliva from intravenous drug users.

Paired serum and saliva samples were collected simultaneously from 50 intravenous drug users with serologically proven hepatitis C virus infection. The oral health of the volunteers was also assessed. Hepatitis C virus RNA was detected by nested PCR, employing primers from the 5' noncoding region. Positive PCR products were sequenced using the Sequenase PCR Product Sequencing Kit (Amersham Life Sciences). HCV RNA was detected in 33 (66%) of the 50 serum samples. HCV RNA was detected in 19 (57.6%) of the corresponding 33 saliva samples. There was no correlation between oral health status or HIV seropositivity and the detection of HCV in saliva. However, subjects with HCV in their saliva were significantly more likely to complain of xerostomia (P < 0.05). Isolate genotypes were identified in paired serum and saliva of 15 intravenous drug users. HCV genotypes 1, 2, 3 and 6 were detected in both specimens. In seven cases, a differing HCV genotype was found in serum compared to the paired saliva specimen. The distributions of genotypes in serum and saliva were very different, with genotype 2a more common in saliva than serum (P < 0.005). These data suggest that in some cases the source of salivary HCV may not be serum transudation along the periodontal membrane or across damaged mucosa, and that an alternative local source, possibly the salivary glands themselves, should be considered.

Molecular and therapeutic advances in the management of chronic hepatitis B and C.

Three hundred million individuals worldwide have persistent hepatitis B virus infection with 1-2 million hepatitis B virus-associated deaths per year, and an estimated 1% of the world's population are infected with hepatitis C virus. Recent advances in molecular biology and host responses have led to an increased understanding of hepatitis B and C virus disease and new potential targets for therapy.

Acalculous nontyphoidal salmonellal cholecystitis requiring surgical intervention despite ciprofloxacin therapy: report of three cases.

Nontyphoidal salmonellal cholecystitis is a rare complication of nontyphoidal salmonellal enterocolitis. We describe three patients with this complication who were hospitalized in a regional infectious disease unit at Ruchill Hospital, Glasgow, Scotland, over a period of 12 months. All three patients were receiving ciprofloxacin therapy before the episodes of cholecystitis became clinically evident, and all required surgical intervention.

Comparison of a weight-based heparin nomogram with traditional heparin dosing to achieve therapeutic anticoagulation.

Optimum anticoagulation with heparin within the first 24 hours of a thrombotic event is critical in preventing a recurrence. We believed that traditional nonweight-based heparin dosing at our institution resulted in delayed anticoagulation. A weight-based heparin nomogram was therefore created and compared to traditional heparin dosing in patients with a diagnosis of acute deep vein thrombosis or pulmonary embolism. Fifty historical control patients were compared to 50 consecutive patients treated prospectively using the weight-based nomogram. The primary outcome assessed was time to achieve therapeutic anticoagulation, defined as an activated partial thromboplastin time (aPTT) of 46-70 seconds (1.5-2.5 times the control aPTT). The weight-based nomogram achieved an aPTT above the therapeutic threshold more rapidly than the control group (10.7 hrs nomogram vs 33.3 hrs control group, p < 0.004). Similarly, the proportion of patients who exceeded the therapeutic threshold at the first aPTT measurement, at 24 hours, and at 48 hours was significantly higher in the nomogram group. There was no difference in the frequency of bleeding complications or recurrent thrombotic events between the two groups. The initial nomogram was revised for patients weighing more than 80 kg owing to a greater frequency of excessive anticoagulation in these patients. Subsequent analysis of 29 patients using the modified nomogram revealed sustained efficacy and a reduced number of supratherapeutic aPTTs. We concluded that a weight-based heparin nomogram is superior to traditional therapy in achieving rapid therapeutic anticoagulation without an increase in adverse outcomes.

Bacterial meningitis--the importance of cerebro-spinal fluid examination.

The role of lumbar puncture in bacterial meningitis has been debated in recent years, especially in the presence of worsening headache, alteration of conscious level, focal neurological signs, papilloedema or a haemorrhagic rash. However valuable bacteriological and epidemiological information will be lost if lumbar puncture is avoided, despite blood cultures being taken. This loss of information will be highlighted if pre-admission antibiotics are administered (this should now be standard practice).