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Implementation practices of tuberculosis preventive therapy for children and HIV-positive adults
Book - Dissertation
Subtitle:a prospective cohort study at primary care
Background: Tuberculosis preventive therapy (TPT) reduces the risk of progression from infection with Mycobacterium tuberculosis to active tuberculosis disease (TB), in particular for high risk groups such as people living with HIV (PLHIV) and children in close contact with a person affected by TB. To reach global TB elimination, TPT needs to be scaled-up. Yet, global TPT uptake is low and once on TPT, few people succeed to complete their TPT course. Targeted TPT guided by tuberculin skin test (TST) could increase the effectiveness of TPT but poses great challenges to patients and human resources, especially in high burden settings. Aim: To evaluate the implementation and coverage of tuberculosis preventive therapy (TPT) in primary care clinics under routine conditions, identify the barriers to scale-up of TPT in people living with HIV and children in close contact with a person affected by TB, and investigate novel health system approaches to effective and efficient routine TPT programs. Methods: Using a behavioural intervention framework, an implementation research study was performed at three primary care clinics in Northern Johannesburg, South Africa. At each clinic, TPT and TST training was given, and each clinic developed a TPT strategy in a participatory manner. TPT uptake was determined among PLHIV (in all 3 clinics) and children in close contact with an adult affected by TB (in one of the 3 clinics). Health care workers fidelity to the guidelines and barriers to TPT and TST implementation under real-life conditions were assessed. In a prospective cohort of PLHIV starting antiretroviral therapy (ART), this PhD research examined TST conversion (i.e. change from an initial negative TST to a positive TST (≥ 5 mm induration)) to determine the optimal timing of TST placement during the first year on ART. The performance and cost implications of three novel strategies to TST reading were investigated among PLHIV: self-reading, fast-tracking and task-shifting of TST reading. The potential of replacing the TST by a monocyte-to-lymphocyte ratio was explored in 171 ART-naïve adults using a cross-sectional study. Results: According to routine register data of the three participating primary care clinics, the proportion of PLHIV initiating TPT increased substantially at the clinic not opting for TST (6% vs 36%), but minimally (34% vs 37% and 0.7% vs 3%) in the two other clinics. Coverage of TPT differed by type of individual: 54% of pregnant women, 16% of individuals with a recent HIV diagnosis, 11% of individuals with a CD4 count under 500 cells/mm³, and 9% of people on ART. Except for screening of TB symptoms among PLHIV, health care workers fidelity to the TPT guidelines was low, with only two-thirds (68%) of symptomatic patients investigated for TB and TST not implemented as intended (<1% coverage). The main barriers that led to low uptake of TPT and TST among PLHIV as cited by the health care workers were operational issues with TST, concerns of health care workers regarding exclusion of active TB, and low patient awareness about TPT. Most (93/170) of the 170 children that had been in contact with an adult affected by TB failed to visit the clinic, and half of the children initiating TPT (24/46) did not adhere to the full 6-month course. To determine the optimal timing of the TST placement during the first year of ART, TST conversion was examined among 231 PLHIV, of which 22% (51/231) were TST positive at the time of ART initiation. Among those who were TST negative at the time of ART initiation, a high rate of TST conversion was observed, with a 22% TST conversion (24/109) after 6 months of ART and an additional 12% TST conversion (9/78) after 1 year on ART. To overcome the burden related to TST reading, three novel strategies (self-reading, fast-tracking and task-shifting) for TST reading were evaluated. Firstly, the performance of TST self-reading was assessed in 278 PLHIV. Of the people who self-read their TST, 97% (269/278) correctly self-identified the presence or absence of any induration [sensitivity 89% (95% CI 80,95) and specificity 99.5% (95% CI 97,100)]. For detection of a positive TST, sensitivity was 90% (95% CI 81,96) and specificity 99% (95% CI 97,100). Secondly, experiences with task-shifting of TST reading to lower cadre health assistants were positive with excellent overall agreement of 256 TST readings (in mm) by lower cadre and high cadre staff (kappa statistic of 0.97, 95% CI 0.94, 1.00). Thirdly, introducing fast-tracking for patients’ TST reading had a positive impact on the patients as the average waiting time for patients was reduced by more than 3 hours, from 254 minutes for a regular clinic visit (n=73) to 38 minutes for a fast-track visit (n=27). The combined novel strategy (fast-tracking + task-shifting + self-reading) was cost-saving in South Africa as it resulted in a saving of 40% of the total TST program cost compared to the standard program. Finally, regarding the potential of the monocyte-to-lymphocyte ratio (MLR) to replace the TST, this PhD research did not find evidence in ART-naïve adults without symptoms suggestive of active TB to support such a hypothesis, as the MLR was not independently associated with TST positivity (aOR 0.83 for every 0.1 unit increase in MLR, 95% CI 0.60, 1.08). Conclusion: The implementation and scale-up of TPT services for people living with HIV and for children in close contact with a TB case face important barriers across the TPT cascade, from poor access to the clinic to low provision and completion of preventive treatment. Among children in close contact with a TB case, access to the clinic for TPT eligibility screening and non-completion of TPT were the key challenges for successful TPT. For PLHIV, key challenges related to TST placement and reading. The novel strategy of TST self-reading could overcome the TST reading challenge from a health care worker and patient perspective as it reduces the number of patients that need to return for TST reading. The fast-tracking and task-shifting of TST reading could further reduce the patient and health system burden associated with targeted TST guided TPT programs and reduce its cost. While the monocyte-to-lymphocyte ratio is unlikely to be a useful alternative to TST, the observation of a high TST conversion during the first year of ART suggests that empiric TPT for all people living with HIV followed by TST assessment after 6 or 12 months of ART could be an effective approach to identify those people in need of (life-)long TPT. Taken together, the findings of this PhD suggest novel health system approaches to TPT that could increase the cost-effectiveness of TPT programs and may result in increased uptake of TPT.
Number of pages: 132