Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factors.

BACKGROUND: Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. METHODS AND FINDINGS: In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. CONCLUSIONS: In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

Detection of left anterior descending coronary artery disease in patients with left bundle branch block.

The detection of coronary artery disease is difficult if a patient has electrocardiographic evidence of left bundle branch block (BBB). Septal blood flow may be reduced in patients with left BBB, despite no angiographic evidence of left anterior descending (LAD) coronary artery disease. We have developed a new method of quantification of Thallium-201 single-photon emission computed tomographic (SPECT) images with the aim of better separating patients with left BBB and LAD disease from those with left BBB alone. The study cohort comprised 8 normal subjects (group I) and 20 patients with left BBB and chest pain who underwent thallium-201 SPECT imaging and coronary angiography. Eight patients (group II) had < or = 50% LAD stenosis, and 12 (group III) had > or = 70% LAD stenosis. Septal abnormality scores on the second short-axis slice from the base were computed, based on comparison of each subject's short-axis circumferential profile with a normal reference curve. This followed a procedure in which each profile was scaled to minimize differences in its absolute level in relation to the reference curve. Septal abnormality scores on stress images were 0.8 +/- 22 for group I, 27 +/- 43 for group II, and 165 +/- 67 for group III (p = 0.15 for group I vs II, and p < 0.0001 between groups I and III, and II and III).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive assessment of myocardium at risk by Tl-201 SPECT imaging in a child with Kawasaki disease. A case report.

Serial two-dimensional echocardiograms documented the formation of giant aneurysms, measuring from 0.55 to 3.1 cm in diameter, in the distribution of the left and right coronary arteries, in a 2 1/2-year-old boy with Kawasaki disease. His global left ventricular function, assessed by M-mode echocardiography, was normal, and no significant wall motion abnormalities could be detected on two-dimensinal evaluation. Cardiac catheterization showed multiple aneurysms with no evidence of stenosis. Although he had no clinical symptoms or electrocardiographic evidence of ischemia, pharmacologic stress and delayed Tl-201 SPECT images revealed prominent stress-induced myocardial ischemia in the left ventricle. A resting gated blood pool study showed hypokinesia in corresponding regions of the left ventricle. This case demonstrates the usefulness of Tl-201 myocardial SPECT imaging and resting gated blood pool studies in the management of coronary artery disease in children with Kawasaki disease.

Reduced left ventricular cavitary activity ("black hole sign") in thallium-201 SPECT perfusion images of anteroapical transmural myocardial infarction.

Apparently reduced left ventricular (LV) cavitary thallium activity in both planar and tomographic perfusion images has been previously observed by these and other investigators. With single-photon emission computerized tomography, we have clinically noted that this "black hole sign" was associated with an aneurysm in the setting of a transmural anterior or anteroapical perfusion defect. We have now prospectively studied the etiology and predictive value of this sign in 84 consecutive patients with an anterior, anteroapical transmural perfusion defect. Of the 84 patients, 49 had both LV aneurysm (confirmed by contrast ventriculography, echocardiography or gated blood pool studies) and a black hole sign. Only 1 patient with an aneurysm did not have the black hole sign, and 2 without aneurysm did. Thus, it is concluded that this sign is highly accurate in diagnosing LV aneurysm. Because thallium-201 single-photon emission computerized tomography imaging is often performed as one of the first diagnostic tests soon after myocardial infarction, this has important clinical management implications.

Failure of perchlorate to inhibit Tc-99m isonitrile binding by the thyroid during myocardial perfusion studies.

The thyroid gland receives an average radiation dose of 3 rads during two Tc-99m isonitrile (MIBI) myocardial perfusion studies, if 20 mCi is administered both at rest and at peak exercise. In patients with coronary artery disease, multiple myocardial perfusion studies may be required, resulting in a high level of thyroid radiation. We attempted to reduce this radiation exposure by blocking thyroidal Tc-99m MIBI uptake with oral potassium perchlorate (KCIO4). Fourteen normal subjects received 0.6g to 0.8g KCIO4 20-25 minutes before tracer injection. Subjects who received KCIO4 at rest (n = 11) did not receive KCIO4 at their stress study, and vice versa (n = 3). Thyroid uptake values were obtained with a thyroid probe 20 minutes after injection for both rest and stress studies and were corrected for saturation effects. There was no difference between fractional thyroid uptake values with and without preceding perchlorate administration: 1.9 +/- 0.5% and 1.8 +/- 0.3% (mean +/- SD), respectively. Failure to block Tc-99m MIBI uptake after intravenous (IV) injection is probably due to high thyroidal blood flow and nonspecific tracer accumulation. The concentration of this radioisotope in adjacent muscles also contributes to the high thyroid radiation dose. In summary, administration of KCIO4 before Tc-99m MIBI studies does not reduce the thyroidal radiation dose or uptake of this tracer, suggesting that thyroidal uptake of this tracer is not mediated by the iodine trapping mechanism.

Effects of vinyl chloride on liver function of exposed workers, evaluated by measurements of plasma clearance of the 99mTc-N-2,4-dimethylacetanilido-iminodiacetate complex.

In 77 males exposed occupationally to vinyl chloride (VC), the plasma clearance (Cl) of 99mTc-N(2,4-dimethylacetanilido)iminodiacetate ('HEPIDA' complex) was determined. The results were juxtaposed with a scaled assessment of liver parenchyma performance based upon clinical examination and a series of biochemical tests. Detection of the diagnosable damage of liver parenchyma by means of the reduced clearance was sensitive (90%) at the reasonable specificity of 74%. Probability of exclusion of liver damage in patients with the clearance above 240 ml min-1 1.73 m-2 amounted to 92%. There was a significant correlation between degree of exposure to VC and the frequency of low clearance values. It appears that the periodic determination of the 99mTc-HEPIDA clearance in workers exposed to VC allows the assessment of incipient liver damage and signals the need for prophylactic measures.

Comparison in rabbits of chole-scintigraphic properties of several 99mTc-IDA derivatives.

Pathways and kinetics of excretion were compared to four 99mTc-IDA derivatives in healthy rabbits of both sexes. Assessment of differences between the compounds was based upon: plasma clearance, characteristics of time-activity curves measured scintigraphically over the liver (time of the peak Tmax; time for decline of activity to half the peak value-T50%), and hepatocytic mean transit time (MTT) as derived after deconvolution of the hepatic time-activity curve. Hepatocyte transit time was short and similar to 99mTc-complexes of Mebrofenin, 2,4-diethyl IDA (HEPIDA) and 3-iodo-2,6-diethylphenylcarbamoylmethyliminodiacetic acid (JODIDA); it was evidently longer for 99mTc-p-butyl-IDA (BIDA). 99mTc-HEPIDA displayed significant urinary elimination; the remaining three compounds were excreted practically completely via the biliary route. It is concluded that optimal parameters were displayed by 99mTc-Mebrofenin and 99mTc-JODIDA.

51Cr-bleomycin in the diagnosis of tumours of the chest.

51Cr-bleomycin was used for the scintigraphic diagnosis of primary and secondary tumours of the thorax. The study was based on observations in 104 patients. The scintigraphy was performed using a gamma camera coupled to an on-line computer. Active lesions were scored using a semiquantitative scale of scores 0 to 5. Images were subdivided into 222 regions considered. In 72 of these, the presence of disease was diagnosed (64 malignant, 8 non-malignant) and 150 regions were classified as free from disease. At the decision threshold of score 2, over-all sensitivity and specificity of the scintigraphic detection of malignant tumours amounted to 97 and 79%, respectively. Inflammatory changes displayed some detectable accumulation of 51Cr-bleomycin but scores attributed to these lesions did not exceed the value of 2.

57Co-bleomycin scintigraphy in staging of carcinoma of the cervix.

65 patients with cervical cancer at various stages of the disease were studied scintigraphically after 57Co-bleomycin administration, active urine being flushed out from the bladder continuously. The patients were submitted to other auxiliary tests and the interpretation of scintigraphic images could thus be verified. Scintigraphic data were classified semiquantitatively by scoring in the range from zero to 5. Results were evaluated in terms of ROC-curves. This method of analysis permitted selection of cut-off levels for binary decisions that yielded satisfactory sensitivity and acceptable specificity of the test.

51Cr-bleomycin in the diagnosis of ocular melanoma.

51Cr-bleomycin was administered to 18 patients suspected of having an ocular melanoma with varying degree of development. The diagnosis was verified prior to surgical removal of the eye-ball by fluorescent angiography and computerized axial tomography. In operated patients histological diagnosis was also available. Scintigraphy after 51Cr-bleomycin administration appeared to be an effective diagnostic measure: sensitivity and specificity reached 90 and 87%, respectively. It is concluded that the method is useful in the preoperative diagnosis of ocular melanoma.

Plasma clearance of 99mTc-N/2,4-dimethyl-acetanilido/iminodiacetate complex as a measure of parenchymal liver damage.

Fifty-two patients were studied with various diseases affecting liver parenchyma. Any disorders of bile transport were excluded on the basis of dynamic liver scintigraphy using intravenously injected N/2,4-dimethyl acetanilido/iminodiacetate 99mTc complex (HEPIDA). The activity concentration of 99mTc-HEPIDA in plasma was measured from 5 through 60 min post injection. Clearance of the substance (ClB) was calculated from blood plasma disappearance curves and compared with results of 13 laboratory tests used conventionally for assessment of damage of the liver and its functional capacity; age and body weight was also included in the analysis. Statistical relations were studied using linear regression analysis of two variables, multiple regression analysis as well as multidimensional analysis of variance. It was demonstrated that 99mTc-HEPIDA clearance is a simple, accurate and repeatable measure of liver parenchyma damage. In males, values of ClB above 245 ml. min-1/1.73 m2 exclude hepatic damage with high probability; values below 195 ml.min-1/1.73 m2 indicate evident impairment of liver parenchyma function.

51Cr-bleomycin, a new oncophilic radiopharmaceutical. II. Scintigraphic diagnosis of malignant neoplasms.

51Cr-bleomycin was used for the scintigraphic detection of tumours and the assessment of the spread of the disease in 20 patients with various malignancies: 7 with Hodgkin's lymphoma, 5 with other malignant lymphomas, 4 cases of cervix carcinoma and 4 other tumours. The scintigraphy was performed using a Toshiba GC 401 gamma camera coupled to an MDSI computer Trinary. Active foci were scored using a semiquantitative scale of 0 to 5. Results of these studies were compared with those of tests similarly carried out with 57Co-bleomycin (in 9 of the cases) and 67Ga-citrate (11 cases); they demonstrated that the properties of 51Cr-bleomycin for scintigraphic detection of neoplastic foci are similar to those of 57Co-bleomycin.