Impact of isoniazid preventive therapy on the evaluation of long-term effectiveness of infant MVA85A vaccination

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

Two large tuberculosis (TB) centres under a well-functioning National TB Programme (NTP) in Benin, West Africa. To assess the feasibility and results of integrating a programme of isoniazid preventive therapy (IPT) in children aged <5 years exposed to TB as part of the existing routine activities of the NTP. All children aged <5 years living in the household of a patient with smear-positive pulmonary TB were examined by a doctor and received IPT if no evidence of TB was detected. The children were followed clinically by a nurse for 6 months. From January 2013 to June 2014, 496 children were examined and prescribed IPT among 499 notified contacts; 86% adhered to IPT for at least 6 months. There were six deaths and three cases of active TB among the children, all during the first 3 months of follow-up. In an African country with moderate TB incidence and a well-functioning NTP, the integration of IPT into the NTP for children aged <5 years exposed to TB in the family was feasible based on simple tools associated with the follow-up of index cases. The rate of adherence to IPT was high.

BackgroundWHO recommends isoniazid preventive therapy (IPT) for young children in close contact with an infectious tuberculosis (TB) case. No models have examined the cost effectiveness of this recommendation.MethodsA decision analysis...

Tuberculosis (TB) is a significant contributor to the international and national burden of disease. Global estimates suggest that there were 10.4 million new cases of TB in 2015. Children accounted for ~10% of these cases, although in South Africa (SA) this figure is thought to be higher. Despite clear evidence that isoniazid preventive therapy (IPT) can reduce the risk of progression from TB infection to disease in TB contacts, IPT has been poorly implemented in SA national TB control programmes. To determine current practices regarding the identification and management of child contacts (&lt;5 years of age) at a primary care clinic in the Nelson Mandela Bay Health District, Eastern Cape Province, SA. A cross-sectional descriptive study was conducted using a retrospective record review of infectious TB index patients aged ≥15 years. Folders of index patients with bacteriologically confirmed pulmonary TB, who started TB treatment between 21 October 2011 and 28 February 2014, were included. A sample size of 246 child contacts was required to obtain adequate power. A 95% confidence interval (CI) was used to determine statistically significant results. Index patient records (N=491) were assessed and 261 child contacts identified. In a high percentage of index patient folders (87.5%; n=430), contacts were documented, although only 0.53 child contacts were identified per index patient. Of the 261 child contacts identified, 184 (70.5%) were screened for TB, 2 started TB treatment and 108/184 (58.7%) started IPT. For the remaining 74 (40.2%) children, there was no documentation of further management. Only 4 (3.7%) children completed the 24-week IPT course. Male patients reported fewer child contacts (χ2 =7.31; p=0.01; odds ratio (OR) 0.6; 95% CI 0.42 - 0.86) and were less likely to bring contacts for screening (χ2=8.98; p=0.003; OR 0.41; 95% CI 0.24 - 0.72). Retreatment index patients were also less likely to bring contacts for screening (χ2=6.37; p=0.01; OR 0.45; 95% CI 0.25 - 0.81) and those who were screened were less likely to initiate IPT (χ2=4.05; p=0.04; OR 0.54; 95% CI 0.3 - 0.95). Despite contacts being well documented, child contacts were poorly identified. The fall-out of children at each step from identification to IPT completion was unacceptably high. Contacts of male patients and retreatment index patients were at greater risk of poor management. Recommendations to improve IPT delivery at national and local level include a review of the national IPT guidelines, considering the relative success of shorter courses of TB prophylaxis, the use of standardised IPT stationery, staff training and the involvement of community health workers in contact management.

SettingChildren especially those <5 years of age exposed to pulmonary tuberculosis (TB) are at a high risk of severe TB disease and death. Isoniazid preventive therapy (IPT) has been shown...

Urban clinical research site in Durban, South Africa. To describe outcomes associated with the implementation of isoniazid preventive therapy (IPT) in a cohort of tuberculosis (TB) treatment-experienced human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART). We conducted a secondary analysis of data collected between October 2009 and October 2013 from patients enrolled in a prospective cohort study conducted in Durban, South Africa. Of the 402 patients enrolled in the parent study, 344 (85.6%) were eligible for IPT, 212 of whom (61.6%) initiated IPT. Of those who initiated IPT, 184 (86.8%) completed the 6-month course, while 24 (11.3%) permanently discontinued IPT, 3.8% of whom due to side effects. More women than men initiated IPT (n = 130, 61.3% vs. n = 82, 38.7%, P = 0.001). Overall median adherence to IPT was 97.6% (interquartile range 94.2-99.4). There were 22 cases of incident TB in this cohort: 13 occurred before IPT and 9 after (incidence rate ratio 0.67, 95%CI 0.29-1.58, P = 0.362). IPT implementation among ART and TB treatment-experienced patients was well tolerated, with good completion rates and fewer TB cases diagnosed after IPT.

In 2012, Peru's National TB Program (NTP) reported approximately 2400 incident cases of tuberculosis (TB) disease in children aged <15 years. Peru's TB burden is concentrated in the Lima metropolitan area, particularly in poor districts such as El Agustino and La Victoria, where this study was conducted. To identify barriers to the treatment of childhood tuberculous infection and TB disease in Lima from the perspective of front-line providers and patients' families. We conducted 10 semi-structured focus groups with 53 purposefully sampled primary care providers, community health workers, and parents/guardians of pediatric TB patients. We also completed nine in-depth interviews with National TB Program administrators and pulmonologists specializing in TB. Two authors performed inductive thematic analysis and identified emerging themes. Four main treatment barriers emerged from the data: 1) dosing errors, 2) time- and labor-intensive preparation and administration of medications, 3) provider concern that isoniazid preventive therapy (IPT) generates isoniazid resistance, and 4) poor adherence to IPT. Our findings highlight the urgent need for child-friendly formulations, provider and parent/guardian education about IPT, and strategies to promote adherence to IPT, including support and supervision by health workers and/or regimens with fewer doses.

Background: The World Health Organization (WHO) recommended isoniazid preventive therapy (IPT) to decrease the effects of tuberculosis (TB) on human immunodeficiency virus (HIV) patients. However, not enough research has been conducted to determine the impact of IPT on TB incidence and their predictors. Therefore, the goal of this study was to evaluate how IPT affects the incidence of TB and identify factors that are predictive of TB among HIV/AIDS patients.Methods: A total of 588 patients at Debre Tabor General Hospital (DTGH) who had taken IPT between December 2009 and January 2016 participated in the current study, which then followed them for 3 years and compared them to patients who did not receive IPT during the study period. The data were gathered from patient registries and charts. IPT users’ and nonusers’ TB‐free survival curves were compared using log‐rank testing. Predictors were identified using bivariate and multivariate Cox proportional hazards models.Results: In this study, 1656 person‐years (PYs) follow‐ups on 588 patients found 82 additional TB cases, with an overall incidence rate (IR) of 4.95/100 PY. When compared to individuals who were not on IPT, the TB IR among patients living with human immunodeficiency virus (PLHIV) on IPT was significantly lower (1.94/100 PY vs. 8.32/100 PY). A baseline CD4 cell count &lt; 200 cells/uL, history of TB, Hgb level &lt; 10 g/dL, BMI &lt; 18.5 kg/m2, and not receiving IPT are independent predictors of TB among HIV/AIDS patients.Conclusion: The frequency of TB was high among PLHIV patients who did not receive IPT. It was discovered that a low CD4 cell count at baseline, a history of TB, IPT status, Hgb level, and BMI independently predicted the presence of TB. Therefore, addressing the independent predictors that are connected to a higher risk of TB in PLHIV as well as isoniazid (INH) prophylaxis has a significant impact on reducing the incidence of TB.

Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (β = 0.04 [95% CI:-0.14, 0.22]), HAZ (β = 0.14 [95% CI:-0.06, 0.34]), and WHZ [β = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (β to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.

How can this be? Preventing death in patients with HIV-associated tuberculosis [Editorial

Thibela TB: Design and methods of a cluster randomised trial of the effect of community-wide isoniazid preventive therapy on tuberculosis amongst gold miners in South Africa

Tuberculosis Trends, Vietnam

The Lesotho Ministry of Health issued guidelines on active case finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in April 2011. ACF has been recommended in maternal and child health (MCH) settings globally, however, the feasibility of implementing IPT within MCH in countries with high concurrent HIV and TB epidemics is unknown. The study evaluated the implementation of ACF and IPT guidelines in MCH settings in 2 health facilities in Lesotho. This descriptive prospective study analyzed data collected during routine services. Categorical data and continuous variables were summarized using descriptive statistics. The χ test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. Data from 160 HIV-positive and 640 HIV-negative women were reviewed. Within this study population, 99.8% of women were screened for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%) HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2 (1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up. Predictors of IPT initiation among HIV-positive women included gestational age at the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval: -0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than for prevention of mother-to-child transmission prophylaxis only (odds ratio, 4.59; 95% confidence interval: 1.32 to 15.93). Implementation of ACF and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among HIV-positive women was high, but with a high rate of loss to follow-up.

BackgroundShort-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use.MethodsWe developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated.ResultsWhen prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact.ConclusionsAll modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.