ResearchPad - pathogens https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Assessing entomological risk factors for arboviral disease transmission in the French Territory of the Wallis and Futuna Islands]]> https://www.researchpad.co/article/elastic_article_13872 The French overseas Territory of the Wallis and Futuna Islands, located in the South Pacific, has been affected by several dengue epidemics, but did not face Zika or chikungunya outbreaks, unlike other neighboring islands. The near-exclusive presence of the Aedes polynesiensis mosquito in the islands of Wallis and Futuna confirmed the role played by this mosquito as a vector of dengue fever. A local Ae. polynesiensis population was recently shown to be able to transmit the Zika virus under experimental conditions, but its susceptibility to the chikungunya virus was still unknown, and recent data on the presence of other potential arbovirus vectors were missing. Therefore, we investigated the entomological risk factors for the transmission of arboviral diseases in the Wallis and Futuna Islands. We reported the occurrence and distribution of different Aedes species, especially the abundant presence of Ae. polynesiensis across the territory and the spread of Ae. aegypti in the island of Wallis. Our results demonstrated the ability of local Ae. polynesiensis populations to transmit the chikungunya virus. These findings highlight the risk of arbovirus transmission in the Wallis and Futuna Islands and provide relevant data to guide prevention and vector control strategies in the territory.

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<![CDATA[Genome reconstruction of the non-culturable spinach downy mildew <i>Peronospora effusa</i> by metagenome filtering]]> https://www.researchpad.co/article/elastic_article_13800 Peronospora effusa (previously known as P. farinosa f. sp. spinaciae, and here referred to as Pfs) is an obligate biotrophic oomycete that causes downy mildew on spinach (Spinacia oleracea). To combat this destructive many disease resistant cultivars have been bred and used. However, new Pfs races rapidly break the employed resistance genes. To get insight into the gene repertoire of Pfs and identify infection-related genes, the genome of the first reference race, Pfs1, was sequenced, assembled, and annotated. Due to the obligate biotrophic nature of this pathogen, material for DNA isolation can only be collected from infected spinach leaves that, however, also contain many other microorganisms. The obtained sequences can, therefore, be considered a metagenome. To filter and obtain Pfs sequences we utilized the CAT tool to taxonomically annotate ORFs residing on long sequences of a genome pre-assembly. This study is the first to show that CAT filtering performs well on eukaryotic contigs. Based on the taxonomy, determined on multiple ORFs, contaminating long sequences and corresponding reads were removed from the metagenome. Filtered reads were re-assembled to provide a clean and improved Pfs genome sequence of 32.4 Mbp consisting of 8,635 scaffolds. Transcript sequencing of a range of infection time points aided the prediction of a total of 13,277 gene models, including 99 RxLR(-like) effector, and 14 putative Crinkler genes. Comparative analysis identified common features in the predicted secretomes of different obligate biotrophic oomycetes, regardless of their phylogenetic distance. Their secretomes are generally smaller, compared to hemi-biotrophic and necrotrophic oomycete species. We observe a reduction in proteins involved in cell wall degradation, in Nep1-like proteins (NLPs), proteins with PAN/apple domains, and host translocated effectors. The genome of Pfs1 will be instrumental in studying downy mildew virulence and for understanding the molecular adaptations by which new isolates break spinach resistance.

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<![CDATA[Virus detections among patients with severe acute respiratory illness, Northern Vietnam]]> https://www.researchpad.co/article/elastic_article_13805 Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2–3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7–22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

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<![CDATA[A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar]]> https://www.researchpad.co/article/elastic_article_13833 Bloodstream infection (BSI) is common among persons seeking healthcare for severe febrile illness in low-and middle-income countries. Data on community-onset BSI are few for some countries in Asia, including Myanmar. Such data are needed to inform empiric antimicrobial treatment of patients and to monitor and control antimicrobial resistance. We performed a one year, prospective study collecting information and blood cultures from patients presenting with fever at a tertiary referral hospital in Yangon, Myanmar. We found that almost 10% of participants had a bloodstream infection, and that Salmonella enterica serovars Typhi and Paratyphi A were the most common pathogens. Typhoidal Salmonella were universally resistant to ciprofloxacin. More than half of Escherichia coli and Klebsiella pneumoniae were resistant to extended-spectrum cephalosporins and resistance to carbapenems was also identified in some isolates. We show that typhoid and paratyphoid fever are common, and fluoroquinolone resistance is widespread. Extended-spectrum cephalosporin resistance is common in E. coli and K. pneumoniae and carbapenem resistance is present. Our findings inform empiric antimicrobial management of severe febrile illness, underscore the value of routine use of blood cultures, indicate that measures to prevent and control enteric fever are warranted, and suggest a need to monitor and mitigate antimicrobial resistance among community-acquired pathogens.

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<![CDATA[Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009–2017: A cross-sectional analysis]]> https://www.researchpad.co/article/elastic_article_13850 Between 2,000 and 19,000 Special Immigrant Visa holders (SIVH) from Iraq and Afghanistan have resettled in the United States annually since 2008.Per the Immigration and Nationality Act, SIVH, like other immigrants and refugees, must be examined by a physician before arriving in the US. Results of these overseas examinations are transmitted by the Centers for Disease Control and Prevention (CDC) to US state and local health departments via CDC’s Electronic Disease Notification system (EDN).Increasing provider knowledge about the health conditions most commonly encountered in SIVH as well as any differences in health conditions between SIVH from Iraq and Afghanistan may facilitate diagnostic screening, examination, and referrals to additional healthcare providers in the US.Information about the health of SIV populations is limited and would be beneficial for US clinicians who see SIVH in their clinics.What did the researchers do and find?In this cross-sectional analysis, we analyzed overseas medical exam data in CDC’s EDN for 19,167 SIV Iraqi and Afghan adults who resettled to the United States from April 2009 through December 2017.Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use.In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH.What do these findings mean?State public health agencies and clinicians screening SIVH should consider screening for diabetes among those with risk factors and prompt referral and management of obesity, hypertension, and smoking.Behavioral risk factor counseling and referral to culturally appropriate chronic disease prevention programs can be initiated at screening visits and subsequently reemphasized with primary care providers and other healthcare professionals.Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. ]]> <![CDATA[Interaction between host genes and <i>Mycobacterium tuberculosis</i> lineage can affect tuberculosis severity: Evidence for coevolution?]]> https://www.researchpad.co/article/elastic_article_13824 Susceptibility to tuberculosis (TB) is affected by genetic variation in both the human host and the causative bacterium, Mycobacterium tuberculosis. However, prior studies of the genetics of each species have not explained a large part of TB risk. The possibility exists that risk can be better estimated from patterns of variation in the two species as a unit, such that some combinations provide increased risk, or in the presence of TB, increased disease severity. We hypothesized that alleles in the two species that have co-existed for long periods are more likely to reduce disease severity so as to promote prolonged co-occurrence. We tested this by studying TB severity in two patient cohorts from Uganda for which paired MTB-human DNA were available. We examined severity, as measured by the Bandim TBscore, and assessed whether there was an interaction between MTB lineage and SNPs in the host with this metric. Our results indicate that the most recent TB lineage (L4.6/Uganda) when found together with an ancestral allele in SLC11A1 resulted in more severe disease. This finding is consistent with the conclusion that MTB and human have coevolved to modulate TB severity.

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<![CDATA[Determinants of HIV testing among Filipino women: Results from the 2013 Philippine National Demographic and Health Survey]]> https://www.researchpad.co/article/elastic_article_13810 The prevalence of having ever tested for HIV in the Philippines is very low and is far from the 90% target of the Philippine Department of Health (DOH) and UNAIDS, thus the need to identify the factors associated with ever testing for HIV among Filipino women.MethodsWe analysed the 2013 Philippine National Demographic and Health Survey (NDHS). The NDHS is a nationally representative survey which utilized a two-stage stratified design to sample Filipino women aged 15–49. We considered the following exposures in our study: socio-demographic characteristics of respondent and her partner (i.e., age of respondent, age of partner, wealth index, etc.), sexual practices and contraception (i.e., age at first intercourse, condom use, etc.), media access, tobacco use, HIV knowledge, tolerance to domestic violence, and women’s empowerment. The outcome variable is HIV testing. We used logistic regression for survey data to study the said associations.ResultsOut of 16,155 respondents, only 372 (2.4%) have ever tested for HIV. After adjusting for confounders, having tertiary education (adjusted odds ratio (aOR) = 2.15; 95% Confidence Interval (CI): 1.15–4.04), living with partner (aOR = 1.72; 95% CI: 1.19–2.48), tobacco use (aOR = 1.87; 95% CI: 1.13–3.11); belonging to the middle class (aOR = 2.72; 95% CI: 1.30–5.67), richer (aOR = 3.00; 95% CI: 1.37–5.68), and richest (aOR = 4.14; 95% CI: 1.80–5.91) populations, having weekly television access (aOR = 1.75; 95% CI: 1.04–2.94) or internet access (aOR = 2.01; 95% CI: 1.35–3.00), living in a rural area (aOR = 1.87; 95% CI: 1.34–2.61); and being a Muslim (aOR = 2.30; 95% CI: 1.15–4.57) were associated with ever testing for HIV.ConclusionsThe low percentage of respondents who test for HIV is a call to further strengthen efforts to promote HIV testing among Filipino women. Information on its determinants can be used to guide the crafting and implementation of interventions to promote HIV testing to meet DOH and UNAIDS targets. ]]> <![CDATA[Instigation of indigenous thermophilic bacterial consortia for enhanced oil recovery from high temperature oil reservoirs]]> https://www.researchpad.co/article/elastic_article_13812 The purpose of the study involves the development of an anaerobic, thermophilic microbial consortium TERIK from the high temperature reservoir of Gujarat for enhance oil recovery. To isolate indigenous microbial consortia, anaerobic baltch media were prepared and inoculated with the formation water; incubated at 65°C for 10 days. Further, the microbial metabolites were analyzed by gas chromatography, FTIR and surface tension. The efficiency of isolated consortia towards enhancing oil recovery was analyzed through core flood assay. The novelty of studied consortia was that, it produces biomass (600 mg/l), bio-surfactant (325 mg/l), and volatile fatty acids (250 mg/l) at 65°C in the span of 10 days, that are adequate to alter the surface tension (70 to 34 mNm -1) and sweep efficiency of zones facilitating the displacement of oil. TERIK was identified as Clostridium sp. The FTIR spectra of biosurfactant indicate the presence of N-H stretch, amides and polysaccharide. A core flooding assay was designed to explore the potential of TERIK towards enhancing oil recovery. The results showed an effective reduction in permeability at residual oil saturation from 2.14 ± 0.1 to 1.39 ± 0.05 mD and 19% incremental oil recovery.

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<![CDATA[Murine gammaherpesvirus infection is skewed toward Igλ+ B cells expressing a specific heavy chain V-segment]]> https://www.researchpad.co/article/elastic_article_13826 Murine gammaherpesvirus 68 is a rodent pathogen that is closely related to the human gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated virus. All know gammaherpesviruses are associated with the development of lymphomas, as well as other cancers, in a small subset of infected individuals–particularly those with underlying defects in their immune system (i.e., transplant recipients and HIV infected patients). Because there are very limited small animal models for the human gammaherpesviruses, studies on murine gammaherepsviruses 68 can provide important insights into critical aspects of gammaherpesvirus infections and the association of these viruses with disease development. Another feature of all gammaherpesviruses is their ability to establish a chronic infection of their host–where the virus is maintained for the lifetime of the infected individual. The major target cell harboring chronic gammaherepsvirus infection are B lymphocytes–the cells in the immune system that produce antibodies in response to infections. Here we provide a detailed characterization of the populations of B lymphocytes that become infected by murine gammaherpesvirus 68. This has led to the identification of a specific population of B lymphocytes that is preferentially infected by the virus. This supports a model in which murine gammaherpesvirus infection of B lymphocytes is not random. However, it remains unclear why the virus targets this specific population of B cells for infection.

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<![CDATA[Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: A cohort study]]> https://www.researchpad.co/article/elastic_article_13858 Despite many studies demonstrating differences in HIV-related outcomes between men and women on antiretroviral therapy (ART) in sub-Saharan Africa, few studies use a probability sample that would enable them to offer regionally representative estimates.Many studies taken from routine service delivery settings are unable to account for outcomes among individuals lost to follow-up, which may threaten the validity of estimates comparing mortality in men and women.Furthermore, whether differences in survival between men and women vary across other important sociodemographic characteristics (such as age) remains underexplored.What did the researchers do and find?We used a multistage sampling approach to enumerate an analysis population of HIV-positive patients visiting public health facilities in 4 provinces in Zambia (Lusaka, Southern, Eastern, and Western).We estimated the association between sex and mortality overall and by age, adjusting for other sociodemographic and clinical characteristics.Of 49,129 adults newly initiating ART, the mortality rate was almost twice as high in men compared to women.Analysis of age-by-sex interactions revealed particularly elevated mortality among young males (as compared to females of the same age). While mortality rates appeared to fall with age among men, mortality rates rose with age among women, and by 50 years of age, women had a 2–3 times higher rate of death compared to women under 30.What do these findings mean?Among adults living with HIV in Zambia, men on average experience greater mortality compared to women, but this difference varies markedly by age, even after adjustment for other sociodemographic and clinical characteristics (e.g., baseline level of immunosuppression).Additional means of engaging and supporting younger men in HIV care is urgently needed and may include improved access to self-testing, use of financial incentives, and male-friendly services that feature flexible hours, an integrated multi-disease care model, and reduced visit frequency.Rising mortality associated with age in women greater than would be expected in the general population suggests that health services targeting women of reproductive age may be in part responsible for good clinical outcomes in younger women, but also highlights the need for specific programs to engage older women in care. ]]> <![CDATA[A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis]]> https://www.researchpad.co/article/elastic_article_13863 Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25–2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

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<![CDATA[Time-to-Death approach in revealing Chronicity and Severity of COVID-19 across the World]]> https://www.researchpad.co/article/elastic_article_13808 The outbreak of coronavirus disease, 2019 (COVID-19), which started from Wuhan, China, in late 2019, have spread worldwide. A total of 5,91,971 cases and 2,70,90 deaths were registered till 28th March, 2020. We aimed to predict the impact of duration of exposure to COVID-19 on the mortality rates increment.MethodsIn the present study, data on COVID-19 infected top seven countries viz., Germany, China, France, United Kingdom, Iran, Italy and Spain, and World as a whole, were used for modeling. The analytical procedure of generalized linear model followed by Gompertz link function was used to predict the impact lethal duration of exposure on the mortality rates.FindingsOf the selected countries and World as whole, the projection based on 21st March, 2020 cases, suggest that a total (95% Cl) of 76 (65–151) days of exposure in Germany, mortality rate will increase by 5 times to 1%. In countries like France and United Kingdom, our projection suggests that additional exposure of 48 days and 7 days, respectively, will raise the mortality rates to10%. Regarding Iran, Italy and Spain, mortality rate will rise to 10% with an additional 3–10 days of exposure. World’s mortality rates will continue increase by 1% in every three weeks. The predicted interval of lethal duration corresponding to each country has found to be consistent with the mortality rates observed on 28th March, 2020.ConclusionThe prediction of lethal duration was found to have apparently effective in predicting mortality, and shows concordance with prevailing rates. In absence of any vaccine against COVID-19 infection, the present study adds information about the quantum of the severity and time elapsed to death will help the Government to take necessary and appropriate steps to control this pandemic. ]]> <![CDATA[Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth]]> https://www.researchpad.co/article/elastic_article_13878 Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study’s objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41–63%), 82% negative predictive value (NPV, 95% CI 73–88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81–95%), 81% NPV (95% CI 77–85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81–95%) with superior NPV (87%, 95% CI 84–90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

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<![CDATA[A model for the assessment of bluetongue virus serotype 1 persistence in Spain]]> https://www.researchpad.co/article/elastic_article_11225 Bluetongue virus (BTV) is an arbovirus of ruminants that has been circulating in Europe continuously for more than two decades and has become endemic in some countries such as Spain. Spain is ideal for BTV epidemiological studies since BTV outbreaks from different sources and serotypes have occurred continuously there since 2000; BTV-1 has been reported there from 2007 to 2017. Here we develop a model for BTV-1 endemic scenario to estimate the risk of an area becoming endemic, as well as to identify the most influential factors for BTV-1 persistence. We created abundance maps at 1-km2 spatial resolution for the main vectors in Spain, Culicoides imicola and Obsoletus and Pulicaris complexes, by combining environmental satellite data with occurrence models and a random forest machine learning algorithm. The endemic model included vector abundance and host-related variables (farm density). The three most relevant variables in the endemic model were the abundance of C. imicola and Obsoletus complex and density of goat farms (AUC 0.86); this model suggests that BTV-1 is more likely to become endemic in central and southwestern regions of Spain. It only requires host- and vector-related variables to identify areas at greater risk of becoming endemic for bluetongue. Our results highlight the importance of suitable Culicoides spp. prediction maps for bluetongue epidemiological studies and decision-making about control and eradication measures.

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<![CDATA[New estimates of the Zika virus epidemic attack rate in Northeastern Brazil from 2015 to 2016: A modelling analysis based on Guillain-Barré Syndrome (GBS) surveillance data]]> https://www.researchpad.co/article/elastic_article_7754 The mandatory reporting of the Zika virus (ZIKV) disease began region-wide in February 2016, and it is believed that ZIKV cases could have been highly under-reported before that. Given the Guillain-Barré syndrome (GBS) is relatively well reported, the GBS surveillance data has the potential to act as a reasonably reliable proxy for inferring the true ZIKV epidemics. We developed a mathematical model incorporating weather effects to study the ZIKV-GBS epidemics and estimated the key epidemiological parameters. It was found that the attack rate of ZIKV was likely to be lower than 33% over the two epidemic waves. The risk rate from symptomatic ZIKV case to develop GBS was estimated to be approximately 0.0061%. The analysis suggests that it would be difficult for another ZIKV outbreak to appear in Northeastern Brazil in the near future.

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<![CDATA[Potency and breadth of human primary ZIKV immune sera shows that Zika viruses cluster antigenically as a single serotype]]> https://www.researchpad.co/article/elastic_article_7747 The recent emergence of Zika virus as an important human pathogen has raised questions about the durability and breadth of Zika virus immunity following natural infection in humans. While global epidemic patterns suggest that Zika infection elicits a protective immune response that is likely to offer long-term protection against repeat infection by other Zika viruses, only one study to date has formally examined the ability of human Zika immune sera to neutralize different Zika viruses. That study was limited because it evaluated human immune sera no more than 13 weeks after Zika virus infection and tested a relatively small number of Zika viruses. In this study, we examine twelve human Zika immune sera as far as 3 years after infection and test the sera against a total of eleven Zika virus isolates. Our results confirm the earlier study and epidemic patterns that suggest Zika virus exists in nature as a single serotype, and infection with one Zika virus can be expected to elicit protective immunity against repeat infection by any Zika virus for years to decades after the first infection.

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<![CDATA[Medusa: Software to build and analyze ensembles of genome-scale metabolic network reconstructions]]> https://www.researchpad.co/article/elastic_article_7734 Uncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles and perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org) and from github (https://github.com/opencobra/Medusa), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest.

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<![CDATA[Interventions to improve self-management of adults living with HIV on Antiretroviral Therapy: A systematic review]]> https://www.researchpad.co/article/elastic_article_7726 Since its initial recognition, HIV has been responsible for around 35 million deaths globally. The introduction of Antiretroviral Therapy has helped to reduce mortality from HIV. However, the resulting increased longevity has influenced the experience of people living with HIV, which now manifests as a chronic condition requiring effective self-management. This review aimed to identify and evaluate the effectiveness of interventions to improve self-management of adults living with HIV on Antiretroviral therapy.MethodsThe review included published experimental studies addressing interventions to improve self-management of adults living with HIV on Antiretroviral Therapy. Studies were included if they addressed two or more outcomes of self-management, as defined by the Theory of Individual and Family Self-Management. The search covered four databases and was limited to papers published in the English language from 2001 to March 30, 2019. The reference lists of included studies were further searched for additional studies. Two independent reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI SUMARI) assessed the methodological quality of the reviewed papers. Data extraction was undertaken using the JBI SUMARI standardized data extraction tool. As the included papers were not homogeneous, it was not possible to conduct a meta-analysis. A narrative synthesis was undertaken to synthesize the findings of the included studies.ResultsThe search identified 337 articles from which 10 experimental and 2 quasi-experimental studies were included. The total participant sample in the included studies was 1661 adults living with HIV. The overall evidence quality of the findings was considered moderate. Many of the studies included in this review comprised multi-component interventions to improve self-management. Skills training, in conjunction with other forms of interventions, particularly phone counseling, was commonly employed and generally effective in improving self-management outcomes. Counseling with a symptom management manual was another employed and effective intervention, followed by technology-assisted self-management interventions. The most common outcomes measured were maintaining medication adherence and quality of life, followed by symptom management, self-efficacy, coping, and social support.ConclusionsInterventions to improve self-management varied across studies. However, promising outcomes achieved in the majority of studies through interventions comprising a combination of skills training, phone counseling, counseling with symptom management manuals, and technology-assisted interventions. ]]> <![CDATA[Abrogation of pathogenic attributes in drug resistant <i>Candida auris</i> strains by farnesol]]> https://www.researchpad.co/article/elastic_article_7651 Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5–125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump- associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.

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<![CDATA[Virulence factors and antibiograms of <i>Escherichia coli</i> isolated from diarrheic calves of Egyptian cattle and water buffaloes]]> https://www.researchpad.co/article/elastic_article_8462 Diarrhea caused by Escherichia coli in calves is an important problem in terms of survivability, productivity and treatment costs. In this study, 88 of 150 diarrheic animals tested positive for E. coli. Of these, 54 samples had mixed infection with other bacterial and/or parasitic agents. There are several diarrheagenic E. coli pathotypes including enteropathogenic E. coli (EPEC), Shiga-toxin producing E. coli (STEC), enterotoxigenic E. coli (ETEC) and necrotoxigenic E. coli (NTEC). Molecular detection of virulence factors Stx2, Cdt3, Eae, CNF2, F5, Hly, Stx1, and ST revealed their presence at 39.7, 27.2, 19.3, 15.9, 13.6, 9.0, 3.4, and 3.4 percent, respectively. As many as 13.6% of the isolates lacked virulence genes and none of the isolate had LT or CNF1 toxin gene. The odds of isolating ETEC from male calves was 3.6 times (95% CI: 1.1, 12.4; P value = 0.042) that of female calves, whereas the odds of isolating NTEC from male calves was 72.9% lower (95% CI: 91.3% lower, 15.7% lower; P value = 0.024) than that in females. The odds of isolating STEC in winter was 3.3 times (95% CI: 1.1, 10.3; P value = 0.037) that of spring. Antibiograms showed 48 (54.5%) of the isolates to be multi-drug resistant. The percent resistance to tetracycline, streptomycin, ampicillin, and trimethoprim-sulfamethoxazole was 79.5, 67.0, 54.5, and 43.0, respectively. Ceftazidime (14.8%), amoxicillin-clavulanic acid (13.6%) and aztreonam (11.3%) showed the lowest resistance, and none of the isolates was resistant to imipenem. The results of this study can help improve our understanding of the epidemiological aspects of E. coli infection and to devise strategies for protection against it. The prevalence of E. coli pathotypes can help potential buyers of calves to avoid infected premises. The antibiograms in this study emphasizes the risks associated with the random use of antibiotics.

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