Medically Significant Vector-Borne Viral Diseases in Iran.

Vector-borne viral diseases (VBVDs) continue to pose a considerable public health risk to animals and humans globally. Vectors have integral roles in autochthonous circulation and dissemination of VBVDs worldwide. The interplay of agricultural activities, population expansion, urbanization, host/pathogen evolution, and climate change, all contribute to the continual flux in shaping the epidemiology of VBVDs. In recent decades, VBVDs, once endemic to particular countries, have expanded into new regions such as Iran and its neighbors, increasing the risk of outbreaks and other public health concerns. Both Iran and its neighboring countries are known to host a number of VBVDs that are endemic to these countries or newly circulating. The proximity of Iran to countries hosting regional diseases, along with increased global socioeconomic activities, e.g., international trade and travel, potentially increases the risk for introduction of new VBVDs into Iran. In this review, we examined the epidemiology of numerous VBVDs circulating in Iran, such as Chikungunya virus, Dengue virus, Sindbis virus, West Nile virus, Crimean-Congo hemorrhagic fever virus, Sandfly-borne phleboviruses, and Hantavirus, in relation to their vectors, specifically mosquitoes, ticks, sandflies, and rodents. In addition, we discussed the interplay of factors, e.g., urbanization and climate change on VBVD dissemination patterns and the consequent public health risks in Iran, highlighting the importance of a One Health approach to further surveil and to evolve mitigation strategies.

Genetic diversity of Dengue virus serotypes circulating among Aedes mosquitoes in selected regions of northeastern Nigeria.

The flaviviruses are mosquito borne pathogens that continue to pose a considerable public health risk to animals and humans. The members of this group includes, Dengue virus (DENV), Yellow fever virus (YVF), Japanese encephalitis virus (JEV), West Nile virus (WEV) and Zika virus (ZKV). The DENV mosquito vector is endemic to tropical and subtropical climates, placing ∼40% of the world's population at direct risk of dengue infection. Currently, in Nigeria the status of DENV serotypes circulating among mosquito vectors is unknown. Our study was designed to identify and characterize the DENV serotypes circulating in Aedes mosquito populations collected in selected sites in Nigeria. The mosquitoes were collected and identified morphologically to species level using colored identification keys of Rueda. Generally, each species identified was tested in pools of 20 individuals of each Aedes species. RT-PCR and semi nested PCR were used to detect DENV serotypes in mosquitoes and characterized using Sanger sequencing methods. The results showed that DENV serotypes were detected in 58.54% (24/41) of the pools of Aedes mosquitoes from Mubi, Numan and Yola screened. All DENV1-4 serotypes were detected in Ae. aegypti. While DENV 1, 2 and 4 were detected in Ae. albopictus. And only DENV 2 was detected in Ae. galloisi with DENV4 serotype being reported for the first time in Nigeria. DENV2 (37.8%) was the most detected serotypes, while double and triple co-infections of serotypes were detected in 24.4% of the pools. Phylogenetic analysis revealed a strong evolutionary relatedness of DENV serotypes in our study with that of South and Southeast Asia, North America, and other African countries. This is the first reports on the natural DENV serotypes co-infection among Aedes species pools in Nigeria, which can create possible interaction with other flaviviruses causing animal and human diseases. In addition, our study postulates the possible linkage between DENV serotypes infection and human febrile flu-like disease burden being experienced by host communities in northeastern Nigeria.

Risk factors for Rift Valley fever virus seropositivity in one-humped camels (Camelus dromedarius) and pastoralist knowledge and practices in Northern Nigeria.

Rift Valley fever (RVF) is a complex emerging arboviral hemorrhagic disease that causes significant illness in animals and humans. Camel trade across the land borders between Nigeria and the Niger Republic occurs frequently and poses a significant risk for RVF transmission to pastoralists and traders. We carried a cross-sectional study between November 2016 and April 2017 in two northern States (Katsina and Jigawa) known for camel trade in Nigeria to investigate the seroprevalence and potential risk factors for RVFV occurrence. We collected 720 sera and administered questionnaire to pastoralists. We used the competitive enzyme-linked immunosorbent assay (c-ELISA) to determine the previous exposure to RVFV infection. We retrieved  environmental information from public data sources that might explain RVFV seropositivity at  the LGA level. To asses potential risk factors,we categorized LGAs with RVFV as "1" and those without a case" 0". We fitted a logistic model to the data  and estimated odds ratios and 95% confidence intervals. An overall 19.9% prevalence was reported among camel herd-the highest seropositivity (33.3%) was recorded in SuleTankarkar LGA. In the multivariable model, only rain-fed croplands was significantly associated with RVFV antibodies occurrence p = 0.048 (OR = 0.87, 95% CI: 0.76-0.99). Only a minority of the respondents, 19.3% (n = 17/88), knew that RVF is zoonotic. Separation of healthy animals from the infected animals was carried out by 53.4% (47/88) pastoralists while 59.1% (52/88) pastoralists still use ethnoveterinary practices to control or mitigate disease outbreaks. Our study demonstrates the presence of RVFV antibodies among camel in Nigeria and the associated risk factors. These findings highlight the need for enhancing surveillance and control efforts and the public health education of camel pastoralists. Further investigation to unravel the zoonotic transmission potential to pastoralists and other animal species is pertinent.

Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that represents a major threat to global health. ZIKV infections in adults are generally asymptomatic or present with mild symptoms. However, recent outbreaks of ZIKV have revealed that it can cause Congenital Zika Syndrome in neonates and Guillain-Barré syndrome in adults. Currently, no ZIKV-specific vaccines or antiviral treatments are available. In this study, we tested the efficacy of convalescent plasma IgG hyperimmune product (ZIKV-IG) isolated from individuals with high neutralizing anti-ZIKV titers as a therapeutic candidate against ZIKV infection using a model of ZIKV infection in Ifnar1-/- mice. ZIKV-IG successfully protected mice from lethal ZIKV challenge. In particular, ZIKV-IG treatment at 24 hours after lethal ZIKV infection improved survival by reducing weight loss and tissue viral burden and improving clinical score. Additionally, ZIKV-IG eliminated ZIKV-induced tissue damage and inflammation in the brain and liver. These results indicate that ZIKV-IG is efficacious against ZIKV, suggesting this human polyclonal antibody is a viable candidate for further development as a treatment against human ZIKV infection.

Evaluation of levels of interleukin-6, interleukin-8 and some haematologic parameters of dogs with cutaneous wounds.

The aim of the study was to investigate the time-course of serum and wound fluids interleukin (IL)-6 and IL-8 levels in dogs with cutaneous wounds and their relationship with some haematologic parameters. The experimental group comprised of six adult dogs that underwent surgery with wounds (n = 6) on the mid lateral aspect of the right antebrachium; and control group of six, apparently, healthy intact (free from cutaneous wounds) adult dogs, comprising equal number of both sexes. Vital signs evaluated were within normal limits. Samples of blood, serum and wound fluids harvested pre- and at 12 h, 36 h, 60 h, 156 h and 324 h post-injury, were utilised for IL-6 and IL-8 assay and haematology. Peak concentrations of IL-6 in wound fluid (1.33. ±â€¯0.33 ng/mL) and serum (0.82 ±â€¯0.24 ng/mL) of the experimental group at 12 h post-operation were higher (P < 0.01) than the control (0.30 ±â€¯0.05 ng/mL). Concentrations of IL-8 at 12 h and 60 h in wound fluid (0.21 ±â€¯0.05 ng/mL and 0.22 ±â€¯0.11 ng/mL) respectively were lower (P < 0.05) than serum (0.71 ±â€¯0.21 ng/mL and 0.73 ±â€¯0.24 ng/mL) respectively in the experimental group and corresponding values recorded in controls (0.34 ±â€¯0.09 ng/mL and 0.36 ±â€¯0.14 ng/mL). The haematological and biochemical parameters exhibited minimum fluctuations, but values were within normal ranges. Significant correlations were obtained between serum and wound fluid IL-6 (r = 0.827, P < 0.05); wound fluid IL-6 and monocyte count (r = 0.818, P < 0.04); wound fluid IL-6 and haematocrit (r = -0.894, P < 0.05). There was a positive correlation between serum IL-8 and serum IL-6 (r = 0.622, P > 0.05) and serum IL-8 and wound fluid IL-8 (r = 0.718, P > 0.05) in the experimental group. In conclusion, IL-6 and IL-8 exerted modulated inflammatory processes following cutaneous wounds in dogs. Further studies are required to investigate the expression patterns of IL-6 and IL-8 in cutaneous wounds in order to improve the quality of management of cutaneous wounds.

Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice.

Alveolar echinococcosis (AE) is a severe hepatic disorder caused by larval infection by the fox tapeworm Echinococcus multilocularis. The course of parasitic development and host reactions are known to vary significantly among host species, and even among different inbred strains of mice. As reported previously, after oral administration of parasite eggs, DBA/2 (D2) mice showed a higher rate of cyst establishment and more advanced protoscolex development in the liver than C57BL/6 (B6) mice. These findings strongly suggest that the outcome of AE is affected by host genetic factor(s). In the present study, the genetic basis of such strain-specific differences in susceptibility/resistance to AE in murine models was studied by whole-genome scanning for quantitative trait loci (QTLs) using a backcross of (B6×D2)F(1) and D2 mice with varying susceptibility to E. multilocularis infection. For cyst establishment, genome linkage analysis identified one suggestive and one significant QTL on chromosomes (Chrs.) 9 and 6, respectively, whereas for protoscolex development, two suggestive and one highly significant QTLs were detected on Chrs. 6, 17 and 1, respectively. Our QTL analyses using murine AE models revealed that multiple genetic factors regulated host susceptibility/resistance to E. multilocularis infection. Moreover, our findings show that establishment of the parasite cysts in the liver is affected by QTLs that are distinct from those associated with the subsequent protoscolex development of the parasite, indicating that different host factors are involved in the host-parasite interplay at each developmental stage of the larval parasite. Further identification of responsible genes located on the identified QTLs could lead to the development of effective disease prevention and control strategies, including an intensive screening and clinical follow-up of genetically high-risk groups for AE infection.

Distinctive and critical roles for cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in mice.

Respiratory viral infections result in severe pulmonary injury, to which host immune response may be a significant contributor. At present, it is not entirely clear the extent to which lung injury is a necessary consequence of host defense. In this report, we use functional genomics approach to characterize the key roles of cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in resistant C57BL/6J and susceptible DBA/2J mice. Infected mice manifested an immune-inflammatory response characterized by the pulmonary influx of neutrophils and mononuclear cells. DBA/2J mice mounted a vigorous immune response, with significant up-regulation of cytokine/chemokine genes in two successive waves through the course of infection. Whereas, C57BL/6J mice displayed an efficient immune response with less severe pathology and clusters of immune-inflammatory responsive genes were exclusively up-regulated on day 4 in this strain. Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections.