S Moses

Targeted case finding for hepatitis B using dry blood spot testing in the British-Chinese and South Asian populations of the North-East of England.

Chronic infection with the hepatitis B virus (HBV) is a frequent cause of cirrhosis and liver cancer. Targeted HBV screening is recommended by the Centre for Disease Control (CDC) and Prevention for subjects born in countries with >2% HBV prevalence. However, there are no UK guidelines. Here, we applied the (CDC) recommendations to the British–Chinese and British–South Asian community of North‐East (NE) England. British–Chinese and South Asian subjects were invited to attend for HBV education and screening sessions held in community centres. Hepatitis B surface antigen (HBsAg) and hepatitis B core total antibody (HBcAb) were tested with dry blood spot tests. South Asians were also tested for hepatitis C antibody (HCVAb). A total of 1126 subjects (606 Chinese and 520 South Asian) were screened. Sixty‐two (5.5%) were HBsAg positive. Ten of these reported a previous diagnosis of HBV. The prevalence of HBsAg positivity was 4.6% when previously diagnosed individuals were excluded. The HBsAg prevalence was significantly higher in the Chinese subjects compared with South Asians (8.7% VS. 1.7% P < 0.001). In Chinese subjects, HBsAg positivity was highest in subjects born in Vietnam (17.4%), followed by China (11%), Hong Kong (7.8%) and the UK (6.7%). Subjects from Pakistan had the highest HBsAg and HCV Ab prevalence in the South Asians (3.1% and 1.8%, respectively). Ten percentage of HBsAg positive patients who had follow‐up assessment had active disease requiring antiviral treatment. Undiagnosed HBV infection was above the 2% threshold for screening suggested by the CDC in the British–Chinese and Pakistani community of NE England, which provides evidence for a UK HBV‐targeted screening programme.

Hepatitis B virus infection: pathogenesis, reactivation and management in hematopoietic stem cell transplant recipients

Hepatitis B virus (HBV) is a partially double stranded DNA virus that can integrate into host cell chromosomes as covalently closed circular DNA forms. HBV reactivation following hematopoietic stem cell transplantation in recipients with evidence of past HBV exposure, as well as exacerbation of a current HBV infection in HBV carrier recipients, secondary to chemotherapy and post-transplant immunosuppression that affect both humoral and cell-mediated control of HBV infection, are well documented in the literature. Management options include HBV-DNA screening and antiviral prophylaxis. Nucleos(t)ide analogues have been used at the start of chemotherapy and pretransplantation, with the course continuing for 6 months. However, depending on the serum HBV-DNA level, the antiviral agent might be given until a therapeutic end point is reached.

Hepatitis B in pregnancy

Objective Vertical transmission of the hepatitis B virus (HBV) is the commonest mode of infection and can be prevented with immunoprophylaxis of the infant and antiviral therapy in the mother. Our aim was to review a cohort of subjects with HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA levels that required treatment to prevent transmission, and to review the management of mothers and infants. Methods A retrospective case-note review was conducted of all the HBV-infected pregnant women and their infants who attended the Newcastle obstetric services from 2007 to 2011. Results There were 113 pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg) positive) during 2007–11. 71% of mothers were first diagnosed with HBV during pregnancy. The mothers were born in 28 different countries. 69% of mothers had an HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than 1.0×107 IU/mL so would be eligible for antiviral therapy to prevent transmission to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV requiring treatment. All infants born to HBeAg-positive mothers received hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a full HBV vaccination course. One infant born to an HBeAg-negative mother was hepatitis B surface antigen positive 1 year post-delivery. Conclusions One in six women had active HBV requiring treatment or high HBV-DNA levels that would benefit from antiviral treatment to reduce the transmission risk. HBIG was administered appropriately but completion of the vaccination course was suboptimal.

P54 CHASE-B (Chinese Hepatitis Awareness, Surveillance and Education): a pilot of targeted case finding for hepatitis B virus (HBV) in the British-Chinese community

Introduction Chronic HBV (cHBV) is a frequent cause of cirrhosis and liver cancer. Many infected individuals are unaware of their condition. Migrants from countries with high prevalence of cHBV, such as China and the Far East (seroprevalence 7–12%), are a high risk group for cHBV. Targeted HBV screening and vaccination is recommended by the AASLD1 and the European Liver Patients Association (ELPA)2 in high risk groups including subjects born in endemic areas. However, there are no current UK guidelines. Aim To apply AASLD and ELPA recommendations to British-Chinese community of North East (NE) England. Method Members of the NE Chinese community were invited to attend screening sessions at the Newcastle Chinese Healthy Living Centre [charity registration no. 1125227]. Dry blood spots were obtained by finger prick and tested for HBsAg and HBcAb (Abbott ARCHITECT). HBsAg positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. Results 575 subjects were screened in 10 sessions (mean age 49±17 years, 61% female). 53 (9%) were HBsAg positive (48% female) indicating cHBV. 10 of these reported being previously diagnosed with HBV, but were not under follow-up. The prevalence of HBsAg positivity was 7.5% when previously diagnosed individuals were excluded. 80 (14%) subjects had past infection with HBV (HBsAg negative, HBcAb positive). Individuals with past HBV were significantly older than HBsAg positive and HBsAg, HBcAb negative subjects (p<0.001). The prevalence of HBsAg positivity was highest in subjects born in Vietnam (17.4%, 4/23), followed by China (11.5%, 24/157), Hong Kong (8.3%, 18/288), the UK (6.7%, 5/75) and other (6.2%, 2/32). Only 12% of subjects reported previous vaccination against HBV. To date, 25 of the HBsAg positive individuals have been seen in our clinic. 1 was HBeAg positive (immunotolerant) and 24 were HBeAg negative. Of these, 3 have active disease (including 1 cirrhotic) and have been started on treatment. 14 have inactive cHBV and 7 are undergoing observation to determine disease activity. No cases of co-infection with HCV, HIV or Delta were found. Conclusion 1. Undiagnosed cHBV is common in the British-Chinese community of NE England, including subjects born in the UK. 2. A proportion had active cHBV requiring treatment. 3. If these results were applied to the entire UK British-Chinese population targeted screening should lead to approximately 32 250 newly diagnosed cases of cHBV. 4. These results provide evidence for a UK HBV screening and vaccination program for the British-Chinese community.

Haemophagocytic lymphohistiocytosis following fludarabine/cyclophosphamide chemotherapy for chronic lymphocytic leukaemia

Antonella Anastasia* Carmelo Carlo-Stella* Paolo Corradini Flavia Salvi Chiara Rusconi Alessandro Pulsoni Stefan Hohaus Patrizia Pregno Simonetta Viviani Ercole Brusamolino Stefano Luminari Laura Giordano Armando Santoro Department of Oncology and Haematology, Humanitas Cancer Centre, Humanitas Clinical and Research Centre, Rozzano (MI), Department of Medical Biotechnology and Translational Medicine, University of Milano, Department of Haematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Chair of Haematology, University of Milano, Milano, Division of Haematology, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Division of Haematology, Niguarda Ca’ Granda Hospital, Milano, Department of Cellular Biotechnologies and Haematology, “Sapienza” University, Institute of Haematology, Universit a Cattolica S. Cuore, Roma, Haematology, A.O. Citt a della Salute e della Scienza, Torino, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Division of Haematology, Policlinico S Matteo, Pavia, and Department of Diagnostic Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. E-mail: carmelo.carlostella@cancercenter.humanitas.it

Global burden of herpes simplex type 2

www.thelancet.com/infection Vol 9 June 2009 333 In conclusion, considering the complications and defective functioning of the cellular immune system as a consequence of chronic coinfection of M tuberculosis and HIV, we believe that the strategy of inducing nonneutralising antibodies by therapeutic vaccination might not be appropriate for these patients. The primary goal in treating patients with coinfection should be the rejuvenation of the immune system, making it functionally fi t before implementing any vaccination strategies. However, common features of these two infectious agents, such as use of the same receptor (dendritic cell-specifi c intercellular adhesion molecule-3grabbing non-integrin) by both glycoprotein 120 of HIV and mannosylated lipoarabinomannan of M tuberculosis, complicate the dissection of pathogenesis due to individual pathogens in patients with coinfection. In addition, two important factors that govern the immune response to pathogens and vaccination have to be considered: nutrition and intestinal parasite burden. This point is crucial since most of the patients with coinfection are in developing countries and it is well known that nutrition and intestinal parasite burden can bias the type of immune response to pathogens and vaccines. Therefore, the pathogenesis of coinfection might not be the same among patients in developing and developed countries. As individuals living with coinfection of HIV and tuberculosis grow older, it will become important to consider the immune system that is aff ected by infections, nutritional status, past therapeutic history, and age. Therefore, the need of the hour in these patients will be a thorough investigation of the pathogenesis of coinfection and identifying appropriate therapeutic strategies that boost the immune system.

PTU-115 Hepatitis B in Pregnancy: what Happens to the Infants?

Introduction Antenatal screening for Hepatitis B (HBV) has been offered to all pregnant women in the UK since 2000. Immunoprophylaxis of infants is essential to reduce the risk of vertical transmission. It is recommended that HBV vaccination (4 serial doses) be given to all infants born to HBV positive mothers. In addition, Hepatitis B immunoglobulin (HBIG) is recommended for infants of Hepatitis B e antigen (HBeAg) positive mothers. Infants should have post-vaccination testing between 9–18 months. Hepatitis B surface antigen (HBsAg) negative infants with anti-HBs levels > 10iu/ml need no further management. If anti-HBs is < 10iu/ml infants should receive a second vaccination series. Our aim was to evaluate the management of infants born to HBV positive mothers. Methods All HBV positive pregnant women seen in our hospital between January 2008 and November 2011 were identified from an obstetric database. We examined if the infants received the recommended vaccinations, HBIG and post-vaccination testing. Results From a total of 99 pregnancies data was available for 76 infants. All 15 infants born to HBeAg positive mothers were given HBIG at birth. 7 mothers had a HBV DNA > 107 IU/ml. 2 were treated with antiviral therapy during pregnancy. 58 (76.3%) infants received a full vaccination course. Only 35 (54.7%) of the 64 infants who should have had their post-vaccination status checked to date have had this completed. 34 (97.1%) had an adequate response to vaccination. One infant (who received 3 vaccinations) is HBsAg positive with a viral load of 5.4 × 103 iu/ml. The mother was HBeAg negative with a viral load of 1.7 × 103 iu/ml. Conclusion HBIG was administered appropriately to the infants at highest risk of vertical transmission of HBV. However, completion of the 4 dose HBV vaccination in infants was suboptimal postpartum and post- vaccination testing was inadequate. Efforts to improve this are now in place and include: prospective data collection to improve quality of data; development of a central reminder system to advise family doctors 2 weeks before each vaccination dose is due and ensure this is completed; and introduction of dry blood spot testing of the infants to improve the acceptability of testing. Disclosure of Interest None Declared

PMO-162 Pregnant mothers with chronic hepatitis B (HBV): how often is treatment needed?

Introduction HBV is a common cause of chronic liver disease worldwide. Vertical transmission is the commonest mode of infection. Since 2000 antenatal HBV screening is offered to all pregnant women in the UK. The British Viral Hepatitis Group recommend treating mothers with an HBV DNA level of >107 IU/ml with antivirals in the 3rd trimester to reduce the transmission risk. Few studies have evaluated the epidemiology/management of pregnant patients with HBV in the UK. We reviewed the management of mothers with HBV attending our obstetric services. Methods Retrospective notes review of all HBV positive mothers who attended the obstetric service from January 07 to November 11. Data were collected on patient demographics, viral serology, HBV DNA and ALT levels and HBV management during their first pregnancy in the time period. Results 81 HBsAg positive mothers (median age 28, 18–44) had 113 pregnancies in the study period. 96% were referred to the viral hepatitis service; however 28% of women did not attend >1 appointment. The mothers were born in 28 countries, most commonly China (30%) followed by countries in Eastern Europe (17%), Africa (16%), South Asia (16%) and elsewhere (21%). 29% were known to have chronic HBV (cHBV). All mothers were tested for HBeAg/Ab status: 15% were HBeAg positive, 85% HBeAg negative and 79% anti-HBe positive. 85% had HBV DNA checked during the pregnancy. 9% had active HBeAg positive cHBV (HBV DNA >20 000 IU/ml, ALT >40), 3% had active HBeAg negative cHBV (HBV DNA >2000 and ALT >40), 9% were immunotolerant (HBeAg positive, ALT <40), 60% were inactive carriers (HBV DNA <2000 and ALT <40) and 19% were indeterminate. 13% of mothers had a HBV DNA >107 IU/ml, but only two patients were treated with tenofovir in the 3rd trimester. Of the eight patients with active HBV, six were successfully treated post-partum with oral antivirals/PEG-Interferon and two became inactive. 20% of inactive carriers experienced a post-partum flare in ALT that settled spontaneously. Conclusion A high proportion of HBV infected mothers were born overseas; >1 in 6 had active cHBV or HBV DNA >107 IU/ml and were eligible for treatment to reduce the vertical transmission risk and/or prevent disease progression. All HBV infected mothers should be assessed for treatment and efforts to improve attendance at clinic appointments need to be intensified. Competing interests None declared.

Extensive oral herpes simplex virus type 1 infection in a haematopoietic stem cell transplant recipient not responding to aciclovir

Department of Virology, Health Protection Agency Microbiology Services, Newcastle, UK Department of Haematology, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK Department of Microbiology, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK Antiviral Unit, Health Protection Agency Microbiology Services, Colindale, UK Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland

Unsupervised self-initiation of antiretroviral drugs in a newly diagnosed HIV-1 infected haemodialysis patient.

A 50-year-old Afro-Caribbean male with underlying hypertenion and chronic kidney disease stage 5 was found to be HIV-1 ntibody positive after annual screening for HIV in the renal unit. e had been expecting this result as his new female partner had een found to be HIV-1 infected having been admitted to hospial recently from the accident and emergency department with uberculosis. He had been on haemodialysis for the preceding years and was active on the national cadaveric kidney translant list, from which he was suspended pending control of his IV infection. His baseline HIV-1 RNA load was 92,400 copies/ml 5.0 log10) with a CD4 count of 251 cells/mm3 (19%). No antiretroiral resistance mutations were found on baseline HIV-1 drug esistance testing. The partner also had wild-type virus on baseine testing. He was booked in to the HIV clinic where he was o be started on combination antiretroviral therapy (cART) but efaulted his first clinic appointment and was seen 3 months after