Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas.
Contact investigation and TB preventive treatment of children under five years of age who are close contacts of a TB case is a key component of TB prevention. However, the uptake of TB preventive treatment is low in many high-TB burden settings. This study explores factors affecting the implementation of TB contact investigation and preventive treatment among children in Malaysia's city of Kota Kinabalu, Sabah State. This study was conducted in three primary health clinics between 2019 and 2020. We purposively sampled 34 parents and guardians of child contacts eligible for TB preventive treatment, and 25 healthcare providers involved in the management of child contacts. We conducted thematic analysis of semi-structured interviews and focus group discussions to illicit factors affecting implementation and uptake of TB contact investigation and TB preventive therapy. Six main themes emerged from the analyses-four of these relating to contact investigation and two relating to TB preventive therapy. Factors affecting TB contact investigation were addressed under system related factors (external factors, stakeholder collaboration, healthcare workers' and clients' concerns), clinic related factors (perceived performance, clinic schedule, and space), healthcare worker related factors (cooperation, commitment, knowledge, misconception, counselling and communication) and patient and contact related factors (cooperation and commitment). Factors affecting TB preventive treatment delivery were addressed under guardian related factors (cooperation, commitment, knowledge and misconception) and treatment related factors (child-friendly form and adverse effects). To address gaps and barriers identified in our study, we recommend developing system capacity to maintain routine contact investigation and preventive treatment in the context of external program risks, providing training to healthcare workers to address misconceptions, safeguarding vulnerable clients against the risk of detention and deportation while accessing care, ensuring public and private services are provided regardless of migration status, and improving processes and resources for contact investigation and preventive treatment.
Colorectal cancer (CRC) is the third most prevalent form of cancer, after lung cancer and breast cancer, with the second highest death incidence. Over the years, natural compounds have been explored as an alternative to conventional cancer therapies such as surgery, radiotherapy, and chemotherapy. Curcumin, an active constituent of turmeric has been associated with various health benefits. It has gained much attention as an anticancer agent due to its ability to regulate multiple cell signaling pathways, including NF-κB, STAT3, activated protein-1 (AP-1), epidermal growth response-1 (Egr-1), and p53, which are crucial in cancer development and progression. Nevertheless, the clinical application of curcumin is greatly restricted because of its low water solubility, poor oral absorption, and rapid metabolism. These issues have led to the development of curcumin nanoformulations to overcome the limitations of the compound. Nanotechnology-based delivery systems have been widely used in improving the delivery of poorly-water soluble drugs. Besides, these systems also come with the added benefits of possible cellular targeting and improvement in cellular uptake. An ideal improved formulation should display a greater anticancer activity compared to free curcumin, and at the same time be non-toxic to the normal cells. In this review, we focus on the design and development of various nanoformulations to deliver curcumin for use in CRC such as liposomes, micelles, polymer nanoparticles, nanogels, cyclodextrin complexes, solid lipid nanoparticles (SLN), phytosomes, and gold nanoparticles. We also discuss the current pre-clinical and clinical evidences of curcumin nanoformulations in CRC therapy, analyse the research gap, and address the future direction of this research area.
Background: Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a new entity described in the 2016 World Health Organization (WHO) classification of brain tumors. While DL-GNT is predominantly an indolent tumor that affects young boys, high-grade DL-GNT is unusual and seldom reported in children. Case Presentation: In this report, we describe the challenges and pitfalls associated with diagnosing this high-grade variant in a tuberculosis-endemic region. We highlight the importance of identifying non-typical imaging findings, i.e., non-enhancing cystic lesions with high T2 signal along the leptomeningeal surface, that may expedite the diagnosis of this condition. Histopathologic correlations with MR spectroscopy findings are also discussed. Conclusion: We provide the first clinical imaging report of utilizing MR spectroscopy to distinguish DL-GNT from tuberculosis with histopathologic correlation.
Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.
CONCLUSION: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.
Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.