Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

Hookworm prevalence in the EMINI study sites (Mbeya region, Tanzania, 2008/2009).

<p>Color shading of Voronoi polygons drawn around each household indicates household prevalence, labels indicate site name and site prevalence.</p

Lowess smoothed plot of hookworm prevalence over age in EMINI participants (Mbeya region, Tanzania 2008/2009).

<p>Prevalence rises sharply from birth to adolescence and reaches a plateau in early adulthood after which it stays relatively stable.</p

Univariable associations of considered variables with hookworm infection^*.

<p>CI = confidence interval; EVI = enhanced vegetation index; LST = land surface temperature; OR = odds ratio; SES = socio-economic status.</p>*<p>From separate logistic regression models which only include one covariate, adjusted for household clustering using robust variance estimates.</p

Characteristics of study participants and environmental conditions at their places of residence in Kyela and Itaka site.

<p>IQR = inter-quartile range; EPG = eggs per gram of feces; EVI = enhanced vegetation index; LST = land surface temperature; N = number of observations; SES = socio-economic status.</p>*<p>Median for continuous and proportion in percent for binary variables; IQR, minimum and maximum values are not given for binary variables.</p>†<p>According to Montresor 1998 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002408#pntd.0002408-Montresor1" target="_blank">[21]</a>.</p

Multivariable associations of selected ecological and adjustment variables with hookworm infection status^*.

<p>CI = confidence interval; EVI = enhanced vegetation index; LST = land surface temperature; OR = odds ratio; SES = socio-economic status.</p>*<p><a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002408#s3" target="_blank">Results</a> of logistic regression adjusted for within-household clustering with robust variance estimates with each model containing only those variables for which data are shown in the Table.</p>†<p>Performed on pooled dataset combining all nine sites.</p>‡<p>Moderated model for Kyela and Itaka sites with site-interaction terms for environmental variables.</p>§<p>Missing stratum not shown.</p

Linear predictions of hookworm infection probabilities for population density, EVI, and latrine coverage.

<p>According to the site-specific models for Kyela and Itaka, adjusted for all variables shown in the site-specific models in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002408#pntd-0002408-t003" target="_blank">Table 3</a>.</p

Characteristics of the study participants and environmental conditions at their places of residence.

<p>EPG = eggs per gram of feces; EVI = enhanced vegetation index; IQR = inter-quartile range; LST = land surface temperature; N = number of observations; SES = socio-economic status.</p>*<p>Median for continuous and proportion in percent for binary variables; IQR, minimum and maximum values only shown for continuous variables.</p>†<p>According to Montresor, 1998 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002408#pntd.0002408-Montresor1" target="_blank">[21]</a>.</p

De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy

Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features1–6. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons