Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct ...correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections.
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the ...effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.
We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%.
Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61).
This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.
None.
For the Hindi translation of the abstract see Supplementary Materials section.
Dengue is one of the fairly prevalent viral infections at the world level transmitted through mosquitoes (
Aedes aegypti
and
Aedes albopictus
). Due to various environmental factors, dengue cases ...surged rapidly at the global level in recent decades, with 193245 cases in 2021 and an increment of 110473 cases in 2022. There is no antidote available against dengue and other
flaviviruses
. In the absence of a dengue vaccine or specific antiviral, medicinal plants or their products can be the only choice for its effective management.
Ocimum sanctum
is known as ‘‘The Incomparable One,’’ ‘‘Mother Medicine of Nature’’ and ‘‘Queen of Herbs’’ in Ayurveda, and is considered an "elixir of life" supreme in both healthcare and spiritual terms. In present study eugenol was isolated in
O.sanctum.
Eugenol (1-hydroxy-2-methoxy-4-allylbenzene) has been substantially responsible for its therapeutic potential. High-performance thin-layer chromatography, Fourier transform infrared spectroscopy and ultraviolet–visible spectroscopy were applied to identify the compound. The Rf value of isolated compound was same in the chromatogram (0.69 + 0.05) with compare to standard. The safe dose of plant and eugenol were found as < 31.25 μg/ml and < 15.62 µg/ml. The anti-dengue activity was assessed in C6/36 cell lines, their effect was determined through Quantitative PCR. The NMR of the isolated eugenol showed similar properties as the commercial marker compound. The eugenol and SFE extract of
O. sanctum
showed the inhibition of 99.28% and completely against Dengue-2, respectively. Docking study exposed that the interaction of eugenol with NS1 and NS5 dengue protein showed the binding energy as − 5.33 and − 5.75 kcal/mol, respectively. The eugenol from the
O. sanctum
plant has the potential to be a good source of future treatment medications for dengue illness, as well as a valuable tool in its successful management
Key Points
The optimal yield of the supercritical fluid extraction extract was 0.13 g/10 g (1.3% w/w) at 150 bar pressure
40 °C temperature and Ocimum sanctum extract and isolated Eugenol significantly inhibited the DENV-2 virus at a concentration of < 31.25 μg/ml & < 15.62 µg/ml. The isolated extract was identified as Eugenol
In silico study confirmed the binding energy of ligand with dengue as − 5.33 and − 5.75 kcal/mol, respectively
Influenza surveillance is an important tool to identify emerging/reemerging strains, and defining seasonality. We describe the distinct patterns of circulating strains of the virus in different areas ...in India from 2009 to 2013.
Patients in ten cities presenting with influenza like illness in out-patient departments of dispensaries/hospitals and hospitalized patients with severe acute respiratory infections were enrolled. Nasopharangeal swabs were tested for influenza viruses by real-time RT-PCR, and subtyping; antigenic and genetic analysis were carried out using standard assays.
Of the 44,127 ILI/SARI cases, 6,193 (14.0%) were positive for influenza virus. Peaks of influenza were observed during July-September coinciding with monsoon in cities Delhi and Lucknow (north), Pune (west), Allaphuza (southwest), Nagpur (central), Kolkata (east) and Dibrugarh (northeast), whereas Chennai and Vellore (southeast) revealed peaks in October-November, coinciding with the monsoon months in these cities. In Srinagar (Northern most city at 34°N latitude) influenza circulation peaked in January-March in winter months. The patterns of circulating strains varied over the years: whereas A/H1N1pdm09 and type B co-circulated in 2009 and 2010, H3N2 was the predominant circulating strain in 2011, followed by circulation of A/H1N1pdm09 and influenza B in 2012 and return of A/H3N2 in 2013. Antigenic analysis revealed that most circulating viruses were close to vaccine selected viral strains.
Our data shows that India, though physically located in northern hemisphere, has distinct seasonality that might be related to latitude and environmental factors. While cities with temperate seasonality will benefit from vaccination in September-October, cities with peaks in the monsoon season in July-September will benefit from vaccination in April-May. Continued surveillance is critical to understand regional differences in influenza seasonality at regional and sub-regional level, especially in countries with large latitude span.
A 11-year-old boy with acute myeloid leukemia was brought for treatment of severe acute respiratory infection in the National Capital Region, New Delhi, India. Avian influenza A(H5N1) infection was ...laboratory confirmed. Complete genome analysis indicated hemagglutinin gene clade 2.3.2.1a. We found the strain to be susceptible to amantadine and neuraminidase inhibitors.
To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited ...setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4–6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5–18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) median (IQR) were significantly higher in non-survivors as compared to survivors 1061 (581, 2750) vs 309.5 (140, 720.08),
p
value = 0.045. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.
Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite ...study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia.
Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death.
Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality.
High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.
Leucas cephalotes is a common ethnomedicinal plant widely used by traditional healers for the treatment of Malaria and other types of fever. Oleanolic acid and its derivatives have been reported for ...various types of pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, anti-HIV and anti-HCV activity.
L.cephalotes plant extracts were prepared by supercritical fluid extraction (SFE) method and oleanolic acid was isolated by preparatory thin-layer chromatography. The compound was identified and characterize by using ultraviolet-visible spectroscopy (UV-VIS), Fourier transform infra-Red spectroscopy (FT-IR) and high-performance thin-layer chromatography (HPTLC). The structure of the compound was elucidated by proton nuclear magnetic resonance (
HNMR) and carbon nuclear magnetic resonance (
CNMR) and the purity checked by differential scanning calorimetry (DSC). The MTT assay was used to determine the toxicity of plant extract and oleanolic acid using a microplate reader at 595 nm. The anti-dengue activity of plant extract and oleanolic acid was tested in vitro and in silico using real-time RT-PCR.
The optimum yield of the extract was obtained at 40 °C temperature and 15Mpa pressure. The maximum non-toxic dose (MNTD) of plant extract and oleanolic acid were found as 46.87 μg/ml and 93.75 μg/ml, respectively in C6/36 cell lines. UV spectrophotometer curve of the isolated compound was overlapped with standard oleanolic acid at 232 nm. Superimposed FT-IR structure of the isolated compound was indicated the same spectra at 3433, 2939, 2871, 1690, 1500,1463, 1387, 1250, 1209, 1137 and 656 position as per marker compound. HPTLC analysis showed the retention factor of L. cephalotes extract was 0.19 + 0.06 as similar to the standard oleanolic acid chromatogram. The NMR structure of the isolated compound was identified as similar to the marker oleanolic acid structure. DSC analysis revealed the purity of isolated oleanolic acid was 98.27% with a melting point of 311.16 °C. Real-time RT PCR results revealed that L. cephalotes supercritical extract and isolated oleanolic acid showed 100 and 99.17% inhibition against the dengue - 2 virus when treated with MNTD value of plant extract (46.87 μg/ml) and the test compound (93.75 μg/ml), respectively. The molecular study demonstrated the binding energy of oleanolic acid with NS1and NS5 (non-structural protein) were - 9.42 & -8.32Kcal/mol, respectively.
The SFE extract L. cephalotes and its active compound, oleanolic acid inhibiting the activity of dengue-2 serotype in the in vitro and in silico assays. Thus, the L.cephalotes plant could be an excellent source for drug design for the treatment of dengue infection.
Aedes aegypti mosquitoes are common vectors for dengue virus and chikungunya virus. In areas where both viruses cocirculate, they can be transmitted together. During a dengue outbreak in Delhi in ...2006, 17 of 69 serum samples were positive for chikungunya virus by reverse transcription-PCR; 6 samples were positive for both viruses.
A major DHF outbreak occurred in Delhi in 1996. Following this another outbreak was reported in the year 2003. In the years 2004 and 2005, though no outbreak was reported, a definitely higher number ...of samples were received in the virology laboratory of A.I.I.M.S. from suspected cases of dengue infection. This study was designed to compare the serological and virological profiles of confirmed dengue cases in the years 2003, 2004 and 2005.
Out of 1820 serum samples received from suspected cases in all three years, 811 (44.56%) were confirmed as dengue infection serologically. Out of these confirmed dengue cases maximum cases, in all three years, were seen in the age group 21-30 years. There was an increase in the number of samples received in the post monsoon period (September to November) with a peak in the second and third week of October. More samples were received from DHF cases in the year 2005 than 2004 and 2003. All four dengue serotypes were seen co-circulating in the year 2003, followed by complete predominance of dengue serotype 3 in 2005.
Epidemiology of dengue is changing rapidly in Delhi. Dengue infections are seen every year thus making it an endemic disease. After co-circulation of all serotypes in 2003, now dengue serotype 3 is emerging as the predominant serotype.
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