Power and type 1 error of different methods.

<p>Powers (left hand plots) are defined as the proportion of replicates (out of 1000) in which both simulated disease loci are detected, with ‘detection’ corresponding to any SNP within 40 kb of the simulated disease locus reaching the specified <i>p</i>-value threshold. Type 1 errors (right hand plots) are defined as the proportion of null SNPs (out of 20,000 = 20 null SNPs times 1000 simulation replicates) that reach the specified <i>p</i>-value threshold. Horizontal dashed lines indicate the target <i>p</i>-value thresholds (i.e. the expected type 1 error rates).</p

Genomic control factors achieved in naive analysis of a single replicate of the simulated longitudinal data sets.

a<p>See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004445#pgen-1004445-t002" target="_blank">Table 2</a> for description of methods.</p

Summary of methods/software packages investigated.

<p>Summary of methods/software packages investigated.</p

Genomic control factors obtained using different software packages and different strategies for modelling kinships.

<p>PLINK =  analysis in PLINK with no adjustment made for relatedness. Other methods/software packages are listed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004445#pgen-1004445-t001" target="_blank">Table 1</a> (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004445#pgen-1004445-t002" target="_blank">Table 2</a> for abbreviated names of methods). Pedigree  =  theoretical kinships based on known pedigree relationships used to adjust for relatedness. Thinned  =  kinships based on 1900 ‘thinned’ SNPs used to adjust for relatedness. Pruned  =  kinships based on 50,129 ‘pruned’ SNPs used to adjust for relatedness. Full  =  kinships based on 545,433 SNPs used to adjust for relatedness.</p

Changing demographics of visceral leishmaniasis in northeast Brazil: Lessons for the future

<div><p>Background</p><p>Visceral leishmaniasis (VL) caused by <i>Leishmania infantum</i> became a disease of urban areas in Brazil in the last 30 years and there has been an increase in asymptomatic <i>L</i>. <i>infantum</i> infection with these areas.</p><p>Methodology/Principal findings</p><p>A retrospective study of human VL was performed in the state of Rio Grande do Norte, Brazil, for the period of 1990–2014. The data were divided into five-time periods. For all VL cases, data on sex, age, nutritional status and childhood vaccination were collected. Geographic information system tools and statistical models were used to analyze the dispersion of human VL. The mean annual incidence of VL was 4.6 cases/100,000 inhabitants, with total 3,252 cases reported. The lethality rate was 6.4%. Over time the annual incidence of VL decreased in the 0–4 years (<i>p</i><0.0001) and 5–9 (p <0.0001) age groups, but increased in ages 20–39 (p<0.001) and >40 years (p<0.0001). VL occurred more often in males (β₂ = 2.5; p<0.0001). The decreased incidence of VL in children was associated with improved nutritional status and childhood immunizations including measles, poliomyelitis, BCG, and hepatitis B. Human VL correlated temporally and geographically with canine <i>L</i>. <i>infantum</i> infection (p = 0.002, R² = 0.438), with rainfall and with <i>Lutzomyia longipalpis</i> density (r = 0.762). Overall, the incidence of VL decreased, while VL-AIDS increased, especially between 2010–2014. VL was more frequently found in areas that lacked urban infrastructure, detected by lack of garbage collection and sewers, whereas HIV infection was associated with higher levels of schooling and evidence of higher socioeconomic status.</p><p>Conclusion/Significance</p><p>The demographics of VL in northeastern Brazil have changed. Disease incidence has decreased in children and increased in adults. They were associated with improvements in nutrition, socioeconomic status and immunization rates. Concurrent VL-AIDS poses a serious challenge for the future.</p></div

Analysis of a 25-year time series of visceral leishmaniasis, VL/AIDS and HIV in the state of Rio Grande do Norte, Brazil.

<p><b>A.</b> Incidence of VL, AIDS, and VL-AIDS co-infections in Rio Grande do Norte 1990 to 2014. <b>B.</b> VL incidence by 100,000 inhabitants and the percent of VL lethality by five-year period.</p

Identifying Leprosy and Those at Risk of Developing Leprosy by Detection of Antibodies against LID-1 and LID-NDO

<div><p>Leprosy is caused by <i>Mycobacterium leprae</i> infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of <i>M</i>. <i>leprae</i> infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7–10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, <i>p</i><0.001; LID-NDO, r = 0.82, <i>p</i><0.001), with higher sensitivity than bacilloscopy. According to <i>Receiver Operating Curve</i>, LID-1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3–79) months after recruitment. A linear generalized model using LID-1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas.</p></div

Risk factors for visceral leishmaniasis.

<p><b>A.</b> Association of Vaccination coverage with decreased the incidence of visceral leishmaniasis in children. Association between VL incidence(y) and vaccine coverage (x). <i>y</i> = 6.574 + 11.481<i>x</i>² − 10.13<i>x</i>³, <i>R</i>² = 0.82. <b>B.</b> Correlation between human VL and <i>L</i>. <i>infantum</i> infected dogs. <b>C.</b> Variation in rainfall index and its relation to the incidence of VL.</p

The spread of visceral leishmaniasis by micro region in a 25-year period.

<p>A. Map of Brazil showing in yellow the state of Rio Grande do Norte. Temporal and spatial distributions of human VL in the state of Rio Grande do Norte, 1990 to 2014, (cases/100,000 inhabitants).</p