On the Dynamics of Dengue Virus type 2 with Residence Times and Vertical Transmission

A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors' vertical transmission and between patches human dispersal is introduced. Dispersal is modeled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions under which the disease dies out or persists are established. Analytical and numerical results highlight the role of hosts' dispersal in mitigating or exacerbating disease dynamics. The framework is used to explore dengue dynamics using, as a starting point, the 2002 outbreak in the state of Colima, Mexico

Sequence-specific detection of different strains of LCMV in a single sample using tentacle probes

Abstract Background Virus infections often result in quasispecies of viral strains that can have dramatic impacts on disease outcomes. However, sequencing of viruses to determine strain composition is time consuming and often cost-prohibitive. Rapid, cost-effective methods are needed for accurate measurement of virus diversity to understand virus evolution and can be useful for experimental systems. Methods We have developed a novel molecular method for sequence-specific detection of RNA virus genetic variants called Tentacle Probes. The probes are modified molecular beacons that have dramatically improved false positive rates and specificity in routine qPCR. To validate this approach, we have designed Tentacle Probes for two different strains of Lymphocytic Choriomeningitis Virus (LCMV) that differ by only 3 nucleotide substitutions, the parental Armstrong and the more virulent Clone-13 strain. One of these mutations is a missense mutation in the receptor protein GP1 that leads to the Armstrong strain to cause an acute infection and Clone-13 to cause a chronic infection instead. The probes were designed using thermodynamic calculations for hybridization between target or non-target sequences and the probe. Results Using this approach, we were able to distinguish these two strains of LCMV individually by a single nucleotide mutation. The assay showed high reproducibility among different concentrations of viral cDNA, as well as high specificity and sensitivity, especially for the Clone-13 Tentacle Probe. Furthermore, in virus mixing experiments we were able to detect less than 10% of Clone-13 cDNA diluted in Armstrong cDNA. Conclusions Thus, we have developed a fast, cost-effective approach for identifying Clone-13 strain in a mix of other LCMV strains

Role of short-term dispersal on the dynamics of Zika virus in an extreme idealized environment

In November 2015, El Salvador reported their first case of Zika virus (ZIKV) infection, an event followed by an explosive outbreak that generated over 6000 suspected cases in a period of two months. National agencies began implementing control measures that included vector control and recommending an increased use of repellents. Further, in response to the alarming and growing number of microcephaly cases in Brazil, the importance of avoiding pregnancies for two years was stressed. In this paper, we explore the role of mobility within communities characterized by extreme poverty, crime and violence. Specifically, the role of short term mobility between two idealized interconnected highly distinct communities is explored in the context of ZIKV outbreaks. We make use of a Lagrangian modeling approach within a two-patch setting in order to highlight the possible effects that short-term mobility, within highly distinct environments, may have on the dynamics of ZIKV outbreak when the overall goal is to reduce the number of cases not just in the most affluent areas but everywhere. Outcomes depend on existing mobility patterns, levels of disease risk, and the ability of federal or state public health services to invest in resource limited areas, particularly in those where violence is systemic. The results of simulations in highly polarized and simplified scenarios are used to assess the role of mobility. It quickly became evident that matching observed patterns of ZIKV outbreaks could not be captured without incorporating increasing levels of heterogeneity. The number of distinct patches and variations on patch connectivity structure required to match ZIKV patterns could not be met within the highly aggregated model that is used in the simulations. Keywords: Vector-borne diseases, Zika virus, Residence times, Multi-patch mode

Vertical Transmission in a Two-Strain Model of Dengue Fever

The role of vertical transmission in vectors has rarely been addressed in the study of dengue dynamics and control, in part because it was not considered a critical population-level factor. In this paper, we apply the pioneering model- ing ideas of Ross and MacDonald, motivated by the context of the 2000–2001 dengue outbreak in Peru, to assess the dynamics of multi-strain competition. An invading strain of dengue virus (DENV-2) from Asia rapidly circulated into Peru eventually displacing DENV-2 American. A host-dengue model that con- siders the competing dynamics of these two DENV-2 genotypes, the resident or the American type and the invasive more virulent Asian strain, is introduced and analyzed. The model incorporates vertical transmission by DENV-2 Asian a potentially advantageous trait. Conditions for competitive exclusion of dengue strains are established. The model is used to show that lower transmission rates of DENV-2 Asian are sufficient for displacing DENV-2 American in the presence of vertical transmission.National Institute of General Medical Sciences/[1R01GM100471-01]/NIH/Estados UnidosUCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de MatemáticaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Matemáticas Puras y Aplicadas (CIMPA

Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.

Post-exposure vaccination with vaccinia virus (VACV) has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ) was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV). Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses

Protection of wt VACV infected animals by post-exposure vaccination with v50ΔB13RMγ at one, two and three days post-infection.

<p>Groups of 5 to 10 C57BL/6 mice were infected intranasally with 10⁶ pfu (~100 LD_50s) of wt VACV. Animals were treated with 10⁷ pfu of v50ΔB13RMγ at one (▲), two (●) or three (♦) days post-infection. One group was infected with 10⁷ pfu (~1000 LD_50s) of wt VACV and treated with 10⁷ pfu of v50ΔB13RMγ at one day post-infection (∆). Controls animals were infected with wt VACV and then mock-treated (■), or animals were mock-infected and mock-treated (◊). (A) Comparison of survival curves was done using the log-rank test. (B) Recovery of wt VACV infected animals by post-exposure vaccination with v50ΔB13RMγ at one, two and three days post-infection. The graph indicates the relative sickness of each group of animals during the course of the infection. Lines ending prematurely indicate death of all the animals from the group. A value of 0 indicates that all the animals from that group were healthy.</p

Viral spread of wt VACV in infected animals.

<p>Groups of 3 C57BL/6 mice were infected intranasally with 10⁶ pfu of wt VACV. Animals remained untreated (A) or were treated one day post-infection with 10⁷ pfu of v50ΔB13RMγ (B). Replication of v50ΔB13RMγ in the tissues from the treated group was examined by X-gal staining (C). Error bars indicate the standard error of the mean. Data represent a pool of two independent experiments using 3 mice per group. </p

Post-exposure protection of wt VACV infected animals treated with v50ΔB13RMγ using different routes of treatment.

<p>Groups of 12 to 15 C57BL/6 mice were infected intranasally with 10⁶ pfu of wt VACV. Animals were treated one day post-infection with 10⁷ pfu of v50ΔB13RMγ intranasally, IN (▲), intranasally using the other nostril, INON (∆), intramuscularly, IM (○) or via scarification, SCA (<b>●</b>). One group of animals was infected with wt VACV and then mock-treated (■), another group was mock-infected and mock-treated (◊). Comparison of survival curves was done using the log-rank test.</p