Direct and indirect costs for hospitalized patients with dengue in Southern Sri Lanka.

BACKGROUND: The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system. METHODS: From June 2017-December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars. RESULTS: A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%. CONCLUSIONS: Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.

Comparison of two rapid test kits with real time polymerase chain reaction for early diagnosis of dengue in Sri Lanka.

Dengue is among the deadliest insect-borne diseases circulating in Sri Lanka. Most of the infections that are diagnosed early are manageable. However, delays in diagnosis may cause fatalities. We evaluated the dengue NS1 antigen card and NS1 SD kit for early diagnosis of dengue using samples from 116 RT-PCR-positive patients admitted within 5 days of the fever onset. RT-PCR tests were performed as standard tests. IgM and IgG ELISA tests were carried out to identify primary and secondary infections. Of the 116 patients who tested positive for dengue using PCR, 48 were positive using NS1 antigen card and 45 were positive using NS1 SD. Patients with 100 copies or higher viral load showed a higher sensitivity in both antigen card and NS1 SD. Of 34 primary infections evaluated, 23 were positive by NS1 antigen card, while the positivity was 21 by NS1 SD. Of the 30 secondary infections evaluated, 15 were positive by NS1 antigen card while 14 by NS1 SD. Our findings showed that while the rapid tests are convenient and much easier to use than PCR, they are less sensitive and need improvement. Until then, clinical diagnosis should have more emphasis on the early diagnosis of dengue.

Genetics of common variable immunodeficiency: role of transmembrane activator and calcium modulator and cyclophilin ligand interactor.

Common variable immunodeficiency (CVID) is the most common clinically manifested primary immunodeficiency, which represents a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. The hallmark of the disease is the elevated susceptibility to recurrent infections of respiratory and gastrointestinal tract, mainly due to encapsulated bacteria while a significant proportion of patients with CVID develop autoimmune and lymphoproliferative complications. The primary cause of CVID is still not known. However, a number of distinct genetic defects including in inducible co-stimulator (ICOS), B-cell-activating factor receptor (BAFFR) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been identified in a minority of patients with CVID. Mutations in tumour necrosis factor receptor superfamily (TNFRSF) member, TACI, are more frequently found to be associated to the disease in about 10% of patients with CVID, but may require additional immunologic defects for complete expression of the phenotype, as unaffected heterozygotes have also been described. Clinically, patients with TACI mutations could present with the complete spectrum of complications seen in CVID. Recent animal studies have provided substantial information on TACI signalling, yet it still offers an outstanding opportunity for further exploration of the aetiology, as a large part of it remains poorly understood. In this review, we aim at giving an insight into the genetics underlying the CVID and particularly at outlining the role of TACI and its relative contribution to the development of CVID-like phenotypes in human.

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial.

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.

Thermolabile H-2Kb molecules expressed by transporter associated with antigen processing-deficient RMA-S cells are occupied by low-affinity peptides.

RMA-S cells do not express functional TAP, yet they express MHC class I molecules at the cell surface, especially at reduced temperatures (26 degrees C). It is generally assumed that such class I molecules are "empty," devoid of any associated peptide. A radiochemical approach was used to label class I-associated peptides and to determine the extent to which Kb molecules in RMA-S cells are associated with peptides. These studies revealed that at 26 degrees C Kb molecules in RMA-S cells are occupied with self-peptides. Such peptides stably associate with Kb at 26 degrees C but easily dissociate from them at 37 degrees C, suggesting low-affinity interactions between Kb and the associated peptides. At 26 degrees C, at least some of these Kb molecules are stably expressed in a peptide-receptive state on the cell surface, whereas at 37 degrees C they are short lived and are only transiently capable of binding and presenting exogenously supplied OVA 257-264 peptide for presentation to CD8+ Kb-restricted T lymphocytes. Thus contrary to current models of class I assembly in TAP-deficient RMA-S cells, the presumably "empty" molecules are in fact associated with peptides at 26 degrees C. Together, our data support the existence of an alternative mechanism of peptide binding and display by MHC class I molecules in TAP-deficient cells that could explain their ability to present Ag.

Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol.

Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1+ natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells.