Prophylactic Isoniazid Therapy Research Articles

Monitoring Adalimumab concentration, Adalimumab antibodies, fecal calprotectin, and QuantiFERON test positivity in patients with inflammatory bowel disease

<p><strong>Introduction.</strong> Inflammatory bowel diseases (IBD) are a serious global health problem affecting mostly younger and middle-aged persons. Despite the availability of variety of treatment approaches, the disease often progresses unpredictably. Biological drugs offer hope for IBD treatment. Our research share our preliminary findings regarding the monitoring of adalimumab (ADM) and adalimumab antibodies (ADA) concentrations, fecal calprotectin levels, and the frequency of QuantiFERON test positivity in IBD patients treated with biological drugs.<strong> </strong></p> <p><strong>Methods.</strong> The study was designed as a retrospective, descriptive, single-center study and was conducted at the University Clinical Center of the Republic of Srpska, Banja Luka, from January 2018 to June 2022. Medical records of patients treated at the Internal Medicine Clinic were analyzed. Patients were categorized based on underlying disease and duration of biological therapy. ADM and ADA concentrations were monitored at intervals, and QuantiFERON test positivity and fecal calprotectin levels were recorded. Statistical methods, including analysis of Variance (ANOVA) and paired t-test were performed using the SPSS program version 29.</p> <p><strong>Results.</strong> Medical records of 117 patients were analyzed. Most of them, 44 were treated with adalimumab. Male patients were predominant (59.10%) in our study over females. Patients were also categorized based on the length of biological therapy. ADM and ADA concentrations increased with time (after 6, 12, 18 and 24 months), but without statistical significance. Fecal calprotectin levels decreased after 12 and 24 months of treatment. Out of the total number of patients, 53.83% of QuantiFERON positive patients were treated with adalimumab. Prophylactic isoniazid therapy was carried out in 63.6% of patients.</p> <p><strong>Conclusion. </strong>Our initial experience in monitoring biological drug concentrations and fecal calprotectin levels in IBD patients showed a decrease in fecal calprotectin levels and an increase in ADM and ADA concentrations over time but there were no statistically significant differences.</p>

Initiation of Isoniazid Prophylactic Therapy among Newly Diagnosed HIV-Positive Persons in Three High HIV-Burden Districts of South Africa

Background: South Africa is experiencing the worst HIV-driven tuberculosis (TB) epidemic in the world. More than 300,000 new cases of active TB are reported in the country each year with 60% co-infected with HIV. Isoniazid preventive therapy (IPT) is a key public health intervention for the prevention of TB among people living with HIV (PLHIV) and is recommended as part of a comprehensive HIV and AIDS care strategy. However, program data suggests that coverage of IPT service to be very low. This study aims to assess IPT initiation rate among newly diagnosed HIV-positive persons in three high HIV-burden districts of South Africa. Methods: A cross-sectional study was conducted using routine data generated from pre-ART and ART programs in 35 purposively selected primary health care (PHC) clinics in South Africa. The facilities were selected from three high HIV-burden districts with a mix of urban and rural settings. TB screening and IPT initiation status was assessed within a window period of one-year post HIV diagnosis. Initiation rate of IPT services among newly diagnosed HIV-positive persons was assessed. The chi-squared test was used to determine whether there was a significant difference in the proportion of newly diagnosed HIV-positive persons who were initiated on IPT by sex, age group, pregnancy status, health facility, district and location of facility. Results: We identified 12,413 newly diagnosed HIV patients aged 12-years-old and above between June 1, 2014 and March 31, 2015. TB screening was not conducted among 33% of newly diagnosed HIV-positive persons to rule out or confirm the presence of active TB. IPT was initiated in 42.2% of known IPT-eligible HIV-positive persons. Initiation of IPT services was lower in younger patients aged 12 to 20-years-old compared to older patients. The proportion of pregnant women who were initiated on IPT was higher compared to the proportion in non-pregnant women (51.0% and 40.1% respectively; P Conclusion: This analysis shows that initiation rate of IPT services among newly diagnosed HIV positive persons was low in the 35 participating facilities during the period under investigation. There was variability in IPT initiation rates across the facilities included in this study and among different sub-groups of the study sample. This study has identified specific population groups and geographic settings that should be targeted by programs to improve IPT services. There is a need to identify factors that contributed to the low initiation rate of IPT services among young HIV positive persons, women with unrecorded pregnancy status and in facilities located in inner city of Johannesburg. Customized interventions tailored to the specific needs of facilities and population groups should be instituted to strengthen uptake of IPT services.

Predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy at Suhul Hospital, Tigrai, Northern Ethiopia: a retrospective follow-up study

BackgroundEthiopia is striving to achieve a goal of “zero human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-related deaths.” However, little has been documented on the factors that hamper the progress towards achieving this goal. Therefore, the ultimate aim of this study was to determine predictors of mortality among adult people living with HIV/AIDS on antiretroviral therapy (ART).MethodsA retrospective follow-up study was employed on all adult HIV/AIDS patients who started ART between January 1 and December 30, 2010, at Suhul Hospital, Tigrai Region, Northern Ethiopia. Data were collected by trained fourth-year Public Health students using a checklist. Finally, the collected data were entered into SPSS version 16. Then after, Kaplan-Meier curves were used to estimate survival probability, the log-rank test was used for comparing the survival status, and Cox proportional hazards model were applied to determine predictors of mortality.ResultsThe median follow-up period was 51 months (ranging between 1 and 60 months, inter-quartile range (IQR) = 14 months). At the end of follow-up, 37 (12.5%) patients were dead. The majority of these cumulative deaths, 19 (51.4%) and 29 (78.4%), occurred within 3 and 4 years of ART initiation respectively. Consuming alcohol (adjusted hazard ratio (AHR) = 2.23, 95% CI = 1.15, 4.32), low body weight (AHR = 2.38, 95% CI = 1.03, 5.54), presence of opportunistic infections (AHR = 2.18, 95% CI = 1.09, 4.37), advanced WHO clinical stage (AHR = 2.75, 95% CI = 1.36, 5.58), and not receiving isoniazid prophylactic therapy (AHR = 3.00, 95% CI = 1.33, 6.74) were found to be independent predictors of mortality.ConclusionThe overall mortality was very high. Baseline alcohol consumption, low body weight, advanced WHO clinical stage, the presence of opportunistic infections, and not receiving isoniazid prophylactic therapy were predictors of mortality. Strengthening behavioral and nutritional counseling with close clinical follow-up shall be given much more emphasis in the ART care and support program.

Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.

To compare the incidence of anti tuberculosis drug-induced hepatotoxicity (ATDH) with those on old vs. revised WHO doses in human immunodeficiency virus (HIV) negative children. The secondary objective was to determine the overall incidence of hepatitis in children on Anti tubercular treatment (ATT) and isoniazid prophylactic therapy (IPT). Children attending pediatric outpatient / admitted in wards, on ATT/ IPT between January 2007 and December 2017 (11 y) were included. Children were divided into Group 1 (treated based on old doses, from January 2007 to December 2011) and Group 2 (treated based on revised doses from January 2012 to December 2017). Children with multi drug resistant tuberculosis (MDRTB) and pre-existing liver disease were excluded. A total of 515 children were enrolled. Twelve children developed ATDH with an overall incidence of 2.3%. Five out of 260 (1.9%) developed hepatitis with old doses vs. 7 of the 255 (2.7%) with revised doses; this difference was not statistically significant. When calculated only for active TB (excluding children on IPT), overall incidence of hepatitis was 2.7%. Comparison between group 1 (2.04%) and group 2 (3.5%) was again not statistically significant. Ten out of 12 children who developed hepatitis were restarted on ATT without recurrence. No child on IPT developed hepatitis. There was no mortality. Revised WHO dosing does not increase incidence of hepatitis compared to old dosing in HIV negative children. Overall incidence was 2.3%. Hepatitis did not occur with IPT.

Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: a meta–analysis

BackgroundChildren are highly susceptible to tuberculosis; thus, there is need for safe and effective preventive interventions. Our objective was to evaluate the efficacy of isoniazid in prevention of tuberculosis morbidity and mortality in children aged 15 years or younger by performing a meta-analysis of randomized controlled trials. To our knowledge, this is the first meta-analysis evaluating efficacy of isoniazid prophylaxis in prevention of tuberculosis in children.MethodsA systematic search of the literature was done to identify randomized controlled trials evaluating isoniazid prophylaxis efficacy among children. Each study was evaluated for relevance and validity for inclusion in the analysis. Subgroup analyses were conducted based on study quality, HIV status, tuberculosis endemicity, type of prophylaxis and age of participants.ResultsEight studies comprising 10,320 participants were included in this analysis. Upon combining data from all eight studies, isoniazid prophylaxis was found to be efficacious in preventing development of tuberculosis, with a pooled RR of 0.65 (95% CI 0.47, 0.89) p = 0.004 , with confidence intervals adjusted for heterogeneity. Among the sub-group analyses conducted, only age of the participants yielded dramatic differences in the summary estimate of efficacy, suggesting that age might be an effect modifier of the efficacy of isoniazid among children, with no effect realised in children initiating isoniazid at four months of age or earlier and an effect being present in older children. Excluding studies in which isoniazid was initiated at four months of age or earlier yielded an even stronger effect (RR = 0.41 (95% CI 0.31, 0.55) p <0.001). Data on the effect of isoniazid on all-cause mortality, excluding studies in which isoniazid was initiated in infants, yielded an imprecise estimate of mortality benefit (RR = 0.58 (95% CI 0.31, 1.09) p = 0.092).ConclusionIsoniazid prophylaxis reduces the risk of developing tuberculosis by 59% among children aged 15 years or younger excluding children initiated during early infancy for primary prophylaxis (RR = 0.41, 95% CI 0.31, 0.55 p < 0.001) . However, further studies are needed to assess effects on mortality and to determine prophylaxis effectiveness in very young children and among HIV-infected children.

Vitamin D Status in HIV-Infected Patients With and Without Tuberculosis

Tuberculosis (TB) is a leading cause of death in human immunodeficiency virus (HIV)-infected individuals. Efforts to reduce the burden of TB include isoniazid prophylactic therapy (IPT) for latent TB infection (LTBI).1 However, IPT confers a risk of hepatotoxicity and requires at least six months of therapy.2 Therefore, additional strategies to reduce the burden of active TB are needed. Vitamin D supplementation may decrease the progression of LTBI to active TB. Primarily, in vitro studies demonstrate that 1,25-dihydroxyvitamin D (1,25[OH]2D) enhances macrophage function, thereby augmenting immunologic control of mycobacteria.3 The benefit of vitamin D supplementation is suggested by the observation of increased rates of clearance of TB from sputum in HIV-uninfected individuals.4 Vitamin D, however, may have detrimental effects in HIV-infected patients. In vitro, vitamin D depresses cell mediated immune function, 5 which could hasten progression of LTBI to active disease. This may limit vitamin D supplementation as an adjunct for TB control. Given vitamin D’s conflicting mechanisms of action on the immune system, we conducted a study in Botswana, an area of high TB and HIV prevalence,6 to determine if there was evidence for differences in 25-hydroxyvitamin D (25-OHD) levels in HIV-infected individuals with and without active TB. We hypothesized that 25-OHD levels would be significantly lower in HIV-infected individuals with active TB as compared to those without active TB.

Tuberculin skin test conversion and reactivity rates among adults with and without human immunodeficiency virus in urban settings in Ethiopia.

To investigate whether low CD4+ T-cell counts in healthy and human immunodeficiency virus (HIV)-infected Ethiopians influence tuberculosis (TB) immunological memory, tuberculin skin test (TST) conversion and reactivity rates were investigated among adults with and without HIV infection in urban settings in Ethiopia. Reaction to the TST was analyzed with purified protein derivative by the Mantoux technique. A total of 1,286 individuals with TST results of > or = 5-mm (n = 851) and < or = 4-mm (n = 435) induration diameters were included. Individuals with < or = 4-mm induration sizes were followed up for 21.4 +/- 9.5 months (mean +/- standard deviation) to observe skin test conversion. The overall TST reactivity (> or = 5-mm induration diameter) was 66.2% (n = 851). Reactivity was significantly lower among HIV-positive persons (40.5%) than among HIV-negative persons (68.7%) (P < 0.001). Of the above persons, 32 incident TB patients were checked for their TST status 13.05 +/- 11.1 months before diagnosis and reactivity was found among 22 (68.7%) of them. Of the TST-negative persons with 0- to 4-mm indurations who were followed up for 3 years, the conversion rate to positivity was 17.9/100 person-years of observation (PYO) (14.4/100 PYO and 18.3/100 PYO in HIV-positive and -negative persons, respectively). Despite lower absolute CD4+ T-cell numbers in Ethiopians, higher TST conversion and reactivity rates show the presence of a higher rate of latent TB infection and/or transmission. The lower TST positivity rate before a diagnosis of TB disease showed the lower sensitivity of the test. This indicates the need for other sensitive and specific diagnostic and screening methods to detect TB infection, particularly among HIV-positive persons, so that they can be given prophylactic isoniazid therapy.

PID17: DETERMINATION OF THE COST-EFFECTIVENESS OF A TUBERCULOSIS PREVENTION PROGRAM ALONG THE US/ MEXICO BORDER USING MARKOV PROCESS MODELING WITHIN A PREVENTION EFFECTIVENESS FRAMEWORK

A prevention effectiveness analysis framework was used to estimate the costefifectiveness of a county administered tuberculosis prevention program along the U.S. / Mexico border. The tuberculosis prevention program under study used prophylactic isoniazid therapy in patients who have tested positive for tuberculosis infection. This analysis determined the cost-effectiveness of the current program versus no program from the perspective of the county government and was modeled for two time periods; five years and 15 years post preventive therapy initiation. Costs were calculated using actual data from tuberculosis prevention and active tuberculosis treatment programs as well as hospital discharge data. The outcome of interest, cases of active tuberculosis averted, was calculated through a Monte Carlo simulated Markov process model. Average and incremental cost-effectiveness ratios were then calculated for the tuberculosis prevention program scenario. The cost-effectiveness ratios were calculated separately with the inclusion or exclusion of the tuberculosis contagion costs. The results of the cost-effectiveness ratio calculations established that the prevention of active tuberculosis cases with the tuberculosis prevention program is considerably cost-effective. Every baseline incremental cost-effectiveness ratio, across the five and 15 year analysis periods (irrespective of contagion costs) determined in this prevention effectiveness study demonstrated cost savings. Additionally, the cost savings were substantial. The results indicate that rather than incurring costs to avert active

Does Isoniazid Reduce Side Effects of Intravesical Bacillus Calmette-Guerin Therapy in Superficial Bladder Cancer? Interim Results of European Organization for Research and Treatment of Cancer Protocol 30911

We analyzed the influence of the tuberculostatic agent isoniazid on the incidence and severity of adverse effects of intravesical bacillus Calmette-Guerin (BCG) therapy in patients with superficial bladder cancer. In a prospective randomized multicenter study the side effects of intravesical instillations with Tice strain BCG with and without isoniazid were compared in patients with stages pTa and pT1 bladder tumors. Isoniazid was given orally at a dose of 300 mg. daily at every instillation in an attempt to decrease the side effects of BCG. No differences in local or systemic adverse reactions after intravesical immune therapy with BCG could be observed between patients treated with or without prophylactic isoniazid therapy. However, analysis of liver function tests after BCG with isoniazid showed slightly more liver toxicity compared to BCG alone. Prophylactic administration of isoniazid during BCG instillations provides no decrease in any known side effect of BCG. In contrast, transient liver function disturbances are encountered slightly more frequently when isoniazid is administered. The use of prophylactic isoniazid in patients treated with BCG is not recommended.

Physicians' Ability to Provide Initial Primary Care to an HIV-Infected Patient

Primary care physicians are providing care for an increasing number of persons infected with the human immunodeficiency virus (HIV). This study assesses the ability of primary care physicians to provide initial care for a patient with recently diagnosed HIV infection. A standardized patient (SP) was trained to portray an asymptomatic person with HIV infection seeking a primary care physician. Physicians took a medical history and counseled the SP; their performances were assessed by the SP and through a brief written examination. In addition, physicians distributed questionnaires to HIV-infected patients in their practices to assess actual performance. The study participants consisted of 121 primary care physicians. A minority of physicians recommended standard primary care screening tests and vaccinations, including viral hepatitis screening (35%), syphilis serologic testing (32%), and pneumococcal vaccination (23%). While most physicians (87%) indicated they would obtain CD4 cell counts, only 50% indicated they would start appropriate Pneumocystis carinii pneumonia prophylaxis. Although this patient presented documentation of a positive tuberculin skin test and no prior therapy for tuberculosis, only 53% of the physicians recommended prophylactic isoniazid. While 75% of the physicians asked this SP about condom use, number of sexual partners, or contact with previous sexual partners. Physicians with the most HIV experience were more likely to recommended P carinii pneumonia prophylaxis, coinfection screening, pneumococcal vaccination, and isoniazid prophylactic therapy. However, physicians' HIV experience was not associated with assessing this SP's risk of infecting others or with counseling regarding condom use. Questionnaires distributed to HIV-infected patients of these physicians generally confirmed these findings. Basic HIV preventive and primary care may not be adequately performed by many primary care physicians. Physicians' HIV experience was associated with better performance of HIV primary care tasks, but not with screening and counseling concerning the spread of HIV infection.

The prescribing of prophylactic isoniazid therapy for tuberculosis is in decline

The prescribing of prophylactic isoniazid therapy for tuberculosis is in decline

Management of tuberculin reactors in children and adolescents previously vaccinated with BCG.

Between 1960 and 1981, 142 Bacillus Calmette-Guérin (BCG)-vaccinated children and adolescents were evaluated in the Children's Chest Clinic, Bellevue Hospital. These patients came from 28 countries and had positive tuberculin reactions and/or exposure to active tuberculosis. Antituberculous therapy was given to 8 with active tuberculosis, to 8 with calcified pulmonary primary lesions and to 105 positive tuberculin reactors without disease. In a 1 1/2- to 16-year follow-up no tuberculous disease occurred, and two patients with previously negative roentgenograms developed calcified pulmonary lesions. Guidelines are given for the management of patients previously vaccinated with BCG with special reference to the value of prophylactic isoniazid therapy for those considered infected by Mycobacterium tuberculosis but without evidence of disease.

Isoniazid hepatitis in adolescents

Prophylactic isoniazid therapy is currently recommended for adolescents with positive tuberculin reactions because of the risk of activation of tuberculosis in this age group. Since this drug has been associated with hepatic dysfunction in adults, the present study was undertaken to evaluate its effect on liver function in teen-agers. Accordingly, liver function tests were performed on 178 adolescents prior to and following administration of INH. Abnormalities in SGPT values were encountered in 10% of these patients and occurred in the main within the first 10 weeks of testing, suggesting INH maybe hepatotoxic. However, jaundice was notably absent in the patients with enzyme elevations and prompted a further investigation into the possible effect of INH on bilirubin metabolism. Thus, Sprague-Dawley rats were given four daily injections of INH. These animals manifested increased hepatic bilirubin glucuronyl transferase activity when compared with control rats, supporting the hypothesis that enzymatic induction may be responsible for the absence of jaundice in our adolescent subjects.

Lymphogranuloma Venereum A Cause of Cervical Lymphadenopathy

CERVICAL lymphadenopathy is a relatively common clinical problem. Differential diagnosis includes hematological, lymphoreticular, or metastatic malignancies, mycobacterial, bacterial, viral, or rickettsial infections, and diseases of unknown etiology such as sarcoidosis and catscratch fever. In this report, we describe a patient whose cervical lymphadenopathy was the presenting manifestation of lymphogranuloma venereum infection. Report of a Case A 31-year-old graduate student was admitted to the Houston Veterans Administration Hospital because of cervical lymphadenopathy. In the two months before admission, he noted anorexia, easy fatigability, and a 6.5-kg weight loss. Eight days before admission, he began to have a low-grade fever associated with enlarging lymph nodes on the left side of his neck. He denied recent infections of the teeth or tongue, penile lesions, or urethral discharge. Former medical history was unremarkable except for one year of prophylactic isoniazid therapy in 1969 for a positive tuberculin skin test. He admitted to moderate use

Acute Meningoencephalitis

MENINGITIS from drug hypersensitivity is a rare phenomenon. 1 The, following case report illustrates the occurrence of severe aseptic purulent meningoencephalitis in a patient who had received prophylactic isoniazid therapy. Report of a Case A 27-year-old man was hospitalized on Jan 4, 1974, because of fever, chills, myalgia, arthralgia, nausea, vomiting, and severe generalized headache. In August 1973, pleuritic chest pain— thought to be of viral origin—developed. Results of a physical examination and a chest x-ray film were normal. An intermediate purified protein derivative test was again positive (10 mm of induration), as it had been since 1967. Prophylactic isoniazid therapy was initiated with a dose of 300 mg/day. After three days of treatment, fever, weakness, malaise, nausea, and vomiting developed. Findings of a physical examination and liver function studies were normal. When isoniazid therapy was discontinued, the patient rapidly recovered. In December 1973, while in good health and receiving