Stacie C. Stender

Background: Tuberculosis infection (TBI) testing, and treatment are fundamental to achieve TB elimination. TBI testing among close or household contacts (HHCs) has been limited, in part due to perceived complexity and high operational cost. We evaluated the performance of a new near-patient and field-based QIAreach QuantiFERON-TB (QIAreach) against QuantiFERON-TB-Gold-Plus (QFT-Plus) among HHCs of people with TB. Methods: A cross-sectional study was conducted from July 2021 to September 2022 in Lesotho, South Africa and Tanzania. Blood samples were collected from HHCs for paired QFT-Plus and QIAreach processing, testing and interpretation. To evaluate the performance of QIAreach against QFT-Plus as a reference, we determined the: i) prevalence of TBI, ii) total concordance using Cohen’s Kappa, iii) predictors of discordant results using logistic regression, and iv) relationship between time to results and interferon-gamma (IFN-γ) response levels using linear correlation. Results: Out of 964 enrolled HHCs, 464 had paired results, of whom 64.9% (302/465) were female with a cohort median age of 27 years (interquartile range (IQR): 13–45). Overall, 50.9% (236/464) tested positive on QFT-Plus, while 57.1% (265/464) were positive on QIAreach assay. Total concordance between QFT-Plus and QIAreach was 78.4% [353/450, 95% confidence interval (CI): 74.4–82.2, Cohen’s Kappa: 0.5627, p < 0.001]. Discordance between assays was 23.9% (111/464) and was associated with Lesotho site (adjusted odds ratio 2.70, 95%CI: 1.48–4.92, p = 0.001). HHCs with higher IFN-γ response (QFT-Plus) (≥0.35 IU.ml-^l) had a shorter time to results on QIAreach. In addition, a strong negative correlation between QIAreach time to results and IFN-γ response (QFT-Plus) levels (R = −0.64, 95% CI: −0.87 to −0.41, p < 0.001) was observed. Conclusion: QIAreach demonstrated a moderate concordance against QFT-Plus among HHCs in three high-burden countries. Further work is needed to understand and improve its usability in high TB and low resource settings.

Background: Although tuberculosis preventive therapy guidelines support testing for tuberculosis infection in household contacts (HHCs), this adds operational complexity and cost and has often been abandoned. To understand utility of testing, we determined prevalence and risk factors for tuberculosis infection and tuberculosis preventive therapy eligibility among HHCs. Methods: In a cross-sectional study conducted from July 2021 to September 2022 in Lesotho, South Africa, and Tanzania, we enrolled people with microbiologically confirmed pulmonary tuberculosis and their HHCs. HHCs were screened and tested for tuberculosis and tuberculosis infection using Xpert Ultra and QuantiFERON-TB-Gold-Plus, respectively. Generalized linear modelling was used to determine factors associated with tuberculosis infection, using robust standard errors. Tuberculosis preventive therapy eligibility was determined using World Health Organization criteria. Results: We enrolled 342 people with pulmonary tuberculosis and 964 HHCs: 61.9% (597/964) were female with a median age of 18 years (interquartile range, 8–39 years). Overall, tuberculosis prevalence was 3.4% (25/739; 95% confidence interval [CI], 2.2%–4.9%), while tuberculosis infection prevalence was 48.7% (348/714; 95% CI, 45.0%–52.5%). Having tuberculosis infection increased with age per year (adjusted odds ratio [aOR], 1.02; 95% CI, 1.01–1.03), being from Lesotho (aOR, 1.82; 95% CI, 1.04–3.20), previous tuberculosis history (aOR, 2.25; 95% CI, 1.05–4.79), and being HIV negative (aOR, 2.30; 95% CI, 1.31–4.04). Overall, 62.2% (518/833; 95% CI, 58.8%–65.5%) were eligible for tuberculosis preventive therapy. Conclusions: Almost half of tuberculosis-exposed HHCs aged ≥5 years had tuberculosis infection. Approximately two-thirds of HHCs were eligible for tuberculosis preventive therapy, implying that providing tuberculosis preventive therapy without prior testing for tuberculosis infection may be warranted in this population. Further work on cost-effectiveness is warranted when new tests become available. Clinical Trials Registration: ISRCTN10003903.

High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018–February 2020 (prepandemic) and March 2020–February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%–35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4–268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

Background: Women living with HIV have the right to choose whether, when and how many children to have. Access to antiretroviral therapy (ART) and contraceptives, including implants, continues to increase in Kenya. Studies have reported drug-drug interactions leading to contraceptive failures among implant users on ART. This retrospective record review aimed to determine unintentional pregnancy rates among women 15-49 years of age, living with HIV and concurrently using implants and ART in western Kenya between 2011 and 2015. Methods: We reviewed charts of women with more than three months of concurrent implant and ART use. Implant failure was defined as implant removal due to pregnancy or birth after implant placement, but prior to scheduled removal date. The incidence of contraceptive failure was calculated by woman-years at risk, assuming a constant rate. Results: Data from 1,152 charts were abstracted, resulting in 1,190 implant and ART combinations. We identified 115 pregnancies, yielding a pregnancy incidence rate of 6.32 (5.27–7.59), with 9.26 among ETG and 4.74 among LNG implant users, respectively. Pregnancy incidence rates did not differ between EFV- and NVP-based regimens (IRR=1.00, CI: 0.71-1.43). No pregnancies were recorded among women on PI-based regimens, whereas pregnancy rates for efavirenz and nevirapine-containing regimens were similar, at 6.41 (4.70–8.73) and 6.44 (5.13–8.07), respectively. Pregnancy rates also differed significantly by implant type, with LNG implant users half as likely to experience pregnancy as ETG implant users (0.51, CI: 0.33-0.79, p>0.01). Conclusions: Our findings highlight the implications of drug-drug interaction on women’s choices for contraception.

Background: Women living with HIV have the right to choose whether, when and how many children to have. Access to antiretroviral therapy (ART) and contraceptives, including implants, continues to increase due to a multitude of efforts. In Kenya, 4.8% of adults are living with HIV, and in 2017, 54% were receiving an efavirenz-based ART regimen. Meanwhile, 16.1% of all Kenyan married (and 10.4% of unmarried) women used implants. Studies have reported drug interactions leading to contraceptive failures among implant users on ART. This retrospective record review aimed to determine unintentional pregnancy rates among women 15-49 years of age, living with HIV and concurrently using implants and ART in western Kenya between 2011 and 2015. Methods: We reviewed charts of women with more than three months of concurrent implant and ART use. Implant failure was defined as implant removal due to pregnancy or birth after implant placement, but prior to scheduled removal date. The incidence of unintended pregnancy was calculated by woman-years at risk, assuming a constant rate. Results: Data from 1,152 charts were abstracted, resulting in 1,190 implant and ART combinations. We identified 115 pregnancies, yielding a pregnancy incidence rate of 6.32 (5.27–7.59), with 9.26 among ETG and 4.74 among LNG implant users, respectively. No pregnancies were recorded among women on non-NNRTI-based regimens, whereas pregnancy rates for efavirenz and nevirapine-containing regimens were similar, at 6.41 (4.70–8.73) and 6.44 (5.13–8.07), respectively. Conclusions: Our findings highlight the implications of drug interaction on women’s choices for contraception.