After the recent announcement of COVID-19 vaccine efficacy in clinical trials by several manufacturers for protection against severe disease, a comprehensive post-efficacy strategy for the next steps ...to ensure vaccination of the global population is now required. These considerations should include how to manufacture billions of doses of high-quality vaccines, support for vaccine purchase, coordination of supply, the equitable distribution of vaccines and the logistics of global vaccine delivery, all of which are a prelude to a massive vaccination campaign targeting people of all ages. Furthermore, additional scientific questions about the vaccines remain that should be answered to improve vaccine efficacy, including questions regarding the optimization of vaccination regimens, booster doses, the correlates of protection, vaccine effectiveness, safety and enhanced surveillance. The timely and coordinated execution of these post-efficacy tasks will bring the pandemic to an effective, and efficient, close.
Epidemiology of cholera Deen, Jacqueline; Mengel, Martin A; Clemens, John D
Vaccine,
02/2020, Letnik:
38
Journal Article
Recenzirano
Odprti dostop
Cholera is an ancient disease that remains a public health problem in many impoverished locations around the world. Seven pandemics of cholera have been recorded since the first pandemic in 1817, the ...last of which is on going. Overcrowding, poverty, insufficient water and sanitation facilities increase the risk for cholera outbreaks. The epidemiology of cholera in the areas in Asia, Africa and the Americas where the disease occurs continues to evolve.
Differentiation of the continental crust begins with its partial melting. The products of crustal melting are silicic, hydrous, H2O-undersaturated, granitic liquids that are generated within matrices ...of residual crystals. Crustal differentiation requires that felsic magmas form and escape from these solid residua. An important question is whether granitic magmas collect into large batches, within or near their sources, which then give rise to ascent or, alternatively, bleed out of the sources in smaller streams or pulses. We demonstrate that the physical reality is closer to the second alternative, and thus question the validity of the concepts of magma segregation and source fertility, as they are sometimes visualised.
Granitic plutons contain chemically distinct sub-populations formed by source-level entrainment of the peritectic assemblages into the melts. Rapid evacuation at source levels and high ascent rates protect the magmas from wall-rock interactions during their tenure at source depths and during their ascent through cool upper crust. The existence of different types of granites, and hence of clearly defined chemically different magmas within plutons, dictates that felsic magmas must separate efficiently from their anatectic sources and must ascend to the sites of their emplacement with minimal chemical interaction with crust through which the magma must move. Exposed deep-crustal sections are typically lithologically diverse, with the more fertile rocks commonly forming discrete layers surrounded by rocks with contrasting compositions. If the melts were required to segregate and accumulate into large volumes within their hot sources, especially by slow, gravity-driven melt percolation, it is very likely that they would be substantially modified by reaction with diverse source rocks. Thus, the processes mooted to occur in melting, assimilation, storage and homogenisation (MASH) or deep crustal hot (DCH) zones would act to erase original compositional heterogeneities and produce larger batches of more homogeneous magma, perhaps carrying evidence of extensive magma mixing. From various lines of evidence, we conclude that MASH and DCH zones may not exist and, even if they do, they cannot form the sources of most granitic magmas. The intrinsic heterogeneity in crustal source rocks, the likely occurrence of peritectic assemblage entrainment and the inefficiency of magma mixing decree that granitic rocks will retain source-inherited chemical and isotopic heterogeneities. Rapid, semi-continuous and disequilibrium withdrawal of small magma batches from source rocks means that elements of whole-rock, trace-element chemistry and accessory mineral chemistry will be decoupled from major-element variations. This also means that a large source with low nominal fertility (due to low hydrous mineral content, for example) could still produce a substantial granitic pluton, by additions of individually small increments of magma.
Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2) has been developed to be more ...genetically stable with similar tolerability and immunogenicity to that of Sabin type 2 vaccines to mitigate the risk of cVDPV2. We aimed to assess these aspects of nOPV2 in poliovirus vaccine-naive newborn infants.
In this randomised, double-blind, controlled, phase 2 trial we enrolled newborn infants at the Matlab Health Research Centre, Chandpur, Bangladesh. We included infants who were healthy and were a single birth after at least 37 weeks' gestation. Infants were randomly assigned (2:1) to receive either two doses of nOPV2 or placebo, administered at age 0–3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, NCT04693286.
Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 67%) or placebo (n=110 33%). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) of 104 in the placebo group at 8 weeks. In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies.
nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies.
Bill & Melinda Gates Foundation.
•Ivermectin, an FDA-approved anti-parasitic agent, was found to be an inhibitor of SARS-CoV-2 replication in the laboratory.•Ivermectin may be effective for the treatment of early-onset mild COVID-19 ...in adult patients.•Early viral clearance of SARS-CoV-2 was observed in ivermectin treated patients.•Remission of fever, cough and sore throat did not differ among treatment groups. No severe adverse event was observed.•Larger trials will be needed to confirm these preliminary findings.
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
Abstract
Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection ...among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.
Cholera causes substantial morbidity and mortality in the world's poorest populations. For nearly a decade, an inactivated oral cholera vaccine (OCV) stockpile has been available to control and ...prevent outbreaks. In 2017, WHO launched a bold global initiative to reduce mortality from cholera by 90% by 2030, a cornerstone of which is deployment of OCVs from the global stockpile. The current production of OCVs for the stockpile falls well short of the doses needed to accomplish this goal. Besides efforts to enlist additional manufacturers of the current OCVs in the stockpile, inclusion of new-generation inactivated OCVs already in clinical development might offer advantages of enlarged production, improved performance, simplified logistics, and reduced costs. However, logistical, scientific, and ethical barriers make conventional, randomised, phase 3 clinical efficacy trials towards licensure of such new-generation OCVs problematic. The serum vibriocidal antibody response, the traditional immunological surrogate of protection against cholera, is imperfect for use as a standalone outcome. In this Personal View, we describe the need for new thinking on approaches for licensure and recommendations for new-generation inactivated OCVs, and suggest a pathway based on a sequential combination of immunogenicity and effectiveness observational studies.
Plant source water identification using stable isotopes is now a common practice in ecohydrological process investigations. Notwithstanding, little critical evaluation of the approaches for source ...apportionment have been conducted. Here, we present a critical evaluation of the main methods used for source apportionment between vadose and saturated zone water: simple mass balance and Bayesian mixing models. We leverage new isotope stem water samples from a diverse set of tree species in a strikingly uniform terrain and soil conditions at the Christchurch Botanic Garden, New Zealand. Our results show that using δ2H alone in a simple, two‐source mass balance approach leads to erroneous results, particularly an apparent overestimation of groundwater contribution to xylem. Alternatively, using both δ2H and δ18O in a Bayesian inference framework improves the source water estimates and is more useful than the simple mass balance approach, particularly when soil and groundwater contributions are relatively disproportionate. We suggest that plant source water quantification methods should take into consideration the possible effects of 2H/1H fractionation. The Bayesian inference approach used here may be less sensitive to 2H/1H fractionation effects than simple mass balance methods.
Vaccine clinical trials are necessary in low- and middle-income countries (LMICs) because new vaccine candidates are developed against diseases found mainly in these settings, the results of trials ...done in industrialized countries may not be generalizable to LMICs and more institutions in middle-income countries are producing vaccines for use in LMICs.
We searched PubMed and conducted a narrative review on standard, newer and proposed approaches toward obtaining data supportive for vaccine licensure, with a special focus in LMICs.
Of the vaccine trials done worldwide, only a small proportion is conducted in LMICs, but this is likely to increase as more research experience and infrastructure is developed. At present, the majority of vaccine trials follows the standard paradigm of fixed phase 1 to 3 trials, the latter with clinical endpoints, or immunobridging studies when a valid immunocorrelate of vaccine protection exists. Other study designs may help facilitate the generation of data toward licensure of and recommendations for needed vaccines. Increased international collaboration is needed for local capacity building and regulatory oversight to ensure that all studies are conducted under good clinical practice.
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