?ccr5 Genotype Is Associated with Mild Form of Nephropathia Epidemica

Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C–C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE samples and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease

Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia

Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis

Orthohantaviruses, Emerging Zoonotic Pathogens

Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates

Understanding fertilizer adoption and effectiveness on maize in Zambia

Increased fertilizer use will likely be crucial for raising and sustaining farm productivity in Africa, but adoption may be limited by ineffectiveness under certain conditions. This article quantifies the impacts of soil characteristics on maize response to fertilizer in Zambia using a nationally representative sample of 1453 fields, combining economic, farm management and soil analysis data. Depending on soil regimes, average maize yield response estimates range from insignificant (0) to 7 maize kg per fertilizer kg. For the majority of farmers, the estimated average value cost ratio is between 1 and 2, meaning fertilizer use would be fiscally rational, barring uncertainty and transfer costs. Since transfer costs exist and outcomes are uncertain, however, many farmers may sensibly pause before deciding whether to adopt fertilizer. This suggests shifting the emphasis of chronically low fertilizer use in Africa away from explanations of “market failure” toward greater emphasis on improving fertilizer efficacy.ISSN:0306-9192ISSN:1873-565

Understanding Fertilizer Effectiveness and Adoption on Maize in Zambia

As populations continue to rise and land becomes scarcer in Africa’s rural areas, there is increasing urgency for farmers to adopt land management practices that sustainably raise land and labor productivity. Considerable effort has focused on promoting inorganic fertilizers, but it is increasingly recognized that smallholder farmers’ demand for fertilizer can be depressed by soil conditions that reduce crop response to and the profitability of fertilizer use. This article quantifies the impacts of soil characteristics on maize response to fertilizer in Zambia using a nationally representative sample of 1,453 fields. In addition to economic and farm management surveys, composite soil samples were collected and analyzed for several characteristics at the Zambia Agricultural Research Institute

Application of gene therapy in the treatment of superficial digital flexor tendon injury in horses

Background: Tendon injuries are one of the most common causes of orthopedic disorders in horses. Such injuries involve a long course of  treatment and recovery. The most promising method of treating these injuries is the use of recombinant proteins and gene therapy. Aim: In this work, we evaluated the therapeutic efficacy of plasmid DNA (pDNA) containing two species-specific coding sequences, i.e. vascular endothelial growth factor 164 (VEGF164) and fibroblast growth factor 2 (FGF2), in the treatment of severe damage to the tendon of the superficial digital flexor. Methods: A pDNA construct was used to restore the damaged superficial digital flexor tendon in the horse. Results: This study showed that the administration of pDNA encoding VEGF164 and FGF2 genes at the injury area increased the regenerative activities of the damaged tendon. Conclusion: This study shows the therapeutic properties of genetic constructs (pDNA) and contributes to theadvancements in the use of these therapies. Keywords: Fibroblast growth factor 2, Plasmid DNA, Superficial digital flexor, Vascular endothelial growth factor

Hemorrhagic Fever with Renal Syndrome in Asia: History, Pathogenesis, Diagnosis, Treatment, and Prevention

Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed

Differential Cytokine Responses and the Clinical Severity of Adult and Pediatric Nephropathia Epidemica

Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed in children. This limited number of pediatric NE cases means there is an inadequate understanding of disease pathogenesis in this age category. Here, we have analyzed clinical and laboratory data in adults and children with NE to establish whether and how the disease severity differs between the two age groups. Serum cytokines were analyzed in samples collected from 11 children and 129 adult NE patients during an outbreak in 2019. A kidney toxicity panel was also used to analyze urine samples from these patients. Additionally, serum and urine samples were analyzed from 11 control children and 26 control adults. Analysis of clinical and laboratory data revealed that NE was milder in children than in adults. A variation in serum cytokine activation could explain the differences in clinical presentation. Cytokines associated with activation of Th1 lymphocytes were prominent in adults, while they were obscured in sera from pediatric NE patients. In addition, a prolonged activation of kidney injury markers was found in adults with NE, whilst only a short-lasting activation of these markers was observed in children with NE. These findings support previous observations of age differences in NE severity, which should be considered when diagnosing the disease in children