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Luke Nyakarahuka - One of the best experts on this subject based on the ideXlab platform.
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a retrospective cohort investigation of seroprevalence of Marburg Virus and ebolaViruses in two different ecological zones in uganda
BMC Infectious Diseases, 2020Co-Authors: Alex Tumusiime, Stephen Balinandi, Barbara Knust, Ilana J Schafer, Sophia Mulei, Jackson Kyondo, Luke Nyakarahuka, Julius J Lutwama, Pierre E RollinAbstract:Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg Virus and ebolaViruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda. A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filoVirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg Virus and ebolaViruses (filoViruses). Data were analysed in STATA software using risk ratios and odds ratios. Miners in western Uganda were 5.4 times more likely to be filoVirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5–19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1–12.2). Among all participants, filoVirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan Virus only and 0.1% (1/724) to Marburg Virus. One individual seropositive for Sudan Virus also had IgG antibodies reactive to Bundibugyo Virus. The risk factors for filoVirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3–8.5), male sex (AOR = 3.1; 95% CI 1.01–9.5), going inside mines (AOR = 3.1; 95% CI 1.2–8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04–9.1) and contact with suspect filoVirus cases (AOR = 3.9, 95% CI 1.04–14.5). These findings indicate that filoVirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg Virus or ebolaViruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filoVirus epidemics.
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Marburg Virus Disease outbreak in kween district uganda 2017 epidemiological and laboratory findings
PLOS Neglected Tropical Diseases, 2019Co-Authors: Alex Tumusiime, Stephen Balinandi, Trevor Shoemaker, Sophia Mulei, Jackson Kyondo, Godfrey Chemos, Benon Kwesiga, Luke Nyakarahuka, Aaron KofmanAbstract:Introduction In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg Virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. Methods A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg Virus. Results Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg Virus strain responsible for this outbreak was closely related to Virus strains previously shown to be circulating in Uganda. Conclusion This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the Disease.
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knowledge and attitude towards ebola and Marburg Virus Diseases in uganda using quantitative and participatory epidemiology techniques
PLOS Neglected Tropical Diseases, 2017Co-Authors: Daisy Nabadda, Frank Norbert Mwiine, Chisoni Mumba, Luke Nyakarahuka, Eystein Skjerve, Doreen Sitali, Julius J Lutwama, Stephen BalinandiAbstract:Background Uganda has reported five (5) Ebola Virus Disease outbreaks and three (3) Marburg Virus Disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg Virus Disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg Virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg Virus Diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg Virus Disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg Virus Diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg Virus Diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg Virus Disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg Virus Diseases as very severe Diseases with no cure and they believe the Diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these Diseases. Conclusion Communities in Uganda affected by filoVirus outbreaks have moderate knowledge about these Diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral Diseases. The public health sector should enhance this community knowledge gap to empower them more by supplying educational materials for epidemic preparedness in future using appropriate communication channels as proposed by the communities.
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ecological niche modeling for filoViruses a risk map for ebola and Marburg Virus Disease outbreaks in uganda
PLOS Currents, 2017Co-Authors: Luke Nyakarahuka, Frank Norbert Mwiine, Julius J Lutwama, Samuel Ayebare, Gladys Mosomtai, Clovice Kankya, Eystein SkjerveAbstract:Introduction Uganda has reported eight outbreaks caused by filoViruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filoVirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. Methods The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filoVirus - environmental relationships. Presence-only data for filoVirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoViruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. Results We showed that bats as potential reservoirs of filoViruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg Virus Disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filoVirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Conclusions Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filoVirus outbreaks. The risk maps will aid in identifying areas to focus the filoVirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoViruses are mainly limited by the amount of rainfall received in an area.
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Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014
Emerging Infectious Diseases, 2017Co-Authors: Luke Nyakarahuka, Joseph Ojwang, Alex Tumusiime, Stephen Balinandi, Shannon L.m. Whitmer, Simon Kyazze, Sam Kasozi, Milton Wetaka, Issa Makumbi, Melissa DahlkeAbstract:In September 2014, a single fatal case of Marburg Virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg Virus outbreak in Uganda.
Brian R Amman - One of the best experts on this subject based on the ideXlab platform.
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isolation of angola like Marburg Virus from egyptian rousette bats from west africa
Nature Communications, 2020Co-Authors: Brian R Amman, Ibrahim A Bakarr, James Bangura, Jonathan Johnny, Immah Conteh, Alusine H Koroma, Amy J. Schuh, Tara K. Sealy, Brian H. Bird, Ibrahim FodayAbstract:Marburg Virus (MARV) causes sporadic outbreaks of severe Marburg Virus Disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case–fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and Virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats. Egyptian rousette bats (ERBs) are natural reservoirs for Marburg Virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.
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rousette bat dendritic cells overcome Marburg Virus mediated antiviral responses by upregulation of interferon related genes while downregulating proinflammatory Disease mediators
mSphere, 2019Co-Authors: Amy J. Schuh, Tara K. Sealy, Brian R Amman, Joseph Prescott, Jonathan C Guito, Jessica R Spengler, Catherine E Arnold, Lisa Wiggleton Guerrero, Gustavo PalaciosAbstract:ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human Diseases caused by infection with zoonotic viral hemorrhagic fever Viruses. Elucidating mechanisms of how the natural animal reservoirs of these Viruses coexist with these agents without overt Disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg Virus (MARV), a filoVirus and the etiological agent of the highly lethal Marburg Virus Disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filoVirus Diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the Virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg Viruses (MARVs) cause severe human Disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and Virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in Virus replication and shedding, with asymptomatic control of the Virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding Disease are unknown. Because DC infection and modulation are important early events in human Disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.
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Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus)
Viruses, 2019Co-Authors: Megan E. B. Jones, Amy J. Schuh, Tara K. Sealy, Brian R Amman, Brian H. Bird, Sherif R. Zaki, Luke S. Uebelhoer, Timothy D. Flietstra, Joann D. Coleman-mccray, Stuart T. NicholAbstract:Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg Virus (MARV), and Ravn Virus (RAVV; collectively called MarburgViruses) and have been linked to human cases of Marburg Virus Disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient Disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg Virus strain Uganda 371Bat2007, a minimally passaged Virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild Disease caused by a filoVirus in a reservoir bat host and provide support for our experimental model of this Virus-reservoir host system.
Tara K. Sealy - One of the best experts on this subject based on the ideXlab platform.
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isolation of angola like Marburg Virus from egyptian rousette bats from west africa
Nature Communications, 2020Co-Authors: Brian R Amman, Ibrahim A Bakarr, James Bangura, Jonathan Johnny, Immah Conteh, Alusine H Koroma, Amy J. Schuh, Tara K. Sealy, Brian H. Bird, Ibrahim FodayAbstract:Marburg Virus (MARV) causes sporadic outbreaks of severe Marburg Virus Disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case–fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and Virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats. Egyptian rousette bats (ERBs) are natural reservoirs for Marburg Virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.
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rousette bat dendritic cells overcome Marburg Virus mediated antiviral responses by upregulation of interferon related genes while downregulating proinflammatory Disease mediators
mSphere, 2019Co-Authors: Amy J. Schuh, Tara K. Sealy, Brian R Amman, Joseph Prescott, Jonathan C Guito, Jessica R Spengler, Catherine E Arnold, Lisa Wiggleton Guerrero, Gustavo PalaciosAbstract:ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human Diseases caused by infection with zoonotic viral hemorrhagic fever Viruses. Elucidating mechanisms of how the natural animal reservoirs of these Viruses coexist with these agents without overt Disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg Virus (MARV), a filoVirus and the etiological agent of the highly lethal Marburg Virus Disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filoVirus Diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the Virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg Viruses (MARVs) cause severe human Disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and Virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in Virus replication and shedding, with asymptomatic control of the Virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding Disease are unknown. Because DC infection and modulation are important early events in human Disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.
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Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus)
Viruses, 2019Co-Authors: Megan E. B. Jones, Amy J. Schuh, Tara K. Sealy, Brian R Amman, Brian H. Bird, Sherif R. Zaki, Luke S. Uebelhoer, Timothy D. Flietstra, Joann D. Coleman-mccray, Stuart T. NicholAbstract:Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg Virus (MARV), and Ravn Virus (RAVV; collectively called MarburgViruses) and have been linked to human cases of Marburg Virus Disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient Disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg Virus strain Uganda 371Bat2007, a minimally passaged Virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild Disease caused by a filoVirus in a reservoir bat host and provide support for our experimental model of this Virus-reservoir host system.
Amy J. Schuh - One of the best experts on this subject based on the ideXlab platform.
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isolation of angola like Marburg Virus from egyptian rousette bats from west africa
Nature Communications, 2020Co-Authors: Brian R Amman, Ibrahim A Bakarr, James Bangura, Jonathan Johnny, Immah Conteh, Alusine H Koroma, Amy J. Schuh, Tara K. Sealy, Brian H. Bird, Ibrahim FodayAbstract:Marburg Virus (MARV) causes sporadic outbreaks of severe Marburg Virus Disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case–fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and Virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats. Egyptian rousette bats (ERBs) are natural reservoirs for Marburg Virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.
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rousette bat dendritic cells overcome Marburg Virus mediated antiviral responses by upregulation of interferon related genes while downregulating proinflammatory Disease mediators
mSphere, 2019Co-Authors: Amy J. Schuh, Tara K. Sealy, Brian R Amman, Joseph Prescott, Jonathan C Guito, Jessica R Spengler, Catherine E Arnold, Lisa Wiggleton Guerrero, Gustavo PalaciosAbstract:ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human Diseases caused by infection with zoonotic viral hemorrhagic fever Viruses. Elucidating mechanisms of how the natural animal reservoirs of these Viruses coexist with these agents without overt Disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg Virus (MARV), a filoVirus and the etiological agent of the highly lethal Marburg Virus Disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filoVirus Diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the Virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg Viruses (MARVs) cause severe human Disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and Virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in Virus replication and shedding, with asymptomatic control of the Virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding Disease are unknown. Because DC infection and modulation are important early events in human Disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.
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Clinical, Histopathologic, and Immunohistochemical Characterization of Experimental Marburg Virus Infection in A Natural Reservoir Host, the Egyptian Rousette Bat (Rousettus aegyptiacus)
Viruses, 2019Co-Authors: Megan E. B. Jones, Amy J. Schuh, Tara K. Sealy, Brian R Amman, Brian H. Bird, Sherif R. Zaki, Luke S. Uebelhoer, Timothy D. Flietstra, Joann D. Coleman-mccray, Stuart T. NicholAbstract:Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg Virus (MARV), and Ravn Virus (RAVV; collectively called MarburgViruses) and have been linked to human cases of Marburg Virus Disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient Disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID50 of Marburg Virus strain Uganda 371Bat2007, a minimally passaged Virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild Disease caused by a filoVirus in a reservoir bat host and provide support for our experimental model of this Virus-reservoir host system.
Stephen Balinandi - One of the best experts on this subject based on the ideXlab platform.
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a retrospective cohort investigation of seroprevalence of Marburg Virus and ebolaViruses in two different ecological zones in uganda
BMC Infectious Diseases, 2020Co-Authors: Alex Tumusiime, Stephen Balinandi, Barbara Knust, Ilana J Schafer, Sophia Mulei, Jackson Kyondo, Luke Nyakarahuka, Julius J Lutwama, Pierre E RollinAbstract:Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg Virus and ebolaViruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda. A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filoVirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg Virus and ebolaViruses (filoViruses). Data were analysed in STATA software using risk ratios and odds ratios. Miners in western Uganda were 5.4 times more likely to be filoVirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5–19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1–12.2). Among all participants, filoVirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan Virus only and 0.1% (1/724) to Marburg Virus. One individual seropositive for Sudan Virus also had IgG antibodies reactive to Bundibugyo Virus. The risk factors for filoVirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3–8.5), male sex (AOR = 3.1; 95% CI 1.01–9.5), going inside mines (AOR = 3.1; 95% CI 1.2–8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04–9.1) and contact with suspect filoVirus cases (AOR = 3.9, 95% CI 1.04–14.5). These findings indicate that filoVirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg Virus or ebolaViruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filoVirus epidemics.
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Marburg Virus Disease outbreak in kween district uganda 2017 epidemiological and laboratory findings
PLOS Neglected Tropical Diseases, 2019Co-Authors: Alex Tumusiime, Stephen Balinandi, Trevor Shoemaker, Sophia Mulei, Jackson Kyondo, Godfrey Chemos, Benon Kwesiga, Luke Nyakarahuka, Aaron KofmanAbstract:Introduction In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg Virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. Methods A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg Virus. Results Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg Virus strain responsible for this outbreak was closely related to Virus strains previously shown to be circulating in Uganda. Conclusion This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the Disease.
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knowledge and attitude towards ebola and Marburg Virus Diseases in uganda using quantitative and participatory epidemiology techniques
PLOS Neglected Tropical Diseases, 2017Co-Authors: Daisy Nabadda, Frank Norbert Mwiine, Chisoni Mumba, Luke Nyakarahuka, Eystein Skjerve, Doreen Sitali, Julius J Lutwama, Stephen BalinandiAbstract:Background Uganda has reported five (5) Ebola Virus Disease outbreaks and three (3) Marburg Virus Disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg Virus Disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg Virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg Virus Diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg Virus Disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg Virus Diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg Virus Diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg Virus Disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg Virus Diseases as very severe Diseases with no cure and they believe the Diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these Diseases. Conclusion Communities in Uganda affected by filoVirus outbreaks have moderate knowledge about these Diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral Diseases. The public health sector should enhance this community knowledge gap to empower them more by supplying educational materials for epidemic preparedness in future using appropriate communication channels as proposed by the communities.
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Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014
Emerging Infectious Diseases, 2017Co-Authors: Luke Nyakarahuka, Joseph Ojwang, Alex Tumusiime, Stephen Balinandi, Shannon L.m. Whitmer, Simon Kyazze, Sam Kasozi, Milton Wetaka, Issa Makumbi, Melissa DahlkeAbstract:In September 2014, a single fatal case of Marburg Virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg Virus outbreak in Uganda.
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Knowledge on control and prevention of Ebola and Marburg Virus Disease.
2017Co-Authors: Luke Nyakarahuka, Stephen Balinandi, Daisy Nabadda, Frank Norbert Mwiine, Trevor Shoemaker, Chisoni Mumba, Eystein Skjerve, Doreen Sitali, Julius J Lutwama, Clovice KankyaAbstract:Knowledge on control and prevention of Ebola and Marburg Virus Disease.