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Projected Effects of Changing Global Tuberculosis Epidemiology on <i>Mycobacterium tuberculosis</i> Prevalence and Immunoreactivity, 2024–2050
No full textWe assessed how evolving global tuberculosis (TB) trends might influence Mycobacterium tuberculosis immunoreactivity and TB risk among persons immigrating to low-incidence countries. We projected annual risk for infection (ARI) in 168 countries for 2024–2050, focusing on China, India, the Philippines, and Vietnam. We applied projections to the age profile of immigrants to 4 low-incidence countries to estimate changes in M. tuberculosis immunoreactivity prevalence and TB risk under status quo and accelerated ARI decline scenarios. In the status quo 2024 estimate, M. tuberculosis immunoreactivity prevalence ranged from 14.7% in China to 40.1% in the Philippines, declining to 5.8% in China and 23.0% in the Philippines by 2050; TB risk also declined. Accelerated ARI reductions yielded greater relative decreases in disease risk than immunoreactivity prevalence. Declining global TB incidence could reduce M. tuberculosis immunoreactivity and disease risk among immigrant populations, which could inform cost–benefit analyses for future TB screening strategies in low-incidence settings
Widening East-West inequality in life expectancy in Europe during the COVID-19 pandemic: An international comparative study.
Get PDFFor decades, life expectancy in Eastern Europe has lagged behind that in Western Europe, although the gap has narrowed since the mid-2000s. We examined the impact of the COVID-19 pandemic on these long-term trends by estimating and decomposing East-West differences in excess mortality and life expectancy losses. Regression models were used to explore the contribution of multiple factors to the observed differences. While excess mortality was initially low in Eastern Europe, partly due to lower air connectivity, by October 2020 and throughout 2021, the region experienced significantly higher life expectancy losses than Western Europe. These differences could not be attributed to greater frailty in the Eastern European populations. Rather, lower vaccination coverage and less trust in government in Eastern Europe explained about half of the gap in 2021. After the peak of the pandemic, the East-West gap in life expectancy began to narrow again. Our findings highlight that the factors behind the East-West differences in the timing and severity of pandemic-related mortality may have their ultimate origins in differences between societies that were established during the Cold War. Strengthening public health infrastructure and social trust should be considered to mitigate the unequal impact of future crises
Risk of Major Adverse Cardiovascular Events With Dolutegravir Versus Efavirenz-Based Antiretroviral Therapy: Emulated Target Trials Using Routine, De-Identified Data From South Africa.
Get PDFBACKGROUND: Integrase inhibitors, including dolutegravir, may increase risk of major adverse cardiovascular events (MACEs). However, limited data exists from low- and middle-income countries, where tenofovir disoproxil fumarate, lamivudine and dolutegravir (TLD) has largely replaced tenofovir disoproxil fumarate, emtricitabine and efavirenz (TEE).
METHODS: We used de-identified data from a South African managed-healthcare organisation from people living with HIV (PLHIV) without cardiovascular disease, who either initiated TEE or TLD between April 2020-Dec 2023 (initiation cohort) or were receiving TEE in April 2020 and eligible for TLD (transition cohort). In the initiation cohort, we emulated a target trial using pooled logistic regression models with inverse probability of treatment weights and bootstrapped confidence intervals to compare estimated 3-year MACE risk between TLD versus TEE. In the transition cohort, we used similar methods in 44 emulated monthly sequential trials, comparing MACE risk in people transitioned to TLD with those remaining on TEE.
RESULTS: In the initiation cohort, 7310 PLHIV initiated TLD (n=3711) or TEE (n=3599). Median follow-up was 21 months (IQR 10-33), with 18 MACEs with TLD (3-year risk 0.78%, 95%CI 0.38-1.11) and 28 with TEE (3-year risk 1.03%, 0.63-1.55; RR 0.75, 0.31-1.30; RD -0.25, -0.94-0.24). In the transition cohort, 22338 people contributed to 2837 person-trials with TLD and 706615 with TEE. Median follow-up was 25 months (14-36), with 19 MACEs with TLD (3-year risk 0.97%, 0.52-1.62) and 5420 with TEE (3-year risk 1.17%, 0.99-1.37; RR 0.83, 0.45-1.39; RD -0.20, -0.66-0.44).
CONCLUSIONS: Among PLHIV in South Africa we found no increased MACE with TLD
The age-specific concentrations and seroprevalence of antibodies against Salmonella Enteritidis (O:9) and Salmonella Typhimurium (O:4,5) across three sites in Kenya.
Get PDFBACKGROUND: Seroprevalence studies can indicate the age-distribution of first infection with non-typhoidal Salmonella (NTS) and estimate the rate of infection by age.
METHOD: We collected 1254 paired samples of serum and stool from healthy children and adults in Kilifi, Nairobi, and Siaya counties in Kenya, areas of low, medium and high incidence of invasive NTS disease (iNTS), respectively. We quantified the age and site-specific geometric mean concentrations (GMCs) of IgG and IgA antibodies against S. Enteritidis O-antigen (O:9, serogroup D) and S. Typhimurium O-antigen (O:4,5, serogroup B) using an in-house standardised ELISA. Serum concentrations were estimated against a previously calibrated reference serum.
RESULTS: Maternally derived O:9 IgG and O:4,5 IgG antibodies were detectable in 100% of neonates and the GMC decreased by 40% (95%CI [25%-52%]) per month in the first six months of life. GMCs of IgA were low in neonates. After age 6 months, the O:9 and O:4,5 IgG and IgA GMCs increased sharply with age across all sites, reaching a plateau in early adulthood. The rate of increase in IgG GMCs by age was highest for O:9 in Nairobi, and for O:4,5 in Kilifi. Mixture modelling defined a threshold of 14.1 AU for O:9 IgG and 28.2 AU for O:4,5 IgG. Seroprevalence also increased by age. The GMCs of O:4,5 IgG were 2 times higher for carriers of serogroup B Salmonella than non-carriers.
DISCUSSION: Maternal antibodies to non-typhoidal Salmonella decay rapidly from 0-5months after which incident infection with both serogroups occurs. To be effective, control efforts should be implemented before primary infection
Model-based cost-effectiveness analysis of first-line pharmacotherapy combinations in adults with chronic heart failure and reduced ejection fraction.
Get PDFBACKGROUND: Pharmacotherapy combinations have been shown to improve survival and reduce hospitalisations in adults with chronic heart failure with reduced ejection fraction (HFrEF); however, their cost-effectiveness when used as first-line treatment remains uncertain.
METHODS: A lifetime cohort Markov model was developed from the perspective of the NHS in England to assess the cost-effectiveness of five first-line pharmacotherapy combinations: (i) angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker (BB) (NICE-recommended treatment at the time of analysis); (ii) ACEI/ARB, BB and mineralocorticoid receptor antagonists (MRA); (iii) angiotensin receptor-neprilysin inhibitor (ARNI), BB and MRA; (iv) ACEI/ARB, BB, MRA and sodium-glucose cotransporter-2 inhibitor (SGLT2i); and (v) ARNI, BB, MRA and SGLT2i. Baseline hospitalisation and mortality rates were informed by real-world data, while treatment effects (HRs) were derived from a review of randomised controlled trials.
RESULTS: Among individuals able to tolerate an ACEI, the combination of ACEI, BB, MRA and SGLT2i (cost, £12 124; quality-adjusted life years (QALYs), 5.72) was found to be the most cost-effective first-line treatment option with an incremental cost-effectiveness ratio (ICER) of £7699.Among individuals unable to tolerate an ACEI, the combination of ARNI, BB, MRA and SGLT2i (cost, £18 950; QALYs, 6.04) was found to be the most cost-effective first-line treatment option with an ICER of £15 821. The next most cost-effective first-line treatment option was the combination of ARB, BB, MRA and SGLT2i (cost, £11 842; QALYs, 5.59). These findings were primarily driven by the greater relative QALY gain of ARNI compared with ARB.
CONCLUSIONS: This study demonstrates that a first-line quadruple pharmacotherapy combination is cost-effective compared with a stepwise approach for treating people with HFrEF, suggesting that wider adoption of early initiation of quadruple pharmacotherapy may improve health outcomes and optimise healthcare resource use
A vision for estimation of the instantaneous reproductive number.
Get PDFThe reproductive number, Rt, is a popular metric used for monitoring infectious diseases. Rt describes the expected number of infections that will be generated from a single infection at time t, which maps nicely to the likelihood that disease incidence will increase, decrease, or remain constant in the near future. Although this metric has existed for decades, it became more widely used during the COVID-19 pandemic and there was a subsequent proliferation of new estimation methods and software tools. This rapid development of methods and tools presents many opportunities and challenges for users, researchers, and decision makers. In recognition of this growth, we convened a three-day "collabathon" in September 2024 to bring together researchers and public health practitioners to identify challenges and areas for future development in Rt estimation and to begin work in these areas. Here we provide a high-level summary of current methods and report on the findings from the collabathon, including a summary of current challenges and recommendations for future development, evaluation and interpretation of Rt
Mental health support for British Bangladeshi youth: multi-stakeholder qualitative study of priorities and preferences.
Get PDFBACKGROUND: Despite young British Bangladeshis experiencing a higher prevalence of mental health problems than the White British population, they are comparatively underrepresented in mental health research and fewer access services.
AIMS: This study aimed to identify priorities and preferences for mental health support among young British Bangladeshis, as well as strategies to enhance the cultural appropriateness and accessibility of services.
METHOD: A qualitative study was conducted in London and Leicester, with participants recruited through voluntary and community organisations. In-depth interviews were held with young people with lived experience of mental health problems (n = 12), their family members (n = 7) and Bangladeshi community workers from voluntary sector organisations (n = 7). Data were analysed using thematic framework analysis.
RESULTS: Participants' priorities for mental health support included reducing stigma, raising awareness, and addressing intergenerational and identity-related stressors. Preferences centred on culturally and linguistically appropriate care delivered by therapists familiar with Bangladeshi values in trusted community settings. Suggested strategies for improving existing services included enhancing access by providing support in trusted community spaces, building trust through the involvement of culturally aware professionals, and involving families and community leaders to reduce stigma and promote open discussion around youth mental health.
CONCLUSIONS: This study identifies a need for culturally tailored, linguistically accessible and community-rooted mental health support for British Bangladeshi youth. Representatives from these communities should be actively involved in the development of future programmes and policies, ensuring that support is both relevant and sustainable
Boyhood, Online Harms, and Strength-based Educative Approaches in an Era of Digital Restrictions
Get PDFPartly in response to growing public moral concern about young people’s social media consumption and how this affects their wellbeing, the Australian government has enacted legislation to limit social media access for young people under 16 years of age. While these measures are framed around improving student focus, wellbeing, and safety, public discussion has also intersected with broader anxieties about online masculinity-related content and its powerful influence on boys and young men (BYM). Within an education context, school psychologists and counsellors are increasingly called upon to respond to concerns from teachers and parents regarding the diverse range of risks that digital spaces can pose to BYM, including issues related to internet addiction, online gambling, body image, sexting, extremism, among others. While we have seen some investments in e-safety oriented educational interventions to address these issues, we have also seen notable critiques suggesting they are insufficiently informed by young people’s perspectives and priorities. Drawing from 20 interviews with Australian BYM, this article captures how a diverse cohort of BYM navigate online spaces and their perspectives on its influence in terms of their identity formation, relationships, and wellbeing. We identify four key themes present in the data: (1) negotiating addiction and self-regulation; (2) social connection, belonging, and fear of missing out (FOMO); (3) engaging in comparisons with subsequent emotional consequences; and (4) reflecting on the importance of safeguarding. The research highlights the complexity of BYM’s online experiences and challenges risk-focussed narratives by revealing their perceived agency and the context-specific strategies they use to navigate digital spaces. As educators and school-based mental health professionals consider next steps for developing effective e-safety education, we foreground the importance of adopting a strength-based approach where the experiences of young people are carefully considered
Healthcare utilisation among mothers of newborns with invasive group B Streptococcus disease: a 20-year national cohort study.
Get PDFOBJECTIVE: Long-term healthcare utilisation (HCU) among mothers of infants with neonatal, invasive group B Streptococcus disease (iGBS) remains understudied; identifying these patterns could provide better support for affected families and address the iGBS public health burden. DESIGN: Cohort study. SETTING: Population of Denmark. PARTICIPANTS: 1565 mothers of infants with iGBS and 44 976 matched comparators from 1997 through 2021, with follow-up until 2022, using national health and social registry data. PRIMARY AND SECONDARY OUTCOME MEASURES: HCU including primary, inpatient, outpatient, psychiatric and surgical care was evaluated as period prevalence ratio (PPR) and rate ratios compared across three time periods (0-6 years, 7-13 years and 14-20 years) using a modified Poisson regression model and negative binomial regression with 95% CIs. RESULTS: Mothers of newborns with iGBS had higher PPRs of psychiatric care contacts in the first 0-6 years and 14-20 years following iGBS compared with the comparison cohort (RR0-61.12 (95% CI 0.93 to 1.35), RR14-201.24 (95% CI 0.97 to 1.58)). Exposed mothers had similar PPRs of primary, inpatient and outpatient care use as comparators, except for a slightly higher inpatient care use 7-13 years following iGBS. Exposed mothers had higher RRs for primary, inpatient, outpatient and psychiatric care contacts than mothers in the comparison cohort. CONCLUSION: Mothers of iGBS-exposed infants had elevated psychiatric healthcare use and increased primary, and outpatient care visits compared with matched comparators, suggesting heightened healthcare needs and psychosocial burden of caregiving up to 20 years post-iGBS
Assessing the effectiveness of a depression-integrated model in adult HIV care in Uganda (the HIV+D trial): a cluster-randomised controlled trial.
Get PDFBACKGROUND: Although depression is common in people with HIV, mental health interventions are not available to the vast majority of people with HIV in Africa. We aimed to test the effectiveness of the HIV+D collaborative stepped care depression intervention in adult HIV care in Uganda. METHODS: A cluster-randomised controlled trial was done at 40 randomly selected primary HIV care centres (clusters) at public health-care facilities in three districts in Uganda. The 40 clusters were randomly allocated (1:1) to enhanced usual care only (EUC arm) or to HIV+D intervention plus EUC, with the randomisation stratified by level of health facility. We recruited adults (aged 18 years or older) with HIV with depression, defined by the locally validated version of the Patient Health Questionnaire 9 (PHQ-9). Participants were consecutively recruited into the study clinics until there was a maximum of 30 participants per cluster. HIV+D was coordinated by a lay counsellor and involved four sequential steps of psychoeducation, behavioural activation, antidepressant medication, and referral. EUC comprised sharing screening results with the HIV clinic physician and training on the WHO guidelines for depression management in routine care. The primary outcome was PHQ-9 scores at 3 months. The trial is registered with the ISRCTN registry (ISRCTN86760765) and is completed. FINDINGS: 8441 people with HIV were referred to the trial, and 1115 (13%) were enrolled between May 3 and Dec 31, 2021. The mean age was 38 years, 859 (77%) were female, 535 were enrolled in the EUC group, and 580 were enrolled in the HIV+D plus EUC group. Primary outcome data were available for 1097 (98%) participants. We observed high levels of fidelity, with 290 (92%) of 316 participants in the HIV+D plus EUC intervention group receiving the recommended 4-10 sessions of behavioural activation. At 3 months, the mean PHQ-9 scores were lower in the HIV+D plus EUC group, at 3·0 (SD 3·2) compared with the EUC group, at 7·6 (SD 4·2; adjusted mean difference 4·4; 95% CI 3·4-5·5; p<0·0001; effect size [d]=1·34). This effect was sustained, although attenuated, at 12 months (adjusted mean difference 1·9; 95% CI 1·0-2·8; p<0·0001; d=0·81). Baseline depression severity scores moderated the HIV+D plus EUC intervention effect, with the intervention having stronger effects for those with baseline scores in the severe range (≥20) than for those whose scores were in the moderate range (10-19) both at 3 and 12 months (p values for effect modification were <0·001 and 0·005, respectively). There was no evidence of effect modification by sex nor baseline HIV viral load. One participant in the HIV+D plus EUC group was hospitalised because of severe depression. INTERPRETATION: The HIV+D plus EUC intervention had a significant and sustained effect on depression compared with EUC. This intervention offers a scalable approach to integrate mental health care for adult HIV care settings. FUNDING: Wellcome Trust Senior Research Fellowship in Public Health and Tropical Medicine