Rosario Montoya

Background: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL).Methods: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ≥15 years for “patients” (n=1545) starting treatment for tuberculosis disease in health centres; “contacts” (n=3180) who shared a patient's household for ≥6 h·week⁻¹; and randomly selected “controls” (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place.Findings: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (pversusthose with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001).Conclusions: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.

Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings. Optimization: Patients with smear-positive pulmonary TB before treatment and healthy control participants provided sputa. These were divided into equal aliquots that were tested directly or after NaOH centrifuge-decontamination. Each aliquot was cultured and used to prepare slides (n = 80). FDA microscopy used: 1 or 3 drops of sputum; with/out acid-alcohol wash; with/out phenol sterilization; with 0/30/60 seconds KMnO₄ quenching. Control samples all had negative culture and microscopy results. FDA microscopy had higher sensitivity when performed directly (without centrifuge-decontamination) on 1 drop of sputum (P0.1). Validation: The 2 protocols that performed best in the optimization experiments were reassessed operationally by comparing duplicate slides (n = 412) stained with KMnO₄ quenching for 30 versus 60 seconds. FDA microscopy results were similar (P = 0.4) and highly reproducible, with 97% of counts agreeing within +/-1 logarithm. Storage: Smear microscopy slides and aliquots of the sputum from which they were made were stored for 4 weeks. Twice-weekly, paired slides (n = 80) were stained with freshly prepared versus stored FDA and read quantitatively. Storing sputum, microscopy slides or FDA solution at 4°C or room temperature had no effect on FDA microscopy results (all P>0.2). Cost: Material costs for each slide tested by FDA microscopy using reagents purchased locally were USD $0.05 and required the same equipment, time and skills as auramine acid-fast microscopy. We recommend a simple, bio-secure protocol for FDA microscopy that provides sensitive and repeatable results without requiring centrifugation.

Objectives Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access amongst patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes. Methods In a prospective cohort study in Callao, Peru, we recruited and interviewed 2,584 patients with tuberculosis between 2007‐2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016‐2017. Data were analysed using logistic regression and by calculating relative risks (RR). Results Between 2007‐2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (p<0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all p<0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% versus 13%, RR=1.5; p=0.001) or an adverse treatment outcome (29% versus 23% RR=1.3; p=0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third. Conclusion Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.

Cash transfers are key interventions in the World Health Organisation’s post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project. Newly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings). To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders. Over 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally. Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering. Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to the initial bank-provider being limited; and conditions requiring participation of all TB-affected household members (e.g. community meetings) being hard to achieve. Refinements were made to improve project acceptability and future impact: the initial bank-provider was changed; conditional and unconditional cash transfers were combined; cash transfer sums were increased to a locally-appropriate, evidence-based amount; and cash transfer size varied according to patient household size to maximally reduce mitigation of TB-related costs and be more responsive to household needs. A novel TB-specific socioeconomic intervention including conditional cash transfers has been designed, implemented, refined and is ready for impact assessment, including by the CRESIPT project. The lessons learnt during this research will inform policy-makers and decision-makers for future implementation of related interventions.

Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.