scholarly journals A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana

2021 ◽  
Author(s):  
Nicholas O. Opoku ◽  
Michael E. Gyasi ◽  
Felix Doe ◽  
Daphne Lew ◽  
Augustine R. Hong ◽  
...  
Keyword(s):  
Adverse Events ◽  
Geometric Mean ◽  
Onchocerca Volvulus ◽  
Moderate Intensity ◽  
Special Focus ◽  
Ivermectin Treatment ◽  
Slit Lamp ◽  
Treatment Naïve ◽  
Study Participants ◽  
Kinetics Of

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (ACs) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 μg/kg. Out of 231 people, 79 enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3–86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3–5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.

scholarly journals Ivermectin Treatment Response in Onchocerca Volvulus Infected Persons with Epilepsy: A Three-Country Short Cohort Study

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 617
Author(s):  
Alfred Dusabimana ◽  
Dan Bhwana ◽  
Stephen Raimon ◽  
Bruno P. Mmbando ◽  
An Hotterbeekx ◽  
...  
Keyword(s):  
Democratic Republic Of Congo ◽  
Geometric Mean ◽  
Infection Intensity ◽  
Post Treatment ◽  
Onchocerca Volvulus ◽  
Ivermectin Treatment ◽  
Positive Skin ◽  
History Of ◽  
Pre Treatment ◽  
Study Sites

Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.

scholarly journals Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blinded, Randomised, Placebo-Controlled Phase 2 Trial

2021 ◽  
Author(s):  
Szu-Min Hsieh ◽  
Ming-Che Liu ◽  
Yen-Hsu Chen ◽  
Wen-Sen Lee ◽  
Shinn-Jang Hwang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aluminium Hydroxide ◽  
Large Scale ◽  
Geometric Mean ◽  
Phase 2 ◽  
Protein Vaccine ◽  
Multi Centre Study ◽  
Phase 2 Trial ◽  
Double Blinded ◽  
Study Participants

Background We have assessed the safety and immunogenicity of MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide against COVID-19. Methods This is a phase 2, prospective, double-blinded, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 mcg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652. Findings From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) was recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662.3 (408 IU/mL), the GMT ratio was 163.2, and the seroconversion rate was 99.8%. Interpretation MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials, and could enable regulatory considerations for Emergency Use Authorisation (EUA). Funding Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.

scholarly journals The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled trial

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jutamas Saoraya ◽  
Lipda Wongsamita ◽  
Nattachai Srisawat ◽  
Khrongwong Musikatavorn
Keyword(s):  
Adverse Events ◽  
Organ Failure ◽  
Fluid Resuscitation ◽  
Infusion Rate ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Endothelial Glycocalyx ◽  
Open Label ◽  
Randomized Controlled ◽  
Standard Rate

Abstract Background Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. Methods A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician’s discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. Results We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35–52 ml/kg) vs. 53 ml/kg (IQR 46–64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66–1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. Conclusions In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. Trial registration Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064

scholarly journals Physical properties and water absorption kinetics of three varieties of Mucuna beans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajibola B. Oyedeji ◽  
Olajide P. Sobukola ◽  
Ezekiel Green ◽  
Oluwafemi A. Adebo
Keyword(s):  
Physical Properties ◽  
Water Absorption ◽  
Rate Constant ◽  
Geometric Mean ◽  
Seed Mass ◽  
Activation Energies ◽  
Mucuna Pruriens ◽  
Absorption Kinetics ◽  
Kinetics Of ◽  
Soaking Temperature

AbstractThe physical properties and water absorption kinetics of three varieties of Mucuna beans (Mucuna pruriens, Mucuna rajada and Mucuna veracruz) were determined in this study. Physical properties including length, width, thickness, geometric mean diameter, sphericity, porosity, bulk density, area, volume and one thousand seed mass were calculated while hydration kinetics was studied by soaking Mucuna beans in water at 30 °C, 40 °C and 50 °C and measuring water uptake at 9 h interval. Peleg’s equation was used to model the hydration characteristics and Arrhenius equation was used to describe the effect of temperature on Peleg’s rate constant k1 and to obtain the activation energies for soaking. Significant variations were observed in almost all the physical properties of the different varieties, however, there were no significant differences (p < 0.05) in their thicknesses and bulk densities. The effectiveness of fit of Peleg’s model (R2) increased with increase in soaking temperature. Peleg’s rate constant k1 decreased with increase in soaking temperature while k2 increased with temperature increase. Activation energies of Mucuna pruriens, Mucuna rajada and Mucuna veracruz were 1613.24 kJ/mol, 747.95 kJ/mol and 2743.64 kJ/mol, respectively. This study provides useful information about the properties of three varieties of Mucuna beans that could be of importance to processors and engineers for process design and optimization.

scholarly journals High-dose oral and intravenous rifampicin for the treatment of tuberculous meningitis in predominantly HIV-positive Ugandan adults: a phase II open-label randomised controlled trial

2021 ◽  
Author(s):  
Fiona V Cresswell ◽  
David B Meya ◽  
Enock Kagimu ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Geometric Mean ◽  
Standard Of Care ◽  
Hiv Positive ◽  
High Dose ◽  
Open Label ◽  
Dose Oral ◽  
Csf Levels

Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events. Results We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46–56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P&lt;0.001). In CSF, standard-of-care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27mg/L, compared with 1.74mg/L (95%CI 1.2–2.5) for IV-20 and 2.17mg/L (1.6–2.9) for PO-35 regimens (p&lt;0.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (p=0.34) Conclusion Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe, and respectively resulted in exposures ~6- and ~8-fold higher than standard-of-care, and CSF levels above the MIC

scholarly journals Safety and Immunogenicity of a Novel Staphylococcus aureus Vaccine: Results from the First Study of the Vaccine Dose Range in Humans

2010 ◽  
Vol 17 (12) ◽  
pp. 1868-1874 ◽  
Author(s):  
Clayton Harro ◽  
Robert Betts ◽  
Walter Orenstein ◽  
Eun-Jeong Kwak ◽  
Howard E. Greenberg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Adverse Events ◽  
Immune Responses ◽  
Geometric Mean ◽  
Dose Range ◽  
Vaccine Dose ◽  
Double Blind Study ◽  
Mean Concentration ◽  
Positive Immune Response

ABSTRACT Merck V710 is a novel vaccine containing the conserved Staphylococcus aureus iron surface determinant B shown to be protective in animal models. A phase I, multicenter, double-blind study of the dose range was conducted to assess the immunogenicity and safety of an adjuvanted liquid formulation of V710. A total of 124 adults (18 to 55 years of age) were randomized 1:1:1:1 to receive one 0.5-ml intramuscular injection of V710 (5 μg, 30 μg, or 90 μg) or saline placebo. A positive immune response was defined as at least a 2-fold increase in IsdB-specific IgG levels from baseline levels. Local and systemic adverse events were assessed for 5 and 14 days, respectively, following vaccination. Positive immune responses were detected in 12 (67%) of the 18 subjects in the groups receiving 30 and 90 μg V710 tested at day 10. At day 14, a significantly greater proportion of subjects manifested a positive immune response with higher geometric mean concentrations in the V710 30-μg (86%; geometric mean concentration of 116 μg/ml) and 90-μg (87%; geometric mean concentration of 131 μg/ml) dose groups than in the V710 5-μg (29%; geometric mean concentration of 51 μg/ml) or placebo (4%; geometric mean concentration of 23 μg/ml) groups. Immune responses were durable through day 84. Subjects <40 and ≥40 years of age had comparable immune responses. The most common adverse events were injection-site pain, nausea, fatigue, and headache, usually of mild intensity. No immediate reactions or serious adverse events were reported. In this first study of V710 in humans, a single 30-μg or 90-μg dose was more immunogenic than the 5-μg dose or placebo. Immune responses were evident by 10 to 14 days after vaccination in most responders.

Effects of priming exercise on the speed of adjustment of muscle oxidative metabolism at the onset of moderate-intensity step transitions in older adults

2012 ◽  
Vol 302 (10) ◽  
pp. R1158-R1166 ◽  
Author(s):  
Gabriela De Roia ◽  
Silvia Pogliaghi ◽  
Alessandra Adami ◽  
Christina Papadopoulou ◽  
Carlo Capelli
Keyword(s):  
Older Adults ◽  
Cardiac Output ◽  
Oxidative Metabolism ◽  
Functional Decline ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Healthy Older Adults ◽  
Speed Of Adjustment ◽  
Priming Exercise ◽  
Kinetics Of

Aging is associated with a functional decline of the oxidative metabolism due to progressive limitations of both O2 delivery and utilization. Priming exercise (PE) increases the speed of adjustment of oxidative metabolism during successive moderate-intensity transitions. We tested the hypothesis that such improvement is due to a better matching of O2 delivery to utilization within the working muscles. In 21 healthy older adults (65.7 ± 5 yr), we measured contemporaneously noninvasive indexes of the overall speed of adjustment of the oxidative metabolism (i.e., pulmonary V̇o2 kinetics), of the bulk O2 delivery (i.e., cardiac output), and of the rate of muscle deoxygenation (i.e., deoxygenated hemoglobin, HHb) during moderate-intensity step transitions, either with (ModB) or without (ModA) prior PE. The local matching of O2 delivery to utilization was evaluated by the ΔHHb/ΔV̇o2 ratio index. The overall speed of adjustment of the V̇o2 kinetics was significantly increased in ModB compared with ModA ( P < 0.05). On the contrary, the kinetics of cardiac output was unaffected by PE. At the muscle level, ModB was associated with a significant reduction of the “overshoot” in the ΔHHb/ΔV̇o2 ratio compared with ModA ( P < 0.05), suggesting an improved O2 delivery. Our data are compatible with the hypothesis that, in older adults, PE, prior to moderate-intensity exercise, beneficially affects the speed of adjustment of oxidative metabolism due to an acute improvement of the local matching of O2 delivery to utilization.

Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment

The Lancet ◽  
2001 ◽  
Vol 357 (9266) ◽  
pp. 1415-1416 ◽  
Author(s):  
Achim Hoerauf ◽  
Sabine Mand ◽  
Ohene Adjei ◽  
Bernhard Fleischer ◽  
Dietrich W Büttner
Keyword(s):  
Onchocerca Volvulus ◽  
Ivermectin Treatment

AN EPIDEMIOLOGICAL STUDY ON SELECTED RISK FACTORS OF STROKE AMONG ADULTS LIVING IN A SLUM OF KOLKATA.

2021 ◽  
pp. 8-11
Author(s):  
Tanushree Mondal ◽  
V. Abhinesh ◽  
Soumitra Mondal ◽  
Shibasish Banerjee ◽  
Debasis Das
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Alcohol Consumption ◽  
Public Health Intervention ◽  
Simple Random Sampling ◽  
Blood Cholesterol ◽  
Moderate Intensity ◽  
Cross Sectional ◽  
Permanent Disability ◽  
Study Participants

Introduction: Stroke is a major cause of permanent disability. Currently, the burden of stroke in terms of mortality, morbidity and disability is increasing across the world including India. The main risk factor of stroke are high blood pressure, tobacco smoking, obesity, high blood cholesterol and diabetes mellitus. Lifestyle factors that increase the risk of stroke include smoking, drinking alcohol, high fat diet. Objective: To identify the socio demographic prole of study population and to nd out the proportion of selected risk factors of stroke among the study subjects and to assess different risk factors among them. Methodology:An observational descriptive cross sectional study was undertaken in urban eld practice area of a teaching institute of Kolkata. By 2 using the formula 4pq/l , total 200 participants were selected by simple random sampling and they were interviewed during house to house visit with WHO STEPS questionnaire for Non Communicable Diseases (NCD). Results: The mean age of the participants was 42.39 years and 33.5% participants were overweight with high BMI. Only 26 % participants were hypertensive and most of them (57.69%) had duration of hypertension more than 1 year. Majority (72.03%) did not have diabetes mellitus. Most (61%) of study participants had done moderate intensity physical activity regularly. Almost 25.5% study participants consume tobacco products and Most of the study 92.8% participants consumed alcohol 1-4 times in past 30 days. Signicant association were seen between gender and smoking (p=0.005), Gender and alcohol consumption (p=0.000), Religion and alcohol consumption (p=0.03), Occupation category and alcohol consumption (p=0.002), Marital status and hypertension (p=0.001). Conclusion: Effective public health intervention required promote regular exercise and healthy eating, avoiding alcohol and tobacco. Periodic screening for hypertension and diabetes and early diagnosis and treatment are key strategy for stroke prevention.

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