Estimated gridded population counts for 1975 and urban extents mask.

<p>A) Each map pixel contains the log₁₀ transformed count of the total population +1 (to avoid negative values for population counts), aged ≥ 5 years estimated to live in that map pixel in 1975. Summing pixels by country, the totals show < 0.8% difference to the United Nations World Population Prospects (2012 Revision) country census figures for 1975. B) Red pixels delineate pixels that are classified as urban extents according the Global Rural-Urban Mapping Project (GRUMP V1.0). Estimates in urban pixels and water bodies do not count towards the population totals of numbers infected shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004328#pntd.0004328.t004" target="_blank">Table 4</a>. In both panels the white boundary denotes the OCP limits.</p

Predictive inference for threshold exceedance and endemicity class membership.

<p>A) The posterior predictive probability that microfilarial prevalence for each map pixel is less than 35%. The model output is mapped on a continuous scale from 0 to 1, with dark red representing a high degree of certainty that prevalence does not exceed the threshold of 35%. B) The continuous posterior predictive probability that microfilarial prevalence exceeds the threshold for hyperendemicity of 60%. C) Model output as in Fig 4B but categorised into broad probability intervals. Maps of this nature may have utility for the optimal targeting of current and novel control interventions by programme managers. Light-grey areas are pixels with a probability < 50% of exceeding the 60% threshold; pink pixels denote that the probability of exceeding hyperendemicity lies between 50% and 75%; deep-red colours represent a probability > 75% of exceeding this threshold. D) The probability of each map pixel being in the endemicity class to which it was assigned (<i>Ρ</i>_<i>class</i>). With 4 endemicity classes the probability ranges from a minimum of 0.25 to 1, with a value of one meaning that all realisations from the predictive posterior were assigned to the same endemicity class. In all panels the red boundary denotes the OCP limits.</p

The spatial distribution of onchocerciasis microfilarial prevalence in West Africa.

<p>A) The mean of the predictive posterior distribution of microfilarial prevalence in the population aged ≥ 5 years (<i>P</i>_<i>mf</i>) for each pixel in the study area. There are no pseudo-absence data points in this model (i.e., pragmatically-generated points of zero-prevalence in areas of known absence of disease) and, therefore, the grey areas in the north of the map, where predictions of prevalence are very low, are entirely determined by the value of the environmental covariates (the closest villages are too distal to exert a spatial effect). The white boundary denotes the limits of the OCP area. B) Endemicity class classifications for the mean of the predictive posterior, based on a modification of the OCP endemicity categories. Areas where prevalence is very low are shown by sub-dividing the hypoendemic class into two categories, a non-endemic/sporadic endemicity class, where microfilarial prevalence is <10%, and a hypoendemic class where prevalence ≥10% but <35%. Other categories are mesoendemic: ≥35% and < 60%; hyperendemic: ≥ 60% and < 80%, and highly hyperendemic (or holoendemic): ≥ 80%.</p

<i>In vitro</i> phenotyping results ordered by molecular type, VNI subtype, and high frequency MLST type.

<p>* CSF survival was not performed for one of the eight VNB isolates.</p><p><i>In vitro</i> phenotyping results ordered by molecular type, VNI subtype, and high frequency MLST type.</p

Phylogenetic and Bayesian analysis of concatenated nucleotide sequences.

<p>(A) SplitsTree neighbour network shows diverse VNII and VNB, and clonal VNI clades. (B) Analysis of VNI clustering using StructureHARVESTER and ΔK shows optimal number of K clusters is 3. (C) Use of STRUCTURE allows VNI sequences to be subdivided into 3 distinct populations: VNI(a), VNI(b), VNI(c).</p

Plots of model performance.

<p>A) Scatter-plot of observed versus estimated microfilarial prevalence in those aged ≥ 5 years (<i>P</i>_<i>mf</i>) at validation locations. The Pearson’s correlation coefficient between observed and estimated values was 0.693. The 1:1 line of perfect correlation is shown for reference. The data are coloured by the absolute difference between observed and expected values, mapped from a continuum between 0 and 1. B) Receiver Operating Characteristic (ROC) curves for each endemicity class (black line, hypoendemic; red line, mesoendemic; green line, hyperendemic; blue line, holoendemic). AUC values for each endemicity class are also displayed on the plot. C) Probability-probability plot of the proportion of true values of <i>P</i>_<i>mf</i> at validation locations that exceed their predicted probability threshold for a series of probability thresholds from 1% to 100%. Deviation from the 1:1 dashed line in this plot represents the difference between the distributions of observed and estimated microfilarial prevalence values at validation locations. D) Frequency histogram of observed and estimated <i>P</i>_<i>mf</i> at validation locations, classified according to their true class (Observed <i>P</i>_<i>mf</i> panel) and estimated endemicity class (Expected <i>P</i>_<i>mf</i> panel).</p

Maps of the Onchocerciasis Control Programme area.

<p>A) Map showing the area covered by the Onchocerciasis Control Programme (OCP) in West Africa. The red dashed line delineates the limit of anti-vectorial and/or anti-parasitic activities carried out by the OCP between 1975 and 2002. B) Map of the operational phases of the OCP. Until 1987 the method of control was almost exclusively anti-vectorial, through larviciding of vector breeding habitats. From 1987 ivermectin was used extensively, and almost exclusively in the Western Extension zones. C) Locations of the village surveys which met the criteria for inclusion in this study. A total of 737 survey sites were selected, from 5,817 surveys. The survey data displayed are coloured by endemicity class of crude microfilarial prevalence in the population aged ≥5 years. For the cut-off values of microfilarial prevalence corresponding to each endemicity category see Main Text and legend of <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004328#pntd.0004328.g003" target="_blank">Fig 3B</a>.</p

Maps of uncertainty in predictive posterior realisations.

<p>A) The population weighted index of uncertainty is calculated as in [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004328#pntd.0004328.ref061" target="_blank">61</a>] and is a pragmatic representation of how important uncertainty in the predictive posteriors is likely to be. The uncertainty index is calculated by taking the log₁₀(<i>pop</i>₇₅ +1)×1/<i>P</i>_<i>class</i> where <i>pop</i>₇₅ is the population count for 1975 and <i>Ρ</i>_<i>class</i> is the probability of endemicity class assignment (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004328#pntd.0004328.g004" target="_blank">Fig 4D</a>). B) Map of the variance of predictive posteriors. Higher values mean more diffuse posterior distributions and hence greater uncertainty in model estimates. The lowest uncertainty is found in pixels proximal to data locations. In both panels the red boundary denotes the OCP limits.</p

Median <i>in vitro</i> phenotyping values ordered by molecular type, VNI Subtype and high frequency MLST.

<p>Kruskal Wallis analysis performed on groups, and p values shown. Overall median is plotted in red. (A) Survival in <i>ex vivo</i> CSF, (B) Laccase Activity normalised to H99 reference strain, (C) <i>In vitro</i> phagocytosis of isolates by J774 cells (per 1 μl lysate).</p

Clinical characteristics and survival of patients infected with different lineages of <i>C neoformans</i>.

<p>(A) Patient survival by molecular type; VNB isolates (n = 8) were associated with significantly worse outcome compared to VNI and VNII isolates at 70 days (p = 0.01) and 365 days (p = 0.003) follow-up in Cox’s proportional hazard survival analysis. (B) Patient survival by high frequency MLST type. (C) Number of patients with and without altered mental status by molecular group (% with altered mental status indicated above each bar). (D) Baseline fungal burden, showing variation by high frequency MLST type.</p