Modeling of malaria vaccine effectiveness on disease burden and drug resistance in 42 African countries.

BACKGROUND: The emergence of antimalarial drug resistance poses a major threat to effective malaria treatment and control. This study aims to inform policymakers and vaccine developers on the potential of an effective malaria vaccine in reducing drug-resistant infections. METHODS: A compartmental model estimating cases, drug-resistant cases, and deaths averted from 2021 to 2030 with a vaccine against Plasmodium falciparum infection administered yearly to 1-year-olds in 42 African countries. Three vaccine efficacy (VE) scenarios and one scenario of rapidly increasing drug resistance are modeled. RESULTS: When VE is constant at 40% for 4 years and then drops to 0%, 235.7 (Uncertainty Interval [UI] 187.8-305.9) cases per 1000 children, 0.6 (UI 0.4-1.0) resistant cases per 1000, and 0.6 (UI 0.5-0.9) deaths per 1000 are averted. When VE begins at 80% and drops 20 percentage points each year, 313.9 (UI 249.8-406.6) cases per 1000, 0.9 (UI 0.6-1.3) resistant cases per 1000, and 0.9 (UI 0.6-1.2) deaths per 1000 are averted. When VE remains 40% for 10 years, 384.7 (UI 311.7-496.5) cases per 1000, 1.0 (0.7-1.6) resistant cases per 1000, and 1.1 (UI 0.8-1.5) deaths per 1000 are averted. Assuming an effective vaccine and an increase in current levels of drug resistance to 80% by 2030, 10.4 (UI 7.3-15.8) resistant cases per 1000 children are averted. CONCLUSIONS: Widespread deployment of a malaria vaccine could substantially reduce health burden in Africa. Maintaining VE longer may be more impactful than a higher initial VE that falls rapidly.

Malaria can become resistant to the drugs used to treat it, posing a major threat to malaria treatment and control. An effective vaccine has the potential to reduce both resistant infections and antimalarial drug use. However, how successfully a vaccine can protect against infection (vaccine efficacy) and the impact of increasing drug resistance remain unclear. Using a mathematical model, we estimate the impact of malaria vaccination in 42 African countries over a 10-year period in multiple scenarios with differing vaccine efficacy and drug resistance. Our model suggests that a moderately effective vaccine with sustained protection over a long period could avert more resistant infections and deaths than a vaccine that is highly protective initially but lowers in efficacy over time. Nevertheless, implementation of an effective malaria vaccine should be accelerated to mitigate the health and economic burden of drug resistance.

Synthesis and structural properties of a 2D Zn(II) dodecahydroxy-closo-dodecaborate coordination polymer.

In this work, we discuss the synthesis and characterization of a 2D coordination polymer composed of a dianionic perhydroxylated boron cluster, [B12(OH)122-], coordinated to Zn(II)-the first example of a transition metal-coordinated [B12(OH)12]2- compound. This material was synthesized via cation exchange from the starting cesium salt and then subjected to rigorous characterization prior to and after thermal activation. Numerous techniques, including XRD, FTIR, SEM, TGA, and solid-state NMR revealed a 2D coordination polymer composed of sheets of Zn(II) ions intercalated between planes of boron clusters. The as-synthesized material was then evacuated of solvent via thermal treatment, and atomic-level changes from this transformation were elucidated through a combination of 1D and 2D solid-state NMR analyses of 11B and 1H nuclei, suggesting the full removal of coordinated solvent molecules. Evidence also suggested that [B12(OH)122-] can adjust its coordination to Zn(II) in the solid-state through hemilability of its numerous -OH ligands.

Public health facility quality and child immunization outcomes in rural India: A decomposition analysis.

Universal coverage of routine childhood vaccines remains a challenge in many low- and middle-income countries (LMICs). In India, vaccination campaigns have increased full immunization coverage among 12-23 month old children from an estimated 62% in 2015-2016 to 76% in 2019-2020. Long-term improvements in coverage will likely require systemic changes to both the supply and demand sides of immunization programs. However, the effect of health system inputs on child vaccination outcomes remains poorly quantified in India. We examined the association between the quality of public health facilities and child vaccination outcomes in rural India using data from the nationally representative Integrated Child Health and Immunization Survey (2015-2016) which covered 1,346 public primary health sub-centers and 44,571 households. We constructed two indices of sub-center quality using multiple correspondence analysis: one related to the general health infrastructure quality and the other measuring vaccine service delivery. Using probit regression, we analyzed the relationship between vaccination outcomes in children under 2 years of age and sub-center quality, controlling for household socioeconomic characteristics. Additionally, we conducted Fairlie decomposition analysis by wealth group - bottom wealth quintile relative to the top four wealth quintiles- to examine factors contributing to gaps in immunization between rich and poor households. Infrastructure quality index was positively associated with completion of seven vaccination outcomes: full immunization, DPT-1 (first dose of diphtheria, pertussis, and tetanus), DPT-2, DPT-3, Bacillus Calmette-Guérin (BCG), hepatitis B (birth dose), and on-time vaccination (OTV). Vaccine service delivery index was positively associated with completion of measles vaccination. The distribution of infrastructure quality contributed to increased gaps in full immunization and OTV between rich and poor households, while greater proximity to vaccination site for poorer households reduced these gaps. Improved quality of health facilities, particularly facilities used by low-income households, may improve vaccination outcomes.

Public finance of universal routine childhood immunization in India: district-level cost estimates.

India's Universal Immunization Programme (UIP) is among the largest routine childhood vaccination programmes in the world. However, only an estimated 65% of Indian children under the age 2 years were fully vaccinated in 2019. We estimated the cost of raising childhood vaccination coverage to a minimum of 90% in each district in India. We obtained vaccine price data from India's comprehensive multi-year strategic plan for immunization. Cost of vaccine delivery by district was derived from a 2018 field study in 24 districts. We used propensity score matching methods to match the remaining Indian districts with these 24, based on indicators from the National Family Health Survey (2015-16). We assumed the same unit cost of vaccine delivery in matched pair districts and estimated the total and incremental cost of providing routine vaccines to 90% of the current cohort of children in each district. The estimated national cost of providing basic vaccinations-one dose each of Bacillus Calmette-Guerin (BCG) and measles vaccines, and three doses each of oral polio (OPV) and diphtheria, pertussis and tetanus vaccines-was $784.91 million (2020 US$). Considering all childhood vaccines included in UIP during 2018-22 (one dose each of BCG, hepatitis B and measles-rubella; four doses of OPV; two doses of inactivated polio; and three doses each of rotavirus, pneumococcal and pentavalent vaccines), the estimated national cost of vaccines and delivery to 90% of target children in each district was $1.73 billion. The 2018 UIP budget for vaccinating children, pregnant women and adults was $1.17 billion (2020 US$). In comparison, $1.73 billion would be needed to vaccinate 90% of children in all Indian districts with the recommended schedule of routine childhood vaccines. Additional costs for infrastructural investments and communication activities, not incorporated in this study, may also be necessary.

AB2X6 Compounds and the Stabilization of Trirutile Oxides.

The properties of crystalline materials tend to be strongly correlated with their structures, and the prediction of crystal structure from only the composition is a coveted goal in the field of inorganic materials. However, even for the simplest compositions, such prediction relies on a complex network of interactions, including atomic or ionic radii, ionicity, electronegativity, position in the periodic table, and magnetism, to name only a few important parameters. We focus here on the AB2X6 (AB2O6 and AB2F6) composition space with the specific goal of finding new oxide compounds in the trirutile family, which is known for unusual one-dimensional (1D) antiferromagnetic behavior. Through machine learning methods, we develop an understanding of how geometric and bonding constraints determine the crystallization of compounds in the trirutile structure as opposed to other ternary structures in this space. In combination with density functional theory (DFT) calculations, we predict 16 previously unreported candidate trirutile oxides. We successfully prepare one of these and show it forms in the disordered rutile structure, under the preparation conditions adopted here.

Modelling COVID-19 transmission in Africa: countrywise projections of total and severe infections under different lockdown scenarios.

OBJECTIVES: As of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios. DESIGN: We developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB). RESULTS: In the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis. CONCLUSION: The COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.

Associations between private vaccine and antimicrobial consumption across Indian states, 2009-2017.

Vaccines can reduce antibiotic use and, consequently, antimicrobial resistance by averting vaccine-preventable and secondary infections. We estimated the associations between private vaccine and antibiotic consumption across Indian states during 2009-2017 using monthly and annual consumption data from IQVIA and employed fixed-effects regression and the Arellano-Bond Generalized Method of Moments (GMM) model for panel data regression, which controlled for income and public sector vaccine use indicators obtained from other sources. In the annual data fixed-effects model, a 1% increase in private vaccine consumption per 1000 under-5 children was associated with a 0.22% increase in antibiotic consumption per 1000 people (P < 0.001). In the annual data GMM model, a 1% increase in private vaccine consumption per 1000 under-5 children was associated with a 0.2% increase in private antibiotic consumption (P < 0.001). In the monthly data GMM model, private vaccine consumption was negatively associated with antibiotic consumption when 32, 34, 35, and 44-47 months had elapsed after vaccine consumption, with a positive association with lags of fewer than 18 months. These results indicate vaccine-induced longer-term reductions in antibiotic use in India, similar to findings of studies from other low- and middle-income countries.

The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010-2017.

BACKGROUND: Influenza, which peaks seasonally, is an important driver for antibiotic prescribing. Although influenza vaccination has been shown to reduce severe illness, evidence of the population-level effects of vaccination coverage on rates of antibiotic prescribing in the United States is lacking. METHODS: We conducted a retrospective analysis of influenza vaccination coverage and antibiotic prescribing rates from 2010 to 2017 across states in the United States, controlling for differences in health infrastructure and yearly vaccine effectiveness. Using data from IQVIA's Xponent database and the US Centers for Disease Control and Prevention's FluVaxView, we employed fixed-effects regression analysis to analyze the relationship between influenza vaccine coverage rates and the number of antibiotic prescriptions per 1000 residents from January to March of each year. RESULTS: We observed that, controlling for socioeconomic differences, access to health care, childcare centers, climate, vaccine effectiveness, and state-level differences, a 10-percentage point increase in the influenza vaccination rate was associated with a 6.5% decrease in antibiotic use, equivalent to 14.2 (95% CI, 6.0-22.4; P = .001) fewer antibiotic prescriptions per 1000 individuals. Increased vaccination coverage reduced prescribing rates the most in the pediatric population (0-18 years), by 15.2 (95% CI, 9.0-21.3; P < .001) or 6.0%, and the elderly (aged 65+), by 12.8 (95% CI, 6.5-19.2; P < .001) or 5.2%. CONCLUSIONS: Increased influenza vaccination uptake at the population level is associated with state-level reductions in antibiotic use. Expanding influenza vaccination could be an important intervention to reduce unnecessary antibiotic prescribing.

Isolation of a Bimetallic Cobalt(III) Nitride and Examination of Its Hydrogen Atom Abstraction Chemistry and Reactivity toward H2.

Room temperature photolysis of the bis(azide)cobaltate(II) complex [Na(THF)x][(ketguan)Co(N3)2] (ketguan = [(tBu2CN)C(NDipp)2]-, Dipp = 2,6-diisopropylphenyl) (3a) in THF cleanly forms the binuclear cobalt nitride Na(THF)4{[(ketguan)Co(N3)]2(µ-N)} (1). Compound 1 represents the first example of an isolable, bimetallic cobalt nitride complex, and it has been fully characterized by spectroscopic, magnetic, and computational analyses. Density functional theory supports a CoIII═N═CoIII canonical form with significant π-bonding between the cobalt centers and the nitride atom. Unlike other group 9 bridging nitride complexes, no radical character is detected at the bridging N atom of 1. Indeed, 1 is unreactive toward weak C-H donors and even cocrystallizes with a molecule of cyclohexadiene (CHD) in its crystallographic unit cell to give 1·CHD as a room temperature stable product. Notably, addition of pyridine to 1 or photolyzed solutions of [(ketguan)Co(N3)(py)]2 (4a) leads to destabilization via activation of the nitride unit, resulting in the mixed-valent Co(II)/Co(III) bridged imido species [(ketguan)Co(py)][(ketguan)Co](µ-NH)(µ-N3) (5) formed from intermolecular hydrogen atom abstraction (HAA) of strong C-H bonds (BDE ∼ 100 kcal/mol). Kinetic rate analysis of the formation of 5 in the presence of C6H12 or C6D12 gives a KIE = 2.5 ± 0.1, supportive of a HAA formation pathway. The reactivity of our system was further probed by photolyzing benzene/pyridine solutions of 4a under H2 and D2 atmospheres (150 psi), which leads to the exclusive formation of the bis(imido) complexes [(ketguan)Co(µ-NH)]2 (6) and [(ketguan)Co(µ-ND)]2 (6-D), respectively, as a result of dihydrogen activation. These results provide unique insights into the chemistry and electronic structure of late 3d metal nitrides while providing entryway into C-H activation pathways.

CsV_{3}Sb_{5}: A Z_{2} Topological Kagome Metal with a Superconducting Ground State.

Recently discovered alongside its sister compounds KV_{3}Sb_{5} and RbV_{3}Sb_{5}, CsV_{3}Sb_{5} crystallizes with an ideal kagome network of vanadium and antimonene layers separated by alkali metal ions. This work presents the electronic properties of CsV_{3}Sb_{5}, demonstrating bulk superconductivity in single crystals with a T_{c}=2.5 K. The normal state electronic structure is studied via angle-resolved photoemission spectroscopy and density-functional theory, which categorize CsV_{3}Sb_{5} as a Z_{2} topological metal. Multiple protected Dirac crossings are predicted in close proximity to the Fermi level (E_{F}), and signatures of normal state correlation effects are also suggested by a high-temperature charge density wavelike instability. The implications for the formation of unconventional superconductivity in this material are discussed.

Cardiovascular resistance to thrombosis in 13-lined ground squirrels.

13-lined ground squirrels (Ictidomys tridecemlineatus) enter hibernation as a survival strategy during extreme environmental conditions. Typical ground squirrel hibernation is characterized by prolonged periods of torpor with significantly reduced heart rate, blood pressure, and blood flow, interrupted every few weeks by brief interbout arousals (IBA) during which blood flow fluctuates dramatically. These physiological conditions should increase the risk of stasis-induced blood clots and myocardial ischemia. However, ground squirrels have adapted to survive repeated bouts of torpor and IBA without forming lethal blood clots or sustaining lethal ischemic myocardial damage. The purpose of this study was to determine if ground squirrels are resistant to thrombosis and myocardial ischemia during hibernation. Blood markers of coagulation, fibrinolysis, thrombosis, and ischemia, as well as histological markers of myocardial ischemia were measured throughout the annual hibernation cycle. Hibernating ground squirrels were also treated with isoprenaline to induce myocardial ischemia. Thrombin-antithrombin complex levels were significantly reduced (p < 0.05) during hibernation, while D-dimer level remained unchanged throughout the annual cycle, both consistent with an antithrombotic state. During torpor, the ground squirrels were in a hyperfibrinolytic state with an elevated ratio of tissue plasminogen activator complexed with plasminogen activator inhibitor to total plasminogen activator inhibitor (p < 0.05). Histological markers of myocardial ischemia were reversibly elevated during hibernation with no increase in markers of myocardial cell death in the blood. These data suggest that ground squirrels do not form major blood clots during hibernation through suppression of coagulation and a hyperfibrinolytic state. These animals also demonstrate myocardial resistance to ischemia.

Unraveling the Chemical Nature of the 3D "Hollow" Hybrid Halide Perovskites.

The newly introduced class of 3D halide perovskites, termed "hollow" perovskites, has been recently demonstrated as light absorbing semiconductor materials for fabricating lead-free perovskite solar cells with enhanced efficiency and superior stability. Hollow perovskites derive from three-dimensional (3D) AMX3 perovskites ( A = methylammonium (MA), formamidinium (FA); M = Sn, Pb; X = Cl, Br, I), where small molecules such as ethylenediammonium cations ( en) can be incorporated as the dication without altering the structure dimensionality. We present in this work the inherent structural properties of the hollow perovskites and expand this class of materials to the Pb-based analogues. Through a combination of physical and spectroscopic methods (XRD, gas pycnometry, 1H NMR, TGA, SEM/EDX), we have assigned the general formula (A)1- x( en) x(M)1-0.7 x(X)3-0.4 x to the hollow perovskites. The incorporation of en in the 3D perovskite structure leads to massive M and X vacancies in the 3D [ MX3] framework, thus the term hollow. The resulting materials are semiconductors with significantly blue-shifted direct band gaps from 1.25 to 1.51 eV for Sn-based perovskites and from 1.53 to 2.1 eV for the Pb-based analogues. The increased structural disorder and hollow nature were validated by single crystal X-ray diffraction analysis as well as pair distribution function (PDF) analysis. Density functional theory (DFT) calculations support the experimental trends and suggest that the observed widening of the band gap is attributed to the massive M and X vacancies, which create a less connected 3D hollow structure. The resulting materials have superior air stability, where in the case of Sn-based hollow perovskites it exceeds two orders of temporal magnitude compared to the conventional full perovskites of MASnI3 and FASnI3. The hollow perovskite compounds pose as a new platform of promising light absorbers that can be utilized in single junction or tandem solar cells.

Crystal Structure Evolution and Notable Thermal Expansion in Hybrid Perovskites Formamidinium Tin Iodide and Formamidinium Lead Bromide.

The temperature-dependent structure evolution of the hybrid halide perovskite compounds, formamidinium tin iodide (FASnI3, FA+ = CH[NH2]2+) and formamidinium lead bromide (FAPbBr3), has been monitored using high-resolution synchrotron X-ray powder diffraction between 300 and 100 K. The data are consistent with a transition from cubic Pm3m (No. 221) to tetragonal P4/mbm (No. 127) for both materials upon cooling; this occurs for FAPbBr3 between 275 and 250 K, and for FASnI3 between 250 and 225 K. Upon further cooling, between 150 and 125 K, both materials undergo a transition to an orthorhombic Pnma (No. 62) structure. The transitions are confirmed by calorimetry and dielectric measurements. In the tetragonal regime, the coefficients of volumetric thermal expansion of FASnI3 and FAPbBr3 are among the highest recorded for any extended inorganic crystalline solid, reaching 219 ppm K-1 for FASnI3 at 225 K. Atomic displacement parameters of all atoms for both materials suggest dynamic motion is occurring in the inorganic sublattice due to the flexibility of the inorganic network and dynamic lone pair stereochemical activity on the B-site. Unusual pseudocubic behavior is displayed in the tetragonal phase of the FAPbBr3, similar to that previously observed in FAPbI3.

Solution-Phase Conversion of Bulk Metal Oxides to Metal Chalcogenides Using a Simple Thiol-Amine Solvent Mixture.

A thiol-amine solvent mixture is used to dissolve ten inexpensive bulk oxides (Cu2O, ZnO, GeO2, As2O3, Ag2O, CdO, SnO, Sb2O3, PbO, and Bi2O3) under ambient conditions. Dissolved oxides can be converted to the corresponding sulfides using the thiol as the sulfur source, while selenides and tellurides can be accessed upon mixing with a stoichiometric amount of dissolved selenium or tellurium. The practicality of this method is illustrated by solution depositing Sb2Se3 thin films from compound inks of dissolved Sb2O3 and selenium that give high photoelectrochemical current response. The direct band gap of the resulting material can be tuned from 1.2-1.6 eV by modulating the ink formulation to give compositionally controlled Sb2Se(3-x)S(x) alloys.