Estimating Viral Prevalence with Data Integration for Adaptive Two-Phase Pooled Sampling

1. The COVID-19 pandemic has highlighted the importance of efficient sampling strategies and statistical methods for monitoring infection prevalence, both in humans and reservoir hosts. Pooled testing can be an efficient tool for learning pathogen prevalence in a population. Typically pooled testing requires a second phase follow up procedure to identify infected individuals, but when the goal is solely to learn prevalence in a population, such as a reservoir host, there are more efficient methods for allocating the second phase samples. 2. To estimate pathogen prevalence in a population, this manuscript presents an approach for data integration with two-phased testing of pooled samples that allows more efficient estimation of prevalence with less samples than traditional methods. The first phase uses pooled samples to estimate the population prevalence and inform efficient strategies for the second phase. To combine information from both phases, we introduce a Bayesian data integration procedure that combines pooled samples with individual samples for joint inferences about the population prevalence. 3. Data integration procedures result in more efficient estimation of prevalence than traditional procedures that only use individual samples or a single phase of pooled sampling. 4. The manuscript presents guidance on implementing the first phase and second phase sampling plans using data integration. Such methods can be used to assess the risk of pathogen spillover from reservoir hosts to humans, or to track pathogens such as SARS-CoV-2 in populations.

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Ecological Factors Characterizing the Prevalence of Bacterial Tick-Borne Pathogens in Ixodes ricinus Ticks in Pastures and Woodlands

Applied and Environmental Microbiology ◽

10.1128/aem.00610-10 ◽

2010 ◽

Vol 76 (13) ◽

pp. 4413-4420 ◽

Cited By ~ 75

Author(s):

Lénaïg Halos ◽

Séverine Bord ◽

Violaine Cotté ◽

Patrick Gasqui ◽

David Abrial ◽

...

Keyword(s):

Forest Fragmentation ◽

Ixodes Ricinus ◽

Spotted Fever ◽

Ecological Factors ◽

Adult Tick ◽

Reservoir Host ◽

Host Community ◽

Infection Prevalence ◽

Spotted Fever Group ◽

Reservoir Hosts

ABSTRACT Ecological changes are recognized as an important driver behind the emergence of infectious diseases. The prevalence of infection in ticks depends upon ecological factors that are rarely taken into account simultaneously. Our objective was to investigate the influences of forest fragmentation, vegetation, adult tick hosts, and habitat on the infection prevalence of three tick-borne bacteria, Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, and Rickettsia sp. of the spotted fever group, in questing Ixodes ricinus ticks, taking into account tick characteristics. Samples of questing nymphs and adults were taken from 61 pastures and neighboring woodlands in central France. The ticks were tested by PCR of pools of nymphs and individual adults. The individual infection prevalence was modeled using multivariate regression. The highest infection prevalences were found in adult females collected in woodland sites for B. burgdorferi sensu lato and A. phagocytophilum (16.1% and 10.7%, respectively) and in pasture sites for Rickettsia sp. (8.7%). The infection prevalence in nymphs was lower than 6%. B. burgdorferi sensu lato was more prevalent in woodlands than in pastures. Forest fragmentation favored B. burgdorferi sensu lato and A. phagocytophilum prevalence in woodlands, and in pastures, the B. burgdorferi sensu lato prevalence was favored by shrubby vegetation. Both results are probably because large amounts of edges or shrubs increase the abundance of small vertebrates as reservoir hosts. The Rickettsia sp. prevalence was maximal on pasture with medium forest fragmentation. Female ticks were more infected by B. burgdorferi sensu lato than males and nymphs in woodland sites, which suggests an interaction between the ticks and the bacteria. This study confirms the complexity of the tick-borne pathogen ecology. The findings support the importance of small vertebrates as reservoir hosts and make a case for further studies in Europe on the link between the composition of the reservoir host community and the infection prevalence in ticks.

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Missing two key parameters in the pooled testing strategy

10.21203/rs.3.rs-1028619/v1 ◽

2021 ◽

Author(s):

Xuhua Xia

Keyword(s):

Maximum Likelihood ◽

Maximum Likelihood Estimators ◽

Infection Prevalence ◽

Testing Strategy ◽

Significant Saving ◽

Pooled Testing ◽

Testing Strategies ◽

Testing Data ◽

Pooled Samples ◽

Time Resource

Abstract The pooled testing strategy [1] misses two key parameters, the infection prevalence p and its variance mentioned many times in the paper as the key determinants of any pooled testing strategy. For illustrating their methods, the authors used p from other studies that employed individual tests. It turned that that no statistical estimators for p and its variance have ever been derived for testing data of pooled samples since the first formulation of testing strategies based on pooled sampled in 1943 [2]. Here I derive the maximum likelihood estimators for p and its variance based on tests of pooled samples. This should result in significant saving in time, resource, and costs.

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Examining prevalence and diversity of tick-borne pathogens in questing Ixodes pacificus ticks in California.

Applied and Environmental Microbiology ◽

10.1128/aem.00319-21 ◽

2021 ◽

Author(s):

Daniel J. Salkeld ◽

Danielle M. Lagana ◽

Julie Wachara ◽

W. Tanner Porter ◽

Nathan C. Nieto

Keyword(s):

Lyme Disease ◽

Reservoir Host ◽

Infection Prevalence ◽

Borrelia Miyamotoi ◽

Ixodes Pacificus ◽

Granulocytic Anaplasmosis ◽

Pathogen Prevalence ◽

Local Host ◽

Host Ecology ◽

Pathogen Occurrence

Tick-borne diseases in California include Lyme disease (caused by Borrelia burgdorferi), infections with Borrelia miyamotoi, and human granulocytic anaplasmosis (caused by Anaplasma phagocytophilum). We surveyed multiple sites and habitats (woodland, grassland, coastal chaparral) in California to describe spatial patterns of tick-borne pathogen prevalence in western black-legged ticks (Ixodes pacificus). We found that several species of Borrelia – B. burgdorferi, B. americana and B. bissettiae - were observed in habitats such as coastal chaparral that does not harbor obvious reservoir host candidates. Describing tick-borne pathogen prevalence is strongly influenced by the scale of surveillance: aggregating data from individual sites to match jurisdictional boundaries (e.g., county or state) can lower the reported infection prevalence. Considering multiple pathogen species in the same habitat allows a more cohesive interpretation of local pathogen occurrence. Importance Understanding the local host ecology and prevalence of zoonotic diseases is vital for public health. Using tick-borne diseases in California, we show that there is often a bias to our understanding and that studies tend to focus on particular habitats e.g., Lyme disease in oak woodlands. Other habitats may harbor a surprising diversity of tick-borne pathogens but have been neglected, e.g., coastal chaparral. Explaining pathogen prevalence requires descriptions of data at a local scale; otherwise, aggregating the data can misrepresent the local dynamics of tick-borne diseases.

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Updated and Validated Pan-Coronavirus PCR Assay to Detect All Coronavirus Genera

Viruses ◽

10.3390/v13040599 ◽

2021 ◽

Vol 13 (4) ◽

pp. 599

Author(s):

Myndi G. Holbrook ◽

Simon J. Anthony ◽

Isamara Navarrete-Macias ◽

Theo Bestebroer ◽

Vincent J. Munster ◽

...

Keyword(s):

Host Species ◽

High Sensitivity ◽

Respiratory Illness ◽

Reservoir Host ◽

Pcr Assay ◽

Wildlife Reservoirs ◽

Viral Surveillance ◽

Reservoir Hosts

Coronavirus (CoV) spillover events from wildlife reservoirs can result in mild to severe human respiratory illness. These spillover events underlie the importance of detecting known and novel CoVs circulating in reservoir host species and determining CoV prevalence and distribution, allowing improved prediction of spillover events or where a human–reservoir interface should be closely monitored. To increase the likelihood of detecting all circulating genera and strains, we have modified primers published by Watanabe et al. in 2010 to generate a semi-nested pan-CoV PCR assay. Representatives from the four coronavirus genera (α-CoVs, β-CoVs, γ-CoVs and δ-CoVs) were tested and all of the in-house CoVs were detected using this assay. After comparing both assays, we found that the updated assay reliably detected viruses in all genera of CoVs with high sensitivity, whereas the sensitivity of the original assay was lower. Our updated PCR assay is an important tool to detect, monitor and track CoVs to enhance viral surveillance in reservoir hosts.

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

Parasites & Vectors ◽

10.1186/s13071-020-04569-2 ◽

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.

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Pooled Sputum for Xpert MTB/RIF Testing: A Cost Effectiveness Diagnostic Tool in Mwanza, Tanzania

10.21203/rs.3.rs-599005/v1 ◽

2021 ◽

Author(s):

Shimba Henerico ◽

Richard V. Makapa ◽

Bernard C. Okamo ◽

Benson R. Kidenya ◽

Geoffrey Japhet ◽

...

Keyword(s):

Cost Effectiveness ◽

Low Income ◽

Public Health Problem ◽

Positive Sample ◽

Low Income Countries ◽

Global Public Health ◽

Testing Strategy ◽

Pooled Testing ◽

The Individual ◽

Pooled Samples

Abstract Background: Tuberculosis (TB) is a global public health problem, with the highest burden occurring in low-income countries, wherein the use of more sensitive diagnostics, such as Xpert MTB/RIF (GeneXpert), is still limited by costs. Testing of pooled samples from various individuals has been thought and thus investigated as a cost saving strategy to diagnose some diseases including TB. Then in cases where a pool is positive, retesting of the individual samples in that pool is done to identify the positive sample. We assessed the utility of a pooled testing strategy to optimize the affordability of GeneXpert for the diagnosis of TB Mwanza Tanzania. Methods: Remainder of samples from presumptive TB patients submitted for routine TB diagnosis were used for pooled samples (5 per pool) testing. The agreement of the results between individual sample testing against pooled samples testing and cost-effectiveness were assessed.Results: A total of 250 individual routinely submitted samples for TB diagnosis were tested using the established protocols. The median age of study participants was 35 [IQR 27 – 40] years and 143 (57.2%) were males. Of the 250 samples, 28 (11.2%) were detected to have MTB whereas 222 (88.8%) samples, were negative. Of the 50 sputum pools made, MTB were detected in 17 (34.0%) pools. Following retesting of these 17 positive pools, all 28 (100%) individual MTB samples were detected with the overall agreement being 100% (With the sensitivity of 100% and specificity of 100%). The number of individual MTB positive ranged from 1 to 3 per pool. Using pooling of sputum samples, the technique saved 115 (46.0%) of the cartridges in running 250 samples. This is equivalent to saving US$ 1147.7. Conclusion: The pooled sputum testing strategy reduced cartridge costs by 46.0%. The use of the pooled testing strategy reduces costs and has the potential to increase the affordability of GeneXpert testing in countries with limited resources. Pooled sputum for Xpert MTB/RIF can be used as an affordable diagnostic and/or screening tool in resource limited settings, such as Tanzania.

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Ecological niche modeling of Babesia sp infection in wildlife experimentally evaluated in questing Ixodes ricinus.

Geospatial health ◽

10.4081/gh.2020.843 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Stefania Zanet ◽

Ezio Ferroglio ◽

Elena Battisti ◽

Paolo Tizzani

Keyword(s):

Ecological Niche Modeling ◽

Roe Deer ◽

Infection Prevalence ◽

Tick Abundance ◽

Preventive Actions ◽

Presence Data ◽

Alpine Chamois ◽

Suitable Area ◽

Reservoir Hosts ◽

Babesia Spp

Tick-borne diseases and especially protozoa of the genus Babesia, are gaining increasing attention as emerging zoonotic pathogens. Zoonotic species like B. venatorum and B. microti have wild animals as main reservoir hosts. We propose a habitat suitability model for Babesia spp., as tool for institutions and policy makes to better understand the entity of Babesia presence, to improve diagnostic awareness and to optimize screening and preventive actions. The probability of presence of Babesia spp. was estimated using as presence data, wild ruminants positive by PCR to Babesia spp. which were correlated to environmental factors that can favor or limit vector and host availability. We developed three separate models to discriminate the different roles of Red deer and Roe deer and Alpine chamois in Babesia spp. epidemiology. A comprehensive model using all presence data from all ungulates species was also developed. The overall suitable area for Babesia spp. in this simulation is of 3723 km2, which correspond to 15.51% of the background regional territory. The model developed was empirically validated assessing tick abundance in randomly chosen areas classified by the model as moderately or highly suitable for Babesia spp. Collected ticks were tested by PCR for Babesia spp. to confirm model predictions as infection prevalence with Babesia spp. was significantly higher in areas predicted as highly suitable compared to those classified by the model as moderately suitable for Babesia spp. (X2=5.05 p<0.05, Odds Ratio OR= 2.12 CI95% 1.1-4.1).

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The influence of landscape and environmental factors on ranavirus epidemiology in amphibian assemblages

10.1101/167395 ◽

2017 ◽

Author(s):

Brian J. Tornabene ◽

Andrew R. Blaustein ◽

Cheryl J. Briggs ◽

Dana M. Calhoun ◽

Pieter T. J. Johnson ◽

...

Keyword(s):

Environmental Factors ◽

Host Species ◽

Dilution Effect ◽

Variance Partitioning ◽

Lower Probability ◽

Infection Prevalence ◽

Taxonomic Richness ◽

Amphibian Disease ◽

Competing Models ◽

Reservoir Hosts

ABSTRACTAimTo quantify the influence of a suite of landscape, abiotic, biotic, and host-level variables on ranavirus disease dynamics in amphibian assemblages at two biological levels (site and host-level).LocationWetlands within the East Bay region of California, USA.MethodsWe used competing models, multimodel inference, and variance partitioning to examine the influence of 16 landscape and environmental factors on patterns in site-level ranavirus presence and host-level ranavirus infection in 76 wetlands and 1,377 amphibian hosts representing five species.ResultsThe landscape factor explained more variation than any other factors in site-level ranavirus presence, but biotic and host-level factors explained more variation in host-level ranavirus infection. At both the site- and host-level, the probability of ranavirus presence correlated negatively with distance to nearest ranavirus-positive wetland. At the site-level, ranavirus presence was associated positively with taxonomic richness. However, infection prevalence within the amphibian population correlated negatively with vertebrate richness. Finally, amphibian host species differed in their likelihood of ranavirus infection: American Bullfrogs had the weakest association with infection while Western Toads had the strongest. After accounting for host species effects, hosts with greater snout-vent length had a lower probability of infection.Main conclusionsStrong spatial influences at both biological levels suggest that mobile taxa (e.g., adult amphibians, birds, reptiles) may facilitate the movement of ranavirus among hosts and across the landscape. Higher taxonomic richness at sites may provide more opportunities for colonization or the presence of reservoir hosts that may influence ranavirus presence. Higher host richness correlating with higher ranavirus infection is suggestive of a dilution effect that has been observed for other amphibian disease systems and warrants further investigation. Our study demonstrates that an array of landscape, environmental, and host-level factors were associated with ranavirus epidemiology and illustrates that their importance vary with biological level.

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Evolution of Nipah Virus Infection: Past, Present, and Future Considerations

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010024 ◽

2021 ◽

Vol 6 (1) ◽

pp. 24

Author(s):

Naomi Hauser ◽

Alexis C. Gushiken ◽

Shivakumar Narayanan ◽

Shyam Kottilil ◽

Joel V. Chua

Keyword(s):

Case Fatality Rate ◽

Nipah Virus ◽

Case Fatality ◽

Therapeutic Agents ◽

Reservoir Host ◽

Fruit Bats ◽

Intermediate Hosts ◽

Mode Of Transmission ◽

Human Infections ◽

Reservoir Hosts

Nipah virus (NiV) is a zoonotic paramyxovirus of the Henipavirus genus first identified in Malaysia in 1998. Henipaviruses have bat reservoir hosts and have been isolated from fruit bats found across Oceania, Asia, and Africa. Bat-to-human transmission is thought to be the primary mode of human NiV infection, although multiple intermediate hosts are described. Human infections with NiV were originally described as a syndrome of fever and rapid neurological decline following contact with swine. More recent outbreaks describe a syndrome with prominent respiratory symptoms and human-to-human transmission. Nearly annual outbreaks have been described since 1998 with case fatality rates reaching greater than 90%. The ubiquitous nature of the reservoir host, increasing deforestation, multiple mode of transmission, high case fatality rate, and lack of effective therapy or vaccines make NiV’s pandemic potential increasingly significant. Here we review the epidemiology and microbiology of NiV as well as the therapeutic agents and vaccines in development.

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Ecological dynamics of emerging bat virus spillover

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.2124 ◽

2015 ◽

Vol 282 (1798) ◽

pp. 20142124 ◽

Cited By ~ 213

Author(s):

Raina K. Plowright ◽

Peggy Eby ◽

Peter J. Hudson ◽

Ina L. Smith ◽

David Westcott ◽

...

Keyword(s):

Land Use ◽

Ebola Virus ◽

Land Use Changes ◽

Nipah Virus ◽

Reservoir Host ◽

Hendra Virus ◽

Marburg Virus ◽

Virus Shedding ◽

Viral Shedding ◽

Reservoir Hosts

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.

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