Tuberculosis Prophylaxis Research Articles

Follow-up testing of interferon-gamma release assays are useful in ankylosing spondylitis patients receiving anti-tumor necrosis factor alpha for latent tuberculosis infection.

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFα). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFα and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFα, including type and treatment duration. The median duration of anti-TNFα was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFα in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFα.Graphical

Ülkemizde bir status epileptikus nedeni: İzoniazid zehirlenmesi

A cause of status epilepticus in Turkey: Isoniazide intoxication In Turkey, isoniazide (INH) is widely used for the prophylaxis and treatment of tuberculosis. Acute overdose of INH may cause metabolic acidosis, repetitive seizures and coma. A 17 year old patient was admitted to our emergency clinic with generalized convulsive status epilepticus. Her initial laboratory studies revealed hyperglycemia, leucosytosis, metabolic acidosis, hypopotasemia and high creatinin kinase (CPK) levels. Her seizures continued under standard anticonvulsive therapy. As acute toxic exposure of INH was suspected, piridoxin infusion was started. Her seizures ended. She became awake, alert and responsive. On the third day, serum transaminase and CPK levels increased. As a conclusion, INH is widely used for treatment of tuberculosis in our country. That’s why INH toxicity should be suspected in any patient with refractory seizures, hyperglycemia and metabolic acidosis.

TUBERCULOSIS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS.

Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50% and is higher in allogeneic HSCT than in autologous. There is no consensus regarding the screening with tuberculin skin test or QuantiFERON-TB gold, primary prophylaxis for latent TB, and whether the epidemiologic query should be emphasized in developing countries with high prevalence of TB.

Central Nervous System vasculitis associated with Hepatitis C virus infection: A brain MRI-supported diagnosis

BackgroundThe Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, being the Central Nervous System (CNS) rarely involved. Case reportWe report a case of a 54year-old black man with arterial hypertension who presented with progressively worsening headaches, apathy, somnolence and left hemiparesis. Brain MRI showed an acute ischemic lesion in the left anterior cerebral artery (ACA) and an old ischemic infarct in the right ACA territory. Brain MRI with gadolinium revealed mural thickening and contrast enhancement of the A1 and A2 segments of the ACAs, of the middle and distal basilar artery and of the P1 segment of the left posterior cerebral artery, suggesting active vasculitis. Digital angiography confirmed those irregularities and stenosis. Laboratory evaluation revealed ESR (73mm/h), transaminase elevation, elevated HCV viral load genotype 2, positive IGRA, negative cryoglobulins, CSF protein elevation with oligoclonal bands (mirror pattern) and no pleocytosis; investigation excluded other infectious causes. Pegylated interferon alpha-2a and ribavirin, corticotherapy and tuberculosis prophylaxis were started with clinical and imagiological improvement. ConclusionThe typical inflammation signs of the vascular wall demonstrated by the gadolinium-enhanced MRI strengthened the hypothesis of CNS vasculitis. The association with HCV infection is rare but should be investigated once specific therapeutic is required.

Executive summary of the Consensus Document of GeSIDA and Spanish Secretariat for the National Plan on AIDS on combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2013)

In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4+ lymphocyte count is <500cells/μL; if the CD4+ lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >105copies/mL, CD4+ lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined.

Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies

Infection is one of the leading causes of morbidity and mortality in systemic lupus erythematosus (SLE). Bacterial infections are most frequent, followed by viral and fungal infections. The impaired cellular and humoral immune functions seen in patients with SLE are predisposing conditions, whilst disease activity, prednisone doses over 7.5-10 mg/day, high doses of methylprednisolone or cyclophosphamide are well-recognised risk factors for infection. The first six months after rituximab treatment and the use of more than three courses are also associated with an increased susceptibility for infection. It has not been established whether belimumab, azathioprine and mycophenolate mofetil increase the risk of serious infections. Most vaccines are effective and safe in SLE patients, although vaccination should be avoided during periods of active disease. Live virus vaccines are contraindicated for immunosuppressed patients. Influenza and pneumococcal vaccines are universally recommended. Tuberculosis prophylaxis should be considered in selected cases. Therefore, it is advisable not to exceed doses of 5 mg/day of prednisone in chronic treatment. Methylprednisolone and cyclophosphamide should be used in low-dose regimens. Antimalarials have a well-known protective role against infection, in addition to other beneficial properties, thus, hydroxychloroquine is recommended for all SLE patients where no contraindication exists.

365 Predictors of silicosis in an industry wide study in the South African gold mining industry

ObjectivesDespite the scale of the silicosis problem in the South African goldmining industry, studies in active miners are scarce. A large randomised cluster trial of isoniazid tuberculosis prophylaxis provided an...

Donor-Derived Tuberculosis (TB) Infection in Lung Transplant Despite Following Recommended Algorithm

Donor-Derived Tuberculosis (TB) Infection in Lung Transplant Despite Following Recommended Algorithm

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade

Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.

Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.). Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

More than just great quotes: An introduction to the Canadian Tri-Council's qualitative requirements.

Although at times misunderstood by the general research community, qualitative research has developed out of diverse, rich and complex philosophical traditions and theoretical paradigms. In the most recent Canadian Tri-Council policy statement on the ethical conduct of research involving humans, a chapter was devoted to a summary of methods and methodological requirements that characterize robust qualitative research, despite the diversity of approaches. To dispel common misperceptions about qualitative research and introduce the unfamiliar reader to these requirements, the work of a qualitative study on isoniazid preventive therapy for prophylaxis of tuberculosis published in AIDS is critiqued alongside each of the Tri-Council's nine requirements.

Anti-Tuberculous Prophylaxis after Renal Transplantation: Are Patients Being Treated?

Background: Renal transplantation provides the optimal renal replacement therapy albeit in the context of an associated immunocompromised state. This places recipients at increased risk of infective complications with Tuberculosis 20 - 70 times more common in renal transplant recipients. Recent guidelines regarding routine Tuberculosis prophylaxis have been published in the United Kingdom by the British Thoracic Society (mandating Isoniazid 300mg for six months). However, concerns have been raised about drug interactions with immunosuppressnts as well as the risk of hepatic dysfunction. We aimed to investigate prophylactic regimens in use amongst Renal Transplant units nationally. This is an area of particular relevance given the increasing prevalence of the disease nationally combined with the documented deleterious effects on both patient and graft outcome. Methods: All renal transplantation centres across Great Britain and Ireland were approached for tuberculosis prophylaxis protocols post-transplantation. This was achieved via the designated renal transplant pharmacist for each centre who was approached by e-mail and telephonically sequentially with a standardised questionnaire. This enquired as to medication used for prophylaxis, including dosage and duration of treatment as well as patient demographics warranting inclusion for treatment. Results: 24/25 (96%) transplant centres in Great Britain and Ireland responded. All centres giving prophylaxis did so in the form of Isoniazid with variable dosages given across the majority of centres although a propensity for either 200mg or 300mg was noted. (no prophylaxis: 4 centres; Isoniazid 200mg: 5 centres; Isoniazid 300mg: 8 centres; others: 6 centres) In addition, duration of prophylaxis offered also varied, with many centres offering no prophylaxis and 6 months prophylaxis having the highest incidence (no prophylaxis: 4 centres; 6 months:7 centres; 1year:4 centres; lifelong:3 centres; others: 5 centres.) There appears to be no patient demographic standard for prophylaxis in the United Kingdom with great variance amongst individual units. Discussion: Tuberculosis remains an important pathogen in the immunocompromised host particularly in areas with high prevalence of the disease. Prophylaxis therefore has a potentially crucial role in the post-transplant population to prevent possible graft dysfunction and patient morbidity. There appears to be no national consensus or adherence to recently published guidelines to ensure standardised ‘best practice’. This is occurring despite that the fact that within certain urban communities nationally, tuberculosis has reached endemic levels. It is important that a rigorous approach to TB prophylaxis is undertaken to prevent unnecessary morbidity and mortality in the transplant population. Guidelines should be adhered to thereby ensuring optimal outcomes, particularly in light of the great variability in prophylactic regimens nationally.

Correlación de la respuesta a antígenos de Mycobacterium tuberculosis y la prueba cutánea tuberculina en pacientes con artritis reumatoide

Rheumatoid arthritis patients under treatment with anti-TNF-α are at a high risk of developing active tuberculosis, and therefore, screening for latent tuberculosis infection is recommended before anti-TNF-α therapy. To compare the tuberculin test and IFNγ production induced by culture filtrate proteins(CFPs) and Mycobacterium tuberculosis-specific CFP-10 antigens in rheumatoid arthritis patients. An analytic transversal study was conducted in rheumatoid arthritis patients treated at Hospital Universitario San Vicente Fundación between January and December 2007. IFNγ production in response to CFPs and CFP-10 was measured in the supernatants of whole blood cultures and evaluated for correlations with tuberculin reactivity. The degree of concordance between both tests was also established. Forty-five patients were included, of which 14 (31.1%) had a tuberculin reaction of ≥10 mm of induration, 9 (20%) produced IFNγ in response to CFP-10, and 7 were positive for both tests. The correlation between tests was r=0.53 (IC 95%:0.28-0.72), and the global concordance between tests was80%, with a Kappa coefficient of 0.48 (IC95%:0.20-0.76). Only two tuberculin (-)/CFP-10+ "anergic" patients were observed. By contrast, six tuberculin +/CFP-10(-) "tuberculin false-positive" patients were observed. These data suggest that the tuberculin test is not an appropriate tool for determining the need for tuberculosis prophylaxis.

Is Isoniazid Safe for Liver Transplant Candidates With Latent Tuberculosis?

Isoniazid (INH) is recommended for tuberculosis prophylaxis in non–liver transplant recipients. However, there is a great reluctance to prescribe this agent for liver transplant candidates and recipients due to the risk of precipitating further hepatic decompensation. We analyzed the records of liver transplantation candidates undergoing a purified protein derivative (PPD) test (tuberculosis skin test) between 2008 and 2010. Patients with no respiratory symptoms, PPD test > 10 mm, and normal chest radiography were diagnosed as latent tuberculosis and prescribed INH (300 mg) per day for 6 months. The 191 patients submitted to a PPD test and those on tuberculosis prophylaxis underwent blood tests and clinical evaluations monthly to detect hepatotoxicity of patients The 33 subjects (17.2%) with a PPD test ≥ 10 mm displayed an average Model for End-stage Liver Disease score of 20 (range: 9–29) and Child-Pugh A/B score. The main causes for liver disease were chronic hepatitis C, hepatocellular carcinoma, and alcohol abuse. Among 27 patients who received INH, 18 (66.6%) completed 6 months of prophylaxis. Eight who had shorter treatment courses of 2 to 4 months had undergone transplantation. One patient had to stop treatment because of clinical decompensation due to spontaneous bacterial peritonitis without a transaminases elevation. Six patients did not receive INH: previous tuberculosis treatment, transplantation before initiating prophylaxis, or removal from the liver candidacy list. No patient showed clinical decompensation or laboratory abnormalities associated with use of INH. The average values of alanine aminotransferase pre- and posttreatment were similar (69 and 72 U/l respectively), demonstrating that tuberculosis prophylaxis with INH was safe for liver transplant candidates.

Hepatobiliary Quiz-3 (2012)

Hepatobiliary Quiz-3 (2012)

Hepatobiliary Quiz-3 (2012)

Hepatobiliary Quiz-3 (2012)

Isoniazid Pharmacokinetics, Pharmacodynamics, and Dosing in South African Infants

There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing. Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L. In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L. INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L.

Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation

A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28-month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette-Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT-GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT-GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT-GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] -0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI -0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT-GIT outcomes was 2.80 per 100 person-years (95% CI 0.07-15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person-years (95% CI 0-8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT-GIT test was poor, regardless of BCG vaccination history.

Miliary tuberculosis occurred after immunosuppressive drug in PNH patient with completely cured tuberculosis; a case report

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder that presents with hemolytic anemia, marrow failure and thrombophilia. During acute attacks, corticosteroid can alleviate the hemolytic paroxysm, but the prolonged administration induces serious toxicity including immunosuppression. So American thoracic society (ATS) for tuberculosis (TB) recommends prophylactic anti-TB medication in patients with a long-term steroid therapy. However, in the patient who was treated for active TB in the past, there are no guidelines of the test for determining patients who have latent TB infection (LTBI) and no recommendations of TB prophylaxis if there is no evidence of reactivation at present. A 40-year-old male patient presented with fever and aggravated weakness for a week. He was diagnosed with PNH a month ago and took corticosteroid for 3 weeks. In the past, he was diagnosed with pulmonary TB and completely cured after treatment. According to guideline, he was not indicated with TB prophylaxis. However, he caught miliary TB, progressed to acute respiratory distress syndrome. We experience this embarrassing case, and emphasize the need to investigate multicentral TB prevalence and to make the guidelines of anti-TB medication in subgroups of hematologic diseases including PNH.

Anti‐tuberculosis prophylaxis following renal transplantation: acceptable variations?

Guidelines suggest tuberculosis (TB) prophylaxis in renal transplant recipients originating in endemic areas or in those at risk from non-endemic countries. Concern remains that these guidelines may fail to provide adequate prophylaxis for a cohort of patients who remain at potential risk. We aimed to determine variation patterns among different transplant units within the United Kingdom (UK) with regard to TB prophylaxis policy. The renal pharmacist at each of the 25 UK renal transplant centers was contacted. Specific information was obtained relating to drug prophylaxis given, duration of treatment, as well as which transplant recipients were eligible for treatment. A 96% response rate (24/25 centers) was achieved. Prophylaxis regimens varied from no prophylaxis to isoniazid 300mg given life-long. The most common duration of treatment was 6months post transplantation (at 7 centers). Variations existed in the concurrent use of pyridoxine. A wide discrepancy was seen in the determination of who should receive prophylaxis, with no clear association with frequency of TB incidence in the region. A marked discrepancy exists among national renal transplant units in pharmacologic prophylaxis for TB, as well in the selection of individuals for this treatment.