Wolbachia wMel strain-mediated effects on dengue virus vertical transmission from Aedes aegypti to their offspring.

BACKGROUND: Dengue virus serotypes (DENV-1 to -4) can be transmitted vertically in Aedes aegpti mosquitoes. Whether infection with the wMel strain of the endosymbiont Wolbachia can reduce the incidence of vertical transmission of DENV from infected females to their offspring is not well understood. METHODS: A laboratory colony of Vietnamese Ae. aegypti, both with and without wMel infection, were infected with DENV-1 by intrathoracic injection (IT) to estimate the rate of vertical transmission (VT) of the virus. VT in the DENV-infected mosquitoes was calculated via the infection rate estimation from mosquito pool data using maximum likelihood estimation (MLE). RESULTS: In 6047 F1 Vietnamese wild-type Ae. aegypti, the MLE of DENV-1 infection was 1.49 per 1000 mosquitoes (95% confidence interval [CI] 0.73-2.74). In 5500 wMel-infected Ae. aegypti, the MLE infection rate was 0 (95% CI 0-0.69). The VT rates between mosquito lines showed a statistically significant difference. CONCLUSIONS: The results reinforce the view that VT is a rare event in wild-type mosquitoes and that infection with wMel is effective in reducing VT.

Magnitude and patterns of severe Plasmodium vivax monoinfection in Vietnam: a 4-year single-center retrospective study.

Introduction: Infection with Plasmodium vivax is a recognized cause of severe malaria including deaths. The exact burden and patterns of severe P. vivax monoinfections is however still not well quantified, especially in P. vivax endemic regions. We examined the magnitude and patterns of severe malaria caused by monoinfections of P. vivax and associated predictors among patients admitted to a tertiary care center for malaria in Vietnam. Methods: A retrospective cohort study was conducted based on the patients' medical records at the Hospital for Tropical Diseases from January 2015 to December 2018. Extracted information included demographic, epidemiologic, clinical, laboratory and treatment characteristics. Results: Monoinfections with P. vivax were found in 153 (34.5, 95% CI 30.3-39.1%) patients of whom, uncomplicated and severe malaria were documented in 89.5% (137/153, 95% CI 83.7-93.5%) and 10.5% (16/153, 95% CI 6.5-16.3%), respectively. Patterns of severe malaria included jaundice (8 cases), hypoglycemia (3 cases), shock (2 cases), anemia (2 cases), and cerebral malaria (1 case). Among 153 patients, 73 (47.7%) had classic malaria paroxysm, 57 (37.3%) had >7 days of illness at the time of admission, and 40 (26.1%) were referred from other hospitals. A misdiagnosis as having other diseases from malaria cases coming from other hospitals was up to 32.5% (13/40). Being admitted to hospital after day 7th of illness (AOR = 6.33, 95% CI 1.14-35.30, p = 0.035) was a predictor of severe malaria. Severe malaria was statistically associated with longer hospital length of stay (p = 0.035). Early and late treatment failures and recrudescence were not recorded. All patients recovered completely. Discussion: This study confirms the emergence of severe vivax malaria in Vietnam which is associated with delayed hospital admission and increased hospital length of stay. Clinical manifestations of P. vivax infection can be misdiagnosed which results in delayed treatment. To meet the goal of malaria elimination by 2030, it is crucial that the non-tertiary hospitals have the capacity to quickly and correctly diagnose malaria and then provide treatment for malaria including P. vivax infections. More robust studies need to be conducted to fully elucidate the magnitude of severe P. vivax in Vietnam.

Higher dose corticosteroids in hospitalised COVID-19 patients with hypoxia but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

BackgroundLow-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality. On 11 May 2022, the independent Data Monitoring Committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only to this comparison due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support continues. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FindingsBetween 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1{middle dot}56; 95% CI 1{middle dot}18-2{middle dot}06; p=0{middle dot}0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5). InterpretationIn patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation. FundingUK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).

Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

We studied the development and persistence of neutralising antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs with different pre-existing immune statuses (group 1 (G1): n=21, and group 2 (G2): n=26 without and with prior breakthrough Delta variant infection, respectively). The study participants had completed primary immunisation with ChAdOx1-S and booster vaccination with BNT162b2. Neutralising antibodies were measured using a surrogate virus neutralisation assay. Of the 21 study participants in G1, neutralising antibodies against ancestral strain, Delta variant, BA.1 and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralising antibodies to the study viruses at week two post booster dose. Of the 26 study participants in G2, neutralising antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralising antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralising activities against ancestral strain and Delta variant, as compared to those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasise the importance of the first booster dose in producing cross-neutralising antibodies against Omicron variant. A second booster dose might be needed to maintain long-term protection against Omicron variant.

Depression, anxiety, and stress among frontline health workers during the second wave of COVID-19 in southern Vietnam: A cross-sectional survey.

Health workers around the world have taken on massive frontline roles in the fight against COVID-19, often under intense pressure and in the face of uncertainty. In this study, we determined the rates of depression, anxiety, stress and related factors among health workers in COVID-19 designated hospitals in southern Vietnam during the second wave of COVID-19. From July-September 2020, we collected self-administered surveys from 499 health workers in 14 hospitals that were designated for the care and treatment of patients with COVID-19. The survey included sections on demographics, co-morbid health conditions, symptoms experienced during patient care, a depression, anxiety and stress assessment (DASS-21), and other related factors. We used logistic regression models to identify factors associated with depression, anxiety and stress, and adjusted for confounding factors. 18%, 11.5%, 7.7% of participants had symptoms of depression, anxiety, and stress, respectively with the majority at mild and moderate levels. The risk factors for increased mental health impact included long working hours, experiencing physical symptoms, fear of transmission to family, COVID-19 related stigma, and worry when watching media about COVID-19. Psychological counseling and training in infection prevention were protective factors that reduced the risk of mental health problems. Further exploration of the association between physical symptoms experienced by health workers and mental health may guide interventions to improve health outcomes. More routine COVID-19 testing among health workers could reduce anxieties about physical symptoms and alleviate the fear of transmitting COVID-19 to family and friends. Medical institutions need to ensure that health workers have access to basic trainings prior to initiation of work, and mental health support during the pandemic and into the future.

Enamel Softening Can Be Reduced by Rinsing with a Fluoride Mouthwash Before Dental Erosion but Not with a Calcium Solution.

PURPOSE: This in-situ-study investigated if rinsing the oral cavity with a calcium containing solution or a fluoride containing mouthwash immediately before an erosive attack leads to reduced enamel softening. MATERIALS AND METHODS: Bovine enamel samples (n = 240) with measured baseline surface microhardness (KHN) were assigned to five series (S1-5). Twelve participants carried out each series as follows: Four enamel samples of the associated test series were placed in an intraoral appliance and carried in each participants' mouth. After 30 min, the participants either rinsed the oral cavity for 60 s with 30 ml of a solution prepared from a 1,000 mg calcium effervescent tablet dissolved in 100 ml water (S2), an 800 mg calcium containing mineral supplement powder (5 g) dissolved in 200 ml water (S3), a fluoride (500 ppm) mouthwash (S4), a fluoride (500 ppm) and stannous chloride (800 ppm) containing mouthwash (S5), or did not rinse with any test solution before the erosive attack (S1, negative control). The participants subsequently rinsed the oral cavity with 100 ml of a soft drink (Sprite Zero) for 60 s to simulate the erosive attack and immediately afterwards with water to stop the erosive process. As final step, surface microhardness was measured a second time and hardness loss (∆KHN) calculated. Differences of ∆KHN between the series were investigated by fitting a mixed effect model to the data set. RESULTS: The highest loss of microhardness and thus softening of enamel (mean of ∆KHN; lower/upper confidence level) was observed in the negative control (S1: 60.2; 67.6/52.8). While no statistically significant difference (P > 0.05) compared to S1 could be found in S2 (50.0; 57.4/42.5) and S3 (54.6; 62.1/47.2), statistically significantly less softening of enamel (P < 0.001) was discovered in S5 (33.8; 41.2/26.4) and S4 (41.8.2; 49.3/34.4). S5 showed the overall lowest values for ∆KHN and thus best protection from enamel softening. CONCLUSION: Rinsing with a fluoride mouthwash or a fluoride and stannous chloride containing mouthwash immediately before an erosive attack reduces the softening of enamel. None of the investigated calcium-containing solutions was able to reduce erosion induced softening of enamel.

Ultra-widefield photoacoustic microscopy with a dual-channel slider-crank laser-scanning apparatus for in vivo biomedical study.

Photoacoustic microscopy (PAM) is an important imaging tool that can noninvasively visualize the anatomical structure of living animals. However, the limited scanning area restricts traditional PAM systems for scanning a large animal. Here, we firstly report a dual-channel PAM system based on a custom-made slider-crank scanner. This novel scanner allows us to stably capture an ultra-widefield scanning area of 24 mm at a high B-scan speed of 32 Hz while maintaining a high signal-to-noise ratio. Our system's spatial resolution is measured at ∼3.4 µm and ∼37 µm for lateral and axial resolution, respectively. Without any contrast agent, a dragonfly wing, a nude mouse ear, an entire rat ear, and a portion of mouse sagittal are successfully imaged. Furthermore, for hemodynamic monitoring, the mimicking circulating tumor cells using magnetic contrast agent is rapidly captured in vitro. The experimental results demonstrated that our device is a promising tool for biological applications.

Crustal fingering facilitates free-gas methane migration through the hydrate stability zone.

Widespread seafloor methane venting has been reported in many regions of the world oceans in the past decade. Identifying and quantifying where and how much methane is being released into the ocean remains a major challenge and a critical gap in assessing the global carbon budget and predicting future climate [C. Ruppel, J. D. Kessler. Rev. Geophys. 55, 126-168 (2017)]. Methane hydrate ([Formula: see text]) is an ice-like solid that forms from methane-water mixture under elevated-pressure and low-temperature conditions typical of the deep marine settings (>600-m depth), often referred to as the hydrate stability zone (HSZ). Wide-ranging field evidence indicates that methane seepage often coexists with hydrate-bearing sediments within the HSZ, suggesting that hydrate formation may play an important role during the gas-migration process. At a depth that is too shallow for hydrate formation, existing theories suggest that gas migration occurs via capillary invasion and/or initiation and propagation of fractures (Fig. 1). Within the HSZ, however, a theoretical mechanism that addresses the way in which hydrate formation participates in the gas-percolation process is missing. Here, we study, experimentally and computationally, the mechanics of gas percolation under hydrate-forming conditions. We uncover a phenomenon-crustal fingering-and demonstrate how it may control methane-gas migration in ocean sediments within the HSZ.

SARS-CoV-2 detection in nasopharyngeal throat swabs by metagenomics

Metagenomics could detect SARS-CoV-2 in all eight nasopharyngeal/throat swabs with high/low viral loads, and rhinovirus in a co-infected patient. The sequenced viruses belonged to lineage B1. Because metagenomics could detect novel pathogen and co-infection, and generate sequence data for epidemiological investigation, it is an attractive approach for infectious-disease diagnosis.

The natural history and transmission potential of asymptomatic SARS-CoV-2 infection

BackgroundLittle is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. MethodsWe conducted a prospective study at a quarantine centre for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. ResultsBetween March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. ConclusionsAsymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.

Duration of viral detection in throat and rectum of a patient with COVID-19

The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.

Design, Fabrication, and Evaluation of Multifocal Point Transducer for High-Frequency Ultrasound Applications.

The present study illustrates the design, fabrication, and evaluation of a novel multifocal point (MFP) transducer based on polyvinylidene fluoride (PVDF) film for high-frequency ultrasound application. The fabricated MFP surface was press-focused using a computer numerical control (CNC) machining tool-customized multi-spherical pattern object. The multi-spherical pattern has five spherical surfaces with equal area and connected continuously to have the same energy level at focal points. Center points of these spheres are distributed in a linear pattern with 1 mm distance between each two points. The radius of these spheres increases steadily from 10 mm to 13.86 mm. The designed MFP transducer had a center frequency of 50 MHz and a -6 dB bandwidth of 68%. The wire phantom test was conducted to study and demonstrate the advantages of this novel design. The obtained results for MFP transducer revealed a significant increase (4.3 mm) of total focal zone in the near-field and far-field area compared with 0.48 mm obtained using the conventional single focal point transducer. Hence, the proposed method is promising to fabricate MFP transducers for deeper imaging depth applications.