Tuberculosis Preventive Therapy Research Articles

Izoniazidom navodené poškodenie pečene sprevádzané ikterom

Summary: Isoniazid belongs to the first line antituberculosis drugs and can be used for the treatment of both active and latent tuberculosis infections. It is a part of combined regimens, for the preventive treatment of tuberculosis isoniazid can be used in monotherapy as well. Even though elevations in serum aminotransferases levels during isoniazid therapy are seen frequently, the development of symptomatic hepatitis is rare, according to specialised literature. This article describes a case of a patient who developed drug-induced liver injury accompanied by jaundice during the isoniazid preventive treatment of tuberculosis. It also provides a summary of the currently known risk factors, pathogenesis, and incidence of hepatotoxicity observed throughout therapy with this antituberculosis drug. We also illustrate the process of diagnosing drug--induced liver injury in clinical practice settings with the utilisation of the updated RUCAM score. Key words: jaundice – isoniazid – drug-induced liver injury – tuberculosis preventative therapy – updated RUCAM score.

Prevalence and incidence rates of tuberculosis in people with HIV during the coronavirus 2019 pandemic: a single center retrospective analysis

Background Tuberculosis (TB) poses a significant risk to people with HIV (PWH), with heightened incidence and prevalence rates, especially in countries with a high TB burden. This study assesses the prevalence and incidence rates of TB among PWH during the COVID-19 pandemic, and on treatment outcomes in TB-HIV co-infections. Methods A retrospective study was conducted at Suddhavej Hospital, Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand, from January 2020 to September 2023, involving newly diagnosed adult PWH. Data were collected on TB prevalence and incidence rates, with TB cases categorized as definite or possible. The primary outcomes were TB prevalence and incidence rates per 100,000 person-years of follow-up. Results Among 171 newly diagnosed PWH, the prevalence of TB was 5.85%, with an incidence rate of 4,568.71 per 100,000 person-years. All but one TB cases were diagnosed before antiretroviral therapy (ART) initiation. There was no incident TB during the follow-up period during ART. Nearly half of the TB cases required therapeutic trials without microbiological confirmation. Conclusions The study revealed a high prevalence and incidence rate of TB among PWH during the COVID-19 pandemic, comparable to pre-pandemic rates in Thailand. The findings highlight the necessity of comprehensive TB screening prior to ART initiation and the cautious implementation of universal TB preventive therapy. The use of molecular diagnostics, in addition to symptom screening, can enhance TB diagnosis among PWH, though accessibility remains an issue in many regions.

Genetic and clinical predictors of rifapentine and isoniazid pharmacokinetics in paediatrics with tuberculosis infection.

Twelve weekly doses of rifapentine and isoniazid (3HP regimen) are recommended for TB preventive therapy in children with TB infection. However, they present with variability in the pharmacokinetic profiles. The current study aimed to develop a pharmacokinetic model of rifapentine and isoniazid in 12 children with TB infection using NONMEM. Ninety plasma and 41 urine samples were collected at Week 4 of treatment. Drug concentrations were measured using a validated HPLC-UV method. MassARRAY® SNP genotyping was used to investigate genetic factors, including P-glycoprotein (ABCB1), solute carrier organic anion transporter B1 (SLCO1B1), arylacetamide deacetylase (AADAC) and N-acetyl transferase (NAT2). Clinically relevant covariates were also analysed. A two-compartment model for isoniazid and a one-compartment model for rifapentine with transit compartment absorption and first-order elimination were the best models for describing plasma and urine data. The estimated (relative standard error, RSE) of isoniazid non-renal clearance was 3.52 L·h-1 (23.1%), 2.91 L·h-1 (19.6%), and 2.58 L·h-1 (20.0%) in NAT2 rapid, intermediate and slow acetylators. A significant proportion of the unchanged isoniazid was cleared renally (2.7 L·h-1; 8.0%), while the unchanged rifapentine was cleared primarily through non-renal routes (0.681 L·h-1; 3.6%). Participants with the ABCB1 mutant allele had lower bioavailability of rifapentine, while food prolonged the mean transit time of isoniazid. ABCB1 mutant allele carriers may require higher rifapentine doses; however, this must be confirmed in larger trials. Food did not affect overall exposure to isoniazid and only delayed absorption time.

Influenza and the risk of active tuberculosis occurrence among individuals with latent tuberculosis infection: A national cohort study in South Korea (2015–2020)

BackgroundInfluenza's potential impact on active tuberculosis (TB) development has been debated, with limited clinical evidence. To address this, we explored the association between influenza episodes and TB incidence in a national cohort of individuals with latent TB infection (LTBI). MethodsWe examined adults (≥20 years) diagnosed with LTBI between 2015 and 2020, using the Health Insurance Review and Assessment Service's national database in South Korea. We collected demographic data, comorbidities, and influenza episodes within 6 months before and after the initial LTBI diagnosis (prior vs. subsequent episode). We stratified the analysis into groups with and without TB preventive therapy (TPT). ResultsAmong 220,483 LTBI subjects, 49% received TPT, while 51% did not. The average age was 48.4 years, with 52% having comorbidities. A prior and subsequent influenza episode was identified in 3221 and 4580 individuals, respectively. Of these, 1159 (0.53%) developed incident TB over an average follow-up of 1.86 years. The incidence rates of TB were comparable between individuals with and without prior and/or subsequent influenza episodes in the TPT group, but 1.4 times higher in the non-TPT group for those with such episodes. Cox proportional-hazards regression analysis indicated that influenza was not a risk factor for incident TB in the TPT group. However, a subsequent influenza episode significantly increased TB risk in the non-TPT group (hazard ratio: 1.648 [95% CI, 1.053–2.580]). ConclusionsIn individuals with LTBI not receiving TPT, experiencing an influenza episode may elevate the risk of developing active TB.

TB preventive therapy: uptake and time to initiation during implementation of ‘7-1-7’

TB preventive therapy: uptake and time to initiation during implementation of ‘7-1-7’

Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis

ObjectivesThis study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis...

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.

Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

<sec id="st1"><title>BACKGROUND</title>Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.</sec><sec id="st2"><title>METHODS</title>This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).</sec><sec id="st3"><title>RESULTS</title>There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.</sec><sec id="st4"><title>CONCLUSIONS</title>Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management.</sec>.

Long-Term Protective Effect of Tuberculosis Preventive Therapy in a Medium/High Tuberculosis Incidence Setting.

The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7]). In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis.

Burden of Tuberculosis in End Stage Renal Disease Patients Undergoing Maintenance Hemodialysis: A Multicenter Study and Experience from Ethiopian Dialysis Setting.

Patients with end stage renal disease (ESRD) are at a higher risk of developing tuberculosis (TB) due to the immunosuppressed state along with concomitant comorbidities and socioeconomic and demographic factors. Data on the prevalence of tuberculosis in ESRD are scarce despite the high burden of the disease in developing nations. A multicenter, cross-sectional study was conducted at eight dialysis centers in Addis Ababa on the prevalence of TB among CKD patients on maintenance hemodialysis from August 2022 to October 2022 G.C. The study enrolled 263 participants selected by systematic random sampling. Data were collected by reviewing the patient's electronic medical records. The Collected data were analyzed using SPSS version 26.0. Our study found a 27% prevalence of TB in patients with ESRD receiving maintenance hemodialysis (MHD). Pulmonary tuberculosis was the most prevalent form, and lymphadenitis was the most common extra-pulmonary tuberculosis (EPTB). Only 5.6% of the study participants had microbiologic evidence of TB. Chemistry and cytological studies from pleural fluid and imaging evidences were commonly used diagnostic modalities. The presence of HIV infection, longer duration of dialysis (>1 year), and contact history with a known TB patient were all significantly associated with higher prevalence of TB among the study participants. Although there is a strong association between TB and CKD, there are no local data from Ethiopia. Our study identified a higher prevalence of TB among CKD patients on MHD. Thus, maintaining a high index of suspicion and early diagnosis and treatment of TB among ESRD patients on MHD and use of TB preventive therapy (TPT) is important in decreasing morbidity and mortality.

Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial

Background: Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24–45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol: The IMPROVE trial is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early, week 2) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured in a drug-drug interaction sub-study of 15 eligible participants. Discussion: The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration: ISRCTN18437550 (05/11/2021)

Timeliness metrics for screening and preventing TB in household contacts of pulmonary TB patients in Kenya

BACKGROUND: The study assessed whether a “7-1-7” timeliness metric for screening and TB preventive therapy (TPT) could be implemented for household contacts (HHCs) of index patients with bacteriologically confirmed pulmonary TB under routine programmatic settings in Kenya.METHODS: A longitudinal cohort study conducted among index patients and their HHCs in 12 health facilities, Kiambu County, Kenya.RESULTS: Between January and June 2023, 95% of 508 index patients had their HHCs line-listed within 7 days of initiating anti-TB treatment (“First 7”). In 68% of 1,115 HHCs, screening outcomes were ascertained within 1 day of line-listing (“Next 1”). In 65% of 1,105 HHCs eligible for further evaluation, anti-TB treatment, TPT or a decision for no drugs was made within 7 days of screening (“Second 7”). Altogether, 62% of screened HHCs started TPT during the “7-1-7” period compared with 58% in a historical cohort. Main barriers to TPT uptake were HHCs not consulting clinicians, HHCs being unwilling to initiate TPT and drug shortages. Healthcare workers felt that a timeliness metric was valuable for streamlining HHC management and proposed “3-5-7” as a workable alternative.CONCLUSIONS: The national TB programme must generate awareness about TPT, ensure uninterrupted drug supplies and assess whether the “3-5-7” metric can be operationalised.

Prevalence and predictors of persistent low-level HIV viraemia: a retrospective cohort study among people receiving dolutegravir-based antiretroviral therapy in Southern Nigeria.

Persistent low-level viraemia (PLLV) is a risk factor for virologic failure among people receiving antiretroviral therapy (ART). We assessed the prevalence and predictors of PLLV among individuals receiving Dolutegravir-based ART in southern Nigeria. This retrospective cohort study used routine program data from electronic medical records of persons receiving Dolutegravir-based first-line ART in 154 PEPFAR/USAID-supported health facilities in Akwa Ibom and Cross Rivers states, Nigeria. Clients on first-line Dolutegravir-based ART ⩾6 months, who had a viral load result in the 12 months preceding October 2021 (baseline), and a second viral load result by September 2022 were included. Persons with low-level viraemia (LLV) (viral load 51-999 copies/ml) received additional adherence support. The outcome analysed was PLLV (two consecutive LLV results). Indices were summarized using descriptive statistics, and predictors of PLLV were determined using multivariate logistic regression. In total, 141,208 persons on ART were included, of which 63.3% (n = 89,944) were females. The median age was 36 [29-44] years, median ART duration was 19 [11-42] months. At the end of the study, 10.5% (14,759/141,208) had initial LLV, 90.1% (13,304/14,759) of which attained undetectable viral load (⩽50 copies/ml), and 1.1% (163/14,759) transitioned to virologic failure (⩾1000 copies/ml) by the end of the study. PLLV prevalence was 0.9% (1292/141,208). Increasing ART duration [adjusted odds ratio (aOR) = 1.0; 95% confidence interval (CI): 1.005-1.008; p < 0.001] and viral suppression (<1000 copies/ml) before initial LLV (aOR = 1.7; 95% CI: 1.50-2.00; p < 0.001) were positively associated with PLLV, while receipt of tuberculosis preventive therapy reduced the likelihood of PLLV (aOR = 0.3; 95% CI: 0.10-0.94; p = 0.039). PLLV was uncommon among individuals receiving dolutegravir-based ART and was associated with longer ART duration, prior viral suppression, and non-receipt of tuberculosis preventive therapy. This strengthens recommendations for continuous adherence support and comprehensive health services with ART, to prevent treatment failure.

Tuberculosis screening characteristics amongst freshmen in Changping District, Beijing, China

BackgroundScreening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT.MethodsThe prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, x2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${x}^{2}$$\\end{document} was obtained using the formula x2=\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${x}^{2}=$$\\end{document} nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China.ResultsAmong 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17–20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening.ConclusionsThe data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools.

The effect of antenatal isoniazid preventive therapy on birth outcomes in Western Kenya.

BACKGROUND: Pregnant women living with HIV (WLHIV) are at high risk for TB. There are limited data to inform whether TB preventive therapy is safe in pregnancy.METHODS: We completed a retrospective study of antenatal and birth records of mother-infant dyads at two health care facilities in Kisumu, Kenya. Among pregnant WLHIV, we assessed the relationship of antenatal isoniazid preventive therapy (IPT) with birth outcomes (preterm birth, low birth weight [LBW], congenital anomalies, and perinatal death).RESULTS: Of 576 mother-infant pairs, most women were on antiretroviral therapy (574, 99.7%) with viral suppression (518, 89.9%) and one-quarter had IPT exposure during pregnancy (152, 26.4%). The prevalence of preterm birth was lower among women with antenatal IPT exposure (21% vs. 30%; P = 0.03). LBW, congenital anomaly and perinatal death were not associated with antenatal IPT; however, we observed a trend toward fewer composite poor birth outcomes among women taking antenatal IPT (26% vs 33%; P = 0.08). Controlling for maternal age and viral load, IPT use during pregnancy was associated with lower odds of preterm birth (aOR 0.62, 95% CI 0.40-0.98; P = 0.04).CONCLUSION: In a programmatic setting in Western Kenya, IPT use was not associated with adverse birth outcomes.

Outcomes and Challenges in the Programmatic Implementation of Tuberculosis Preventive Therapy among Household Contacts of Pulmonary TB Patients: A Mixed-Methods Study from a Rural District of Karnataka, India.

The National TB Elimination Programme (NTEP) of India is implementing tuberculosis preventive treatment (TPT) for all household contacts (HHCs) of pulmonary tuberculosis patients (index patients) aged <5 years and those HHCs aged >5 years with TB infection (TBI). We conducted an explanatory mixed-methods study among index patients registered in the Kolar district, Karnataka during April-December 2022, to assess the TPT cascade and explore the early implementation challenges for TPT provision. Of the 301 index patients, contact tracing home visits were made in 247 (82.1%) instances; a major challenge was index patients' resistance to home visits fearing stigma, especially among those receiving care from the private sector. Of the 838 HHCs, 765 (91.3%) were screened for TB; the challenges included a lack of clarity on HHC definition and the non-availability of HHCs during house visits. Only 400 (57.8%) of the 692 eligible HHCs underwent an IGRA test for TBI; the challenges included a shortage of IGRA testing logistics and the perceived low risk among HHCs. As HHCs were unaware of their IGRA results, a number of HHCs actually eligible for TPT could not be determined. Among the 83 HHCs advised of the TPT, 81 (98%) initiated treatment, of whom 63 (77%) completed treatment. Though TPT initiation and completion rates are appreciable, the NTEP needs to urgently address the challenges in contact identification and IGRA testing.

Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial

Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. National Institute on Alcohol Abuse and Alcoholism. For the Runyankole translation of the abstract see Supplementary Materials section.

Towards tuberculosis elimination: reaching the most at-risk populations with tuberculosis preventive therapy

Towards tuberculosis elimination: reaching the most at-risk populations with tuberculosis preventive therapy

Perinatal tuberculosis-An approach to an under-recognized diagnosis.

Tuberculosis (TB) in young infants (<3 months of age), often referred to as perinatal TB, is underdiagnosed, leading to severe morbidity and high mortality. Perinatal TB includes both congenital and postnatal transmission of Mycobacterium tuberculosis. We aimed to increase an awareness of TB in neonates and young infants and to provide guidance on the assessment and management when in contact with mothers with TB during or soon after pregnancy. Approximately 217,000 pregnant women develop TB annually; if they are not diagnosed and treated during pregnancy, their infants are at high risk of adverse birth outcomes and TB disease. Although safe and effective antituberculosis treatment regimens are available during pregnancy, the diagnosis of TB is challenging. Infants born to mothers newly diagnosed with TB, not receiving any effective treatment or with cultures not yet negative, should be assessed for TB disease or M. tuberculosis infection. TB preventive therapy should be instituted if the infant is clinically well but exposed to TB, while prompt initiation of TB treatment is essential if TB disease is presumed. HIV status of mother and infant should be considered as this will affect the management. Further research is needed for the diagnosis and prevention of TB during pregnancy, an early diagnosis of TB in infants, and antituberculosis drug pharmacokinetics in young infants.

Household costs incurred under community- and facility-based service-delivery models of tuberculosis preventive therapy for children: a survey in Cameroon and Uganda

Background Tuberculosis preventive treatment (TPT) in child household contacts is recommended by World Health Organization (WHO) but limited data has been reported on the costs experienced by households with children receiving TPT. Methods We evaluated the economic impact on households with children receiving TPT within a service-delivery model cluster-randomised controlled trial in Cameroon and Uganda. The intervention included community health worker-led home-based child-contact screening, TPT initiation and monitoring, and referral of children with presumptive tuberculosis or side effects, and was compared with each country’s facility-based standard of care (control). We used a retrospective cross-sectional survey adapted from the WHO Global task force on tuberculosis patient cost surveys. All costs were collected between February 2021 and March 2021 and are presented in 2021 US$. Results The median household costs estimated using the human capital approach were higher in the control arm ($62.96 [interquartile range, IQR; $19.78-239.74] in Cameroon and $35.95 [IQR; $29.03-91.26] in Uganda) compared to the intervention arm ($2.73 [IQR; $2.73-14.18] in Cameroon and $4.55 [IQR; $3.03-6.06] in Uganda). Using a threshold of 20% of annual household income, 15% (95%CI; 5-31%) of households in Cameroon and 14% (95%CI; 4-26%) in Uganda experienced catastrophic costs in the control compared to 3% (95%CI; 1- 8%) in Cameroon and 3% (95%CI; 1-8%) in Uganda in the intervention. Using the output-based approach to estimate income losses increased costs by 14-32% in the control and 13-19% in the intervention across the two countries. The proportion of participants experiencing any dissaving was higher in the control, 53% (95%CI; 36-71%) in Cameroon and 50% (95%CI; 31-69%) in Uganda, compared to 18% (95%CI; 10-29%) in Cameroon and 17% (95%CI; 8-28%) in Uganda in the intervention. Conclusions Households with child contacts initiated on TPT under a facility-based model incur significant costs. Community-based interventions help to reduce these costs but do not eliminate catastrophic expenditures. Registration https://clinicaltrials.gov/ct2/show/NCT03832023.