Leprosy in Malawi. 1. Sensitivity and specificity of the diagnosis and the search for risk factors for leprosy

The sensitivity and specificity of the diagnosis of leprosy in the context of a total population survey are examined. It is apparent that diagnostic tools are unsatisfactory with regard to reaching a highly sensitive and specific case definition of paucibacillary leprosy, particularly in actively found suspects. Histopathological examination of 4 mm punch biopsy specimens contributed appreciably to both the sensitivity and specificity of the diagnosis of leprosy, though there was evidence for false positive and false negative histopathology results. The needs for high sensitivity during the intake phase of a vaccine trial and for high specificity during follow-up surveys for risk factors are discussed.     

Interpreting tests for iron deficiency among adults in a high HIV prevalence African setting: routine tests may lead to misdiagnosis

We evaluated peripheral blood tests to diagnose iron deficiency on medical wards in Blantyre, Malawi, where infection and HIV are prevalent. We compared full blood count, ferritin and serum transferrin receptor (TfR) levels with an estimation of iron in bone marrow aspirates. Of consecutive adults admitted with severe anaemia (haemoglobin <7 g/dl), 81 had satisfactory bone marrow aspirates. The main outcome measures were the validity of each test (sensitivity, specificity, and positive and negative predictive values) and likelihood ratios (LR) for iron deficiency. Twenty patients (25%) were iron deficient and 64 (79%) were HIV-positive. Iron deficiency was more common in HIV-negative compared with HIV-positive patients (59% vs. 16%; P<0.001). In HIV-positive patients, the optimal ferritin cut-off was 150 microg/l (sensitivity 20%, specificity 93%, LR 2.7), but no test was accurate enough to be clinically useful. In HIV-negative patients, ferritin was the single most accurate test (cut-off <70 microg/l, 100% specificity, 90% sensitive, LR if positive infinity, LR if negative 10). TfR measurement did not improve the accuracy. Mean cell volume was not a good predictor of iron status except in HIV-negative patients (cut-off <85 fl, specificity 71%, sensitivity 90%). In populations with high levels of infection and HIV, an HIV test is necessary to interpret any tests of iron deficiency. In HIV-negative patients, ferritin is the best blood test for iron deficiency, using a higher cut-off than usual. For HIV-positive patients, it is difficult to diagnose iron deficiency without bone marrow aspirates.     

Estimating sensitivity and specificity from positive predictive value, negative predictive value and prevalence: application to surveillance systems for hospital-acquired infections

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are terms usually associated with diagnostic testing. Although these concepts have been expanded from diagnostic assays to surveillance systems, these systems are not like diagnostic assays. In attempting to estimate the sensitivity and specificity of surveillance systems, situations may arise where only the PPV, NPV and prevalence are known. We aim to demonstrate the equivalence of two methods for calculating sensitivity and specificity from PPV, NPV and prevalence. The formulae for sensitivity and specificity are calculated from first principles and compared with the adjustment of a standard contingency table. We have illustrated this method using a review of a sample of surgical site infection cases following coronary artery bypass grafting. The derived prevalence from the sample is an estimate of the population prevalence and is the value that must be used in the formulae for sensitivity and specificity as functions of PPV, NPV and prevalence to obtain the same estimates as those obtained from the adjusted contingency table. The general proof of this principle is provided as an Appendix. The sensitivity and specificity of surveillance systems can be calculated by two equivalent methods when only PPV, NPV and prevalence are known.     

Monoclonal antibody based ELISA tests to detect antibodies against neuraminidase subtypes 1, 2 and 3 of avian influenza viruses in avian sera

The objective of this study was the development and the evaluation of competitive ELISA assays based on monoclonal antibodies for the detection of antibodies specific for neuraminidase type 1 (N1), 2 (N2) and 3 (N3) in avian sera. A total of 1450 sera from different avian species (854 negative, 185 positive to N1, 136 positive to N2, 219 positive to N3 and 56 positive to other N subtypes sera) were analysed in parallel by the three ELISAs. ROC analyses were performed to enable the selection of best cut-off values and estimation of diagnostic specificity and sensitivity. In addition, the correlation between the new developed ELISAs and the neuraminidase inhibition test was evaluated on a limited number of sera. The validation process of the three ELISAs proved excellent diagnostic performances, with very high specificity and sensitivity, ranging from 99.4 to 99.8% and from 97.6 to 100%, respectively in the three assays. The discriminating potential between antibodies elicited against homologous and heterologous N validates the test for use in “DIVA” assays, to distinguish between vaccinated and infected birds.     

Biases in the assessment of diagnostic tests

Diagnostic tests are traditionally characterized by simple measures of efficacy such as the sensitivity and the specificity. These measures, though widely recognized and easy to understand, are subject to definitional arbitrariness. Moreover, studies constructed to estimate the sensitivity and specificity are susceptible to a variety of biases. In this paper the various potential problems are described with reference to examples from the diagnostic literature. These difficulties have implications for the design of diagnostic test evaluations, and the choice of suitable measures of test efficacy.     

Accuracy of routine diagnostic tests used in paracoccidioidomycosis patients at a university hospital

The identification of appropriate laboratory measures to confirm clinical hypotheses is important in routine paracoccidioidomycosis medical care. The clinical records and laboratory reports of 401 paracoccidioidomycosis patients attended at the Tropical Diseases Area, Faculdade de Medicina de Botucatu, from 1974 to 2008 were reviewed. Direct mycological (DM), cell block (CB), histopathological (HP), and double immunodiffusion (DID) tests were evaluated before treatment. Typical Paracoccidioides brasiliensis yeast forms were observed in clinical specimens of 86% of the patients, but 14% were detected only by serological test. DM of 51 different tissue specimens produced 74.5% sensitivity, and 62.5% sensitivity was observed in 112 sputum samples. CB in 483 sputum samples generated 55.3% sensitivity. HP performed in 239 samples from different tissues revealed 96.7% sensitivity. Serology carried out in 351 patients and 200 healthy controls provided 90.0% sensitivity, 100.0% specificity, 100.0% positive predictive value, 85.1% negative predictive value and 93.6% accuracy. Comparisons of laboratory measurements performed in the same patient showed that sensitivity decreases from HP to DID to CB and DM, with the last two assays providing similar sensitivities. This study demonstrated that P. brasiliensis identification by HP, CB, and/or DM associated with DID is sufficient to establish the laboratorial diagnosis of paracoccidioidomycosis in practically all cases.     

Sporadic vs familial classification given etiologic heterogeneity: I. Sensitivity, specificity, and positive and negative predictive value

Environmental factors are etiologically important in many non-Mendelian familial disorders in man. Because such disorders often occur as "sporadic" cases, (ie, an affected individual with no affected relatives), it is tempting to assume that such cases represent an "environmental" form of the disorder. This paper presents an evaluation of the sensitivity, specificity, and positive and negative predictive power (PPV and NPV) of this "sporadic vs familial classification." The model assumes etiologic heterogeneity with a subpopulation of cases due to a "major" environmental event acting independent of genotype and the remaining cases resulting from a generalized single major locus (SML). Sibship size is modeled by a truncated negative binomial distribution. For rare disorders, this classification has high sensitivity and NPV but low specificity and PPV. As the disorder becomes more common, sensitivity and NPV fall while specificity and PPV rise. The power of the method increases substantially with increasing sibship size up to four or five, but further increases in power are minimal. MZ twins add considerable power to the method but aunts and uncles add little if anything. Both a correlational (phi) and an agreement-based (kappa) statistic indicate that, under most realistic circumstances, the relationship between etiology and family history is modest.     

On simultaneous assessment of sensitivity and specificity when combining two diagnostic tests

Diagnostic tests are seldom adopted in isolation. Few tests have high sensitivity and specificity simultaneously. In these cases, one can increase either the sensitivity or the specificity by combining two component tests under either the 'either positive' rule or the 'both positive' rule. However, there is a tradeoff between sensitivity and specificity when these rules are applied. We propose three statistical procedures to simultaneously assess the sensitivity and specificity when combining two component tests. Measurements of interest include rate difference and rate ratio. Our empirical results demonstrate that (i) the asymptotic test procedures for both measurements and approximate test procedure for rate difference possess inflated type I error rate; (ii) the exact test procedures for both measurements possess deflated type I error rate; and (iii) the approximate (unconditional) test procedure for rate ratio becomes an reliable alternative and nicely controls the actual type I error rate in small to moderate sample sizes. Moreover, the approximate (unconditional) test procedure is computationally less intensive than the exact (unconditional) test procedure. We illustrate our methodologies with a real example from a residual nasopharyngeal carcinoma (RNP) study.     

环境水体中感染性胃肠道病毒检测方法研究进展

胃肠道病毒,是全球范围内引起经水传播的疾病的主要病原物。寻找检测水环境中具有感染性病毒的方法是当务之急。传统细胞培养是鉴定病毒感染力的金标准,但是仍存在费时、费力、成本高且有些病毒（诺如病毒）无法培养的缺点。常用的分子生物学检测方法在检测水中病毒时,虽然有很高的灵敏度和特异性,但亦存在病毒基因拷贝数和感染力之间缺乏相关性的局限性。本文遂对目前国内外在检测感染性病毒的相关研究方面,能部分克服传统细胞培养和直接聚合酶链式反应（PCR）在检测感染性病毒时之局限性的研究成果作一综述报道。     

Birth intervals, breastfeeding and determinants of childhood mortality in Malawi

Childhood mortality in Malawi is analyzed by employing proportional hazards models. The analysis uses highly reliable data collected from the 1992 Demographic and Health Survey (DHS) of Malawi. The results show that the substantial birth interval and maternal age effects are largely limited to the infant period. The influence of social and economic variables on the mortality risk and on the relationship between biodemographic variables and mortality risk is much enhanced with increasing age of the child. It has also been found that consideration of breastfeeding status of the child does not significantly alter interpretation of effects of preceding birth interval length on mortality risk, but does partially diminish the succeeding birth interval effect. The results are discussed and then summarized in the context of policy implications for Malawi. The paper addresses a very important issue in Malawi and it adds valuable insights to the base of knowledge in childhood mortality in sub-Sahara Africa.     

Leprosy in Espírito Santo State, Brazil: a growing endemic?]

This study provides a trend analysis of leprosy among patients in the State of Espírito Santo, Brazil, from 1980 to 2003. Using temporal series statistical models, an upward trend was identified throughout the period in the overall detection rate (p<0.05), with an apparent stabilization at the end of the period. We also observed an upward trend for the following periods: (i) 1980-1987 in the <15 and >or=50-year age groups and for paucibacillary forms; (ii) 1988-1995 for the 15-19, 20-29, and >or=50-year groups and for multibacillary forms; and (iii) 1996-2003 in the 20-29-year group and paucibacillary forms. The indicators for evaluation of the endemic indicate: stable levels in grade 2 disability (mean of 6%); a proportion of less than 10% of cases in individuals<15 years of age; and a treatment dropout rate of approximately 6%. Prevalence showed a sharp decline. The upward trend can be explained partially by greater surveillance sensitivity, but the high proportion of individuals<15 highlights the need for studies aimed at better knowledge of residual sources of infection, especially in the household.     

Ｔ ＳＰＯＴ．ＴＢ、痰涂片和ＴＢ ＤＮＡ 平行检测在结核病中的诊断评价

摘要：目的　评价Ｔ ＳＰＯＴ．ＴＢ、痰涂片及ＴＢ ＤＮＡ３种检测方法在结核病中的诊断价值。方法　选取１０３
例结核病患者,同时选取４５例非结核患者作为对照,应用３种方法平行检测,比较其对结核病的诊断效
果。结果　无论结核总体组、肺结核组, 还是肺外结核组,Ｔ ＳＰＯＴ．ＴＢ 的阳性率和敏感度（８８．３５％、
９１．４３％和８１．８２％）以及ＡＵＣ 均为最高（０．８７５、０．８９０和０．８４２）,痰ＴＢ ＤＮＡ 次之,痰涂片最低;特异
度比较,痰涂片最高（１００％）、Ｔ ＳＰＯＴ．ＴＢ 次之（８６．６７％）、痰ＴＢ ＤＮＡ 最低（７７．７８％）;３ 组中Ｔ
ＳＰＯＴ．ＴＢ与痰ＴＢ ＤＮＡ 阳性率比较,χ
２＝１５．６４６、６．２９５、１０．８８２,犘＝０．０００、０．０１２、０．００１;胸水ＴＢ
ＤＮＡ 的阳性率（９３．９４％）显著高于痰ＴＢ ＤＮＡ 的阳性率（４２．４２％） （χ
２＝２０．１８４,犘＝０．０００）。结论　
Ｔ ＳＰＯＴ．ＴＢ有较好的敏感度和特异度,对结核病的诊断具有较高的价值;胸水ＴＢ ＤＮＡ 检测对于结核性
胸膜炎不失为可选择的诊断方法。
关键词：分枝杆菌,结核;Ｔ 细胞斑点试验;痰涂片;聚合酶链反应;诊断性试验
中图分类号：Ｒ５２　　文献标识码：Ａ　　文章编号：１００９ ６６３９ （２０１４）０５ ０４７３ ０４     

FeNO、ECP及IgE联合检测对学龄期支气管哮喘的诊断价值

目的探讨呼出气一氧化氮(FeNO)、免疫球蛋白E(IgE)、嗜酸粒细胞阳离子蛋白(ECP)联合检测对学龄期支气管哮喘患儿的诊断价值。方法选择2020年1—9月河南省某医院收治的100例学龄期支气管哮喘患儿为观察组,选择同期在该院进行体检的100名健康儿童作为对照组。比较2组研究对象的FeNO、IgE、ECP水平和最大呼气流量占预计值百分比(PEF%)、第1秒用力呼气容积占预计值百分比(FEV1%)。并绘制受试者工作曲线(ROC),分析FeNO、IgE、ECP联合诊断学龄期支气管哮喘的效能。结果观察组研究对象FeNO、IgE、ECP水平高于对照组,差异均有统计学意义(P<0.05)。观察组研究对象PEF%、FEV1%低于对照组,差异均有统计学意义(P<0.05)。FeNO、IgE、ECP水平分别与PEF%、FEV1%呈负相关(P<0.05)。FeNO、IgE、ECP联合诊断学龄期支气管哮喘的曲线下面积(AUC)为0.891,特异度、敏感度分别为0.974、0.785,均高于各指标单一检测的数值。结论FeNO、IgE、ECP水平升高与学龄期支气管哮喘的发生密切相关,与患者肺功能相关指标呈负相关,三者联合检测学龄期支气管哮喘具有较高敏感度和特异度,能够提高检出率,值得临床推广。     

Methods for assessing the accuracy of PCR-based tests: comparisons and extensions

Polymerase chain reaction (PCR) based tests are commonly used to diagnose various infections. Such tests are assumed to be highly 'sensitive', however, no consensus definition of, or method for estimating, sensitivity exists. Hughes and Totten proposed that sensitivity be defined as a function of the number of target DNA molecules in the sample with specificity corresponding to the case where there is no target DNA molecule present. They then developed parametric, non-parametric and semi-parametric models for estimating the sensitivity curve. In this paper a general model is proposed that yields their three models as special cases when specificity is assumed to be 1.0. We also extend the general model to incorporate covariates. Simulation studies are used to compare the different estimators. The methods are applied to data from a PCR-based test for Mycoplasma genitalium.     

Virology, diagnostic tests, epidemiology and transmission mechanisms of hepatitis C virus infection

The hepatitis C virus is a human virus, classified within a third type (Hepacivirus) of the Flaviviridae family. It is a spherical virus, of approximately 50 nm in diameter, with a glycoprotein covering that contains lipids, and its genome is a simple chain RNA molecule. It is characterised by a high degree of genomic heterogeneity, whose evolutionary consequence in the long term is the appearance of genetically different viral groups, genotypes and quasispecies. There are different diagnostic techniques for detecting hepatitis C virus infection. Serological assays: the detection of specific IgG against HCV by means of enzyme immunoassays is the most practical method for diagnosing infection by this virus. Supplementary immunblot tests are employed to confirm the specificity of the results of the EIA test. Molecular assays: qualitative and quantitative techniques have been developed for detecting RNA-HCV, based on the direct detection of the virions. The pathogeny of hepatitis C is not well understood. Its world prevalence is estimated at some 3%, which is why routine screening for its detection is not recommended. HCV transmission basically occurs through percutaneous exposure to infected blood, with higher rates observed in imprisoned persons, vagabonds, intravenous drug addicts, haemophiliacs and patients on haemodialysis. Although it can be transmitted sexually, it seems that this path is not very efficient, with a greater prevalence observed in persons with multiple sexual partners. Vertical transmission is estimated at some 2%, reaching 20% in cases of maternal coinfection with HIV.     

手术部位感染风险预警模型构建

目的构建手术部位感染风险预警模型,为筛查高危人群、发现疑似感染病例提供帮助。方法回顾性收集2013年1月—2015年12月国内6所医院5 067例腹部外科手术患者病例资料,将所有病例按照6︰4的比例随机分为建模组和验证组,采用logistic回归建立预警模型,以ROC曲线下面积(AUC)评价模型的判别能力,以约登指数最大作为最佳截断点。结果高危患者预警模型AUC为0.823,灵敏度为78.81%,特异度为74.33%,阳性预测值为19.67%,阴性预测值为97.78%。疑似感染病例判别模型AUC为0.978,灵敏度93.38%,特异度95.62%,阳性预测值62.95%,阴性预测值为99.45%。结论此研究建立的预警模型判别能力较好,可以为医院感染信息系统的预警和判别开发提供参考。     

Estimation of prevalence on the basis of screening tests

Estimates of disease prevalence based on screening tests can be severely biased unless adjusted for the sensitivity and specificity of the screening test. One such adjusted estimate, the maximum likelihood estimator proposed by Levy and Kass, can yield an extreme estimate of zero or one that has undesirable characteristics such as a standard error of zero. We develop here a Bayesian estimator which always falls between zero and one. Users without specialized software can use the maximum likelihood estimate for most circumstances and, in special cases, such as a zero estimate of prevalence, turn to the Bayesian estimate. Others can use software to carry out a complete Bayesian solution. We have provided a method to obtain numerical values for the Bayesian estimate for those ranges of sample size (20-100), sensitivity (0.7-0.9) and specificity (0.7-0.9) for which the use of this estimator seems most practical.     

Proficiency of nucleic acid tests for avian influenza viruses, Australasia

An avian influenza quality assurance program was used to provide information for laboratories on the sensitivity and specificity of their avian influenza nucleic acid testing. Most laboratories were able to correctly detect clinically relevant amounts of influenza virus (H5N1), and results improved as each subsequent panel was tested.     

Evaluation of serological diagnostic indices for mucocutaneous leishmaniasis: immunofluorescence tests and enzyme-linked immunoassays for IgG, IgM and IgA antibodies

The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of immunofluorescence (IF) and enzyme-linked immunoassays (ELISA) for IgG, IgM and IgA antibodies were assessed on sera from mucocutaneous leishmaniasis patients and controls. The sensitivity of the IgG-ELISA test was 93.3% with 95% confidence interval higher than what could be due to a random test not associated with the disease. The specificity of all tests, except the IgM-ELISA, gave indices that could not have been due to chance. The IgG-ELISA and IgG-IF had the highest positive predictive value and the kappa statistic showed that the strength of agreement between the disease and the test was strongest for IgG-ELISA. The IgG-ELISA had a negative predictive value with 95% confidence limits that were not due to chance alone. Efficiency was highest for IgG-ELISA and IgG-IF. These results were obtained using sera from patients with severe or long-standing disease and from controls in whom the disease was ruled out by a negative Montenegro skin test. In field surveys where the differences between cases and controls are less easy to define the diagnostic indices of these tests may vary with the disease prevalence.