High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an Isoniazid Preventive Therapy Trial.
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ABSTRACT:
SUBMITTER: Cranmer LM
PROVIDER: S-EPMC6095832 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an Isoniazid Preventive Therapy Trial.
Cranmer Lisa M LM Draper Heather R HR Mandalakas Anna M AM Kim Soyeon S McSherry George G Krezinski Emma E Coetzee Joan J Mitchell Charles C Nachman Sharon S van der Linde Mercia M Cotton Mark F MF Hesseling Anneke C AC
The Pediatric infectious disease journal 20181001 10
Young HIV-exposed children are at high risk for TB infection. We performed QuantiFERON-TB Gold among HIV-exposed children in South Africa at enrolment and 1-year follow-up. The incidence of TB infection was high for HIV+ (11 cases per 100 child-years) and HIV-exposed uninfected children (15 cases per 100 child-years). QuantiFERON-TB Gold may identify HIV-exposed children at risk for TB disease progression. ...[more]
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Project description:BackgroundThe dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period.MethodsWe randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization.ResultsAntiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P=0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P=0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups.ConclusionsPrimary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.).
| S-EPMC3164539 | biostudies-literature
Project description:In sub-Saharan Africa, where the emergence of HIV has caused dramatic increases in tuberculosis (TB) case notifications, new strategies for TB control are necessary. Isoniazid preventive therapy (IPT) for HIV-TB coinfected individuals reduces the reactivation of latent Mycobacterium tuberculosis infections and is being evaluated as a potential community-wide strategy for improving TB control. We developed a mathematical model of TB/HIV coepidemics to examine the impact of community-wide implementation of IPT for TB-HIV coinfected individuals on the dynamics of drug-sensitive and -resistant TB epidemics. We found that community-wide IPT will reduce the incidence of TB in the short-term but may also speed the emergence of drug-resistant TB. We conclude that community-wide IPT in areas of emerging HIV and drug-resistant TB should be coupled with diagnostic and treatment policies designed to identify and effectively treat the increasing proportion of patients with drug-resistant TB.
| S-EPMC1459015 | biostudies-literature
Project description:BackgroundIPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.ObjectivesTo measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.MethodsA retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, "IPT-only," "IPT-before-ART," "IPT-and-ART started simultaneously," "ART-only," and "IPT-after-ART" on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.ResultsOf 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of "IPT-only" (aHR = 0.36, 95% CI = 0.19-0.66) and "ART-only" (aHR = 0.32, 95% CI = 0.24-0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08-0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10-0.42) provided further reduction of TB at ? 80%.ConclusionsIPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.
| S-EPMC4126726 | biostudies-literature
Project description:ObjectiveTo identify the incidence of and predictors for tuberculosis in children living with HIV in Northern Ethiopia.DesignObservational, retrospective follow-up study.MethodsA total of 645 HIV-infected children were observed between September 2009 and September 2014. Cox regression analysis was used to identify predictors for developing TB.ResultsThe incidence rate of tuberculosis was 4.2 per 100 child-years. Incidence of tuberculosis was higher for subjects who were not on cotrimoxazole preventive therapy, were not on isoniazid preventive therapy, had delayed motor development, had a CD4 cell count below the threshold, had hemoglobin level less than 10 mg/dl and were assessed as World Health Organization (WHO) clinical stage III or IV.ConclusionIncidence of TB in children living with HIV was high. This study reaffirmed that isoniazid preventive therapy is one of the best strategy to reduce incidence of TB in children living with HIV. All children living with HIV should be screened for TB but for children with delayed motor development, advanced WHO clinical stage, anemia or immune suppression, intensified screening is highly recommended.
| S-EPMC4829210 | biostudies-literature
Project description: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.
| S-EPMC7560814 | biostudies-literature
Project description:SettingWorld Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV.ObjectiveTo assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries.DesignSurvey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa.ResultsICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03).ConclusionsImplementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.
| S-EPMC4830552 | biostudies-literature
Project description:BackgroundTuberculosis (TB) and HIV makeup a deadly synergy of infectious disease, and the combined effect is apparent in resource limited countries like Ethiopia. Previous studies have demonstrated inconsistent results about the protective effect of isoniazid preventive therapy (IPT) on active TB incidence among HIV positive patients receiving ART. Therefore, the aim of this meta-analysis was, first, to determine the protective effect of IPT on active tuberculosis incidence, and second, to assess the pooled incidence of active TB among HIV positive patients taking ART with and without IPT intervention in Ethiopia.MethodsPubMed, Google scholar and Cochran library databases were searched from April 1 to 30, 2018. Two independent authors explored and assessed studies for eligibility, and extracted data based on predefined criteria. Studies that reported TB incidence among HIV positive patients taking ART in Ethiopia with and without IPT concomitant intervention, and with a clear stratified data on the incidence of TB based on the duration of IPT intervention were selected. A random effects model was used to estimate risk ratios and the pooled incident TB with the respective 95% confidence intervals.ResultsWe identified 7 suitable studies in this analysis. Accordingly, IPT reduced the risk of TB incidence by 74%, risk ratio (RR) 0.26 (95% CI; 0.16-0.43%), compared to no IPT group. Moreover, IPT for 12 months reduced incident TB by 91% (RR: 0.09, 95% CI: 0.04 to 0.21), whereas 6 months IPT averted TB incidence by 63% (RR: 0.37, 95% CI: 0.26 to 0.52). The overall pooled incident TB among HIV infected patients receiving ART was 10.30% (95% CI; 7.57-13.02%). Specifically, incident TB among study cohorts with and without IPT was 3.79% (95% CI; 2.03-5.55%) and 16.32% (95% CI; 11.57-21.06%) respectively.ConclusionIPT reduced the risk of incident TB among HIV positive patients receiving ART in Ethiopian settings. Moreover, the duration of IPT intervention has effect on its protective role. Thus, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis.Study protocol registrationCRD42018090804.
| S-EPMC6511123 | biostudies-literature
Project description:INTRODUCTION:HIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because infancy is a time of rapid progression from primary infection to active TB disease, it is important to define when and how TB preventive interventions exert their effect in order to develop effective prevention strategies in this high-risk population. METHODS AND ANALYSIS:We designed a non-blinded randomised controlled trial to determine efficacy of isoniazid (INH) to prevent primary Mtb infection among HEU children. Target sample size is 300 (150 infants in each arm). Children are enrolled at 6 weeks of age from maternal and child health clinics in Kenya and are randomised to receive 12 months of daily INH ~10?mg/kg plus pyridoxine or no INH. The primary endpoint is Mtb infection, assessed by interferon-gamma release assay QuantiFERON-TB Gold Plus (QFT-Plus) or tuberculin skin test after 12 months post-enrolment. Secondary outcomes include severe adverse events, expanded Mtb infection definition using additional QFT-Plus supernatant markers and determining correlates of Mtb infection. Exploratory analyses include a combined outcome of TB infection, disease and mortality, and sensitivity analyses excluding infants with baseline TB-specific responses on flow cytometry. ETHICS AND DISSEMINATION:An external and independent Data and Safety Monitoring Board monitors adverse events. Results will be disseminated through peer-reviewed journals, presentations at local and international conferences to national and global policy-makers, the local community and participants. TRIAL REGISTRATION NUMBER:NCT02613169; Pre-results.
| S-EPMC7045242 | biostudies-literature
Project description:IntroductionIsoniazid preventive therapy (IPT) is effective in treating tuberculosis (TB) infection and hence limiting progression to active disease. However, the durability of protection, associated factors and cost-effectiveness of IPT remain uncertain in low-and-middle income countries, Uganda inclusive. The Uganda Ministry of health recommends a single standard-dose IPT course for eligible people living with HIV (PLHIV). In this study we determined the incidence, associated factors and median time to TB diagnosis among PLHIV on Antiretroviral therapy (ART) who initiated IPT.Materials and methodsWe conducted a retrospective cohort study at eleven The AIDS Support Organization (TASO) centers in Uganda. We reviewed medical records of 2634 PLHIV on ART who initiated IPT from 1st January 2016 to 30th June 2018, with 30th June 2021 as end of follow up date. We analyzed study data using STATA v.16. Incidence rate was computed as the number of new TB cases divided by the total person months. A Frailty model was used to determine factors associated with TB incidence.ResultsThe 2634 individuals were observed for 116,360.7 person months. IPT completion rate was 92.8%. Cumulative proportion of patients who developed TB in this cohort was 0.83% (22/2634), an incidence rate of 18.9 per 100,000 person months. The median time to TB diagnosis was 18.5 months (minimum- 0.47; maximum- 47.3, IQR: 10.1-32.4). World Health Organization (WHO) HIV clinical stage III (adjusted hazard ratio (aHR) 95%CI: 3.66 (1.08, 12.42) (P = 0.037) and discontinuing IPT (aHR 95%CI: 25.96(4.12, 169.48) (p = 0.001)), were associated with higher odds of TB diagnosis compared with WHO clinical stage II and IPT completion respectively.ConclusionIncidence rates of TB were low overtime after one course of IPT, and this was mainly attributed to high completion rates.
| S-EPMC9109920 | biostudies-literature
Project description: Not available
| S-EPMC7365362 | biostudies-literature