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1.
J Viral Hepat ; 30(12): 914-921, 2023 12.
Article in English | MEDLINE | ID: mdl-37700492

ABSTRACT

Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme. Between July 2017 and June 2022, data were collected prospectively on HCV test offer and uptake rates, HCV Antibody (HCV-Ab) and HCV-RNA positivity, treatment starts and outcomes for new inmates incarcerated in three prisons. Rates of HCV-Ab and RNA positivity at reception, incidence of new HCV infections and reinfection following treatment were determined. From a total of 39,652 receptions, 33,028 (83.3%) were offered HCV testing and 20,394 (61.7%) completed testing. Including all receptions, 24.5% of tests (n = 4995) were HCV-Ab positive and 8.4% of tests (n = 1713) were HCV-RNA positive. When considering the first test for each individual (median age 34 years; 88.1% male), 14.8% (n = 1869) and 7.2% (n = 905) were HCV-Ab and HCV-RNA positive, respectively. The incidence of new HCV-Ab and RNA positivity was 5.1 and 3.3 per 100 person-years, respectively. Of 1145 HCV viraemic individuals, 18 died within 6 months and 150 were rapidly transferred out of area, leaving 977 individuals with outcomes. Of these, 835 (85.5%) received antivirals and 47 spontaneously cleared the infection, leaving 95 (9.7%) untreated. 607 (72.7%) achieved SVR. 95 patients had reinfection post-treatment (rate 10.1 cases per 100 person-years). Testing for HCV has increased in our prisons and the majority with viraemia are initiated on antiviral treatment. Reassuringly, a significant fall in frequency of HCV-RNA positivity at prison reception was observed suggesting progress towards HCV elimination.


Subject(s)
Hepatitis C , Prisoners , Substance Abuse, Intravenous , Humans , Male , Adult , Female , Prisons , Reinfection , Substance Abuse, Intravenous/epidemiology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepacivirus/genetics , RNA , England/epidemiology , Hepatitis C Antibodies , Antiviral Agents/therapeutic use
2.
J Viral Hepat ; 26(1): 101-108, 2019 01.
Article in English | MEDLINE | ID: mdl-30315691

ABSTRACT

With recent advances in antiviral therapy, there is an opportunity to eliminate hepatitis C virus (HCV) from the UK population. HCV is common in incarcerated individuals, with previous estimates suggesting ~7% of the UK prison population is anti-HCV antibody positive. Increasing diagnosis and treatment of HCV in prison is a priority in seeking to eliminate transmission in the general population. Thus the study aimed to assess the impact implementation of: (a) A universal offer of blood borne virus testing (UOBBVT) using dry blood spot testing for prisoners at reception to increase diagnosis; (b) Telemedicine clinics (TC) within North East England (NEE) prisons to increase HCV treatment rates. UOBBVT was initially implemented at Her Majesty's Prison (HMP) Durham, commencing March 2016. From March 2016 to February 2017, 2831 of 4280 (66%) new receptions were offered blood borne virus (BBV) testing. Of these, 1495 (53% of offered) accepted BBV testing, of whom 95 (6.4%) were HCV antibody positive, with 47 of those 95 (49.5%) HCV RNA positive, suggesting a prevalence of active infection in the tested population of 3.1% (95% CI 2.4%-4.2%). Between August 2015 and October 2017, 80 individuals were seen in the TC and 57 (71%) commenced antiviral therapy. Of those with known outcome (n = 29), 100% achieved sustained virological response. In the year prior to implementation, only four patients received HCV treatment. In conclusion, a universal offer of BBV testing to inmates presenting at HMP reception coupled with linkage into specialist care via TC can substantially increase rates of testing, diagnosis and treatment of HCV in this high-prevalence population.


Subject(s)
Dried Blood Spot Testing/statistics & numerical data , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Prisoners/statistics & numerical data , Telemedicine/statistics & numerical data , Antiviral Agents/therapeutic use , England , Hepatitis C/prevention & control , Hepatitis C Antibodies/blood , Humans , Male , Pilot Projects , Prevalence , Prisons
3.
Int J Infect Dis ; 74: 97-99, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30048817

ABSTRACT

OBJECTIVES: This study sought to identify the incidence of, and risk factors for, acute kidney injury (AKI) in adults treated with parenteral aciclovir. METHODS: A single-centre retrospective cohort study of prospectively acquired electronic clinical, pharmacy and laboratory data was performed with approval of the Caldicott guardian. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria, prior to analysis of baseline patient and treatment-related risk factors. RESULTS: 269 aciclovir treatment episodes were identified in 268 patients. Overall incidence of AKI was 13%. Half of AKI episodes were KDIGO grade 2/3. In univariate analysis, AKI occurred more frequently in patients with pre-existing chronic kidney disease (CKD), diabetes, and in patients treated with higher daily doses of aciclovir. There was also a trend to increased age in patients with AKI. In a binomial logistic regression model only CKD and daily dose remained significant independent factors. CONCLUSIONS: AKI is an important side effect of parenteral aciclovir, the incidence of which is comparable to established nephrotoxic drugs such as aminoglycosides. Patients with pre-existing chronic kidney disease or receiving higher total doses are at greatest risk, reinforcing the clinical importance of appropriate dose adjustment for ideal body weight and baseline renal function.


Subject(s)
Acute Kidney Injury/etiology , Acyclovir/adverse effects , Acute Kidney Injury/metabolism , Acyclovir/administration & dosage , Administration, Intravenous , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Kidney/drug effects , Kidney/metabolism , Logistic Models , Male , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
4.
J Med Microbiol ; 66(9): 1291-1296, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28868996

ABSTRACT

Purpose. To evaluate the Luminex NxTAG respiratory pathogen panel (NxTAG RPP) for the detection of respiratory viruses in clinical samples from patients with the symptoms of respiratory infection.Methodology. The NxTAG RPP was compared to an in-house multiplex real-time PCR panel (LDT) for the detection of respiratory viruses in 314 clinical samples from patients with the symptoms of respiratory infection.Results. Thirty-one samples were negative in both tests and 193 samples contained a single virus that was detected in both tests. Polymicrobial infections were detected in 74 samples, with 268 samples overall having concordant results in both assays, and there were a total of 51 discordant results in 44 samples. Two samples were invalid in the NxTAG RPP assay and were excluded from the final analysis. The overall agreement between the NxTAG RPP and LDT was very high, as indicated by the Kappa coefficients, which ranged from 0.85 for metapneumovirus up to 0.96 for RSV A, and the overall percentage agreement values of 96.2 % for enterovirus/rhinovirus and 100 % for influenza A, influenza B, PIV 4 and RSV B.Conclusion. The NxTAG RPP is a sensitive and specific test for the detection of respiratory viruses and the high sample throughput and low hands-on time make the NxTAG RPP assay suitable for screening clinical samples for respiratory pathogens.

5.
Eur J Gastroenterol Hepatol ; 28(10): 1172-8, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27388147

ABSTRACT

AIMS/OBJECTIVES/BACKGROUND: Individuals with current or previous infection with the hepatitis B virus (HBV) can experience viral reactivation when treated with immunosuppression. Rituximab, an anti-CD20 antibody used to treat many diseases, has potent immunosuppressant effects with a high risk of causing HBV reactivation. Reactivation can range from elevated liver enzymes to acute severe hepatitis with liver failure and a significant mortality risk. HBV screening and appropriate use of prophylactic antiviral therapy can prevent reactivation. This work describes the introduction of a local policy for HBV testing in patients before rituximab treatment and assesses its impact. METHODS AND RESULTS: A baseline review (before policy introduction) of 90 patients showed that only 21 (23%) had hepatitis B surface antigen (HBsAg) and 17 (19%) had hepatitis B core antibody (anti-HBcAb) tested before receiving rituximab. Following introduction of the policy (on the basis of international guidelines), improved laboratory reporting protocols and targeted education sessions, two further reviews of HBV testing rates among patients being initiated onto rituximab were performed. There was a marked increase in pre-rituximab testing for HBsAg from 23 to 79% and for anti-HBcAb from 19 to 78%. Throughout the study period, a total of one (0.8%) HBsAg-positive and six (4.7%) anti-HBcAb-positive patients were identified. CONCLUSIONS: This work clearly indicates that simple strategies can markedly improve appropriate HBV screening. In our cohort, 6% (of whom only 43% had recognized HBV risk factors) required antiviral prophylaxis, which emphasizes the importance of universal screening before rituximab. Reinforcement of the guidelines and ongoing education is needed to further increase testing rates.


Subject(s)
Hepatitis B virus/drug effects , Hepatitis B/diagnosis , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Rituximab/therapeutic use , Virus Activation/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Education, Medical, Continuing , Female , Guideline Adherence , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , Humans , Immunosuppressive Agents/adverse effects , Inservice Training , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians' , Predictive Value of Tests , Program Evaluation , Retrospective Studies , Risk Factors , Rituximab/adverse effects , Young Adult
6.
Sci Transl Med ; 7(307): 307ra154, 2015 Sep 30.
Article in English | MEDLINE | ID: mdl-26424569

ABSTRACT

Type I interferon (IFN-α/ß) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/ß in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/ß receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/ß. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/ß responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/ß in human antiviral immunity.


Subject(s)
Antiviral Agents/metabolism , Immunity , Receptor, Interferon alpha-beta/deficiency , Fatal Outcome , Genes, Recessive , Genetic Complementation Test , Humans , Infant , Interferons/metabolism , Receptor, Interferon alpha-beta/metabolism , Signal Transduction
8.
Frontline Gastroenterol ; 5(2): 111-117, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24683447

ABSTRACT

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.

11.
Proc Natl Acad Sci U S A ; 110(8): 3053-8, 2013 Feb 19.
Article in English | MEDLINE | ID: mdl-23391734

ABSTRACT

Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections.


Subject(s)
Genetic Predisposition to Disease , STAT2 Transcription Factor/genetics , Virus Diseases/genetics , Base Sequence , Cells, Cultured , Child, Preschool , DNA Primers , Female , Humans , Interferon Type I/metabolism , Oligonucleotide Array Sequence Analysis , Pedigree , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Virus Diseases/metabolism
12.
J Infect ; 62(1): 87-92, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21073896

ABSTRACT

OBJECTIVES: Viral load (VL) measurement is critical for monitoring the effectiveness of highly active antiretroviral therapy (HAART). HAART aims to maintain plasma HIV RNA at undetectable levels. A VL <50 copies/ml was previously considered undetectable. After introducing more sensitive assays many patients with VL <50 copies/ml were found to have very low-level viraemia (VLLV), defined as a detectable VL <40 copies/ml. This study aimed to determine the significance of VLLV. METHODS: This retrospective case-control study included 69 individuals on HAART with VLLV. Immunological and virological outcomes over 36 months were compared to those of 70 well-matched controls with persistently undetectable VL. RESULTS: We detected no significant association between VLLV and the development of virological failure or inferior immunological outcomes. However, individuals with VLLV were significantly less likely to achieve subsequent sustained virological suppression (VL <50 copies/ml, p<0.001), including completely undetectable suppression (undetectable VL <40 copies/ml, p=0.002). CONCLUSIONS: The significance of VLLV has been uncertain. Our results clearly suggest that VLLV is predictive of future suboptimal virological control, particularly a reduced likelihood of achieving virological suppression. Further work should confirm our findings and evaluate strategies for managing VLLV in HAART-treated patients.


Subject(s)
HIV Infections/drug therapy , HIV Infections/virology , Viral Load/drug effects , Viremia/diagnosis , Viremia/virology , Adult , Aged , Antiretroviral Therapy, Highly Active , Female , HIV Infections/immunology , HIV-1/drug effects , HIV-1/isolation & purification , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Viral Load/immunology , Viremia/immunology
16.
Indian Pediatr ; 41(10): 1045-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15523132

ABSTRACT

We describe a rare case of non-antibiotic associated severe C. difficile diarrhea in a 7-week-old boy. He had massive fluid loss and electrolyte imbalance. He required total parentral nutrition for 10 days and eventually recovered with oral metronidazole. Most of the reported cases in literature are associated with prior antibiotic exposure or in hospitalized patients.


Subject(s)
Clostridioides difficile , Clostridium Infections/therapy , Diarrhea, Infantile/microbiology , Anti-Infective Agents/therapeutic use , Clostridium Infections/drug therapy , Diarrhea, Infantile/drug therapy , Humans , Infant , Male , Metronidazole/therapeutic use , Parenteral Nutrition, Total
17.
Emerg Infect Dis ; 10(7): 1282-9, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15324550

ABSTRACT

An outbreak of Q fever occurred in South Wales, United Kingdom, from July 15 through September 30, 2002. To investigate the outbreak a cohort and nested case-control study of persons who had worked at a cardboard manufacturing plant was conducted. The cohort included 282 employees and subcontractors, of whom 253 (90%) provided blood samples and 214 (76%) completed questionnaires. Ninety-five cases of acute Q fever were identified. The epidemic curve and other data suggested an outbreak source likely occurred August 5-9, 2002. Employees in the factory's offices were at greatest risk for infection (odds ratio 3.46; 95% confidence interval 1.38-9.06). The offices were undergoing renovation work around the time of likely exposure and contained straw board that had repeatedly been drilled. The outbreak may have been caused by aerosolization of Coxiella burnetii spore-like forms during drilling into contaminated straw board.


Subject(s)
Coxiella burnetii , Disease Outbreaks , Industry , Occupational Exposure , Paper , Q Fever/epidemiology , Case-Control Studies , Coxiella burnetii/isolation & purification , Humans
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