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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract Background Malaria is a major cause of mortality and morbidity in Uganda. Despite Uganda’s efforts to distribute bed nets, only half of households have achieved the World Health Organization (WHO) Universal Coverage Criteria (one bed net for every two household members). The role of peer influence on bed net ownership remains underexplored. Data on the complete social network of households were collected in a rural parish in southwestern Uganda to estimate the association between household bed net ownership and peer household bed net ownership. Methods Data on household sociodemographics, bed net ownership, and social networks were collected from all households across one parish in southwestern Uganda. Bed nets were categorized as either purchased or free. Purchased and free bed net ownership ratios were calculated based on the WHO Universal Coverage Criteria. Using network name generators and complete census of parish residents, the complete social network of households in the parish was generated. Linear regression models that account for network autocorrelation were fitted to estimate the association between households’ bed net ownership ratios and bed net ownership ratios of network peer households, adjusting for sociodemographics and network centrality. Results One thousand seven hundred forty-seven respondents were interviewed, accounting for 716 households. The median number of peer households to which a household was directly connected was 7. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion. The median bed net ownership ratios were 0.67 for all bed nets, 0.33 for free bed nets, and 0.20 for purchased bed nets. In adjusted multivariable models, purchased bed net ownership ratio was associated with average household wealth among peer households (b = 0.06, 95% CI 0.03, 0.10), but not associated with average purchased bed net ownership ratio of peer households. Free bed net ownership ratio was associated with the number of children under 5 (b = 0.08, 95% CI 0.05, 0.10) and average free bed net ownership ratios of peer households (b = 0.66, 95% CI 0.46, 0.85). Conclusions Household bed net ownership was associated with bed net ownership of peer households for free bed nets, but not for purchased bed nets. The findings suggest that public health interventions may consider leveraging social networks as tools for dissemination, particularly for bed nets that are provided free of charge. …

Tropical Medicine &International Health, Accepted Article.

For many years, I have been contacted by clinicians for advice managing adult and pediatric patients who have repeated catheter-related bloodstream infections (CRBSIs) and whose lives depend on long-term central venous access for chemotherapy, hemodialysis, or parenteral nutrition. Despite these repeated infections, these patients did not have the benefit of prophylactic antimicrobial lock therapy. This may be a missed opportunity as there is an abundance of data in the literature to support this preventative measure for such patients, many of whom have limited alternative access sites.

This year marks the 200th anniversary of birth of Louis Pasteur, the scientist whose name has been immortalized by a series of ground-breaking discoveries that have revolutionized our understanding of life and have brought a tremendous insight into the field of life sciences, including microbiology, chemistry, medicine, agriculture, and many others (Fig. 1).

First cases of the ongoing COVID-19 pandemic were identified in France in January 2020 and on February 28, 2020, in Corsica, an island situated in the Mediterranean Sea. A major outbreak hit early the ultra-peripheral region in the following of three imported cases returning from religious gathering in mainland France. Corsica has one of the oldest population in the world and a limited beds capacity in its 2 hospitals. Therefore, the healthcare systems were rapidly overwhelmed by influx of difficult-to-transfer patients in particular elderly cases.

The Omicron variant was first reported in South Africa on November 24, 2021 and has now spread to many countries [1]. Early evidence suggested reduced neutralisation antibody response of vaccines against infection with Omicron [2], raising a critical question about the infectiousness period following vaccination.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

AbstractWhen first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time.

AbstractThe EPCR-rs867186-G allele has been linked to high plasma level of soluble-EPCR and controversially associated with either susceptibility or resistance to severe and cerebral malaria. In this study, quantitative-ELISA and sequencing were used to assess sEPCR levels and EPCR-rs867186 polymorphism in blood samples from Beninese children with different clinical presentations of malaria. Our findings show that sEPCR levels were higher at admission to hospital than during convalescence and that EPCR-rs867186-G-allele was associated with increased sEPCR plasma levels, severe malaria and mortality (p-values < .0001,  = .03 and = .04, respectively), suggesting a role of sEPCR in the pathogenesis of severe malaria.

AbstractIn the northeastern and upper Midwestern United States, Babesia microti and Borreliella burgdorferi use Ixodes scapularis ticks as vector and Peromyscus leucopus mice as major reservoir host. We previously established, in a 5-year field trial, that a reservoir-targeted OspA vaccine reduces the prevalence of B. burgdorferi-infected ticks. We accessed ticks and mouse blood samples collected during the trial, extracted DNA and amplified the B. microti 18S rRNA gene. Vaccine deployment reduced the prevalence of ticks coinfected with B. microti and that of mice infected with B. microti. Breaking the enzootic cycle of B. burgdorferi may reduce the incidence of babesiosis.

ABSTRACTBackgroundUndernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined.MethodsWe conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at five sites in the Regional Prospective Observational Research on Tuberculosis (RePORT) India consortium (2015-2019). Using multivariable Poisson regression, we assessed independent associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after two months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion.FindingsSevere undernutrition (BMI < 16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR]: 2.05; 95% confidence interval [CI]: 1.42-2.91 and 2.20; 95% CI: 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR: 1.81; 95% CI: 1.27-2.61). Severe stunting (height-for-age z-score < -3) was associated with unfavorable outcomes (aIRR: 1.52; 95% CI: 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a four and five-fold higher rate of death, respectively.InterpretationsPremorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need for addressing this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

AbstractBackgroundLinezolid-induced myelosuppression limits optimal therapy in cardiosurgical patients with deep-seated infections at current doses.MethodsAdult patients who received a cardiac surgery intervention and linezolid for a documented or presumed serious Gram-positive infection were evaluated. Therapeutic monitoring data, dosing, concomitant medications, and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic model was constructed to identify covariates and test potential drug-drug interactions that may account for interpatient variability. Simulations from the final model identified doses that achieve a target therapeutic trough concentration of 2-8 mg/L.ResultsThis study included 150 patients (79.3% male) with sepsis and hospital acquired pneumonia in 71.7% as the primary indication. The population had a median (min-max) age, body weight and estimated glomerular filtration rate (eGFR) of 66 (30–85) years, 76 (45–130) kg and 46.8 (4.9–153.7) mL/min, respectively. The standard linezolid dosage regimen achieved the therapeutic range in only 54.7% of patients. Lower than standard doses were necessary in the majority of patients (77%). A two-compartment Michaellis-Menten clearance model with weight, kidney function, and the number of interacting drugs were identified as covariates that best fit the concentration-time data. Cyclosporine had the greatest effect on lowering the maximum elimination rate (Vmax) of linezolid. Empiric linezolid doses of 300 to 450 mg every 12 hours based on eGFR and the number of interacting medications is suggested by this analysis.ConclusionsLower empiric linezolid doses in cardiosurgical patients may avoid toxicities. Confirmatory studies are necessary to verify these potential drug interactions.

AbstractBackgroundAn increase of infections after transrectal prostate biopsy (PB), related to an increasing number of patients with ciprofloxacin-resistant rectal flora, necessitates the exploration of alternatives for the traditionally standard used empirical prophylaxis with ciprofloxacin. We compared infectious complication rates after transrectal PB using empirical ciprofloxacin prophylaxis versus culture-based prophylaxis.MethodsIn this non-blinded, randomized trial, between April 4, 2018 to July 30, 2021, we enrolled 1538 patients from 11 Dutch hospitals undergoing transrectal PB. After rectal swab collection, patients were 1:1 randomized to receive empirical prophylaxis with oral ciprofloxacin (control group; CG), or culture-based prophylaxis (intervention group; IG). Primary outcome was any infectious complication within seven days post-biopsy. Secondary outcomes were infectious complications within 30 days, and bacteremia and bacteriuria within seven and 30 days post-biopsy. For primary outcome analysis, the Chi-square test stratified for hospital was used. Trial registration number: NCT03228108.ResultsData from 1288 patients (83.7%) were available for analysis (CG: 652 and IG: 636). Infection rates within seven days post-biopsy were 4.3% (n = 28) (CG) and 2.5% (n = 16) (IG) (p-value: 0.08; reduction: -1.8%; 95% CI -0.004 to 0.040). Ciprofloxacin-resistant bacteria were detected in 15.2% (n = 1288). In the CG, the presence of ciprofloxacin-resistant rectal flora resulted in a 6.2 fold higher risk of early post-biopsy infection.ConclusionsOur study supports the use of culture-based prophylaxis to reduce infectious complications after transrectal PB. Despite adequate prophylaxis, post-biopsy infections can still occur. Therefore, culture-based prophylaxis must be weighed against other strategies that could reduce post-biopsy infections.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract The Omicron transmission has infected nearly 600,000 people in Shanghai from March 26 to May 31, 2022. Combined with different control measures taken by the government in different periods, a dynamic model was constructed to investigate the impact of medical resources, shelter hospitals and aerosol transmission generated by clustered nucleic acid testing on the spread of Omicron. The parameters of the model were estimated by least square method and MCMC method, and the accuracy of the model was verified by the cumulative number of asymptomatic infected persons and confirmed cases in Shanghai from March 26 to May 31, 2022. The result of numerical simulation demonstrated that the aerosol transmission figured prominently in the transmission of Omicron in Shanghai from March 28 to April 30. Without aerosol transmission, the number of asymptomatic subjects and symptomatic cases would be reduced to 130,000 and 11,730 by May 31, respectively. Without the expansion of shelter hospitals in the second phase, the final size of asymptomatic subjects and symptomatic cases might reach 23.2 million and 4.88 million by May 31, respectively. Our results also revealed that expanded vaccination played a vital role in controlling the spread of Omicron. However, even if the vaccination rate were 100%, the transmission of Omicron should not be completely blocked. Therefore, other control measures should be taken to curb the spread of Omicron, such as widespread antiviral therapies, enhanced testing and strict tracking quarantine measures. This perspective could be utilized as a reference for the transmission and prevention of Omicron in other large cities with a population of 10 million like Shanghai.…

Abstract Background In order to verify the existence of an anthrax outbreak, determine its scope, grasp the epidemiological characteristics and find out the cause of the outbreak and recommend preventive and control measures. Methods Etiological hypothesis was developed through descriptive epidemiological methods. Hypotheses were tested by analyzing epidemiological methods by comparing the differences in the incidence of different exposure types. Nucleic acid detection and bacterial isolation and culture in the BSL-2 laboratories. SPSS 21 was used to conduct statistical analysis. Results A total of 126 family, workshop, shop environment samples and meat samples were collected, and 6 samples were collected from skin lesions of suspected cutaneous anthrax cases. 41 samples were positive by rPCR and 8 strains of Bacillus anthracis were cultivated. Participated in slaughtering, cutting beef of sick cattles was significantly associated with cutaneous anthrax (RR 3.75, 95% CI 1.08–13.07), this behavior is extremely dangerous. Conclusions Comprehensive analysis of laboratory results and epidemiological survey results and environmental assessments, we judge this epidemic to be an outbreak of cutaneous anthrax, associated with slaughtering and other processes from infected cattle imported from other province. …

Abstract Background Long-lasting insecticidal nets (LLINs) play a key role in reducing malaria transmission in endemic countries. In a previous study, the authors demonstrated a substantial decrease in the bioefficacy of LLINs for malaria prevention delivered to Papua New Guinea (PNG) between 2013 and 2019. This coincided with a rise in malaria cases in the country. The present study was aimed at determining the underlying cause of the reduced bioefficacy observed in these LLINs. The main hypothesis was that a change in the coating formulation of the respective LLIN product was responsible, and had led to significantly altered product properties and performance. Methods A set of PermaNet® 2.0 LLIN samples (n = 12) manufactured between 2007 and 2019 was subjected to combustion ion chromatography in order to understand the chemistry of the LLIN polymer coating formulation. In addition, World Health Organization (WHO) LLIN standard wash tests and cone bioassays were conducted to further characterize the change in product performance that occurred between 2012 and 2013. Results High polymer fluorine content (average 3.2 g/kg) was measured in PermaNet® 2.0 manufactured up to 2012, whereas nets which were manufactured after 2012 contained very little polymer fluorine (average 0.04 g/kg) indicating a coating formulation change from a fluorocarbon (FC)-based to a non-FC-based formulation. The coating formulation change as part of the manufacturing process thus resulted in a significant reduction in bioefficacy. In addition, the manufacturing change affected wash resistance leading to a faster reduction in 24 h mosquito mortality in the non-FC-coated product with consecutive washes. Conclusion A change in coating formulation of PermaNet® 2.0 resulted in reduced product performance in PNG. Post-2012 PermaNet® 2.0 LLINs should not be considered to be the same product as PermaNet® 2.0 LLINs produced prior to and in 2012. Coating formulation changes should be validated to not impact LLIN product performance. …

Tropical Medicine &International Health, Accepted Article.

Tropical Medicine &International Health, Accepted Article.

New England Journal of Medicine, Volume 387, Issue 21, Page 1969-1978, November 2022.

New England Journal of Medicine, Volume 387, Issue 21, November 2022.

New England Journal of Medicine, Volume 387, Issue 21, November 2022.

Abstract Objectives Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004–2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay. Design and methods Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient. Results Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases. Conclusions Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining. …

Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection.

Human infection with parvovirus B19 causes a range of clinical manifestations, including benign erythema infectiosum in children, arthralgias in adults, aplastic crisis in patients with bone marrow failure, and potentially fatal congenital hydrops fetalis. Persistent parvovirus B19 infection is a rare disease presentation mostly seen in adult women or immunocompromised individuals. Treatment options include corticosteroids and intravenous immunoglobulin; however, viral clearance is difficult to obtain and rarely maintained.

Since the start of the Coronavirus Disease 2019 (COVID-19) pandemic in early 2020, over 564 million confirmed cases and over 6 million deaths have been reported globally (July 22nd, 2022)(WHO, 2022a). In the Netherlands (total population: 17.6 million), 8.3 million inhabitants have officially been diagnosed with COVID-19 (WHO, 2022b). This number is an underestimation of the actual number of cases, since not all people were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

To determine the impact of a booster dose on the humoral response in individuals inoculated with a complete schedule of any SARS-CoV-2 vaccine, we evaluated the neutralizing antibody (NAb) titers of homologous or heterologous booster doses over a 90-days period in CoronaVac vaccinees from three centers in Santiago, Chile.

A 33-year-old man presented at the hospital because of a left axillary adenitis which appeared one month before. He had no prior medical history and was up-to-date on his vaccinations. He had two dogs and had been in recent contact with cattle in the course of his work as a rat exterminator. Physical examination revealed a growing and inflammatory axillary lesion associated with a dry cough. Blood analysis revealed hypereosinophilia (eosinophils count: 2.53x109/L). The Gram staining of the lymph node aspiration showed Gram-variable filamentous branching rods (Fig.

We aimed to generate comprehensive estimates of the appropriateness of outpatient antibiotic prescriptions at primary healthcare facilities (PHFs) in China.

Objective: Women with HIV (WWH) have heightened heart failure (HF) risk. Plasma OPN (osteopontin) is a powerful predictor of HF outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated HF risk.Design: Prospective, cross-sectionalMethods: We analyzed relationships between plasma OPN and cardiac structure/ function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH).Results: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ=0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ=0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ=0.49, P = 0.03) and myocardial steatosis (ρ=0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on non-classical (CD14-CD16+) monocytes (whole group:ρ=0.36, P = 0.04; WWH:ρ=0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH:ρ=0.54, P = 0.01; WWOH:ρ=0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters.Conclusions: Among WWH, plasma OPN, a powerful predictor of HF outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in HF pathogenesis among WWH.Clinicaltrials.gov Registration: NCT02874703Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).Design: Cross-sectional.Methods: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).Results: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1–Q3) CVD risk was 4.5% (2.6–6.9). Forty percentage had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had ≥1 vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers.Conclusions: Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH.Clinical Trials Registration: NCT02344290Graphical abstract, http://links.lww.com/QAD/C694Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.Design: HIV-positive subjects with efavirenz (EFV) or a protease inhibitor-based antiretroviral therapy (ART) were randomized to switch EFV or protease inhibitor to raltegravir (RAL group, n = 19) or to continue unchanged ART [EFV/protease inhibitor (EFV/PI) group, n = 22]. Age-matched and weight-matched HIV-negative subjects (n = 10) were included for comparison.Methods: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.Results: At week 24, microbiota diversity (Chao1 index) was higher in RAL than EFV/PI group (P = 0.014), and RAL group did not differ from HIV-negative subjects. In subgroup analysis switching from EFV (P = 0.043), but not from a protease inhibitor to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P = 0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P = 0.01 and P = 0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged.Conclusion: Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.