A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission.

BACKGROUND: Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samples from Mycobacterium tuberculosis short-read WGS data. We then evaluate three approaches for reconstructing the underlying mixed constituent strain sequences. This allows these samples to be included in downstream analysis to gain insights into the epidemiology and transmission of mixed infections. METHODS: We employed a Gaussian mixture model to cluster allele frequencies at mixed sites (hSNPs) in each sample to identify signals of multiple strains. Building upon our previous tool, MixInfect, we increased the accuracy of classifying in vitro mixed samples through multiple improvements to the bioinformatic pipeline. Major and minor proportion constituent strains were reconstructed using three approaches and assessed by comparing the estimated sequence to the known constituent strain sequence. Lastly, mixed infections in a real-world Mycobacterium tuberculosis population from Moldova were detected with MixInfect2 and clusters of recent transmission that included major and minor constituent strains were built. RESULTS: All 36/36 in vitro mixed and 12/12 non-mixed samples were correctly classified with MixInfect2, and major strain proportions were estimated with high accuracy (within 3% of the true strain proportion), outperforming previous tools. Reconstructed major strain sequences closely matched the true constituent sequence by taking the allele at the highest frequency at hSNPs, while the best-performing approach to reconstruct the minor proportion strain sequence was identifying the closest non-mixed isolate in the same population, though no approach was effective when the minor strain proportion was at 5%. Finally, fewer mixed infections were identified in Moldova than previous estimates (6.6% vs 17.4%) and we found multiple instances where the constituent strains of mixed samples were present in transmission clusters. CONCLUSIONS: MixInfect2 accurately detects samples with evidence of mixed infection from short-read WGS data and provides an excellent estimate of the mixture proportions. While there are limitations in reconstructing the constituent strain sequences of mixed samples, we present recommendations for the best approach to include these isolates in further analyses

Primary prevention in hospitals in 20 high-income countries in Europe - A case of not "Making Every Contact Count"?

This article provides a snapshot of primary prevention activities in hospitals in 20 European high-income countries, based on inputs from experts of the Observatory's Health Systems and Policies Monitor (HSPM) network using a structured questionnaire. We found that in the vast majority of countries (15), there are no systematic national policies on primary prevention in hospitals. Five countries (Cyprus, Finland, Ireland, Romania and the United Kingdom) reported systematic primary prevention activities in hospitals, although in one of them (Cyprus) this was due to the fact that small hospitals in rural areas or less populated districts host providers of primary care. In two of the five countries with systematic national policies on primary prevention, there are no incentives (financial or otherwise) to provide these interventions. The remaining three countries (Finland, Romania and the United Kingdom) report the existence of incentives, but only two of them (Romania and the United Kingdom) provide financial incentives in the form of additional funding. Only two of the 20 countries (Ireland and the United Kingdom) make explicit use of the Making Every Contact Count (MECC) approach. Overall, it can be concluded that there is little focus on primary prevention in hospitals in Europe, which may be seen as a missed opportunity

Disability-inclusive graduation programme intervention on social participation among ultra-poor people with disability in North Uganda: a cluster randomized trial.

BACKGROUND: People with disabilities encounter significant barriers to social participation due to inaccessible environments and negative attitudes. This study evaluated the effectiveness of a comprehensive disability-inclusive graduation (DIG) programme in enhancing social participation among ultra-poor people with disabilities in rural Uganda. METHODS: A two-arm, cluster-randomized controlled trial was conducted in four Northern Ugandan districts, involving 96 intervention and 89 control clusters. The DIG intervention encompassed four pillars: Livelihoods, Social Protection, Financial Inclusion, and Social Empowerment. The study identified households with disabilities using the Washington Group Short Set questions, verified by BRAC programme managers, comprising 370 working-age people with disabilities in the intervention group and 321 in the control group at baseline. Treatment clusters received an 18-month DIG intervention from December 2020 to June 2022. Social participation was measured using the SINTEF Participation Question Set at baseline, immediately post-intervention, and 16 months post-intervention, covering household and societal participation domains. Intervention effects were analyzed through linear mixed-effects regression models, reporting minimally adjusted and fully adjusted mean differences (MAMD and FAMD) with 95% confidence intervals. RESULTS: Immediately after the intervention, the DIG programme showed a positive trend in overall social participation (3.04 point increase in intervention group vs. - 0.29 in control), though not statistically significant in fully adjusted analysis (FAMD = 3.14, 95% CI = (- 1.26, 7.54); p = 0.17), possibly due to sample size limitations and variability in individual responses. A larger improvement in societal participation was observed favouring the intervention group (5.92 point increase versus 0.21 in control), with the fully adjusted analysis approaching statistical significance (FAMD = 5.84, 95% CI = (- 0.01, 11.69); p = 0.05). No significant differences were found in the domain of household participation. At 16 months post-intervention, no significant differences were observed between the intervention and control groups in overall scores or any subdomain, suggesting challenges in maintaining initial improvements over time. CONCLUSIONS: The DIG programme showed short-term positive effects on social participation among ultra-poor people with disabilities, especially in societal engagement. The absence of long-term sustained improvements underscores the complexity of disability inclusion in resource-constrained settings. Future interventions should develop strategies like extended support or booster sessions to maintain initial gains. TRIAL REGISTRATION: Registry for International Development Impact Evaluations (RIDIE-STUDY-ID-626008898983a) and ISRCTN (ISRCTN-78592382)

Comparison of an Open versus List-Based Dietary Recall Method to Assess Unhealthy Feeding Practices among Infants and Young Children.

BACKGROUND: Collecting accurate dietary data is critical for assessing infant and young child feeding practices, identifying populations at risk, and using evidence to inform policy. In 2021, World Health Organization/United Nations Children's Fund released new indicators of unhealthy food and beverage consumption and recommended that survey administrators use either an open or list-based method. OBJECTIVES: This study compared infants' and young children' unhealthy food consumption estimated using an open 24-h recall (24HR) compared with list-based 24HR among young children living in peri-urban Cambodia and explored the effect of social desirability bias on respondents' responses. METHODS: We conducted a secondary analysis of unhealthy food consumption estimated in a longitudinal cohort study implemented from June 2021 through January 2022 in the rural/peri-urban district of Khsach Kandal, Kandal Province, Cambodia (567 children aged 10-13.9 mo at baseline). Each month, for 5 mo, data were collected via an open 24HR. At the 6th month, half of the children were randomly assigned to also receive a list-based 24HR to collect data on unhealthy food consumption. RESULTS: The prevalence of sweet beverage and unhealthy food consumption and zero fruit and vegetable consumption among young children was high. We observed that the percentage of children consuming sweet foods was significantly higher when estimated using the list-based compared with an open 24HR method (61.6% compared with 43.8%; P = 0.012). An association between social desirability bias and reported consumption of salty/fried foods was also observed across both groups; however, this relationship was more pronounced among caregivers who received the list-based 24HR than the open 24HR (P = 0.004). CONCLUSIONS: Researchers must carefully consider the method used for 24HR because this may have implications for respondents' recall and memory. As more evidence is collected on the rising consumption of unhealthy food and beverages among young children, researchers should take into consideration the effects of caregiver's susceptibility to social desirability bias when analyzing these consumption patterns

The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa [version 2; peer review: 3 approved, 1 approved with reservations]

Female genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) are gender-specific manifestations of urogenital schistosomiasis. Morbidity is a consequence of prolonged inflammation in the human genital tract caused by the entrapped eggs of the waterborne parasite, Schistosoma (S.) haematobium.Both diseases affect the sexual and reproductive health (SRH) of millions of people globally, especially in sub-Sahara Africa (SSA). Awareness and knowledge of these diseases is largely absent among affected communities and healthcare workers in endemic countries. Accurate burden of FGS and MGS disease estimates, single and combined, are absent, mostly due to lack of awareness of both diseases and absence of standardized methods for individual or population-based screening and diagnosis. In addition, there are disparities in country-specific FGS and MGS knowledge, research and implementation approaches, and diagnosis and treatment. There are currently no WHO guidelines to inform practice. The BILGENSA (Genital Bilharzia in Southern Africa) Research Network aimed to create a collaborative multidisciplinary network to advance clinical research of FGS and MGS across Southern African endemic countries. The workshop was held in Lusaka, Zambia over two days in November 2022. Over 150 researchers and stakeholders from different schistosomiasis endemic settings attended. Attendees identified challenges and research priorities around FGS and MGS from their respective countries. Key research themes identified across settings included: 1) To increase the knowledge about the local burden of FGS and MGS; 2) To raise awareness among local communities and healthcare workers; 3) To develop effective and scalable guidelines for disease diagnosis and management; 4) To understand the effect of treatment interventions on disease progression, and 5) To integrate FGS and MGS within other existing sexual and reproductive health (SRH) services. In its first meeting, the BILGENSA Network set forth a common research agenda across S. haematobium endemic countries for the control of FGS and MGS

The triple impact of economic hardship, insecurity, and flooding on access to antiretroviral therapy: a focus on people living with HIV/AIDS in Maiduguri, Nigeria

Background: The multifaceted impact of economic hardship, insecurity, and flooding on access to antiretroviral therapy (ART) among people living with HIV/AIDS (PLHIV) in Maiduguri, Nigeria is highlighted by this article. While ART has transformed HIV from a fatal condition to a manageable chronic illness, achieving consistent access in regions facing socioeconomic and environmental challenges such as Maiduguri remains a critical issue. Factors such as inflation, poverty, and high transportation costs hinder PLHIV’s ability to obtain treatment and related medical services. Although antiretroviral drugs are subsidised in Nigeria, associated costs, including transport-fare and laboratory fees, place a significant burden on patients. This financial strain disrupts adherence to treatment, risking clinical failures and drug resistance. Insecurity due to the Boko Haram insurgency exacerbates these challenges. Methods: A comprehensive literature search was conducted using keywords such as ART, economic hardship, Maiduguri, flooding, and insecurity to identify relevant articles from Scopus, PubMed, and Google Scholar. Boolean operators "AND" and "OR" were applied to construct precise search strings, ensuring broad yet targeted retrieval of relevant studies. A total of 27 articles were included based on their relevance, methodological quality, and contribution to the study's aim. Eligible publications encompassed original research, systematic and narrative reviews, meta-analyses, perspectives, and grey literature, with priority given to studies published in English within the last ten years. A snowballing bibliometric approach was also employed to identify additional relevant literature. Full-text articles were critically analyzed and narratively synthesized under appropriate subheadings. Conclusion: There is an urgent need for comprehensive strategies that address these interlinked issues. Bolstering healthcare infrastructure, developing climate-resilient HIV prevention strategies, and enhancing policy frameworks for emergency health response, strengthening government coordination and securing both local and international support are vital for sustaining ART access. These could assist to improving health outcomes for vulnerable populations such as PLHIV in conflict and disaster-affected areas like Maiduguri

Development and Validation of the Global Diet Quality Score (GDQS) for Children 24 to 59 Months of Age.

OBJECTIVES: To develop the Global Diet Quality Score (GDQS) for children aged 24-59 months and evaluate its performance in predicting outcomes related to nutrient adequacy and diet-related noncommunicable disease (NCD) risk. BACKGROUND: The GDQS is a food-based metric developed and validated for capturing diets' contributions to nutrient adequacy and NCD risk among adult men and nonpregnant and nonlactating women aged ≥15 years globally. Despite the importance of ensuring healthy diets in preschool children and the need for systematic monitoring, no food-based metrics exist that holistically measure diet quality among children aged 24-59 months in diverse populations. METHODS: We developed candidate versions of the GDQS for children aged 24-59 months by adapting the gram cutoff values used for adults to account for children's lower energy requirements. Using dietary data sets from Bangladesh, Burkina Faso, China, Ethiopia, Mexico, the United Kingdom, and the United States, we evaluated candidate versions' performance in predicting energy-adjusted nutrient intakes and adequacy, nutritional biomarkers, and overweight using Spearman's correlation and multivariable-adjusted regression models, and we statistically compared performance of the strongest candidate with that of the Minimum Dietary Diversity-Women (MDD-W) indicator and Global Dietary Recommendations (GDR) score. RESULTS: The GDQS exhibited significant (P < .05) positive correlations with energy-adjusted intakes of protein, fiber, and most micronutrients in most data sets; significant negative correlations with added sugar and saturated fat in 2 data sets; and inconsistent correlations with monounsaturated and polyunsaturated fat. In multivariable-adjusted models, the GDQS, MDD-W, and GDR were positively associated with serum folate in Ethiopia (and the GDQS was in the United Kingdom), and the GDR was positively associated with high-density lipoprotein cholesterol in China (P < .05). The GDQS was more strongly associated with the mean probability of adequacy of 8 nutrients than the GDR in 2 data sets, whereas the MDD-W outperformed the GDQS in 3 data sets (P < .05). CONCLUSION: The GDQS is a useful metric for measuring diet quality among children aged 24-59 months in diverse populations

The unintended outcome: a retrospective cross-sectional study using a urine lateral flow assay to detect ART use reveals non-disclosure of taking ART in South Africa's public health system.

INTRODUCTION: Differentiated service delivery (DSD) models for HIV and tuberculosis (TB) care prioritize efficient resource allocation and targeted interventions, and benefit from accurate assessment of patients' antiretroviral therapy (ART) pill-taking status. Accurate ART use identification is essential for ensuring proper care transition services rather than unnecessary initiation. A point-of-care urine tenofovir (TFV) assay may identify undisclosed ART use in settings with high rates of TB and HIV coinfection. METHODS: A cohort of people living with HIV (PWH) presenting for routine care, including newly diagnosed and those returning to care, and reporting no ART use within 90 days, was enrolled in a clinic-based cross-sectional study of TB prevalence which tested for TB using sputum and urine-based TB tests in two clinics in KwaZulu-Natal, South Africa. CD4 counts were determined at the time of ART initiation, per national guidelines. A novel urine-based lateral flow assay (LFA) which detects TFV ingested within the past 4-7 days was used to assess ART use from thawed urine samples, which were collected concurrently with the self-report assessment. Conditional logistic regression models assessed predictors of ART non-disclosure. RESULTS: Between 12/2021 and 5/2024, 404 PWH (40% male) reporting no recent ART use presented for ART initiation. TB testing identified 14 (3%) PWH with undiagnosed TB. Seventy-nine (20%) had detectable TFV in urine indicating undisclosed ART use, with a median CD4 count of 466 cells/mm3 (IQR 277-625) compared to 322 cells/mm3 (IQR 175-490, p = 0.001) in those without undisclosed ART use. In a multivariable model, undisclosed ART use was associated with older age, rural clinic site, higher CD4 count and having active TB, but not with gender, education or employment. CONCLUSIONS: Among people presenting for HIV treatment initiation, 20% had evidence of ART use within 4-7 days by TFV urine LFA testing. Integration of point-of-care urine TFV assays into DSD models of HIV care may support providers to engage PWH about treatment challenges, address potential barriers to disclosure and facilitate seamless transfers between clinics. If successful, this strategy may reduce duplicative care entries and promote more efficient use of resources

Adolescent mental, sexual and reproductive health in Ghana: a stakeholder analysis of actors' influence over policy formulation and implementation

One in five adolescents (10-19) live in sub-Saharan Africa. Despite the availability of policies targeted at this age group, policy formulation, implementation, and gains in adolescent health continue to be underwhelming. Actors or stakeholders are architects of policy, bringing their ideological values, interests, power, and positions to policy formulation and implementation and thus influencing the policy process. We analysed multi-level stakeholder interests, positions, power and their influence on adolescent sexual, reproductive and mental health policy formulation and implementation in Ghana, West Africa, using a single-case study design with multiple embedded sub-units of analysis. The case was defined as actors, their power, interests, positions, and the influence on policy formulation and implementation processes in adolescent sexual, reproductive and mental health. A conceptual framework of conflict and synergies between stakeholder interests, power, and positions and the influence on policy formulation and implementation was used to guide the analysis. Data was obtained from key informant in-depth interviews with 18 global and national level and 16 sub-national level stakeholders; 4 focus group discussions with district health management teams, 9 with frontline health workers and 20 with in and out of school adolescents in four districts in the Greater Accra region of Ghana. The multiple stakeholders in adolescent health, including adolescents themselves, had sometimes synergistic and sometimes divergent and conflicting views on policy agendas, formulation and approaches to implementation. Unresolved conflicts between powerful stakeholders in the public or bureaucratic arena stalled or hampered policy formulation and implementation, whereas consensus and adequate resourcing moved processes forward. It is important to invest effort in understanding actors, their power, positions and interests in context to inform policy content and framing to increase the chances of consensus and effective policy formulation and implementation processes

Is Checking for Sequential Positivity Violations Getting You Down? Try sPoRT!

BACKGROUND: Sequential positivity is often a necessary assumption for drawing causal inferences, such as through marginal structural modeling. Unfortunately, verification of this assumption can be challenging because it usually relies on multiple parametric propensity score models, unlikely to all be correctly specified. Therefore, we propose a new algorithm, called sequential Positivity Regression Tree (sPoRT), to overcome this issue and identify the subgroups found to be violating this assumption, allowing for insights about the nature of the violations and potential solutions. METHODS: We present different versions of sPoRT based on either stratifying or pooling over time under static or dynamic treatment strategies. This methodologic development was motivated by a real-life application of the impact of the timing of initiation of HIV treatment with and without smoothing over time, which we also use to demonstrate the method. RESULTS: The illustration of sPoRT demonstrates its easy use and the interpretability of the results for applied epidemiologists. Furthermore, an R notebook showing how to use sPoRT in practice is available at github.com/ArthurChatton/sPoRT-notebook. CONCLUSIONS: The sPoRT algorithm provides interpretable subgroups violating the sequential positivity violation, allowing patterns and trends in the confounders to be easily identified. We finally provided practical implications and recommendations when positivity violations are identified