Browsing by Author "Nyakarahuka, Luke"
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Item Cutaneous anthrax associated with handling carcasses of animals that died suddenly of unknown cause: Arua District, Uganda, January 2015–August 2017(PLoS Neglected Tropical Diseases, 2021) Loy Aceng, Freda; Riolexus Ario, Alex; Alitubeera, Phoebe Hilda; Matinda Neckyon, Mukasa; Kadobera, Daniel; Sekamatte, Musa; Okethwangu, Denis; Bulage, Lilian; Harris, Julie R.; Nguma, Willy; Birungi Ndumu, Deo; Buule, Joshua; Nyakarahuka, Luke; Zhu, Bao-PingAnthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May–June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidencebased control measures. Methods A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015–August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths. Results There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/ 10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30–39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3–11), butchering (ORM-H = 22, 95%CI: 5.5–89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95% CI: 3.0–16) were associated with illness. Conclusions Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015–2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly.Item Discovery and Characterization of Bukakata orbivirus (Reoviridae:Orbivirus), a Novel Virus from a Ugandan Bat(Viruses, 2019) Fagre, Anna C.; Lee, Justin S.; Kityo, Robert M.; Bergren, Nicholas A.; Mossel, Eric C.; Nakayiki, Teddy; Nalikka, Betty; Nyakarahuka, Luke; Gilbert, Amy T.; Kerbis Peterhans, Julian; Crabtree, Mary B.; Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Schuh, Amy J.; Nichol, Stuart T.; Lutwama, Julius J.; Miller, Barry R.; Kading, Rebekah C.While serological and virological evidence documents the exposure of bats to medicallyimportant arboviruses, their role as reservoirs or amplifying hosts is less well-characterized. We describe a novel orbivirus (Reoviridae:Orbivirus) isolated from an Egyptian fruit bat (Rousettus aegyptiacus leachii) trapped in 2013 in Uganda and named Bukakata orbivirus. This is the fifth orbivirus isolated from a bat, however genetic information had previously only been available for one bat-associated orbivirus. We performed whole-genome sequencing on Bukakata orbivirus and three other bat-associated orbiviruses (Fomede, Ife, and Japanaut) to assess their phylogenetic relationship within the genus Orbivirus and develop hypotheses regarding potential arthropod vectors. Replication kinetics were assessed for Bukakata orbivirus in three different vertebrate cell lines. Lastly, qRT-PCR and nested PCR were used to determine the prevalence of Bukakata orbivirus RNA in archived samples from three populations of Egyptian fruit bats and one population of cave-associated soft ticks in Uganda. Complete coding sequences were obtained for all ten segments of Fomede, Ife, and Japanaut orbiviruses and for nine of the ten segments for Bukakata orbivirus. Phylogenetic analysis placed Bukakata and Fomede in the tick-borne orbivirus clade and Ife and Japanaut within the Culicoides/phlebotomine sandfly orbivirus clade. Further, Bukakata and Fomede appear to be serotypes of the Chobar Gorge virus species. Bukakata orbivirus replicated to high titers (106–107 PFU/mL) in Vero, BHK-21 [C-13], and R06E (Egyptian fruit bat) cells. Preliminary screening of archived bat and tick samples do not support Bukakata orbivirus presence in these collections, however additional testing is warranted given the phylogenetic associations observed. This study provided complete coding sequence for several bat-associated orbiviruses and in vitro characterization of a bat-associated orbivirus. Our results indicate that bats may play an important role in the epidemiology of viruses in the genus Orbivirus and further investigation is warranted into vector-host associations and ongoing surveillance efforts.Item First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years(The American journal of tropical medicine and hygiene, 2019) Shoemaker, Trevor R.; Nyakarahuka, Luke; Balinandi, Stephen; Ojwang, Joseph; Tumusiime, Alex; Mulei, Sophia; Kyondo, Jackson; Lubwama, Bernard; Sekamatte, Musa; Namutebi, Annemarion; Tusiime, Patrick; Monje, Fred; Mayanja, Martin; Ssendagire, Steven; Dahlke, Melissa; Kyazze, Simon; Wetaka, Milton; Makumbi, Issa; Borchert, Jeff; Zufan, Sara; Patel, Ketan; Whitmer, Shannon; Brown, Shelley; Davis, William G.; Klena, John D.; Nichol, Stuart T.; Rollin, Pierre E.; Lutwama, JuliusIn March 2016, an outbreak of Rift Valley fever (RVF) was identified in Kabale district, southwestern Uganda. A comprehensive outbreak investigation was initiated, including human, livestock, and mosquito vector investigations. Overall, four cases of acute, nonfatal human disease were identified, three by RVF virus (RVFV) reverse transcriptase polymerase chain reaction (RT-PCR), and one by IgM and IgG serology. Investigations of cattle, sheep, and goat samples from homes and villages of confirmed and probable RVF cases and the Kabale central abattoir found that eight of 83 (10%) animals were positive for RVFV by IgG serology; one goat from the home of a confirmed case tested positive by RT-PCR. Whole genome sequencing from three clinical specimens was performed and phylogenetic analysis inferred the relatedness of 2016 RVFV with the 2006–2007 Kenya-2 clade, suggesting previous introduction of RVFV into southwestern Uganda. An entomological survey identified three of 298 pools (1%) of Aedes and Coquillettidia species that were RVFV positive by RT-PCR. This was the first identification of RVFV in Uganda in 48 years and the 10th independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010.Item Genetic Diversity of Bundibugyo Ebolavirus from Uganda and the Democratic Republic of Congo(bioRxiv, 2021) Omara, Isaac Emmanuel; Kiwuwa-Muyingo, Sylvia; Balinandi, Stephen; Nyakarahuka, Luke; Kiconco, Jocelyn; Kayiwa, John Timothy; Mboowa, Gerald; Jjingo, Daudi; Lutwama, Julius J.The Ebolavirus is one of the deadliest viral pathogens which was first discovered in the year 1976 during two consecutive outbreaks in the Democratic Republic of Congo and Sudan. Six known strains have been documented. The Bundibugyo Ebolavirus in particular first emerged in the year 2007 in Uganda. This outbreak was constituted with 116 human cases and 39 laboratory confirmed deaths. After 5 years, it re-emerged and caused an epidemic for the first time in the Democratic Republic of Congo in the year 2012 as reported by the WHO. Here, 36 human cases with 13 laboratory confirmed deaths were registered. Despite several research studies conducted in the past, there is still scarcity of knowledge available on the genetic diversity of Bundibugyo Ebolavirus. We undertook a research project to provide insights into the unique variants of Bundibugyo Ebolavirus that circulated in the two epidemics that occurred in Uganda and the Democratic Republic of CongoItem How Severe and Prevalent are Ebola and Marburg Viruses? A Systematic Review and Meta-Analysis of the Case Fatality Rates and Seroprevalence(BMC infectious diseases, 2016) Nyakarahuka, Luke; Kankya, Clovice; Krontveit, Randi; Mayer, Benjamin; Mwiine, Frank N.; Lutwama, Julius; Skjerve, EysteinEbola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24–100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases.Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA.The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0–76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5–80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%–11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5–2.0%, I2 = 94.8%). The most severe species of ebolavirus was Zaire ebolavirus while Bundibugyo Ebolavirus was the least severe.The pooled CFR and seroprevalence for Ebola and Marburg viruses were found to be lower than usually reported, with species differences despite high heterogeneity between studies. Countries with an improved health surveillance and epidemic response have lower CFR, thereby indicating need for improving early detection and epidemic response in filovirus outbreaks.Item Knowledge and Attitude towards Ebola and Marburg Virus Diseases in Uganda Using Quantitative and Participatory Epidemiology Techniques(PLoS neglected tropical diseases, 2017) Nyakarahuka, Luke; Skjerve, Eystein; Nabadda, Daisy; Sitali, Doreen Chilolo; Mumba, Chisoni; Mwiine, Frank N.; Lutwama, Julius J.; Balinandi, Stephen; Shoemaker, Trevor; Kankya, CloviceUganda 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.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.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.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.Item Knowledge, perceptions, and exposure to bats in communities living around bat roosts in Bundibugyo district, Uganda: implications for viral haemorrhagic fever prevention and control(BioMed Central Ltd, 2024-03) Lesley Rose Ninsiima; Nyakarahuka, Luke; Kisaka, Steven; Collins GK. Atuheire; Mugisha, Lawrence; Odoch, Terence; Javier Sánchez Romano; Klein, Jörn; Mor, Siobhan M; Kankya, CloviceAbstract BackgroundBats are a reservoir for many viruses causing haemorrhagic fevers. Proximity to bats is a risk factor for virus spillover to animals and humans. We conducted this study to assess knowledge, perceptions, and exposure to bats in communities living near bat roosts in Bundibugyo District, Uganda.MethodsA cross-sectional study using mixed methods with both quantitative and qualitative data was conducted between September and December 2022. Participants for the quantitative data (survey) (n = 384) resided near bat caves and/or roost sites and were selected using multistage random sampling. The survey investigated participants’ prior exposure to bats, as well as knowledge and perceptions of bat exposure. Logistic regression was used to determine factors associated with bat exposure. Participants for the qualitative data (focus group discussions) (n = 10, 6–8 participants each) were purposely selected based on engagement in guano mining, hunting, and farming activities. Perceived risk associated with bat-related activities were identified and ranked in the focus group discussions using participatory epidemiology tools.ResultsIn total, (214/384, 55.7%) had a history of bat exposure and (208/384, 54.2%) had poor knowledge of risk factors associated with bat exposure. Increased exposure to bats was associated with being male (OR = 1.6; 95% CI: 1.0, 2.4 p-value = 0.038), staying in urban areas (OR = 1.9; p-value = 0.010), hunting (OR = 10.9; p-value = 0.024), and positive perception to bat guano being safe as fertiliser (OR = 2.5; p-value = 0.045). During the proportional piling process, a total of 7 risk factors were identified by 10 groups with hunting during an outbreak and consumption of bats being the most frequently identified. Overall, there was a strong statistical agreement in the ranking across the 10 focus groups (W = 0.52; p < 0.01; n = 10). Based on the provided data, the adjusted odds ratio of 0.7 for the good measures (p-value = 0.112), suggests a potential protective effect on the risk of bat exposure.ConclusionCommunities living around bat roosts frequently come into contact with bats, yet there is inadequate awareness regarding the behaviors that can lead to the transmission of bat- borne diseases to humans. It is essential to undertake educational initiatives and preventive measures to minimise the risks of bat-related infections. The need for targeted health communication and education efforts to address these knowledge gaps and promote an accurate understanding of bats and disease transmission. Understanding of diseases associated with bats will minimize bat-related health risks especially in communities engaged in wildlife hunting.Item Multidistrict Outbreak of Marburg Virus Disease—Uganda, 2012(The Journal of infectious diseases, 2015) Knust, Barbara; Schafer, Ilana J.; Wamala, Joseph; Nyakarahuka, Luke; Okot, Charles; Shoemaker, Trevor; Dodd, Kimberly; Gibbons, Aridth; Balinandi, Stephen; Tumusiime, Alex; Campbell, Shelley; Newman, Edmund; Lasry, Estrella; DeClerck, Hilde; Boum, Yap; Makumbi, Issa; Bosa, Henry Kyobe; Mbonye, Anthony; Aceng, Jane Ruth; Nichol, Stuart T.; Ströher, Ute; Rollin, Pierre E.In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription–polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection.Item Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats(Infection Ecology & Epidemiology, 2018) Kading, Rebekah C.; Kityo, Robert M.; Mossel, Eric C.; Borland, Erin M.; Nakayiki, Teddie; Nalikka, Betty; Nyakarahuka, Luke; Ledermann, Jeremy P.; Panella, Nicholas A.; Gilbert, Amy T.; Crabtree, Mary B.; Kerbis Peterhans, Julian; Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Nichol, Stuart T.; Powers, Ann M.; Lutwama, Julius J.; Miller, Barry R.A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011–2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion: Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats (Epomophorus labiatus) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.Item Prevalence and Antimicrobial Susceptibility Patterns of Bacteria from Milkmen and Cows with Clinical Mastitis in and around Kampala, Uganda(PloS one, 2013) Kateete, David Patrick; Kabugo, Usuf; Baluku, Hannington; Nyakarahuka, Luke; Kyobe, Samuel; Okee, Moses; Najjuka, Christine Florence; Joloba, Moses LutaakomeIdentification of pathogens associated with bovine mastitis is helpful in treatment and management decisions. However, such data from sub-Saharan Africa is scarce. Here we describe the distribution and antimicrobial susceptibility patterns of bacteria from cows with clinical mastitis in Kampala, Uganda. Due to high concern of zoonotic infections, isolates from milkmen are also described.Ninety seven milk samples from cows with clinical mastitis and 31 nasal swabs from milkmen were collected (one sample per cow/human). Fifty eight (60%) Gram-positive isolates namely Staphylococci (21), Enterococci (16), Streptococci (13), Lactococci (5), Micrococci (2) and Arcanobacteria (1) were detected in cows; only one grew Staphylococcus aureus. Furthermore, 24 (25%) coliforms namely Escherichia coli (12), Klebsiella oxytoca (5), Proteus vulgaris (2), Serratia (2), Citrobacter (1), Cedecea (1) and Leclercia (1) were identified. From humans, 24 Gram-positive bacteria grew, of which 11 were Staphylococci (35%) including four Staphylococcus aureus. Upon susceptibility testing, methicillin-resistant coagulase-negative staphylococci (CoNS) were prevalent; 57%, 12/21 in cows and 64%, 7/11 in humans. However, methicillin-resistant Staphylococcus aureus was not detected. Furthermore, methicillin and vancomycin resistant CoNS were detected in cows (Staphylococcus hominis, Staphylococcus lugdunensis) and humans (Staphylococcus scuiri). Also, vancomycin and daptomycin resistant Enterococci (Enterococcus faecalis and Enterococcus faecium, respectively) were detected in cows. Coliforms were less resistant with three pan-susceptible isolates. However, multidrug resistant Klebsiella, Proteus, Serratia, Cedecea, and Citrobacter were detected. Lastly, similar species grew from human and bovine samples but on genotyping, the isolates were found to be different. Interestingly, human and bovine Staphylococcus aureus were genetically similar (spa-CC435, spa-type t645 corresponding to ST121) but with different susceptibility patterns.CoNS, Enterococci, Streptococci, and Escherichia coli are the predominant pathogens associated with clinical bovine-mastitis in Kampala, Uganda. Multidrug resistant bacteria are also prevalent. While similar species occurred in humans and cows, transmission was not detected.Item Prevalence, antimicrobial susceptibility and risk factors associated with non-typhoidal Salmonella on Ugandan layer hen farms(BMC veterinary research, 2017) Odoch, Terence; Wasteson, Yngvild; L’Abée-Lund, Trine; Muwonge, Adrian; Kankya, Clovice; Nyakarahuka, Luke; Tegule, Sarah; Skjerve, EysteinNon-typhoidal Salmonella (NTS) are among the leading global foodborne pathogens and a significant public health threat. Their occurrence in animal reservoirs and their susceptibilities to commonly used antimicrobials are poorly understood in developing countries. The aim of this study was to estimate the prevalence, determine antimicrobial susceptibility and identify risk factors associated with NTS presence in laying hen farms in Uganda through a cross-sectional study. Results: Pooled faecal samples were collected from 237 laying hen farms and these were analysed for NTS following standard laboratory procedures. In total, 49 farms (20.7%; 95% Confidence interval (CI): 15.6–25.6%) were positive for NTS presence. Altogether, ten Salmonella serotypes were identified among the confirmed 78 isolates, and the predominant serotypes were Salmonella Newport (30.8%), S. Hadar (14.1%), S. Aberdeen (12.8%), S. Heidelberg (12.8%), and S. Bolton (12. 8%). Phenotypic antimicrobial resistance was detected in 45(57.7%) of the isolates and the highest resistance was against ciprofloxacin (50.0%) followed by sulphonamides (26.9%) and sulphamethoxazole/trimethoprim (7.7%). Resistance was significantly associated with sampled districts (p = 0.034). Resistance to three or more drugs, multi-drug resistance (MDR) was detected in 12 (15.4%) of the isolates, 9 (75%) of these were from Wakiso district. A multivariable logistic model identified large farm size (OR = 7.0; 95% CI: 2.5–19.8) and the presence of other animal species on the farm (OR = 5.9; 95% CI: 2.1–16.1) as risk factors for NTS prevalence on farms. Having a separate house for birds newly brought to the farms was found to be protective (OR = 0,4; 95% CI: 0.2–0.8). Conclusion: This study has highlighted a high prevalence and diversity of NTS species in laying hen farms in Uganda and identified associated risk factors. In addition, it has demonstrated high levels of antimicrobial resistance in isolates of NTS. This could be because of overuse or misuse of antimicrobials in poultry production. Also importantly, the insights provided in this study justifies a strong case for strengthening One Health practices and this will contribute to the development of NTS control strategies at local, national and international levels.Item Rapid establishment of a frontline field laboratory in response to an imported outbreak of Ebola virus disease in western Uganda, June 2019(PLOS Neglected Tropical Diseases, 2021) Schuh, Amy J.; Kyondo, Jackson; Graziano, James; Balinandi, Stephen; Kainulainen, Markus H.; Tumusiime, Alex; Nyakarahuka, Luke; Mulei, Sophia; Baluku, Jimmy; Lonergan, William; Mayer, Oren; Masereka, Rastus; Masereka, Fredrick; Businge, Esther; Gatare, Alphonse; Kabyanga, Loice; Muhindo, Samuel; Mugabe, Raymond; Makumbi, Issa; Kayiwa, Joshua; Makoba Wetaka, Milton; Brown, Vance; Ojwang, Joseph; Nelson, Lisa; Millard, Monica; Nichol, Stuart T.; Montgomery, Joel M.; Taboy, Celine H.; Lutwama, Julius J.; Klena, John D.The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in <3 hours. The integration of the field laboratory into Uganda’s National VHF Program also enabled patient specimens to be referred to Entebbe for confirmatory EBOV testing and testing for other hemorrhagic fever viruses that circulate in Uganda.Item Seroepidemiological investigation of Crimean Congo hemorrhagic fever virus in livestock in Uganda, 2017.(Public Library of Science, 2023-11) Nyakarahuka, Luke; Kyondo, Jackson; Telford, Carson; Whitesell, Amy; Tumusiime, Alex; Mulei, Sophia; Baluku, Jimmy; Cossaboom, Caitlin M; Cannon, Deborah L; Montgomery, Joel M; Lutwama, Julius J; Nichol, Stuart TAbstract Crimean-Congo Hemorrhagic fever (CCHF) is an important zoonotic disease transmitted to humans both by tick vectors and contact with fluids from an infected animal or human. Although animals are not symptomatic when infected, they are the main source of human infection. Uganda has reported sporadic human outbreaks of CCHF in various parts of the country since 2013. We designed a nationwide epidemiological study to investigate the burden of CCHF in livestock. A total of 3181 animals were sampled; 1732 cattle (54.4%), 1091 goats (34.3%), and 358 sheep (11.3%) resulting in overall livestock seropositivity of IgG antibodies against CCHF virus (CCHFV) of 31.4% (999/3181). Seropositivity in cattle was 16.9% and in sheep and goats was 48.8%. Adult and juvenile animals had higher seropositivity compared to recently born animals, and seropositivity was higher in female animals (33.5%) compared to male animals (24.1%). Local breeds had higher (36.8%) compared to exotic (2.8%) and cross breeds (19.3%). Animals that had a history of abortion or stillbirth had higher seropositivity compared to those without a history of abortion or stillbirth. CCHFV seropositivity appeared to be generally higher in northern districts of the country, though spatial trends among sampled districts were not examined. A multivariate regression analysis using a generalized linear mixed model showed that animal species, age, sex, region, and elevation were all significantly associated with CCHFV seropositivity after adjusting for the effects of other model predictors. This study shows that CCHFV is actively circulating in Uganda, posing a serious risk for human infection. The results from this study can be used to help target surveillance efforts for early case detection in animals and limit subsequent spillover into humans.Item Severe morbidity and hospital-based mortality from Rift Valley fever disease between November 2017 and March 2020 among humans in Uganda(BMC, 2024-05) Anywaine, Zacchaeus; Hansen, Christian; Warimwe, George M; Abu-Baker Mustapher, Ggayi; Nyakarahuka, Luke; Balinandi, Stephen; Ario, Alex Riolexus; Lutwama, Julius J; Elliott, Alison; Kaleebu, PontianoAbstract Background Rift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda. Methods Between November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software. Results Overall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days. Conclusion RVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.Item Social Dynamics of Ebola Virus Disease: A Case of Bundibugyo District, Uganda(Health, 2019) Kankya, Clovice; Nabadda, Daisy; Kabonesa, Consolata; Nyakarahuka, Luke; Muleme, James; Okware, Samuel; Asaba, RichardEbola Virus Disease (EVD) presents with a high global mortality and is known to be a highly infectious disease with devastating and gendered effects on the social fabric, yet most of the science has focused on the disease’s biology. However, little has been documented with regard to the gender and social aspects of Ebola Virus Disease (EVD) in two sub counties (Kikyo and Bundibugyo Town Council) in Bundibugyo District in Western Uganda. The study was set to examine the gender differences in the level of knowledge, attitudes and perceptions about EVD. Methods: The study employed a cross-sectional design using both quantitative and qualitative data collection methods. A structured questionnaire was administered to 254 respondents, 50% of whom were women. Simple random sampling was used to select the participants. Questionnaire data were analysed using SPSS at univariate and bivariate levels. Qualitative methods such as key informant interviews (with 6 participants) and Focus Group Discussions (three, one with men alone, another with women alone and the last one with both men and women) were also used to collect additional information from participants. Results: The findings indicated that socio-demographically, the majority (35%) of the respondents were aged between 20 and 29 years, 53% of whom were females. More women (about 56%) compared to men (44%) attained secondary education while more men (about 51% versus 49% of the women) reported that they were married. In terms of religion, the majority of the survey participants were Catholics (59% females and 49% males). With regard to communities’ knowledge about EVD, there was no significant relationship between men and women in terms of prior knowledge about EVD, risk factors and control measures. However, slightly more males (about 51%) than females (49%) had heard about EVD and more males (about 52%) than females (48%) admitted that they were at risk of contracting the disease. On the control measures, slightly more females than males (about 53% vs. 47% respectively) proposed avoiding contact with infected persons. The results further revealed that more males (about 51%) than females (49%) were willing to relate with EVD survivors, and this was due to the latter’s fear of contracting the disease. The major devastating effects of EVD that were reported included loss of lives, disruption of peoples movements, isolation of people, disruption of children’s school activities, stigma and discrimination of survivors. More females (about 52%) than males (about 48%) reported that EVD survivors were discriminated during the EVD outbreak in Bundibugyo District. Conclusions: This study has shown that whereas both men and women demonstrate average knowledge about EVD, there is need for more training and sensitization targeting women who have delusions about the severity of the disease, its risk factors, stigma and the integration of survivors in the affected communities. Communities also need to be sensitized about the gender roles that increase both the burden of EVD and the risk of men and women contracting the disease. This will lead to more culturally sensitive responses to EVD outbreaks in future.Item Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda, July 2018- January 2019(PLoS neglected tropical diseases, 2019) Mirembe, Bernadette Basuta; Musewa, Angella; Kadobera, Daniel; Kisaakye, Esther; Birungi, Doreen; Eurien, Daniel; Nyakarahuka, Luke; Balinandi, Stephen; Tumusiime, Alex; Kyondo, Jackson; Mbula Mulei, Sophia; Baluku, Jimmy; Kwesiga, Benon; Ndugwa Kabwama, Steven; Zhu, Bao-Ping; Harris, Julie R.; Lutwama, Julius Julian; Alex, Riolexus ArioCrimean-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, diarrhea, 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 the 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 (OR M-H = 18, 95% CI = 3.2-1) 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 (OR M-H = 9.3, 95%CI = 1.9–46). CCHF outbreaks occurred sporadically during 2018–2019, both within and outside the ‘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.Item Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae)(Scientific reports, 2021) Fagre, Anna C.; Lewis, Juliette; Miller, Megan R.; Mossel, Eric C.; Lutwama, Julius J.; Nyakarahuka, Luke; Nakayiki, Teddy; Kityo, Robert; Nalikka, Betty; Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Foy, Brian; Schountz, Tony; Anderson, John; Kading, Rebekah C.Serological cross-reactivity among flaviviruses makes determining the prior arbovirus exposure of animals challenging in areas where multiple flavivirus strains are circulating. We hypothesized that prior infection with ZIKV could be confirmed through the presence of subgenomic flavivirus RNA (sfRNA) of the 3′ untranslated region (UTR), which persists in tissues due to XRN-1 stalling during RNA decay. We amplified ZIKV sfRNA but not NS5 from three experimentally-infected Jamaican fruit bats, supporting the hypothesis of sfRNA tissue persistence. Applying this approach to 198 field samples from Uganda, we confirmed presence of ZIKV sfRNA, but not NS5, in four bats representing three species: Eidolon helvum (n = 2), Epomophorus labiatus (n = 1), and Rousettus aegyptiacus (n = 1). Amplified sequence was most closely related to Asian lineage ZIKV. Our results support the use of sfRNA as a means of identifying previous flavivirus infection and describe the first detection of ZIKV RNA in East African bats.Item Temporal, spatial and household dynamics of Typhoid fever in Kasese district, Uganda(PLoS ONE, 2019) Basuta Mirembe, Bernadette; Mazeri, Stella; Callaby, Rebecca; Nyakarahuka, Luke; Kankya, Clovice; Muwonge, AdrianTyphoid fever affects 21 million people globally, 1% of whom succumb to the disease. The social, economic and public health consequences of this disease disproportionately affect people in Africa and Asia. In order to design context specific prevention strategies, we need to holistically characterise outbreaks in these settings. In this study, we used retrospective data (2013–2016) at national and district level to characterise temporal and spatial dynamics of Typhoid fever outbreaks using time series and spatial analysis. We then selected cases matched with controls to investigate household socio-economic drivers using a conditional logistic regression model, and also developed a Typhoid fever outbreak-forecasting framework. The incidence rate of Typhoid fever at national and district level was ~ 160 and 60 cases per 100,000 persons per year, respectively, predominantly in urban areas. In Kasese district, Bwera sub-county registered the highest incidence rate, followed by Kisinga, Kitholhu and Nyakiyumbu sub-counties. The male-female case ratio at district level was at 1.68 and outbreaks occurred between the 20th and 40th week (May and October) each year following by seven weeks of precipitation. Our forecasting framework predicted outbreaks better at the district level rather than national. We identified a temporal window associated with Typhoid fever outbreaks in Kasese district, which is preceded by precipitation, flooding and displacement of people. We also observed that areas with high incidence of Typhoid fever also had high environmental contamination with limited water treatment. Taken together with the forecasting framework, this knowledge can inform the development of specific control and preparedness strategies at district and national level.