INH Preventive Therapy Research Articles

Participant perspectives on incentives for TB preventative therapy adherence and reduced alcohol use: A qualitative study.

Economic incentives to promote health behavior change are highly efficacious for substance use disorders as well as increased medication adherence. Knowledge about participants' experiences with and perceptions of incentives is needed to understand their mechanisms of action and optimize future incentive-based interventions. The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial enrolled people with HIV (PWH) in Uganda with latent tuberculosis and unhealthy alcohol use in a 2x2 factorial trial that incentivized recent alcohol abstinence and isoniazid (INH) adherence on monthly urine testing while on INH preventive therapy. We interviewed 32 DIPT study participants across trial arms to explore their perspectives on this intervention. Participants described 1) satisfaction with incentives of sufficient size that allowed them to purchase items that improved their quality of life, 2) multiple ways in which incentives were motivating, from gamification of "winning" through support of pre-existing desire to improve health to suggesting variable effects of extrinsic and intrinsic motivation, and 3) finding value in learning results of increased clinical monitoring. To build effective incentive programs to support both reduced substance use and increased antimicrobial adherence, we recommend carefully selecting incentive magnitude as well as harnessing both intrinsic motivation to improve health and extrinsic reward of target behavior. In addition to these participant-described strengths, incorporating results of clinical monitoring related to the incentive program that provide participants more information about their health may also contribute to health-related empowerment.

Biomarker-confirmed suboptimal adherence to isoniazid preventive therapy among children with HIV in western Kenya.

The aim of this study was to assess the level and correlates of biomarker-confirmed adherence to isoniazid (INH) preventive therapy (IPT) among children with HIV (CLHIV). This prospective cohort study assessed adherence among CLHIV on IPT in public sector HIV clinics from 2019 through 2020. Adherence was assessed by pill counts or caregiver or self-reports, and urine biomarkers (in-house dipstick and Isoscreen). Both urine biomarker tests detect INH metabolites within 48 h of ingestion. Consistent adherence was defined as having positive results on either biomarker at all visits. Correlates of biomarker-confirmed nonadherence at each visit were evaluated using generalized estimating equations. The in-house dipstick was validated using Isoscreen as the reference. Among 97 CLHIV on IPT with adherence assessments, median age was 10 years (IQR 7-13). All were on ART at IPT initiation (median duration 46 months [IQR 4-89]); 81% were virally suppressed (<1000 copies/ml). At all visits, 59% ( n = 57) of CLHIV reported taking at least 80% of their doses, while 39% ( n = 38) had biomarker-confirmed adherence. Viral nonsuppression (adjusted risk ratio [aRR] = 1.65; 95% confidence interval [95% CI] 1.09-2.49) and the sixth month of IPT use (aRR = 2.49; 95% CI 1.34-4.65) were independent correlates of biomarker-confirmed nonadherence at each visit. Sensitivity and specificity of the in-house dipstick were 98.1% ( 94.7 - 99.6%) and 94.7% ( 88.1 - 98.3%) , respectively, versus Isoscreen. Biomarker-confirmed adherence to IPT was sub-optimal and was associated with viral nonsuppression and duration of IPT. Urine dipstick testing may be useful in assessing adherence to IPT in clinical care.

Central Nervous System Tuberculosis (CNS-TB) in treated HIV-infected adults in Tikur Anbessa Specialized Hospital, Ethiopia: A cross sectional study

BackgroundCentral nervous system (CNS) tuberculosis (TB) is a calamitous infection with high rates of morbidity and mortality. Underlying HIV infection often increases susceptibility for acquiring TB and also complicates TB treatment. The study objectives were to assess the burden of CNS TB and associated factors in treatment experienced HIV infected adults. MethodsA single-center observational cross-sectional study was conducted between December 2019 and June 2020. Both descriptive and analytical statistics were used to analyze the data. ResultsNinety-five HIV infected adults with presumptive TB-HIV co-infection on combination antiretroviral therapy for median of 144 months were assessed. The mean age was 40.8 years (1SD = 12.4). Male to female ratio was 1:2. The prevalence of CNS tuberculosis was 56.8% (TB menigitis 53.7%, tuberculoma 2.1%, and spinal TB 1.1%). Patients with CNS TB were younger compared to those with extra CNS TB (38.6 vs. 43.6 years, p = 0.04). A higher proportion of patients with CNS TB had undetectable HIV RNA compared to those with extra CNS TB (55.8% vs. 36.8% p = 0.04). In multivariate regression analysis, advanced disease stages, deferred cotrimoxazole preventive therapy (CPT), and deferred INH preventive therapy (IPT) were found to be independent predictors of CNS TB. Although not statistically significant, the trend for HIV-associated cognitive decline was higher in the group with CNS TB. ConclusionThe prevalence of CNS TB was higher among HIV-infected adults with TB-HIV co-infection. TB meningitis was the most common type of CNS TB. Advanced disease stages, deferred CPT, and deferred IPT were predictors of CNS tuberculosis. Although statistically not-significant, the trend for HAND was higher in the group diagnosed with CNS tuberculosis.

First description of the katG gene deletion in a Mycobacterium tuberculosis clinical isolate and its impact on the mycobacterial fitness

Isoniazid (INH) is the cornerstone of the anti-tuberculosis regimens and emergence of Mycobacterium tuberculosis (Mtb) resistant strains is a major threat to our ability to control tuberculosis (TB) at global level. Mutations in the gene coding the catalase KatG confer resistance to high level of INH. In this paper, we describe for the first time a complete deletion of the genomic region containing the katG gene in an Mtb clinical strain isolated in Italy in a patient with HIV infection that previously completed INH preventive therapy. We genotypically characterized the Mtb strain and showed that katG deletion confers high-level resistance to INH (MIC > 25.6 μg/mL). The katG deletion did not impact significantly on Mtb fitness as we did not detect enhanced susceptibility to H2O2 compared to the wild type Mtb strains nor impaired growth in in vitro infection models. These findings highlight the ability of Mtb to acquire resistance to INH while maintaining fitness and pathogenic potential.

Adherence to Isoniazid Preventive Therapy among children living with tuberculosis patients in Delhi, India: An exploratory prospective study

INH Preventive Therapy (IPT) substantially reduces the risk of incidence of TB disease in pediatric household contacts of TB patients. The National TB Elimination Program (NTEP) of India prescribes a daily regimen of Isoniazid to all under-6 pediatric contacts for 6 months duration.We conducted, this exploratory prospective study (June to Nov’ 2020) to assess adherence to IPT and reasons for nonadherence among child contacts of microbiologically confirmed, drug sensitive, non-PLHIV Tuberculosis patients in Delhi, India. The study outcomes included the initiation, adherence and completion of IPT. The caregivers of the child TB contacts were interviewed face to face by the field investigator. The data were entered on EpiData 3.1 and analysed with IBM SPSS 25.The INH adherence was assessed in a total of 86 household child TB contacts. IPT had been initiated in 62 (72.1%) child TB contacts of which 61 (98.4%) received INH within 1 month of starting of ATT-DOTS therapy in the index TB patient of the household. Furthermore, the failure to initiate IPT was reported by 24 (27.9%) child TB contacts. Within the cohort of child TB contacts who were not initiated with IPT, the ATT-DOTS duration in the index-TB patient was ≥5 months in 18 (75%) cases, 1–2 months in 3 (12.5%) cases, and <1 month in also 3 (12.5%) cases. Reasons for non-initiation (n = 24) were reported as refusal by the family in 12 (50%) cases mostly due to concern over side-effects of the drug, while non-provision of the drug by the DOTS provider was also observed in 12 (50%) cases.The mean (SD) INH adherence in the INH initiated cohort was 5.6 (2.0) (n = 62). Reasons for INH non-adherence were attributed to forgetfulness (n = 23, 37.1%), carelessness (n = 24, 38.7%), and intermittent stopping of the medication (n = 17, 27.4%) on the child falling sick, perceived drug side effects, and running out of drug stocks.INH non-adherence defined as at-least two missed INH doses in the previous 7 days was observed in 47 (54.7%) participants (n = 86). On bivariate analysis, none of the household sociodemographic characteristics showed any statistically significant association with the rate of INH non-adherence in the child TB contacts.The findings of the present study indicate the need to periodically assess adherence and persistence to IPT in the child TB contacts as high intermittent missed dosing rates can undermine the effectiveness of IPT in preventing incident disease.

Isoniazid Preventive Therapy in Contacts of Multidrug-Resistant Tuberculosis.

Rationale: The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection.Objectives: To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.Methods: In a prospective cohort study conducted between September 2009 and August 2012, we identified 4,500 index patients with tuberculosis and 14,044 tuberculosis-exposed household contacts who we followed for 1 year for the occurrence of incident tuberculosis disease. Although Peruvian national guidelines specify that INH preventive therapy should be provided to contacts aged 19 years old or younger, only half this group received INH preventive therapy.Measurements and Main Results: Among 4,216 contacts under 19 years of age, 2,106 contacts (50%) initiated INH preventive therapy at enrollment. The protective effect of INH was more extreme in contacts exposed to drug-sensitive tuberculosis (adjusted hazard ratio, 0.30; 95% confidence interval, 0.18-0.48) and to multidrug-resistant tuberculosis (adjusted hazard ratio, 0.19; 95% confidence interval, 0.05-0.66) compared with those exposed to mono-INH-resistant tuberculosis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.23-2.80). In the second independent study, tuberculosis occurred in none of the 76 household contacts who received INH preventive therapy compared with 3% (8 of 273) of those who did not.Conclusions: Household contacts who received INH preventive therapy had a lower incidence of tuberculosis disease even when they had been exposed to an index patient with multidrug-resistant tuberculosis. INH may have a role in the management of latent multidrug-resistant tuberculosis infection.

Phenotypic isoniazid resistance and associated mutations in pediatric tuberculosis

Background and objectivesTuberculosis (TB) remains one of the most challenging global health problems as resistance to first-line antimycobacterial drugs continues to rise in many countries worldwide. Isoniazid-resistant TB without MDR-TB poses a serious threat to the management and control of TB across the world. The aim of this study was to investigate the extent of katG315 and inhA-15 mutations in Mycobacterium tuberculosis strains isolated from pediatric TB patients from a tertiary care hospital. Material and methodsA total of 51 pulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to INH was detected by 1% proportion method. katG315 and inhA-15 genes were amplified by PCR and detection of mutations in katG315 and inhA-15 genes was done by sequencing. ResultA sample size of only 51 could be achieved due to short duration of the study. 36/51 (70.6%) culture isolates were obtained and put for drug susceptibility test, 5(13.89%) were resistant for isoniazid. M. tuberculosis DNA was found in fifty samples. Mutations in either katG315 or inhA-15 genes were found in 7/50 (14%) samples. Six of seven (85.7%) had mutation in katG315 gene and 1/7 (14.2%) had mutation in inhA-15 gene. ConclusionINH resistance not only reduces the probability of treatment success, but may also facilitate the spread of MDR-TB and reduce the effectiveness of INH preventive therapy (IPT) therefore quantification of the magnitude of INH resistant TB and variation in frequency of isoniazid resistance associated mutations is important.

High compliance of six-month INH preventive therapy in HIV patients: A stepping stone for the future

Introduction: Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. Isoniazid preventive therapy (IPT) is one of the widely recommended interventions aimed to reduce the burden of TB (Tuberculosis) in people living with HIV. Methodology: A Retrospective analysis from clinical records, of all diagnosed HIV patients registered at ART (Anti-Retroviral Therapy) center of a tertiary care health institute) & initiated on six-month IPT (INH Preventive Therapy) during the period of November 2017 to December 2018 was conducted. Results: A total of 575 HIV patients (554 (96%) adults and 21(4%) pediatric patients) were initiated on six-month IPT. These included 298 (52%) males and 277 (48%) female patients. 435 (76%) patients completed full six months of therapy. 15(2%) stopped treatment prior to completion of six months. 120(21%) patients were on regular therapy at the time of study. 5 patients were taking the IPT irregularly at the time of study. Among the 15 HIV patients who stopped IPT prior to completion of therapy duration, reasons for stopping IPT were adverse drug reactions (ADRs) in 8(53 %) patients, refusal in 4 (27%) patients and increased pill burden in 3 (20%) patients. The compliance rate of IPT in HIV patients was 97%. Discussion: IPT Compliance is a potentially important factor in the disease course of HIV and hence an important determinant of survival rates in these patients. Appropriate monitoring and counselling may further increase the compliance rate of IPT among HIV patients. Conclusion: HIV patients initiated on IPT have a good compliance rate for completion of regular six-month IPT. Keywords: Human immunodeficiency; HIV; TB.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

The twin epidemics: Prevalence of TB/HIV co-infection and its associated factors in Ethiopia; A systematic review and meta-analysis.

BackgroundTuberculosis and HIV/AIDS are the major public health problems in many parts of the world particularly in resource limited countries like Ethiopia. Although studies have been conducted on the prevalence and associated factors of TB / HIV co-infection in Ethiopia, there is no comprehensive data on the magnitude and risk factors at a national and regional levels. Therefore, this review is aimed to summarize the prevalence of TB /HIV co-infection in Ethiopia using meta-analysis based on a systematic review of published articles & grey literatures.MethodsTo conduct this systematic review and meta-analysis, major databases such as Pub Med, Google scholar, CINAHL, Africa Journals Online and Google were systematically searched using search terms. PRISMA guideline was followed in the study. Two authors extracted all necessary data using a standardized data extraction format, and analysis was done using STATA version 11. A Statistical heterogeneity across the studies was evaluated by using Cochran’s Q test and I2 statistic. The pooled effect size was conducted in the form of prevalence and associations were measured using odds ratio. Moreover, the univariate meta regression was performed by considering the sample size to determine potential sources of heterogeneity. The Egger’s weighted regression and Begg’s rank correlation tests were used to assess potential publication biases.ResultsThis meta-analysis included 21 studies with a total of 12,980 participants. The pooled prevalence of TB / HIV Co-infection was 25.59% (95% CI (20.89%–30.29%). A significant association was found between low CD4 counts (OR: 3.53; 95% CI: 1.55, 8.06), advanced WHO stage (OR: 6.81; 95% CI: 3.91, 11.88) and TB/ HIV/AIDS Co-infection.ConclusionThis finding revealed that the magnitude of TB /HIV co-infection in Ethiopia is increasing and deserves special attention. Low CD4 count and advanced WHO stage are contributing factors for dual infection. Establishing mechanisms such as Conducting surveillance to determine HIV burden among TB patients and TB burden among HIV patients, and intensifying the three I’s (Intensive case finding, INH Preventive Therapy and Infection control) should be routine work of clinicians. Moreover, early screening & treatment should be provided to those patients with low CD4 count and advanced WHO stage.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

A community-based isoniazid preventive therapy for the prevention of childhood tuberculosis in Ethiopia.

BACKGROUND:Although children in contact with adults with tuberculosis (TB) should receive isoniazid (INH) preventive therapy (IPT), this is rarely implemented.OBJECTIVE:To assess whether a community-based approach to provide IPT at the household level improves uptake and adherence in Ethiopia.METHODS:Contacts of adults with smear-positive pulmonary TB (PTB+) were visited at home and examined by health extension workers (HEWs). Asymptomatic children aged <5 years were offered IPT and followed monthly.RESULTS:Of 6161 PTB+ cases identified by HEWs in the community, 5345 (87%) were visited, identifying 24 267 contacts, 7226 (29.8%) of whom were children aged <15 years and 3102 (12.7%) were aged <5 years; 2949 contacts had symptoms of TB and 1336 submitted sputum for examination. Ninety-two (6.9%) were PTB+ and 169 had TB all forms. Of 3027 asymptomatic children, only 1761 were offered (and accepted) IPT due to INH shortage. Of these, 1615 (91.7%) completed the 6-month course. The most frequent reason for discontinuing IPT was INH shortage.CONCLUSION:Contact tracing contributed to the detection of additional TB cases and provision of IPT in young children. IPT delivery in the community alongside community-based TB interventions resulted in better acceptance and improved treatment outcome.

Isoniazid-resistant tuberculosis: a cause for concern?

The drug isoniazid (INH) is a key component of global tuberculosis (TB) control programmes. It is estimated, however, that 16.1% of TB disease cases in the former Soviet Union countries and 7.5% of cases outside of these settings have non-multidrug-resistant (MDR) INH resistance. Resistance has been linked to poorer treatment outcomes, post-treatment relapse and death, at least for specific sites of disease. Multiple genetic loci are associated with phenotypic resistance; however, the relationship between genotype and phenotype is complex, and restricts the use of rapid sequencing techniques as part of the diagnostic process to determine the most appropriate treatment regimens for patients. The burden of resistance also influences the usefulness of INH preventive therapy. Despite seven decades of INH use, our knowledge in key areas such as the epidemiology of resistant strains, their clinical consequences, whether tailored treatment regimens are required and the role of INH resistance in fuelling the MDR-TB epidemic is limited. The importance of non-MDR INH resistance needs to be re-evaluated both globally and by national TB control programmes.

Three cases of intentional isoniazid overdose - a life-threatening condition.

Currently, isoniazid (INH) overdose seems to be a growing and life-threatening problem, partly due to the recent national roll-out of INHpreventive therapy (IPT) for HIV-positive adults. We present three cases, two of which were fatal, seen at Frere and Cecilia Makiwanehospitals, East London, South Africa over the past 16 months.

Quantiferon Gold-in-tube assay for TB screening in HIV infected children: influence of quantitative values.

BackgroundHIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children.MethodsHIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed.ResultsEighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up.ConclusionsQFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-516) contains supplementary material, which is available to authorized users.

Tuberculosis case finding and isoniazid preventive therapy among people living with HIV at public health facilities of Addis Ababa, Ethiopia: a cross-sectional facility based study.

BackgroundActivities to decrease the burden of tuberculosis (TB) among people living with HIV (PLHIV) include intensified TB case-finding (ICF), Isoniaizid (INH) preventive therapy (IPT) and infection control in health-care and congregate settings (IC). Information about the status of collaborative TB/HIV care services which decreases the burden of TB among PLHIV in Ethiopia is limited. The purpose of the study was to assess TB case finding and provision of IPT among PLHIV in Addis Ababa.MethodsA cross sectional, facility-based survey was conducted between June 2011 and August 2011. Data was collected by interviewing 849 PLHIV from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to analyze findings and the results are described in this report.ResultsThe proportion of PLHIV who have been screened for TB during any one of their follow-up cares was 92.8%. Eighty eight (10.4%) of the study participants have been diagnosed for TB during their HIV follow-up cares. PLHIV who had never been diagnosed for TB before they knew their positive HIV status were nearly four times more likely to be diagnosed for TB during follow-up cares than those diagnosed before (AOR [95% CI]: 3.78 [1.69-8.43]). Nearly a third (28.7%) of all interviewed PLHIV self reported that they had been treated with IPT.ConclusionsIt can be concluded that ICF for TB and IPT among PLHIV in Addis Ababa need boosting. Hence, it is recommended to put into practice the national and global guidelines to improve ICF and IPT among PLHIV in the city.

Evaluation of efficacy and adherence to INH preventive therapy in children at risk to develop active tuberculosis

Abstract Objectives Revised National Tuberculosis Control Program and Indian Academy of Pediatrics advocate 6 months of INH Preventive Therapy (IPT) for children less than 6 years who are in contact with an infectious pulmonary tuberculosis case, irrespective of their BCG or nutritional status. Isoniazid is also recommended by Indian Pediatric Nephrology group for children with nephrotic syndrome who are asymptomatic mantoux positive (latent tuberculosis) and who require steroid therapy. Poor adherence to INH is a major barrier in implementing IPT. Objective of this study was to evaluate the efficacy of IPT in preventing active disease in the above groups and to assess the adherence to IPT in these children. Methods Prospective study conducted at department of paediatrics at a tertiary care teaching hospital, from April 2006 to October 2011. Study involved initiation of IPT in groups mentioned above (group 1 – children less than 6 years in contact with infectious adults and group 2 – asymptomatic mantoux positive children with nephrotic syndrome requiring steroid therapy) and follow-up of cohort at regular intervals for development of active disease and adherence to prescribed therapy. Results A total of 50 children were included in the study (group 1 – 31 children and group 2 – 19 children). Forty-three (86%) children completed 6 months of prescribed INH treatment. Mean duration of follow-up was 12.29 (±13.13) months post-treatment. None of children who adhered to treatment developed active disease. Conclusions Our study suggests that IPT is effective in preventing active disease in both children in contact with infectious adults and those with nephrotic syndrome and latent infection. Adherence can be enhanced by counseling of parents at the start of therapy and reemphasis during subsequent follow-ups.

Point-of-Care Urine Tests for Smoking Status and Isoniazid Treatment Monitoring in Adult Patients

BackgroundPoor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs.Methodology/Principal Findings200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment.ConclusionsIsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Lack of adherence to isoniazid chemoprophylaxis in children in contact with adults with tuberculosis in Southern Ethiopia.

SettingHawassa, Southern Region of Ethiopia.ObjectivesTo determine compliance to isoniazid (INH) preventive therapy (IPT) and its effectiveness in preventing (TB) disease in children in contact with adults with pulmonary TB (PTB).DesignThis was a prospective cohort study of children <15 years old in contact with adults with smear-positive PTB. Asymptomatic children ≤5 years were provided IPT independently of their Tuberculin Skin Test (TST) status and children >5 years old were given advice but did not receive IPT, as recommended by the National TB control programme. Compliance to IPT and incidence of clinical TB were determined monthly for six months and then quarterly for up to 30 months.ResultsOne hundred and eighty four children in contact with 83 smear-positive PTB cases were identified. Eighty two were ≤5 and 102>5 years old. Only 27 (33%) of 82 children given IPT took it for >4 months and 10 (12%) completed the 6-month course. The main reason for non-compliance was the perception that drugs were not necessary when the child was healthy. Eleven children (all except one >5 years old) developed symptoms of TB disease and initiated treatment, resulting in an incidence of 28.6 cases for all and 53.5 for children >5 years old per 1000 children-year.ConclusionCompliance to IPT in children is poor in Southern Region of Ethiopia and this was associated with the parents' perception of the low importance of chemoprophylaxis in asymptomatic children. Poor compliance might be an important barrier for the wider implementation of IPT.Trial RegistrationClinicaltrials.gov NCT00456469

Adverse effect other than liver dysfunction in treatment of latent tuberculous infection by isoniazid

To study the frequency and degree of adverse effect, other than liver dysfunction, of isoniazid (INH) preventive therapy in Japanese people. Chart review of Japanese persons who started isoniazid preventive chemotherapy in the two clinics in Tokyo, from 2003/1/1 to 2004/12/31. There were 779 cases who did not transiently or completely stop INH preventive therapy because of adverse effect, and 20 cases who stopped INH transiently or completely because of adverse effect other than liver damage (total 799 cases). Of those cases, 153 cases (153/799=19.1%) experienced one or more adverse effect other than liver damage, and 20 cases (20/799=2.5%) of these 153 cases stopped INH transiently (12 cases) or completely (8 cases). For each category of adverse effect, digestive system symptoms were most frequent (5.9%), and then in frequency order, lethargy or easy-fatigability (4.6%), central nervous symptoms (4.5%), skin eruptions (2.6%), acne (2.5%), alcohol intolerance-like symptoms (2.5%), peripheral neuropathy (0.4%), arthralgia or limb pain (0.3%). Adverse effect requiring stopping INH transiently or completely were skin eruption (1.3%), digestive system symptoms (1.1%), central nervous symptoms (0.6%), acne (0.1%). Most of the adverse effect were not serious, and not required hospitalization. In isoniazid (INH) preventive therapy in Japanese people, adverse effect other than liver damage were not infrequent, but most of them are not serious, and do not disturb continuation of preventive therapy in most cases.