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A large body of evidence suggests that low parasite carriage in Plasmodium falciparum asymptomatic infection is required for the maintenance of malaria immunity. However, the fact that treating such infections has little to no impact on subsequent clinical malaria is rarely noted. In this paper, we review data and argue that low-density parasite carriage in asymptomatic infection may not support host immune processes and that parasites are virtually under the host's immunological radar. We also discuss factors that may be constraining parasitemia in asymptomatic infections from reaching the threshold required to cause clinical symptoms. A thorough understanding of this infectious reservoir is essential for malaria control and eradication because asymptomatic infections contribute significantly to Plasmodium transmission. [ABSTRACT FROM AUTHOR]

This paper describes the methods for developing and optimizing a laboratory-developed assay (LDA) for detecting clade II human mpox virus using the automated Panther Fusion platform and Open Access software. Various concentrations of reagents in a primer-probe mix were tested to optimize the LDA. The LDA was validated using 10 previously characterized positive and 10 negative human mpox samples, resulting in 95% accuracy and 100% precision. The LDA resulted in 100% specificity among previously tested HSV1-, HSV2-, and VZV-positive human samples. Several spiked media extensions were also validated and achieved 98% accuracy and 100% precision across all collection media types. The assay's limit of detection was calculated to be 1.475 copies/reaction, and the polymerase chain reaction efficiency resulted in 89.87% (slope, −3.5911; R 2 = 0.9947). The methods described here can be applied to the rapid optimization and development of LDAs for many possible pathogens of public health importance. [ABSTRACT FROM AUTHOR]

Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health. The importance of ID research in understanding diseases, leading to treatments and vaccines, is emphasized, along with the need to address persistent and new infections, antimicrobial resistance, and threats like HIV and influenza. The paper analyzes the physician-scientist workforce's struggles, including funding, training, and research-practice integration gaps. We suggest increased funding, better training, and mentorship, more collaborative and interdisciplinary research, and improved recognition systems. The article stresses the urgency of supporting physician-scientists in ID, advocating for proactive prevention and preparedness, and calls for immediate action to enhance ID research and care. [ABSTRACT FROM AUTHOR]

Background. We compared the results of a serum-based measles immunoglobulin M (IgM) test with results of tests using paired reconstituted dried filter paper blood spot (DBS) samples to assess the feasibility of using DBS samples for measles diagnostic procedures. Methods. We collected 588 paired serum and DBS samples from 349 children aged 8 months through 12 years at Mulago Hospital in Kampala, Uganda; of these samples, 513 (87%) were collected from children with a clinical diagnosis of measles 0-33 days after rash, and 75(13%) were collected from children hospitalized for other reasons. Eluted DBS and serum samples were tested using a commercial measles IgM enzyme immunoassay. Detection of viral RNA was attempted on a subset of 20 DBS by reverse-transcriptase polymerase chain reaction. Results. Among the 513 sample pairs collected from children with measles, the concordances for samples collected during days 0-6 and >1 week after rash were 95.7% and 100%, respectively (P < .01). The relative sensitivity and specificity of the DBS-based assay during the first week were 98.7%and 88.9%, respectively, and the sensitivity and specificity >1 week after rash were 100% and 100%, respectively. Viral RNA was detected in 5 (26%) of 19 DBS samples tested. Among 75 sample pairs collected fromchildren hospitalized for other reasons, concordance was 94.7%. Conclusions. DBS samples are a feasible alternative sample for measles diagnostic procedures in high-incidence settings. [ABSTRACT FROM AUTHOR]

Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents. [ABSTRACT FROM AUTHOR]

The Journal of Infectious Diseases expresses gratitude to its authors, reviewers, and readers for their support in 2023. The journal received 2121 manuscripts for peer review, an increase from the previous year. The editors acknowledge the important role of reviewers in improving and publishing scientifically sound studies. The journal introduced new article formats, such as "Viewpoints," and launched a Mentoring Pilot Program for junior faculty. In 2024, the journal plans to issue calls for papers on antimicrobial resistance, microbiome science, and vaccine science. They also aim to highlight topics important to junior investigators and career development in the field of infectious diseases. The journal will offer guaranteed reviews for Fellows of the Infectious Diseases Society of America and work to simplify submission requirements across their journals. They also plan to feature cover art and original art in their articles. The editors express their excitement for the progress made and their eagerness to consider new ideas with the support of their authors, reviewers, and readers. [Extracted from the article]

Background: Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper.Methods: An enzyme-linked immunosorbent assay (ELISA) targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection.Results: In the ELISA, the anti-EBOV IVIG was shown to have a 7-fold increase in immunoglobulin G (IgG) titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately 5- to 6-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or 2 days after infection.Conclusions: These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and postexposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses. [ABSTRACT FROM AUTHOR]

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB. [ABSTRACT FROM AUTHOR]

In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera's elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of cholera's epidemiology in African countries which appear different from the Ganges Delta. [ABSTRACT FROM AUTHOR]

Background: Insecticide-based vector control is responsible for reducing malaria mortality and morbidity. Its success depends on a better knowledge of the vector, its distribution, and resistance status to the insecticides used. In this paper, we assessed Anopheles gambiae sensu lato (A gambiae s.l.) population resistance to pyrethroids in different ecological settings.Methods: The World Health Organization standard bioassay test was used to assess F0A gambiae s.l. susceptibility to pyrethroids. Biochemical Synergist assays were conducted with piperonyl butoxide (PBO), S,S,S-tributyl phosphotritioate, and diethyl maleate. L1014F, L1014S, and N1575Y knockdown resistance (kdr) mutations were investigated using TaqMan genotyping.Results: Anopheles gambiae sensu lato was composed of Anopheles arabienisis, Anopheles coluzzii, and A gambiae in all study sites. Anopheles gambiae sensu lato showed a strong phenotypic resistance to deltamethrin and permethrin in all sites (13% to 41% mortality). In many sites, pre-exposure to synergists partially improved the mortality rate suggesting the presence of detoxifying enzymes. The 3 kdr (L1014F, L1014S, and N1575Y) mutations were found, with a predominance of L1014F, in all species.Conclusions: Multiple resistance mechanisms to pyrethroids were observed in A gambiae s.l. in Mali. The PBO provided a better partial restoration of susceptibility to pyrethroids, suggesting that the efficacy of long-lasting insecticidal nets may be improved with PBO. [ABSTRACT FROM AUTHOR]

Background: While risk of outdoor transmission of respiratory viral infections is hypothesized to be low, there are limited data on SARS-CoV-2 transmission in outdoor compared to indoor settings.Methods: We conducted a systematic review of peer-reviewed papers indexed in PubMed, EMBASE, and Web of Science and preprints in Europe PMC through 12 August 2020 that described cases of human transmission of SARS-CoV-2. Reports of other respiratory virus transmission were included for reference.Results: Five identified studies found a low proportion of reported global SARS-CoV-2 infections occurred outdoors (<10%) and the odds of indoor transmission was very high compared to outdoors (18.7 times; 95% confidence interval, 6.0-57.9). Five studies described influenza transmission outdoors and 2 adenovirus transmission outdoors. There was high heterogeneity in study quality and individual definitions of outdoor settings, which limited our ability to draw conclusions about outdoor transmission risks. In general, factors such as duration and frequency of personal contact, lack of personal protective equipment, and occasional indoor gathering during a largely outdoor experience were associated with outdoor reports of infection.Conclusions: Existing evidence supports the wide-held belief that risk of SARS-CoV-2 transmission is lower outdoors but there are significant gaps in our understanding of specific pathways. [ABSTRACT FROM AUTHOR]

In response to the opioid crisis, IDSA and HIVMA established a working group to drive an evidence- and human rights-based response to illicit drug use and associated infectious diseases. Infectious diseases and HIV physicians have an opportunity to intervene, addressing both conditions. IDSA and HIVMA have developed a policy agenda highlighting evidence-based practices that need further dissemination. This paper reviews (1) programs most relevant to infectious diseases in the 2018 SUPPORT Act; (2) opportunities offered by the "End the HIV Epidemic" initiative; and (3) policy changes necessary to affect the trajectory of the opioid epidemic and associated infections. Issues addressed include leveraging harm reduction tools and improving integrated prevention and treatment services for the infectious diseases and substance use disorder care continuum. By strengthening collaborations between infectious diseases and addiction specialists, including increasing training in substance use disorder treatment among infectious diseases and addiction specialists, we can decrease morbidity and mortality associated with these overlapping epidemics. [ABSTRACT FROM AUTHOR]

A number of countries are planning the use of "immunity passports" as a way to ease restrictive measures and allow infected and recovered people to return to work during the COVID-19 pandemic. This paper brings together key scientific uncertainties regarding the use of serological tests to assure immune status and a public health ethics perspective to inform key considerations in the ethical implementation of immunity passport policies. Ill-conceived policies have the potential to cause severe unintended harms that could result in greater inequity, the stigmatization of certain sectors of society, and heightened risks and unequal treatment of individuals due to erroneous test results. Immunity passports could, however, be used to achieve collective benefits and benefits for specific populations besides facilitating economic recovery. We conclude that sector-based policies that prioritize access to testing based on societal need are likely to be fairer and logistically more feasible, while minimizing stigma and reducing incentives for fraud. Clear guidelines need to be set out for which sectors of society should be prioritized for testing, and rigorous mechanisms should be in place to validate test results and identify cases of reinfection. [ABSTRACT FROM AUTHOR]

The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition. Immediate antibiotic treatment is lifesaving for some patients, but a substantial fraction of patients initially diagnosed with sepsis have noninfectious conditions. Aggressive time-to-antibiotic targets risk promoting antibiotic overuse and antibiotic-associated harms for this subset of the population. An accurate understanding of the precise relationship between time-to-antibiotics and mortality for patients with possible sepsis is therefore critical to finding the best balance between assuring immediate antibiotics for those patients who truly need them versus allowing clinicians some time for rapid investigation to minimize the risk of overtreatment and antibiotic-associated harms for patients who are not infected. More than 30 papers have been published assessing the relationship between time-to-antibiotics and outcomes, almost all of which are observational cohort studies. Most report significant associations but all have important limitations. Key limitations include focusing just on the sickest subset of patients (only patients requiring intensive care and/or patients with septic shock), blending together mortality estimates from patients with very long intervals until antibiotics with patients with shorter intervals and reporting a single blended (and thus inflated) estimate for the average increase in mortality associated with each hour until antibiotics, and failure to control for large potential confounders including patients' presenting signs and symptoms and granular measures of comorbidities and severity of illness. In this study, we elaborate on these potential sources of bias and try to distill a better understanding of what the true relationship between time-to-antibiotics and mortality may be for patients with suspected sepsis or septic shock. [ABSTRACT FROM AUTHOR]

The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support potential policy recommendations. The evidence necessary includes an assessment of the performance for TB and resistance detection as well as an assessment of the operational characteristics of these platforms. The performance assessment should include analytical studies to confirm the limit of detection and assay ability to detect mutations conferring resistance across globally representative strains. The analytical evaluation is typically followed by multisite clinical evaluation studies to confirm diagnostic performance in sites and populations of intended use. This paper summarizes the considerations for the design of these analytical and clinical studies. [ABSTRACT FROM AUTHOR]

The degradation of spatial resolution in star-forming regions, observed at large distances (d≳ 1 kpc) with Herschel, can lead to estimates of the physical parameters of the detected compact sources (clumps), which do not necessarily mirror the properties of the original population of cores. This paper aims at quantifying the bias introduced in the estimation of these parameters by the distance effect. To do so, we consider Herschel maps of nearby star-forming regions taken from the Herschel Gould Belt survey, and simulate the effect of increased distance to understand what amount of information is lost when a distant star-forming region is observed with Herschel resolution. In the maps displaced to different distances we extract compact sources, and we derive their physical parameters as if they were original Herschel infrared Galactic Plane Survey maps of the extracted source samples. In this way, we are able to discuss how the main physical properties change with distance. In particular, we discuss the ability of clumps to form massive stars: we estimate the fraction of distant sources that are classified as high-mass stars-forming objects due to their position in the mass versus radius diagram, that are only 'false positives'. We also give a threshold for high-mass star formation M >1282 (r/[pc])1.42 M☉. In conclusion, this paper provides the astronomer dealing with Herschel maps of distant star-forming regions with a set of prescriptions to partially recover the character of the core population in unresolved clumps. [ABSTRACT FROM AUTHOR]

This paper presents a new development of orbital elements for the four outer planets in analytical series. These series complete the series DEA431, for which the terms for the terrestrial planets are given in an earlier paper. As the source of planetary coordinates, the development uses the latest long-term numerical ephemerides DE431, which are valid over 30 000 yr [-13 000, 17 000]. The author's modification of the frequency analysis method is used as the expansion tool. The obtained results are compared with those given by recent analytical theories of planetary motion, namely VSOP2013 and TOP2013. The number of terms in DEA431 is about one order of magnitude lower than that in either VSOP2013 or TOP2013. The extensive analytical theories of the motion of the outer planets are more precise than the compact DEA431 series over time intervals of several hundreds of years; the three compared analytical series are of about the same accuracy over time intervals of a few thousand years; and DEA431 has a higher accuracy than both VSOP2013 and TOP2013 when representing the coordinates of the outer planets over longer time intervals, such as tens of thousands of years. Over 24 000 yr centred at epoch J2000, the maximum difference between themean orbital longitudes of the outer planets given by theDE431 numerical ephemerides and the DEA431 analytical series is 0."08 for Jupiter, 0."22 for Saturn, 0."10 for Uranus, and 0. "05 for Neptune. The coefficients of the DEA431 series for all the outer planets and the corresponding FORTRAN routines for calculating the orbital elements and rectangular coordinates of the planets are available on the SAI web-server. [ABSTRACT FROM AUTHOR]

Background The innovative human brain organoid model represents a unique opportunity to better understand the genesis of congenital brain abnormalities, particularly microcephaly, caused by Zika virus (ZIKV) infection during early pregnancy. Methods A systematic review was conducted to investigate how ZIKV leads to microcephaly in a novel experimental model that mimics early brain development. Studies were gathered by searching MEDLINE/Pubmed, LILACS, and LiSSa for reports on effects of ZIKV infection on human brain organoids. From 146 identified papers, 13 articles were selected for review. Results This review found that ZIKV of African, Latin American, and Asian lineages caused productive replication after 72 hours, preferentially infected neural progenitor cells over mature neurons, reduced both cell populations, and caused premature differentiation. Limited data involving only African and Latin American lineages showed a reduction in populations of proliferating cells and intermediate cells, and overall decreased viability. Furthermore, all 3 lineages caused heightened apoptosis and reduced organoid size. Conclusions This review concludes that, in organoids, ZIKV causes productive replication, infects neural progenitor cells over mature neurons, decreases both populations, causes premature differentiation, induces apoptosis, and reduces size. [ABSTRACT FROM AUTHOR]

Background: The innovative human brain organoid model represents a unique opportunity to better understand the genesis of congenital brain abnormalities, particularly microcephaly, caused by Zika virus (ZIKV) infection during early pregnancy.Methods: A systematic review was conducted to investigate how ZIKV leads to microcephaly in a novel experimental model that mimics early brain development. Studies were gathered by searching MEDLINE/Pubmed, LILACS, and LiSSa for reports on effects of ZIKV infection on human brain organoids. From 146 identified papers, 13 articles were selected for review.Results: This review found that ZIKV of African, Latin American, and Asian lineages caused productive replication after 72 hours, preferentially infected neural progenitor cells over mature neurons, reduced both cell populations, and caused premature differentiation. Limited data involving only African and Latin American lineages showed a reduction in populations of proliferating cells and intermediate cells, and overall decreased viability. Furthermore, all 3 lineages caused heightened apoptosis and reduced organoid size.Conclusions: This review concludes that, in organoids, ZIKV causes productive replication, infects neural progenitor cells over mature neurons, decreases both populations, causes premature differentiation, induces apoptosis, and reduces size. [ABSTRACT FROM AUTHOR]

We investigated a norovirus outbreak (genotype GII.2) affecting 9 members of a soccer team. Illness was associated with touching a reusable grocery bag or consuming its packaged food contents (risk difference, 0.636; P < .01). By polymerase chain reaction, GII norovirus was recovered from the bag, which had been stored in a bathroom used before the outbreak by a person with norovirus-like illness. Airborne contamination of fomites can lead to subsequent point-source outbreaks. When feasible, we recommend dedicated bathrooms for sick persons and informing cleaning staff (professional or otherwise) about the need for adequate environmental sanitation of surfaces and fomites to prevent spread. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial pathogens of the respiratory tract in patients with cystic fibrosis (CF). Although P. aeruginosa chronic bronchial infection is associated with a poorer prognosis, the consequences of S. aureus colonization on CF outcomes are controversial.Methods: In this paper, murine models of infection resembling traits of the CF human airways disease have been revisited using an infection schedule that mimics the sequence of events of pulmonary disease in CF patients. First, mice were infected with S. aureus, embedded in agar beads; this was followed by P. aeruginosa infection and analysis of bacterial load, leukocyte infiltration, and lung tissue damage.Results: We reveal that (1) S. aureus promotes severe lesions including abscess formation, (2) S. aureus increases the risk of subsequent chronic P. aeruginosa respiratory infection, and (3) once the chronic infection has been established, P. aeruginosa influences most of the inflammatory responses independent of S. aureus.Conclusions: Our findings established the significance of S. aureus colonization per se and the impact on the subsequent P. aeruginosa infection. This would point towards a thorough assessment for the need of treatment against S. aureus. [ABSTRACT FROM AUTHOR]

Zika virus was discovered in East Africa in 1947 by the Rockefeller Foundation during investigations on the ecology of yellow fever. Although it was subsequently shown to have widespread distribution in Africa and Asia, it was not known to cause epidemics until 2007. This paper describes the history of the virus discovery, emergence and evolution as an epidemic virus, and the its evolving clinical spectrum. [ABSTRACT FROM AUTHOR]

Macrophages are specialized phagocytic cells involved in clearing invading pathogens. Previously we reported that engulfment and cell motility protein 1 (ELMO1) in macrophages mediates bacterial internalization and intestinal inflammation. Here we studied the role of ELMO1 in the fate of internalized targets. ELMO1 is present in the intracellular vesicles and enhances accumulation of the protein LC3B following engulfment of Salmonella or treatment with autophagy-inducing rapamycin. The protein ATG5 and the kinase ULK1 are involved in classical autophagy, while LC3-associated phagocytosis is ULK1 independent. ATG5 but not ULK1 cooperated with ELMO1 in LC3 accumulation after infection, suggesting the ELMO1 preferentially regulated LC3-associated phagocytosis. Because LC3-associated phagocytosis delivers cargo for degradation, the contribution of ELMO1 to the lysosome degradation pathways was evaluated by studying pH and cathepsin B activity. ELMO1-depleted macrophages showed a time-dependent increase in pH and a decrease in cathepsin B activity associated with bacterial survival. Together, ELMO1 regulates LC3B accumulation and antimicrobial responses involved in the clearance of enteric pathogens. This paper investigated how innate immune pathways involving ELMO1 work in a coordinated fashion to eliminate bacterial threats. ELMO1 is present in the phagosome and enhances bacterial clearance by differential regulation of lysosomal acidification and enzymatic activity. [ABSTRACT FROM AUTHOR]

Patient-centered care is a central pillar of the World Health Organization’s End TB Strategy. Understanding where patients access health services is a first step to planning for the placement of services to meet patient needs and preferences. The patient-pathway analysis (PPA) methodology detailed in this article was developed to better understand the alignment between patient care seeking and tuberculosis service availability. A PPA describes the steps that people with tuberculosis take from the initial care visit to cure. The results of a PPA reveal programmatic gaps in care seeking, diagnosis, treatment initiation, and continuity of care. They can be used as inputs to an evidence-based process of identifying and developing interventions to address the gaps in patient care. This paper summarizes the steps to conduct a PPA and serves as the basis for understanding country case studies that profile the use of PPA. [ABSTRACT FROM AUTHOR]

Until recently, waste management for national immunization programs was limited to sharps waste, empty vaccine vials, or vaccines that had expired or were no longer usable. However, because wild-type 2 poliovirus has been eradicated, the World Health Organization's (WHO's) Strategic Advisory Group of Experts on Immunization deemed that all countries must simultaneously cease use of the type 2 oral polio vaccine and recommended that all countries and territories using oral polio vaccine (OPV) "switch" from trivalent OPV (tOPV; types 1, 2, and 3 polioviruses) to bivalent OPV (bOPV; types 1 and 3 polioviruses) during a 2-week period in April 2016. Use of tOPV after the switch would risk outbreaks of paralysis related to type 2-circulating vaccine-derived poliovirus (cVDPV2). To minimize risk of vaccine-derived polio countries using OPV were asked to dispose of all usable, unexpired tOPV after the switch to bOPV. In this paper, we review the rationale for tOPV disposal and describe the global guidelines provided to countries for the safe and appropriate disposal of tOPV. These guidelines gave countries flexibility in implementing this important task within the confines of their national regulations, capacities, and resources. Steps for appropriate disposal of tOPV included removal of all tOPV vials from the cold chain, placement in appropriate bags or containers, and disposal using a recommended approach (ie, autoclaving, boiling, chemical inactivation, incineration, or encapsulation) followed by burial or transportation to a designated waste facility. This experience with disposal of tOPV highlights the adaptability of national immunization programs to new procedures, and identifies gaps in waste management policies and strategies with regard to disposal of unused vaccines. The experience also provides a framework for future policies and for developing programmatic guidance for the ultimate disposal of all OPV after the eradication of polio. [ABSTRACT FROM AUTHOR]

It has been well established in the past decades that the central black hole masses of galaxies correlate with dynamical properties of their harbouring bulges. This notion begs the question of whether there are causal connections between the active galactic nucleus (AGN) and its immediate vicinity in the host galaxy. In this paper, we analyse the presence of circumnuclear star formation in a sample of 15 AGN using mid-infrared observations. The data consist of a set of 11.3 μm polycyclic aromatic hydrocarbon emission and reference continuum images, taken with ground-based telescopes, with sub-arcsecond resolution. By comparing our star formation estimates with AGN accretion rates, derived from X-ray luminosities, we investigate the validity of theoretical predictions for the AGN-starburst connection. Our main results are: (i) circumnuclear star formation is found, at distances as low as tens of parsecs from the nucleus, in nearly half of our sample (7/15); (ii) star formation luminosities are correlated with the bolometric luminosity of the AGN (LAGN) only for objects with LAGN ≥ 1042 erg s-1; (iii) low-luminosity AGNs (LAGN < 1042 erg s-1) seem to have starburst luminosities far greater than their bolometric luminosities. [ABSTRACT FROM AUTHOR]

Determining the ages of red-giant stars is a key problem in stellar astrophysics. One of the difficulties in this determination is to know the evolutionary state of the individual stars - i.e. have they started to burn Helium in their cores? That is the topic of this paper. Asteroseismic data provide a route to achieving this information. What we present here is a highly autonomous way of determining the evolutionary state from an analysis of the power spectrum of the light curve. The method is fast and efficient and can provide results for a large number of stars. It uses the structure of the dipole-mode oscillations, which have a mixed character in red-giant stars, to determine some measures that are used in the categorization. It does not require that all the individual components of any given mode be separately characterized. Some 6604 redgiant stars have been classified. Of these, 3566 are determined to be on the red-giant branch, 2077 are red-clump and 439 are secondary-clump stars. We do not specifically identify the low-metallicity, horizontal-branch stars. The difference between red-clump and secondaryclump stars is dependent on the manner in which Helium burning is first initiated. We discuss that the way the boundary between these classifications is set may lead to mis-categorization in a small number of stars. The remaining 522 stars were not classified either because they lacked sufficient power in the dipole modes (so-called depressed dipole modes) or because of conflicting values in the parameters. [ABSTRACT FROM AUTHOR]

Background: As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province.Methods: A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi.Results: Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%).Conclusions: Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities. [ABSTRACT FROM AUTHOR]

Background: The modalities of malaria transmission along the Thailand-Myanmar border are poorly understood. Here we address the relevance of using a specific Anopheles salivary biomarker to measure the risk among humans of exposure to Anopheles bites.Methods: Serologic surveys were conducted from May 2013 to December 2014 in 4 sentinel villages. More than 9400 blood specimens were collected in filter papers from all inhabitants at baseline and then every 3 months thereafter, for up to 18 months, for analysis by enzyme-linked immunosorbent assay. The relationship between the intensity of the human antibody response and entomological indicators of transmission (human biting rates and entomological inoculation rates [EIRs]) was studied using a multivariate 3-level mixed model analysis. Heat maps for human immunoglobulin G (IgG) responses for each village and survey time point were created using QGIS 2.4.Results: The levels of IgG response among participants varied significantly according to village, season, and age (P<.001) and were positively associated with the abundance of total Anopheles species and primary malaria vectors and the EIR (P<.001). Spatial clusters of high-IgG responders were identified across space and time within study villages.Conclusions: The gSG6-P1 biomarker has great potential to address the risk of transmission along the Thailand-Myanmar border and represents a promising tool to guide malaria interventions. [ABSTRACT FROM AUTHOR]

Background. Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals. Methods. We searched literature published during 1995-2009 for papers reporting on measles outbreaks. Papers identified were reviewed by 2 reviewers to select those that mentioned ORI. World Bank classification of country income was used to identify reports of outbreaks in middle- and low-income countries. Results. We identified a total of 485 articles, of which 461 (95%) were available. Thirty-eight of these papers reported on a total of 38 outbreaks in which ORI was used. ORI had a clear impact in 16 (42%) of these outbreaks. In the remaining outbreaks, we were unable to independently assess the impact of ORI. Conclusions. These findings generally support ORI in middle- and low-income countries. However, the decision to conduct ORI and the nature and extent of the vaccination response need to be made on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Presents a follow-up article to the paper "Clindamycin-Associated Colitis Due to a Toxin-Producing Species of Clostridium in Hamsters," by J.G. Bartlett and colleagues in "Journal of Infectious Disease" dated 1977. Background to the previous paper; Summary of studies included; Postscript on highlights of subsequent developments.

To evaluate methods for detection of genital human papillomavirus (HPV) DNA in men, samples were obtained from 3 consecutive groups of 10 men attending a sexually transmitted disease clinic by use of (1) a saline-wetted Dacron swab alone, (2) a saline wetted cytobrush, or (3) emery paper (600A-grit Wetordry Tri-M-ite; 3M) abrasion followed by a saline-wetted Dacron swab. By use of a polymerase chain reaction ­based assay, 45% of emery-paper samples were found to be positive for β-globin, compared with 23% of swab-alone and 0% of cytobrush samples. Subsequently, emery paper and saline-wetted Dacron swabs were used to obtain penile shaft, glans, foreskin, and scrotum samples from 318 male university students. Urine samples were also obtained. Of 1323 samples tested, 1288 (97%) were found to be positive for β-globin. HPV DNA was detected in samples from 104 men (33%): 24% from the penile shaft, 16% from the glans, 28% from the foreskin, 17% from the scrotum, and 6% in urine. The HPV prevalence was similar for circumcised and uncircumcised men. Testing multiple sites increased the number of men for whom HPV DNA was detected. [ABSTRACT FROM AUTHOR]

This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC).Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P < .05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per milliliter (P < .05, odds ratio >10), aged ≥ 50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P < .05) in Ebola patients who died.These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality. [ABSTRACT FROM AUTHOR]

Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.Methods: In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data.Results: Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate.Conclusions: A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations.Clinical Trials Registration: ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). [ABSTRACT FROM AUTHOR]

Background. A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. Methods. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 μg, 7.5 μg, or 15 μg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Results. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 μg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. Conclusions. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. [ABSTRACT FROM AUTHOR]

Background. Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission. Methods. Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission. Results. Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Twofifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas. Conclusions. Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase. [ABSTRACT FROM AUTHOR]

The author discusses the paper "Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence," by F. Oechslin and colleagues. Topics discussed include the treatment of Pseudomonas aeruginosa infection, the combination of antimicrobial therapy and phage therapy for treating the infection, and the reduction of virulence.

The article presents an editorial commentary on the paper "Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness," by D. M. Morens and colleges. The paper reviews 109 published autopsy series from the 1918 pandemic. According to the author, the findings are striking in the context of modern conceptions of the 1918 pandemics: the great majority of deaths could be attributed to secondary bacterial pneumonia.

Somalia, one of the most unstable countries in the world, has been without a permanent government for nearly 2 decades. With a health system in total disarray, coverage of basic health interventions remains low and, maternal and child mortality is among the highest in the world. Health partners jointly outlined an integrated package of critical child survival interventions to be delivered through a population-based delivery strategy known as Child Health Days (CHDs), to reduce child mortality. Using this strategy, key child survival interventions are delivered to the community with an objective of reaching children <5 years and women of childbearing age in all districts of Somalia every 6 months. Through this strategy, immunization services were reached in remote areas, and coverage disparity between the urban and rural areas was reduced from 17% (42% urban and 25% rural) to 10% (50% urban and 60% rural). In addition, infants were reached with a third dose of diphtheria-pertussis-tetanus vaccine, achieving 51% coverage during 2009 and 66% in 2010. This paper summarizes the challenges of scaling up child interventions in the troubled context of Somalia by reviewing the planning, implementation, and achievements of CHDs as well as reflecting on challenges for the future of child survival in Somalia. [ABSTRACT FROM AUTHOR]

Background. We systematically reviewed the evidence for an association between male circumcision and Human Papillomavirus (HPV) infection and genital warts in men. Methods. PubMed and Embase were searched to 15 September 2010. The measure of effect was the adjusted odds ratio (OR) or rate ratio (RR) when present and the crude estimate otherwise. Random effects meta-analyses were used to calculate summary measures of effect. Results. We identified 23 papers about the association between circumcision and HPV DNA. Circumcised men were less likely to have prevalent genital HPV infection than uncircumcised men (summary OR, 0.57, 95% confidence interval [CI], 0.45-0.71) with between-study heterogeneity (P-heterogeneity = 0.006; I22 = 50.5%; 19 studies). Similar summary associations were seen in clinical and methodological subgroups. The effect of circumcision was stronger at the glans/corona (OR, 0.47; 95% CI, 0.37-0.60) and urethra (OR, 0.35; 95% CI, 0.12- 1.05) compared with sites more distal to the foreskin. There was weak evidence that circumcision was associated with decreased HPV incidence (summary RR, 0.75, 95% CI, 0.57-0.99; 3 studies) and increased HPV clearance (summary RR, 1.33; 95% CI, 0.89-1.98; 3 studies) but no evidence of an association with prevalent genital warts (OR, 0.93, 95% CI, 0.65-1.33; 15 studies). Conclusions. Several countries are expanding access to voluntary medical male circumcision to reduce HIV prevalence. This could provide additional benefit in reducing HPV prevalence. [ABSTRACT FROM AUTHOR]

Rubella, usually a mild rash illness in children and adults, can cause serious consequences when a pregnant woman is infected, particularly in early pregnancy. These serious consequences include miscarriage, fetal death or an infant born with birth defects (i.e., congenital rubella syndrome (CRS)). The primary purpose for rubella vaccination is the prevention of congenital rubella infection including CRS. Since 1969, several rubella virus vaccines have been licensed for use; however, until the 1990s, use of rubella-containing vaccine (RCV) was limited primarily to developed countries. In 1996, it was estimated that 110,000 infants with CRS were born annually in developing countries. In 2000, the first World Health Organization rubella vaccine position paper was published to guide introduction of RCV in national childhood immunization schedules. From 1996 to 2009, the number of countries that introduced RCV into their national routine childhood immunization programs increased by 57% from 83 countries in 1996 to 130 countries in 2009. In addition, three of the six WHO regions established rubella control and CRS prevention goals: Region of the Americas and Europe rubella elimination by 2010 and 2015, respectively, and Western Pacific Region-accelerated rubella control and CRS prevention by 2015. Also, during this time period, the number of rubella cases reported decreased from 670,894 in 2000 to 121,344 in 2009. Rubella control and prevention of CRS can be accelerated by integrating with current global measles mortality reduction and regional elimination activities. [ABSTRACT FROM AUTHOR]

Background. Information on measles vaccine effectiveness (VE) is critical to help inform policies for future global measles control goals. Methods. We reviewed results of VE studies published during 1960-2010. Results. Seventy papers with 135 VE point estimates were identified. For a single dose of vaccine administered at 9-11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%-91%) and 92.0% (IQR, 86%-96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%- 95.0%) and 92.5% (IQR, 84.8%-97.0%) when vaccine was received at 9-11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%-98.3%). Conclusions. The VE of the first dose of measles-containing vaccine administered at 9-11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles. [ABSTRACT FROM AUTHOR]

Introduction. High rates of hepatitis C virus (HCV) transmission are found in samples of people who inject drugs (PWID) throughout the world. The objective of this paper was to meta-analyze the effects of risk-reduction interventions on HCV seroconversion and identify the most effective intervention types.Methods. We performed a systematic review and meta-analysis of published and unpublished studies. Eligible studies reported on the association between participation in interventions intended to reduce unsafe drug injection and HCV seroconversion in samples of PWID.Results. The meta-analysis included 26 eligible studies of behavioral interventions, substance-use treatment, syringe access, syringe disinfection, and multicomponent interventions. Interventions using multiple combined strategies reduced risk of seroconversion by 75% (pooled relative risk, .25; 95% confidence interval, .07–.83). Effects of single-method interventions ranged from .6 to 1.6.Conclusions. Interventions using strategies that combined substance-use treatment and support for safe injection were most effective at reducing HCV seroconversion. Determining the effective dose and combination of interventions for specific subgroups of PWID is a research priority. However, our meta-analysis shows that HCV infection can be prevented in PWID. [ABSTRACT FROM PUBLISHER]

Only a few of the recommendations made in this supplement are implemented in ongoing HIV remission studies that involve an analytical treatment interruption. The absence of these recommendations in protocols puts sexual partners of study participants at serious risk. This paper addresses one possible barrier to implementation: a certain misunderstanding among sponsors and research entities. [ABSTRACT FROM AUTHOR]

Investigates challenges and strategies for laboratory diagnosis of measles in an international setting. Characteristics of an ideal specimen collection method; Assessment of the utilities of oral fluid and filter paper collection methods in supporting measles diagnosis and strain surveillance.

Summarizes papers presented at the United States National Institute of Diabetes and Digestive and Kidney Diseases' 'HIV-Infection, Mucosal Immunity, and Pathogenesis' symposium in Bethesda, Maryland on September 11 to 13, 1997. Magnitude of the AIDS epidemic; Importance of tissues in viral replication; Factors that may be related to increases in the levels of HIV-1 in genital secretions in women.

An introduction to the journal is presented in which the editor discusses various papers of the issue on topics including public health importanceof measles and rubella, feasibility of measles eradication, and cost-effectiveness of measles eradication.

A letter to the editor is presented in response to the paper "Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever," by S.C. Kliks, A. Nisalak, W.E. Brandt, L. Wall, and D.S. Burke in a 1989 issue.

The article comments on the paper "The Rebound Effect and the Emergence of Pyrimethamine Resistance in Plasmodium Falciparum After Single-Dose Sulfadoxine-Pyrimethamine," by F. Marks, V. von Kalckreuth, and R. Kobbe, published in the December 2005 issue of the Journal of Infectious Diseases. The researchers show that the first P. falciparum infections after sulfadoxine-pyrimethamine treatment of 9-month-old aparasitemic infants near Kumasi, Ghana, were highly resistant to sulfadoxine-pyrimethamine. The prevalence of drug-resistant falciparum infections was higher in the treated group than in the placebo group from week 9 until week 26 after treatment. The prevalence of all infections was higher in the treated group during the same interval, although this difference was not significant, possibly because of the small sample size.

Comments on G. Boivin, J. Handfield, E. Toma, R. Lalonde and M.G. Bergeron's paper on the detection of cytomegalovirus late antigen in peripheral blood leucocytes (PBL) of patients with HIV-associated lymphoma. Correlation of antigenemia and viremia with cytomegalovirus disease; Shell vial assay; Total number of positive cells/150,000 PBL.