scholarly journals Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness

2021 ◽  
Author(s):  
Maryam Aliee ◽  
Matt J Keeling ◽  
Kat S Rock
Keyword(s):  
Neglected Tropical Diseases ◽  
Asymptomatic Infection ◽  
Parasite Infection ◽  
Human Infection ◽  
Sleeping Sickness ◽  
Blood Parasites ◽  
Transmission Model ◽  
Infection Prevalence ◽  
Symptomatic Infection ◽  
Detection Rates

Gambiense human African trypanosomiasis (gHAT, sleeping sickness) is one of several neglected tropical diseases (NTDs) where there is evidence of asymptomatic human infection but there is uncertainty of the role it plays in transmission and maintenance. To explore possible consequences of asymptomatic infections, particularly in the context of elimination of transmission, a goal set to be achieved by 2030, we propose a novel dynamic transmission model to account for the asymptomatic population. This extends an established framework, basing infection progression on a number of experimental and observation gHAT studies. Asymptomatic gHAT infections include those in people with blood-dwelling trypanosomes, but no discernible symptoms, or those with parasites only detectable in skin. Given current protocols, asymptomatic infection with blood parasites may be diagnosed and treated, based on observable parasitaemia, in contrast to many other diseases for which treatment (and/or diagnosis) may be based on symptomatic infection. We construct a model in which exposed people can either progress to either asymptomatic skin-only parasite infection, which would not be diagnosed through active screening algorithms, or blood-parasite infection, which is likely to be diagnosed if tested. We add extra parameters to the baseline model including different self-cure, recovery, transmission and detection rates for skin-only or blood infections. Performing sensitivity analysis suggests all the new parameters introduced in the asymptomatic model can impact the infection dynamics substantially. Among them, the proportion of exposures resulting in initial skin or blood infection appears the most influential parameter. For some plausible parameterisations, an initial fall in infection prevalence due to interventions could subsequently stagnate even under continued screening due to the formation of a new, lower endemic equilibrium. Excluding this scenario, our results still highlight the possibility for asymptomatic infection to slow down progress towards elimination of transmission. Location-specific model fitting will be needed to determine if and where this could pose a threat.

scholarly journals Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness

2021 ◽  
Vol 17 (9) ◽  
pp. e1009367
Author(s):  
Maryam Aliee ◽  
Matt J. Keeling ◽  
Kat S. Rock
Keyword(s):  
Neglected Tropical Diseases ◽  
Asymptomatic Infection ◽  
Parasite Infection ◽  
Human Infection ◽  
Sleeping Sickness ◽  
Blood Parasites ◽  
Transmission Model ◽  
Infection Prevalence ◽  
Symptomatic Infection ◽  
Detection Rates

Gambiense human African trypanosomiasis (gHAT, sleeping sickness) is one of several neglected tropical diseases (NTDs) where there is evidence of asymptomatic human infection but there is uncertainty of the role it plays in transmission and maintenance. To explore possible consequences of asymptomatic infections, particularly in the context of elimination of transmission—a goal set to be achieved by 2030—we propose a novel dynamic transmission model to account for the asymptomatic population. This extends an established framework, basing infection progression on a number of experimental and observation gHAT studies. Asymptomatic gHAT infections include those in people with blood-dwelling trypanosomes, but no discernible symptoms, or those with parasites only detectable in skin. Given current protocols, asymptomatic infection with blood parasites may be diagnosed and treated, based on observable parasitaemia, in contrast to many other diseases for which treatment (and/or diagnosis) may be based on symptomatic infection. We construct a model in which exposed people can either progress to either asymptomatic skin-only parasite infection, which would not be diagnosed through active screening algorithms, or blood-parasite infection, which is likely to be diagnosed if tested. We add extra parameters to the baseline model including different self-cure, recovery, transmission and detection rates for skin-only or blood infections. Performing sensitivity analysis suggests all the new parameters introduced in the asymptomatic model can impact the infection dynamics substantially. Among them, the proportion of exposures resulting in initial skin or blood infection appears the most influential parameter. For some plausible parameterisations, an initial fall in infection prevalence due to interventions could subsequently stagnate even under continued screening due to the formation of a new, lower endemic equilibrium. Excluding this scenario, our results still highlight the possibility for asymptomatic infection to slow down progress towards elimination of transmission. Location-specific model fitting will be needed to determine if and where this could pose a threat.

scholarly journals Blood Parasite Infection Prevalence in Kampong Chicken Breeder’s Group in Garut

2017 ◽  
Vol 3 (6) ◽  
pp. 308
Author(s):  
Djoko Legowo ◽  
Syifa Husnul Khotimah ◽  
Lucia Tri Suwanti
Keyword(s):  
Parasite Infection ◽  
Blood Parasite ◽  
Blood Parasites ◽  
Infection Prevalence ◽  
Blood Samples ◽  
Negative Results

The Aim of this research was to determine the blood parasite infection prevalence in Garut District. The research was conducted in November-December 2016. 160 samples of blood were obtained from eight subdistrict at Kampong Chicken Breeder’s Group (KEPAK) in Garut District smeared with 3% Giemsa solution and examined under a microscope with 1000x magnification. The merozoite and gametocyte that was discovered recorded. The data that obtained was analyzed descriptively. A parasites were found in 11 blood samples (6.88%). The genus of blood parasites is Leucocytozoon sp., while Plasmodium sp., Haemoproteus sp., and Trypanosoma avium sp. are not found in this research (0%). All of blood infected parasite only found at Tarogong Kidul subdistrict and seven other subdistricts showed negative results.  Keyword: Blood parasite, Leucocytozoon, KEPAK, Kampong Chicken

scholarly journals Spatial and temporal patterns of the emerging tick-borne pathogen Borrelia miyamotoi in blacklegged ticks (Ixodes scapularis) in New York

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
F. Keesing ◽  
D. J. McHenry ◽  
M. H. Hersh ◽  
R. S. Ostfeld
Keyword(s):  
New York ◽  
Ixodes Scapularis ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Infection ◽  
Ixodid Ticks ◽  
Transovarial Transmission ◽  
Infection Prevalence ◽  
Borrelia Miyamotoi ◽  
Spatial And Temporal Patterns ◽  
Reservoir Hosts

AbstractBorrelia miyamotoi, a bacterium that causes relapsing fever, is found in ixodid ticks throughout the northern hemisphere. The first cases of human infection with B. miyamotoi were identified in 2011. In the eastern USA, blacklegged ticks (Ixodes scapularis) become infected by feeding on an infected vertebrate host, or through transovarial transmission. We surveyed B. miyamotoi prevalence in ticks within forested habitats in Dutchess County, New York, and identified possible reservoir hosts. To assess spatial variation in infection, we collected questing nymphal ticks at > 150 sites. To assess temporal variation in infection, we collected questing nymphs for 8 years at a single study site. We collected questing larval ticks from nine plots to estimate the amount of transovarial transmission. To evaluate potential reservoir hosts, we captured 14 species of mammal and bird hosts naturally infested with larval blacklegged ticks and held these hosts in the laboratory until ticks fed to repletion and molted to nymphs. We determined infection for all ticks using quantitative polymerase chain reaction. The overall infection prevalence of questing nymphal ticks across all sites was ~ 1%, but prevalence at individual sites was as high as 9.1%. We detected no significant increase in infection through time. Only 0.4% of questing larval ticks were infected. Ticks having fed as larvae from short-tailed shrews, red squirrels, and opossums tended to have higher infection prevalence than did ticks having fed on other hosts. Further studies of the role of hosts in transmission are warranted. The locally high prevalence of B. miyamotoi in the New York/New England landscape suggests the importance of vigilance by health practitioners and the public.

scholarly journals Characterization of Salmonella serotypes prevalent in asymptomatic people and patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haiyan Xu ◽  
Weibing Zhang ◽  
Kai Zhang ◽  
Yue Zhang ◽  
Zhenyu Wang ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Asymptomatic Infection ◽  
Resistance Rate ◽  
Human Infection ◽  
The Other ◽  
Resistance Testing ◽  
Multi Drug Resistance ◽  
Discriminative Ability ◽  
Source Of Infection ◽  
The Difference

Abstract Background Infection with Salmonella enterica usually results in diarrhea, fever, and abdominal cramps, but some people become asymptomatic or chronic carrier as a source of infection for others. This study aimed to analyze the difference in serotype, antimicrobial resistance, and genetic profiles between Salmonella strains isolated from patients and those from asymptomatic people in Nantong city, China. Methods A total of 88 Salmonella strains were collected from patients and asymptomatic people from 2017 to 2018. Serotyping, antimicrobial susceptibility testing, and PFGE analysis were performed to analyze the characteristics of these strains. Results Twenty serotypes belonging to 8 serogroups were identified in the 88 Salmonella strains. S. Typhimurium remained to be the predominant serotype in strains from both patients and asymptomatic people. Among the 27 strains from patients, S. Enteritidis and S. Rissen were shown as the other two major serotypes, while S. London, S. Derby, and S. Meleagridis were demonstrated as the other significant serotypes among the 61 strains from asymptomatic people. Antimicrobial resistance testing revealed that 84.1% of strains from both resources were multi-drug resistant. PFGE displayed a highly discriminative ability to differentiate strains belonging to S. Derby, S. Typhimurium, etc., but could not efficiently differentiate serotypes like S. Enteritidis. Conclusions This study’s results demonstrated that S. Typhimurium could cause human infection in both symptomatic and asymptomatic state; S. London, S. Derby, and S. Meleagridis usually cause asymptomatic infection, while S. Enteritidis infection mainly results in human diseases. The high multi-drug resistance rate detected in the antimicrobial resistance and diverse PFGE profiles of these strains implied that the strains were isolated from different sources, and the increased surveillance of Salmonella from both patients and asymptomatic people should be taken to control the disease.

scholarly journals Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 113
Author(s):  
Helen E. Everett ◽  
Fabian Z. X. Lean ◽  
Alexander M. P. Byrne ◽  
Pauline M. van Diemen ◽  
Shelley Rhodes ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Humoral Response ◽  
Asymptomatic Infection ◽  
Human Infection ◽  
Viral Rna ◽  
Post Inoculation ◽  
Upper Respiratory Tract ◽  
Infection Dynamics ◽  
Genomic Sequence Analysis ◽  
Upper Respiratory

Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.

scholarly journals Topographic mapping of the interfaces between human and aquatic mosquito habitats to enable barrier targeting of interventions against malaria vectors

2018 ◽  
Vol 5 (5) ◽  
pp. 161055
Author(s):  
Victoria M. Mwakalinga ◽  
Benn K. D. Sartorius ◽  
Alex J. Limwagu ◽  
Yeromin P. Mlacha ◽  
Daniel F. Msellemu ◽  
...  
Keyword(s):  
Epidemiological Survey ◽  
Human Infection ◽  
Transmission Risk ◽  
Malaria Vectors ◽  
Topographic Mapping ◽  
Infection Prevalence ◽  
Selective Targeting ◽  
Water Accumulation ◽  
Local Water ◽  
Source Management

Geophysical topographic metrics of local water accumulation potential are freely available and have long been known as high-resolution predictors of where aquatic habitats for immature Anopheles mosquitoes are most abundant, resulting in elevated densities of adult malaria vectors and human infection burden. Using existing entomological and epidemiological survey data, here we illustrate how topography can also be used to map out the interfaces between wet, unoccupied valleys and dry, densely populated uplands, where malaria vector densities and infection risk are focally exacerbated. These topographically identifiable geophysical boundaries experience disproportionately high vector densities and malaria transmission risk, because this is where Anopheles mosquitoes first encounter humans when they search for blood after emerging or ovipositing in the valleys. Geophysical topographic indicators accounted for 67% of variance for vector density but for only 43% for infection prevalence, so they could enable very selective targeting of interventions against the former but not the latter (targeting ratios of 5.7 versus 1.5 to 1, respectively). So, in addition to being useful for targeting larval source management to wet valleys, geophysical topographic indicators may also be used to selectively target adult Anopheles mosquitoes with insecticidal residual sprays, fencing, vapour emanators or space sprays to barrier areas along their fringes.

scholarly journals HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection

2021 ◽  
Author(s):  
Danillo G Augusto ◽  
Tasneem Yusufali ◽  
Noah D Peyser ◽  
Xochitl Butcher ◽  
Gregory M Marcus ◽  
...  
Keyword(s):  
Critical Role ◽  
Human Leukocyte ◽  
Asymptomatic Infection ◽  
Baseline Survey ◽  
Symptomatic Infection ◽  
Symptomatic Disease ◽  
Leukocyte Antigen ◽  
Hla Genotyping ◽  
Asymptomatic Individuals ◽  
Test Result

Background. Evidence has shown that a large proportion of SARS-CoV-2 infected individuals do not experience symptomatic disease. Owing to its critical role in immune response, we hypothesized that variation in the human leukocyte antigen (HLA) loci may underly asymptomatic infection. Methods. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Among 21,893 individuals who completed the baseline survey, our discovery (N=640) and replication (N=788) cohorts were comprised of self-identified White subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with asymptomatic vs. symptomatic infection. Results. HLA-B*15:01 was significantly increased in asymptomatic individuals in the discovery cohort compared to symptomatic (OR = 2.45; 95%CI 1.38-4.24, p = 0.0016, pcorr = 0.048), and we reproduced this association in the replication cohort (OR= 2.32; 95%CI = 1.10-4.43, p = 0.017). We found robust association of HLA-B*15:01 in the combined dataset (OR=2.40 95% CI = 1.54-3.64; p = 5.67 x10-5) and observed that homozygosity of this allele increases more than eight times the chance of remaining asymptomatic after SARS-CoV-2 infection (OR = 8.58, 95%CI = 1.74-34.43, p = 0.003). Finally, we demonstrated the association of HLA-B*15:01 with asymptomatic SARS-Cov-2 infection is enhanced by the presence of HLA-DRB1*04:01 Conclusion. HLA-B*15:01 is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.

scholarly journals Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

2020 ◽  
Author(s):  
Joel Hellewell ◽  
Timothy W. Russell ◽  
Rupert Beale ◽  
Gavin Kelly ◽  
Catherine Houlihan ◽  
...  
Keyword(s):  
Vulnerable Populations ◽  
Research Unit ◽  
Asymptomatic Infection ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Symptomatic Infection ◽  
Testing Frequency ◽  
Peak Sensitivity ◽  
Pcr Test ◽  
Over Time

AbstractBackgroundRoutine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time.MethodsWe fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection, we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection.FindingsWe estimated that the probability that the PCR test detected infection peaked at 77% (54 - 88%) 4 days after infection, decreasing to 50% (38 - 65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33-76%) of symptomatic cases prior to onset and 94% (75-99%) of asymptomatic cases within 7 days if test results were returned within a day.InterpretationOur results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.FundingWellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI)

scholarly journals Total Synthesis of (+)-Spiroindimicin A via Asymmetric Palladium-Catalyzed Spirocyclization

2021 ◽  
Author(s):  
Zhen Zhang ◽  
Sneha Ray ◽  
Leah Imlay ◽  
Lauren Callaghan ◽  
Hanspeter Niederstrasser ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Human Health ◽  
Neglected Tropical Diseases ◽  
Indole Alkaloids ◽  
Sleeping Sickness ◽  
Tropical Diseases ◽  
African Sleeping Sickness ◽  
Palladium Catalyzed ◽  
Natural Precursor

<p>The spiroindimicins are a unique class of chlorinated indole alkaloids characterized by three heteroaromatic rings structured around a congested spirocyclic stereocenter. Here, we report the first total synthesis of (+)-spiroindimicin A, which bears a challenging C-3’/C-5’’-linked spiroindolenine. We detail our initial efforts to effect a biomimetic oxidative spirocyclization from its proposed natural precursor, lynamicin D, and describe how these studies shaped our final abiotic 9-step solution to this complex alkaloid built around a key asymmetric Pd-catalyzed spirocyclization. Scalable access to spiroindimicins A, H, and their congeners has enabled discovery of their activity against several parasites relevant to human health, providing potential starting points for new therapeutics for the neglected tropical diseases leishmaniasis and African sleeping sickness.</p>

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