Outbreak Of Hemorrhagic Fever Research Articles

Analysis of climatic variability and dengue hemorrhagic fever incidence at the Tsunami Area Banda Aceh City

The rebuilding of post-tsunami community residential an area in Banda Aceh City has created a new ecosystem and at the same time a public health problem. The construction of new settlements has an impact on the emergence of Aedes aegypti habitat. The post-tsunami climate factor is thought to be one of the factors that cause outbreaks of dengue hemorrhagic fever (DHF) cases every year in Banda Aceh City. This study aims to analyze the relationship between climatic variability with the DHF incidence cases from 2010-2020 at the tsunami area Banda Aceh City. The study uses monthly DHF case data obtained from the Banda Aceh City Health Office. Monthly climate data were obtained from the Meteorology, Climatology, and Geophysics Agency of Aceh Province. Spearman’s correlation analysis shows that temperature, humidity, rainfall, and wind velocity have a significant relationship with the DHF incidence cases. Humidity and rainfall are positively correlated with DHF incidence, while temperature and wind velocity shows a negative correlation with DHF incidence. This study shows that climate is one of the factors influential in the DHF incidence cases at the tsunami area Banda Aceh City.

Filovirus Neutralising Antibodies: Mechanisms of Action and Therapeutic Application.

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013–2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics.

Crimean-Congo hemorrhagic fever outbreak in Turkey amid the coronavirus disease 2019 (COVID-19) pandemic; a debacle for the healthcare system of Turkey.

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Evaluation by simulation of clinical trial designs for evaluation of treatment during a viral haemorrhagic fever outbreak

Viral haemorrhagic fevers are characterized by irregular outbreaks with high mortality rate. Difficulties arise when implementing therapeutic trials in this context. The outbreak duration is hard to predict and can be short compared to delays of trial launch and number of subject needed (NSN) recruitment. Our objectives were to compare, using clinical trial simulation, different trial designs for experimental treatment evaluation in various outbreak scenarios. Four type of designs were compared: fixed or group-sequential, each being single- or two-arm. The primary outcome was 14-day survival rate. For single-arm designs, results were compared to a pre-trial historical survival rate pH. Treatments efficacy was evaluated by one-sided tests of proportion (fixed designs) and Whitehead triangular tests (group-sequential designs) with type-I-error = 0.025. Both survival rates in the control arm pC and survival rate differences Δ (including 0) varied. Three specific cases were considered: “standard” (fixed pC, reaching NSN for fixed designs and maximum sample size NMax for group-sequential designs); “changing with time” (increased pC over time); “stopping of recruitment” (epidemic ends). We calculated the proportion of simulated trials showing treatment efficacy, with K = 93,639 simulated trials to get a type-I-error PI95% of [0.024; 0.026]. Under H0 (Δ=0), for the “standard” case, the type-I-error was maintained regardless of trial designs. For “changing with time” case, when pC > pH, type-I-error was inflated, and when pC < pH it decreased. Wrong conclusions were more often observed for single-arm designs due to an increase of Δ over time. Under H1 (Δ=+0.2), for the “standard” case, the power was similar between single- and two-arm designs when pC = pH. For “stopping of recruitment” case, single-arm performed better than two-arm designs, and fixed designs reported higher power than group-sequential designs. A web R-Shiny dashboard was developed: https://pmn-bch.shinyapps.io/simu-vhf/. At an outbreak beginning, group-sequential two-arm trials should be preferred, as the infected cases number increases allowing to conduct a strong randomized control trial. Group-sequential designs allow early termination of trials in cases of harmful experimental treatment. After the epidemic peak, fixed single-arm design should be preferred, as the cases number decreases but this assumes a high level of confidence on the pre-trial historical survival rate.

Evaluation by simulation of clinical trial designs for evaluation of treatment during a viral haemorrhagic fever outbreak

BackgroundViral haemorrhagic fevers are characterized by irregular outbreaks with high mortality rate. Difficulties arise when implementing therapeutic trials in this context. The outbreak duration is hard to predict and can be short compared to delays of trial launch and number of subject needed (NSN) recruitment. Our objectives were to compare, using clinical trial simulation, different trial designs for experimental treatment evaluation in various outbreak scenarios.MethodsFour type of designs were compared: fixed or group-sequential, each being single- or two-arm. The primary outcome was 14-day survival rate. For single-arm designs, results were compared to a pre-trial historical survival rate pH. Treatments efficacy was evaluated by one-sided tests of proportion (fixed designs) and Whitehead triangular tests (group-sequential designs) with type-I-error = 0.025. Both survival rates in the control arm pC and survival rate differences Δ (including 0) varied. Three specific cases were considered: “standard” (fixed pC, reaching NSN for fixed designs and maximum sample size NMax for group-sequential designs); “changing with time” (increased pC over time); “stopping of recruitment” (epidemic ends). We calculated the proportion of simulated trials showing treatment efficacy, with K = 93,639 simulated trials to get a type-I-error PI95% of [0.024;0.026].ResultsUnder H0 (Δ = 0), for the “standard” case, the type-I-error was maintained regardless of trial designs. For “changing with time” case, when pC > pH, type-I-error was inflated, and when pC < pH it decreased. Wrong conclusions were more often observed for single-arm designs due to an increase of Δ over time. Under H1 (Δ = + 0.2), for the “standard” case, the power was similar between single- and two-arm designs when pC = pH. For “stopping of recruitment” case, single-arm performed better than two-arm designs, and fixed designs reported higher power than group-sequential designs. A web R-Shiny application was developed.ConclusionsAt an outbreak beginning, group-sequential two-arm trials should be preferred, as the infected cases number increases allowing to conduct a strong randomized control trial. Group-sequential designs allow early termination of trials in cases of harmful experimental treatment. After the epidemic peak, fixed single-arm design should be preferred, as the cases number decreases but this assumes a high level of confidence on the pre-trial historical survival rate.

Temporal and spatial characteristics of the dengue hemorrhagic fever outbreak in Hanoi in 2017

Dengue hemorrhagic fever/dengue fever is a mosquito-borne viral disease that has re-emerged in recent years. In 2017, the largest recorded outbreak of dengue appeared in Hanoi, Vietnam, with over 37,000 cases and seven deaths. This study aimed to describe the temporal and spatial characteristics of the dengue hemorrhagic fever outbreak in Hanoi in 2017. We used heat maps, hotspot and cold spot, and cluster analysis to describe and analyze the development of the outbreak of dengue hemorrhagic fever in all 30 districts of the city of Hanoi. The results show that in 2017, Hanoi experienced the most serious dengue outbreak since 1992 with 37,665 cases recorded including seven deaths (CFR: 0.02%), or 492 cases per 100,000 persons, which makes dengue a serious public health threat in Hanoi. The outbreak not only produced a very large number of cases, but also expanded by space, with 25 districts having an incidence greater than 100 cases per 100,000 persons. The highest incidences were still concentrated in the urban and suburban areas. Dengue hemorrhagic fever is currently a serious public health issue in Hanoi, which needs attention especially for prevention.

Ultrasensitive point-of-care immunoassay for secreted glycoprotein detects Ebola infection earlier than PCR.

Ebola virus (EBOV) hemorrhagic fever outbreaks have been challenging to deter due to the lack of health care infrastructure in disease-endemic countries and a corresponding inability to diagnose and contain the disease at an early stage. EBOV vaccines and therapies have improved disease outcomes, but the advent of an affordable, easily accessed, mass-produced rapid diagnostic test (RDT) that matches the performance of more resource-intensive polymerase chain reaction (PCR) assays would be invaluable in containing future outbreaks. Here, we developed and demonstrated the performance of a new ultrasensitive point-of-care immunoassay, the EBOV D4 assay, which targets the secreted glycoprotein of EBOV. The EBOV D4 assay is 1000-fold more sensitive than the U.S. Food and Drug Administration-approved RDTs and detected EBOV infection earlier than PCR in a standard nonhuman primate model. The EBOV D4 assay is suitable for low-resource settings and may facilitate earlier detection, containment, and treatment during outbreaks of the disease.

The Early Vigilance of Dengue Hemorrhagic Fever Outbreak in the Community

Early Awareness of Extraordinary Events of Dengue Hemorrhagic Fever (DHF) was asked to community (n= 130). Precautions were measured based on community knowledge, attitudes, and behavior. Knowledge, attitude, and behavior are constructs (in the form of a composite variable) from an early awareness of DHF outbreak. The result showed that the knowledge related to the transmission factor and the proliferation of dengue disease was quite good (72.3%). The DHF risk control was also good (93.9%) while the dengue fever eradication was still poor (67.7%). However, the attitude showed that it is still not ready to act on the basis of consciousness. Meanwhile, the results of the data analysis identified that the model of the early awareness measurement on DHF outbreak which consisted of construct variables (knowledge, attitude, and action) were a perfect fit. Based on the measurement model, the level of community awareness on DHF disease can be measured. This showed that the level of early awareness of DHF disease was good 76.2% and only 3.8% were less alert. This means although the less alert percentage is quite small, if people have an attitude of indifference to the prevention of DHF then the impact will affect a wider community.

Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda, July 2018-January 2019.

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda's 'cattle corridor', no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks. We defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018-30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4). We identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda's 'cattle corridor'. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6-36 years, with persons aged 20-44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (ORM-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (ORM-H = 9.3, 95%CI = 1.9-46). CCHF outbreaks occurred sporadically during 2018-2019, both within and outside 'cattle corridor' districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.

Effect of Favipiravir on some epidemic infections: A mini review

Favipiravir is a modern antiviral drug that can be used in developing viral pandemics, such as the Ebola virus, H1N1 flu, Lassa fever, and haemorrhagic fever outbreaks in Argentina in 2009. A. Chain conclusion Favipiravir is transformed to favipiravir-RTP and inserted into the RNA strand that is elongating. Then, since favipiravir acts as a chain terminator, chain elongation slows down at incorporation site of favipiravir and does not continue. The proofreading enzyme cannot repair this complex of RNA-favipiravir and it will be discarded as excessive RNA, which causes the extinction of the viral genome. Mutagenesis with lethal consequences Ribavirin is used in the RNA elongating process until completion. The single strand of RNA with several ribavirin incorporation sites incorporates ribavirin or acts as mRNA for the production of viral proteins. Due to incorporation of ribavirin onto viral RNA, a mismatching of the base pairs (transition mutation) will occur. Translation of this mutated RNA will then cause mutations in the sequence of amino acid residues of the protein, result in impaired of protein function. Viral proteins that have lost their function are unable to replicate or generate infectious viral particles, and the virus is no longer infectious. As a result, lethal mutagenesis ends viral infection in a different way than chain termination. Favipiravir’s clinical trial against Ebola virus-infected patients has not yet been formally approved, and further research is required. Favipiravir, on the other hand, poses a risk of embryo toxicity and teratogenicity. As a result, the Japanese Ministry of Health, Welfare and Labor have been approved this medication with recommendations for more clinical use until August 15, 2014, when they approved the use of favipiravir due to the Ebola virus epidemic in West Africa. The aim of this review is to investigate the potential impact of favipiravir on infections espectially RNA-virus infections, according to previous published investigations, and thus to encourage rapid approval of this interesting antivirus in emergencies.

New circulation of genotype V of Crimean-Congo haemorrhagic fever virus in humans from Spain.

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral disease caused by the Crimean-Congo haemorrhagic fever virus (CCHFV). CCHFV has been implicated in severe viral haemorrhagic fever outbreaks. During the summer of 2016, the first two cases with genotype III (Africa 3) were reported in Spain. The first objective of our study was to determine the presence of CCHFV among patients with febrile illness during the spring and summer periods in 2017 and 2018. Finally, we perform a phylogenetic analysis to determine the genotype of the virus. We prospectively evaluated patients aged 18 years and older who came to the emergency department at the Salamanca's University Hospital (HUS) with fever. Specific IgM and IgG antibodies against CCHFV by ELISA and one immunofluorescence assay against two different proteins (nucleoprotein and glycoprotein C) was done. Moreover, molecular detection by Real Time PCR was performed in all collected samples. A phylogenetic analysis was carried out to genetically characterize CCHFV detected in this study. A total of 133 patients were selected. The mean age was 67.63 years and 60.9% were male. One-third of the patients presented an acute undifferentiated febrile illness. Three patients had anti-CCHFV IgG antibodies, suggesting a previous infection. One patient had anti-CCHFV IgM antibodies and a confirmatory RT-PCR. Phylogenetic analysis indicated that the virus corresponds to the European genotype V. This patient came to the emergency department at HUS in August 2018 presenting an acute febrile syndrome with thrombopenia and liver impairment. We describe a new circulation of European genotype V CCHFV in Spain. Moreover, this study suggests that CCHFV is an identifiable cause of febrile illness of unknown origin in Spain. Thus, CCHF could be suspected in patients with fever, liver damage, and/or haemorrhagic disorders, particularly in people with risk activities who present in the spring or summer.

Angiomotin Counteracts the Negative Regulatory Effect of Host WWOX on Viral PPxY-Mediated Egress.

Filoviridae family members Ebola (EBOV) and Marburg (MARV) viruses and Arenaviridae family member Lassa virus (LASV) are emerging pathogens that can cause hemorrhagic fever and high rates of mortality in humans. A better understanding of the interplay between these viruses and the host will inform about the biology of these pathogens, and may lead to the identification of new targets for therapeutic development. Notably, expression of the filovirus VP40 and LASV Z matrix proteins alone drives assembly and egress of virus-like particles (VLPs). The conserved PPxY Late (L) domain motifs in the filovirus VP40 and LASV Z proteins play a key role in the budding process by mediating interactions with select host WW-domain containing proteins that then regulate virus egress and spread. To identify the full complement of host WW-domain interactors, we utilized WT and PPxY mutant peptides from EBOV and MARV VP40 and LASV Z proteins to screen an array of GST-WW-domain fusion proteins. We identified WW domain-containing oxidoreductase (WWOX) as a novel PPxY-dependent interactor, and we went on to show that full-length WWOX physically interacts with eVP40, mVP40 and LASV Z to negatively regulate egress of VLPs and of a live VSV/Ebola recombinant virus (M40). Interestingly, WWOX is a versatile host protein that regulates multiple signaling pathways and cellular processes via modular interactions between its WW-domains and PPxY motifs of select interacting partners, including host angiomotin (AMOT). Notably, we demonstrated recently that expression of endogenous AMOT not only positively regulates egress of VLPs, but also promotes egress and spread of live EBOV and MARV. Toward the mechanism of action, we show that the competitive and modular interplay among WWOX-AMOT-VP40/Z regulates VLP and M40 virus egress. Thus, WWOX is the newest member of an emerging group of host WW-domain interactors (e.g. BAG3; YAP/TAZ) that negatively regulate viral egress. These findings further highlight the complex interplay of virus-host PPxY/WW-domain interactions and their potential impact on the biology of both the virus and the host during infection.Author Summary Filoviruses (Ebola [EBOV] and Marburg [MARV]) and arenavirus (Lassa virus; LASV) are zoonotic, emerging pathogens that cause outbreaks of severe hemorrhagic fever in humans. A fundamental understanding of the virus-host interface is critical for understanding the biology of these viruses and for developing future strategies for therapeutic intervention. Here, we identified host WW-domain containing protein WWOX as a novel interactor with VP40 and Z, and showed that WWOX inhibited budding of VP40/Z virus-like particles (VLPs) and live virus in a PPxY/WW-domain dependent manner. Our findings are important to the field as they expand the repertoire of host interactors found to regulate PPxY-mediated budding of RNA viruses, and further highlight the competitive interplay and modular virus-host interactions that impact both the virus lifecycle and the host cell.

Ebola virus triggers receptor tyrosine kinase-dependent signaling to promote the delivery of viral particles to entry-conducive intracellular compartments.

Filoviruses, such as the Ebola virus (EBOV) and Marburg virus (MARV), are causative agents of sporadic outbreaks of hemorrhagic fevers in humans. To infect cells, filoviruses are internalized via macropinocytosis and traffic through the endosomal pathway where host cathepsin-dependent cleavage of the viral glycoproteins occurs. Subsequently, the cleaved viral glycoprotein interacts with the late endosome/lysosome resident host protein, Niemann-Pick C1 (NPC1). This interaction is hypothesized to trigger viral and host membrane fusion, which results in the delivery of the viral genome into the cytoplasm and subsequent initiation of replication. Some studies suggest that EBOV viral particles activate signaling cascades and host-trafficking factors to promote their localization with host factors that are essential for entry. However, the mechanism through which these activating signals are initiated remains unknown. By screening a kinase inhibitor library, we found that receptor tyrosine kinase inhibitors potently block EBOV and MARV GP-dependent viral entry. Inhibitors of epidermal growth factor receptor (EGFR), tyrosine protein kinase Met (c-Met), and the insulin receptor (InsR)/insulin like growth factor 1 receptor (IGF1R) blocked filoviral GP-mediated entry and prevented growth of replicative EBOV in Vero cells. Furthermore, inhibitors of c-Met and InsR/IGF1R also blocked viral entry in macrophages, the primary targets of EBOV infection. Interestingly, while the c-Met and InsR/IGF1R inhibitors interfered with EBOV trafficking to NPC1, virus delivery to the receptor was not impaired in the presence of the EGFR inhibitor. Instead, we observed that the NPC1 positive compartments were phenotypically altered and rendered incompetent to permit viral entry. Despite their different mechanisms of action, all three RTK inhibitors tested inhibited virus-induced Akt activation, providing a possible explanation for how EBOV may activate signaling pathways during entry. In sum, these studies strongly suggest that receptor tyrosine kinases initiate signaling cascades essential for efficient post-internalization entry steps.

Lipid-specific oligomerization of the Marburg virus matrix protein VP40 is regulated by two distinct interfaces for virion assembly

Marburg virus (MARV) is a lipid-enveloped virus harboring a negative-sense RNA genome, which has caused sporadic outbreaks of viral hemorrhagic fever in sub-Saharan Africa. MARV assembles and buds from the host cell plasma membrane where MARV matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane inner leaflet and undergo a dynamic and extensive self-oligomerization into the structural matrix layer. The MARV matrix layer confers the virion filamentous shape and stability but how host lipids modulate mVP40 oligomerization is mostly unknown. Using in vitro and cellular techniques, we present a mVP40 assembly model highlighting two distinct oligomerization interfaces: the (N-terminal domain [NTD] and C-terminal domain [CTD]) in mVP40. Cellular studies of NTD and CTD oligomerization interface mutants demonstrate the importance of each interface in matrix assembly. The assembly steps include protein trafficking to the plasma membrane, homo-multimerization that induced protein enrichment, plasma membrane fluidity changes, and elongations at the plasma membrane. An ascorbate peroxidase derivative (APEX)-transmission electron microscopy method was employed to closely assess the ultrastructural localization and formation of viral particles for wildtype mVP40 and NTD and CTD oligomerization interface mutants. Taken together, these studies present a mechanistic model of mVP40 oligomerization and assembly at the plasma membrane during virion assembly that requires interactions with phosphatidylserine for NTD–NTD interactions and phosphatidylinositol-4,5-bisphosphate for proper CTD–CTD interactions. These findings have broader implications in understanding budding of lipid-enveloped viruses from the host cell plasma membrane and potential strategies to target protein–protein or lipid–protein interactions to inhibit virus budding.

Viral Haemorrhagic Fever Epidemics and Health Workers: Investigating the Level of Preparedness in a Tertiary Hospital in Nigeria

Aim: This study assessed the state of infection prevention and control (IPC) with an emphasis on a hospital’s preparedness for mitigating the spread of viral haemorrhagic fevers (VHFs) to staff.&#x0D; Methods: This convergent parallel mixed-methods study obtained data on IPC using an observational checklist in clinical departments and units; key informant interviews of stakeholders; and a structured self-administered questionnaire with frontline health workers. Both qualitative and quantitative data analyses were conducted to determine the IPC practice and level of preparedness of the hospital for the threat of VHFs.&#x0D; Results: The frontline clinical staff who responded to the questionnaires were aged 31 – 40 years (53.8%), male (50.3%) and medical doctors (72.2%). Some of the respondents had received training in hand washing (41.5%), use of PPE (35.1%) and standard precaution for VHFs (26.8%). Fewer respondents consistently used gloves (36.8%), face masks (8.6%), aprons (8.5%) and sharps containers (26.7%) during patient care. Amenities available for IPC varied across the 184 clinical service points in the hospital’s 19 departments. More service points had waste bins (86%), washing sinks (80%) and running water (74%) while a few had a standard operating procedure for hand washing (6%) and cabinets for storing PPEs (12%). The most significant challenge to the use of IPC measures was the inadequacy of amenities such as full PPE gear, respirator, aprons, and face masks within the clinical service points.&#x0D; Conclusion: There is a poor level of preparedness for outbreaks of VHFs and this calls for strengthening administrative, engineering and environmental control in health facilities to stem outbreaks among health.

Reanalysis of the 2000 Rift Valley fever outbreak in Southwestern Arabia.

The first documented Rift Valley hemorrhagic fever outbreak in the Arabian Peninsula occurred in northwestern Yemen and southwestern Saudi Arabia from August 2000 to September 2001. This Rift Valley fever outbreak is unique because the virus was introduced into Arabia during or after the 1997-1998 East African outbreak and before August 2000, either by wind-blown infected mosquitos or by infected animals, both from East Africa. A wet period from August 2000 into 2001 resulted in a large number of amplification vector mosquitoes, these mosquitos fed on infected animals, and the outbreak occurred. More than 1,500 people were diagnosed with the disease, at least 215 died, and widespread losses of domestic animals were reported. Using a combination of satellite data products, including 2 x 2 m digital elevation images derived from commercial satellite data, we show rainfall and potential areas of inundation or water impoundment were favorable for the 2000 outbreak. However, favorable conditions for subsequent outbreaks were present in 2007 and 2013, and very favorable conditions were also present in 2016-2018. The lack of subsequent Rift Valley fever outbreaks in this area suggests that Rift Valley fever has not been established in mosquito species in Southwest Arabia, or that strict animal import inspection and quarantine procedures, medical and veterinary surveillance, and mosquito control efforts put in place in Saudi Arabia following the 2000 outbreak have been successful. Any area with Rift Valley fever amplification vector mosquitos present is a potential outbreak area unless strict animal import inspection and quarantine proceedures are in place.

Detection and characterization of a novel strain of Chapare virus during an outbreak of viral hemorrhagic fever in Bolivia, 2019

Background: Bolivian hemorrhagic fever is caused by Machupo virus (MACV), which was first isolated and characterized in 1963, and has since caused sporadic outbreaks with notable re-emergence in 2007 in the Beni region. A novel New World arenavirus, Chapare virus (CHAPV), was identified as the etiology for one fatal case of hemorrhagic fever, now known as Chapare hemorrhagic fever (CHHF), in 2004 in Cochabamba. No CHHF cases have been identified since. In June 2019, the Bolivian Epidemiology Services in Caranavi reported three hemorrhagic fever cases of unknown etiology. Specimens from two of the cases tested negative at the Bolivian Center for Tropical Diseases (CENETROP) for MACV, Dengue, and Yellow Fever virus. Because a viral hemorrhagic fever was suspected, human specimens were sent to the Viral Special Pathogens Branch, Centers for Disease Control and Prevention (USA) for further testing and identification in the Biosafety Level-4 (BSL4) lab. Methods and materials: Using a combination of next generation sequencing and virus isolation, we were able to identify and characterize the virus circulating in Caranavi as a strain of Chapare virus. Based on the initial sequencing data, we designed primers and probes to develop specific real-time RT-PCR assays for the S and L segments of the virus. Results: In collaboration with the Pan American Health Organization, we deployed the assays to CENETROP and provided training for specimen processing. We detected CHAPV RNA in a variety of human (blood, serum, tracheal aspirates, urine, semen) and rodent specimens associated with the outbreak. Conclusion: Since Machupo and Chapare viruses are BSL4 agents they require special biosafety precautions and inactivation methods during specimen processing. Molecular techniques are preferred when handling viral hemorrhagic fever specimens in laboratories that do not have BSL4. Our approach of initial characterization in CDC's BSL4 lab and then deployment of the molecular assays for continued testing in Bolivia has been successful to detect the presence of viral RNA in survivors, identify potential rodent reservoirs, and build local capacity for rapid diagnosis and response to future suspect CHHF cases. This work demonstrates that international partnerships can aid urgent public health responses and highlights the need to enhance laboratory capacity in Bolivia.

Ecological Aspects of the Outbreak of Hemorrhagic Fever with Renal Syndrome in the Territory of the Saratov Region

Ecological Aspects of the Outbreak of Hemorrhagic Fever with Renal Syndrome in the Territory of the Saratov Region

Ecological Aspects of an Outbreak of Hemorrhagic Fever with Renal Syndrome in the Territory of the Saratov Region

Hemorrhagic fever with renal syndrome (HFRS) is classifed as a most widely spread natural-focal zoonotic infection in the forest and forest-steppe regions of Russia, taking a leading position by the incidence rate among the population. The Saratov region is enzootic as regards to HFRS, but it is not included in the list of constituent entities characterized by sustainably high morbidity rates. In some years, given favorable ecological conditions, explosive growth in the numbers of the red vole (the main carrier of Hantavirus) is registered, which leads to epidemic complications. In the winter 2018– 2019season, an intensive subniveal breeding of the red vole occurred, which led to an increase in the numbers of the species in the spring. The density of such animals increased, they began to spread widely across the territory. Intensive and extensive epizooties in rodent settlements developed in the natural foci of HFRS. This was especially evident in the territory of the forest park zone “Kumysnaya Polyana”, located in the vicinity of the regional center. The numbers of rodents in ravine and floodplain deciduous forests increased everywhere and amounted to 37.6% in spring and 53.7% in autumn per 100 capture gears, which was 1.6–2 times higher than the average long-term level. The index of dominance of the red vole has also doubled and amounted to 69.5%. In general, the infection rate of rodents increased by 2-3 times in the region. This indicator in the territory of the Saratov forest park was 20.6% in spring and 35.3% in autumn. Against this background, a record outbreak of HFRS was registered in 2019, namely, 109.7 cases per 100 thousand of the population, which was ten times higher than the long-term indicator (7.2). The results of this research should be taken into account when organizing and conducting epizootiological monitoring and preventive measures in the natural foci of HFRS and other zoonotic infections.

Onsite Mentorship Model for Isolation and Management of Viral Hemorrhagic Fever Syndromes at a Ugandan Hospital

Background:Uganda is prone to viral hemorrhagic fever (VHF) outbreaks. Infection prevention and control capacity is critical to supporting patient care, to preventing nosocomial transmission to health workers, and to limiting spread within the community. Offsite didactic training may increase healthcare worker knowledge, but this approach may be inadequate for assuring confident execution of practical clinical tasks in patient care settings. We aimed to develop a competency-based, onsite mentorship model for sentinel case isolation and management of viral hemorrhagic fever syndromes in Uganda. Methods: The Naguru Regional Referral Hospital (China Uganda Friendship Hospital) Kampala was selected as a site for training after its designation by the Uganda Ministry of Health (MoH) as facility for isolation of healthcare workers with suspected or confirmed VHF. The need for mentorships was determined from information from training providers, MoH assessments, hospital management, and key hospital staff. A list of skills was developed by reviewing WHO case management guidelines and Uganda-approved VHF trainings. The skills, exercised using scenario-based drills, focused on safety practices, identification and isolation of suspect cases, and delivery of optimized clinical care to suspected cases of VHF, among others. Trained facilitators (n = 2–4) supervised drills attended by staff from Naguru and other Kampala-based health facilities. Drills were scheduled weekly and were ordered to progressively increase in complexity. Specific drills could be repeated at the subsequent mentorship visit if gaps were identified. Results: Over 3 months, 12 drills were completed (Table 1). Cadres trained included 10 medical doctors, 12 nurses, 3 clinical officers, 5 laboratory technicians, 6 hygienists, 2 security officers, and 3 administrative officers. On average, 8 hospital staff attended weekly drills. During 3 months of the intervention, 1 suspected case of VHF and 3 cases with laboratory confirmed cholera were managed by the hospital team, and staff demonstrated the capacity for safe handling of patients with infectious bodily fluids. Barriers encountered included practice fatigue from repeated drills, challenges with team cohesion since members were from different institutions, limited personal protective equipment for repeated trainings, and competing routine hospital activities that reduced numbers of staff available for training. Repeated drills included clinical management, cadaver management, and infectious spills. Conclusions: This onsite mentorship project supported healthcare workers to gain confidence in the management of suspected VHF infection and other highly infectious diseases. Continued mentorship, hospital administration support and increase in exercise complexity are needed to consolidate on these gains.Funding: NoneDisclosures: Mohammed Lamorde reports contract research for Janssen Pharmaceutica, ViiV, and Mylan.