Tuberculosis treatment loss to follow-up in children exposed at home: A prospective cohort study.

Background: Loss to follow-up (LTFU) from tuberculosis (TB) treatment and care is a significant public health problem. It is important to understand what drives LTFU in children - a population whose treatment and management depend on an adult caregiver - to better provide support services to families affected by TB. Methods: We conducted a prospective cohort study of household contacts in Lima, Peru (2009-12). Using multilevel logistic regression analysis, we explored individual-level characteristics of children and their adult household members with TB disease to identify risk factors for LTFU among children initiated on treatment for TB. Results: A total of 154 child (0-14 years) household contacts were diagnosed with TB and initiated on treatment. While most (n = 133, 86.4%) had a successful outcome, 20 (13.0%) children were LTFU. Six (30.0%) children were LTFU within three months, nine (45.0%) between five to seven months, and three (15.0%) after seven months of treatment being initiated. In univariable analysis, children with index patients above 25 years of age had decreased odds of being LTFU (odds ratio = 0.26; 95% confidence interval = 0.08-0.84) compared to children with index patients 25 years or younger. Conclusions: In this cohort, more than 10% of children sick with TB who were exposed to the disease at home were LTFU. An integrated, family-centred TB prevention and management approach may reduce barriers to a child completing their course of TB treatment.

Barriers and facilitators to tuberculosis diagnosis in Lima, Peru: a mixed methods study.

BACKGROUND: Tuberculosis (TB) infectiousness decreases significantly with only a few days of treatment, but delayed diagnosis often leads to late treatment initiation. We conducted a sequential explanatory mixed methods study to understand the barriers and facilitators to prompt diagnosis among people with TB. METHODS: We enrolled 100 adults who started TB treatment in the Carabayllo district of Lima, Peru, between November 2020 and February 2022 and administered a survey about their symptoms and healthcare encounters. We calculated total diagnostic delay as time from symptom onset to diagnosis. We conducted semi-structured interviews of 26 participants who had a range of delays investigating their experience navigating the health system. Interview transcripts were inductively coded for concepts related to diagnostic barriers and facilitators. RESULTS: Overall, 38% of participants sought care first from public facilities and 42% from the private sector. Only 14% reported being diagnosed with TB on their first visit, and participants visited a median of 3 (interquartile range [IQR] health facilities before diagnosis. The median total diagnostic delay was 9 weeks (interquartile range [IQR] 4-22), with a median of 4 weeks (IQR 0-9) before contact with the health system and of 3 weeks (IQR 0-9) after. Barriers to prompt diagnosis included participants attributing their symptoms to an alternative cause or having misconceptions about TB, and leading them to postpone seeking care. Once connected to care, variations in clinical management, health facility resource limitations, and lack of formal referral processes contributed to the need for multiple healthcare visits before obtaining a diagnosis. Facilitators to prompt diagnosis included knowing someone with TB, supportive friends and family, referral documents, and seeing a pulmonologist. CONCLUSIONS: Misinformation about TB among people with TB and providers, poor accessibility of health services, and the need for multiple encounters to obtain diagnostic tests were major factors leading to delays. Extending the hours of operation of public health facilities, improving community awareness and provider training, and creating a formal referral process between the public and private sectors should be priorities in the efforts to combat TB.

Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

OBJECTIVE: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis. METHODS: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for age and sex. RESULTS: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta-analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%-14.9%, four studies). Age-and sex-standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self-report or medical records was 3.4% (95% CI 2.6%-4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta-analysis. There were limited data for other non-communicable diseases. CONCLUSION: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non-communicable diseases and address shared risk factors.

History of tuberculosis disease is associated with genetic regulatory variation in Peruvians.

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.

Proof of concept of the Universal Baby video innovation for early child development in Lima, Peru.

OBJECTIVE: Community-based video interventions offer an effective and potentially scalable early interaction coaching tool for caregivers living in low resource settings. We tested the Universal Baby (UB) video innovation; an early interaction coaching tool using video sourced and produced locally with early child development (ECD) expert supervision. METHODS: This proof-of-concept study enrolled 40 caregivers of children ages 10-18 months assigned to intervention and control groups by health establishments in Carabayllo, Lima, Peru. Mother/child dyads received 12 weekly group health education sessions with social support. Of those, 16 caregivers also received 6 UB videos featuring brain science education and local clips of responsive, reciprocal interaction, also known as "serve and return" interaction. Survey data assessed feasibility and acceptability of the intervention. We assessed improved quality of mother/child interaction using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). RESULTS: We found the program feasible. We successfully trained the local team to produce UB videos using locally-sourced footage and delivered the videos as part of a community-based intervention. We also found it to be acceptable in that participants enthusiastically received the UB videos, reporting they enjoyed being videotaped, and learned how to recognize and appropriately respond to their child's nuanced sounds and gestures. The median change in total PICCOLO scores favored the intervention group compared to the control group. CONCLUSIONS: UB offers great potential as a sustainable, potentially scalable, and culturally appropriate tool to promote equity for child development among young children living in low resource homes globally.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Exploring the Role of the Private Sector in Tuberculosis Detection and Management in Lima, Peru: A Mixed-Methods Patient Pathway Analysis.

In Latin America, little is known about the involvement of private health-care providers in tuberculosis (TB) detection and management. We sought to gain a better understanding of current and potential roles of the private sector in delivering TB services in Peru. We conducted a mixed-methods study in North Lima, Peru. The quantitative component comprised a patient pathway analysis assessing the alignment of TB services with patient care-seeking behavior. The qualitative component comprised in-depth interviews with 18 private health-care providers and 5 key informants. We estimated that 77% of patients sought care initially at a facility with TB diagnostic capacity and 59% at a facility with TB treatment capacity. Among private facilities, 43% offered smear microscopy, 13% offered radiography, and none provided TB treatment. Among public-sector facilities, 100% offered smear microscopy, 26% offered radiography, and 99% provided TB treatment. Private providers believed they offered shorter wait times and a faster diagnosis, but they struggled with a lack of referral systems and communication with the public sector. Nonrecognition of private-sector tests by the public sector led to duplicate testing of referred patients. Although expressing willingness to collaborate with public-sector programs for diagnosis and referral, private providers had limited interest in treating TB. This study highlights the role of private providers in Peru as an entry point for TB care. Public-private collaboration is necessary to harness the potential of the private sector as an ally for early diagnosis.

Programmatic implementation of depression screening and remote mental health support sessions for persons recently diagnosed with TB in Lima, Peru during the COVID-19 pandemic.

Background: Few studies have explored a stepped care model for delivering mental health care to persons with tuberculosis (TB). Here, we evaluated depression screening and remote low-intensity mental health interventions for persons initiating TB treatment in Lima, Peru during the COVID-19 pandemic. Methods: We used the Patient Health Questionnaire 9 (PHQ-9) to screen participants for depressive symptoms (PHQ-9 ≥ 5). Participants with PHQ-9, 5-14 received remote Psychological First Aid (PFA) or Problem Management Plus (PM+). Participants were reevaluated 6 months after intervention completion. We then compared the change in median PHQ-9 scores before and after intervention completion. Those with PHQ-9 ≥ 15 were referred to higher-level care. Findings: We found that 62 (45.9%) of the 135 participants had PHQ-9 ≥ 5 at baseline. Then, 54 individuals with PHQ-9, 5-9 received PFA, of which 44 (81.5%) were reevaluated. We observed significant reductions in median PHQ-9 scores from 6 to 2 (r = 0.98; p < 0.001). Four participants with PHQ-9, 10-14 received PM+ but were unable to be reevaluated. Four participants with PHQ-9 ≥ 15 were referred to higher-level care. Conclusions: Depressive symptoms were common among persons recently diagnosed with TB. We observed improvements in depressive symptoms 6 months later for most participants who received remote sessions of PFA.

Who Transmits Tuberculosis to Whom: A Cross-Sectional Analysis of a Cohort Study in Lima, Peru.

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. In the triage cohort (n = 387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n = 191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Identifying adolescents at risk for suboptimal adherence to tuberculosis treatment: A prospective cohort study.

Adolescents account for an estimated 800,000 incident tuberculosis (TB) cases annually and are at risk for suboptimal adherence to TB treatment. Most studies of adolescent TB treatment adherence have used surveillance data with limited psychosocial information. This prospective cohort study aimed to identify risk factors for suboptimal adherence to rifampicin-susceptible TB treatment among adolescents (10-19 years old) in Lima, Peru. We collected psychosocial data using self-administered surveys and clinical data via medical record abstraction. Applying k-means cluster analysis, we grouped participants by psychosocial characteristics hypothesized to impact adherence. Then, we conducted mixed effects regression to compare suboptimal adherence-defined as <90% (missing >10% of doses)-between clusters. Treatment setting (facility vs. home) and drug formulation (single drug vs. fixed dose combination) were interaction terms. Of 249 participants, 90 (36.1%) were female. Median age was 17 (IQR: 15, 16.6) years. We identified three clusters-A, B, and C-of participants based on psychosocial characteristics. Cluster C had the lowest support from caregivers, other family members, and friends; had the weakest motivation to complete TB treatment; were least likely to live with their mothers; and had experienced the most childhood adversity. Among the 118 (47.4%) participants who received facility-based treatment with single drug formulations, adherence did not differ between Clusters A and B, but Cluster C had six-fold odds of suboptimal adherence compared to Cluster A. In Clusters B and C, adherence worsened over time, but only in Cluster C did mean adherence fall below 90% within six months. Our findings have implications for the care of adolescents with TB. When caring for adolescents with low social support and other risk factors, clinicians should take extra measures to reinforce adherence, such as identifying a community health worker or peer to provide treatment support. Implementing newly recommended shorter regimens also may facilitate adherence.

Retention and Viral Suppression Among Adolescents Newly Initiating Antiretroviral Therapy in Adult HIV Care in Lima, Peru: A Retrospective Cohort Study.

PURPOSE: Published data on outcomes among adolescents newly initiating antiretroviral treatment in the Latin American context are sparse. We estimated the frequency of sustained retention with viral load suppression (i.e., successful transition) and identified predictors of successful transition into adult care among youth (aged 14-21 years) with recently acquired HIV in Lima, Peru. METHODS: A retrospective cohort study was conducted among 184 adolescents and young adults who initiated antiretroviral therapy in an adult public sector HIV clinic between June 2014 and June 2019. Sustained retention (no loss-to-follow-up or death) with viral suppression was calculated for the first 12 and 24 months following treatment initiation. We conducted regression analyses to assess factors associated with successful transition to adult HIV care, including gender, age, occupation, nationality, pregnancy, same-sex sexual behavior, presence of treatment supporter, number of living parents, and social risk factors that may adversely influence health (e.g., lack of social support, economic deprivation). RESULTS: Patients were predominantly male (n = 167, 90.8%). Median age was 19 years (interquartile range: 18-21). Frequency of sustained retention with viral load suppression was 42.4% (78/184) and 35.3% (30/85) at 12 and 24 months following treatment initiation. In multivariable analyses, working and/or studying was inversely associated with successful transition into adult care at 12 months; number of known living parents (relative risk: 2.20; 95% confidence interval: 1.12, 4.34) and absence of social risk factors (relative risk: 1.68; 95% confidence interval: 0.91, 3.11) were positively associated with successful transition at 24 months. DISCUSSION: Sustained retention in HIV care was uncommon. Parental support and interventions targeting social risk factors may contribute to successful transition into adult HIV care in this group.

A costing framework to compare tuberculosis infection tests.

OBJECTIVE: To develop a framework to estimate the practical costs incurred from, and programmatic impact related to, tuberculosis (TB) infection testing-tuberculin skin tests (TST) versus interferon gamma release assay (IGRA)-in a densely populated high-burden TB area. METHODS: We developed a seven-step framework that can be tailored to individual TB programmes seeking to compare TB infection (TBI) diagnostics to inform decision-making. We present methodology to estimate (1) the prevalence of TBI, (2) true and false positives and negatives for each test, (3) the cost of test administration, (4) the cost of false negatives, (5) the cost of treating all that test positive, (6) the per-test cost incurred due to treatment and misdiagnosis and (7) the threshold at which laboratory infrastructure investments for IGRA are outweighed by system-wide savings incurred due to IGRA utilisation. We then applied this framework in a densely populated, peri-urban district in Lima, Peru with high rates of Bacillus Calmette-Guérin (BCG) vaccination. FINDINGS: The lower sensitivity of TST compared with IGRA is a major cost driver, leading to health system and societal costs due to misdiagnosis. Additionally, patient and staff productivity costs were greater for TST because it requires two patient visits compared with only one for IGRA testing. When the framework was applied to the Lima setting, we estimate that IGRA-associated benefits outweigh infrastructural costs after performing 672 tests. CONCLUSIONS: Given global shortages of TST and concerns about costs of IGRA testing and laboratory capacity building, this costing framework can provide public health officials and TB programmes guidance for decision-making about TBI testing locally. This framework was designed to be adaptable for use in different settings with available data. Diagnostics that increase accuracy or mitigate time to treatment should be thought of as an investment instead of an expenditure.

Utility of Mycobacterium tuberculosis genome sequencing snapshots to assess transmission dynamics over time.

We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) "snapshots" at a sentinel site within Lima, Peru for evaluating local transmission dynamics over time. Within a 17 km2 area, 15/70 (21%) isolates with WGS collected during 2011-2012 and 22/81 (27%) collected during 2020-2021 were clustered (p = 0.414), and additional isolates clustered with those from outside the area. Isolates from the later period were disproportionately related to large historic clusters in Lima from the earlier period. WGS snapshots at a sentinel site may not be useful for monitoring transmission, but monitoring the persistence of large transmission clusters might be.

Perinatal depression and implementation of the "Thinking Healthy program" support intervention in an impoverished setting of Lima, Peru: Assessment before and during the COVID-19 pandemic.

Socios En Salud (SES) implemented the Thinking Healthy program (THP) to support women with perinatal depression before and during the COVID-19 pandemic in Lima Norte. We carried out an analysis of the in-person (5 modules) and remote (1 module) THP intervention. Depression was detected using PHQ-9, and THP sessions were delivered in women with a score (PHQ-9 ≥ 5). Depression was reassessed and pre- and post-scores were compared. In the pre-pandemic cohort, perinatal depression was 25.4% (47/185), 47 women received THP and 27 were reassessed (57.4%), and the PHQ-9 score median decreased from 8 to 2, p < 0.001. In the pandemic cohort, perinatal depression was 47.5% (117/247), 117 women received THP and 89 were reassessed (76.1%), and the PHQ-9 score median decreased from 7 to 2, p < 0.001. THP's modalities helped to reduce perinatal depression. Pregnant women who received a module remotely also reduced depression.

Spatially-targeted tuberculosis screening has limited impact beyond household contact tracing in Lima, Peru: A model-based analysis.

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened.

Exploring the role of the private sector in tuberculosis detection and management in Lima, Peru: a mixed-methods patient pathway analysis.

In Latin America, little is known about the involvement of private healthcare providers in TB detection and management. We sought to gain a better understanding of current and potential roles of the private sector in delivering TB services in Peru. We conducted a mixed-methods study in Lima, Peru. The quantitative component comprised a patient pathway analysis assessing the alignment of TB services with patient care-seeking behavior. The qualitative component comprised in-depth interviews with 18 private healthcare providers and 5 key informants. We estimated that 77% of patients initially sought care at a facility with TB diagnostic capacity and 59% at a facility with TB treatment capacity. The lack of TB services at initial care-seeking location was driven by the 41% of patients estimated to seek care first at a private facility. Among private facilities, 43% offered smear microscopy, 13% offered radiography, and none provided TB treatment. Among public sector facilities, 100% offered smear microscopy, 26% offered radiography, and 99% provided TB treatment. Interviews revealed that private providers believed that they offered shorter wait times and a quicker diagnosis, but they struggled with a lack of follow-up systems and communication barriers with the public sector. While expressing willingness to collaborate with public sector programs for diagnosis and referral, private providers had limited interest in treating TB. This study highlights the role of private providers in Peru as an entry point for TB care. Public-private collaboration is necessary to harness the potential of the private sector as an ally for early diagnosis.

The COVID-19 pandemic as a catalyst for integrated global mental healthcare and tuberculosis care.

Mental disorders are common among persons with tuberculosis (TB), and the COVID-19 pandemic has only amplified the mental and physical health consequences of this deadly synergy. Here, we call to attention the immense vulnerability of people with TB to mental disorders during the pandemic and highlight the unique challenges and opportunities that the pandemic brings to the future integration of global TB and mental healthcare. We argue that the pandemic era is an ideal period to accelerate this integration and we provide research and policy recommendations to actualise this urgent need.