Novel Relapsing Fever Spirochete in Bat Tick

Novel Relapsing Fever Spirochete in Bat Tic

A Phase 2a clinical trial of Molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus

Molnupiravir (800 mg dose) accelerated SARS-CoV-2 RNA clearance in patients with COVID-19 compared to placebo

Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection.COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7–7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001).The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.NCT04405570

Benefits and risks of antiretroviral therapy for perinatal HIV prevention.

CAPRISA, 2016.Abstract available in pdf

Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase

Ras/Rap1-specific endopeptidase (RRSP) is a cytotoxic effector domain of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin of highly virulent strains of <i>Vibrio vulnificus</i>. RRSP blocks RAS-MAPK kinase signaling by cleaving Ras and Rap1 within the switch I region between Y32 and D33. Although the RRSP processing site is highly conserved among small GTPases, only Ras and Rap1 have been identified as proteolytic substrates. Here we report that residues Y32 and D33 at the scissile bond play an important role in RRSP substrate recognition, while the nucleotide state of Ras has an only minimal effect. In addition, substrate specificity is generated by residues across the entire switch I region. Indeed, swapping the Ras switch I region into either RalA or RhoA, GTPases that are not recognized by RRSP, generated chimeras that are substrates of RRSP. However, a difference in the processing efficiency of Ras switch I in the context of Ras, RalA, or RhoA indicates that protein regions outside Ras switch I also contribute to efficient RRSP substrate recognition. Moreover, we show that synthetic peptides corresponding to the Ras and Rap1, but not RalA, switch I regions are cleaved by RRSP, demonstrating sequence-specific substrate recognition. In conclusion, this work demonstrates that the GTPase recognition of RRSP is independent of the nucleotide state and is mainly driven by the Ras and Rap1 switch I loop and also influenced by additional protein–protein interactions, increasing the substrate specificity of RRSP

Rickettsia parkeri Rickettsiosis, Arizona, USA

In the United States, all previously reported cases of Rickettsia parkeri rickettsiosis have been linked to transmission by the Gulf Coast tick (Amblyomma maculatum). Here we describe 1 confirmed and 1 probable case of R. parkeri rickettsiosis acquired in a mountainous region of southern Arizona, well beyond the recognized geographic range of A. maculatum ticks. The likely vector for these 2 infections was identified as the Amblyomma triste tick, a Neotropical species only recently recognized in the United States. Identification of R. parkeri rickettsiosis in southern Arizona demonstrates a need for local ecologic and epidemiologic assessments to better understand geographic distribution and define public health risk. Education and outreach aimed at persons recreating or working in this region of southern Arizona would improve awareness and promote prevention of tickborne rickettsioses

Machine Learning Algorithms Using Routinely Collected Data Do Not Adequately Predict Viremia to Inform Targeted Services in Postpartum Women Living With HIV

BackgroundAdherence to antiretroviral treatment (ART) among postpartum women with HIV is essential for optimal health and prevention of perinatal transmission. However, suboptimal adherence with subsequent viremia is common, and adherence challenges are often underreported. We aimed to predict viremia to facilitate targeted adherence support in sub-Saharan Africa during this critical period.MethodsData are from PROMISE 1077BF/FF, which enrolled perinatal women between 2011 and 2014. This analysis includes postpartum women receiving ART per study randomization or country-specific criteria to continue from pregnancy. We aimed to predict viremia (single and confirmed events) after 3 months on ART at &gt;50, &gt;400, and &gt;1000 copies/mL within 6-month intervals through 24 months. We built models with routine clinical and demographic data using the least absolute shrinkage and selection operator and SuperLearner (which incorporates multiple algorithms).ResultsAmong 1321 women included, the median age was 26 years and 96% were in WHO stage 1. Between 0 and 24 months postpartum, 42%, 31%, and 28% of women experienced viremia &gt;50, &gt;400, and &gt;1000 copies/mL, respectively, at least once. Across models, the cross-validated area under the receiver operating curve ranged from 0.74 [95% confidence interval (CI): 0.72 to 0.76] to 0.78 (95% CI: 0.76 to 0.80). To achieve 90% sensitivity predicting confirmed viremia &gt;50 copies/mL, 64% of women would be classified as high risk.ConclusionsUsing routinely collected data to predict viremia in &gt;1300 postpartum women with HIV, we achieved moderate model discrimination, but insufficient to inform targeted adherence support. Psychosocial characteristics or objective adherence metrics may be required for improved prediction of viremia in this population

Development of an expert derived ICD-AIS map for serious AIS3+ injury identification

Objective: The objective of the mapping project was to develop an expert derived map between the International Statistical Classification of Diseases and Related Health Problems (ICD) clinical modifications (CM) and the Abbreviated Injury Scale (AIS) to be able to relate AIS severity to ICD coded data road traffic collision data in EU datasets. The maps were developed to enable the identification of serious AIS3+ injury and provide details of the mapping process for assumptions to be made about injury severity from mass datasets. This article describes in detail the mapping process of the International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) and the International Classification of Diseases Tenth Revision, Clinical Modification (ICD-10-CM) codes to the Abbreviated Injury Scale 2005, Update 2008 (AIS08) codes to identify injury with an AIS severity of 3 or more (AIS3+ severity) to determine ‘serious’ (MAIS3+) road traffic injuries.Methods: Over 19,000 ICD codes were mapped from the following injury categories; injury ICD-9-CM (Chapter 17) codes between ‘800 and 999.9’ and injury ICD-10-CM (Chapter 19) ‘S’ and ‘T’ prefixed codes were reviewed and mapped to an AIS08 category and then relate the severity to three groups; AIS3+, AIS Results: In total 2,504 ICD-9-CM codes were mapped to the AIS, of which 780 (31%) were assigned an AIS3+ severity. For the16,508 ICD-10-CM mapped codes a total of 2,323 (14%) were assigned an AIS3+ severity. Some 17% (n=426) and 27% (n=4,485) of ICD-9-CM and ICD-10-CM codes respectively were assigned to AIS9 (no-map) following the mapping process. It was evident there were ‘problem’ codes that could not be easily mapped to an AIS code to reflect severity. Problem maps affect the specificity of the map and severity when used to translate historical data in large datasets.Conclusions: The Association for the Advancement in Automotive Medicine, AAAM-endorsed expert-derived map offers a unique tool to road safety researchers to establish the number of MAIS3+ serious injuries occurring on the roads. The detailed process offered in this paper will enable researchers to understand the decision making and identify limitations when using the AIS08/ICD map on country-specific data. The results could inform protocols for dealing with problem codes to enable country comparisons of MAIS3+ serious injury rates.</div