Temporal, spatial and household dynamics of Typhoid fever in Kasese district, Uganda

<div><p>Typhoid 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 20^th and 40^th 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.</p></div

Clinical and Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever in Humans in Uganda, 2013-2019

Crimean-Congo Hemorrhagic Fever (CCHF) is endemic in Uganda, yet its epidemiology remains largely uncharacterized. To better understand its occurrence within Uganda, case reports of patients hospitalized with CCHF between 2013 and 2019 were reviewed. Further, genome sequences of CCHF-positive RNA obtained during this period were determined for phylogenetic comparisons. We found that a total of 32 cases (75% males; CFR, 31.2%), aged between 9 to 68 years, were reported during the study period. Most cases were detected during July to December of each outbreak year (81.2%; P < 0.01) and were located along the "cattle corridor" (68.7%, P = 0.03). The most common presenting symptoms were fever (93.8%), hemorrhage (81.3%), headache (78.1 %), fatigue (68.8%), vomiting (68.8%), and myalgia (65.6%). In five patients for whom hematological data were available, varied abnormalities were observed including thrombocytopenia, leukopenia, anemia, lymphopenia, lymphocytosis, polycythemia, and microcytosis. About 56.3% (P = 0.47) of patients reported tick bites or exposure to livestock as their potential source of infection. Person-to-person transmission was suspected for two cases. Using unbiased metagenomics, we found that the viral S- and L- segments have remained conserved in Africa 2 Glade since the 1950s. In contrast, the M segment split into two geographically interspersed Glades; one that belongs to Africa 2 and another that is ancestral to Africa 1 and 2. Overall, this data summarizes information on the history and clinical presentation of human CCHF in Uganda. Importantly, it identifies vulnerable populations as well as temporal and geographic regions in Uganda where surveillance and control interventions could be focused

Rabies mortality and morbidity associated with animal bites in Africa: a case for integrated rabies disease surveillance, prevention and control: a scoping review

OBJECTIVE: The objective of this scoping review was to map the current situation and available evidence and gaps on rabies morbidity, mortality, integrated rabies surveillance programmes, and existing prevention and control strategies in Africa. METHODS: We conducted a systematic scoping review following the Joanna Briggs methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist. Medline, Embase, CINAHL (EBSCOHost), Scopus, Web of Science and rabies web conferences were used to search for peer-reviewed publications between January 1946 and May 2020. Two researchers reviewed the studies and extracted data based on author (year) and region, study design and data collection duration, participants/comparators, interventions, control conditions/exposures and outcomes (rabies mortality and morbidity) and key findings/gaps/challenges. The results were reported narratively using Arksey and O'Malley's methodological framework. RESULTS: Electronic search yielded 2775 records, of which 43 studies were included. A total of 543 714 bite victims were censored through the included studies. Most of the victims were less than 15 years of age. The studies included rabies morbidity (21) and mortality (15) fluctuating in space and time across Africa depending on countries' rabies prevention and control practices (16). Others were surveillance (nine studies); surveillance and prevention (five studies); management and control (seven studies); and surveillance, prevention and control (six studies). We found challenges in rabies reporting, existing dog vaccination programmes and post-exposure prophylaxis availability or compliance. CONCLUSION: This study found challenges for dog rabies control and elimination in Africa and the need for a policy to drive the goal of zero dog-transmitted rabies to humans by 2030.This is an open-access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build on this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial (see http://creativecommons.org/licenses/by-nc/4.0/)

Exposure of Egyptian Rousette Bats (\u3ci\u3eRousettus aegyptiacus\u3c/i\u3e) and a Little Free-Tailed Bat (\u3ci\u3eChaerephon pumilus\u3c/i\u3e) to Alphaviruses in Uganda

The reservoir for zoonotic o’nyong-nyong virus (ONNV) has remained unknown since this virus was first recognized in Uganda in 1959. Building on existing evidence for mosquito bloodfeeding on various frugivorous bat species in Uganda, and seroprevalence for arboviruses among bats in Uganda, we sought to assess if serum samples collected from bats in Uganda demonstrated evidence of exposure to ONNV or the closely related zoonotic chikungunya virus (CHIKV). In total, 652 serum samples collected from six bat species were tested by plaque reduction neutralization test (PRNT) for neutralizing antibodies against ONNV and CHIKV. Forty out of 303 (13.2%) Egyptian rousettes from Maramagambo Forest and 1/13 (8%) little free-tailed bats from Banga Nakiwogo, Entebbe contained neutralizing antibodies against ONNV. In addition, 2/303 (0.7%) of these Egyptian rousettes contained neutralizing antibodies to CHIKV, and 8/303 (2.6%) contained neutralizing antibodies that were nonspecifically reactive to alphaviruses. These data support the interepidemic circulation of ONNV and CHIKV in Uganda, although Egyptian rousette bats are unlikely to serve as reservoirs for these viruses given the inconsistent occurrence of antibody-positive bats

Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018–2019 epidemic

Rift Valley fever (RVF) is an emerging, zoonotic, arboviral hemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we fitted a mathematical model to seroprevalence livestock and human RVF case data from the 2018–2019 epidemic in Mayotte to estimate viral transmission among livestock, and spillover from livestock to humans through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the epidemic size. The rate of spillover by direct contact was about twice as high as vector transmission. Assuming 30% of the population were farmers, each transmission route contributed to 45% and 55% of the number of human infections, respectively. Reactive vaccination immunizing 20% of the livestock population reduced the number of human cases by 30%. Vaccinating 1 mo later required using 50% more vaccine doses for a similar reduction. Vaccinating only farmers required 10 times as more vaccine doses for a similar reduction in human cases. Finally, with 52.0% (95% credible interval [CrI] [42.9–59.4]) of livestock immune at the end of the epidemic wave, viral reemergence in the next rainy season (2019–2020) is unlikely. Coordinated human and animal health surveillance, and timely livestock vaccination appear to be key to controlling RVF in this setting. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases

Discovery and Characterization of Bukakata orbivirus (\u3ci\u3eReoviridae:Orbivirus\u3c/i\u3e), a Novel Virus from a Ugandan Bat

While serological and virological evidence documents the exposure of bats to medically important 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

Discovery and Characterization of Bukakata orbivirus (\u3ci\u3eReoviridae:Orbivirus\u3c/i\u3e), a Novel Virus from a Ugandan Bat

While serological and virological evidence documents the exposure of bats to medically important 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

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

First laboratory confirmation and sequencing of Zaire ebolavirus in Uganda following two independent introductions of cases from the 10th Ebola Outbreak in the Democratic Republic of the Congo, June 2019.

Uganda established a domestic Viral Hemorrhagic Fever (VHF) testing capacity in 2010 in response to the increasing occurrence of filovirus outbreaks. In July 2018, the neighboring Democratic Republic of Congo (DRC) experienced its 10th Ebola Virus Disease (EVD) outbreak and for the duration of the outbreak, the Ugandan Ministry of Health (MOH) initiated a national EVD preparedness stance. Almost one year later, on 10th June 2019, three family members who had contracted EVD in the DRC crossed into Uganda to seek medical treatment. Samples were collected from all the suspected cases using internationally established biosafety protocols and submitted for VHF diagnostic testing at Uganda Virus Research Institute. All samples were initially tested by RT-PCR for ebolaviruses, marburgviruses, Rift Valley fever (RVF) virus and Crimean-Congo hemorrhagic fever (CCHF) virus. Four people were identified as being positive for Zaire ebolavirus, marking the first report of Zaire ebolavirus in Uganda. In-country Next Generation Sequencing (NGS) and phylogenetic analysis was performed for the first time in Uganda, confirming the outbreak as imported from DRC at two different time point from different clades. This rapid response by the MoH, UVRI and partners led to the control of the outbreak and prevention of secondary virus transmission

Rift Valley Fever – epidemiological update and risk of introduction into Europe

Rift Valley fever (RVF) is a vector-borne disease transmitted by a broad spectrum of mosquito species, especially Aedes and Culex genus, to animals (domestic and wild ruminants and camels) and humans. Rift Valley fever is endemic in sub-Saharan Africa and in the Arabian Peninsula, with periodic epidemics characterised by 5–15 years of inter-epizootic periods. In the last two decades, RVF was notified in new African regions (e.g. Sahel), RVF epidemics occurred more frequently and low-level enzootic virus circulation has been demonstrated in livestock in various areas. Recent outbreaks in a French overseas department and some seropositive cases detected in Turkey, Tunisia and Libya raised the attention of the EU for a possible incursion into neighbouring countries. The movement of live animals is the most important pathway for RVF spread from the African endemic areas to North Africa and the Middle East. The movement of infected animals and infected vectors when shipped by flights, containers or road transport is considered as other plausible pathways of introduction into Europe. The overall risk of introduction of RVF into EU through the movement of infected animals is very low in all the EU regions and in all MSs (less than one epidemic every 500 years), given the strict EU animal import policy. The same level of risk of introduction in all the EU regions was estimated also considering the movement of infected vectors, with the highest level for Belgium, Greece, Malta, the Netherlands (one epidemic every 228–700 years), mainly linked to the number of connections by air and sea transports with African RVF infected countries. Although the EU territory does not seem to be directly exposed to an imminent risk of RVFV introduction, the risk of further spread into countries neighbouring the EU and the risks of possible introduction of infected vectors, suggest that EU authorities need to strengthen their surveillance and response capacities, as well as the collaboration with North African and Middle Eastern countries.info:eu-repo/semantics/publishedVersio