At the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was ...witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission was human-to-human contact and hence resulted in a rapid surge across the globe where more than 24 million people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy, and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir, and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.
Abstract
Background
Vaccine hesitancy is a complex phenomenon that threatens global health. Present-day communication technology has paved the way for self-education but also contributed to the ...infodemic surrounding vaccination. This has resulted in pockets of people who are reluctant, refuse recommended vaccinations, or choose to delay being vaccinated. The present study was designed to estimate the magnitude of hesitancy towards the COVID-19 vaccination and determine its associated factors in the community.
Methods
This cross-sectional study was conducted among 776 adults aged ≥ 18 years in 15 clusters in Puducherry district, India, between March 2022 and May 2022. Face-to-face interviews were conducted using a validated, structured questionnaire. Socio-demographic variables, co-morbidities, attitudes towards vaccination, etc., were expressed as frequencies and percentages. Vaccine hesitancy was dichotomized with the median score as the cut-off and reported as a proportion with a 95% confidence interval. Univariate and multivariate analyses were carried out to determine the factors associated with vaccine hesitancy.
Results
The mean age of participants was 43.3 ± 14.8 years, with the majority being female (67.0%). Nearly 92.4%, 74.4%, and 0.5% of participants received their first, second, and precautionary doses, respectively, during the study period. Among the unvaccinated, 93.2% were unwilling to receive any dose of vaccination. More than half of the participants were hesitant towards vaccination, according to the vaccine hesitancy scale. Participants aged above 45 years were less hesitant, while those educated up to school level, belonging to the upper socio-economic class, never tested for COVID-19 in the past, and having a negative attitude towards vaccination were significantly associated with higher vaccine hesitancy.
Conclusions
It is imperative to address vaccine hesitancy by alleviating existing fears and misconceptions in the community through efficient communication strategies to win the fight against current as well as future public health emergencies.
Vector control is a key intervention against mosquito borne diseases. However, conventional methods have several limitations and alternate strategies are in urgent need. Vector control with ...endectocides such as ivermectin is emerging as a novel strategy. The short half-life of ivermectin is a limiting factor for its application as a mass therapy tool for vector control. Isoxazoline compounds like fluralaner, a class of veterinary acaricides with long half-life hold promise as an alternative. However, information about their mosquitocidal effect is limited. We explored the efficacy of fluralaner against laboratory reared vector mosquitoes-Aedes aegypti, Anopheles stephensi, and, Culex quinquefasciatus. 24 h post-blood feeding, fluralaner showed a significant mosquitocidal effect with LC
values in the range of 24.04-49.82 ng/mL for the three different mosquito species tested. Effects on life history characteristics (fecundity, egg hatch success, etc.) were also observed and significant effects were noted at drug concentrations of 20, 25 and 45 ng/mL for Ae. aegypti, An. stephensi, and, Cx. quinquefasciatus respectively. At higher drug concentration of 250 ng/mL, significant mortality was observed within 1-2 h of post blood feeding. Potent mosquitocidal effect coupled with its long half-life makes fluralaner an excellent candidate for drug based vector control strategies.
Shrimp grow-out and hatchery systems are being affected by bacterial disease particularly
Vibrios
. The use of chemotherapeutic agents in aquaculture practices has to lead to the development of ...resistance among aquatic bacteria. Thus, health management becomes of major importance in aquaculture. Under this situation, progressing bio-inhibitors from marine resources are most appropriate to be considered against pathogenic bacteria. Molecular docking is an appropriate tool in structural biology and computer-assisted drug design to predict and neutralize a target protein of known diseases. In this study, marine macro-alga
Ulva fasciata
was aimed at developing inhibitors against luminescence disease-causing pathogenic bacteria
Vibrio harveyi
.
U. fasciata
was collected from Thoothukudi, Tamil Nadu, India. Extract of
U. fasciata
was tested against growth and virulence factors of
V. harveyi
during
Penaeus monodon
larviculture. Further
U. fasciata
extract was subjected to GC–MS analysis to identify the biomolecules. The homology modeling of virulent protein, hemolysin of
V. harveyi
was designed in this study. Hence, it was aimed for molecular docking against the biomolecules identified from
U. fasciata
extract. During shrimp larviculture, the extract of
U. fasciata
(200 μg mL
−1
) exhibited reduction on Cumulative Percentage of Mortality (32.40%) in postlarvae against challenge of
V. harveyi
infection. Biomolecule Methyl dehydroabietate had showed highest binding affinity among the compounds was evaluated in molecular docking study. Statistical analysis had revealed significant differences (
p
< 0.05) in trials. Therefore, it was proved that the bio-inhibitors from
U. fasciata
will be a better option for controlling luminescence disease-causing
V. harveyi
in shrimp grow-out practices.
Lymphatic filariasis (LF) is targeted for elimination by the year 2020. As of 2017, 67 of the 72 endemic countries have implemented annual Mass Drug Administration (MDA) for interrupting LF ...transmission. Transmission Assessment Survey (TAS) is the recommended protocol to evaluate the impact of MDA and to decide when to stop MDA in an Evaluation Unit (EU, population ≤2 million). As the human infection levels go down with repeated MDA rounds, it becomes a challenge to select the appropriate survey methods to assess transmission interruption. This study validates a standard protocol for molecular xenomonitoring of infection in vectors (MX) at an EU as a complementary tool for TAS to stop MDA and its utility for post-MDA or post-validation surveillance.
The study was conducted in Cuddalore district, Tamil Nadu, India, which was found eligible for TAS after 15 annual rounds of MDA (4 with DEC alone and 11 with DEC plus albendazole). The district was divided into two EUs as per the TAS protocol and one EU was randomly selected for the study. A two-stage cluster design vector sampling, developed and validated at a sub-district level, was implemented in 30 randomly selected clusters in the EU. Female Culex quinquefasciatus were collected placing gravid traps overnight (1800-0600 hrs) inside the premises of systematically selected households. Pools of 20-25 blood-fed, semi-gravid and gravid Cx. quinquefasciatus were subjected to real-time quantitative PCR (polymerase chain reaction) assay for detecting Wuchereria bancrofti DNA. Pool infection rate (% of pools positive for W. bancrofti DNA), and the estimated prevalence of W. bancrofti DNA in mosquitoes and its 95% confidence interval were calculated. Additionally, in these 30 clusters, microfilaria (Mf) survey among individuals >5 years old was carried out. School-based TAS was conducted using Immunochromatographic Card Test (ICT) in the EU. Prepared itemized cost-menu for different cost components of MX survey and TAS were estimated and compared.
MX survey showed that only 11 (3.1%) of the 358 pools (8850 Cx.quinquefasciatus females), collected from 30 clusters, were found positive for W. bancrofti DNA. The estimated vector infection rate was 0.13% (95% CI: 0.07-0.22%), below the provisional threshold (0.25%) for transmission interruption. Of 1578 children tested in the TAS, only four (0.25%) were positive for filarial antigenemia, and it is well below the critical cut-off (18 positives) for stopping MDA. Among 9804 persons tested in the 30 clusters, only four were found positive for Mf (0.04%; 95% CI: 0.01-0.1%). The Mf-prevalence was <1% threshold for transmission interruption in humans. The estimated costs for TAS and MX per EU were $14,104 USD and $14,259 USD respectively.
The result of MX protocol was in good agreement with that of TAS, providing evidence to recommend MX as a complementary tool to TAS to decide on stopping MDA. MX can also be a potential surveillance tool for post-MDA and post-validation phases as it could detect sites with residual infection and risk of resurgence of transmission. MX is economically feasible as its cost is slightly higher than that of TAS.
Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments ...of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository.
We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment.
We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention.
The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management.
Long-lasting insecticidal nets (LLINs) are the most favoured vector control tools worldwide. Timely monitoring and evaluation of LLINs is important to sustain the impact of this promising vector ...control method and for replacement of worn-out and those rendered ineffective. During the mid-2017, LLINs were distributed by the National Vector Borne Disease Control Programme (NVBDCP) in high malaria endemic districts of the eastern coastal state of Odisha. The study was carried out to assess the field performance of the LLINs post 30 months of distribution in Koraput district of Odisha state.
A total of 130 households were randomly selected from three villages of Laxmipur CHC in Koraput district, Odisha, India; one each from hilltop, foothill and plain terrain. The net users were interviewed to elicit information on usage, washing practices, physical integrity, bio-efficacy and survivorship of LLINs to confirm the claimed three-year life of the LLINs.
74.8% of the LLINs were physically present after 30 months of distribution. The numbers (%) of LLINs used previous night varied from 30 to 61% between study villages. 74% respondents were using the LLINs throughout the year and 26% only seasonally. Of the total, 85% of the nets were reported to be washed and 95% nets were dried under shade as recommended. Altogether, 58% of the surveyed nets were found torn with holes. Of these, 74 (57%) nets were in good condition, 10 (8%) nets were in serviceable and 45 (35%) nets were badly torn and needed replacement. A total of 45 (93.75%), 68 (80%) and 71 (63.8%) LLINs were physically present in hilltop, foothill and plain villages, respectively. The LLINs did meet the efficacy criteria, given the 100% mortality to the exposed Anopheles jeyporiensis mosquitoes post 30 months distribution.
The findings of this study were communicated to the programme officials of the state and LLINs were replenished soon after 31st month post-distribution of LLINs.
Wolbachia
, an intracellular maternally transmitted endosymbiont, has been shown to interfere with the replication of dengue virus in
Aedes aegypti
mosquitoes. The
Wolbachia
-transinfected
Ae. ...aegypti
has been currently released in many countries to test its effectiveness in preventing the transmission of dengue virus. ICMR-Vector Control Research Centre in collaboration with World Mosquito Program Monash University, Australia, has generated two new
Wolbachia
-introgressed
Ae. aegypti
Puducherry (Pud) lines
via
backcrossing
Ae. aegypti
females of Australian (Aus) strains, infected with
w
Mel and
w
AlbB
Wolbachia
with wild-type
Ae. aegypti
Puducherry (Pud) males.
Wolbachia
infections are known to induce a fitness cost and confer benefit on the host mosquito populations that will influence spread of the
Wolbachia
into native wild mosquito populations during the field release. Hence, the induced fitness cost or benefit/advantage in the two newly generated
Ae. aegypti
(Pud) lines was assessed in the laboratory in comparison with the wild-type
Ae. aegypti
(Pud) strain. In addition, maternal transmission (MT) efficiency, induced cytoplasmic incompatibility (CI), and insecticide resistance status of the two (Pud) lines were determined to assess the likely frequency of
w
Mel and
w
AlbB infections in the native wild population after field invasion. The study shows that
w
Mel and
w
AlbB infections did not induce any fitness cost on the two newly generated (Pud) lines. Rather, in terms of wing length, fecundity, egg hatch rate, and adult survival, the
Wolbachia
introgression conferred fitness benefits on the (Pud) lines compared to uninfected
Wolbachia
free wild
Ae. aegypti
population.
w
Mel and
w
AlbB exhibited a high maternal transmission (99–100%) and induced nearly complete (98–100%) cytoplasmic incompatibility. Both the (Pud) lines were resistant to deltamethrin, malathion, DDT, and temephos, and the level of resistance was almost the same between the two lines as in the wild type. Overall, the stable association of
w
Mel and
w
AlbB established with
Ae. aegypti
and the reproductive advantages of the (Pud) lines encourage a pilot release in the field for population replacement potential.
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