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PLoS Neglected Tropical Diseases Apr 2020In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir,...
BACKGROUND
In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain.
METHODOLOGY AND MAIN FINDINGS
Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient with multiple myeloma and symptomatic active VL, and 2 immunocompetent patients with untreated active VL. All blood donors were negative for both xenodiagnosis and conventional PCR.
CONCLUSIONS / SIGNIFICANCE
There is no consensus amongst authors on the definition of an 'asymptomatic case' nor on the tools for screening; we, therefore, have adopted one for the sake of clarity. Immunocompetent subjects, both infected asymptomatics and those treated for VL, are limited in number and appear to have no epidemiological relevance. The impact is limited for immunocompetent patients with untreated active VL, whilst immunosuppressed individuals undergoing immunosuppressive therapy and immunosuppressed individuals HIV / L. infantum coinfected were the most infectious towards sand flies. It is noteworthy that the HIV / L. infantum coinfected patient with asymptomatic leishmaniasis was easily infectious to sand flies for a long time, despite being under continuous prophylaxis for leishmaniasis. Accordingly, screening for latent Leishmania infection in HIV-infected patients is recommended in scenarios where transmission occurs. In addition, screening for VL in HIV-infected patients who have spent time in VL-endemic areas should also be implemented in non-endemic areas. More research is needed to better understand if some asymptomatic coinfected individuals contribute to transmission as 'super-spreaders'.
Topics: Adult; Animals; Antibodies, Protozoan; Asymptomatic Diseases; DNA, Protozoan; Disease Reservoirs; Disease Transmission, Infectious; Female; Humans; Leishmania infantum; Leishmaniasis, Visceral; Leukocytes, Mononuclear; Male; Middle Aged; Psychodidae; Spain
PubMed: 32324738
DOI: 10.1371/journal.pntd.0008253 -
Clinical Microbiology and Infection :... Feb 2022The role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown. (Review)
Review
BACKGROUND
The role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown.
OBJECTIVES
To determine infectiousness and probable contribution of asymptomatic persons (at the time of testing) to pandemic SARS-CoV-2 spread.
DATA SOURCES
LitCovid, medRxiv, Google Scholar, and WHO Covid-19 databases (to 31 March 2021) and references in included studies.
STUDY ELIGIBILITY CRITERIA
Studies with a proven or hypothesized transmission chain based either on serial PCR cycle threshold readings and/or viral culture and/or gene sequencing, with adequate follow-up.
PARTICIPANTS
People exposed to SARS-CoV-2 within 2-14 days to index asymptomatic (at time of observation) infected individuals.
INTERVENTIONS
Reliability of symptom and signs was assessed within contemporary knowledge; transmission likelihood was assessed using adapted causality criteria.
METHODS
Systematic review. We contacted all included studies' corresponding authors requesting further details.
RESULTS
We included 18 studies from a diverse setting with substantial methodological variation (this field lacks standardized methodology). At initial testing, prevalence of asymptomatic cases was 12.5-100%. Of these, 6-100% were later determined to be presymptomatic, this proportion varying according to setting, methods of case ascertainment and population. Nursing/care home facilities reported high rates of presymptomatic: 50-100% (n = 3 studies). Fourteen studies were classified as high risk of, and four studies as at moderate risk of symptom ascertainment bias. High-risk studies may be less likely to distinguish between presymptomatic and asymptomatic cases. Six asymptomatic studies and four presymptomatic studies reported culturing infectious virus; data were too sparse to determine infectiousness duration. Three studies provided evidence of possible and three of probable/likely asymptomatic transmission; five studies provided possible and two probable/likely presymptomatic SARS-CoV-2 transmission.
CONCLUSION
High-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates.
Topics: Bias; COVID-19; Humans; Pandemics; Reproducibility of Results; SARS-CoV-2
PubMed: 34757116
DOI: 10.1016/j.cmi.2021.10.015 -
Journal of the Pediatric Infectious... Nov 2021Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease,... (Review)
Review
Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease, including pseudomembranous colitis and toxic megacolon, healthy infants are asymptomatically colonized at high rates. The mechanisms leading to high colonization rates and infant protection from C. difficile are currently unknown; however, the ecology and metabolic state of the intestinal microbiome are factors known to influence C. difficile pathogenesis. In this review, we will examine the aspects of the early-life microbiome that may contribute to the incidence of C. difficile and protection from disease manifestation in infants. We will also discuss whether features of the adult microbiota that enable and restrict C. difficile are prevalent during early-life colonization.
Topics: Adult; Clostridioides; Clostridioides difficile; Clostridium Infections; Enterocolitis, Pseudomembranous; Humans; Infant; Microbiota
PubMed: 34791400
DOI: 10.1093/jpids/piab063 -
Current Topics in Microbiology and... 2007Since Ebola fever emerged in Central Africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission... (Review)
Review
Since Ebola fever emerged in Central Africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission from a hypothetical reservoir host(s) to humans. This research has comprised investigations on a variety of animals and their characterization as intermediate, incidental, amplifying, reservoir, or vector hosts. A viral transmission chain was recently unveiled after a long absence of epidemic Ebola fever. Animal trapping missions were carried out in the Central African rain forest in an area where several epidemics and epizootics had occurred between 2001 and 2005. Among the various animals captured and analyzed, three species of fruit bats (suborder Megachiroptera) were found asymptomatically and naturally infected with Ebola virus: Hypsignathus monstrosus (hammer-headed fruit beats), Epomops franqueti (singing fruit bats), and Myonycteris torquata (little collared fruit bats). From experimental data, serological studies and virus genetic analysis, these findings confirm the importance of these bat species as potential reservoir species of Ebola virus in Central Africa. While feeding bats drop partially eaten fruit and masticated fruit pulp (spats) to the ground, possibly promoting indirect transmission of Ebola virus to certain ground dwelling mammals, if virus is being shed in saliva by chronically and asymptomatically infected bats. Great apes and forest duikers are particularly sensitive to lethal Ebola virus infection. These terrestrial mammals feed on fallen fruits and possibly spats, suggesting a chain of events leading to Ebola virus spillover to these incidental hosts. This chain of events may occur sporadically at different sites and times depending on a combination of the phenology of fruit production by different trees, animal behavior, and various, but as yet still unknown environmental factors, which could include drought. During the reproductive period, infected body fluid can also be shed in the environment and present a potential risk for indirect transmission to other vertebrates.
Topics: Animals; Chiroptera; Disease Reservoirs; Ebolavirus; Filoviridae; Filoviridae Infections; Hemorrhagic Fever, Ebola; Humans; Primates; Risk Assessment; Species Specificity; Zoonoses
PubMed: 17848072
DOI: 10.1007/978-3-540-70962-6_15 -
Malaria Journal Jan 2021Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical...
BACKGROUND
Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.
METHODS
In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria.
RESULTS
With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.
CONCLUSIONS
The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.
Topics: Adult; Asymptomatic Infections; Chemokines; Child; Child, Preschool; Cross-Sectional Studies; Cytokines; Dendritic Cells; Erythrocytes; Female; Humans; Malaria; Malaria, Falciparum; Male; Mali; Middle Aged; Phenotype; Plasmodium falciparum
PubMed: 33407502
DOI: 10.1186/s12936-020-03533-w -
Frontiers in Behavioral Neuroscience 2015Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when... (Review)
Review
Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.
PubMed: 26734709
DOI: 10.3389/fnbeh.2015.00347 -
British Journal of Hospital MedicineThe current impact of Clostridium difficile will have been noticed by many clinicians, particularly those managing elderly patients. Infection with this bacterium can... (Review)
Review
The current impact of Clostridium difficile will have been noticed by many clinicians, particularly those managing elderly patients. Infection with this bacterium can give rise to a wide range of symptoms, from diarrhoea to fulminating colitis and toxic megacolon. Patients may also be asymptomatically colonized by C. difficile. In this article the epidemiology and aetiology of C.difficile infection will be discussed, followed by an explanation of how diagnosis of cases is best achieved, how the disease is optimally treated and how cross-infection can be minimized.
Topics: Clostridioides difficile; Cross Infection; Enterocolitis, Pseudomembranous; Humans; Infection Control; Risk Factors
PubMed: 8909713
DOI: No ID Found -
Indian Journal of Endocrinology and... Jul 2013Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of...
Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups.
PubMed: 23961479
DOI: 10.4103/2230-8210.113754 -
Journal of Fungi (Basel, Switzerland) Dec 2021is the major pathogen of the pea root rot complex in Europe. This wide host range pathogen often asymptomatically colonizes its hosts, making the control strategies...
is the major pathogen of the pea root rot complex in Europe. This wide host range pathogen often asymptomatically colonizes its hosts, making the control strategies challenging. We developed a real-time PCR assay for the detection and quantification of based on the gene sequence alignments. The assay was tested for specificity on a 54-isolate panel representing 35 fungal species and further validated in symptomatic and asymptomatic pea and wheat roots from greenhouse tests. The assay was highly consistent across separate qPCR reactions and had a quantification/detection limit of 3.1 pg of target DNA per reaction in plant tissue. Cross-reactions were observed with DNA extracts of five species. The risk of cross contamination, however, is low as the non-targets have not been associated with pea previously and they were amplified with at least 1000-fold lower sensitivity. Greenhouse inoculation tests revealed a high correlation between the pathogen DNA quantities in pea roots and pea root rot severity and biomass reduction. The assay also detected in asymptomatic wheat roots, which, despite the absence of visible root rot symptoms, caused wheat biomass reduction. This study provides new insights into the complex life style of and can assist in better understanding the pathogen survival and spread in the environment.
PubMed: 35049982
DOI: 10.3390/jof8010041 -
Frontiers in Immunology 2018is an infectious pathogen responsible for millions of deaths worldwide. Diseases caused by this bacterium are classified as pneumococcal diseases. This pathogen... (Review)
Review
is an infectious pathogen responsible for millions of deaths worldwide. Diseases caused by this bacterium are classified as pneumococcal diseases. This pathogen colonizes the nasopharynx of its host asymptomatically, but overtime can migrate to sterile tissues and organs and cause infections. Pneumonia is currently the most common pneumococcal disease. Pneumococcal pneumonia is a global health concern and vastly affects children under the age of five as well as the elderly and individuals with pre-existing health conditions. has a large selection of virulence factors that promote adherence, invasion of host tissues, and allows it to escape host immune defenses. A clear understanding of virulence factors, host immune responses, and examining the current techniques available for diagnosis, treatment, and disease prevention will allow for better regulation of the pathogen and its diseases. In terms of disease prevention, other considerations must include the effects of age on responses to vaccines and vaccine efficacy. Ongoing work aims to improve on current vaccination paradigms by including the use of serotype-independent vaccines, such as protein and whole cell vaccines. Extending our knowledge of the biology of, and associated host immune response to is paramount for our improvement of pneumococcal disease diagnosis, treatment, and improvement of patient outlook.
PubMed: 29988379
DOI: 10.3389/fimmu.2018.01366