Spot Survey Leptospirosis dan Reservoar yang Berpotensi Menularkan di Kecamatan Kuwarasan Kabupaten Kebumen Tahun 2017

Jawa Tengah merupakan provinsi endemis leptospirosis, bahkan pada tahun 2015 menduduki peringkat pertama kasus terbanyak di Indonesia. Sebanyak 20 kota/kabupaten di Jawa Tengah rutin melaporkan adanya kasus leptospirosis. Kabupaten Kebumen merupakan salah satu daerah baru yang melaporkan kasus leptospirosis pada tahun 2017. Kajian ini bertujuan untuk mengetahui faktor risiko penularan serta keberadaan reservoar yang tertangkap dan berpotensi menularkan leptospirosis. Penelitian ini merupakan studi observasional dengan desain potong lintang. Lokasi penelitian di Kabupaten Kebumen sedangkan penangkapan reservoar dilakukan di Desa Mangli Kecamatan Kuwarasan berdasarkan pada laporan kasus terakhir. Pengumpulan data dilakukan pada bulan Maret 2017 dengan wawancara kasus probable serta penangkapan reservoar menggunakan perangkap hidup (single live trap) sebanyak 150 buah selama 2 malam berturut-turut di lingkungan permukiman dan sekitarnya. Data dianalisis secara deskriptif dalam bentuk tabel dan gambar. Hasil penelitian menunjukkan jumlah kasus leptospirosis yang diwawancara sebanyak 9 orang. Sebagian besar kasus leptospirosis (78%) adalah petani/buruh tani dan terkena di sawah pada saat panen. Selain pekerjaan, faktor risiko utama yang berkontribusi yaitu adanya luka terbuka pada kaki, tidak memakai APD pada saat bekerja dan adanya kontak dengan genangan air dalam waktu yang cukup lama. Reservoar yang tertangkap dalam penelitian ini adalah tikus dan cecurut sebanyak 26 ekor dengan species Bandicota indica, Rattus tanezumi, Mus musculus dan Suncus murinus. Hasil pemeriksaan PCR menunjukkan 1 ekor tikus positif bakteri leptosira patogen dan ditemukan pada jarak < 100 meter dengan titik kasus. Hal ini menunjukkan potensi risiko penularan leptospirosis di lokasi tersebut. Perlunya sosialisasi peningkatan kewaspadaan leptospirosis dan tindakan pengendalian reservoar khususnya tikus dan cecurut baik di dalam rumah, sawah maupun lingkungan sekitarnya

Upregulation of tryptophanyl-tRNA synthethase adapts human cancer cells to nutritional stress caused by tryptophan degradation

Tryptophan (Trp) metabolism is an important target in immuno-oncology as it represents a powerful immunosuppressive mechanism hijacked by tumors for protection against immune destruction. However, it remains unclear how tumor cells can proliferate while degrading the essential amino acid Trp. Trp is incorporated into proteins after it is attached to its tRNA by tryptophanyl-tRNA synthestases. As the tryptophanyl-tRNA synthestases compete for Trp with the Trp-catabolizing enzymes, the balance between these enzymes will determine whether Trp is used for protein synthesis or is degraded. In human cancers expression of the Trp-degrading enzymes indoleamine-2,3-dioxygenase-1 (IDO1) and tryptophan-2,3-dioxygenase (TDO2) was positively associated with the expression of the tryptophanyl-tRNA synthestase WARS. One mechanism underlying the association between IDO1 and WARS identified in this study is their joint induction by IFN gamma released from tumor-infiltrating T cells. Moreover, we show here that IDO1- and TDO2-mediated Trp deprivation upregulates WARS expression by activating the general control non-derepressible-2 (GCN2) kinase, leading to phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2 alpha) and induction of activating transcription factor 4 (ATF4). Trp deprivation induced cytoplasmic WARS expression but did not increase nuclear or extracellular WARS levels. GCN2 protected the cells against the effects of Trp starvation and enabled them to quickly make use of Trp for proliferation once it was replenished. Computational modeling of Trp metabolism revealed that Trp deficiency shifted Trp flux towards WARS and protein synthesis. Our data therefore suggest that the upregulation of WARS via IFN gamma and/or GCN2-peIF2 alpha-ATF4 signaling protects Trp-degrading cancer cells from excessive intracellular Trp depletion

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use