Low Middle-income Countries Research Articles

QLTI-09. CLINICAL TRIALS IN NEURO-ONCOLOGY: DESIGN, LOGISTICS, CHALLENGES, AND PRACTICAL CONSIDERATIONS

Abstract Timely, secure and reliable transportation, precise handling and storage of biological specimens are critical for the success of clinical research. Research in neuro-oncology often involves complex assays such as next-generation sequencing where the integrityof brain tumor specimens is paramount. These challenges are pronounced in most Lower Middle-Income Countries (LMIC), due to climatic factors and infrastructure limitations, necessitating stringent measures to preserve sample quality and their genetic data integrity for downstream analysis. In this study, we conducted extensive cohort analysis on 80 tissues randomly picked samples of the 3600 samples collected across India to assess the impact of collection protocols, transportation logistics, and long-term storage on the genetic material of tissues. The quality and quantity of the isolated nucleic acids was determined by BioAnalyzer and Qubit parameters. Tissue samples were collected and stored at -80°C in RNAstable® within 4-12 hrs of collection. The DNA and RNA obtained from tissue samples stored for over one year was found to be of good quality with corresponding DNA Integrity Number (DIN) and RNA Integrity Number (RIN)between 7-9. Also, optimum quantity of DNA and RNA was obtained for whole exome and transcriptome sequencing. Upon sequencing, these samples showed good read coverage of 100X or more. These findings provide critical insights into the measures necessary for optimizing sample preservation and transportation to ensure accurate research outcomes. The results indicate that appropriate sample collection, transportation, and long-term storage of bio-specimens can be used effectively for future research. Additionally, the outcome underscores the potential for long-term studies in neuro-oncology using archived biological samples without compromising data integrity.

EXTH-38. EVALUATION OF STORAGE CONDITIONS ON SERUM-DERIVED EXTRACELLULAR VESICLES IN BRAIN TUMOR SAMPLES

Abstract Tumor-derived Extracellular Vesicles (EVs) are emerging as potential liquid biopsy tool in the field of cancer diagnosis and therapeutic targets. The functionality of EVs depends on its diverse cargo, which is known to alter host-receipient cells. Nevertheless, extracting EVs while preserving its integrity and functionality of its contents is challenging, specifically in Low-middle Income countries (LMIC) countries. Our study focussed on extraction of serum derived EVs analysis from brain-tumor samples encompassing Oligodendrogliomas, Astrocytomas and Glioblastomas. The stability of EVs were examined in serum stored for 2 years at -80°C to understand the effect of preservation and storage in different conditions, that were left exposed to room temperature for variable periods of time before freezing. To explore the optimal suitable conditions, EVs were isolated from serum samples using IZON column size-exclusion based-method, and evaluated for structural integrity and stability through nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) technology. Interestingly, the majority of isolated vesicles exhibited round, intact structure with bilayer membrane of size varying between 30 - 250nm. Moreover, protein content of EVs positive markers (CD63, CD81 and CD9) was also detected with minimal contaminations evidenced by weak bands for negative marker (ApoB), as determined by Western blot analysis. Further, column-based EV-derived RNA demonstrated optimal yield and purity was confirmed by RNA integrity number (RIN) using Qubit. While cryopreservation had minimum detrimental effects on mRNA sample quality, leaving it exposed to room temperature before freezing had a significant effect on EV isolation, as samples were often haemolyzed. This will provide insights in optimizing pre-analytical and analytical procedures for more effective outcomes in the clinical setting

End-of-life care awareness in a low–middle-income country: a plea for improvement

End-of-life care awareness in a low–middle-income country: a plea for improvement

The 4A climate action framework

Climate action under the Paris Agreement (PA) requires a strategic approach that addresses the climate action needs of the participating countries. The most relevant documents for identifying such needs are the nationally determined contributions (NDCs) submitted by the parties to the PA. Academia has paid insufficient attention to this dataset and has attempted to clarify climate action pathways by utilizing various established theories from different fields. As a result, a strategic framework for global climate action is lacking. This article examines the NDCs of 19 lower-middle-income countries (LMICs) to consolidate their climate action needs into a cohesive framework. A grounded theory approach with process coding techniques is employed, and the data are analyzed through three coding cycles: initial process coding, focused process coding, and conceptual process coding. The results suggest a 4 A cyclic process: assess, arrange, access, and action, which forms an integrated global response to climate change.

Get inspired - A pilot qualitative study of global health volunteering with commonwealth partnerships for antimicrobial stewardship

Abstract Introduction The Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS), funded by the UK Department of Health and Social Care's Fleming Fund, managed by the Commonwealth Pharmacists Association and Tropical Health and Education Trust, aim to build antimicrobial stewardship (AMS) capacity in low/middle-income countries (LMICs) through health-partnerships with the UK.1 CwPAMS-Phase-2 (CwPAMS2) was launched in March 2023, and supports 24 UK-LMIC partnerships delivering AMS interventions in 73 health facilities across eight African countries: Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia. Since CwPAMS1 inception (2019), UK NHS volunteers have actively provided support for capacity building in LMIC-partner organisations.2,3 Aim To explore the impact of CwPAMS volunteering, in particular, to understand potential benefits and how it could be better integrated into NHS systems. Methods UK volunteers were identified through CwPAMS2 participation and leadership roles. Non-probabilistic, purposive sampling was used; a small number of volunteers were approached via email to pilot the qualitative, semi-structured interview. Data were collected between April/May-2024 with 5 UK volunteers, as well as their line managers; all agreed to scheduled, recorded discussions indicating consent. Interviews focused on the impact of volunteering experiences on UK NHS institutions, and how these could be more formally integrated into continuous professional development (CPD) pathways. Qualitative data was thematically analysed. No ethical approval was required for this study (programme evaluation). Results Volunteers had just begun their direct work in CwPAMS2, with >1000 combined days contributed, and <1000 more needed to reach anticipated outcomes. Interviewees reported benefits to the NHS through shifts in health workforce attitude, perspective and behaviours, consequently influencing wider teams (horizontally and vertically). Changes were regarded as extremely relevant and impactful to the NHS and staff CPD goals. A prominent theme from interviews was the significant impact of global health volunteering on recruitment and retention. Individuals spoke about an injection of motivation, passion and enthusiasm into work - a reminder of the importance of their roles and the reason for staying in their jobs longer: ‘it is a reason to come and join the team and a reason to stay’. A ‘can do’, problem-solving attitude also evolved, in stark contrast with non-volunteering staff e.g. volunteers identified/solved problems rather than reporting them to senior staff, as described by one manager. There was widespread appreciation for the NHS and the resources available in the UK, compared to LMICs. Shared examples of new systems, processes and clinical skills gained and transferred from LMICs into the NHS included: the ability to make alcohol hand gel in-house; dealing with malaria cases; improving stock management systems. Discussion/Conclusion Staff retention is a considerable challenge for the NHS. Volunteering is a great opportunity for personal/professional growth, fostering leadership and motivation, whilst simultaneously improving healthcare practices. Global health volunteering could be integrated into formal CPD pathways in the NHS to capitalise on the relatively small investment in staff time in return for knowledge and skills development. Full implementation of the questionnaire to assess the impact of CwPAMS volunteering on individuals and institutions is planned for delivery at the end of the programme.

Factors influencing the uptake of antenatal care in Uganda: a mixed methods systematic review

BackgroundIn 2016, the World Health Organization (WHO) recommended increasing antenatal care (ANC) visits from four to eight to reduce maternal morbidity and mortality. However, many low-middle income countries (LMICs), including Uganda, struggle to achieve even the basic four ANC visits. To further improve ANC attendance, understanding the perceptions and beliefs of end users is crucial. This systematic review explores the perceptions, experiences, and behavior of pregnant or previously pregnant women, their families and healthcare workers on ANC attendance in Uganda.MethodsThe review includes qualitative and quantitative studies published from January 2012 to September 2022. Outcomes include early initiation of ANC visits and any attendance or utilization of routine ANC services. The Critical Appraisal Skills Programme (CASP) checklist was used to assess the quality of included studies.ResultsWe searched 7 databases, identified 725 references and assessed 107 in full text for eligibility based on selected inclusion criteria. Forty-seven studies were eligible and are included in this review. Quantitative findings highlight socioeconomic factors like occupation, wealth index, and marital status as key determinants of ANC uptake and timely uptake of care, favoring higher wealth, younger age, marriage, and media access. Qualitative evidence reveals challenges to ANC attendance including financial constraints, cultural beliefs, gendered decision-making, and geographical distance from healthcare facilities. Potential solutions involve financially empowering women, providing reliable ANC equipment and medication, and community engagement and education.ConclusionsThis review offers valuable insights for policymakers and healthcare providers seeking to tailor interventions that address the unique needs and challenges faced by pregnant women, their families, and healthcare workers in Uganda. By doing so, it may enhance ANC accessibility and quality, ultimately aligning with the WHO’s recommendation of eight ANC contacts (ANC8) and contributing to reducing maternal morbidity and mortality rates.

Improving health outcomes among older adults in India: effectiveness and implementability of a novel comprehensive geriatric assessment based intervention

Background There is significant evidence on the benefits of comprehensive assessment in older adults. But this evidence is primarily from western countries and in secondary care settings. National policies in India recognize this need and envision community-based screening and facility-based assessment programs integrated into the care pathways for the elderly. However, this is yet to translate into specific interventions, primarily due to lack of complex interventions necessary and evidence of their effectiveness. This study aims to design and pilot an integrated (Community + Facility) Elderly Health Status Assessment and Screening (EHSAS) intervention to improve health outcomes of older adults and assess its feasibility for implementation in Indian rural settings. Methods We propose a hybrid design where we will build the complex intervention, develop and validate the tools needed, pilot it using an exploratory cluster randomized trial and evaluate its implementatbility using the Exploration-Preparation-Implementation-Sustainment (EPIS) framework. Conclusions This study will fill critical gaps in evidence regarding the effectiveness of geriatric screening and assessment in community and primary care settings in low-middle income countries and provide validated tools and implementation models for adoption into national programs. Registration CTRI/2023/07/055661

Efficacy and Safety Profile of Different Schedules of Adjuvant Trastuzumab Therapy among Patients with HER2-Positive Breast Cancer: Real-World Experience from a Tertiary Cancer Center in South India

One year of adjuvant trastuzumab is the standard of care for HER2-positive breast cancer. In low–middle income countries, delivery of 1-year trastuzumab is challenging due to significant financial burden. Evidence for shorter durations of adjuvant trastuzumab is gaining popularity in this regard. In this study, we compared the effectiveness and safety of 1 year versus shorter durations of adjuvant trastuzumab practiced in our center. In total, 312 patients were included in this analysis. The median age was 52 years. More than two-thirds of patients (67.6%) had stage 2 disease and majority were hormone-receptor-positive (62.5%). The median follow-up duration was 50 months. The 4-year disease-free survival was 97.3%. The 4-year disease-free survival for shorter durations of adjuvant trastuzumab was 98% compared with 96.7% in 1-year trastuzumab therapy group. In univariate analysis, stage at diagnosis was the only factor which had statistically significant association with disease-free survival. In multivariate analysis, none of the variables were found to be predictive of survival. Two patients (0.6%) had significant left ventricular ejection fraction decline.Shorter durations of adjuvant trastuzumab have comparable 4-year disease-free survival to standard 1-year therapy and is an alternative adjuvant treatment option for HER2-positive breast cancer patients in resource-limited settings.

Solid waste management in Ugandan developing cities: Material flow analysis and sustainable practices for reducing the global warming potential.

The introduction of appropriate solid waste management (SWM) strategies can foster the mitigation of waste open dumping and burning in low-income developing cities. In this work, the SWM system in Gulu (Uganda) has been studied, and a material flow analysis, also of informal flows of waste, has been carried out. Moreover, the effectiveness of the SWM system of St. Mary's Lacor Hospital in Gulu was evaluated. Waste has been characterized and a material flow analysis allowed to highlight the difference with the current situation in the remaining part of Gulu. The sustainable practices already implemented in the hospital compound were studied to be replicated in Gulu to mitigate SWM impact in terms of global warming potential. Inadequate financial resources pose a hurdle for Gulu municipality in managing municipal solid waste (MSW) effectively. The SWM system of the hospital demonstrated both financial and managerial competence, paving the way to promote waste recycling actions acting as a hub for fostering sustainable and health-conscious valourization technologies, while discouraging waste open burning and dumping. This study estimated that the total CO2-eq emissions from open dumping and open burning avoided in 2030-2050, if Gulu would appropriately dispose of MSW by 2030, are equal to about 17,000 metric tonnes per year (t year-1). This work suggests appropriate strategies to mitigate waste open burning in low-middle income countries. The results can be helpful for waste management planners and practitioners providing important information for the use of appropriate technologies in low-middle income developing cities.

E-dengue System Insights: Exploring the Factors Influencing Dengue-related Deaths in an Urbanized State in a Low-Middle Income Country (LMIC)

BackgroundDengue has emerged as a rapidly escalating health issue in low- and middle-income countries, with its burden and geographic spread increasing over the years. Malaysia, in particular, has witnessed a significant rise in dengue cases, accompanied by a spike in mortality rates. Several studies have identified various factors, primarily focusing on the 27 clinical aspects of severe dengue infection and the development of dengue-related fatalities. Expanding on this focus, this study aims to identify the demographic, clinical, and environmental factors contributing to dengue mortality, providing a more comprehensive understanding of the variables influencing dengue-related fatalities.MethodsThis study utilized a 1:2 case-control design, analyzing data from the E-dengue system database and medical records from January 2015 to December 2022, involving 219 participants (73 dengue fatalities as cases and 146 recovered patients as controls). Dengue deaths were confirmed by the Penang State Mortality Review Committee, and controls were randomly selected from laboratory-confirmed dengue cases. Statistical analyses were performed using SPSS software, including descriptive statistics, chi-square tests, and multivariable logistic regression to identify predictors of dengue mortality, with variables included in the multivariable model if p < 0.05.ResultsSeveral significant predictors of dengue-related mortality, including clinical and environmental factors were identified. Key predictors were a platelet count below 50,000/µL (OR 15.70; 95% CI: 5.65–43.53), presence of one comorbid condition (OR 2.90; 95% CI: 1.22–6.90), more than two comorbid conditions (OR 10.15; 95% CI: 3.53–29.23), bronchial asthma (OR 12.00; 95% CI: 1.08-132.13), and outbreak locality status (OR 2.3; 95% CI: 1.11–4.79). An interaction was also found between locality status and platelet levels.ConclusionThe study emphasizes the need for developing risk profiles for dengue patients by integrating factors such as platelet levels, comorbidities, and locality status to improve clinical care. Nuanced protocols are needed to address the specific challenges of single-case and outbreak areas. In single-case localities, patients with low platelet counts (below 100,000/µL) should be prioritized for rapid intervention to mitigate severe outcomes. In outbreak areas, healthcare systems should bolster resources and apply comprehensive triage approaches considering platelet levels and other risk factors. Implementing predictive models that account for geographical factors can enhance resource allocation and preparedness for dengue outbreaks. These recommendations aim to empower public health personnel, healthcare providers, and communities to collectively reduce dengue-related mortality rates.

Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis

BackgroundThe high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs).MethodsWe performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach.ResultsSix studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%).ConclusionThe 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%.

Safety of thyroidectomy as day care surgery at a rural setting in Eastern Uganda.

The practice of day care surgery is less embraced in many low-middle-income countries (LMIC), and even less for some procedures considered major such as thyroidectomy. Here we examine the safety of day care thyroidectomy at Kyabirwa Surgical Center, a stand-alone day care surgery center in rural Eastern Uganda. This was a retrospective cohort study conducted between 2019 and 2023. All patients who had day care thyroidectomy were included. Demographics, diagnosis, investigation findings, pathology reports, and surgery outcomes were collected. Postoperative follow-up data up to 30days were also collected. Data were analyzed using R version 4.3.2. A total of 51 patients underwent same-day thyroidectomy, with an average age of 44.9±12.1years and 98% female. Procedures included total thyroidectomy (5, 9.8%), subtotal thyroidectomy (26, 51.0%), and lobectomy (20, 39.2%). Average size of the glands was 7.9±2.21cm. The majority 46 (90.2%) were of benign pathology. All patients were discharged by the evening of the same day. Complications encountered included hypocalcemia (1), hypertrophic scar (1), seroma (2), and transient recurrentlaryngeal nerve injury (1). Overall complications rate was 9.8%. Gland size was statistically significant between patients with no complications (7.68±2.06cm) versus complications (9.90±2.82, p<0.05). With overall low complication rates, these findings suggest that thyroidectomy can safely be performed on a day care basis in a rural LMIC setting with suboptimal health care delivery.

MSOR12 Presentation Time: 8:55 AM: Skin Brachytherapy, an Alternative Treatment for Non-Melanoma Skin Cancer: A Case Series from a Low Middle Income Country, Latin American Experience

MSOR12 Presentation Time: 8:55 AM: Skin Brachytherapy, an Alternative Treatment for Non-Melanoma Skin Cancer: A Case Series from a Low Middle Income Country, Latin American Experience

Outcomes of laser hemorrhoidoplasty for grade II–IV hemorrhoidal disease in Bangladesh

Background: Laser hemorrhoidoplasty is a minimally invasive procedure to treat hemorrhoids and has shown better outcomes. Less is known about its utility in a lower middle-income country; Bangladesh. Method: Between March 2023 and December 2023, 86 patients with grade II–IV hemorrhoids underwent laser hemorroidoplasty. Follow up was assessed on 1st week, 2nd week, and 6th week including pain, satisfaction, symptom improvement, incapacity for work, complications, reduction, and recurrence. Results: The study included 86 patients, with a higher proportion of male participants (73.3%) and a mean age of 55.43±13.6 years. The majority of subjects (68.60%) had grade 3 hemorrhoids. The average surgery duration was 14.70±4.70 minutes All individuals experienced substantial decreases in the size of their hemorrhoids (100%) and reported high levels of satisfaction after the operation (97.7%). The use of the Wilcoxon signed-rank test demonstrated a statistically significant reduction in both the Visual Analog Scale (VAS) and Patient Global Impression of Improvement (PGI-I) ratings during the three subsequent observation periods (1st week, 2nd week, and 6th week). The 6th week complication rate was 19.8%. Additional mucopexy was performed on all patients with grade IV and three patients with grade III hemorrhoids. Conclusion: Laser hemorroidoplasty is a day-care procedure, that is safe and efficacious and can be used in rural area settings with good patient satisfaction. Mucopexy is required in some cases of large hemorrhoidal mass to prevent recurrence.

Impact of the 100 days mission for vaccines on COVID-19: a mathematical modelling study

The COVID-19 pandemic has underscored the beneficial impact of vaccines. It also highlighted the need for future investments to expedite an equitable vaccine distribution. The 100 Days Mission aims to develop and make available a new vaccine against a future pathogen with pandemic potential within 100 days of that pathogen threat being recognised. We assessed the value of this mission by estimating the impact that it could have had on the COVID-19 pandemic. Using a previously published model of SARS-CoV-2 transmission dynamics fitted to excess mortality during the COVID-19 pandemic, we projected scenarios for three different investment strategies: rapid development and manufacture of a vaccine, increasing manufacturing capacity to eliminate supply constraints, and strengthening health systems to enable faster vaccine roll-outs and global equity. Each scenario was compared against the observed COVID-19 pandemic to estimate the public health and health-economic impacts of each scenario. If countries implemented non-pharmaceutical interventions (NPIs) as they did historically, the 100 Days Mission could have averted an estimated 8·33 million deaths (95% credible interval [CrI] 7·70-8·68) globally, mostly in lower-middle income countries. This corresponds to a monetary saving of US$14·35 trillion (95% CrI 12·96-17·87) based on the value of statistical life-years saved. Investment in manufacturing and health systems further increases deaths averted to 11·01 million (95% CrI 10·60-11·49). Under an alternative scenario whereby NPIs are lifted earlier on the basis of vaccine coverage, the 100 Days Mission alone could have reduced restrictions by 12 600 days (95% CrI 12 300-13 100) globally while still averting 5·76 million deaths (95% CrI 4·91-6·81). Our findings show the value of the 100 Days Mission and how these can be amplified through improvements in manufacturing and health systems equity. However, these investments must be enhanced by prioritising a more equitable global vaccine distribution. Schmidt Science Fellowship in partnership with the Rhodes Trust, WHO, UK Medical Research Council, Coalition for Epidemic Preparedness Innovations.

PP517 Topic: AS23–Rehabilitation: Early Mobilization/Interdisciplinary Care/Developmental Care/Other: FEASIBILITY AND SHORT-TERM IMPACT OF NURSE-DRIVEN EARLY MOBILIZATION PROTOCOL IN A PICU OF A LOW MIDDLE INCOME COUNTRY: A QUALITY IMPROVEMENT STUDY

PP517 Topic: AS23–Rehabilitation: Early Mobilization/Interdisciplinary Care/Developmental Care/Other: FEASIBILITY AND SHORT-TERM IMPACT OF NURSE-DRIVEN EARLY MOBILIZATION PROTOCOL IN A PICU OF A LOW MIDDLE INCOME COUNTRY: A QUALITY IMPROVEMENT STUDY

The Interplay of Foreign Direct Investment in Unravelling the Nexus of Technological Innovation and Economic Dynamics: An Integrated Study Using Vector Error Correction Model

Most lower-middle income countries prioritise innovation, with foreign direct investment (FDI) as a key funding source for sustainable development. This article studies the interplay between FDI, technological innovation (measured by patent-granted residents), gross domestic product (GDP), research and development (R&amp;D) expenditure (RDE) and inflation of the Indian economy from 2002–2003 to 2022–2023. It uses a vector error correction model, Johansen cointegration tests, Granger causality tests, the impulse response function and variance decomposition. The study finds two cointegration relationships between the variables. GDP and RDE have a significant positive effect on technological innovation in the long term. Neither FDI nor inflation shows such an impact. FDI policies should therefore consider factors such as a conducive regulatory framework, tax breaks and grants for R&amp;D to enhance their impact on innovation. JEL Codes: O31, O32, F21, F23, E01, O47

Patterns of Amphotericin B Use and Factors Related to Mortality in a Low-Middle Income Country: An Observational and Longitudinal Study

Background/Objectives: Amphotericin B is indicated in deep systemic fungal infections. The aim was to determine the sociodemographic, clinical and pharmacological variables of a group of Colombian patients treated with amphotericin B and factors associated with mo rtality. Methods: A longitudinal observational retrospective study on the use of amphotericin B in Colombia was conducted between January 2015 and December 2022. The multivariate analysis sought to identify variables related to mortality. Results: A total of 310 patients were identified, with a median age of 44.0 years, and 71.0% were women. Conventional amphotericin B was the most used (74.8%). The main uses were cryptococcosis (38.7%), histoplasmosis (31.9%) and candidiasis (29.4%). More than a third of patients died during hospitalization (40.3%). An increase in the Charlson Comorbidity Index score (HR: 1.13; 95% CI: 1.05–1.22) and in the qSOFA score (HR: 1.34; 95% CI: 1.04–1.73), coinfection by Mycobacterium tuberculosis (HR: 2.09; 95% CI: 1.32–3.31) and the requirement of vasopressors (HR: 4.20; 95% CI: 2.16–8.15) or invasive mechanical ventilation (HR: 2.73; 95% CI: 1.40–5.33) increased the probability of in-hospital death. In contrast, those who received systemic corticosteroids (HR: 0.43; 95% CI: 0.26–0.70) had a lower risk. Conventional amphotericin B is the most used drug mainly treating Cryptococcus neoformans infections. Conclusions: The use of amphotericin B was consistent with clinical practice guideline recommendations. In-hospital mortality was common, and factors such as increased comorbidities, higher qSOFA scores, coinfection with Mycobacterium tuberculosis and invasive procedures like mechanical ventilation were linked to increased mortality.

New advances in RSV: Is prevention attainable?

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI), hospitalization, and mortality in infants and young children globally. The greatest burden of severe disease and mortality occurs in low-middle income countries (LMICs), with large and vulnerable childhood populations. The highest rates of RSV-hospitalization occur in healthy-term infants under 3 months of age. Preterm infants, children with chronic lung disease of prematurity, Down's syndrome, congenital heart disease, or immunodeficiency also have a higher risk of severe RSV-LRTI. Early-life RSV-LRTI has also been associated with chronic sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment. A RSV pre-fusion (F) maternal vaccine and long-acting monoclonal antibody (nirsevimab) have been licensed for the prevention of RSV-LRTI in infants and young children. Studies show high efficacy and effectiveness particularly for preventing severe RSV-LRTI. Maternal RSV vaccine given at 24-36 weeks of pregnancy was effective in preventing RSV medically attended LRTI and severe RSV-LRTI through 6 months after birth in a phase 3 study conducted in 18 countries over two RSV seasons. Vaccination was safe with no significant difference in adverse events between infants born to mothers who received RSV preF vaccine compared to placebo. A numerical imbalance in preterm births that occurred predominantly in South Africa, unrelated to vaccine timing or gestational age at vaccination and unassociated with mortality, coincided with COVID-19 delta and omicron waves. Nirsevimab, given as a single dose prior or during the RSV season, had high efficacy in preventing RSV-LRTI hospitalization in infants in preterm and in full-term infants, as well as in young children with underlying conditions through 150 days post administration in phase 2 and 3 trials. High effectiveness against hospitalization or severe disease in infants and in at-risk children up to 2 years of age has also been reported in several countries where implementation has occurred. RSV-LRTI is now a preventable disease in infants and young children. Rapid implementation of these highly effective interventions has occurred in many high-income countries, but access remains very limited in LMICs. Access to such RSV preventive interventions is urgently needed for all children to strengthen child health and promote global equity.

Emerging integrase resistance in an international perinatal virtual clinic.

The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC). A retrospective cohort study. Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV). One hundred fourteen cases referred for virological failure between October 2018 and January 2024. Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4+ cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described. Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4+ cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1). Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.