Multiple Modes Of Transmission Research Articles

Functional characterization of Francisella tularensis subspecies holarctica genotypes during tick cell and macrophage infections using a proteogenomic approach.

Tularemia is a vector-borne disease caused by the Gram-negative bacterium Francisella tularensis. Known hosts and vectors in Europe are hare and ticks. F. tularensis is transmitted from ticks and animals, but also from the hydrotelluric environment and the consumption of contaminated water or food. A changing climate expands the range in which ticks can live and consequently might contribute to increasing case numbers of tularemia. Two subspecies of F. tularensis are human pathogenic. Francisella tularensis tularensis (Ftt) is endemic in North America, while Francisella tularensis holarctica (Fth) is the only subspecies causing tularemia in Europe. Ft is classified as a category A bioterrorism agent due to its low infectious dose, multiple modes of transmission, high infectivity and potential for airborne transmission and has become a global public health concern. In line with the European survey and previous phylogenetic studies, Switzerland shows the co-distribution of B.6 and B.12 strains with different geographical distribution and prevalence within the country. To establish itself in different host environments of ticks and mammals, F. tularensis presumably undergoes substantial changes on the transcriptomics and proteomic level. Here we investigate the transcriptomic and proteomic differences of five strains of Fth upon infection of rabbit macrophages and tick cells.

Clinico-epidemiological Characteristics and Short-term Outcomes of Neonates Born to COVID-19 Positive Mothers at a Tertiary Care Hospital in North Karnataka- A Retrospective Study

Introduction: Coronavirus Disease-2019 (COVID-19) infection in pregnant women can have important effects on the perinatal and neonatal outcomes. Multiple modes of transmission of infection from mother to the newborn have been suggested as also the increased risk of complications in COVID-19 infected neonates. Aim: To study the clinico-epidemiological characteristics and short-term outcomes of neonates born to mothers infected with COVID-19 in relation to maternal COVID-19 severity and co-morbidities and to compare the same between COVID-19 infected and non infected neonates. Materials and Methods: This was a retrospective study of 174 neonates born to COVID-19 positive mothers admitted and delivered from 1st August 2020 to 31st October 2020, at Belagavi Institute of Medical Sciences (BIMS), North Karnataka, India. Data was collected from medical records about the clinical and epidemiological characteristics of the mothers and their neonates, symptoms and severity of COVID-19 and their management and short-term outcomes. Pearson’s Chi-square or Fisher’s-exact test was used for statistical analysis. The p-value of less than 0.05 was considered statistically significant. Results: Out of 174, 18 (10.35%) neonates tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The rates of pre-maturity and low birth weight amongst all 174 neonates were 17.24% and 24.14%, respectively. There were no significant differences in demographic features, in the need for resuscitation and incidence of complications like prematurity, low birth weight, birth asphyxia, meconium aspiration syndrome, sepsis between COVID-19 infected and non infected neonates. However, an increased risk of Early Onset Sepsis (EOS) (OR– 2.21) in COVID-19 infected neonates. None of the COVID- 19 infected neonates required Continuous Positive Airway Pressure (CPAP) or mechanical ventilation and all were discharged subsequently. In this study there were 3(1.72%) deaths, all among COVID-19 non infected, neonates. Conclusion: The incidence of COVID-19 infection in neonates born to COVID-19 infected mothers in this study was 10.35%. Most of the infections in neonates were of less severity without a significantly increased need for respiratory support and without significant mortality.

Simultaneous Dual Recordings From Vestibular Hair Cells and Their Calyx Afferents Demonstrate Multiple Modes of Transmission at These Specialized Endings.

In the vestibular periphery, transmission via conventional synaptic boutons is supplemented by post-synaptic calyceal endings surrounding Type I hair cells. This review focusses on the multiple modes of communication between these receptors and their enveloping calyces as revealed by simultaneous dual-electrode recordings. Classic orthodromic transmission is accompanied by two forms of bidirectional communication enabled by the extensive cleft between the Type I hair cell and its calyx. The slowest cellular communication low-pass filters the transduction current with a time constant of 10–100 ms: potassium ions accumulate in the synaptic cleft, depolarizing both the hair cell and afferent to potentials greater than necessary for rapid vesicle fusion in the receptor and potentially triggering action potentials in the afferent. On the millisecond timescale, conventional glutamatergic quantal transmission occurs when hair cells are depolarized to potentials sufficient for calcium influx and vesicle fusion. Depolarization also permits a third form of transmission that occurs over tens of microseconds, resulting from the large voltage- and ion-sensitive cleft-facing conductances in both the hair cell and the calyx that are open at their resting potentials. Current flowing out of either the hair cell or the afferent divides into the fraction flowing across the cleft into its cellular partner, and the remainder flowing out of the cleft and into the surrounding fluid compartment. These findings suggest multiple biophysical bases for the extensive repertoire of response dynamics seen in the population of primary vestibular afferent fibers. The results further suggest that evolutionary pressures drive selection for the calyx afferent.

Sensitive and Specific qPCR and Nested RT-PCR Assays for the Detection of Tobacco Streak Virus in Soybean

Tobacco streak virus (TSV) is a reemerging and understudied pathogen of soybean (Glycine max). Management of TSV is challenging due to the multiple modes of transmission, widespread susceptibility of commercial soybean, and lack of reliable diagnostic tests for the virus. Soybean plants with TSV-like, virus-like, or no symptoms were collected from commercial and research fields in seven counties in Wisconsin. Two sensitive assays were developed for the detection of TSV: a fluorescent dye-based quantitative reverse-transcription PCR (qPCR) assay and a nested reverse-transcription PCR (nRT-PCR). TSV was detected in 47 and 91% of symptomatic samples using the qPCR and nRT-PCR assays, respectively, suggesting that the nRT-PCR assay has higher sensitivity for detecting TSV. The qPCR assay’s limit of detection was determined at 10 fg and the assay was used to estimate the viral load in TSV-symptomatic samples. The titer of TSV in these samples was determined by absolute quantification and ranged from 15 fg to 0.796 ng. The two assays reported here provide diagnostic tools for the rapid and accurate detection of TSV that can aid in monitoring outbreaks, assessing management strategies, or screening soybean cultivars or accessions for resistance to the virus. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Family trio-based sequencing in 404 sporadic bilateral hearing loss patients discovers recessive and De novo genetic variants in multiple ways

Hereditary hearing loss (HL) has high genetic and phenotypical heterogeneity including the overlapping and variable phenotypic features. For sporadic HL without a family history, it is more difficult to indicate the contribution of genetic factors to define a pattern of inheritance. We assessed the contribution of genetic variants and patterns of inheritance by a family trio-based sequencing and provided new insight into genetics. We conducted an analysis of data from unrelated sporadic patients with HL (n = 404) who underwent trio-based whole-exome sequencing (trio-WES) or proband-only WES (p-WES) or targeted exome sequencing (TES), and the samples of their unaffected-parents (n = 808)were validated. A molecular diagnosis was rendered for 191 of 404 sporadic HL patients (47.3%) in multiple modes of inheritance, including autosomal recessive (AR), autosomal dominant (AD) caused by de novo variants, copy-number variants (CNVs), X-linked recessive, and dual genetic diagnosis. Among these patients, 83 (43.5%) cases were diagnosed with variants in rare genes. Sporadic HL patients were identified by multiple modes of transmission. Observed variations in rare genes and multiple modes of inheritance can strikingly emphasize the important etiological contribution of recessive and de novo genetic variants to a large cohort of sporadic HL cases plus their parents.

A hospital cluster of COVID-19 associated with a SARS-CoV-2 superspreading event.

Background/purposeSuperspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE.MethodsWe performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied.ResultsPatient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9).ConclusionThe host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

A Cluster of Coronavirus Disease 2019 (COVID-19) Cases on an Inpatient Hospital Unit Involving Multiple Modes of Transmission

Background: The Ohio State University Wexner Medical Center identified a cluster of coronavirus disease 2019 (COVID-19) cases on an inpatient geriatric stroke care unit involving both patients and staff. The period of suspected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission and exposure on the unit was December 20, 2020, to January 1, 2021, with some patients and staff developing symptoms and testing positive within the 14 days thereafter. Methods: An epidemiologic investigation was conducted via chart review, staff interviews, and contact tracing to identify potential patient and staff linkages. All staff who worked on the unit were offered testing regardless of the presence of symptoms as well as all patients admitted during the outbreak period. Results: In total, 6 patients likely acquired COVID-19 in the hospital (HCA). An additional 6 patients admitted to the unit during the outbreak period subsequently tested positive but had other possible exposures outside the hospital (Fig. 1). One patient failed to undergo COVID-19 testing on admission but tested positive early in the cluster and is suspected to have contributed to patient to employee transmission. Moreover, 32 employees who worked on the unit in some capacity during this period tested positive, many of whom became symptomatic during their shifts. In addition, 18 employees elected for asymptomatic testing with 3 testing positive; these were included in the total. Some staff also identified potential community exposures. Additionally, staff reported an employee who was working while symptomatic with inconsistent mask use (index employee) early in the outbreak period. The index employee likely contributed to employee transmission but had no direct patient contact. Our epidemiologic investigation ultimately identified 12 employees felt to be linked to transmission based on significant, direct patient care provided to the patients within the outbreak period (Fig. 1). In addition, 3 employees had an exposure outside the hospital indicating likely community transmission. Conclusions: Transmission was felt to be multidirectional and included employee-to-employee, employee-to-patient, and patient-to-employee transmission in the setting of widespread community transmission. Interventions to stop transmission included widespread staff testing, staff auditing regarding temperature and symptom monitoring, and re-education on infection prevention practices. Particular focus was placed on appropriate PPE use including masking and eye protection, hand hygiene, and cleaning and disinfection practices throughout the unit. SARS-CoV-2 admission testing and limited visitation remain important strategies to minimize transmission in the hospital.Funding: NoDisclosures: None

Pregnancy Fasting in Ramadan: Toward a Biocultural Framework

ABSTRACT Pregnancy fasting poses a paradox: why would a woman restrict her diet during a period of increased nutritional need? This qualitative, cross-sectional study applied biological and cultural evolutionary theories of pregnancy diet to emic models of fasting with the aim of establishing a testable biocultural framework of pregnancy fasting. The research took place with Muslim women residing in Mysore, India. In-depth interviews were conducted with pregnant women who have experience and knowledge of fasting during during the holy month of Ramadan. Our findings indicate that pregnancy fasting is socially acquired via multiple modes of transmission and that women do not fast according to mainstream evolutionary theories of pregnancy diet, but perhaps to gain moral capital.

Transmissibility and transmission of respiratory viruses.

Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.

1790. Single-Center Experience and Lessons Learnt from Management of Nipah Virus Outbreak in India

BackgroundNipah virus (NiV) is re-emerging zoonotic RNA virus belonging to Paramyxoviridae family. Suspecting Nipah virus in a NiV naive tropical area is a challenge. NiV management is further confounded by acute presentation, high mortality, broad species tropism, multiple modes of transmission, difficulty to diagnose and lack of definitive treatment.MethodsRecent NiV outbreak that lasted for approximately 1 month (2–29 May 2018) and resulted in 23 cases with a case-fatality rate of 91%. We present clinical summary and management of five cases managed at Baby Memorial Hospital, Kozhikode, India from May 17, 2018 to May 30, 2018 and were epidemiologically linked to the index case. All patients presented with initial nonspecific prodromal symptoms of fever, muscle pain, watery diarrhea. Median age was 53 years, four were males, median hospital stay was 3 days, median incubation period of was days. Further complications, included encephalitis with viral bronchopneumonia/acute respiratory distress syndrome (ARDS) in 100 %, patients, encephalitis with viral bronchopneumonia/ARDS with myocarditis in 60 %patients, despite attempted therapy with ribavirin all patients developed cardiorespiratory arrest and succumbed to the illness. ResultsHematological Investigations showed normal TLC with a mean of 7,920 cells/ mm3, mild thrombocytopenia (mean 1,57,800) high Hb 16.12(SD1.10), ESR 19 mm/hr, DLC-N 82% high relative neutrophilic cytosis. Normal liver and renal function, Na+ 133 meq/L. CSF analysis showed high opening pressure, 100% lymphocytic pleocytosis, mean CSF sugar 118 mg/100mL, CSF protein 73.6. CT chest -bilateral airspace opacities and ground glassing. Brain FLAIR sequence showed nonspecific hyperintensities in white matter and brainstem correlating with vasculitic changes. Laboratory diagnosis of NiV was made by Real-Time RT–PCR on throat swab, blood, urine and cerebrospinal fluid by Manipal virus research center and National Institute of Virology. Pathological autopsy was done in 2 cases and found noncontributory.ConclusionWe report clinical and public health management experience from one of the three hospitals managing the patients affected with NiV. Managing outbreaks of high infectivity requires persistent organized and committed healthcare interventions Disclosures All authors: No reported disclosures.

529. Halting Multi-Modal Transmission of a Novel Carbapenemase-Producing Enterobacteriaceae Outbreak

BackgroundIn January 2018, the first case of anOXA-48 carbapenem-resistant Klebsiella pneumoniae (OXA-48 CRKP) was identified in a North Carolina hospital in a patient arriving from Eastern Europe. Over the next year across multiple inpatient adult units, 14 patients had clinical isolates and 2 patients had positive rectal surveillance screens for OXA-48 CRKP.MethodsInvestigation activities to characterize the OXA-48 CRKP epidemiology included: >1000 rectal colonization screens of epidemiologically linked patients, chart reviews of infected and colonized patients, hand hygiene and environmental cleaning observations on affected units, environmental sampling to include endoscopes, sinks and toilets, and molecular analyses (pulsed-field gel electrophoresis and whole-genome sequencing).ResultsMolecular analyses confirmed a clonal outbreak. All environmental cultures including endoscope cultures performed were negative for OXA-48 CRKP. All cases were explained by at least one of three mechanisms: (1) time/space overlap on same unit (presumed lack of hand hygiene or contamination of shared patient equipment), (2) patient housed in room where previously infected patient was housed (presumed inadequate terminal disinfection/contaminated environment), or (3) a single upper gastrointestinal endoscope. Interventions included surveillance to identify and isolate colonized patients, discharge room cleaning of OXA-48 CRKP patients enhanced by ultraviolet light disinfection, curtain laundering, and discarding unused patient supplies, and monitoring and feedback for compliance with hand hygiene, cleaning, and use of personal protective equipment. A single endoscope used between multiple OXA-48 CRKP patients with no other known transmission link was quarantined upon identification, sterilized with ethylene oxide, and ultimately placed out of service.ConclusionA clonal outbreak of a novel carbapenemase-producing Enterobacteriaceae likely spread via multiple modes of transmission. The investigation was complicated by infrequent identification of colonization among patients epidemiologically linked to known cases. Multiple interventions based on epidemiological links were necessary to halt hospital-wide transmission.Disclosures All authors: No reported disclosures.

Epidemiology of Norovirus Outbreaks Reported to the Public Health Emergency Event Surveillance System, China, 2014⁻2017.

We conducted a retrospective analysis of norovirus outbreaks reported to the National Public Health Emergency Event Surveillance System (PHEESS) in China from January 1, 2014 to December 31, 2017. We reviewed all acute gastroenteritis outbreaks (n = 692) submitted to PHEESS to identify the frequency, seasonality, geographic distribution, setting, and transmission mode of outbreaks due to norovirus. A total of 616 norovirus outbreaks resulting in 30,848 cases were reported. Among these outbreaks, 571 (93%) occurred in school settings including 239 (39%) in primary schools, 136 (22%) in childcare facilities, and 121 (20%) in secondary schools. The majority of outbreaks (63%) were due to person-to-person transmission, followed by multiple modes of transmission (11%), foodborne (5%) and waterborne (3%) transmission. These findings highlight the importance of improving hand hygiene and environmental disinfection in high-risk settings. Developing a standard and quantitative outbreak reporting structure could improve the usefulness of PHEESS for monitoring norovirus outbreaks.

Modelling multi‐species and multi‐mode contact networks: Implications for persistence of bovine tuberculosis at the wildlife–livestock interface

Abstract Individual‐ and species‐level heterogeneity in contact rates can alter the ability of a pathogen to invade a host community. Many pathogens have multiple modes of transmission—by direct or indirect contact. It is important to identify the role of heterogeneity in different types of transmission when managing the risk of disease spillover at the interface among different host species. We developed a network‐based analysis to explore how individual‐ and species‐level heterogeneity shape multi‐mode contact networks. We applied this network‐based approach to contact data from proximity loggers collected in a multi‐species host community that contributes to the spillover of the disease bovine tuberculosis (bTB) to cattle populations in Michigan, USA. We used this approach to (a) quantify how individual‐ and species‐level heterogeneity influence direct and indirect contacts in this system, (b) explore how management interventions to control spillovers, such as the installation of deer fences, can alter observed contact networks and c) predict the role that wildlife species have in maintaining bTB in the community. We found that individual‐ and species‐level heterogeneity disproportionately influenced indirect and direct contact networks, with individual‐level heterogeneity having a greater effect on indirect contact networks and species‐level heterogeneity having a greater effect on direct contact networks. We also found that the installation of deer fences significantly reduced deer‐specific indirect contacts. We used the results from our network analysis to show that white‐tailed deer (Odocoileus virginianus) could act as the sole reservoir host for bTB in this community with important implications for understanding past bTB dynamics and managing the persistence of bTB in the future. Synthesis and applications. Analyses of epidemiological networks rarely account for multiple modes of contact, which can lead to an incomplete understanding of how individual‐ and species‐level heterogeneity affect disease transmission. The multi‐mode, multi‐species network analysis we develop in this study illustrates that individual‐ and species‐level heterogeneity can play significantly different roles depending on the type of contact network considered. This has important implications when managing disease at the wildlife–livestock interface, where strategies may need to be multi‐pronged to account for the variable role of heterogeneity on different modes of contact.

Induction of defence related enzymes and phenols by sar chemicals and biocontrol agents against karnal bunt (Tilletia indica Mitra) of wheat

Karnal bunt (KB) or partial bunt of wheat (Tilletia indica Mitra) is a disease of quarantine importance and difficult to control as it has multiple modes of transmission. In the absence of desirable resistance, the use of systemic acquired resistance (SAR) chemicals and bio-control agents (BCAs) might be useful for its effective management. Thus, role of SAR chemicals viz. jasmonic acid, salicylic acid and bio-control agents viz. Trichoderma viride, and Pseudomonas fluorescens was studied in KB resistant (ALDAN) and susceptible (HD2967) genotypes. Foliar application of salicylic acid at 10 ppm recorded the maximum level of total phenols while maximum activity of peroxidase, phenylalanine ammonia lyase and polyphenol oxidase was found at 50 ppm. Similarly, JA at 50 ppm was found to induce peroxidase, polyphenol oxidase and phenylalanine ammonia lyase and total phenols to the maximum extent and recorded the lowest average coefficient of infection in the test genotypes ALDAN and HD 2967 among all other treatments, respectively. However, no significant difference in ACI in the test genotypes ALDAN and HD 2967 was observed with the application of JA at 50 and 100 ppm. Seed + foliar treatment with BCAs was found to be better in induction of peroxidase, polyphenol oxidase and phenylalanine ammonia lyase and total phenols as compared to seed treatment alone. These findings can be useful in understanding the biochemical basis of resistance and devising an innovative strategy for the effective management of KB.

Notes from the Field: Multiple Modes of Transmission During a Thanksgiving Day Norovirus Outbreak - Tennessee, 2017.

Notes from the Field: Multiple Modes of Transmission During a Thanksgiving Day Norovirus Outbreak - Tennessee, 2017.

The large graph limit of a stochastic epidemic model on a dynamic multilayer network

ABSTRACTWe consider a Markovian SIR-type (Susceptible → Infected → Recovered) stochastic epidemic process with multiple modes of transmission on a contact network. The network is given by a random graph following a multilayer configuration model where edges in different layers correspond to potentially infectious contacts of different types. We assume that the graph structure evolves in response to the epidemic via activation or deactivation of edges of infectious nodes. We derive a large graph limit theorem that gives a system of ordinary differential equations (ODEs) describing the evolution of quantities of interest, such as the proportions of infected and susceptible vertices, as the number of nodes tends to infinity. Analysis of the limiting system elucidates how the coupling of edge activation and deactivation to infection status affects disease dynamics, as illustrated by a two-layer network example with edge types corresponding to community and healthcare contacts. Our theorem extends some earlier results describing the deterministic limit of stochastic SIR processes on static, single-layer configuration model graphs. We also describe precisely the conditions for equivalence between our limiting ODEs and the systems obtained via pair approximation, which are widely used in the epidemiological and ecological literature to approximate disease dynamics on networks. The flexible modeling framework and asymptotic results have potential application to many disease settings including Ebola dynamics in West Africa, which was the original motivation for this study.

Sex-biased prevalence in infections with heterosexual, direct, and vector-mediated transmission: A theoretical analysis.

Three deterministic Kermack-McKendrick-type models for studying the transmission dynamics of an infection in a two-sex closed population are analyzed here. In each model it is assumed that infection can be transmitted through heterosexual contacts, and that there is a higher probability of transmission from one sex to the other than vice versa. The study is focused on understanding whether and how this bias in transmission reflects in sex differences in final attack ratios (i.e. the fraction of individuals of each sex that eventually gets infected). In the first model, where the other two transmission modes are not considered, the attack ratios (fractions of the population of each sex that will eventually be infected) can be obtained as solutions of a system of two nonlinear equations, that has a unique solution if the net reproduction number exceeds unity. It is also shown that the ratio of attack ratios depends solely on the ratio of gender-specific susceptibilities and on the basic reproductive number of the epidemic Ro, and that the gender-specific final attack-ratio is biased in the same direction as the gender-specific susceptibilities. The second model allows also for infection transmission through direct, non-sexual, contacts. In this case too, an analytical expression is derived from which the attack ratios can be obtained. The qualitative results are similar to those obtained for the previous model, but another important parameter for determining the value of the ratio between the attack ratios in the two sexes is obtained, the relative weight of direct vs. heterosexual transmission (namely, ρ). Quantitatively, the ratio of final attack ratios generally will not exceed 1.5, if non-sexual transmission accounts for most transmission events (ρ≥0.6) and the ratio of gender-specific susceptibilities is not too large (say, 5 at most). The third model considers vector-borne, instead of direct transmission. In this case, we were not able to find an analytical expression for the final attack ratios, but used instead numerical simulations. The results on final attack ratios are actually quite similar to those obtained with the second model. It is interesting to note that transient patterns can differ from final attack ratios, as new cases will tend to occur more often in the more susceptible sex, while later depletion of susceptibles may bias the ratio in the opposite direction. The analysis of these simple models, despite their lack of realism, can help in providing insight into, and assessment of, the potential role of gender-specific transmission in infections with multiple modes of transmission, such as Zika virus (ZIKV), by gauging what can be expected to be seen from epidemiological reports of new cases, disease incidence and seroprevalence surveys.

Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era.

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples from both human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control.This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.

Structural basis for cholinergic regulation of neural circuits in the mouse olfactory bulb.

Odor information is regulated by olfactory inputs, bulbar interneurons, and centrifugal inputs in the olfactory bulb (OB). Cholinergic neurons projecting from the nucleus of the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus are one of the primary centrifugal inputs to the OB. In this study, we focused on cholinergic regulation of the OB and analyzed neural morphology with a particular emphasis on the projection pathways of cholinergic neurons. Single-cell imaging of a specific neuron within dense fibers is critical to evaluate the structure and function of the neural circuits. We labeled cholinergic neurons by infection with virus vector and then reconstructed them three-dimensionally. We also examined the ultramicrostructure of synapses by electron microscopy tomography. To further clarify the function of cholinergic neurons, we performed confocal laser scanning microscopy to investigate whether other neurotransmitters are present within cholinergic axons in the OB. Our results showed the first visualization of complete cholinergic neurons, including axons projecting to the OB, and also revealed frequent axonal branching within the OB where it innervated multiple glomeruli in different areas. Furthermore, electron tomography demonstrated that cholinergic axons formed asymmetrical synapses with a morphological variety of thicknesses of the postsynaptic density. Although we have not yet detected the presence of other neurotransmitters, the range of synaptic morphology suggests multiple modes of transmission. The present study elucidates the ways that cholinergic neurons could contribute to the elaborate mechanisms involved in olfactory processing in the OB. J. Comp. Neurol. 525:574-591, 2017. © 2016 Wiley Periodicals, Inc.

Human T-Lymphotropic Virus type 1 infection in an Indigenous Australian population: epidemiological insights from a hospital-based cohort study.

BackgroundThe Human T Lymphotropic Virus type 1 (HTLV-1) subtype C is endemic to central Australia where each of the major sequelae of HTLV-1 infection has been documented in the socially disadvantaged Indigenous population. Nevertheless, available epidemiological information relating to HTLV-1c infection is very limited, risk factors for transmission are unknown and no coordinated program has been implemented to reduce transmission among Indigenous Australians. Identifying risk factors for HTLV-1 infection is essential to direct strategies that could control HTLV-1 transmission.MethodsRisk factors for HTLV-1 infection were retrospectively determined for a cohort of Indigenous Australians who were tested for HTLV-1 at Alice Springs Hospital (ASH), 1st January 2000 to 30th June 2013. Demographic details were obtained from the ASH patient management database and the results of tests for sexually transmitted infections (STI) were obtained from the ASH pathology database.ResultsAmong 1889 Indigenous patients whose HTLV-1 serostatus was known, 635 (33.6 %) were HTLV-1 Western blot positive. Only one of 77 (1.3 %) children tested was HTLV-1 infected. Thereafter, rates progressively increased with age (15–29 years, 17.3 %; 30–49 years, 36.2 %; 50–64 years, 41.7 %) reaching 48.5 % among men aged 50–64 years. In a multivariable model, increasing age (OR, 1.04; 95 % CI, 1.03–1.04), male gender (OR, 1.41; 95 % CI, 1.08–1.85), residence in the south (OR, 10.7; 95 % CI, 7.4–15.6) or west (OR, 4.4; 95 % CI, 3.1–6.3) of central Australia and previous STI (OR, 1.42; 95 % CI, 1.04–1.95) were associated with HTLV-1 infection. Infection was acquired by three of 351 adults who were tested more than once during the study period (seroconversion rate, 0.24 (95 % CI = 0.18–2.48) per 100 person-years).ConclusionsThis study confirms that HTLV-1 is highly endemic to central Australia. Although childhood infection was documented, HTLV-1 infection in adults was closely associated with increasing age, male gender and STI history. Multiple modes of transmission are therefore likely to contribute to high rates of HTLV-1 infection in the Indigenous Australian population. Future strategies to control HTLV-1 transmission in this population require careful community engagement, cultural understanding and Indigenous leadership.