Environmental Surveillance of Vibrio cholerae O1/O139 in the Five African Great Lakes and Other Major Surface Water Sources in Uganda

Cholera is a major public health problem in the African Great Lakes basin. Two hypotheses might explain this observation, namely the lakes are reservoirs of toxigenic Vibrio cholerae O1 and O139 bacteria, or cholera outbreaks are a result of repeated pathogen introduction from the neighboring communities/countries but the lakes facilitate the introductions. A prospective study was conducted in Uganda between February 2015 and January 2016 in which 28 selected surface water sources were tested for the presence of V. cholerae species using cholera rapid test and multiplex polymerase chain reaction. Of 322 water samples tested, 35 (10.8%) were positive for V. cholerae non O1/non O139 and two samples tested positive for non-toxigenic atypical V. cholerae O139. None of the samples tested had toxigenic V. cholerae O1 or O139 that are responsible for cholera epidemics. The Lake Albert region registered the highest number of positive tests for V. cholerae non O1/non O139 at 47% (9/19). The peak period for V. cholerae non O1/non O139 positive tests was in March–July 2015 which coincided with the first rainy season in Uganda. This study showed that the surface water sources, including the African Great Lakes in Uganda, are less likely to be reservoirs for the observed V. cholerae O1 or O139 epidemics, though they are natural habitats for V. cholerae non O1/non O139 and atypical non-toxigenic V. cholerae O139. Further studies by WGS tests of non-toxigenic atypical V. cholerae O139 and physicochemical tests of surface water sources that supports V. cholerae should be done to provide more information. Since V. cholerae non O1/non O139 may cause other human infections, their continued surveillance is needed to understand their potential pathogenicity

Molecular characterization of <i>Vibrio cholerae</i> responsible for cholera epidemics in Uganda by PCR, MLVA and WGS

<div><p>Background</p><p>For almost 50 years sub-Saharan Africa, including Uganda, has experienced several outbreaks due to V<i>ibrio cholerae</i>. Our aim was to determine the genetic relatedness and spread of strains responsible for cholera outbreaks in Uganda.</p><p>Methodology/Principal findings</p><p>Sixty-three <i>V</i>. <i>cholerae</i> isolates collected from outbreaks in Uganda between 2014 and 2016 were tested using multiplex polymerase chain reaction (PCR), multi-locus variable number of tandem repeat analysis <b>(</b>MLVA) and whole genome sequencing (WGS). Three closely related MLVA clonal complexes (CC) were identified: CC1, 32% (20/63); CC2, 40% (25/63) and CC3, 28% (18/63). Each CC contained isolates from a different WGS clade. These clades were contained in the third wave of the 7^th cholera pandemic strain, two clades were contained in the transmission event (T)10 lineage and other in T13. Analysing the dates and genetic relatedness revealed that <i>V</i>. <i>cholerae</i> genetic lineages spread between districts within Uganda and across national borders.</p><p>Conclusion</p><p>The <i>V</i>. <i>cholerae</i> strains showed local and regional transmission within Uganda and the East African region. To prevent, control and eliminate cholera, these countries should implement strong cross-border collaboration and regional coordination of preventive activities.</p></div

Phylogram of <i>V</i>. <i>cholerae</i> WGS data.

<p>Forty-one sequences from African isolates representing T10, T11 and T12 were included. Solid lines and black arrows demarcate the boundaries of the transmission events (T). Dotted lines and outlined arrows demarcate the boundaries of the clonal complexes (CC) in Uganda. Dashed arrows identify specific isolates from locations outside Uganda inferred to be examples of cross-border spread. The sequences within the Ugandan clades were less than five nucleotides apart. Those sequences in the Tanzanian clades were less than nine nucleotides from the Ugandan sequences of the closest clade. The radial lines are proportional to the number of nucleotide differences.</p

MLVA CC for <i>V</i>. <i>cholerae</i> associated with outbreaks in Uganda.

<p>Each genotype is represented by five numbers indicating the number of repeats at the five loci, VC0147, VC0436-7 (intergenic), VC1650, VCA0171 and VCA0283. ‘N = ‘ reports the number of isolates with that genotype. The lines connecting the boxes indicate variation at a single locus. Part A is Clonal Complex 1, Part B is Clonal Complex 2, and Part C is Clonal Complex 3.</p

District of origin, number of isolates by year of isolate identification and serotype of <i>V</i>. <i>cholerae</i> isolates tested using PCR, MLVA and WGS.

<p>District of origin, number of isolates by year of isolate identification and serotype of <i>V</i>. <i>cholerae</i> isolates tested using PCR, MLVA and WGS.</p

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage

INTRODUCTIONAmyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.METHODSIndividuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition.RESULTSPostcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating (R) scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures.DISCUSSIONWe demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials.Highlights Mutation position influences A beta burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between A beta burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage