Clinical and laboratory profile of Expanded Dengue Syndrome: experience of 2019 outbreak from Dhaka, Bangladesh.

BACKGROUND OBJECTIVES: Bangladesh is afflicted with periodic dengue outbreak every few years and one of the worst upsurges was recorded in 2019 during which there was an increasing trend of dengue with unusual symptoms which were not so common before. This study aims to describe the experience of three tertiary care centres of Dhaka regarding the clinical and laboratory, hospital outcome and management profile of the Expanded Dengue Syndrome (EDS) cases admitted from the 2019 outbreak. METHODS: The current work was a cross-sectional observational study which took place from August 1 to December 31 2019 at three major tertiary care centres in Dhaka, Bangladesh. Out of total 2017 screened dengue cases, 49 met the inclusion criteria and 39 were enrolled after taking informed written consent. Data was analysed using Microsoft Excel and Graph pad prism 9.3.1. A probability value of p<0.05 was considered statistically significant. RESULTS: Out of the 39 cases, majority were male (79.49%) with median (±IQR) age of 33(±9) years. Hypertension (4; 10.26%) was the most commonly associated co-morbidity. Among the systemic manifestations, most prevalent was hepatitis (38.49%) followed by encephalopathy (12.82%). Majority of the patients were suffering from primary infection (85%). Case fatality rate was 15.38%. Hepatitis and meningoencephalitis were the predominant cause of death. This study records the only known case report of Acute respiratory dress syndrome (ARDS) complicating dengue from Bangladesh. None of the patients from our cohort were managed by steroids. Only two (5.13%) out of 39 cases received antibiotics. INTERPRETATION CONCLUSION: In the year 2019, an unusual rise in EDS cases with about 15.4% fatalities were observed in this study. Hepatitis was the most common presentation and cause of death. Here, we report the first ARDS case encountered in Bangladesh. Despite the multifaceted presentation of EDS, indiscriminate use of antibiotics and steroid was minimal. Early recognition of multifarious features of EDS is important for choosing the targeted treatment option which can avert many deaths. The results of this study underline the necessity for more in-depth research into the risk factors that are contributing to mortality in EDS cases.

Outcome of Intra-articular Injection of Total Stromal Cells and Platelet-Rich Plasma in Primary Knee Osteoarthritis: A Randomized Clinical Trial.

INTRODUCTION:  Mesenchymal stem cell (MSC) therapy appeared promising in knee osteoarthritis (OA). We examined if a single intra-articular (IA) autologous total stromal cells (TSC) and platelet-rich plasma (PRP) injection improved knee pain, physical function, and articular cartilage thickness in knee OA. METHODS:  The study was performed in the physical medicine and rehabilitation department of Bangabandhu Shaikh Mujib Medical University, Dhaka, Bangladesh. Knee OA was diagnosed according to the American College of Rheumatology criteria and randomly assigned to treatment (received TSC and PRP) and control groups. Kallgreen-Lawrance (KL) scoring system was used to grade primary knee OA. The Visual Analogue Scale (VAS, 0-10 cm) for pain, WOMAC (Western Ontario and McMaster Universities Arthritis Index) for physical function, and medial femoral condylar cartilage (MFC) thickness (millimeters) under ultrasonogram (US) were documented and compared between groups before and after treatment. Statistical Package analyzed data for Social Scientists (SPSS 22.0; IBM Corp, Armonk, NY) was used for data analysis. Pre- and post-intervention outcomes were measured using the Wilcoxon-sign test, whereas Mann-Whitney U-test calculated the difference between groups; a p-value <0.05 was considered statistically significant.  Result: In the treatment group, 15 received IA-TSC and PRP preparation, and in the control group, 15 patients received no injection, but quadricep muscle-strengthening exercise. There was no significant difference between groups regarding VAS for pain, WOMAC physical function, and cartilage thickness before starting the treatment and two weeks after intervention. VAS for pain and WOMAC physical function scores improved profoundly in the treatment group after 12 and 24 weeks of intervention; the pain and physical function scores difference between groups was also significant. However, significant mean femoral cartilage thickness was not changed until the end of 24 weeks (U=175.00, p=0.009 two-tailed and U= 130.00, p=0.016 two-tailed, respectively, for right and left knee). CONCLUSION:  Single TSC and PRP injection reduces knee pain and improves physical function and cartilage thickness in knee OA. While pain and physical function improvement happen earlier, cartilage thickness change takes more time.

Clinical Profile, Severity Spectrum, and Hospital Outcome of Dengue Patients in a Tertiary Care Hospital in Dhaka City.

Background Bangladesh saw its most severe dengue outbreak in 2019, with the highest number of deaths reported. This study investigated the clinical characteristics, severity spectrum, and potential outcomes of dengue in patients admitted to a tertiary care institution in Dhaka. Methods This prospective observational study was done between May 2019 to April 2020. A total of 478 nonstructural protein 1 (NS1) antigen positive confirmed dengue cases were finally enrolled. The dengue patient's stratification and severity grading were performed according to the World Health Organization (WHO) dengue guidelines, for diagnosis, treatment, prevention, and control (2009). In addition, in-hospital outcomes were assessed in terms of mortality. Results The patient's mean age was 33.90±15.82 (SD) years. The male-to-female ratio was 1.23:1. In addition to fever, the most common symptoms were myalgia (67.78%) and rashes (58.58%). According to WHO classification 33.90% of patients (n=162) were in group A, 49.40% (n=236) were in group B, and 16.70% (n=80) were in group C. The overall mortality was 1.23% in groups A, 2.97% in group B, and 11.25% in group C. The mortality was higher in the more severe group with statistical significance (p<0.001). The mean hospital stay time was significantly less in the surviving group (survival vs. death: 3.07±1.78 vs. 5.61±3.13 SD {days}, p<0.001). Leukopenia and thrombocytopenia were commonly seen in all of the severity groups. Conclusion Dengue epidemics are increasing in Bangladesh. Many group B and C cases are fatal. To reduce mortality and morbidity, health care providers must remain alert. This challenge requires public health interventions and hospital readiness.

A Young Lady With Myopericarditis: An Unusual Presentation of COVID-19 Infection.

Fever, sore throat, cough, and shortness of breath are the characteristic clinical manifestations of coronavirus disease 2019 (COVID-19). As the epidemic spreads, it is evident that the infection can affect not only the lungs but also other organs. By attaching to the angiotensin-converting enzyme-2 receptor (ACE-2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lung injury. SARS-CoV-2 can also cause damage to the heart and blood vessels as these organs have abundant ACE-2 receptors. Here, we present a 28-year-old lady with shortness of breath, chest pain, low blood pressure, and a pulse rate that fluctuates widely. She had SARS-CoV-2-induced myopericarditis after further testing. Initially, we treated her with high-dose prednisolone and other supportive medications. Then, we also added colchicine and ibuprofen due to the initial poor response, and the result was satisfying after two weeks of treatment.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans.

Scrub typhus is a febrile infection caused by the obligate intracellular bacterium Orientia tsutsugamushi, which causes significant morbidity and mortality across the Asia-Pacific region. The control of this vector-borne disease is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, and a potentially large rodent reservoir of unclear significance, coupled with a lack of accurate diagnostic tests. Development of an effective vaccine is highly desirable. This however requires better characterization of the natural immune response of this neglected but important disease. Here we implement a novel IFN-γ ELISpot assay as a tool for studying O. tsutsugamushi induced cellular immune responses in an experimental scrub typhus rhesus macaque model and human populations. Whole cell antigen for O. tsutsugamushi (OT-WCA) was prepared by heat inactivation of Karp-strain bacteria. Rhesus macaques were infected intradermally with O. tsutsugamushi. Freshly isolated peripheral blood mononuclear cells (PBMC) from infected (n = 10) and uninfected animals (n = 5) were stimulated with OT-WCA, and IFN-γ secreting cells quantitated by ELISpot assay at five time points over 28 days. PBMC were then assayed from people in a scrub typhus-endemic region of Thailand (n = 105) and responses compared to those from a partially exposed population in a non-endemic region (n = 14), and to a naïve population in UK (n = 12). Mean results at Day 0 prior to O. tsutsugamushi infection were 12 (95% CI 0-25) and 15 (2-27) spot-forming cells (SFC)/106 PBMC for infected and control macaques respectively. Strong O. tsutsugamushi-specific IFN-γ responses were seen post infection, with ELISpot responses 20-fold higher than baseline at Day 7 (mean 235, 95% CI 200-270 SFC/106 PBMC), 105-fold higher at Day 14 (mean 1261, 95% CI 1,097-1,425 SFC/106 PBMC), 125-fold higher at Day 21 (mean 1,498, 95% CI 1,496-1,500 SFC/106 PBMC) and 118-fold higher at Day 28 (mean 1,416, 95% CI 1,306-1,527 SFC/106 PBMC). No significant change was found in the control group at any time point compared to baseline. Humans from a scrub typhus endemic region of Thailand had mean responses of 189 (95% CI 88-290) SFC/106 PBMC compared to mean responses of 40 (95% CI 9-71) SFC/106 PBMC in people from a non-endemic region and 3 (95% CI 0-7) SFC/106 PBMC in naïve controls. In summary, this highly sensitive assay will enable field immunogenicity studies and further characterization of the host response to O. tsutsugamushi, and provides a link between human and animal models to accelerate vaccine development.