A Survey of Latent Tuberculosis Screening and Treatment Practices in a Tertiary Centre.

Aim Knowledge of latent tuberculosis infection (LTBI) screening and treatment practices are lacking in Ireland, where LTBI is not programmatically surveyed or managed. The aim of this research was to describe current clinical practice when screening and treating patients for LTBI in a tertiary referral centre in Ireland. Methods A 17-question survey relating to LTBI screening and management practices with both open-ended questions and close ended multiple-choice questions was created using SurveyMonkey. The survey target sample was healthcare workers in the tertiary centre who direct LTBI screening and treatment for patients at risk of TB disease in their respective departments. Results The response rate to the survey was 45% (21/47). Seventy-one percent (15/21) of those surveyed responded to the question "What barriers exist to screening patients for latent TB in your clinical practice?". Fifty-three percent (8/15) said that they found it difficult to access LTBI testing and 27% (4/15) cited accessing the interferon-gamma release assay (IGRA) result as a barrier. Forty-three percent (9/21) responded that there was not a clear referral pathway for patients that they would like specialist input on when diagnosing and managing patients with LTBI. Conclusion Access to LTBI testing, LTBI test results, TB specialist services and the use of rifamycin-based regimens should be improved in this tertiary centre. Consideration should be given to developing a national LTBI education programme for healthcare professionals and updating national LTBI treatment guidelines.

Patients Accessing Ambulatory Care for HIV-infection: Epidemiology and Prevalence Assessment.

This study describes the demographics and treatment status of HIV-infected adults accessing ambulatory care in the Republic of Ireland and estimates diagnosed HIV prevalence rates. 3254 HIV-infected adults attended 1 of the 6 specialist HIV centres in the 12- month period 1st July 2009 to 30th June 2010. 2023/3254 (62%) were male, 1761/3133 (56%) Irish and 1048/3133 (34%) African. 1924/3098 (62%) resided in the Dublin area. The mean age was 39.8 years (SD 9.3); probable route of acquisition was available for 2898/3254 (89%); heterosexual acquisition accounted for 1442 (50%), MSM 777 (27%) and IDU 598 (21%). 2574/3202 (80%) were on highly active antiretroviral therapy (HAART). Of these 87% had HIV-RNA levels < 50cpm and 94% < 500cpm. The HIV diagnosed prevalence rate is estimated at 1.09/1000 nationally and at 2.25/1000 in the Dublin area for 15-59 year olds.

Sex trafficking in Ireland from a health care perspective.

Sex trafficking within Ireland is a hidden phenomenon. In 2010, 78 alleged victims were reported to An Garda Siochina and the recorded levels of human trafficking into Ireland have remained at this level for the last four years. Despite this, no Irish guidelines or referral pathways exist to assist health care professionals. This paper highlights that health care professionals are not aware of this occurrence nor have they been trained to identify victims. Due to a lack of awareness many potential opportunities to detect these victims may be missed. While there is no single set of symptoms or signs that differentiates sex-trafficked victims from other sex workers, an awareness of common physical and psychological health problems associated with sex trafficking by health care professionals may increase victim detection rates. This paper summarises indicators, approach mechanisms, screening questions and a referral guideline relevant to the Irish health care system. This step-by-step guide can be used by health care professionals who encounter such a situation.

NADH-dependent cytochrome b5 reductase and NADPH methemoglobin reductase activity in the erythrocytes of Oncorhynchus mykiss.

Methemoglobin is oxidized hemoglobin that cannot bind to or dissociate from oxygen. In fish, it is most commonly caused by exposure to excess nitrites and can lead to abnormal swimming, buoyancy, or death. The methemoglobin concentration in mammals is determined by the balance of oxidizing agents versus reducing enzymes in erythrocytes. The objective of our studies was to characterize the enzymes that reduce methemoglobin in fish erythrocytes. Whole blood was collected from healthy rainbow trout. Methemoglobin was induced in vitro by NaNO(2) exposure. Methemoglobin reduction in controls was compared to reduction in samples with added NADH, NADPH, or NADPH and methylene blue. Rainbow trout whole blood was also fractionated into cytosol, microsomal, and mitochondria/plasma membranes/nuclei fractions. The fractions were compared for NADH-dependent cytochrome b5 reductase (CB5R) activity and for nitrite induction of methemoglobin. The CB5R activity in rainbow trout erythrocytes was compared to the CB5R activity in equine, feline, and canine erythrocytes. Rainbow trout erythrocytes had significant NADPH methemoglobin reductase activity in the presence of methylene blue (P < 0.001). The CB5R activity was greatest (P < 0.001) in the plasma membrane/mitochondria/nuclei fraction. The CB5R activity in rainbow trout erythrocytes was not significantly different than canine or equine activity but was significantly lower than feline CB5R activity (P < 0.0001). Methemoglobin in rainbow trout erythrocytes can be reduced by CB5R or NADPH-dependent methemoglobin reductase. Unlike mammalian anuclear erythrocytes, which are dependent on soluble CB5R, the nucleated RBCs of rainbow trout use membrane-bound CB5R to reduce methemoglobin.

Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

Hepatitis B viral load and risk for liver cirrhosis and hepatocellular carcinoma in The Gambia, West Africa.

The main objectives of this study were to define the occurrence and levels of hepatitis B virus (HBV) DNA in asymptomatic HBV carriers, cirrhosis patients and hepatocellular carcinoma (HCC) cases from The Gambia, and to evaluate the risk for cirrhosis or HCC associated with HBV viremia. We used sensitive real-time quantitative PCR assays to measure HBV DNA in samples from a case-control study consisting of 60 asymptomatic HBV carriers, 53 cirrhotic patients and 129 HCC cases. Logistic regression was used to estimate the risks of cirrhosis and HCC associated with HBV-DNA levels and HBV e antigenemia (HBeAg) detection (a surrogate marker for viral replication). Detectable HBV viremia and HBeAg positivity were both significantly associated with cirrhosis (increasing risk by fourfold and 11-fold respectively) and with HCC (increasing risk by sixfold and threefold respectively). HBV-DNA levels were significantly higher in both HCC cases and cirrhotic patients compared to asymptomatic carriers (P < 0.01 for both). High-level HBV DNA (>10,000 copies/mL) was strongly associated with both HCC and cirrhosis (17- and 39-fold increased risk). Lower level HBV viremia (200-10,000 copies/mL) conferred a significant risk of HCC, although the association with cirrhosis was not significant. In conclusion, we find that high HBV-DNA levels are strongly associated with the serious sequelae of HBV infection, independent of HBeAg status. While risk for cirrhosis and for HCC notably increases at HBV-DNA levels >or=10,000 copies/mL, low-level viremia was also associated with significant risk for HCC.

Neurological morbidity among human T-lymphotropic-virus-type-1-infected individuals in a rural West African population.

BACKGROUND: Community-based neurological data about human T lymphotropic virus type 1 (HTLV-1) morbidity in sub-Saharan Africa are scarce. OBJECTIVES: To ascertain the prevalence of neurological morbidity, in particular tropical spastic paraparesis (TSP), among HTLV-1-infected subjects and to compare TSP prevalence in HTLV-1-infected with that in non-infected subjects in a rural West African population. METHODS: A cross-sectional study of HTLV-1-infected cases and controls (ratio 4:1) from a rural community (population approximately 10 000, HTLV-1 prevalence 7.7%). One neurologist masked to HTLV-1 serological status assessed all subjects. Clinical criteria were employed to diagnose TSP. RESULTS: From 205 eligible cases and controls, 139 were recruited with a mean age of 56 years, and 113 (81%) were HTLV-1-infected. 108/139 (78%) were female, and 8/113 HTLV-1 infected cases (7.1%) had a definite or probable TSP (all females; mean age 67 years) compared with 0/26 controls. Two with TSP were co-infected with HIV-2. Complaints of back pain and leg weakness were more common in HTLV-1-infected individuals (p = 0.03, p = 0.02), but no single symptom distinguished between subjects with and without TSP. CONCLUSION: We report a prevalence of TSP among HTLV-1-infected persons in this rural West African setting of 7.1%. There are difficulties excluding other potential aetiologies here.

The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats.

Acetaminophen (APAP) overdose in most species is associated with hepatotoxicity because of the metabolite N-acetyl-p-benzoquinoneimine (NAPQI). In dogs and cats, APAP overdose primarily causes methemoglobinemia and hemolysis. Although NAPQI has been proposed as the responsible intermediate in dogs and cats, it lacks chemical or pharmacokinetic characteristics that favor methemoglobin formation. We hypothesized that para-aminophenol (PAP) rather than NAPQI induces methemoglobinemia and that deficient arylamine N-acetyltransferase (NAT) activity in dogs and cats contributes to this species-dependent methemoglobinemia. Erythrocytes from dogs, cats, mice, and rats were exposed in vitro to APAP, NAPQI, and PAP. Only PAP induced methemoglobin and it induced more methemoglobin formation in dog and cat than rat and mouse erythrocytes. PAP also induced more methemoglobin in erythrocytes from Nat1/Nat2 knockout mice than wildtype (WT) mouse erythrocytes (P < 0.05), but less than in dog and cat erythrocytes (P < 0.01). APAP and PAP toxicity were compared in vivo in WT and Nat1/Nat2 knockout mice. APAP caused no hematotoxicity while PAP induced more methemoglobin in NAT1/NAT2 knockout mice than in WT mice (P < 0.05). These results support the hypothesis that PAP is the metabolite responsible for APAP-induced methemoglobinemia and that deficient NAT activity in dogs and cats contributes to this species-dependent toxicity.

An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166/253 of the cohort were receiving treatment at the time of this study and 95% (157/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

Application of a novel, rapid, and sensitive oligonucleotide ligation assay for detection of cancer-predicting mutations in the precore and basal core promoter of hepatitis B virus.

Hepatocellular carcinoma (HCC) and cirrhosis are important causes of mortality worldwide. Persistent hepatitis B virus (HBV) infection is a major cause of these diseases. Double mutations in the basal core promoter (BCP) (A1762T and G1764A) and precore (pre-C) (G1896A) regions of the virus are associated with progression to HCC. The current study is aimed at developing a simple method for screening and detecting BCP and pre-C mutations in HBV carriers. We have developed and validated an oligonucleotide ligation assay (OLA) to detect point mutations in the HBV core gene. We have applied OLA methods to samples from HBV-infected carriers recruited from the Gambia Liver Cancer Study (GLCS) comprising asymptomatic HBsAg carriers, patients with cirrhosis, and patients with HCC. We observed an 89.3% and 95.8% concordance between the OLA and DNA sequencing for BCP and pre-C mutations, respectively. OLA detected the mutations in single-strain infections and in infections with mixtures of wild-type and mutant viruses under conditions where sequencing detected only the single dominant strains. BCP mutations were detected in 75.7% of patients with advanced liver disease (cirrhosis/HCC) compared to 47.6% of asymptomatic carriers, while pre-C mutations were detected in 34.5% of advanced liver disease patients and in 47.6% of asymptomatic HBsAg carriers. There was a significant association between the presence of BCP mutations and advanced liver disease. In conclusion, OLA is a simple, economical, and reliable assay for detection of pre-C and BCP mutations. Its application can lead to improvement in diagnosis and clinical care in regions where HBV is endemic.

Assessing concentration of antibiotics in tissue during oral treatments against piscirickettsiosis.

The use of antimicrobials in aquaculture is increasingly being scrutinized. In Chile, piscirickettsiosis accounts for approximately 90% of the total volume of antibiotics used in marine aquaculture. Treatment failures are frequently reported, but there is limited information on why this occurs. Fish producers have started assessing the level of antibiotics in fish tissues during and immediately after in-feed treatments to determine if they are adequately medicating their fish. In this study, we evaluated the probability of finding antibiotic concentrations in muscle tissue above the minimum inhibitory concentration for 90% of the P. salmonis isolates (MIC90) recently tested in Chile, for two antibiotics commonly used in aquaculture. We found that the proportion of fish with antibiotic concentrations above the MIC90 varied, depending on the product used, species, day of sample collection, and size category of fish within a cage. The proportion of fish above the MIC90 was lower in fish treated with florfenicol than in fish treated with oxytetracycline. Using a mixed-effects logistic model, we modeled the probability of antibiotic concentrations above MIC90 when fish were treated with florfenicol. Our model suggested lower probabilities of having concentrations above MIC90 in Atlantic salmon than in rainbow trout when samples were collected 14 days after the treatment started compared to 7 days, and in the smaller fish within a cage. We discuss these findings and hypothesize about potential issues with treating large populations of fish with in-feed antimicrobials.

Pituitary tuberculoma: a rare cause of sellar mass.

INTRODUCTION: Pituitary tuberculosis is an uncommon cause of sellar mass [1]; the estimated prevalence worldwide is not known, and there have been no reports of the condition occurring in Ireland. Tuberculosis of the pituitary gland may present as a sellar mass or with symptoms of hypopituitarism. CASE PRESENTATION: A 41-year-old woman, with a short prodromal history without endocrine symptoms, was found to have pituitary tuberculosis after the demonstration of a sellar mass on MRI, and lumbar puncture findings consistent with lymphocytic meningitis. CONCLUSION: To our knowledge, this is the first published case of pituitary tuberculoma in Ireland.

Effectiveness of interferon-free therapy for the treatment of HCV-patients with compensated cirrhosis treated through the Irish early access program.

BACKGROUND: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV). METHOD: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined. RESULTS: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV). The discontinuation rate was 5% and the on-treatment mortality rate was 1%. CONCLUSION: The availability of interferon-free regimens represents a significant breakthrough for the treatment of HCV infection. Treatments options, with high SVR12 rates, are now available for patients with compensated cirrhosis who were unsuitable for treatment with interferon-based regimens. Data obtained from studies conducted in real world practice provide robust information fundamental for input into future economic evaluations for agents used for the treatment of HCV infection.

Results of a comprehensive infection control program for reducing surgical-site infections in coronary artery bypass surgery.

OBJECTIVE: To evaluate the efficacy of a comprehensive infection control program on the reduction of surgical-site infections (SSIs) following coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: 1,000-bed tertiary-care hospital. PATIENTS: Persons undergoing CABG with or without concomitant valve surgery from April 1991 through December 1994. INTERVENTIONS: Prospective surveillance, quarterly reporting of SSI rates, chlorhexidene showers, discontinuation of shaving, administration of antibiotic prophylaxis in the holding area, elimination of ice baths for cooling of cardioplegia solution, limitation of operating room traffic, minimization of flash sterilization, and elimination of postoperative tap-water wound bathing for 96 hours. Logistic regression models were fitted to assess infection rates over time, adjusting for severity of illness, surgeon, patient characteristics, and type of surgery. RESULTS: 2,231 procedures were performed. A reduction in infection rates was noted at all sites. The rate of deep chest infections decreased from 2.6% in 1991 to 1.6% in 1994. Over the same period, the rate of leg infections decreased from 6.8% to 2.7%, and of all SSI from 12.4% to 8.9%. The adjusted odds ratio (OR) for all SSIs for the end of 1994 compared to December 31, 1991, was 0.37 (95% confidence interval [CI95], 0.22-0.63). For deep chest and mediastinal infections, the adjusted OR comparing the same period was 0.69 (CI95, 0.28-1.71). CONCLUSIONS: We observed significant reductions in SSI rates of deep and superficial sites in CABG surgery following implementation of a comprehensive infection control program. These differences remained significant when adjusted for potential confounding covariables.

Evaluation of a rapid-format antibody test and the tuberculin skin test for diagnosis of tuberculosis in two contrasting endemic settings.

OBJECTIVE AND SETTING: We evaluated a rapid-format antibody card test and the tuberculin skin test for diagnosis of active tuberculosis (TB) in high (Cairo, Egypt) and low (St. Louis, USA) prevalence areas. DESIGN: Prospective study of hospitalized TB patients and controls with other chest diseases. RESULTS: Test performance varied significantly in the two study sites. The antibody test detected 87% of 71 smear-positive pulmonary TB cases (86% of smear-negative pulmonary cases and 48% of TB meningitis cases) in Egypt; specificity was 82%. The tuberculin test was highly sensitive in Egypt in subjects with pulmonary TB (100%) but not in those with meningitis (23%); specificity was 70%. The sensitivity and specificity of the antibody test in St. Louis were 29% and 79%, respectively; 50% of St. Louis TB cases and 15% of controls had positive tuberculin tests. CONCLUSIONS: This convenient antibody card test may have value for diagnosis of patients suspected of having TB in high prevalence areas like Egypt. However, the specificity of the test is too low for it to be useful as a screening test. Our results suggest that neither the antibody test nor the tuberculin test have much diagnostic utility in low prevalence settings like St. Louis.

Enterobacter cloacae in a haematology/oncology ward--first impressions.

The observation that Enterobacter cloacae has emerged as a cause of infection in a haematology/oncology ward prompted a prospective study over an eight-month period. Sensitivity to antibiotics, plasmid screening and typing methods were used to describe the epidemiology of the organism which was isolated from 22 patients. There was evidence of a limited amount of cross infection. No common sources were found. A large number of distinct strains were identified. E. cloacae infection was associated with prolonged profound leucopenia and broad-spectrum antibiotic therapy.

Paediatric HIV infection in the Republic of Ireland and the need for antenatal screening.

Thirty-seven HIV-infected children have been identified in the Republic of Ireland since 1985. Only 12 (32%) of 37 were followed prospectively from birth. Median age at diagnosis was 18 months (4 weeks to 8 years). In 32 (86%) of 37 cases, HIV infection was acquired as a result of transmission from mother to infant with intravenous drug use (IVDU) the most frequent risk factor for maternal acquisition of HIV. Of these 32 children, median maternal age at delivery was 24 (interquartile range (IQR) 23-26) years with median gestation at delivery 40 (IQR 38-40) weeks. Mode of delivery was by vaginal delivery in all 29 (91%) cases where mode of delivery is known. Only 2 infants were breastfed. Seven children have died at a median age of 9 (0.8-9.6) years. As of July 1997, 12 children have AIDS, 14 have symptomatic disease without AIDS and 3 are asymptomatic. Median age at AIDS diagnosis was 2.6 (0.1-6.5) years. Median survival time post-AIDS diagnosis was 6.5 (1.8-8.3) years. Of 29 living children, 24 mothers and 14 fathers are HIV infected and only 14 children live with both parents. Childhood HIV infection has had a significant personal, social and financial impact on both Irish families and society in general. More effective measures to control HIV infection among intravenous drug users are needed. Antenatal detection of HIV-infected mothers is paramount as vertical transmission can be successfully prevented and morbidity and death can be prevented in the infected infant.

Extramedullary plasmacytoma in a horse with ptyalism and dysphagia.

A Clydesdale mare was examined for weight loss, inappetence, ptyalism, and dysphagia. The main abnormality revealed by serum biochemistry was a marked hyperglobulinemia, and protein electrophoresis revealed a monoclonal gammopathy in the gamma region. The urine was positive for Bence Jones proteins. These findings suggested a plasma cell tumor. The neoplasm could not be located with extensive antemortem examination. At postmortem, neoplastic cells morphologically compatible with plasma cells and positive for equine IgG with imunoperoxidase staining infiltrated the pericardium, mediastinal stromal tissues, adrenal glands, meninges, atrioventricular valves, aorta, abdominal and thoracic fat, and nerves, including the trigeminal nerve. The neoplastic cells invading the cranial nerves were responsible for many of the presenting signs.