Search

Abstract There are 13 globally recognized rubella virus genotypes of which only 2 (1E and 2B) have been detected recently. The largest percentage of all reported rubella virus sequences come from China and Japan with Africa reporting limited data. In a bid to address the lack of rubella genotype data in Uganda and the World Health Organization Africa region, we sought to characterize rubella viruses retrospectively using sera collected from suspected measles patients that turned out rubella IgM positive. Seven sequences belonging to genotype 2B sub-lineage 2B-L2c were obtained. These sequences clustered with other genotype 2B sequences previously reported from Uganda. None of the other genotypes (1E and 1G) reported from Uganda in the earlier years were detected. In addition, none of the sequences were obtained after the introduction of the measles-rubella containing vaccine. The above highlight the need for continuous rubella virological surveillance to confirm interruption of endemic rubella genotype circulation.

Abstract Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition in a glimpse, cVDPVs are causing outbreaks and slowing the polio eradication process. The polio virus protein 1 (VP1) contains the binding site that is key for virus transmission. Understanding the evolution of VP1 among AFP patients could yield more insight into the early events of cVDPVs. Polioviruses were identified from stool specimens of AFP patients using cell culture; and confirmed by the real time RT PCR intra-typic differentiation and vaccine-derived poliovirus assays. Seventy-nine (79) Sabin-like poliovirus 1 (SL1) and 86 Sabin-like poliovirus 3 (SL3) were sequenced. The VP1 amino acid substitutions T106A in Sabin poliovirus 1 and A54V in Sabin poliovirus 3 were common among the AFP patients as has been found in previous studies. Other substitutions that were associated with AFP were: T290A and A54T in SL1 and SL3 respectively. Nucleotide mutations that were common among the AFP patients included T402C, C670A, and T816C in SL1, and G22A, C375Y, A472R, and A694T in SL3 polioviruses. Characterizing mutations that are associated with AFP could contribute to efforts pursued to mitigate the risk of vaccine-derived polioviruses and promote development of safer vaccines.

Abstract Background The global burden of sepsis is concentrated in sub-Saharan Africa, where severe infections disproportionately affect young, HIV-infected adults and high-burden pathogens are unique. In this context, poor understanding of sepsis immunopathology represents a crucial barrier to development of locally-effective treatment strategies. We sought to determine inter-individual immunologic heterogeneity among adults hospitalized with sepsis in a sub-Saharan African setting, and characterize associations between immune subtypes, infecting pathogens, and clinical outcomes. Methods Among a prospective observational cohort of 288 adults hospitalized with suspected sepsis in Uganda, we applied machine learning methods to 14 soluble host immune mediators, reflective of key domains of sepsis immunopathology (innate and adaptive immune activation, endothelial dysfunction, fibrinolysis), to identify immune subtypes in randomly-split discovery (N = 201) and internal validation (N = 87) sub-cohorts. In parallel, we applied similar methods to whole-blood RNA-sequencing data from a consecutive subset of patients (N = 128) to identify transcriptional subtypes, which we characterized using biological pathway and immune cell-type deconvolution analyses. Results Unsupervised clustering consistently identified two immune subtypes defined by differential activation of pro-inflammatory innate and adaptive immune pathways, with transcriptional evidence of concomitant CD56(-)/CD16( +) NK-cell expansion, T-cell exhaustion, and oxidative-stress and hypoxia-induced metabolic and cell-cycle reprogramming in the hyperinflammatory subtype. Immune subtypes defined by greater pro-inflammatory immune activation, T-cell exhaustion, and metabolic reprogramming were consistently associated with a high-prevalence of severe and often disseminated HIV-associated tuberculosis, as well as more extensive organ dysfunction, worse functional outcomes, and higher 30-day mortality. Conclusions Our results highlight unique host- and pathogen-driven features of sepsis immunopathology in sub-Saharan Africa, including the importance of severe HIV-associated tuberculosis, and reinforce the need to develop more biologically-informed treatment strategies in the region, particularly those incorporating immunomodulation.

Abstract Background Prior to the first recorded outbreak of Rift Valley fever (RVF) in Uganda, in March 2016, earlier studies done until the 1970’s indicated the presence of the RVF virus (RVFV) in the country, without any recorded outbreaks in either man or animals. While severe outbreaks of RVF occurred in the neighboring countries, none were reported in Uganda despite forecasts that placed some parts of Uganda at similar risk. The Ministry of Agriculture, Animal Industry and Fisheries (MAAIF) undertook studies to determine the RVF sero-prevalence in risk prone areas. Three datasets from cattle sheep and goats were obtained; one from retrospective samples collected in 2010–2011 from the northern region; the second from the western region in 2013 while the third was from a cross-sectional survey done in 2016 in the south-western region. Laboratory analysis involved the use of the Enzyme Linked Immunosorbent Assays (ELISA). Data were subjected to descriptive statistical analyses, including non-parametric chi-square tests for comparisons between districts and species in the regions. Results During the Yellow Fever outbreak investigation of 2010–2011 in the northern region, a total sero-prevalence of 6.7% was obtained for anti RVFV reacting antibodies (IgG and IgM) among the domestic ruminant population. The 2013 sero-survey in the western region showed a prevalence of 18.6% in cattle and 2.3% in small ruminants. The 2016 sero-survey in the districts of Kabale, Kanungu, Kasese, Kisoro and Rubirizi, in the south-western region, had the respective district RVF sero-prevalence of 16.0, 2.1, 0.8, 15.1and 2.7% among the domestic ruminants combined for this region; bovines exhibited the highest cumulative sero-prevalence of 15.2%, compared to 5.3 and 4.0% respectively for sheep and goats per species for the region. Conclusions The absence of apparent outbreaks in Uganda, despite neighboring enzootic areas, having minimal restrictions to the exchange of livestock and their products across borders, suggest an unexpected RVF activity in the study areas that needs to be unraveled. Therefore, more in-depth studies are planned to mitigate the risk of an overt RVF outbreak in humans and animals as has occurred in neighboring countries.

Abstract Background The Oral Polio Vaccine (OPV or Sabin) is genetically unstable and may mutate to form vaccine-derived polioviruses (VDPVs). Methods In 2014, two VDPVs type 2 were identified during routine surveillance of acute flaccid paralysis (AFP) cases. Consequently, a retrospective VDPV survey was conducted to ensure that there was no circulating VDPV in the country. All Sabin poliovirus isolates identified in Uganda 6 months before and 6 months after were re-screened; Sabin 1 and 3 polioviruses were re-screened for Sabin 2 and Sabin 2 polioviruses were re-screened for VDPVs type 2. The Poliovirus rRT-PCR ITD/VDPV 4.0 assay and sequencing were used respectively. Results The first two VDPVs type2 were identified in Eastern Uganda and the third was identified during the survey from South-western Uganda. These regions had low OPV coverage and poor AFP surveillance indicators. Conclusion The retrospective VDPV survey was a useful strategy to screen for VDPVs more exhaustively. Supplementary surveillance methods need to be encouraged.

Abstract 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.