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Christian Kebede,1 Beletech Fentie,2 Bethelihem Tigabu2 1Department of Pediatrics and Neonatology Nursing, School of Nursing, College of Health Science and Medicine, Wolaita Sodo University, Wolaita Sodo, Ethiopia; 2Department of Pediatrics and Child Health Nursing, School of Nursing, College of Health science and Medicine, University of Gondar, Gondar, EthiopiaCorrespondence: Christian Kebede, Department of Pediatrics and Neonatology Nursing, School of Nursing, College of Health science and Medicine, Wolaita Sodo University, P.O. Box 138, Wolaita Sodo, Ethiopia, Tel +251924741458, Email kebedechristian@gmail.comIntroduction: Jaundice is a common problem that affects up to 50– 60% of full-term babies and 80% of preterm babies. It is a benign condition, but sometimes it can cause profound complications and eventually death. Identifying the treatment outcome of jaundice and the factors affecting it is crucial to preventing the death associated with it.Objective: To determine the treatment outcome of jaundice and its associated factors among neonates treated in neonatal intensive care unit of comprehensive and specialized hospitals of SNNPR, Ethiopia, 2022.Methods: An institution-based retrospective follow up study was conducted from April 2018 to April 2022. The data was checked for completeness and then entered into Epi-data version 4.6 and exported to STATA version 17. The results were presented in frequencies and percentages for categorical variables as well as mean and median for continuous variables. A binary logistic regression model was used to estimate the effect of an independent variable and the outcome variable.Results: A total of 423 charts were reviewed, and 416 (98%) were included in the final analysis. Almost 91.3% (95% CI: 88.2, 93.7) of neonates had improved. Factors significantly associated with the treatment outcome were: residence (AOR = 0.36, 95% CI: 0.2, 0.8); origin of admission (AOR = 0.35, 95% CI: 0.2, 0.8); gestational age (AOR = 0.26, 95% CI: 0.1, 0.8); and total serum bilirubin level (AOR = 0.40, 95% CI: 0.2, 0.9).Conclusion and Recommendation: Improvement was lower compared to other low and middle-income countries; more emphasis should be given to improving treatment outcomes in hospitals.Keywords: hyperbilirubinemia, jaundice, neonate, treatment outcome

ABSTRACT The increase of antibiotic resistance in bacteria has become a major concern for successful diagnosis and treatment of infectious diseases. Over the past few decades, significant progress has been achieved on the development of nanotechnology‐based medicines for combating multidrug resistance in microorganisms. Among these, metallic nanoparticles (MNPs) hold great promise in addressing this challenge due to their broad‐spectrum and robust antimicrobial properties. This review illustrates the antibacterial activities of MNPs and further elucidates how different factors including synthesis method, size, shape, surface charge, pH, dose, type of capping or stabilizing agents of MNPs, and Gram‐type of the bacteria, impact their antibacterial activities, which are expected to promote the future development of more potent MNP‐based antibacterial agents.

A landslide is one of the geological hazards that cause the most disaster in densely populated areas. The landslide that occurred in Gezie Gofa woreda, Gofa Zone, Kencho Shacha Gozdi village, killed more than 250 people. Two landslides occurred on July 22, 2024, at 8:30 and 10:40 AM The first landslide killed six people and demolished three houses. The second landslide killed more than 245 people, including those who came to the site to excavate the buried bodies during the first landslide. The primary objective of this research is to evaluate the landslide causative factors, model the landslide susceptibility, and characterize the landslide disaster on socioeconomic effects that occurred on July 22, 2024. The landslide inventory data, field surveys, laboratory analyses, and various geophysical surveys characterized the current and past landslides of the area. The landslide susceptibility model was modeled using a statistical approach in the GIS. environment. The socioeconomic effects were assessed using field surveys and systematic interviews with the victims. The conditioning factors selected for landslide susceptibility modeling are lithology, geological structures, groundwater, slope, land use or land cover, aspect, curvature, and elevation. The major triggering factor of the landslide in the area was heavy rainfall, which occurred on July 21–22, 2024, between 3:00 a.m.-8:30 a.m. The results reveal that the significant conditioning factors of the landslide in the study area are geological structures (both visible and inferred), groundwater, slopes, and human activities. The characterized socioeconomic effects include the destruction of agricultural land, the demolishing of houses, and the loss of human lives, as well as several people evacuated and sheltered under tents and churches. However, the most momentous disaster in the area is the loss of human life. Based on the research results, it would be better to relocate those people living in the high landslide susceptible zones, and all high landslide-prone areas and mountainous terrain in southern Ethiopia should be mapped, and the people should be aware of the landslide risk areas.

Antimicrobial resistance (AMR) is the top global public health and development threat. It has led to 4·95 million deaths associated with bacterial AMR in 2019, including 1·27 million deaths attributable to bacterial AMR. In addition to causing death and disability, it is projected that by 2030, the annual gross domestic product (GDP) losses due to AMR could range from US$1 trillion to US$3.4 trillion. In the current study, bio-capped silver nanoparticles (AgNPs) showed significant antibacterial activities against both gram-positive and gram-negative MDR bacterial pathogens. 2.50 μg/ml to 100 mg/ml and 3.8 μg/ml to 2.5 mg/ml were the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of AgNPs, while the zone of inhibition (ZOI) was 4 to 25 mm. Particle size, shape, type of capping or stabilizing agent, surface charge, pH, exposure time, concentration, and bacterial type affect the antibacterial activities of AgNPs. Cell wall and membrane damage, destruction of biomolecules (lipids, proteins, and DNA), disruption of the electron transport chain, and proton motive force are mechanisms of action of AgNPs. In general, green-synthesised AgNPs from plants and bacteria (synergistic effect between AgNPs and natural compounds) displayed significant antibacterial activity against a wide range of Gram-positive and Gram-negative MDR bacteria.

An integrated geophysical and geotechnical study evaluated the foundation conditions at the War dam site in northwest Ethiopia. This investigation included the classification of rock quality, shallow seismic refraction, and magnetic approaches. The dam's location comprises quaternary soil deposits and rhyolite rock units that have undergone varied weathering and fracturing. The shallow seismic refraction method distinguishes three layers of p-wave velocities that are less than 1.5 km per second with a depth range of 2–6 m, 1.5–2.5 km per second at a depth range of 15–20 m, and 2.5–3.5 km per second ranging from 20 to 40 m, respectively. Magnetic data were used to identify lineaments, and the RQD value acquired from boreholes ranged from extremely poor to excellent. Lineaments were recognized using the tilt angle approach. The results of the permeability tests demonstrated that the rock mass that serves as the dam's foundation had characteristics that are resistant to low permeability. The maximum and minimum lugeon values obtained from the testing were 9Lu and 0.81Lu, respectively. There are weak zones at and below the surface of the dam site, according to the overall findings acquired from seismic refraction, magnetic, and discontinuity surveying. These results were obtained from monitoring the dam site. These significant structures are directed towards a SW-NE, NE-SW, NNW-SSE, and SSW-NNE orientation. The study assessed the geological suitability of a proposed dam site using seismic refraction and magnetic survey methods. Significant geological variations were observed, particularly in the right abutment and valley floor, indicating the need for targeted grouting. The findings suggest that while the site is generally suitable for dam construction, specific areas require further ground improvement to ensure stability.

The literature has examined the therapeutic properties of flavonoids found in Aloe species. According to reports, Aloe extracts exhibited antioxidant properties of flavonoids like genistein, isovitexin, isorhamnetin, and daidzenin. It has been reported that A. vera, A. arborescens, A. grandidentata, A. perfoliata, A. brevifolia, and A. saponaria all displayed anti-inflammatory therapeutic flavonoids such as vicenin 2, lucenin 2, orientin, and isovitexin. Aloe species extracts have antimicrobial qualities that prevent or stop the growth of germs due to the diverse range of chemicals they contain. Aloe hijazensis flavonoids had antifungal properties reported in the literature. The biological properties of Aloe flavonoids such as antioxidant, anti-inflammatory, antimicrobial, and anti-aging properties, are employed in the treatment and prevention of chronic diseases like diabetes, cancer, COVID-19, and others. Flavonoids derived from the genus Aloe are commonly utilized in pharmaceutical, nutraceutical, and cosmeceutical products for their medicinal potentials. Many flavonoids are proving to have therapeutic effects; however, the flavonoids of the Aloe species, which have been found and shown to have therapeutic properties, are still being thoroughly compiled. Thus, the current objective is to provide a comprehensive overview of the structures, categories, and analyses of the flavonoids that are present in medicinally useful Aloe species.

Currently, research on iron-based superconductors is so interesting because they show uniformity of magnetic and superconducting phases and have variety layered crystal structures with wide applications. The main objective of this article is to focus on the computational study of the interplay of antiferromagnetism and superconductivity using a two-band model of Hamiltonian from electronic structure and double-time temperature-dependent Green’s function formalism for Sr1−xNaxFe2As2 superconductor. From the model Hamiltonian and Green’s function formalism, we found mathematical expressions for the superconducting (Sc) order parameter, the antiferromagnetic (AFM) order parameter, the AFM and Sc transition temperatures. Using these mathematical statements, we plotted the phase illustrations of order parameters versus temperature, transition temperatures versus AFM order parameter using Matplotlib in Python. From these graphs, we have illustrated the interplay of antiferromagnetism and superconductivity, pure superconducting phase, pure antiferromagnetism phase and paramagnetic phase for the Sr1−xNaxFe2As2 superconductor.

Different nanomaterials in single (CeO2), binary (CdS/CeO2 and Ag3PO4/CeO2), ternary CdS/CeO2/Ag3PO4 (4:1 molar ratio) and conductive polymer supported (PANI-CdS/CeO2/Ag3PO4) were synthesized by co-precipitation method. Elemental analysis, crystal structure, surface area, morphology and optical properties of the as-synthesized nanoparticles were characterized. Electrochemical behavior of glassy carbon electrode modified by polyaniline supported CdS/CeO2/Ag3PO4 nanocomposite were also characterized by electrochemical impedance spectroscopy and cyclic voltammetry in 0.1 M of K3[Fe(CN)6] containing 0.1 M KCl at pH 7 with a frequency range of 0.1 to 1000 Hz, with an amplitude of 50 mV. The voltammogramm shows that the process of all as synthesized nanocomposites modified glassy carbon electrode is diffusion controlled. Under optimum conditions, the electrochemical sensor showed Malathion concentrations in linear range of 1-13 × 10−7 M, good reproducibility, and no interference by other pesticides and high recovery values around 98.90%. As-synthesized nanocomposite modified glassy carbon electrode exhibits the lowest detection limit of 3.0 × 10−9 M for Malathion detection. The simplicity of preparation, high sensitivity, good stability and reproducibility of this nanostructured polyaniline supported CdS/CeO2/Ag3PO4 electrode can be a potential candidate for application in the detection of Malathion.

The main focus of this article is to investigate the theoretical interplay of magnetism and superconductivity in a two-band model for the iron-based superconductor Ba1−xKxFe2As2. On the basis of experimental results, the two-band model Hamiltonian was considered. We obtained mathematical statements for the superconductor Ba1−xKxFe2As2 superconducting (SC) transition temperature, spin-density-wave (SDW), transition temperature, superconductivity order parameter, and SDW order parameter from the Bogoliubov transformation formalism and the model Hamiltonian. Furthermore, an expression for the dependence of the SDW transition temperature on the SDW order parameter and the dependence of the SC transition temperature on the SDW order parameter was obtained for Ba1−xKxFe2As2. By substituting the experimental and theoretical values of the parameters in the derived statements, phase diagrams of the SC transition temperature versus the SDW order parameter and the SDW transition temperature versus the SDW order parameters have been plotted to demonstrate the dependence of the SDW order parameter on transition temperatures. By combining the two-phase diagrams, we depicted the possible coexistence of superconductivity and magnetism for the Ba1−xKxFe2As2 superconductor. The phase diagrams of temperature versus SC order parameter and temperature versus SDW order parameter were also plotted to show the dependence of order parameters on temperature for the Ba1−xKxFe2As2 superconductor.

Abstract Background Unsafe abortion accounts for nearly 60% of all gynecologic admissions and almost 30% of all obstetric and gynecologic admissions. Studies on abortion in Ethiopia have given less attention to women’s perceptions and experiences of abortion laws. Although the 2005 revised abortion law allows women to access safe abortion services, still unsafe abortion is one of the leading causes of pregnancy-related deaths. Therefore, the current study aimed to assess women’s knowledge and attitude towards the Ethiopian current abortion law in Bahir Dar City Administration. Methods A community-based cross-sectional study using a systematic random sampling technique was carried out among 403 randomly selected reproductive age women using a pre-tested structured questionnaire in Bahir Dar City Administration from May to June /2017. Data were entered into Epi data version 3.1 and analyzed using SPSS version 21.0 software. Logistic regression was done to identify the possible factors associated with women’s knowledge and attitude towards the Ethiopian current abortion law. Results Three hundred eighty-six respondents partook with a response rate of 95.7%. The study showed that 43% had good knowledge and 38% had a favorable attitude towards the Ethiopian current abortion law. Women’s in the age group of 25–29 years (AOR = 2.7, 95% CI: 1.02, 6.9), partner’s educational status of primary (AOR = 2.9, 95% CI: 1.19, 7.08), secondary (AOR = 5.5, 95% CI: 2.09, 14.4) and college and above (AOR = 8.2, 95% CI: 2.3, 28.6) were significantly associated with good knowledge of the Ethiopian current abortion law. While partner’s educational status; college and above (AOR = 6.15, 95% CI: 1.87, 20.22) was significantly associated with the favorable attitude towards the Ethiopian current abortion law. Conclusions 43% of respondents had good knowledge and 38% had a favorable attitude towards the Ethiopian current abortion law. Forty-nine respondents had a history of abortion of which, 8 occurred through induction. Woman’s age and partner’s education determine the status of knowledge while merely; the partner’s educational status of college and above was significantly associated with the attitude towards Ethiopian current abortion law, respectively.

BackgroundCancer is the second leading cause of death in the world. Knowing the cancer risk factors could help the policy-makers to design appropriate preventive and control strategies.ObjectiveTo investigate the awareness regarding risk factors and determinants of cancers among Bahir Dar city residents, northwest, 2019.MethodsA community-based cross-sectional study was employed. A systematic random sampling technique was carried out to select 845 study participants from May 1 to June 30, 2019. A validated structured cancer awareness measuring tool was used to collect the data. The data were entered into the Epi-data version 3.1 and analyzed using SPSS version 21 software. A simple logistic regression was run, and AOR (adjusted odds ratio) at a 95% confidence interval was used to identify the determinants of awareness regarding risk factors of cancers.ResultsNearly twenty percent of the respondents had a good awareness regarding risk factors of cancers. An orthodox Christian (AOR = 3. 2; 95%CI: 1.8, 5.6), college graduated (AOR = 2. 3; 95%CI:1.1, 4.9), a family member with cancer (AOR = 2. 0; 95%CI: 1.3, 3.3), and living in a rental house (AOR = 0. 6; 95%CI: 0.4, 0.9) were significantly associated with awareness regarding risk factors of cancers.ConclusionThe study revealed that awareness regarding risk factors of cancers was very low in the study area. Being Orthodox Christian, college graduated, a family member with cancer, and living in the rental house were the determinants of awareness regarding risk factors of cancers.

BACKGROUND:Epilepsy is the most common chronic neurologic disorder which affects an estimated 10.5 million children worldwide. Despite the burden, the scarcity of study held in Ethiopia. Hence, the aim of this study was to assess the treatment outcomes of epilepsy and its root causes in children with epilepsy. METHODS:A hospital-based retrospective cohort study was conducted from October 10/2017 up to October 10/2018. A total of 210 study participants who fulfilled the eligibility criteria were included in the study. A structured interviewer-administered questionnaire with a document review was used to collect data. The data were entered into Epi Info version 7.2.1 and analyzed using SPSS version 21. Descriptive statistics were computed. Simple logistic analysis was run (at 95% CI and p-value < 0.05) to identify factors associated with treatment outcome. RESULT:210 eligible patients with epilepsy were recruited for the study. About half of the respondents were females and the majority was within the age group of 5-10 years. Phenobarbital has been the most frequently prescribed drugs and thirteen percent of patients were in the escalation phase of treatment. Eight percent of the study participants had poor adherence to the treatment regimen. About six percent of the study subjects were suffering from an uncontrolled seizure. Being a female child (AOR = 2. 21; 95%CI: 1.11, 4.41) and excellent adherence to anti-epilepsy treatment (AOR = 4. 51; 95%CI: 1.53, 13.42) were significantly associated with treatment outcome. CONCLUSION:This study revealed that many children were suffering from uncontrolled seizure and escalation therapy is being exercised. Being a female child and adherence to anti-epilepsy treatment were significantly associated with treatment outcome. Therefore, attention should be given to adherence counseling to convey a better treatment outcome.

Introduction: The purpose of this review is to examine African Ebola outbreaks from their first discovery to the present, to determine how the medical and public health response has changed and identify the causes for those changes. We sought to describe what is now known about the epidemiology and spread of Ebola virus disease (EVD) from the significant outbreaks that have occurred and outbreak control methods applied under often challenging circumstances. Given the substantial role that the U.S. Government and the U.S. DoD have played in the 2014 to 2016 West African Ebola outbreak, the role of the DoD and the U.S. Africa Command in controlling EVD is described., Materials and Methods: A descriptive method design was used to collect and analyze all available Ebola outbreak literature using the PubMed database. An initial literature search was conducted by searching for, obtaining, and reading original source articles on all major global Ebola outbreaks. To conduct a focused search, we used initial search terms "Ebola outbreak," "Ebola virus disease," "Ebola response," "Ebola countermeasures," and also included each country's name where Ebola cases are known to have occurred. From the 4,673 unique articles obtained from this search and subsequent article title review, 307 articles were identified for potential inclusion. Following abstract and article review, 45 original source articles were used to compile the history of significant Ebola outbreaks. From this compilation, articles focused on each respective subsection of this review to delineate and describe the history of EVD and response, identifying fundamental changes, were obtained and incorporated., Results: We present known Ebola virus and disease attributes, including a general description, seasonality and location, transmission capacity, clinical symptoms, surveillance, virology, historical EVD outbreaks and response, international support for Ebola outbreak response, U.S. DoD support, medical countermeasures supporting outbreak response, remaining gaps to include policy limitations, regional instability, climate change, migration, and urbanization, public health education and infrastructure, and virus persistence and public awareness., Conclusions: The health and societal impacts of EVD on Africa has been far-reaching, with about 35,000 cases and over 15,000 deaths, with small numbers of cases spreading globally. However, the history of combatting EVD reveals that there is considerable hope for African nations to quickly and successfully respond to Ebola outbreaks, through use of endemic resources including Africa CDC and African Partner Outbreak Response Alliance and the U.S. Africa Command with greater DoD reachback. Although there remains much to be learned about the Ebola virus and EVD including whether the potential for novel strains to become deadly emerging infections, invaluable vaccines, antivirals, and public health measures are now part of the resources that can be used to combat this disease., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Cholera remains a significant public health threat for many countries, and the severity largely varies by the population and local conditions that drive disease spread, especially in endemic areas prone to natural disasters and flooding. Epidemiological models can provide useful information to military planners for understanding disease spread within populations and the effectiveness of response options for preventing the transmission among deployed and stationed personnel. This study demonstrates the use of epidemiological modeling to understand the dynamics of cholera transmission to inform emergency planning and military preparedness in areas with highly communicable diseases., Materials and Methods: Areas with higher probability for a potential cholera outbreak in Haiti followed by a natural disaster were identified. The hotspots were then used to seed an extended compartmental model, EpiGrid, to simulate notional spread scenarios of cholera originating in three distinct areas in Haiti. Disease parameters were derived from the 2010 cholera outbreak in Haiti, and disease spread was simulated over a 12-week period under uncontrolled and controlled spread., Results: For each model location, scenarios of mitigated (intervention with 30% transmission reduction via international aid) and unmitigated (without intervention) are simulated. The results depict the geographical spread and estimate the cumulative cholera infection for each notional scenario over the course of 3 months. Disease transmission differs considerably across origin site with an outbreak originating in the department of Nippes spanning the largest geographic area and resulting in the largest number of cumulative cases after 12 weeks under unmitigated (79,518 cases) and mitigated (35,667 cases) spread scenarios., Conclusions: We modeled the notional re-emergence and spread of cholera following the August 2021 earthquake in Haiti while in the midst of the global COVID-19 pandemic. This information can help guide military and emergency response decision-making during an infectious disease outbreak and considerations for protecting military personnel in the midst of a humanitarian response. Military planners should consider the use of epidemiological models to assess the health risk posed to deployed and stationed personnel in high-risk areas., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, military commanders have been challenged with providing appropriate travel guidance for their military and civilian personnel and dependents. This guidance, where promulgated, lacks uniformity. Travel aids and computer applications similarly differ and are not updated as often as jurisdictional travel health guidance is changed. Given the ever-evolving Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants with differing degrees of infectivity, COVID-19 travel guidance will remain relevant for military travelers during the transition from pandemic to endemic phases and for the foreseeable future., Materials and Methods: We reviewed all germane travel guidance promulgated by the U.S, Department of Defense; the U.S. Centers for Disease Control and Prevention; and other federal, state, and international agencies. From these materials, we identified and delineated applicable universal components for COVID-19 travel risk and created a universal Travel Risk Assessment Questionnaire (TRAQ)., Results: We present a universal TRAQ that identifies and allows for a graded most-appropriate response to known travel risk assessment factors including travel restrictions, travel mode, travel time, travel party size, trip duration, COVID-19 incidence rate at travel destination, lodging, planned activities, personal interaction level, vaccination coverage at destination, travel location, traveler's vaccination status, previous COVID-19 infection, mask wear compliance, mask type, and work environment, along with additional considerations and post-travel COVID-19 questions. We provide examples of the use of this questionnaire that describe low, medium, and high risk to the traveler for contracting COVID-19., Conclusion: Our TRAQ provides an easy-to-use format that can enable military, business, or personal travelers to more completely assess their likelihood of COVID-19 exposure and help them to reduce their potential for contracting COVID-19 during travel and subsequently transmitting it to others upon return. It should help commanders and traveling personnel to better assess COVID-19 travel risks through application of known travel risk factors., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The Ebola virus (EBOV) transcriptional regulation involves host protein phosphatases PP1 and PP2A, which dephosphorylate the transcriptional cofactor of EBOV polymerase VP30. The 1E7-03 compound, which targets PP1, induces VP30 phosphorylation and inhibits EBOV infection. This study aimed to investigate the role of PP1 in EBOV replication. When EBOV-infected cells were continuously treated with 1E7-03, the NP E619K mutation was selected. This mutation moderately reduced EBOV minigenome transcription, which was restored by the treatment with 1E7-03. Formation of EBOV capsids, when NP was co-expressed with VP24 and VP35, was impaired with NPE 619K. Treatment with 1E7-03 restored capsid formation by NP E619K mutation, but inhibited capsids formed by WT NP. The dimerization of NP E619K, tested in a split NanoBiT assay, was significantly decreased (~ 15-fold) compared to WT NP. NP E619K bound more efficiently to PP1 (~ 3-fold) but not B56 subunit of PP2A or VP30. Cross-linking and co-immunoprecipitation experiments showed fewer monomers and dimers for NP E619K which were increased with 1E7-03 treatment. NP E619K showed increased co-localization with PP1α compared to WT NP. Mutations of potential PP1 binding sites and NP deletions disrupted its interaction with PP1. Collectively, our findings suggest that PP1 binding to the NP regulates NP dimerization and capsid formation, and that NP E619K mutation, which has the enhanced PP1 binding, disrupts these processes. Our results point to a new role for PP1 in EBOV replication in which NP binding to PP1 may facilitate viral transcription by delaying capsid formation and EBOV replication., Competing Interests: Competing Interests Authors declare no competing interests.

Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic, and Reston (RESTV) is not known to cause a disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously, we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with a reduced inhibition in IFN-I signaling. We hypothesized that modification of eVP24-karyopherin alpha interface to make it similar to bVP24 would attenuate the ability to antagonize IFN-I response. We generated a panel of recombinant EBOVs containing single or combinations of point mutations in the eVP24-karyopherin alpha interface. Most of the viruses appeared to be attenuated in both IFN-I-competent 769-P and IFN-I-deficient Vero-E6 cells in the presence of IFNs. However, the R140A mutant grew at reduced levels even in the absence of IFNs in both cell lines, as well as in U3A STAT1 knockout cells. Both the R140A mutation and its combination with the N135A mutation greatly reduced the amounts of viral genomic RNA and mRNA suggesting that these mutations attenuate the virus in an IFN-I-independent attenuation. Additionally, we found that unlike eVP24, bVP24 does not inhibit interferon lambda 1 (IFN-λ1), interferon beta (IFN-β), and ISG15, which potentially explains the lower pathogenicity of BDBV relative to EBOV. Thus, the VP24 residues binding karyopherin alpha attenuates the virus by IFN-I-dependent and independent mechanisms.

Ethiopia introduced the measles second dose vaccine from the routine expanded immunization program in 2018. Shreds of evidence are scarce on the measles second dose vaccination coverage and its associated factors in Ethiopia. We aimed to assess the measles second dose vaccination coverage and associated factors in Ethiopia using the recent Ethiopian Mini Demographic and Health Survey (EMDHS) 2019 data. An in-depth secondary data analysis was conducted based on the Ethiopian mini demographic and health survey 2019 data; which was a cross-sectional survey targeted on key indicators of maternal and child health. A weighted sample of 965 children was included in the analysis. A multi-level mixed effect logistics regression model was fitted. Adjusted Odds Ratio (AOR) with 95 %CI was reported for statistically significant variables. The measles second dose coverage was 12.36 % (95 %CI = 10.89, 15.44). Not vaccinated for the third dose of pentavalent vaccine (Penta 3) (AOR = 0.60, 95 %CI: 0.37, 0.95), age of the child [13 to 23 months (AOR = 2.14, 95 %CI: 1.05, 4.36), 24 to 36 months (AOR = 2.58, 95 %CI: 1.32, 5.05)], household head educational status [no education (AOR = 0.51,95 %CI: 0.26, 0.99), primary (AOR = 0.44, 95 %CI: 0.23, 0.85)], and living in south nation, nationalities and peoples region (SNNPR) (AOR = 2.83,95 %CI: 1.12, 7.11) were significantly associated with measles second dose vaccination coverage. Measles second dose vaccination coverage was low in Ethiopia. Age of the child, being vaccinated for the Penta 3, educational status of the household head, and region of residence were significant determinants of measles second dose vaccination coverage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Ethiopia is one of the countries in sub-Saharan Africa with the highest rates of severe acute malnutrition. Early recovery is a performance indicator for severe acute malnourished children for the therapeutic feeding. Despite the available interventions to tackle nutritional problems, there is scarce information on time to recovery and its determinants among children with SAM in Ethiopia., Objective: The study is aimed at assessing time to recovery from severe acute malnutrition and its predictors among admitted children aged 6-59 months at the therapeutic feeding center of Pawi General Hospital, northwest Ethiopia, from January 2013 to December 2017., Methods: An institution-based retrospective follow-up study was conducted among 398 children aged 6-59 months. The data were collected by using data extraction sheet. The data were cleaned and entered using EpiData version 4.2.0.0 and exported to Stata version 14 statistical software for further analysis. Kaplan-Meier survival curve was used to estimate median nutritional recovery time after initiation of inpatient treatment, and log-rank test was used to compare time to recovery between groups. The Cox proportional regression model was used to identify the predictors of recovery time. Adjusted hazard rate with its 95% CI was reported to show strength of relationship., Results: The recovery rate was 5.3 per 100 person-day observations, and the median recovery time was 14 days (95% CI: 13-15). The lower chance of early recovery was found among children who were not fully vaccinated (AHR: 0.73 (95% CI: 0.56, 0.96)), while high chance of recovery was found among children who had no anemia (AHR: 1.66 (95% CI: 1.23, 2.23)), TB (AHR: 2.03 (95% CI: 1.11, 3.71)), and malaria infection (AHR: 1.54 (95% CI: 1.09, 2.17)) at admission. Conclusion and Recommendation . The overall nutritional recovery rate was below the accepted minimum standard. Children not fully vaccinated and children without malaria, anemia, and TB comorbidities at admission had a higher chance of recovering early from severe acute malnutrition. Hence, treating comorbidities is vital for prompt nutritional recovery., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Amare Wondim et al.)

Background: Fluid and antimicrobial therapy are the essential parts of sepsis management. The type of fluid to resuscitate with is an unsettled issue in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate the cost-effectiveness of albumin-based resuscitation over crystalloids., Methods: A cost-effectiveness analysis was conducted by extracting data from a database of Sina Hospital, Islamic Republic of Iran. A decision tree was constructed by using Tree Age Pro 2011. The patients were grouped based on the types of fluids used for resuscitation into crystalloid alone or crystalloid + albumin groups at the initial decision node. The patients were followed from the onset of severe sepsis and septic shock upto 28 days. The healthcare payers' perspective was considered in constructing the model. The cost was measured in US dollars and the effectiveness was measured by life years gained., Results: The addition of albumin during resuscitation of patients with severe sepsis and septic shock has an effectiveness gain of 0.09 life years and cost increment of 495.00 USD. The estimated ICER for this analysis was 5500.00 USD per life year gained. The probability that albumin is cost-effective at one GDP per capita is 49.5%., Conclusion: Albumin-based resuscitation is not cost-effective in Iran when a GDP per capita was considered for a life year gain. The cost-effectiveness was insensitive to the cost of standard care. We recomend the caustious use albumin as per the Surviving Sepsis Campaign guideline.

The filoviruses Marburg virus (MARV) and Ebola virus (EBOV) cause hemorrhagic fever in humans and nonhuman primates, with high case fatality rates. MARV VP30 is known to be phosphorylated and to interact with nucleoprotein (NP), but its role in regulation of viral transcription is disputed. Here, we analyzed phosphorylation of VP30 by mass spectrometry, which resulted in identification of multiple phosphorylated amino acids. Modeling the full-length three-dimensional structure of VP30 and mapping the identified phosphorylation sites showed that all sites lie in disordered regions, mostly in the N-terminal domain of the protein. Minigenome analysis of the identified phosphorylation sites demonstrated that phosphorylation of a cluster of amino acids at positions 46 through 53 inhibits transcription. To test the effect of VP30 phosphorylation on its interaction with other MARV proteins, coimmunoprecipitation analyses were performed. They demonstrated the involvement of VP30 phosphorylation in interaction with two other proteins of the MARV ribonucleoprotein complex, NP and VP35. To identify the role of protein phosphatase 1 (PP1) in the identified effects, a small molecule, 1E7-03, targeting a noncatalytic site of the enzyme that previously was shown to increase EBOV VP30 phosphorylation was used. Treatment of cells with 1E7-03 increased phosphorylation of VP30 at a cluster of phosphorylated amino acids from Ser-46 to Thr-53, reduced transcription of MARV minigenome, enhanced binding to NP and VP35, and dramatically reduced replication of infectious MARV particles. Thus, MARV VP30 phosphorylation can be targeted for development of future antivirals such as PP1-targeting compounds. IMPORTANCE The largest outbreak of MARV occurred in Angola in 2004 to 2005 and had a 90% case fatality rate. There are no approved treatments available for MARV. Development of antivirals as therapeutics requires a fundamental understanding of the viral life cycle. Because of the close similarity of MARV to another member of Filoviridae family, EBOV, it was assumed that the two viruses have similar mechanisms of regulation of transcription and replication. Here, characterization of the role of VP30 and its phosphorylation sites in transcription of the MARV genome demonstrated differences from those of EBOV. The identified phosphorylation sites appeared to inhibit transcription and appeared to be involved in interaction with both NP and VP35 ribonucleoproteins. A small molecule targeting PP1 inhibited transcription of the MARV genome, effectively suppressing replication of the viral particles. These data demonstrate the possibility developing antivirals based on compounds targeting PP1., (Copyright © 2018 American Society for Microbiology.)

Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication. IMPORTANCE Ebola virus and other emerging RNA viruses are significant but unpredictable public health threats. Therapeutic approaches with broad-spectrum activity could provide an attractive response to such infections. We describe a novel assay that can identify small molecules that overcome Ebola virus-encoded innate immune evasion mechanisms. This assay identified as hits cancer chemotherapeutic drugs, including doxorubicin. Follow-up studies provide new insight into how doxorubicin induces interferon (IFN) responses, revealing activation of both the DNA damage response kinase ATM and the DNA sensor cGAS and its partner signaling protein STING. The studies further demonstrate that the ATM and cGAS-STING pathways of IFN induction are a point of vulnerability not only for Ebola virus but for other RNA viruses as well, because viral innate immune antagonists consistently fail to block these signals. These studies thereby define a novel avenue for therapeutic intervention against emerging RNA viruses., (Copyright © 2017 Luthra et al.)

Background: Visceral leishmaniasis (VL) is a protozoan disease that is invariably fatal if left untreated. The disease is found in 70 countries with incidence of 0.2 - 0.4 million cases. The mainstay of treatment in resource limited countries like Ethiopia is antimonials, while use of liposomal amphotericin B is reserved for treatment of complicated VL cases. The aim of this study was to assess the safety and efficacy of liposomal amphotericin B in HIV negative VL patients diagnosed with complications., Methods: A retrospective chart review was conducted involving records of patients admitted between January 2009 and December 2014. Baseline sociodemographic, clinical, and treatment outcome data were collected. The doses of liposomal amphotericin B and adverse events related to treatment were retrieved. Categorical and continuous variables respectively were analyzed by Chi-square and Mann-Whitney U tests. A p-value of less than 0.05 was considered statistically significant., Results: A total of 147 patients with severe VL were treated with liposomal amphotericin B in total dose ranges of 20 mg/kg to 35 mg/kg. In the overall treatment outcome analysis, initial cure (30 days after start of treatment) was observed in 128 (87.1 %), treatment failures in 10 (6.8 %), interruptions in 2(1.4 %) and deaths in 7 (4.8 %) patients. Initial cure rate at high dose (24-35 mg/kg total dose) was 96.7 % (59/61) versus 80.2 % (69/86) at lower doses (<24 mg/kg); which was significantly higher (P < 0.01), OR = 4.56: 95 %, Confidence Interval (CI) = 1.17 - 20.78). Ten cases (11.8 %) of treatment failure occurred in the low dose treatment group. The most common adverse events (AEs) were hypokalemia in 39 cases (26.5 %) and infusion related reactions in 16 (10.9 %). The frequency of hypokalemia and infusion related reactions were not significantly different between the low and high dose liposomal amphotericin B., Conclusion: In HIV negative complicated VL patients, high dose of liposomal amphotericin B was found to have high cure rate at the end of treatment. The appropriate dose for better efficacy needs to be determined. Monitoring serum potassium level during treatment with liposomal amphotericin B should be an essential component of the clinical management of VL.

High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels. Adapting the HTS drug discovery process to biocontainment laboratories to develop new drugs for these previously uncharacterized and highly pathogenic agents is now feasible, but HTS at higher biosafety levels (BSL) presents a number of unique challenges. HTS has been conducted with multiple bacterial and viral pathogens at both BSL-2 and BSL-3, and pilot screens have recently been extended to BSL-4 environments for both Nipah and Ebola viruses. These recent successful efforts demonstrate that HTS can be safely conducted at the highest levels of biological containment. This review outlines the specific issues that must be considered in the execution of an HTS drug discovery program for high-containment pathogens. We present an overview of the requirements for HTS in high-level biocontainment laboratories.

The filovirus Ebola (EBOV) causes the most severe hemorrhagic fever known. The EBOV RNA-dependent polymerase complex includes a filovirus-specific VP30, which is critical for the transcriptional but not replication activity of EBOV polymerase; to support transcription, VP30 must be in a dephosphorylated form. Here we show that EBOV VP30 is phosphorylated not only at the N-terminal serine clusters identified previously but also at the threonine residues at positions 143 and 146. We also show that host cell protein phosphatase 1 (PP1) controls VP30 dephosphorylation because expression of a PP1-binding peptide cdNIPP1 increased VP30 phosphorylation. Moreover, targeting PP1 mRNA by shRNA resulted in the overexpression of SIPP1, a cytoplasm-shuttling regulatory subunit of PP1, and increased EBOV transcription, suggesting that cytoplasmic accumulation of PP1 induces EBOV transcription. Furthermore, we developed a small molecule compound, 1E7-03, that targeted a non-catalytic site of PP1 and increased VP30 dephosphorylation. The compound inhibited the transcription but increased replication of the viral genome and completely suppressed replication of EBOV in cultured cells. Finally, mutations of Thr(143) and Thr(146) of VP30 significantly inhibited EBOV transcription and strongly induced VP30 phosphorylation in the N-terminal Ser residues 29-46, suggesting a novel mechanism of regulation of VP30 phosphorylation. Our findings suggest that targeting PP1 with small molecules is a feasible approach to achieve dysregulation of the EBOV polymerase activity. This novel approach may be used for the development of antivirals against EBOV and other filovirus species., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and gamma interferon receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.

Background: Junín virus (JUNV), the etiologic agent of Argentine hemorrhagic fever (AHF), is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir) is a broadly active small molecule RNA-dependent RNA polymerase inhibitor presently in clinical evaluation for the treatment of influenza. We have previously reported on the in vitro activity of favipiravir against several strains of JUNV and other pathogenic New World arenaviruses., Methodology/principal Findings: To evaluate the efficacy of favipiravir in vivo, guinea pigs were challenged with the pathogenic Romero strain of JUNV, and then treated twice daily for two weeks with oral or intraperitoneal (i.p.) favipiravir (300 mg/kg/day) starting 1-2 days post-infection. Although only 20% of animals treated orally with favipiravir survived the lethal challenge dose, those that succumbed survived considerably longer than guinea pigs treated with placebo. Consistent with pharmacokinetic analysis that showed greater plasma levels of favipiravir in animals dosed by i.p. injection, i.p. treatment resulted in a substantially higher level of protection (78% survival). Survival in guinea pigs treated with ribavirin was in the range of 33-40%. Favipiravir treatment resulted in undetectable levels of serum and tissue viral titers and prevented the prominent thrombocytopenia and leucopenia observed in placebo-treated animals during the acute phase of infection., Conclusions/significance: The remarkable protection afforded by i.p. favipiravir intervention beginning 2 days after challenge is the highest ever reported for a small molecule antiviral in the difficult to treat guinea pig JUNV challenge model. These findings support the continued development of favipiravir as a promising antiviral against JUNV and other related arenaviruses.

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

Ebola virus (EBOV) infections are characterized by deficient T lymphocyte responses, T lymphocyte apoptosis, and lymphopenia in the absence of direct infection of T lymphocytes. In contrast, dendritic cells (DC) are infected but fail to mature appropriately, thereby impairing the T cell response. We investigated the contributions of EBOV proteins in modulating DC maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains. They included envelope glycoprotein (GP) domains, as well as innate response antagonist domains (IRADs) previously identified in the VP24 and VP35 proteins. GP expressed by an unrelated vector, but not the wild-type EBOV, was found to strongly induce DC maturation, and infections with recombinant EBOV carrying mutations disabling GP functional domains did not restore DC maturation. In contrast, each of the viruses carrying mutations disabling any IRAD in VP35 induced a dramatic upregulation of DC maturation markers. This was dependent on infection, but not interaction with GP. Disabling of IRADs also resulted in up to a several hundredfold increase in secretion of cytokines and chemokines. Furthermore, these mutations induced formation of homotypic DC clusters, which represent close correlates of their maturation and presumably facilitate transfer of antigen from migratory DC to lymph node DC. Thus, an individual IRAD is insufficient to suppress DC maturation; rather, the suppression of DC maturation and the "immune paralysis" observed during EBOV infections results from a cooperative effect of two or more individual IRADs.

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.

Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) are tick-borne flaviviruses that have close homology but different pathology and disease outcomes. Previously, we reported that C57BL/6 and BALB/c mice were excellent models to study the pathology and clinical signs of human RSSEV and OHFV infection. In the study described here, we found that RSSEV infection induced robust release of proinflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and chemokines (MCP-1, MIP-1β, RANTES and KC) in the brain at 9 and 11dpi, together with moderate to low Th1 and Th2 cytokines. In contrast, OHFV infection stimulated an early and prominent induction of IL-1α, TNF-α, IL-12p70, MCP-1, MIP-1α and MIP-1β in the spleen of infected mice. Collectively our data suggest that a differential host response to infection may lead to the alternate disease outcomes seen following OHFV or RSSEV infection., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the feasibility of using clinical parameters to demonstrate disease progression and differentiate between Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) infection in the mouse model. Adult C57BL/6 and balb/c mice were infected with either OHFV or RSSEV by footpad inoculation and their temperature, body weight, clinical signs complete blood count, and blood chemistries were evaluated for up to 15 days post-infection (dpi). Clinical evaluation showed that OHFV infection seriously affects balb/c mice, which had shorter average survival times (ASTs) than other groups. On the contrary, RSSEV infection of C57BL/6 mice was more severe than in balb/c mice. During these studies, the development of fever was not observed and the body weight of OHFV infected balb/c and C57BL/6 mice began to decline sharply starting from day 7 and 8, respectively, which correlated with disease onset. Peak increase of globulin and neutrophils was demonstrated after 9 dpi in OHFV infected mice; however, the lymphocyte number was not affected. Viremia was undetectable in these animals with either virus infection, but virus was found in most organs tested. These results indicate marked differences in the clinical signs, pathology, and immune response of mice infected with either OHFV or RSSEV and further validate the use of this mouse model system to evaluate human disease., (Copyright 2009 Wiley-Liss, Inc.)