Isoniazid preventive therapy in child household contacts of adults with active TB in Bamako, Mali

BACKGROUND and OBJECTIVE: Isoniazid preventive therapy (IPT) is known to reduce the risk of developing active TB in about 59% in children aged 15 years. We assessed adherence, completion and adverse events among children who were household contacts of a newly diagnosed adult with smear-positive TB in Bamako, Mali.METHODS: Children aged <15 years living in the same house with an adult smear-positive index case were enrolled in the study in the Bamako Region after consent was obtained from the parent or legal guardian. Adherence was assessed based on the number of tablets consumed during 6 months.RESULTS: A total of 260 children aged <15 years were identified as household contacts of 207 adult patients with smear-positive TB during the study period. Among all child contacts, 130/260 (50.0%) were aged 0–4 years and were eligible for IPT; 128/130 (98.5%) were started on IPT and 83/128 (64.8%) completed with good adherence at the end of the 6 months, and without any significant adverse events.CONCLUSION: We successfully implemented IPT with good acceptance, but low completion rate. The Mali National TB Program and partners should expand this strategy to reach more children in Bamako and the whole country and create greater awareness in the population.

Tuberculosis screening coverage and isoniazid preventive therapy among people living with HIV at Gambella Hospital, southwest Ethiopia: a retrospective study design

Objective We aimed to assess the coverage of tuberculosis screening and isoniazid preventive therapy (IPT) among people living with human immunodeficiency virus (PLHIV) at Gambella Hospital, southwest Ethiopia. Methods We conducted a 5-year retrospective study of PLHIV receiving care in an antiretroviral therapy clinic from 1 January 2011 to 30 December 2015. We reviewed a total of 900 medical records of patients with complete information. Result Of the total, 897 (99.7%) PLHIV were screened for tuberculosis, among which 77 (8.6%) were found to be positive for active tuberculosis. Among 820 (91.4%) individuals eligible for IPT, only 545 (66.5%) were provided IPT; 275 (33.5%) eligible PLHIV were not provided IPT. Male sex (adjusted odds ratio [AOR] 1.63) and ages 18–29 years (AOR 0.33) and 30–44 years (AOR 0.31) were significantly associated with the likelihood of tuberculosis infection. Conclusion The present study findings demonstrated that tuberculosis screening for PLHIV at Gambella Hospital was improved in comparison with reports from many African countries and other parts of Ethiopia. Despite this improvement, the implementation rate of IPT was below national and World Health Organization recommendations. Overall, tuberculosis diagnostic approaches and available preventive measures should be strengthened in the study area.

Effect of Isoniazid Preventive Therapy on the Incidence of Tuberculosis among Seropositive Children Attending HIV/AIDS Care in Two General Hospitals, Northwest Ethiopia, 2021

The human immune deficiency virus (HIV) is the strongest risk factor for the incidence of tuberculosis (TB) by way of reactivation of latent or new infection. The provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB. To date, there have been limited clinical data regarding the effectiveness of isoniazid preventive therapy (IPT) on TB incidence. This study aimed to assess the effect of isoniazid preventive therapy on the incidence of tuberculosis for seropositive children in Northwest Ethiopia. Methods. A facility-based retrospective follow-up was employed for reviewing 421 files from 1 January 2015 up to 30 December 2019. EpiData version 3.2 and Stata/14 software were used for data entry and analysis, respectively. Categorical variables at bivariable Cox regression were assessed for candidates transferred at P value <0.25 for multivariable Cox regression to claiming predictors associated with TB incidence rate at 95% CI at P < 0.005 . Result. The overall incidence of TB was found to be 4.99 cases per 100 person-years at 95% CI (3.89–6.53). Missed IPT (AHR = 7.45, 95% CI: 2.96, 18.74, P < 0.001 ), missed cotrimoxazole preventive therapy (CPT) (AHR = 2.4, 95% CI: 1.84–4.74, P < 0.022 ), age ≥ 11 years (AHR = 4.2, 95% CI: 1.04–7.03, P < 0.048 ), MUAC ≤ 11.5 cm (AHR = 4.36, 95% CI: 1.97–9.97, P < 0.001 ), WHO stages III and IV (AHR = 2.04, 95% CI: 1.12–3.74, P < 0.022 ), and CD4 count ≤100 cells/μl (AHR = 3.96, 95% CI: 1.52–10.34, P < 0.005 ) were significantly associated with TB incidence. Conclusion. Concomitant administration of ART with IPT had demoted more than ninety-six percent of new TB incidences for this report. Undertaking in-depth TB screening and frequent follow-up among all these children is critical in order to prevent and control tuberculosis.

Impact of Isoniazid Preventive Therapy on Tuberculosis incidence among people living with HIV: A secondary data analysis using Inverse Probability Weighting of individuals attending HIV care and treatment clinics in Tanzania

Background Information on how well Isoniazid Preventive Therapy (IPT) works on reducing TB incidence among people living with HIV (PLHIV) in routine settings using robust statistical methods to establish causality in observational studies is scarce. Objectives To evaluate the effectiveness of IPT in routine clinical settings by comparing TB incidence between IPT and non-IPT groups. Methods We used data from PLHIV enrolled in 315 HIV care and treatment clinic from January 2012 to December 2016. We used Inverse Probability of Treatment Weighting to adjust for the probability of receiving IPT; balancing the baseline covariates between IPT and non-IPT groups. The effectiveness of IPT on TB incidence was estimated using Cox regression using the weighted sample. Results Of 171,743 PLHIV enrolled in the clinics over the five years, 10,326 (6.01%) were excluded leaving 161,417 available for the analysis. Of the 24,800 who received IPT, 1.00% developed TB disease whereas of the 136,617 who never received IPT 6,085 (4.98%) developed TB disease. In 278,545.90 person-years of follow up, a total 7,052 new TB cases were diagnosed. Using the weighted sample, the overall TB incidence was 11.57 (95% CI: 11.09–12.07) per 1,000 person-years. The TB incidence among PLHIV who received IPT was 10.49 (95% CI: 9.11–12.15) per 1,000 person-years and 12.00 (95% CI: 11.69–12.33) per 1,000 person-years in those who never received IPT. After adjusting for other covariates there was 52% lower risk of developing TB disease among those who received IPT compared to those who never received IPT: aHR = 0.48 (95% CI: 0.40–0.58, P<0.001). Conclusion IPT reduced TB incidence by 52% in PLHIV attending routine CTC in Tanzania. IPTW adjusted the groups for imbalances in the covariates associated with receiving IPT to achieve comparable groups of IPT and non-IPT. This study has added evidence on the effectiveness of IPT in routine clinical settings and on the use of IPTW to determine impact of interventions in observational studies.

Isoniazid preventive therapy use among adult people living with HIV in Zimbabwe

We assessed the prevalence of isoniazid preventive therapy (IPT) uptake and explored factors associated with IPT non-uptake among people living with HIV (PLHIV) using nationally representative data from the Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) 2015–2016. This was a cross-sectional study of 3418 PLHIV ZIMPHIA participants eligible for IPT, aged ≥15 years and in HIV care. Logistic regression modeling was performed to assess factors associated with self-reported IPT uptake. All analyses accounted for multistage survey design. IPT uptake among PLHIV was 12.7% (95% confidence interval (CI): 11.4–14.1). After adjusting for sex, age, rural/urban residence, TB screening at the last clinic visit, and hazardous alcohol use, rural residence was the strongest factor associated with IPT non-uptake (adjusted OR (aOR): 2.39, 95% CI: 1.82–3.12). Isoniazid preventive therapy non-uptake having significant associations with no TB screening at the last HIV care (aOR: 2.07, 95% CI: 1.54–2.78) and with hazardous alcohol use only in urban areas (aOR: 10.74, 95% CI: 3.60–32.0) might suggest suboptimal IPT eligibility screening regardless of residence, but more so in rural areas. Self-reported IPT use among PLHIV in Zimbabwe was low, 2 years after beginning national scale-up. This shows the importance of good TB screening procedures for successful IPT implementation.

Implementation of isoniazid preventive therapy in southern Lima, Peru: an analysis of health center characteristics

Background Tuberculosis (TB) prevention through the use of preventive treatment is a critical activity in the elimination of TB. In multiple settings, limited staffing has been identified as a barrier to managing preventive treatment for TB contacts. This study aims to determine how health center staffing, service type, and TB caseload affects implementation of isoniazid preventive therapy (IPT) for TB contacts in southern Lima. Methods We conducted an ecological study in 2019 in southern Lima, Peru. Through the review of medical records, we identified contacts of TB patients who initiated IPT during 2016–2018, and who were 0–19 years old, the age group eligible for IPT according to Peruvian guidelines. We assessed bivariate associations between health center characteristics (numbers of physicians and nurses, types of services available, annual TB caseload) and IPT initiation and completion using binomial logistic regression. Results Among 977 contacts, 69% took more than a week to start IPT and 41% did not complete IPT. For those who successfully completed IPT, 58% did not complete full medical follow-up. There was no significant difference in IPT completion or adherence based on whether health centers had more physicians and nurses, more comprehensive services, or higher TB caseloads. Among contacts, female sex was associated with delay in initiating IPT (P = 0.005), age 5–19 years old was associated with completion of IPT (P = 0.025) and age < 5 years old was associated with completion of clinical evaluations (P = 0.041). Conclusions There are significant gaps in IPT implementation in health centers of southern Lima, Peru, but insufficient staffing of health centers may not be responsible. Further research is needed to identify how IPT implementation can be improved, potentially through improving staff training or monitoring and supervision. Graphic abstract

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014–2018

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale‐up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75‐fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow‐up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

Early-phase scale-up of isoniazid preventive therapy for people living with HIV in two districts in Malawi (2017)

Background Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes. Methods and findings We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%–86%). Weighted IPT initiation among persons aged <15 years (30% [95% CI: 12%–55%]) was significantly lower than among persons aged ≥15 years (72% [95% CI: 47%–89%]; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%–79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%–90%), similar to non-pregnant women aged ≥15 years (72% [95% CI: 49%–87%]). Lastly, 95% (95% CI: 92%–97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%–98%) of patients receiving IPT began on the same day as ART. Conclusions Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.