Screening and exclusion of Zika virus infection in travellers by an NS1-based ELISA and qRT-PCR.

OBJECTIVES: Zika virus (ZIKV) infection during pregnancy may cause neurological abnormalities in the foetus, and therefore fast and accurate laboratory assays are critical for rapid diagnosis. ELISA based on ZIKV NS1 protein has been developed and shown to be sensitive and highly specific; however, its negative and positive predictive values have not been tested. In this study we evaluated the ability of the NS1-based ELISA to exclude ZIKV infection and serve as a first-line screening tool for travellers. METHODS: We tested samples obtained during the peak of ZIKV infection from 1188 symptomatic and asymptomatic Israeli travellers using NS1-based IgG and IgM ELISA, real-time RT-PCR analysis and ZIKV neutralization. The Kaplan-Maier method was used to evaluate the duration of ZIKV RNA in whole blood and urine samples. RESULTS: NS1-based ELISA identified 20 true-positive, five false-positive and four false-negative cases, resulting in sensitivity and specificity of 83.3% (95%CI: 62-94%) and 97.5% (95%CI: 94-99%) respectively, and positive and negative predictive values of 80% (95%CI: 59-92%) and 98% (95%CI: 95-99%) respectively. Based on 14 RT-PCR-positive cases, median time to detect ZIKV RNA in whole blood was 17.5 days (range 5-58 days) and in urine 10 days (range 5-26 days). CONCLUSIONS: The NS1-based ELISA and RT-PCR in whole blood are highly reliable for identification of ZIKV-negative and -positive cases, respectively. Combination of both assays minimizes the risk of false-negative results, and thus allows the exclusion of ZIKV infection in travellers returning from ZIKV-endemic countries, including those who are pregnant or wish for preconception screening.

An assessment of lead controls for torch cutting and rivet removal on steel structures.

The use of engineering and work practice controls to protect workers from lead-containing dusts and fumes generated during rehabilitation of steel structures is mandated by the Occupational Safety and Health Administration (OSHA) Lead in Construction Standard (1993). Because the implementation and assessment of controls can be problematic in the rugged and dynamic construction environment, industrial hygienists should understand the effectiveness and limitations of controls adopted. The present investigation assesses the efficacy of two controls to reduce lead exposure: paint removal prior to oxy-acetylene torch cutting of steel, and encapsulation of rivets prior to their removal. A task-based exposure assessment approach was used to evaluate these tasks at three sites. Exposures at one site without controls were compared to exposures at sites with controls. Comparison of the results via an analysis of variance (0.05 significance level) indicates that, for torch cutting, exposures at the control site were not significantly different from those at an uncontrolled site (p = 0.14). The results for rivet busting show no significant differences in exposures at the control site compared to the uncontrolled site (p = 0.08). Results are also presented from two control sites where work was done in enclosed spaces. Two main difficulties in applying the controls are explored: technical and managerial. Technical problems during torch cutting included the penetration of paint into the steel profile and the configuration of the structures. For rivet busting, working within an enclosure was an important factor. Management problems arose both from a lack of coordination among different contractors, and from a failure to provide day-to-day guidance and assessment of the control. Important components of a program to implement controls are preplanning and coordination of control implementation, frequent testing of control efficacy, and a method for timely intervention to correct deficiencies.

High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer.

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy (HDC) with busulfan, melphalan and thiotepa (BUMELTT) followed by autologous PBSC infusion in treating patients with advanced ovarian cancer. Thirty-one patients, 18 with stage III/IIIc and 13 with stage IV ovarian cancer, were treated with BU (12 mg/kg), MEL (100 mg/m2) and TT (500 mg/m2) and autologous PBSC rescue. Fifteen patients were in clinical complete remission (CR) at treatment; 11 had platinum-sensitive disease. Sixteen patients were not in CR; two had platinum-sensitive disease. The probabilities of overall survival (OS), event-free survival (EFS) and relapse (R) for all patients at 18 months were 0.57, 0.30 and 0.63; for patients in CR, the rates were 0.87, 0.44 and 0.49 and for patients not in CR, 0.38, 0.13 and 0.81. Two patients (6.5%) died of treatment-related causes. Among the 13 patients with platinum-sensitive disease, all are still alive, with seven having relapsed 129-1021 days after PBSC infusion. OS, EFS and R were 1.00, 0.52 and 0.48. Of the 18 patients with platinum-resistant disease, four remain alive (two in remission). Six patients did not respond and eight relapsed from days 104-429. The OS, EFS and R were 0.33, 0.11 and 0.78. We conclude that BUMELTT is well tolerated in patients with advanced ovarian cancer and results are equivalent to other published HDC regimens.

High-dose busulfan, melphalan, and thiotepa followed by autologous peripheral blood stem cell transplantation in patients with aggressive lymphoma or relapsed Hodgkin's disease.

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy with busulfan (Bu), melphalan (Mel), and thiotepa (TT), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or relapsed Hodgkin's disease (HD). Forty patients, 23 with intermediate (n= 18) or high-grade (n=5) NHL and 17 with HD received Bu (12 mg/kg), Mel (100 mg/kg), TT (450-500 mg/m2) [corrected], and autologous PBSC infusion. Of 27 patients with more advanced disease, 16 had primary refractory disease, 8 were in refractory relapse, and 3 were in third remission. Of 13 patients with less advanced disease, 7 were in untreated or responding first relapse and 3 were in second remission, whereas 3 with high-grade NHL were in first remission. Twenty-nine patients (73%) had received prior radiotherapy (RT) prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival, and relapse for all patients were 0.60, 0.46, and 0.31 (0.85, 0.85, and 0.15 for patients with less advanced disease and 0.48, 0.30, and 0.37 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.17. Severe idiopathic pneumonia syndrome was not observed in any patients with less advanced disease and in only one patient with more advanced disease. A regimen of BuMelTT is well tolerated in patients with aggressive NHL or relapsed HD, and results obtained to date are at least equivalent to other published regimens, including TBI-based regimens. This regimen appears to be a particularly attractive alternative for patients who have already received dose-limiting RT and should be evaluated further in prospective, randomized studies.

High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells.

Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.

Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease.

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.

Non-tropical pyomyositis in children--with report of severe neurological complications.

Pyomyositis appears to occur rarely in temperate climate areas, compared with the incidence of the disease in the tropics. Three young adults with pyomyositis have previously been described in Israel, two of them were newly arrived Ethiopian immigrants. We report three Israeli children with pyomyositis, who presented initially with nonspecific abdominal pain; in one child the course was complicated by spinal cord compression due to extension of the infected mass into the spinal canal. All three patients attained full recovery after antibiotic therapy and surgical drainage. Computed tomography was most valuable in establishing the diagnosis and defining the extent of the process.

Fatal graft-versus-host disease in a patient with lymphoblastic leukemia following normal granulocyte transfusion.

A woman with lymphoblastic lymphoma was treated with combination chemotherapy. She subsequently became febrile while granulocytopenic and was given unirradiated granulocyte transfusions from normal, unrelated donors. She recovered, but 12 days later noted the onset of progressive skin rash, hepatic dysfunction, diarrhea and pancytopenia and, 22 days after her last granulocyte transfusion, died of gram negative septicemia. Histologic examination of multiple tissues including the skin, liver, and intestinal tract showed changes characteristic of acute graft-versus-hose disease (GVHD). Y-chromatin analysis of the patient's peripheral blood just before death indicated the presence of male cells. HLA typing of lymphocytes and skin fibroblasts from the patient and lymphocytes from the family and granulocyte donors was also consistent with engraftment of cells from one of the male granulocyte donors. This donor most likely was homozygous for one of the patient's halotypes, perhaps facilitating engraftment of his cells and subsequent development of transfusion-induced acute GVHD. Until more precise guidelines can be established, we recommend that all cellular blood products given to patients receiving intensive chemotherapy be irradiated with 1500 rad.

Estrogen biosynthesis from testosterone-4-14C by post-ovulatory human ovaries. Comparison between the corpus-luteum ovary and its partner.

PIP: The whole of each ovary from 2 women in the luteal phase of normal cycles was incubated with testosterone-4-carbon-14 in order to test the postulate that an interaction between ovarian compartments might be involved in the post-ovulatory synthesis of estrogens. Estradiol, estriol and estrone were all identified, estriol in only one ovary, from the corpus-luteum ovary. In both women, the corpus-luteum ovary converted more than 60 times as much substrate to estrogens than its non-corpus-luteum partner, and produced markedly lower yields of testosterone, 4-androstene-3, 17-dione(androstene-dione) and of their 16-alpha-hydroxy derivatives. All 4 of these compounds were identified. The 19-hydroxy derivative of testosterone and androstene-dione were also identified, but with a less marked difference between the two ovaries. The markedly lower yields of the 16-alpha-hydroxy derivatives from the corpus-luteum ovaries indicates that they were being further metabolized. The yield of estriol was too low, however, to implicate this steroid as a final product of their conversion.^ieng