The ongoing Zika virus (ZIKV) epidemic in the Americas poses a major global public health emergency. While ZIKV is transmitted from human to human by bites of Aedes mosquitoes, recent evidence ...indicates that ZIKV can also be transmitted via sexual contact with cases of sexually transmitted ZIKV reported in Argentina, Canada, Chile, France, Italy, New Zealand, Peru, Portugal, and the USA. Yet, the role of sexual transmission on the spread and control of ZIKV infection is not well-understood. We introduce a mathematical model to investigate the impact of mosquito-borne and sexual transmission on the spread and control of ZIKV and calibrate the model to ZIKV epidemic data from Brazil, Colombia, and El Salvador. Parameter estimates yielded a basic reproduction number 0 = 2.055 (95% CI: 0.523-6.300), in which the percentage contribution of sexual transmission is 3.044% (95% CI: 0.123-45.73). Our sensitivity analyses indicate that 0 is most sensitive to the biting rate and mortality rate of mosquitoes while sexual transmission increases the risk of infection and epidemic size and prolongs the outbreak. Prevention and control efforts against ZIKV should target both the mosquito-borne and sexual transmission routes.
We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the ...Sustainable Development Goals of the United Nations.
In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.
A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval CI, 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.
Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).
Abstract
Background
The incidence of herpes zoster (HZ) has been increasing in recent decades. Although 2 vaccines for HZ are available, there have been few studies on the incidence rates of HZ and ...postherpetic neuralgia (PHN) since their introduction. This study examined the incidence rates of HZ and PHN from 1994 to 2018 in the United States to determine if they have continued to increase since introduction of the HZ vaccines.
Methods
A de-identified longitudinal administrative claims database, the OptumLabs Data Warehouse, was used to assess incidence rates among individuals continuously enrolled in the database for ≥365 days with no prior history of HZ or PHN. Unstandardized and standardized incidence rates were calculated by year, 10-year age groups, sex, and race/ethnicity.
Results
There were 610 766 individuals with HZ (median age, 56.3; interquartile range, 43.0–68.7 years; 59.8% women; 70.6% white). From 1994 to 2018, the incidence of HZ increased from 286.0 (95% confidence interval CI, 259.1–312.8) to 579.6 (95% CI, 554.2–605.0) cases per 100 000 person-years, an annual increase of 3.1% (95% CI, 2.5–3.6%). Since 2007, annual HZ incidence rates have decreased in individuals ≤20 and >60 years old. The overall incidence rate of PHN was 57.5 (95% CI, 56.0–59.0) cases per 100 000 person-years. The proportion of individuals with HZ who developed PHN was higher from 2007 to 2018 than from 1994 to 2006.
Conclusions
HZ incidence rates have continued to increase in age groups for which HZ vaccines are not currently recommended, warranting a review of current vaccine recommendations.
The incidence rates of herpes zoster and postherpetic neuralgia increased overall in the United States from 1994 to 2018. Since 2007, the observed herpes zoster incidence rates have begun to decline in the youngest and oldest age groups.
About the Authors: Matthew R. Behrend * E-mail: behrend04@gmail.com Affiliations Neglected Tropical Diseases, Bill & Melinda Gates Foundation, Seattle, Washington, United States of America, Blue Well ...8, Seattle, Washington, United States of America ORCID logo http://orcid.org/0000-0002-5664-0520 María-Gloria Basáñez Affiliation: MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Jonathan I. D. Hamley Affiliation: MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Travis C. Porco Affiliation: Francis I. Proctor Foundation for Research in Ophthalmology, Department of Epidemiology and Biostatistics, and Department of Ophthalmology, University of California, San Francisco, United States of America Wilma A. Stolk Affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands Martin Walker Affiliations London Centre for Neglected Tropical Disease Research, Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom, London Centre for Neglected Tropical Disease Research and Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Sake J. de Vlas Affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands ORCID logo http://orcid.org/0000-0002-1830-5668 for the NTD Modelling Consortium Introduction The neglected tropical diseases (NTDs) thrive mainly among the poorest populations of the world.
Onchocerciasis (a filarial disease caused by infection with Onchocerca volvulus and transmitted by blackfly, Simulium, vectors) probably provides the best example of impactful modelling, with its long history of using evidence—mostly from the ONCHOSIM and EPIONCHO transmission models 7—to support decision-making within ongoing multicountry control initiatives (Table 1).
Onchocerciasis modelling and policy impact. https://doi.org/10.1371/journal.pntd.0008033.t001 From the start of the NTD Modelling Consortium in 2015, there have been several other examples of impactful modelling, which could be divided over three major scales of operations: (1) developing WHO guidelines (e.g., for triple-drug therapy, with ivermectin, diethylcarbamazine, and albendazole, against lymphatic filariasis 16, 17); (2) informing funding decisions for new intervention tools (e.g., the development of a schistosomiasis vaccine 18); and (3) guiding within-country targeting of control (e.g., local vector control for human African trypanosomiasis in the Democratic Republic of the Congo 19, 20 and Chad 21).
Relative word frequencies are represented by size of the font. https://doi.org/10.1371/journal.pntd.0008033.g002 Scoring the guidance statements Authors coded the data set individually (MRB, TCP, WAS, SJdV) and jointly (M-GB, JIDH, MW), producing five independently coded sets of data (S1 Table).
A susceptible-infectious-susceptible (SIS) epidemic model that describes the coinfection and cotransmission of two infectious diseases spreading through a single population is studied. The host ...population consists of two subclasses: susceptible and infectious, and the infectious individuals are further divided into three subgroups: those infected by the first agent/pathogen, the second agent/pathogen, and both. The basic reproduction numbers for all cases are derived which completely determine the global stability of the system if the presence of one agent/pathogen does not affect the transmission of the other. When the constraint on the transmissibility of the dually infected hosts is removed, we introduce the invasion reproduction number, compare it with two other types of reproduction number and show the uniform persistence of both diseases under certain conditions. Numerical simulations suggest that the system can display much richer dynamics such as backward bifurcation, bistability and Hopf bifurcation.
To assess the interdevice agreement between swept-source Fourier-domain and time-domain anterior segment optical coherence tomography (AS-OCT).
Fifty-three eyes from 41 subjects underwent CASIA2 and ...Visante OCT imaging. One hundred eighty-degree axis images were measured with the built-in two-dimensional analysis software for the swept-source Fourier-domain AS-OCT (CASIA2) and a customized program for the time-domain AS-OCT (Visante OCT). In both devices, we examined the angle opening distance (AOD), trabecular iris space area (TISA), angle recess area (ARA), anterior chamber depth (ACD), anterior chamber width (ACW), and lens vault (LV). Bland-Altman plots and intraclass correlation (ICC) were performed. Orthogonal linear regression assessed any proportional bias.
ICC showed strong correlation for LV (0.925) and ACD (0.992) and moderate agreement for ACW (0.801). ICC suggested good agreement for all angle parameters (0.771-0.878) except temporal AOD500 (0.743) and ARA750 (nasal 0.481; temporal 0.481). There was a proportional bias in nasal ARA750 (slope 2.44, 95% confidence interval CI: 1.95-3.18), temporal ARA750 (slope 2.57, 95% CI: 2.04-3.40), and nasal TISA500 (slope 1.30, 95% CI: 1.12-1.54). Bland-Altman plots demonstrated in all measured parameters a minimal mean difference between the two devices (-0.089 to 0.063); however, evidence of constant bias was found in nasal AOD250, nasal AOD500, nasal AOD750, nasal ARA750, temporal AOD500, temporal AOD750, temporal ARA750, and ACD. Among the parameters with constant biases, CASIA2 tends to give the larger numbers.
Both devices had generally good agreement. However, there were proportional and constant biases in most angle parameters. Thus, it is not recommended that values be used interchangeably.
Azithromycin has been hypothesized to have activity against SARS-CoV-2.
To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 ...symptoms at day 14.
Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization.
Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92).
The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21.
Among 263 participants who were randomized (median age, 43 years; 174 66% women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16).
Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection.
ClinicalTrials.gov Identifier: NCT04332107.
To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF).
Two patients with retinitis ...pigmentosa and one with Usher syndrome type 2 who participated in a phase 2 clinical trial received CNTF delivered by an encapsulated cell technology implant in one eye and sham surgery in the contralateral eye. Patients were followed longitudinally over 30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO measures of cone spacing and density and optical coherence tomography measures of retinal thickness were correlated with visual function, including visual acuity (VA), visual field sensitivity, and full-field electroretinography (ERG).
No significant changes in VA, visual field sensitivity, or ERG responses were observed in either eye of the three patients over 24 months. Outer retinal layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density decreased by 9.1%, or 223 cones/degree(2) more per year in sham-treated than in CNTF-treated eyes (P = 0.002, linear mixed model).
AOSLO images provided a sensitive measure of disease progression and treatment response in patients with inherited retinal degenerations. Larger studies of cone structure using high-resolution imaging techniques are urgently needed to evaluate the effect of CNTF treatment in patients with inherited retinal degenerations.
The recombinant zoster vaccine had over 90% efficacy in preventing herpes zoster in clinical trials. However, its effectiveness outside of a clinical trial setting has not been investigated. This ...study aimed to assess the effectiveness of the recombinant zoster vaccine in general practice.
A de-identified administrative claims database, the OptumLabs Data Warehouse, was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against herpes zoster in nonimmunocompromised, vaccine age-eligible individuals enrolled in the database for ≥365 days.
A total of 4 769 819 adults were included in this study, with 173 745 (3.6%) adults receiving 2 valid doses of the recombinant zoster vaccine. The incidence rate of herpes zoster was 258.8 (95% confidence interval CI, 230.0-289.4) cases per 100 000 person-years in vaccinated persons compared with 893.1 (95% CI, 886.2-900.0) in unvaccinated persons. Recombinant zoster vaccine effectiveness was 85.5% (95% CI, 83.5-87.3%) overall, with an effectiveness of 86.8% (95% CI, 84.6-88.7%) in individuals 50 to 79 years old compared with 80.3% (95% CI, 75.1-84.3%) in individuals aged 80 and older. In patients with a history of live zoster vaccine within 5 years of study inclusion, vaccine effectiveness was 84.8% (95% CI, 75.3-90.7%).
Recombinant zoster vaccine effectiveness against herpes zoster was high in a real-world setting. Given the low vaccine coverage and high effectiveness, a major public health effort is needed to identify and address barriers to vaccination and increase immunization rates.
The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further ...treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment.
In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions.
In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence.
This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).
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