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Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay.
Methods and Findings
The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (≤ 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%–46%).
Citation: Schüpbach J, Gebhardt MD, Tomasik Z, Niederhauser C, Yerly S, Bürgisser P, et al. (2007) Assessment of Recent HIV-1 Infection by a Line Immunoassay for HIV-1/2 Confirmation. PLoS Med 4(12): e343. https://doi.org/10.1371/journal.pmed.0040343
Academic Editor: Walid Heneine, Centers for Disease Control and Prevention, United States of America
Received: March 8, 2007; Accepted: October 18, 2007; Published: December 1, 2007
Copyright: © 2007 Schüpbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was funded by the Swiss Federal Office of Public Health (SFOPH) contracts No. 04.002598 / 2.24.01.-849 (CHAT Survey), Nos. 05.000323/2.25.02.-23 and 06.000487/2.25.01.-989 (to Swiss HIV Confirmatory Labs), and No. 03.000571/2.31.02.-3 (to Swiss National Center for Retroviruses). The SFOPH had no direct role in the design of this study, but provided anonymized clinical reporting data on the patients investigated in the study. The funders did not have any role in data analysis or the decision to publish the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CI, confidence interval; EIA, enzyme immunoassay; LLR, logistic likelihood ratio; PHI, primary HIV infection; SFOPH, Swiss Federal Office of Public Health; STARHS, serologic testing algorithms for recent HIV seroconversion.
Editors' Summary
Since the first diagnosed cases of AIDS (acquired immunodeficiency syndrome) in 1981, the AIDS epidemic has spread rapidly. Now, 40 million people are infected with HIV (human immunodeficiency virus), the cause of AIDS. HIV infects and kills immune system cells, leaving infected individuals susceptible to other infectious diseases and tumors. The first, often undiagnosed, stage of HIV infection (primary HIV infection) lasts a few weeks and often involves a flu-like illness. During this stage, the immune system begins to respond to HIV by producing antibodies (proteins that recognize viral molecules called antigens). The time needed for these antibodies to appear on testing "seroconversion" (usually 6–12 weeks) is called the window period of the test; HIV antibody tests done during this period give false negative results. During the second, symptom-free stage of HIV infection, which can last many years, the virus gradually destroys the immune system so that by the third stage of infection unusual infections (for example, persistant yeast infections of the mouth) begin to occur. The fourth stage is characterized by multiple AIDS-indicator conditions such as severe bacterial, fungal, or viral infections, and cancers such as Kaposi sarcoma.
Why Was This Study Done?
To monitor the AIDS/HIV epidemic and HIV prevention programs, it is necessary to know how many people in a population have been recently infected with HIV. Serologic testing algorithms for recent HIV seroconversion (STARHS) provide a way to get this information. Early during seroconversion, low levels of antibodies that bind only weakly to their viral antigens (low-affinity antibodies) are made. Later on, antibody concentrations and tightness of binding increase. STARHS calculate the number of recently infected people by analyzing data from special "detuned" HIV antibody assays (for example, a commercially available test called the BED-EIA) that preferentially detect low-concentration, low-avidity antibodies. This type of test cannot, however, be used to determine whether an individual has an HIV infection, because it will miss a substantial fraction of infected people. Diagnosing HIV in an individual person requires more sensitive tests for antibody detection. In this study, the researchers have investigated whether a test called INNO-LIA, which is already being used in some countries to diagnose HIV infection, can also provide information about the recency (newness) of HIV infections.
What Did the Researchers Do and Find?
Between July 2005 and June 2006, 765 HIV infections were newly diagnosed in Switzerland. Using clinical and laboratory information collected at diagnosis, the researchers classified 195 of these infections as recent infections (occurring within the past year) and 161 as older infections. (The remaining infections could not be classified based on the available medical infomation.) The researchers then compared the ability of INNO-LIA (which measures antibodies to five HIV-1 antigens) and BED-EIA to distinguish recent from older HIV infections. BED-EIA correctly identified as recent 65% of the infections classified as recent based on the clinical information, and identified as older 80% of the infections classified as older based on the clinical information. In other words, this test was 65% sensitive (able to detect 65% of the truly recent infections as defined in this study) and was 80% specific (80% accurate in eliminating non-recent infections.) The two best algorithms (mathematical procedures) for converting INNO-LIA data into estimates of recent HV infections had sensitivities of 50% and 40% and specificities of 95% and 99%, respectively. Using actual test results and taking into account these sensitivities and specificities gave estimates of 35% and 33% for the proportion of the whole study population that had been recently infected. BED-EIA gave an estimate of 37%. Finally, a widely used window-based algorithm for recency estimation that uses the numbers of cases that are defined as recent by BED-EIA and the length of the window period for BED-EIA to calculate the annual number of new infections in populations indicated that 41% of the whole study population had been recently infected.
What Do These Findings Mean?
These findings indicate that numbers of recent HIV infections can be extracted from the INNO-LIA HIV diagnostic test and are comparable to those obtained using a window-based algorithm. The test could, therefore, provide a cost-effective means to improve HIV surveillance in countries like Switzerland that already use it for HIV diagnosis. However, because this approach relies on knowing the sensitivity and specificity of the INNO-LIA algorithms, which may vary between populations, the use of these algorithms to estimate numbers of recent HIV infections must be preceded by an assessment of their sensitivity and specificity in each new setting.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040343.
- HIV InSite has comprehensive information on all aspects of HIV/AIDS, including fact sheets on the symptoms of HIV infection, HIV testing, and a chapter on laboratory tests for HIV antibodies
- NAM, a UK registered charity, provides information about all aspects of HIV and AIDS, including fact sheets on the stages of HIV infection and HIV testing
- The US Centers for Disease Control and Prevention (CDC) provides information on HIV/AIDS, including information on HIV testing and on HIV surveillance by the CDC (in English and Spanish)
- Information is available from Avert, an international AIDS charity, on the stages of HIV infection and on HIV testing
- Details on the US Centers for Disease Control and Prevention and the World Health Organiztion HIV classification systems are available from the US Department of Veterans Affairs
Assessment of the number of individuals with early HIV infection is needed for evaluation of the current HIV epidemic and preventive efforts targeted at the different transmission risk populations. Consequently, serologic testing algorithms for recent HIV seroconversion (STARHS) have been developed. These tests utilize the fact that both the concentration and affinity of HIV antibodies in early infection are lower than at later stages [1,2]. The fact that STARHS requires a special assay, which has a deliberately reduced sensitivity compared to HIV screening tests, restricts STARHS to epidemiologic studies. However, for systematic epidemiologic monitoring it would be advantageous if "recency" information (i.e. how recently the infection was acquired) could be simultaneously gained from the same tests being used to diagnose HIV infection.
Here we have investigated whether a second-generation Western blot assay (line immunoassay) provides recency information similar to that of a commercially available STARHS test, which is used for estimating the incidence of recent infections in a population and was originally developed by researchers at the US Centers for Disease Control and Prevention (CDC) [3]. The line immunoassay features standardized antigens of both HIV-1 and HIV-2 and three internal controls. It is currently being used increasingly as a replacement for the traditional first-generation HIV Western blot developed more than 20 years ago [4,5]. The test has recently become mandatory for confirmation of HIV infection and differentiation of HIV-1 and HIV-2 in Switzerland [6].
Patients and Specimens
It is estimated that several hundred thousand HIV screening tests are performed annually in Switzerland. Serum or plasma specimens from all individuals in whom HIV infection was newly diagnosed in Switzerland between 1 July 2005 and 30 June 2006 were selected for the study. By federal ordinance, an epidemiologic questionnaire on each newly diagnosed HIV infection has to be forwarded under code to the Swiss Federal Office of Public Health (SFOPH) by the patient's physician. Of relevance to the present study, the questionnaire contains items about clinical or laboratory signs of recent infection (e.g., symptoms of primary HIV infection, CDC staging [7], and seroconversion).
Definition of Recent or Older Infection
For the purpose of this study an HIV infection was defined as recent on the basis of the physicians' information reported to the SFOPH and by the laboratory results obtained at the time of diagnosis of the HIV infection. Specifically, a recent infection was required to meet one or more of the following conditions. Definition 1: signs of primary HIV infection (PHI) at the time of diagnosis [8]; definition 2: a self-reported or documented negative result of a HIV screening test within 12 mo before HIV diagnosis; or definition 3, laboratory evidence of seroconversion at the time of diagnosis, i.e., a reactive fourth-generation HIV-1/2/O antibody/antigen combination screening test and a positive virus component test (HIV-1 p24 antigen or HIV-1 RNA) combined with a negative or indeterminate antibody assay (third-generation HIV-1/2/O antibody enzyme immunoassay, Western blot, or INNO-LIA). The time window during which an infection was defined as being recent thus was 12 mo. An infection was defined as older if symptoms of CDC stages B or C were present at the time of diagnosis and reported to the SFOPH [7]. Report of no symptoms (CDC stage A) or lack of staging information remained undefined and were either excluded from or included in the analysis depending on the respective evaluation as described under results.
Tests for Recent HIV-1 Infection
All study samples were tested prospectively by the INNO-LIA HIV I/II Score assay (Innogenetics, Ghent, Belgium) in one of the 11 accredited Swiss HIV Confirmatory Labs or the Swiss National Center for Retroviruses (SNCR), the later being commissioned by the SFOPH to serve as the national HIV reference laboratory. INNO-LIA tests were conducted as a mandatory component of the SFOPH HIV testing system [6]. The INNO-LIA HIV I/II Score assay (INNO-LIA) is a Western blot–like line immunoassay that measures antibodies against recombinant proteins or synthetic peptides of HIV-1, HIV-1 group O, or HIV-2, which are coated as discrete lines on a nylon strip with plastic backing. As each test strip also contains three quantitative internal standards, a semiquantitative ranking of the different antibody reactions is possible [9,10].
All INNO-LIA assays were performed by trained laboratory personnel using the manufacturer's 16-h sample incubation protocol. Antibody reaction to each of the seven HIV antigen bands present on the INNO-LIA test strip (sgp120 [including group O peptides], gp41, p31, p24 and p17 of HIV-1, and sgp105 and gp36 of HIV-2) was assessed visually in nine laboratories and by the automated scanner–based LiRAS system (Innogenetics) in three laboratories. Based on the three internal standards, which define reaction levels of 0.5 (+/−), 1, and 3, the antibody reaction to each HIV antigen was classified into one of six possible intensity scores (0, 0.5 [for +/−], 1, 2, 3, or 4) according to the manufacturer's instructions.
Frozen aliquots (−20 °C) of all samples were furthermore sent under code to the SNCR and tested prospectively by the HIV-1 BED Incidence enzyme immunoassay (BED-EIA, Calypte Biomedical Corporation, Lake Oswego, Oregon, United States). BED-EIA was performed as a part of an ethically approved nationwide epidemiologic study (CH.A.T. survey) commissioned by the SFOPH. It aimed at elucidating the circumstances under which new HIV infections in Switzerland occurred (see http://www.bag.admin.ch/hiv_aids/00829/03471/index.html?lang=de for further information). All BED-EIA testing was performed in blinded fashion by a single, highly experienced person and using a Microsoft Excel-based program for automated result interpretation prepared for the study according to Calypte's instructions, which specify a cutoff of 0.8 normalized optical density units (ODn).
Determination of INNO-LIA Window Periods
Window periods for INNO-LIA recency algorithms were determined based on results with 15 seroconversion panels with a total of 105 specimens (Boston Biomedica, West Bridgewater, Massachusetts, United States; panels PRB 903–904, 909–912, 916–919, 922–925, and 927). The INNO-LIA results on these panels were provided by Innogenetics. The raw window period was calculated as the difference in days between the first sample reactive in the most sensitive third-generation HIV-1/2 screening test (based on data from Boston Biomedica) and the first sample ruled "older" by the respective INNO-LIA recency algorithm. To these raw window periods was added a constant of 22 d, which corresponds to the estimated median seroconversion window of sensitive third-generation HIV-1/2 screening assays [11].
Statistical Evaluation
Differences in INNO-LIA reaction intensity in different study subgroups, as assessed in Figure 1, were compared by unpaired t-test. Specificity, sensitivity, diagnostic odds ratio, and logistic likelihood ratio of the BED-EIA and various tentative INNO-LIA HIV I/II Score algorithms for recency, as presented in Tables 1–3, were calculated by means of contingency tables and univariate and multivariate logistic regression analysis, as implemented by the StatView 5.0 program for Macintosh (SAS Institute, Cary, North Carolina, United States). Physicians' information was used as the reference standard for recency in all such evaluations. Estimates for the recent infection rates in Table 4 were obtained by the equation Recency Rate = (ntested recent/ntested + %Specificity/100 − 1) / (%Sensitivity/100 + %Specificity/100 − 1). This equation is based on the relationship ntested recent = ntrue-recent + nfalse-recent, wherein ntrue-recent = ntested × Recency Rate × %Sensitivity/100 and nfalse-recent = ntested × (1 − Recency Rate) × (1 − %Specificity/100). Window-based estimates of the recent infection rate were performed by the equation (nrecent/748) × (365/Window), shown with Table 5.
(A) Sum of antibody scores to env antigens sgp120 and gp41 (top graph), gag antigens p24 and p17 (middle graph) and pol antigen p31 (bottom graph); bars represent means and error bars their 95% confidence intervals. Reaction is stratified according to recency definitions 1, 2, or 3 and other reported staging information (see Methods).
(B) Correct order of recency definitions based on increasing antibody development. Box plots show sum of antibody scores to all five HIV-1 antigen bands. Boxes indicate the median and the 25th and 75th percentile. Horizontal lines located outside of, but closest to the boxes represent the 10th and 90th percentile, respectively. Outliers are plotted individually. The medians of the groups consisting of infections not classified coincide with the 75th percentile (upper limit of box). p-Values on top denote differences between subgroups of recent infections.
Performance of Various Algorithms for Detecting Recent Infection among Cases of Defined Recency Status
Diagnosis of Recent Infection and Test Concordance in Dependence of Stage
Percent Sensitivity of Various Recency Algorithms at Different Phases of Recent Infection
Estimation of the Overall Recent Infection Rate in the Study
INNO-LIA Window Periods Derived from Seroconversion Panels and Estimates for the Recent Infection Rate
A total of 765 newly diagnosed HIV infections were reported to the SFOPH during the 12 mo of the study (July 05–June 06). Seventeen cases were excluded due to missing INNO-LIA results, thus leaving a total of 748 patients for evaluation (97.8%). All infections were by HIV type 1. A total of 195 patients met the definition of a recent infection as described in Methods, and 161 patients met the definition of an older infection. Of these, 84 were reported to be in CDC stage B and 77 in stage C. Remaining unclassified were 392 patients, 252 without symptoms (stage A) and 140 with no information provided. The main characteristics of the study population are summarized in Table 6.
Characteristics of the Study Population
INNO-LIA Reactivity in Dependence of Stage
INNO-LIA reactivity to env bands sgp120 + gp41, gag bands p17 + p24, and pol p31 in the different groups is summarized in Figure 1A. Infections defined as recent had lower mean antibody intensities to all antigens compared to all other groups (p < 0.001 in all comparisons). Those with both symptoms of PHI and a reported negative HIV test within the past 12 mo (thus meeting both recency definitions 1 and 2) had lower antibodies on average than those with reported PHI but no negative HIV test (recency definition 1), and the latter in turn had lower antibody levels than those with a history of a negative HIV test but no PHI symptoms (recency definition 2). Thus, those with both symptoms of PHI and a reported negative test represented an early phase, those with PHI symptoms alone an intermediate phase, and those with a documented negative test alone a late phase of recent infection (Figure 1B). Moreover, infections defined as recent based on their negative or indeterminate results in HIV antibody tests at the time of diagnosis (recency definition 3) showed the lowest antibody reactivity of all, thus classifying themselves as the most recent infections. Figure 1B also shows the p-values for the differences between the various subgroups of recent infection.
Antibody reactions in CDC stage A were similar to those in stages B or C except that antibodies to gag antigens were slightly higher than in stage C (p = 0.01), in agreement with established knowledge [12,13]. The 140 cases with no information were indistinguishable as a group from CDC stage A (Figure 1B) and like A exhibited a trend for higher antibodies to gag antigens compared to CDC stage C (for p17, p = 0.053).
Prediction of Recent Infection in Patients with Defined Recency Status
A first evaluation of recency prediction by BED-EIA or INNO-LIA was based on the 356 cases classified either as recent or older as defined under methods. The BED-EIA classified 127 of the recent 195 infections as recent, exhibiting 65% sensitivity. The low sensitivity of the BED-EIA is due to the longer duration of the interval defined recent (12 mo in this study compared to 153 d in other studies using this test) [2,3,14]. The BED-EIA also classified 129 of the 161 older infections as older, exhibiting 80% specificity. Overall correct results amounted to 72%, the diagnostic odds ratio was 7.4, and the logistic likelihood ratio (LLR) Chi-square was 78.7 (Table 1).
Univariate logistic regression analysis showed that a low antibody score to any of the five HIV-1 antigen bands of the INNO-LIA strip was associated significantly with recent infection (p < 0.0001 for all, data not shown). Algorithms (Alg) 2–6 in Table 1 demonstrate the best power to discriminate between recent and older infection, as indicated by the highest LLR Chi-square achieved when varying the band intensity cut-off. Some of these algorithms exhibited similar or superior strength compared to BED-EIA, as shown by higher diagnostic odds ratios and LLRs. Alg2–6 were considerably more specific than was BED-EIA, but their sensitivities were lower, thus resulting in an overall lower percentage of correct results for INNO-LIA than for BED-EIA.
When using bands in combination and again optimizing cutoffs by means of logistic regression analysis, algorithms with around 98% specificity and 40% sensitivity were developed (Alg7–9). Based on the observation that seroconversion to p31 in Western blot occurs consistently later than to p24 [15,16], we also assessed this criterion alone (Alg10) or in combination (Alg11–13). Despite being a rather weak criterion on its own, Alg10 strongly increased sensitivity, albeit at some cost to specificity, when added to other criteria. Overall correct results by Alg11–13 amounted to around 70%, which was comparable to BED-EIA (72%). Multivariate logistic regression analysis adjusting for sex, transmission risk, and INNO-LIA reading mode (visual or automated) demonstrated no impact of these variables on the strength of the algorithms (unpublished data). Moreover, the reading mode had no significant impact on the INNO-LIA result. Although automated reading was associated with overall slightly lower intensity scores (p = 0.005, Mann-Whitney U test), probably due to the fact that the Liras software counts a score of 4 as 3, this reduction in mean scores had no impact on an algorithm's outcome, as an algorithm's cutoff is always placed at lower scores. For Alg12, for example, the odds ratio for automated versus visual reading for ruling an infection as recent was 1.11 (95% confidence interval [CI] 0.76–1.62; p = 0.60). There was also no difference in the case of single-band algorithms.
Recency Rates in Different Patient Groups and Test Concordance
The proportion of patients ruled to have been infected recently by BED-EIA or INNO-LIA and the concordance of the two procedures in the different patient groups is shown in Table 2. Alg12 was selected for this comparison due to its overall highest rate of correct results (compare to Table 1). In all groups, BED-EIA found considerably more samples recent than did Alg12. Concordance between the two procedures was lowest among recent infections (74%) and highest in CDC stage C (86%). Note again that the relatively low sensitivity of the BED-EIA compared to other studies is due to the longer duration of the interval defined recent in this study.
We next investigated the sensitivity of selected algorithms of Table 1 for detection of the early, intermediate, or late phase of recent infection, as established in Figure 1B. The sensitivity of BED-EIA and all INNO-LIA algorithms decreased from early to intermediate to late phase (Table 3). In the early phase, INNO-LIA algorithms were similar in sensitivity to BED-EIA. In the intermediate and particularly the late phases of recent infection, INNO-LIA was considerably less sensitive than BED-EIA. Thus, the overall higher sensitivity of BED-EIA in Table 1 was due to its better recognition of the intermediate and late phases of recent HIV infection.
Estimation of the Recent Infection Rate in the Entire Study Population
Given the more than 50% cases without reference recency information, the true proportion of recent infections (infections that occurred within the past 12 mo) in the study population was unknown. We estimated this value on the basis of the results of the different recency tests in the entire study population. The equation used for these estimates (see Methods) adjusts for a test's sensitivity and specificity, as determined in Tables 1 and 3.
The BED-EIA ruled 262 (35.3%) of the 748 infections as recent. When entering the sensitivity and specificity determined in Table 1 into the equation, a proportion of 33% recent infections corresponding to 250 cases was calculated (Table 4, model 1). Recency estimates by Alg12 and Alg9 were markedly lower, but yielded identical results to each other (27%, 204 cases), despite their considerable difference in the actual number of infections diagnosed as recent (130 versus 88). For Alg3 which according to Table 3 identifies only early recent infections and did not detect any further recent cases outside the group defined as recent, the estimate was remarkably close (26%).
Application of the sensitivity and specificity rates of the reference group of Table 1 to the unknown group is, however, feasible only if both groups are composed similarly; otherwise bias is introduced. Figure 1B shows that there is indeed considerable heterogeneity. Regarding their overall antibody reaction the unknown group differs significantly from the reference group of Table 1 (Mann-Whitney U test, p < 0.001). The unknown group has very little overlap with the early and intermediate phases of recent infection (Figure 1B). Thus, if the nonclassified infections include any recent infections at all, these are likely to be in the late phase of recent infection. It is therefore appropriate to use the reduced sensitivity rates shown in the last column of Table 3 for this group. Specificity, in contrast, was very similar among the different groups, in particular as regards INNO-LIA (cf. Table 2). Hence, by doing a mixed calculation, i.e., applying the sensitivity of Table 1 to the reference group and the reduced sensitivity of late recent infection of Table 3 to the unknown group while applying the specificity of Table 1 to both groups, we obtained more appropriate estimates for the recent infection rate of the entire study (Table 4, model 2). Compared with model 1 the adjusted model 2 showed an only 12% higher rate of recent infections for the BED-EIA, but as much as 20%–30% higher rates for Alg9 and Alg12, in agreement with the fact that the sensitivity of BED-EIA is reduced less in the late phase of recent infection than is the sensitivity of INNO-LIA (compare to Table 3). With recency rates of 0.35 and 0.33, respectively, Alg12 and Alg9 now showed good agreement with BED-EIA (0.37), while the estimate by Alg3, which does not detect cases in the late phase of recent infection, remained unchanged at 0.26. Alg3 clearly underestimated recent infection.
Window Periods and Window-Based Estimation of the Recency Rate
In order to determine the window periods of the different INNO-LIA algorithms we analyzed INNO-LIA results of 15 seroconversion panels (Table 5; see also Methods). Alg3 (gp41) was associated with the shortest window period among the single band algorithms, followed by Alg5 (p24), Alg6 (p17), Alg2 (sgp120), and Alg4 (p31). The time span of many panels was shorter than the window period of many algorithms. The resulting window information is thus based on too few measurements and not reliable. Nevertheless, we tentatively used this information for an independent estimation of the recent infection rate in our study population. With this approach, BED-EIA yielded a rate of 0.41 compared to 0.37 obtained by model 2 of Table 5. Alg3 (gp41) and Alg5 (p24), whose window periods are the most reliable, both yielded a rate of 0.53. Other INNO-LIA algorithms supported less well by seroconversion panel results yielded rates of up to 0.98, thus confirming that the respective windows are indeed too short.
We demonstrate that a patient's antibody reaction in the INNO-LIA HIV I/II Score assay contains information which, similar to the Calypte BED-EIA, allows a distinction to be made between recent and older HIV-1 infection, thus providing a tool for estimating HIV-1 incidence in a population. Because antibody reactions to the five HIV-1 antigens measured by the INNO-LIA evolve over time after the infection (Figure 1), we evaluated various algorithms for their ability to distinguish between recent and older infection in a cohort of 748 unselected HIV-1 infected patients newly diagnosed during a period of 12 mo in Switzerland. The best INNO-LIA algorithms ruled 40%–50% of the 195 infections defined as being recent (up to 12 mo duration of infection) as recent, while ruling 95%–99% of the 161 infections defined as being older as older. In comparison, a dedicated commercial recency test, the BED-EIA, ruled 65% of the recent samples as recent and 80% of the older samples as older (Table 1). Concordance of the two tests was 74%–86% based on stage (Table 2). Both tests exhibited about 80% sensitivity for the early phase of recent infection, while showing reduced sensitivity for the intermediate and, particularly, late phases of recent infection (Table 3). Based on the sensitivity and specificity rates thus obtained from patients of known recency status we estimated the proportion of recent infections in the entire cohort of 748 patients. Utilizing an adjusted model we obtained recency rates of 0.33 and 0.35 for two INNO-LIA algorithms and of 0.37 for the BED-EIA (Table 4), which was similar to the window-based estimate of 0.41 for the BED-EIA (Table 5). There was higher discrepancy for the INNO-LIA algorithms, due to still-unreliable window period estimates.
All STARHS reported to date utilize window periods, i.e., the mean time from infection to the first positive result of a test. Based on the number of cases ruled recent in a tested population and the length of the window period the annual incidence can be calculated. The approach in our study is fundamentally different. Based on reference information obtained from the treating physicians we first defined two subsets of patients. One subset consisted of patients infected within 12 mo prior to HIV diagnosis (recent infection), and the other of patients who had older infections based on symptoms of CDC stage B or C. We used these two reference subsets to determine the sensitivity and specificity of various recency algorithms (Tables 1–3). Based on the now-known sensitivity and specificity and the number of cases ruled recent by a given algorithm the proportion of recent infections in the entire study population was calculated (Table 4). Thus, while the classical STARHS approach requires reliable window information for the test but no clinical information on the patients tested, our approach requires reliable clinical reference information for a subgroup of patients but no window information for the test.
During seroconversion, an HIV-infected person progresses from seronegativity to a pattern of full reactivity to all major HIV proteins [15]. Defining HIV seroconversion or recent infection as anything less than a full antibody reaction pattern may thus seem trivial. However, as disease progression is associated with decreasing concentrations of many antibodies, there is a second, late phase in HIV infection with incomplete patterns or submaximal concentrations of antibodies [12,13,17–20]. The detection of patients in recent infection by means of differential antibody reactivity thus requires a careful optimization of candidate algorithms with the aim to maximize correct assessment. The best INNO-LIA algorithms compared well with the BED-EIA regarding power to discriminate between recent and older infection and were considerably more specific than the BED-EIA (Table 1).
Unlike the BED-EIA, which due to its deliberately reduced sensitivity compared to HIV screening tests has no role in the diagnosis of HIV infection, the INNO-LIA is an excellent test for confirmation of HIV infection and is superior to (and less expensive than) Western blot for differentiating between HIV-1 and HIV-2 infection [9,10]. Early identification of HIV-2 infection is becoming increasingly important, as HIV-2 cannot be quantitated by any of the FDA-approved tests for HIV-1 RNA measurement [21] and is naturally resistant to several commonly used antiretroviral drugs [22–25]. The INNO-LIA HIV I/II Score assay is CE marked, i.e., approved for diagnostic use in the European Union, but currently cannot be used in the US, as the test is not FDA approved. INNO-LIA based STARHS is not a reasonable option for low-resource countries that use less expensive combinations of HIV screening tests for confirmation of HIV infection.
The recency information provided by the INNO-LIA comes at no additional costs and can be integrated easily into existing national HIV reporting systems. The number of cases for which recency information is available will thus be higher than in systems in which recency information must be gained from costly epidemiologic studies. This fact should result in HIV-1 incidence estimates of overall higher quality. The multicenter nature of the present study and the employment of both visual and automated strip evaluation in the 12 collaborating labs, with no apparent impact on the result, suggests that INNO-LIA-based recency assessment can be transferred to other labs without loss of quality. Studies to clarify this point and to determine whether automated reading is advantageous are currently underway.
In order to obtain an independent estimate of the recent infection rate in our study we also used a window-based approach (Table 5). The resulting infection rate of 0.41 of the BED-EIA was remarkably close to the 0.37 obtained by the adjusted model in Table 4. This agreement of results suggests that, by and large, the information from the physicians was reliable, although we cannot exclude the possibility of misclassification. For example, some PHI cases presenting with severe clinical manifestations may have been misclassified as older infections [26–29]. Altogether, the window based recency assessment by the BED-EIA however validates the sensitivity/specificity-based approach.
As the time span covered by many of the seroconversion panels was too short, sufficiently accurate window information is still lacking for most INNO-LIA algorithms. For Alg3 (gp41) and Alg5 (p24), window periods of 36 d and respectively 38 d were obtained, which is considerably shorter than the 153 d of the BED-EIA and consistent with the low sensitivity of INNO-LIA for the intermediate and late phases of recent infections (Table 3). Alg3 and Alg5 yielded an identical recent infection rate of 0.53, which is somewhat higher than that of BED-EIA (0.41). As the window periods are very short, a few days' difference can have a big effect when calculating an annual rate. For example, increasing the window periods of Alg3 or Alg5 by 6 d, as would result from using an average seroconversion interval of 28 d instead of 22 d (see Methods), would reduce the rate from 0.53 to 0.45. Testing of further panels covering extended time periods thus is urgently needed to define longer INNO-LIA windows with sufficient accuracy. Once established, window-based recency estimates will also be feasible for INNO-LIA algorithms and probably represent the preferred method. Different algorithms will also be usable in combination, which should result in more reliable estimates.
A possible current limitation of INNO-LIA-based recency testing may derive from the influence of infections by non-B subtypes of HIV-1. Like other European countries, Switzerland has a high rate of non-B infections [30] and the proportion of such viruses among newly diagnosed HIV-1 infections has now reached proportions of two-thirds in women and one-third in men (unpublished data from the Swiss genotypic resistance test database). Patients infected with such viruses may produce antibodies of reduced avidity to the subtype B antigens frequently employed in diagnostic tests, thus leading to low-reactivity patterns when tested and subsequent false diagnosis of recent infections. Such an effect has been observed with several early STARHS tests [31,32]. The BED-EIA, developed in order to overcome this problem, therefore features a branched peptide consisting of the immunodominant gp41 B-cell epitope of subtypes B, D, and E [3]. The fact that all INNO-LIA based algorithms were considerably more specific than the BED-EIA suggests that subtype interference should be less a problem for the INNO-LIA than it is for the BED-EIA. Systematic studies are planned to clarify this point.
Another known factor which may impair the specificity of STARHS consists of the reduced antibody concentrations associated with advanced disease stage (Figure 1). A further problem consists of cases that never reach a sufficiently high optical density to qualify as older infection [33]. The Joint United Nations Programme on HIV/AIDS Epidemiology Reference Group has recently issued a warning that the BED-EIA may overestimate HIV-1 incidence and should not be used for routine surveillance applications, and other investigations have also reported overestimation [14,34]. As the specificity of INNO-LIA based algorithms in patients with reported symptoms of AIDS is already high (Table 2), this concern should not be a problem for INNO-LIA. Nevertheless, studies addressing this question by means of well characterized patients of the Swiss HIV Cohort Study (SHCS) are planned.
As shown by Figure 1B, the nonclassified infections differ as group from the classified infections. Application of the sensitivity and specificity rates of the reference classified group to the unknown group will thus introduce bias. As a consequence, model 1 of Table 4, which does not correct for such bias, clearly underestimates the overall rate of recent infections. Although model 2 of Table 4 adjusts for the discrepancy, it is possible that the model still underestimates the true proportion of recent infections in the unknown group and, thus, the entire study population. Given the small difference between window-based and sensitivity/specificity-based recency rate estimates (0.41 compared to 0.37 for the BED-EIA), the influence of such possible further bias in the present study should be small, however. Nevertheless, as window-based recency assessment does not require knowledge of group composition, it should be the preferred method of INNO-LIA based recency assessment once INNO-LIA windows have been established with sufficient precision. Window-based recency assessment should also facilitate transfer of the method to other populations.
In conclusion, we provide proof of principle that a well-standardized line immunoassay for HIV confirmation and type differentiation also contains information on whether an HIV-1 infection is recent. The recency information provided by the INNO-LIA HIV I/II Score is available at no additional expenditure to countries in which this test is routinely used for confirmation of an HIV infection and HIV type differentiation. Utilization of this information could improve HIV surveillance in such countries. Because reliable window periods for INNO-LIA algorithms have not yet been established, INNO-LIA based recency assessment is currently restricted to the sensitivity/specificity approach described here. As the sensitivity and specificity of INNO-LIA algorithms may vary between different populations, it will be necessary to assess them anew when transferring the method to a different study population. Additional studies are needed to establish reliable window periods for the different INNO-LIA algorithms, to clarify the influence of HIV-1 subtype, and to further assess the specificity of the method in advanced disease.
The authors acknowledge the assistance of Katrin Steinbeck in this work and are grateful to Dr. Leslie R. Bisset for critical reading of the manuscript. The corresponding author, Jörg Schüpbach, supplied the information regarding Bruno Güntert's contribution to the manuscript and his competing interests and it is correct to the best of his knowledge.
Author Contributions
JS, RS, and PV designed the study. JS, MDG, DS, and PV analyzed the data. JS, ZT, CN, SY, PB, LM, MG, RD, DS, IS, CA, BM, and BG enrolled patients. JS, SY, PB, LM, MG, DS, and PV contributed to writing the paper. MDG, ZT, CN, SY, PB, LM, MG, RD, DS, IS, CA, GM, BG, SD, and PV collected data or performed experiments for this study. MDG contributed the clinical data (from surveillance) needed for the analysis. Patients included in the present study are based on patients enrolled in the CHAT study, which included all individuals with a newly diagnosed HIV infection for the duration of 1 year. SD and PV were responsible for the design, data collection, and summary of the CHAT study, of which some results are presented in the present study.
- 1. Janssen RS, Satten GA, Stramer SL, Rawal BD, O'Brien TR, et al. (1998) New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA 280: 42–48.
- 2. Parekh BS, McDougal JS (2005) Application of laboratory methods for estimation of HIV-1 incidence. Indian J Med Res 121: 510–518.
- 3. Parekh BS, Kennedy MS, Dobbs T, Pau CP, Byers R, et al. (2002) Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence. AIDS Res Hum Retroviruses 18: 295–307.
- 4. Schupbach J, Popovic M, Gilden RV, Gonda MA, Sarngadharan MG, et al. (1984) Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science 224: 503–505.
- 5. Sarngadharan MG, Popovic M, Bruch L, Schupbach J, Gallo RC (1984) Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science 224: 506–508.
- 6.
[No author listed] (2006) Das schweizerische HIV-Testkonzept—aktualisierte Uebersicht über Technisches Konzept und Laborkonzept. BAG Bulletin. pp. 22–34. Available: http://www.bag.admin.ch/dokumentation/publikationen/01435/01795/index.html?lang=de. Accessed 7 November 2007.
- 7. {No author listed] (1993) From the Centers for Disease Control and Prevention. (1993) revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. JAMA 269: 729–730.
- 8. Hecht FM, Busch MP, Rawal B, Webb M, Rosenberg E, et al. (2002) Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 16: 1119–1129.
- 9. Pollet DE, Saman EL, Peeters DC, Warmenbol HM, Heyndrickx LM, et al. (1991) Confirmation and differentiation of antibodies to human immunodeficiency virus 1 and 2 with a strip-based assay including recombinant antigens and synthetic peptides. Clin Chem 37: 1700–1707.
- 10. Walther L, Putkonen P, Dias F, Biberfeld G, Thorstensson R (1995) Evaluation of HIV-1/HIV-2 immunoblots for detection of HIV-2 antibodies. Clin Diagn Virol 4: 67–79.
- 11. Busch MP, Satten GA (1997) Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure. Am J Med 102: 117–124.
- 12. Lange JM, Goudsmit J, De Wolf F, Coutinho RA, van der Noordaa J (1988) Serological markers in HIV infection. Ann Med Interne (Paris) 139: 80–83.
- 13. Schupbach J, Haller O, Vogt M, Luthy R, Joller H, et al. (1985) Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS. N Engl J Med 312: 265–270.
- 14. Karita E, Price M, Hunter E, Chomba E, Allen S, et al. (2007) Investigating the utility of the HIV-1 BED capture enzyme immunoassay using cross-sectional and longitudinal seroconverter specimens from Africa. AIDS 21: 403–408.
- 15. Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, et al. (2003) Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17: 1871–1879.
- 16. Lindback S, Thorstensson R, Karlsson AC, von Sydow M, Flamholc L, et al. (2000) Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure. Karolinska Institute Primary HIV Infection Study Group. AIDS 14: 2333–2339.
- 17. Lange JM, de Wolf F, Krone WJ, Danner SA, Coutinho RA, et al. (1987) Decline of antibody reactivity to outer viral core protein p17 is an earlier serological marker of disease progression in human immunodeficiency virus infection than anti-p24 decline. AIDS 1: 155–159.
- 18. Pedersen C, Nielsen CM, Vestergaard BF, Gerstoft J, Krogsgaard K, et al. (1987) Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection. Br Med J (Clin Res Ed) 295: 567–569.
- 19. Schmidt G, Amiraian K, Frey H, Stevens RW, Berns DS (1987) Densitometric analysis of Western blot (immunoblot) assays for human immunodeficiency virus antibodies and correlation with clinical status. J Clin Microbiol 25: 1993–1998.
- 20. Manca N, di Marzo Veronese F, Ho DD, Gallo RC, et al. (1987) Sequential changes in antibody levels to the env and gag antigens in human immunodeficiency virus infected subjects. Eur J Epidemiol 3: 96–102.
- 21.
Schüpbach J (2003) Human imunodeficiency viruses. In: Murray PR, Baron EJ, Jorgenson JH, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 8th Ed. Washington (D. C.): ASM Press. pp. 1253–1281.
- 22. Tuaillon E, Gueudin M, Lemee V, Gueit I, Roques P, et al. (2004) Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups. J Acquir Immune Defic Syndr 37: 1543–1549.
- 23. Ntemgwa M, Brenner BG, Oliveira M, Moisi D, Wainberg MA (2007) Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Antimicrob Agents Chemother 51: 604–610.
- 24. Parreira R, Monteiro F, Padua E, Piedade J, Venenno T, et al. (2006) Natural polymorphisms of HIV type 2 pol sequences from drug-naive individuals. AIDS Res Hum Retroviruses 22: 1178–1182.
- 25. Reid P, MacInnes H, Cong ME, Heneine W, Garcia-Lerma JG (2005) Natural resistance of human immunodeficiency virus type 2 to zidovudine. Virology 336: 251–264.
- 26. Berger DS, Bucher G, Nowak JA, Gomatos PJ (1996) Acute primary human immunodeficiency virus type 1 infection in a patient with concomitant cytomegalovirus encephalitis. Clin Infect Dis 23: 66–70.
- 27. Tindall B, Hing M, Edwards P, Barnes T, Mackie A, et al. (1989) Severe clinical manifestations of primary HIV infection. AIDS 3: 747–749.
- 28. Vento S, Di Perri G, Garofano T, Concia E, Bassetti D (1993) Pneumocystis carinii pneumonia during primary HIV-1 infection. Lancet 342: 24–25.
- 29. Tattevin P, Camus C, Arvieux C, Ruffault A, Michelet C (2007) Multiple organ failure during primary HIV infection. Clin Infect Dis 44: e28–29.
- 30. Boni J, Pyra H, Gebhardt M, Perrin L, Burgisser P, et al. (1999) High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland. J Acquir Immune Defic Syndr 22: 174–179.
- 31. Parekh BS, Hu DJ, Vanichseni S, Satten GA, Candal D, et al. (2001) Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand. AIDS Res Hum Retroviruses 17: 453–458.
- 32. Young CL, Hu DJ, Byers R, Vanichseni S, Young NL, et al. (2003) Evaluation of a sensitive/less sensitive testing algorithm using the bioMerieux Vironostika-LS assay for detecting recent HIV-1 subtype B' or E infection in Thailand. AIDS Res Hum Retroviruses 19: 481–486.
- 33. McDougal JS, Parekh BS, Peterson ML, Branson BM, Dobbs T, et al. (2006) Comparison of HIV type 1 incidence observed during longitudinal follow-up with incidence estimated by cross-sectional analysis using the BED capture enzyme immunoassay. AIDS Res Hum Retroviruses 22: 945–952.
- 34. Anonymous (2006) UNAIDS Reference Group on Estimates, Modelling and Projections: statement on the use of the BED assay for the estimation of HIV-1 incidence for surveillance or epidemic monitoring. Wkl Epid Rec 81: 40.


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Lonely Planet recently released its Best in Travel 2014, which includes a list of the top 10 cities for traveling. These cities are spread across the globe and include classics as well as cities that are just coming into their own as traveler destinations. The Lonely Planet list includes some obvious choices like Paris, Cape Town, Zurich, Shanghai, Vancouver, Chicago, and Auckland but it also includes less obvious choices like Trinidad, Cuba, Adelaide, Australia, and Riga, Latvia. Check it out here and then let us know, which cities would you add to the 2014 list?
Abandoned Coal Mines Of West Virginia
West Virginia has been defined by the coal industry in many ways. While the industry still employs miners all over the state, abandoned coal mines are remnants throughout the area of a booming past. Exploring the abandoned coal mines is highly dangerous, but the hobby attracts the likes of spelunkers and urban explorers and it's easy to understand why-the mines are mysterious places that provide a gateway to how life used to be in West Virginia.
According to the website for Coalwood, W.V., the number and location of the abandoned mines is largely unknown. Open shafts and horizontal openings to these abandoned coal mines are often difficult to spot amid the overgrowth. Once inside, abandoned coal mines pose the threat of rusted machinery, dangerous bodies of water and even explosives that are now defected.While the videos and photos available online of these abandoned coal mines are impressive, explorers put themselves at great risk to obtain this kind of footage. What do you think West Virginia officials should do with the abandoned coal mines?
The Government is Back Up and Running, and So Are the National Parks
Everyone rejoice: now that the shutdown is finally over, government employees can get back to work and the rest of us can go out and explore any National Park that we feel like. No sneaking around with the risk of getting fined, you can now travel as you wish.
While some National Parks found ways to open back up during the shutdown, thanks to a handful of states that opted to pay the federal government to keep their parks functioning, today the 400 some National Parks will open back up as the furlough for the 20,000 park employees ends.Beyond National Parks, monuments and memorials managed by the National Park Service will also open back up.
But you know what all this means? After over two weeks of shutdown, you may expect lines and plenty of tourists in the places you have been wanting to visit. But hey, at least they're open.
Sports Map Of America
The talented illustrator Jess Fink over at Slate worked with Chris Kirk on interactive design to create the sports map of America. The map shows which sports are most popular in individual U.S. states with graphics. The full sports map, which can be seen here, includes information on each state, like its official state sport, if there is one, and other sports that were considered when making their decision. Most picks don't come as a surprise -– mountain climbing goes to Colorado, skateboarding to California, and ice hockey to Michigan – but others are less obvious.
Go click around, have some fun and learn a thing or two about the athletic tendencies of Americans by state.
Shutdown Status: States Pay To Reopen Some National Parks
We're going on two weeks of government shutdown, with tourists hoping to see national parks having to sneak in or go home. Thousands of park workers have been furloughed and local businesses who generate income from tourism are feeling the pinch. Several U.S. states are taking matters into their own hands, effectively paying the federal government so that they can reopen.
The status as of today:
Arizona: It's costing $651,000 to open the Grand Canyon for a week, though no money is allotted past that time and some local businesses worry it won't help them in the long run.
Colorado: Over 10,000 visitors went out the Rocky Mountain National Park this weekend after the state reached an agreement to pay over $40,000 per day to keep it open.
New York: The Statue of Liberty re-opened yesterday, costing New York $61,000 per day out of its tourism budget — but visitors generate an estimated $350,000 daily.
South Dakota: Mount Rushmore will cost over $15,000 a day to reopen, with corporate donors helping the state open the park again today.
Utah: 8 attractions will reopen today, including Bryce Canyon and Zion National Park, at a cost of $166,000 per day.
See the status of all the national parks here.

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[Pages 60 - 68]
Mordechai Majerowicz |
As my yearnings for my birth town overcome me and I am shaking with excitement, affection, and longing, I would like to express some of the typical features and memories of the days that Jewish Zloczew was still standing on its ground. Unfortunately, I do not have all the information and details that will testify to the beginning of our town and its development. Nothing remains from past days but vague and foggy memories that were kept in my heart. Time's jaws also bit portions because it has been more than thirty years since I left my town, but my soul's attachment to it did not cease to exist a bit and its reflection is still vivid in my eyes to the fullness of its beauty and glory.
These pages will probably be read by the previous generation, those who still remember our town, the town in which they spent their best years, walked her streets, worked, created, dreamed and struggled for a better future. It's possible that some of their children and grandchildren, who were also born there but were too young to remember those days, will also find it interesting to know something about their ancestors' way of life, customs and traditions, character, writings and legacy until the slaughterer's hand caught them. But, these lines are dedicated mostly to our children and grandchildren, to the young generation born here in this land and in the diaspora; to them, Zloczew is like a sealed book.
Occasionally, the younger generation does not understand the history of the previous generation, and they even have reservations of its experiences, but it's possible that, in days ahead, curiosity, the desire to learn and to search their origin and roots will rise and make them turn to the history of Zloczew and all that surrounded it. For that purpose, we shall remember who, what and how things were.
As little as this stream was, it contained all kinds of currents: right and left, extreme and moderate. Regardless of how apart they were, united they stood in the big and active river of Jewish life, full of interest and work. It isn't one of the easier tasks to turn the eyes to this far and full of deep nostalgia period. They are far and ambivalent- the culture and its terms, the distance and daily life; and deep is the pain in the heart when remembering the beautiful years of youth, because not only did the flowers wither, but the stems and the leaves were torn from their roots as well. Not just the community, but also the entire Jewish town was destroyed and annihilated. The way of life that had developed from the town's unique culture was destroyed and erased, and even more: all the essence and atmosphere of Jewish Zloczew is gone.
You could feel the multi-faceted labor, deeply rooted in the town from the six days of creation, and no strong wind or storm could uproot the strong foundations of the Jewish community. Events and processes of other provincial towns from this destroyed and no longer existing world were also reflected here.
Not only was the Jewish person permeated and interwoven in the generations' texture of the Jewish entity and essence, nature and the environment were also filled with it. Everything breathed air that was soaking in the hidden treasures of Jewishness, not to mention the streets, the alleys and the homes, all completely based upon the Jewish character and contents in other words, Jewishness was reflected upon the unique atmosphere floating above the town and sweeping with it a fullness of a universe. Clearly, this camp included various parts, distinguished by social identity marks, but despite the difference between them, a difference that grew as years passed by, the partnership of fate was maintained. Here, all shared with all joy and grief, sorrow and content.
Nonetheless, Zloczew was different. Following the horrible Holocaust that befell the Jewish people, we shed our tears for the entire Jewish world, a rich world that was uprooted as if it was formed from one piece of material. But in reality, the Jewish town in Congressional Poland had its unique nature and character. It represented a complete mechanism of features. These towns were located next to the big metropolises - Lodz and Warsaw, and their rhythm of life was poured into their provincial habits just as blood flows from the heart to the artery.
The pulse of life of neighboring cities beat in Zloczew. Jews traveled from here to Lodz and Warsaw to sell, work, and to visit relatives. The pace and sizzle of the big cities activities were immersed in the provincial way of life. The outside bubbly centers, and especially the productive industry of Jewish Lodz, brought the dynamic factor of social activity into the Jewish atmosphere and thus opened a window to the wide world. But, as great as the contact with the outside world was, and as much as it brought new ideas and thoughts, it did not weaken the local multi-faceted vitality of the town.
The tough reality of everyday life did not defy the romanticism of glamorous freedom ideas expressed in various ways, and the coherence that erupted from the daily hardships did not intimidate great dreams. As I look back to those years, I am thrown into the simplicity of Jewish atmosphere. During a history of a thousand years of Jewish exile, communities erupted in every corner of the world. I do not intend to point at all the small and big stations in our wanderings, stations in which Jewish life, full of activity, developed and flourished. Nonetheless, a known fact is that in no other place throughout our geographic Diaspora was the drama of the Jewish factor so elevated as it was in the provincial towns of central Poland. Toledo could have been a flourishing garden to our poetry; Magenza could have been the capital of Jewish learning, a center of Torah and knowledge; Medzhibush could have fertilized and fed the sources of Hassidic thought, but all these communities lacked the typical uniqueness of the Shtetls of congressional Poland. They lacked the colorful heavenly rainbow, the natural curiosity to the various worlds, the interest in contradicting ideas and concepts, all found a wide field in this region: pious and secular, Zionists and Bundists, socialists and communists - all these combined and intertwined within the multi-faceted social activity and mingled within the perfection of simplicity and Jewish solidarity. This characteristic was typical of our town of Zloczew.
The respiratory system of the Jewish union was able to absorb into its lungs outside influences without losing its uniqueness and spirit of life. The youth could sing melodies originated elsewhere and mix them with Jewish melodies filled with national ideas. The line between the new literature read in the partisan libraries in town and the literature studied in Beit Hamidrash or Shtibalach was hardly seen because the mutual destiny and the mutual struggle (in all shapes and fronts) for the right to exist with dignity tied the different parts of the Zloczew Jewish union.
The Jewish town, although an integral and inseparable part of the general population, made the impression that it lives far from it and that sometimes moved outside space and time as if it was a community hovering above space and existing in its own era.
The Jewish town celebrated its Sabbaths, its national and religious holidays. The Jewish population was a minority within the general population, but only in the statistic sense. Nonetheless, from the spiritual and psychological sense, Jews lived in their own world as if they were the majority.
In the days of my youth, the town was passed from one hand to the other. This was during World War One, when leaders changed rapidly; the Russians left and the Germans entered. Then came the Poles. Even the expulsion could not steal from the Jews their sense of identity with the town or take away the security that the decree is just temporary. And, indeed, the moment circumstances changed, they all rushed back home, reconstructed the ruins, and again all social life began developing with all its characteristics - rules, details and manners.
But despite the stormy events, not a single factor could remove the Jews from their place. They matched themselves to the changing circumstances and, with great strength and resourcefulness, moved themselves to new sources of income. Their spirits remained unshaken. Although everything can fall apart in times of riots, war and chaos, events did not break their sense of security and belief in Jewish eternity. The belief in the eternity of the people of Israel was deeply rooted in the hearts of our town's Jews.
The youngsters were forced to mature and sober early in life, but they did not give up the sincere belief in a glorious future. They stood on solid ground with both feet and dreamed of ascending to a higher reality. Over the years, since I left my town of Zloczew, I was able to participate and listen to Kol Nidrei in various synagogues and Minyans, but in no other place did its holiness penetrate inside my bones the way it did in the Zloczew synagogue, covered with wax drops of the holy day candles and approaching me from the foggy memories of my childhood years.
I cannot forget the worshippers standing with their heads bowing down with humility, covered with their prayer shawls turned yellow after years of use and tears, and hovering above them is the mystical prophecy that promises a day is coming when wickedness and malice will pass from the earth and heaven's mercy will atone for the transgressions of those who have never transgressed and who never stopped praying to their Deliverer.
That same echo of holiness and great anticipation was felt in the air when Hatikvah had been sung enthusiastically in all the Zionist gatherings in town. It was not a mere singing but an expression of the existing Jewish national 'have' and pathos. [Translator Daphna Brafman notes: 'have' is defined as It's the existing national spiritual and emotional possession. All this possession they put in the singing of Hatikvah, in other words, they sang with all their heart and strength.] That same warmth was felt in the gatherings of the Jewish socialist parties in town, swept in the spirit of romanticism and full of the best of human ideals of liberty, equality and brotherhood. As these parties made sure the distance between them was not too big, they were able to stand close enough to weave their great dream. And it seemed as though the magical harmony from within, despite the deep contradictions and difference of opinions, is what symbolized the typical characteristic of Zloczew - the Jewish town of congressional Poland that, to our great regret, was completely annihilated in our time.
The community's budget was limited because it relied only (if I am not mistaken) on the taxes the Jewish residents of the town paid for slaughtering the poultry and cows. The cemetery was also a source of income for the communal funds, but it was limited and rare because money came only when a wealthy person died.
The ritual bath - Mikvah - was rented to a Jewish resident who paid rent to the community (in my days few Mikvah renters had rotated. Among them were: Shlomo Mikvah-Nikk, Moshe Fishales, Leib-Michael Hershlikowic, or as he was called 'Der Hoikher Leib'.) The bath was opened to men every week on Fridays and before a holiday, but women had special days during the week.
Community expenses were high because there was a need to maintain a rabbi, a shokhet, community clerk and more. Contact between the Jewish population and its community leadership was not frequent and it usually took place for such occasions as weddings, circumcision, or birth, when it was necessary to register the newborn and similar events that required approaching the community and its clerks.
There was also a 'Beit Hamidrash' near by. Those who prayed here were peddlers, traders, craftsmen and others. The place also hosted conferences and gatherings in which speakers and preachers of existing parties spoke: Socialist Zionists etc. Anti-religious activists, like the 'Bund', also used this place for their meetings. There were others who used to gather in 'Beit Hamidrash' to listen to a sermon of a traveling 'Magid'. Groups of young men gathered in 'Beit Hamidrash' for a study in depth of a Gemara page or a chapter of Mishnayot. In my time, I remember three such groups that included: Haim-Meyer Alter, Arieh Bresler, Yitzhak Zommer, Shimshon Zilberberg, Yekhiel Freund, Kalman Krimlovski, Yekhiel-Arie Krimlovski, Barukh Bergman, Yitzhak Gelbart, Faivel Gross, David Hershlikovitch, Yaakov Viroshevski, Arieh Zaltzberg, Moshe-Shimon Klinovski, Avraham Koll, Yehuda-Leibish Kashpitzki, Yoseph Zommer, Avraham-Yehoshua Lukatch, Hersheleh Lantzitzki, Yerakhmiel Freund, Faivel Freund, Meir-Gershon Krakovski, Yekhezkel Kashpitzki, Avraham Shlomkovitch and others. Here they used to recite a chapter of the Mishna in honor of the dead or on the 'yorzeit' of one of the town's dignitaries.
Aside from that, Zloczew had 'Shtibalakh' (small prayer houses) of Hassidic sects of Ger, Alexander or Amashnov.
In order to make the picture complete, we should also mention the 'Minyan' of the 'Bikur Holim' (visiting the sick) society that had organized social activities of many types, and it also had a charity fund (Gemilut Hassidim) that performed great deeds but that, unfortunately, I don't have enough details to present them here.
All these synagogues were an official part of the community, but their maintenance and expenses were upon their worshippers.
The Jewish teachers, with the exception of a teacher of religion, were not allowed inside the public schools. Teachers of religion changed several times during my days. If I am not mistaken, these were the teachers: Avigdor Tsalnik Mashirdaz, Yekhiel (Hilek) Freedman and Emanuel Dawidowicz. The three did not work much with these classes, but it was their official duty. As a matter of fact, they used religion classes for another purpose and under this cover they taught the history of the people of Israel. But, Ultra Orthodox factions could not tolerate it and they made sure that real religion lessons would be taught in school and not some Zionist stuff. Because of that, these excellent teachers were expelled from their position and replaced by a young Ultra Orthodox rabbi, Khanokh-Mordechai Gutfreund who was the son-in-law of Rabbi Damta (who became the rabbi following his death), and he taught religion classes the way the Ultra Orthodox demanded.
In addition to the two public schools, Zloczew had Hebrew and Jewish schools in which pupils from families with national awareness studied. The pupils of these institutions enjoyed the warm support of the town's Zionist organization. But maintenance of these schools was the responsibility of the children's parents and teachers. The teachers included:
The Lubshitz school functioned at the home of r' Avraham-Hirsch Faiwlowicz; Dorkhwolf school- Braudeh and Landau as teachers; Mizrahi school at the home of Avraham Gelbart, and the teachers were- r' Mordechai Baumgarten, Yoseph-Eliezer Moroko for holy studies, Yaakov Freund as Hebrew teacher, and Eliezer Baumgarten for general studies.
Zloczew also had two schools for girls: Beit-Yaakov of the Agudat Israel which was located at the home of r' Avraham-Shmuel Lifshitz, and a private school owned by Channa-Beila Goldring and Retsa Yadvab and operating at the home of the Kozhokh family, or, as it was called, Getsaleh's home.
The school for girls of Channa Beila and Ratsa Yadveb |
To my regret, I have no detailed information about these schools because it was during my early youth and things were not kept in my memory. But, what I do recall is that Rabbi Damta, with another Hassidic group, had established a Talmud Torah to compete with the existing Jewish schools, and especially with the Mizrahi School they viewed as a Treifa (impure). Talmud Torah taught children from the age of five to fifteen years old. They taught the Aleph Bet, Humash, Rashi, Gemara, Tosafot, and also basic math, Polish and more. But this school was not very successful and they had to return to the primitive method of teachings of the Heder in which the children spent twelve hours a day in an overcrowded room. A child who did not know the alphabet yet was forced to continue to Humash and other studies because age determined the subject and not readiness. The conditions in the Heder where they studied Humash were better than the ones for the younger kids but on Thursdays not all came prepared to the Parashat Hashavua's test. The highest levels of holy studies curriculum were the lessons of Gemara, Tosafot and Mishna, taught by the rabbi.
The Moshkovitch sisters with kindergarten children |
I regret not having documents or detailed information about the pre-Zionist period that could testify of the nature of such activity in Zloczew. We only know that the Ultra Orthodox circles were not fond of this activity and influences in town and that they used all tricks and measures to fail this activity.
According to their stories, things were conducted in such a manner until the beginning of World War I in 1914. Jewish refugees came to town after being forced to flee from their homes as a result of the fighting. All public activity ceased when the Russians took over because the new rulers treated the Jewish population with much suspicion. The economical situation turned worse with every passing day.
The Balfour Declaration of 1917 and the hopes and waves of idealistic reawakening it caused encouraged strong activity and a national renaissance in Zloczew. The Zionist organization in town became a collection of groups that later evolved into political parties: Poalei Tsion Smol, Poalei Tsion Yamin, and the Mizrahi.
The leftist Zionist circles and the anti-Zionist groups had no influence.
Following the decisions made at the San-Remo convention in 1922, I remember how women had removed wedding bands and other jewelry to contribute for the land of Israel. That same scene repeats itself when the Hebrew university was opened on Mount Scopus in Jerusalem.
The enthusiasm caused by this enterprise rose far beyond our visions. Activists of the Zionist Organization - under the direction of the late and admired Yaakov Bielawski - did great even in the Siem (parliament) elections of 1922 and 1928. But, at the same time, the Polish government and its local messengers began actions and attacks against Jews. Nonetheless, strong Zionist activity at all levels had received a strong boost.
Activity of the Zionist Organization with its youth group of Hakhaluts Hamerkazi was especially prominent. Many of these youngsters had joined summer colonies and training camps to prepare them for future Aliyah to the land of Israel (see details in the article about Hakhaluts Hamerkazi).
Of hundreds of Zloczew's youth first and most worth mentioning is Hashomer Hatsair with Yaakov Freund as its leader until 1925 (until he left for Israel.) Hashomer Hatsair was an exemplary youth movement in those days.
Other active movements in Zloczew were Dror, Beitar, Poalei Agudat Israel, all running a strong activity for the land of Israel, each according to their own way. I have no information about all the facets of their activities but I am convinced that those who were closer to them can elaborate.
The Melamdim (teachers) were also busy on Market Day. For instance, Lazer (Eliezer) Melamed: his wife had a permanent stand in the market where she sold pottery, dishes, bowls and vases. That is why Lazer-Melamed used to prepare the merchandise a day early and on Market Day he himself used to watch over it so it will not be stolen.
Take Israel-David Melamed for example - what help could he offer his wife on Market Day? After all, he had nothing to trade with and his wife had no stand in the market! Here is this story: the wife of Israel David, Esther-Leah, used to buy fruit, butter, eggs, and especially chickens from the farmers' wives. She kept the chickens and fattened them during the week, and then sold them to the town's wealthy ladies for the Sabbath. What, then, was Israel-David's job?
Indeed, he, too, was a part of the business. He had to pave the way with the saleslady, meaning, to touch and feel the chicken, blow the feathers and offer a low price while approaching other women so they don't raise the price. Only after such a softening preparation would Esther-Leah approach and buy the merchandize. On that day, obviously, Israel-David was unable to teach the children in the Heder, because even a Melamed has to have some Parnassa (livelihood/income)
This and more, one must not forget that every second Jew in our town was a merchant, a peddler, a craftsman, or someone who trades with something. There were Jews who took loans from the three existing funds (Spoldziltchi, Kopitski, and Gemilut Hassidim of the Bikur Holim society), bought scales and sacks and became a grain merchant. Tons of grains were supplied to Zloczew on market day and brought to the local or nearby mills. But the peddlers waited for the farmers along the roadsides and tried to buy from them at a lower price before they arrived in town.
The western side of the rink the central building the old Beit Hamidrash |
The town also had tailors, hat-makers, shoemakers, tinkers, glaziers, harness makers and others who have worked for the area's farmers and supplied their orders. When the farmer came to the craftsman for an order, he used to bring his products for sale, another factor in making these Monday Market Days so thriving and successful. Those people who made all effort to prepare orders were honest and decent men of labor, whose livelihood was founded on spending the entire week in hard work until it was time for Reuven the Shamash to bang on his hammer and call people to come to the synagogue just before the Sabbath. For these laborers, the Sabbath was their only day of rest and on that day the holiness of the Shekhina rested upon them and from it they drew the strength to continue the daily struggle for livelihood.
Not once did many wonder why Zloczew's market attracted so many farmers from the entire region. It's possible that the reason lies in the fact that our town had a place for trade of livestock -Targovitsa- where people bought and sold horses, pigs, cows, calves and more. This is also a place where butchers found a wide place for activity. During summer months May to July, when cows delivered, hundreds of calves were brought to be sold - some to the city of Lodz and others remained to be slaughtered in Zloczew. The slaughterhouse had plenty of work that kept all its employees and others of the meaty business in town. Thus we learn that this field was an important source of income for the Jews of Zloczew.
These women acted in additional social arenas. They took care of widows, not just in direct support, but also made efforts to help their growing orphans study a trade so that later they would be able to provide for the widow and the younger children.
These benevolent women also helped needy mothers of newborn babies, and this help came in the form of a warm meal or other food products given to them after birth so they could regain their strength and be able to fully function in their homes. These women were full of desire to help others and full of compassion. They knew how, when and where to act, and were full of understanding of delicate human needs - they knew where to give material help and to whom they should give spiritual assistance, a good word here and advice there, a stress-releasing smile or a nerve relaxing look - all in wisdom, with Jewish humor, in order to bestow a pleasant and peaceful atmosphere.
Following World War One, when America's Jewry, through the Joint, began sending assistance to their brethren across the sea, money-lending funds were established in almost all the cities and towns through cooperative banks. The Joint had set a rule by which they will match every sum of money deposited to that fund. This principle encouraged action, and rules and regulations by which these funds were managed were written. Loans were granted with very low interest rates, and sometimes with no interest at all, and the borrowers used to return the money by weekly or bi-weekly payments.
The funds assistance did not have a philanthropic nature but aimed at constructive targets, like the establishment of livelihood for craftsmen, shopkeepers or merchants. A regular inspection controlled the activities of the funds and made sure they will fulfill their duty and not deviate from the route set for them. In connection with that, it is important to mention the Moratorium that the Polish government had declared for the farmers and that was used to evade returning debts to Jews. For that reason, and also because of the anti-Semitic economical boycott, more and more Jews needed the lending funds to balance their budget.
Zloczew also had a Gemilut Hassidim fund of the Bikur Holim society. Although this institute did not have books, the help it granted was very crucial. An unwritten, but widely known law, was that the financial aid reached only those in real need, those who were in real trouble due to crises, illness etc, and that they would definitely return every last dime when they recuperated.
All this is gone. Jewish Zloczew, with its institutions, parties, organizations and unions, its social, public and cultural life - no longer exists. The Nazi murderers destroyed and annihilated all and nothing is left but the dear memory, the will and the duty to describe the life and destruction of our community as we mourn for our pure and holy loved ones who had perished in the horrible Shoa.
The destroyed cemetery in 1946. M. Majerowicz is standing by the ruins |
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Updated 14 July 2006 by LA


text:
Baby Wales best be getting stronger, because Beyonce wants to go head to head in 2013. And she's been going about her domination business about as meticulously as William and Catherine Cambridge approached their heir-ing. The Beysus has BIG plans for next year.
First, as you know, she's performing at the Super Bowl.
Then there's that HBO documentary.
Then there will be an album.
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B's first Pepsi ad will air during the Super Bowl. Pepsi, naturally, will be all over her tour next year. B celebrated in Miami this weekend with Jay-Z, Kelly Rowland, and her ma at Art Basel. She updated her Tumblr with all kinds of photos of herself at some of the galleries