This investigation documents the presence of Rocky Mountain spotted fever in eastern Arizona, with common brown dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad distribution of this common tick raises concern about its potential to transmit R. rickettsii in other settings.

SummaryThe 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.

Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.

In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.

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Analysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.

, that precluded cleavage between S1 and S2 could also be triggered to undergo a conformational change at 37°C by soluble receptor at neutral pH or by pH 8 alone. A novel 120-kDa subunit was formed following incubation of the receptortriggered S A59 H716D virions with trypsin at 4°C. The data show that unlike class 1 fusion glycoproteins of other enveloped viruses, the murine coronavirus S protein can be triggered to a membrane-binding conformation at 37°C either by soluble receptor at neutral pH or by alkaline pH alone, without requiring previous activation by cleavage between S1 and S2.As an initial step in virus replication, specialized attachment proteins on virions bind to specific receptors on host cell membranes. The specificity of virus-receptor interactions frequently determines which cells, tissues, and species are susceptible to virus infection. On binding to its specific receptor under optimal conditions of pH and temperature, the viral attachment glycoprotein undergoes one or more programmed conformational changes that exposes a hydrophobic fusion peptide which mediates fusion of the viral envelope with host cell membranes, releasing the viral nucleocapsid into the cytoplasm (24, 61). Class I viral fusion glycoproteins have the general structure of the HA protein of influenza A virus, consisting of an N-terminal receptor binding domain followed by an exposed protease cleavage site, a fusion domain containing several heptad repeats, and transmembrane and cytoplasmic domains (23).So-called pH-independent fusion occurs when the viral envelope can fuse directly with the plasma membrane at neutral pH. Conformational changes in spike glycoproteins of some large minus-strand RNA viruses including paramyxoviruses such as simian virus 5 (SV5) and respiratory syncytial virus, and retroviruses including human immunodeficiency virus type 1 (HIV-1) and avian and murine leukemia viruses are triggered by binding at 37°C to specific receptors on the plasma membrane (1, 9, 24, 61). These pH-independent viruses cause cellto-cell fusion, forming multinucleated syncytia in infected cell cultures and tissues when viral spike proteins expressed on the membrane of a cell are triggered to undergo a fusion-inducing conformational change by binding to a specific virus receptor on an adjacent cell. In contrast, the spike glycoproteins of other large, enveloped RNA viruses including influenza A virus, rabies virus, Ebola virus, and bunyavirus require an acidic environment to trigger the conformational changes in the viral fusion protein that lead to membrane fusion (16,24,44,51,61). Therefore, fusion of these viral envelopes occurs not at the plasma membrane but within the cell at endosomal membranes once the pH drops to 5.5. These pH-dependent or acid-dependent viruses do not induce the formation of multinucleated syncytia in cells and tissues at neutral pH.This report describes conformational changes in the spike glycoprotein (S) of mouse hepatitis virus (MHV), a murine

Summary Background Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents’ Health (2016–30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. Methods For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks’ gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. Findings Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9–2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5–15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8–27·7) per 1000 total births in west and central Africa to 2·9 (2·7–3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7–2·7) from 2000 to 2019, which was lower than the 2·9% (2·5–3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8–4·7) annual rate of reduction in mortality rate among children aged 1–59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0–49·9%, 50 having a decrease of 10·0–24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries...