Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial.

BACKGROUND: Dengue is the most significant mosquito-borne viral disease; there are no specific therapeutics. The antiparasitic drug ivermectin efficiently inhibits the replication of all 4 dengue virus serotypes in vitro. METHODS: We conducted 2 consecutive randomized, double-blind, placebo-controlled trials in adult dengue patients to evaluate safety and virological and clinical efficacies of ivermectin. After a phase 2 trial with 2 or 3 days of 1 daily dose of 400 µg/kg ivermectin, we continued with a phase 3, placebo-controlled trial with 3 days of 400 µg/kg ivermectin. RESULTS: The phase 2 trial showed a trend in reduction of plasma nonstructural protein 1 (NS1) clearance time in the 3-day ivermectin group compared with placebo. Combining phase 2 and 3 trials, 203 patients were included in the intention to treat analysis (100 and 103 patients receiving ivermectin and placebo, respectively). Dengue hemorrhagic fever occurred in 24 (24.0%) of ivermectin-treated patients and 32 (31.1%) patients receiving placebo (P = .260). The median (95% confidence interval [CI]) clearance time of NS1 antigenemia was shorter in the ivermectin group (71.5 [95% CI 59.9-84.0] hours vs 95.8 [95% CI 83.9-120.0] hours, P = .014). At discharge, 72.0% and 47.6% of patients in the ivermectin and placebo groups, respectively had undetectable plasma NS1 (P = .001). There were no differences in the viremia clearance time and incidence of adverse events between the 2 groups. CONCLUSIONS: A 3-day 1 daily dose of 400 µg/kg oral ivermectin was safe and accelerated NS1 antigenemia clearance in dengue patients. However, clinical efficacy of ivermectin was not observed at this dosage regimen.

Isolated pulmonary fusariosis caused by Neocosmospora pseudensiformis in a liver transplant recipient: A case report and review of the literature.

Neocosmospora pseudensiformis (formerly Fusarium pseudensiforme) is a hyaline mold in the Fusarium solani species complex that has been changed to the genus Neocosmospora. Invasive fusariosis is a rare fungal infection in solid organ transplantation. The most commonly reported manifestation of invasive fusariosis in this setting is localized cutaneous fusariosis. Here, we present the first case report of isolated N pseudensiformis pulmonary infection in a patient with non-alcoholic steatohepatitis cirrhosis who underwent orthotopic liver transplantation. A 67-year-old Thai woman developed acute graft rejection, dyspnea, and pulmonary consolidation 6 months after liver transplantation. N pseudensiformis was isolated from her sputum, and her clinical symptoms were improved with voriconazole treatment. However, she succumbed to Acinetobacter baumannii hospital-acquired pneumonia and acute coronary syndrome with cardiogenic shock after 10 days of treatment.

Prevalence and risk factors of vitamin D deficiency among living with HIV adults receiving antiretroviral treatment in tropical area: Cross-sectional study.

Background: There was found HIV infection have a higher rate of vitamin D deficiency (VDD) than the general population, even a slight deficiency, can increase the risk of osteoporosis in adults. This study aimed to determine the prevalence and risk factors of VDD in HIV-infected adults receiving antiretroviral therapy (ART) in a tropical area. Methods: A cross-sectional study of an HIV-clinical population-based cohort was conducted at Police General Hospital (PGH), from 1st August 2020 to 31st July 2021, in Bangkok, Thailand. Serum 25(OH)D level was measured using ECLIA. All other laboratory investigations were conducted at the PGH's central lab center. The descriptive analysis utilized frequency (percentages) and mean (SD) as appropriate variable types. Chi-square tests (χ2) and independent samples t-tests were used to differentiate between VDD and non-VDD groups. To determine the association between VDD and non-VDD, gender, age (years), BMI discrepancy, ART regimens, ART-duration (years), HIV viral load, and CD4 count (cells/mm3). Univariate and multivariable logistics regression was conducted, respectively. Results: Of 602 patients, 66.4% were females with mean age of 45.22 ± 10.23 years. The average serum 25(OH)D level was 18.69 ± 7.23 ng/ml. The prevalence of VDD (<20 ng/ml) and insufficiency (VDI) (20-29.9 ng/ml) was 58.5% and 35.2%, respectively. Risk factors associated with vitamin D inadequacy were increasing age (AOR = 1.05, 95%CI = 1.03-1.07, P < .001), efavirenz (EFV-based) use (AOR = 6.07, 95%CI = 3.57-10.31, P < .001), while male (AOR = 0.44, 95%CI = 0.29-0.66, P < .001), body mass index (BMI) lower than 18.5 (AOR = 0.26; 95% CI, 0.11-0.62, P = .002), protease Inhibitors (PIs-based) use (AOR = 0.18, 95%CI = 0.11-0.30, P < .001),and CD4 count <200 cells/mm3 (AOR = 0.41; 95% CI, 0.20-0.85, P = .017) were associated with less VDD. Conclusion: The implementation of focused strategies for vitamin D supplementation, specifically targeting older patients and patients undergoing EFV-based ART regimen, can serve as a valuable addition to comprehensive HIV management. By optimizing vitamin D levels, there is a potential to improve health outcomes and enhance overall well-being for individuals living with HIV.

Performance of a New Microfluidic Dengue NS1 Immuno-magnetic Agglutination Assay for the Rapid Diagnosis of Dengue Infection in Adults.

Dengue (DENV) infections are a public health concern worldwide and thus early diagnosis is important to ensure appropriate clinical management. The rapid diagnostic test (RDT) targets nonstructural protein 1 (NS1) detection and is the main tool used for diagnostic purpose. In this study, we evaluated the performance of a new rapid and semi-quantitative microfluidic DENV NS1 immuno-magnetic agglutination assay or IMA (ViroTrack Dengue Acute, BluSense Diagnostics, Copenhagen, Denmark). We studied 233 subjects confirmed to have DENV infection (by a real-time reverse transcriptase polymerase chain reaction) and 200 control samples were taken from patients with confirmed diagnoses of other febrile illnesses, in Thailand. Samples were tested using the NS1 antigen (Ag) detection methods: in-house NS1 Ag ELISA (ELISA), SD BIOLINE Dengue NS1 Ag RDT (ICT), and ViroTrack Dengue Acute (IMA). Sensitivities of these tests were 86.3%, 78.9%, and 85.5%, respectively. All tests showed high specificity (100%, 99%, and 97% for ELISA, ICT, and IMA, respectively). The sensitivities of both RDTs were affected by the low sensitivity to DENV-2 and DENV-4. NS1 Ag was detected in every patient on day 1 and day 2 after onset of illness by ELISA and IMA with a decline in detection rates over time after day 6 of illness. NS1 detection rate using ICT decreased from 100% on day 1 of illness to 98.6% on day 2 after onset of illness. By day 6, the detection rate was 45.9%. Thus, IMA performed better than ICT for early and rapid diagnosis of DENV infections in endemic countries.