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The global burden of sepsis is concentrated in sub-Saharan Africa (SSA), where epidemic HIV and unique pathogen diversity challenge the effective management of severe infections. In this context, patient stratification based on biomarkers of a dysregulated host response may identify subgroups more likely to respond to targeted immunomodulatory therapeutics. In a prospective cohort of adults hospitalized with suspected sepsis in Uganda, we applied machine learning methods to develop a prediction model for 30-day mortality that integrates physiology-based risk scores with soluble biomarkers reflective of key domains of sepsis immunopathology. After model evaluation and internal validation, whole-blood RNA sequencing data were analyzed to compare biological pathway enrichment and inferred immune cell profiles between patients assigned differential model-based risks of mortality. Of 260 eligible adults (median age, 32 years; interquartile range, 26–43 years; 59.2% female, 53.9% living with HIV), 62 (23.8%) died by 30 days after hospital discharge. Among 14 biomarkers, soluble tumor necrosis factor receptor 1 (sTNFR1) and angiopoietin 2 (Ang-2) demonstrated the greatest importance for mortality prediction in machine learning models. A clinicomolecular model integrating sTNFR1 and Ang-2 with the Universal Vital Assessment (UVA) risk score optimized 30-day mortality prediction across multiple performance metrics. Patients assigned to the high-risk, UVA-based clinicomolecular subgroup exhibited a transcriptional profile defined by proinflammatory innate immune and necroptotic pathway activation, T-cell exhaustion, and expansion of key immune cell subsets including regulatory and gamma-delta T cells. Clinicomolecular stratification of adults with suspected sepsis in Uganda enhanced 30-day mortality prediction and identified a high-risk subgroup with a therapeutically targetable immunological profile. Further studies are needed to advance pathobiologically informed sepsis management in SSA.

The success of the global polio eradication initiative is threatened by the genetic instability of the oral polio vaccine, which can result in the emergence of pathogenic vaccine-derived polioviruses following prolonged replication in the guts of individuals with primary immune deficiencies or in communities with low vaccination coverage. Through environmental surveillance, circulating vaccine-derived poliovirus type 2 was detected in Uganda in the absence of detection by acute flaccid paralysis (AFP) surveillance. This underscores the sensitivity of environmental surveillance and emphasizes its usefulness in supplementing AFP surveillance for poliovirus infections in the race towards global polio eradication.

Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non-polio enteroviruses (NPEVs). Specific NPEVs have been described in polio-like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

Among a prospective cohort of children and adults admitted to a national COVID-19 treatment unit in Uganda from March to December 2020, we characterized the epidemiology of and risk factors for severe illness. Across two epidemic phases differentiated by varying levels of community transmission, the proportion of patients admitted with WHO-defined severe COVID-19 ranged from 5% (7/146; 95% CI: 2–10) to 33% (41/124; 95% CI: 25–42); 21% (26/124; 95% CI: 14–29%) of patients admitted during the peak phase received oxygen therapy. Severe COVID-19 was associated with older age, male sex, and longer duration of illness before admission. Coinfection with HIV was not associated with illness severity; malaria or tuberculosis coinfection was rare. No patients died during admission. Despite low mortality, hospital incidence of severe COVID-19 during the first epidemic peak in Uganda was substantial. Improvements in vaccine deployment and acute care capacity, including oxygen delivery, are urgently needed to prevent and manage severe COVID-19 in sub-Saharan Africa.

Background Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination. Methodology A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents. Results A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event. Conclusions There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.

In this paper, we report the epidemic characteristics of the three co-circulating influenza viruses (i.e., A/H1N1, A/H3N2, and B) in two tropical African cities—Kampala and Entebbe, Uganda—over an eight-year period (2008–2015). Using wavelet methods, we show that influenza epidemics recurred annually during the study period. In most months, two or more influenza viruses co-circulated at the same time. However, the epidemic timing differed by influenza (sub)type. Influenza A/H3N2 caused epidemics approximately every 2 years in both cities and tended to alternate with A/H1N1 or B. Influenza A/H1N1 and B produced smaller but more frequent epidemics and biennial epidemics of these two viruses tended to be synchronous. In addition, epidemics of A/H3N2 were more synchronized in the two cities (located ca.37 km apart) than that of A/H1N1 or influenza B. Keywords: Influenza, Tropical regions, (sub)type specific, Uganda, Epidemic frequency

Background Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.

Background The association of influenza with meteorological variables in tropical climates remains controversial. Here, we investigate the impact of weather conditions on influenza in the tropics and factors that may contribute to this uncertainty. Methods We computed the monthly viral positive rate for each of the 3 circulating influenza (sub)types (ie, A/H1N1, A/H3N2, and B) among patients presenting with influenza-like illness (ILI) or severe acute respiratory infections (SARI) in 2 Ugandan cities (Entebbe and Kampala). Using this measure as a proxy for influenza activity, we applied regression models to examine the impact of temperature, relative humidity, absolute humidity, and precipitation, as well as interactions among the 3 influenza viruses on the epidemic dynamics of each influenza (sub)type. A full analysis including all 4 weather variables was done for Entebbe during 2007-2015, and a partial analysis including only temperature and precipitation was done for both cities during 2008-2014. Results For Entebbe, the associations with weather variables differed by influenza (sub)type; with adjustment for viral interactions, the models showed that precipitation and temperature were negatively correlated with A/H1N1 activity, but not for A/H3N2 or B. A mutually negative association between A/H3N2 and B activity was identified in both Entebbe and Kampala. Conclusion Our findings suggest that key interactions exist among influenza (sub)types at the population level in the tropics and that such interactions can modify the association of influenza activity with weather variables. Studies of the relationship between influenza and weather conditions should therefore determine and account for co-circulating influenza (sub)types.

Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data before vaccine introduction. Sera collected during case‐based measles surveillance from January 2005 to July 2018 were tested for rubella immunoglobulin M (IgM) antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real‐time reverse‐transcription polymerase chain reaction (RT‐PCR); for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23 196 suspected measles cases serologically tested in parallel for measles and rubella, 5334 (23%) were rubella IgM‐positive of which 2710 (50.8%) cases were females with 2609 (96.3%) below 15 years of age. Rubella IgM‐positive cases were distributed throughout the country and the highest number was detected in April, August, and November. Eighteen (18%) of the 100 sera screened were real‐time RT‐PCR‐positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B were identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves toward control and elimination of rubella and CRS.

BackgroundInfluenza is an important contributor to acute respiratory illness, including pneumonia, and results in substantial morbidity and mortality globally. Understanding the local burden of influenza-associated severe disease can inform decisions on allocation of resources toward influenza control programs. Currently, there is no national influenza vaccination program in Uganda.MethodsIn this study, we used data on pneumonia hospitalizations that were collected and reported through the Health Management Information System (HMIS) of the Ministry of Health, Uganda, and the laboratory-confirmed influenza positivity data from severe acute respiratory illness (SARI) surveillance in three districts (Wakiso, Mbarara, and Tororo) to estimate the age-specific incidence of influenza-associated pneumonia hospitalizations from January 2013 through December 2016.ResultsThe overall estimated mean annual rate of pneumonia hospitalizations in the three districts was 371 (95% confidence interval [CI] 323-434) per 100,000 persons, and was highest among children aged ConclusionsThe burden of influenza-associated pneumonia hospitalizations was substantial in Uganda, and was highest among young children aged

In sub-Saharan Africa, little is known about the epidemiology of pandemic-prone influenza viruses in urban settings. Using data from a prospective sentinel surveillance network, we characterized the emergence, epidemiology, and transmission dynamics of 2009 pandemic A/H1N1 influenza (H1N1pdm09) in Kampala, Uganda. After virus introduction via international air travel from England in June 2009, we estimated the basic reproductive number in Kampala to be 1.06-1.13, corresponding to attack rates of 12-22%. We subsequently identified 613 cases of influenza in Kampala from 2009 to 2015, of which 191 (31.2%) were infected with H1N1pdm09. Patients infected with H1N1pdm09 were more likely to be older adult (ages 35-64) males with illness onset during rainy season months. Urban settings in sub-Saharan Africa are vulnerable to importation and intense transmission of pandemic-prone influenza viruses. Enhanced surveillance and influenza pandemic preparedness in these settings is needed.

Background Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis. A lack of adequate human and dog surveillance, resulting in low prioritization, is often blamed for this paradox. Estimation methods are often employed to describe the rabies burden when surveillance data are not available, however these figures are rarely based on country-specific data. Methods In 2013 a knowledge, attitudes, and practices survey was conducted in Uganda to understand dog population, rabies vaccination, and human rabies risk factors and improve in-country and regional rabies burden estimates. Poisson and multi-level logistic regression techniques were conducted to estimate the total dog population and vaccination coverage. Results Twenty-four villages were selected, of which 798 households completed the survey, representing 4 375 people. Dog owning households represented 12.9% of the population, for which 175 dogs were owned (25 people per dog). A history of vaccination was reported in 55.6% of owned dogs. Poverty and human population density highly correlated with dog ownership, and when accounted for in multi-level regression models, the human to dog ratio fell to 47:1 and the estimated national canine-rabies vaccination coverage fell to 36.1%. This study estimates there are 729 486 owned dogs in Uganda (95% CI: 719 919 – 739 053). Ten percent of survey respondents provided care to dogs they did not own, however unowned dog populations were not enumerated in this estimate. 89.8% of Uganda’s human population was estimated to reside in a community that can support enzootic canine rabies transmission. Conclusions This study is the first to comprehensively evaluate the effect of poverty on dog ownership in Africa. These results indicate that describing a dog population may not be as simple as applying a human: dog ratio, and factors such as poverty are likely to heavily influence dog ownership and vaccination coverage. These modelled estimates should be confirmed through further field studies, however, if validated, canine rabies elimination through mass vaccination may not be as difficult as previously considered in Uganda. Data derived from this study should be considered to improve models for estimating the in-country and regional rabies burden. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0306-2) contains supplementary material, which is available to authorized users.

BACKGROUND A prolonged hepatitis E outbreak occurred between 2009 and 2012 among a semi-nomadic pastoralist population in the Karamoja region of Uganda. As data on the public health problems of nomadic pastoralists in sub-Saharan Africa is limited, we sought to characterize the epidemiology and challenges to control of hepatitis E in such a setting. METHODS A retrospective case-series investigation was undertaken. Surveillance line-lists of suspected hepatitis E cases maintained during the outbreak were analyzed. Standardized interviews and focus group discussions were conducted with key informants involved in outbreak control activities. RESULTS Between August 2009 and September 2012, 987 hepatitis E cases with individual case-based data were identified. Of 22 total deaths, almost half occurred during the first 4 months of the outbreak. Infection attack rates were higher among males and young adults. The average time between onset of jaundice and presentation was approximately 1 week. Challenges to control were related to persistent consumption of untreated water, poor sanitation infrastructure, remote geography, nomadic movement and civil insecurity. CONCLUSIONS The hepatitis E outbreak in Karamoja highlights the emergence of sanitation and hygiene-related disease among semi-nomadic pastoralist populations. Improving sanitation and safe water access and extending health education programs to remote pastoralist communities is crucial to prevent such diseases from becoming endemic.

Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes.

Little is known about the epidemiology of severe acute respiratory infection (SARI) or influenza in sub-Saharan Africa. Characterization of influenza transmission dynamics and risk factors for severe disease and mortality is critical to inform prevention and mitigation strategies.To characterize the epidemiology and transmission dynamics of influenza and risk factors for influenza-associated severe respiratory infection in Uganda.Clinicians at 12 sentinel surveillance sites prospectively collected clinical data and upper respiratory tract samples from consecutive patients who met criteria for SARI and influenza-like illness (ILI). Samples were tested for influenza A and B viruses using real-time reverse transcription-polymerase chain reaction. Spatial and spatiotemporal cluster modeling was performed to identify loci of increased influenza transmission. Morbidity and mortality were assessed through chart review in a defined subset of patients. Univariable and multivariable analyses were used to identify risk factors for severe respiratory infection, prolonged hospitalization, and in-hospital mortality.From October 2010 to June 2015, 9,978 patients met case definitions for SARI and ILI and had samples tested for influenza A and B. Of the 9,978 patient samples tested, 1,113 (11.2%) were positive for influenza. Among 6,057 patients with ILI, 778 samples (12.8%) were positive, and among 3,921 patients with SARI, 335 samples (8.5%) were positive. Significant clustering of influenza cases was observed in urban and periurban areas and during rainy seasons. Among 1,405 cases of SARI with available outcome data, in-hospital mortality was 1.6%. Infection with the 2009 pandemic A/H1N1 subtype and prolonged time to presentation were independently associated with SARI among influenza cases.Influenza is associated with a substantial proportion of acute respiratory infection in Uganda. As influenza vaccination programs are developed in East Africa, timing campaigns to confer protection during rainy seasons should be considered, particularly among high-risk urban populations.

We read with great interest the article by Dr. Riviello and colleagues highlighting the underappreciated burden and largely undefined epidemiology of acute respiratory distress syndrome (ARDS) in resource-limited settings [1]. We fully agree that initiatives to improve recognition of ARDS in such settings are urgently needed, both to facilitate the implementation of feasible therapies and guide the development of context-specific clinical and translational investigations. However, we also believe there is an opportunity to improve care and survival from severe respiratory distress and related critical illness in resource-limited settings with tools that are available now. At present, the majority of patients with severe respiratory distress in low-income countries, particularly those in sub-Saharan Africa, remain cared for on hospital wards not only as a result of limited intensive care facilities but because of under-recognition of severe illness in general. As we have observed while working as clinicians and researchers on such wards in Uganda, early identification of evolving critical illness remains challenged by infrequent vital sign monitoring and lack of standardized management practices for patients with severe respiratory distress and sepsis syndromes, a leading cause of ARDS in resource-limited settings [1, 2]. As prompt recognition and aggressive treatment of early clinical deterioration can often prevent illness progression and death, there remains an ongoing need for the development, validation, and implementation of basic triage tools to systematically guide identification and emergent treatment of severely ill patients in such settings. One such tool that is available now is the “Quick Check” protocol included in the World Health Organization’s Integrated Management of Adolescent and Adult Illness (IMAI) District Clinician Manual. Available as a standalone wall chart and accessible through mobile phone platforms, the “Quick Check” offers clinicians in austere environments a rapid, standardized approach to triage and initial management for patients arriving to the health facility [3]. In the “Quick Check,” for example, all patients with severe respiratory distress are to be placed on supplemental oxygen while vital signs are collected and indications for other emergent therapies are evaluated (e.g., empiric antimicrobials for patients with fever and judicious volume resuscitation for those with concomitant shock) [3]. In addition, recent data from Uganda suggest that “early warning” scores, which allocate points for derangements in vital signs and mental status, can be applied at the bedside to identify hospitalized patients at high risk for decompensation and death from sepsis and other severe illness, thereby providing opportunities for similar targeted interventions [4, 5]. As a result of work done by Dr. Riviello and colleagues, our understanding of the global impact of ARDS and other critical illness continues to improve. As it does, we must remain focused on the need to bolster implementation of basic monitoring measures and interventions to improve outcomes now for the sickest patients in the most resource-limited settings.

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda.

respectively; and Sal02, TR4699 and TR2 having 15, 20 and 23 alleles respectively. Conclusion: In summary, we have identified 6 polymorphic VNTR loci suitable for MLVA analysis of Salmonella Typhi strains. The fivemost diverse VNTR loci will be selected for theMLVA assay and will be used to analyse Salmonella Typhi strains from SSA. This work will assist in rapidly identifying strain relatedness and assist outbreak detection in typhoid fever outbreaks.

Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes.

Background: As the threat of zoonoses and the emergence of pandemic-prone respiratory viruses increases, there is a need to establish baseline information on the incidence of endemic pathogens in countries worldwide. Objectives: To investigate the presence of viruses associated with influenza-like illnesses (ILI) in Uganda. Methods: A cross-sectional study was conducted in which nasopharyngeal swab specimens were collected from patients diagnosed with ILI in Kampala and Entebbe between 14 August2008 – 15 December 2008. A multiplex polymerase chain reaction assay for detecting 12 respiratory viruses was used. Results: A total of 369 patients (52.3% females) was enrolled; the median age was 6 years (range1–70). One or more respiratory viruses were detected in 172 (46.6%) cases and their prevalence were influenza A virus (19.2%), adenovirus (8.7%), human rhinovirus A (7.9%), coronavirusOC43 (4.3%), parainfluenza virus 1 (2.7%), parainfluenza virus 3 (2.7%), influenza B virus (2.2%),respiratory syncytial virus B (2.2%), human metapneumovirus (1.4%), respiratory syncytialvirus A (1.1%), parainfluenza virus 2 (0.5%) and coronavirus 229E (0.5%). There were 24 (14.0%) mixed infections. Conclusions: This study identified some of the respiratory viruses associated with ILI in Uganda.The circulation of some of the viruses was previously unknown in the study population. These results are useful in order to guide future surveillance and case management strategies involving respiratory illnesses in Uganda.

International audience; BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Infant immunization against hepatitis B began in Uganda in 2002.To determine the baseline prevalence of hepatitis B virus (HBV) infection and explore risk factors.A hepatitis B prevalence study was nested in the 2005 national HIV/AIDS serobehavioural survey. Demographic characteristics and risk factors were explored by questionnaire. One third of blood specimens (n=5875) from adults aged 15 to 59 years were tested for hepatitis B core antibodies (HBcAb); positive specimens were tested for hepatitis B surface antigen (HBsAg).HBcAb was present in 52.3% (95% CI: 51.0-53.6) of adults, and HBsAg in 10.3% (9.5-11.1). By 15-19 years of age, 40.0% had been infected with HBV. Prevalence of both markers was significantly higher across northern Uganda, in rural areas, among the poor and least educated, and in uncircumcised men. Other independent predictors of infection were age, ethnic group, occupation, number of sex partners, and HIV and HSV-2 status.Hepatitis B virus infection is highly endemic in Uganda, with transmission occurring in childhood and adulthood. More than 1.4 million adults are chronically infected and some communities disproportionately affected. The hepatitis B infant immunization programme should be sustained and catch-up vaccination considered for older children.

Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines., Author Summary In this report we describe a newly discovered ebolavirus species which caused a large hemorrhagic fever outbreak in western Uganda. The virus is genetically distinct, differing by more than 30% at the genome level from all other known ebolavirus species. The unique nature of this virus created challenges for traditional filovirus molecular based diagnostic assays and genome sequencing approaches. Instead, we quickly determined over 70% of the virus genome using a recently developed random-primed pyrosequencing approach that allowed the rapid development of a molecular detection assay that was deployed in the disease outbreak response. This draft sequence allowed easy completion of the whole genome sequence using a traditional primer walking approach and prompt confirmation that this virus represented a new ebolavirus species. Current efforts to design effective diagnostics, antivirals and vaccines will need to take into account the distinct nature of this important new member of the filovirus family.

Background:Patientswith severe dengue infectionhave shown to have impaired dengue virus (DV) specific T cell responses and higher viral loads. Our previous data have shown that DV-specific T cell responses are suppressed by IL-10. Therefore, we set out to investigate the possible mechanisms of inhibition of DV-specific T cell responses in patients with acute dengue infection. Methods & Materials: 18 adult patients with acute confirmed dengue infection were recruited following informed written consent. The first blood sample was collected during day 3-5 of illness and the second sample was collected 2 days later. Clinical disease severity was classified according to the WHO 2011 dengue guidelines. Flow-cytometry was done on freshly extracted peripheral blood mononucleocytes (PBMCs). Intracellular cytokine staining was done by stimulating PBMCs with DVNS3 overlapping peptides. Expression of CTLA-4, TIM-3, PD-1, CD27 and CD28 were determined in T cells in general and DV-specific T cells. IL-10 quantitative ELISA was done in the patients and in 10 healthy DV seropositive individuals. Results: Expression of IL-10R was significantly higher in both CD4+ T cells (p =0.007) and CD8+ T cells (p =0.005) in patients with acute dengue when compared to healthy individuals. Expression of CTLA-4 was also significantly higher (p

Background Uganda is currently implementing the International Health Regulations (IHR[2005]) within the context of Integrated Disease Surveillance and Response (IDSR). The IHR(2005) require countries to assess the ability of their national structures, capacities, and resources to meet the minimum requirements for surveillance and response. This report describes the results of the assessment undertaken in Uganda. Methods We conducted a descriptive cross-sectional assessment using the protocol developed by the World Health Organisation (WHO). The data collection tools were adapted locally and administered to a convenience sample of HR(2005) stakeholders, and frequency analyses were performed. Results Ugandan national laws relevant to the IHR(2005) existed, but they did not adequately support the full implementation of the IHR(2005). Correspondingly, there was a designated IHR National Focal Point (NFP), but surveillance activities and operational communications were limited to the health sector. All the districts (13/13) had designated disease surveillance offices, most had IDSR technical guidelines (92%, or 12/13), and all (13/13) had case definitions for infectious and zoonotic diseases surveillance. Surveillance guidelines were available at 57% (35/61) of the health facilities, while case definitions were available at 66% (40/61) of the health facilities. The priority diseases list, surveillance guidelines, case definitions and reporting tools were based on the IDSR strategy and hence lacked information on the IHR(2005). The rapid response teams at national and district levels lacked food safety, chemical and radio-nuclear experts. Similarly, there were no guidelines on the outbreak response to food, chemical and radio-nuclear hazards. Comprehensive preparedness plans incorporating IHR(2005) were lacking at national and district levels. A national laboratory policy existed and the strategic plan was being drafted. However, there were critical gaps hampering the efficient functioning of the national laboratory network. Finally, the points of entry for IHR(2005) implementation had not been designated. Conclusions The assessment highlighted critical gaps to guide the IHR(2005) planning process. The IHR(2005) action plan should therefore be developed to foster national and international public health security.