Diagnostic performance of <i>Schistosoma</i> real-time PCR in urine samples from Kenyan children infected with <i>Schistosoma haematobium</i>:day-to-day variation and follow-up after praziquantel treatment

BACKGROUND: In an effort to enhance accuracy of diagnosis of Schistosoma haematobium, this study explores day-to-day variability and diagnostic performance of real-time PCR for detection and quantification of Schistosoma DNA compared to other diagnostic tools in an endemic area before and after treatment. METHODOLOGY: Previously collected urine samples (N = 390) from 114 preselected proven parasitological and/or clinical S. haematobium positive Kenyan schoolchildren were analyzed by a Schistosoma internal transcribed spacer-based real-time PCR after 14 years of storage. Pre-treatment day-to-day fluctuations of PCR and microscopy over three consecutive days were measured for 24 children using intra-class correlation coefficient. A combined 'gold standard' (PCR and/or microscopy positive) was used to measure sensitivity and negative predictive value (NPV) of several diagnostic tools at baseline, two and 18 months post-treatment with praziquantel. PRINCIPAL FINDINGS: All 24 repeatedly tested children were PCR-positive over three days with little daily variation in median Ct-values, while 83.3% were found to be egg-positive for S. haematobium at day 1 and 75.0% at day 2 and 3 pre-treatment, signifying daily fluctuations in microscopy diagnosis. Of all 114 preselected schoolchildren, repeated microscopic measurements were required to detect 96.5% versus 100% of positive pre-treatment cases by single PCR. At two months post-treatment, microscopy and PCR detected 22.8% versus 69.3% positive children, respectively. Based on the 'gold standard', PCR showed high sensitivity (>92%) as compared to >31% sensitivity for microscopy, both pre- and post-treatment. CONCLUSIONS/SIGNIFICANCE: Detection and quantification of Schistosoma DNA in urine by real-time PCR was shown to be a powerful and specific diagnostic tool for detection of S. haematobium infections, with less day-to-day variation and higher sensitivity compared to microscopy. The superior performance of PCR before, and two and 18 months post-treatment provides a compelling argument for PCR as an accurate and reproducible tool for monitoring treatment efficacy

State of Affairs of Tuberculosis in Prison Facilities: A Systematic Review of Screening Practices and Recommendations for Best TB Control

<div><h3>Background</h3><p>Prisoners are at high risk of developing tuberculosis (TB), causing morbidity and mortality. Prison facilities encounter many challenges in TB screening procedures and TB control. This review explores screening practices for detection of TB and describes limitations of TB control in prison facilities worldwide.</p> <h3>Methods</h3><p>A systematic search of online databases (e.g., PubMed and Embase) and conference abstracts was carried out. Research papers describing screening and diagnostic practices among prisoners were included. A total of 52 articles met the inclusion criteria. A meta-analysis of TB prevalence in prison facilities by screening and diagnostic tools was performed.</p> <h3>Results</h3><p>The most common screening tool was symptom questionnaires (63·5%), mostly reporting presence of cough. Microscopy of sputum with Ziehl-Neelsen staining and solid culture were the most frequently combined diagnostic methods (21·2%). Chest X-ray and tuberculin skin tests were used by 73·1% and 50%, respectively, as either a screening and/or diagnostic tool. Median TB prevalence among prisoners of all included studies was 1,913 cases of TB per 100,000 prisoners (interquartile range [IQR]: 332–3,517). The overall annual median TB incidence was 7·0 cases per 1000 person-years (IQR: 2·7–30·0). Major limitations for successful TB control were inaccuracy of diagnostic algorithms and the lack of adequate laboratory facilities reported by 61·5% of studies. The most frequent recommendation for improving TB control and case detection was to increase screening frequency (73·1%).</p> <h3>Discussion</h3><p>TB screening algorithms differ by income area and should be adapted to local contexts. In order to control TB, prison facilities must improve laboratory capacity and frequent use of effective screening and diagnostic tools. Sustainable political will and funding are critical to achieve this.</p> </div

Plot illustrating the median and interquartile range of TB prevalence per 100,000 prison population for different screening and diagnostic tools used in prison facilities.

<p>Plot illustrating the median and interquartile range of TB prevalence per 100,000 prison population for different screening and diagnostic tools used in prison facilities.</p

Steps to enhance TB control in prison facilities for both high and middle/low income countries.

<p>Steps to enhance TB control in prison facilities for both high and middle/low income countries.</p

Measures of TB occurrence by WHO region and income area according to the World Bank classification (median; interquartile range).

<p><i>Note</i>:</p>*<p>data available from one study.</p><p>Source: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053644#pone.0053644-World1" target="_blank">[14]</a>.</p

Flow chart of search strategy.

<p>Flow chart of search strategy.</p

Overview of all screening and diagnostic procedures by income area as classified by the World Bank.

*<p>P-value derived from the Wald Test for the association between a screening procedure and income area.</p><p>Source: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053644#pone.0053644-World1" target="_blank">[14]</a>.</p

Incidence rates of active TB (%) and prison screening and diagnostic procedures by income area as classified by the World Bank.

<p><i>Note:</i> NA: Not available;</p>*<p>Data not precisely available.</p><p>Source: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053644#pone.0053644-World1" target="_blank">[14]</a>.</p

Limitations of current TB control programmes in prison facilities.

<p>Limitations of current TB control programmes in prison facilities.</p

Burden of onchocerciasis-associated epilepsy: first estimates and research priorities

Background Since the 1990s, evidence has accumulated of an increased prevalence of epilepsy in onchocerciasis-endemic areas in Africa as compared to onchocerciasis-free areas. Although the causal relationship between onchocerciasis and epilepsy has yet to be proven, there is likely an association. Here we discuss the need for disease burden estimates of onchocerciasis-associated epilepsy (OAE), provide them, detail how such estimates should be refined, and discuss the socioeconomic impact of OAE, including a cost-estimate for anti-epileptic drugs. Main body Providing OAE burden estimates may aid prevention of epilepsy in onchocerciasis- endemic areas by inciting and informing collaboration between onchocerciasis control programmes and mental health services. Epilepsy not only massively impacts the health of those affected, but it also carries a high socioeconomic burden for the households and communities involved. We used previously published geospatial estimates of onchocerciasis in Africa and a separately published logistic regression model quantifying the association between onchocerciasis and epilepsy to estimate the number of OAE cases. We then applied disability weights for epilepsy to quantify the burden in terms of years of life lived with disability (YLD) and estimate the cost of treatment. We estimate that in 2015 roughly 117 000 people were affected by OAE across onchocerciasis-endemic areas previously under the African Programme for Onchocerciases control (APOC) mandate where OAE has ever been reported or suspected, and another 264 000 persons in onchocerciasis-endemic areas where OAE has never been investigated before. The total number of YLDs due to OAE was 39 300 and 88 700 in these areas respectively, based on a weighted mean disability weight of 0.336. The burden of OAE is approximately 13% of the total YLDs attributable to onchocerciasis and 10% of total YLDs attributable to epilepsy. We estimated that by 2015 the total costs of treatment with anti-epileptic drug for OAE cases would have been a minimum of 12.4 million US$. Conclusions These estimates suggest a considerable health, social and economic burden of OAE in Africa. The treatment and care for people with epilepsy, especially in hyperendemic onchocerciasis areas with high epilepsy prevalence thus requires more financial and human resources