Determining virological, serological and immunological parameters of EBV infection in the development of PTLD

Post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV) seronegative solid organ transplant recipients remains a significant problem, particularly in the first year post-transplant. Immune monitoring of a cohort of high-risk patients indicated that four EBV seronegative transplant recipients developed early-onset PTLD prior to evidence of an EBV humoral response. EBV status has been classically defined serologically, however these patients demonstrated multiple parameters of EBV infection, including the generation of EBV-specific CTL, outgrowth of spontaneous lymphoblastoid cell lines, and elevated EBV DNA levels, despite the absence of a classic EBV antibody response. As EBV serology is influenced by both immunosuppression and cytomegalovirus immunoglobulin treatment, both the EBV-specific CTL response and elevated EBV levels are more reliable indicators of EBV infection post-transplant.     

Occult thyroid carcinomas in the region of Minsk, Belarus. An autopsy study of 215 patients

The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty-nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The δ-5-virus (HDV) was not associated with severe necro-inflammatory lesions, but HDV-positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non-specific for HCV infection, or that these cases represent HCV infection with false-negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co-infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear.     

Anthrax in America 2001-2003

Anthrax caused by Bacillus anthracis in humans is rare. Two recent outbreaks that were intentionally caused occurred among postal employees, politicians, and journalists in the United States. This has caused tremendous fear, and our experience with these "anthrax incidents" has changed our views on the natural history of this disease in people. In this paper, we review the lifecycle and biology of this micro-organism. Anthrax that occurs from a weaponized form of this micro-organism has a specific clinical presentation that requires a suspicion of anthrax exposure to be diagnosed. New methods of testing for anthrax have been developed and may simplify diagnosis in the future. The range of illness caused by B. anthracis from the molecular level to the clinical symptoms is discussed. We also review the diagnostic criteria and differential diagnosis as well as treatment of this condition.     

Campylobacter pylori: clinical, histological, and serological studies.

The presence of Campylobacter pylori, histologically diagnosed gastritis, and antibodies to C pylori were determined in a series of 113 patients undergoing endoscopy. Paired biopsy specimens from the fundus, body, and antrum were collected from 59 patients and from the antrum of 54 patients. The presence of C pylori was confirmed by either culture or silver stain in 30 of 59, 31 of 59, and 54 of 103 biopsy specimens from the fundus, body, and antrum, respectively. Of the specimens which contained C pylori 20 of 30 (66%) from the fundus, 25 of 31 (80%) from the body, and 54 (100%) from the antrum showed gastritis. C pylori and gastritis were shown in seven of nine (78.1%) of patients with gastric ulcers and in nine of 11 (82%) of patients with duodenal ulcers. Using an enzyme linked immunosorbent assay (ELISA) technique to detect IgG antibody to C pylori, all patients with histologically diagnosed gastritis and organisms present had titres of greater than or equal to 640; eight of 39 (21%) of patients without gastritis and without organisms gave similar titres. Hence the presence of C pylori was associated with gastritis and with raised titres of IgG antibody.     

Relation between antithrombin III and clinical and serological parameters in systemic lupus erythematosus.

The increased frequency of thromboembolic events in patients with systemic lupus erythematosus (SLE) has been attributed to reduced or dysfunctional antithrombin III (At-III). We analysed At-III values, measured by three different assay techniques, in SLE patients, patients with rheumatoid arthritis, and normal and hospitalised controls. In addition, attempts were made to correlate At-III activities of SLE patients with specific clinical and serological parameters such as disease activity, renal involvement, previous thrombosis, degree of proteinuria, and serum complement concentrations. Our results failed to show a significantly reduced At-III in SLE with any method. At-III titres did not correlate with disease activity, concentrations of serum complement or albumin (both only minimally reduced in most patients), or a previous history of thrombosis. At-III deficiency does not appear to be an inherent feature of SLE, and reduced activities should only be anticipated when there are specific aetiological factors present, such as massive proteinuria, extensive hepatic disease, or active thrombosis.     

Rotavirus infection in Tanzania: a virological, epidemiological and clinical study among young children.

Rotavirus infection in the Dar es Salaam area of Tanzania was studied in 99 hospitalized children with acute diarrhoea and 99 hospitalized non-diarrhoea referents matched for sex and age. Of the diarrhoea cases 43.4% had rotavirus in the stools as opposed to 15.2% of the referents. The high carrier rate among the referents represents a serious risk of nosocomial transmission. More referents than cases had serum IgG antibodies to rotavirus, 52.5% and 35.4%, respectively (P < 0.02), while there was no correlation with serum IgM and IgA or faecal IgA antibodies. The latex agglutination test had a sensitivity comparable to that of electron microscopy (100%) and a specificity of 93.8%. The Slidex test appeared to be superior to the Rotalex test in that it gives very few false-positive reactions. The SDS-PAGE patterns of 11 RNA segments were compatible with the presence of group A strains with considerable heterogeneity among the strains. Symptoms and signs and some environmental data were recorded. None of them was clearly associated with rotavirus infection among the diarrhoea cases. It is concluded that rotavirus is a major cause of acute infectious diarrhoea in Tanzania.     

Hepatitis C virus genotypes in northern Italy: clinical and virological features.

We analyzed the characteristics of subjects from the same area who were infected with hepatitis C virus genotypes 1 through 4 and subtypes 1a and 1b. Our data are consistent with a rapid evolution in the epidemiology of HCV genotypes and argue against different pathogenic potentials for genotypes 1b and 2.     

An antigen in normal avian cells which confuses virological and serological tests

A cytoplasmic antigen was detected by fluorescent antibody tests in normal lymphoid and fibroblastic cells from chickens and other avian species when explanted and grown in culture. Cells of the bursa of Fabricius were consistently positive but cells of a proportion of thymus, spleen, bone marrow, buffy coat and embryo fibroblast cultures also were positive. Eight of 19 fluorescein-conjugated chicken sera prepared for other studies on a variety of avian pathogens had antibody against the antigen. Uncultured tissues or cultured but unfixed tissues were always negative, and selective blocking and absorption tests confirmed that the fluorescence was due to an antigen-antibody reaction. The antigen was associated with cells transformed by any of 8 strains of Rous sarcoma virus (RSV) but not with cells infected by other avian pathogens, including avian leukosis virus. Tests showed that the antigen was not coded for by RSV or by endogenous (subgroup E) avian leukosis virus genome. It may be coded for by normally non-functional genes which are derepressed in some cells by in vitro cultivation or RSV infection. In vivo derepression in some birds may account for the presence of antibody in sera.     

Quantitation of HIV: correlation with clinical, virological, and immunological status

A quantitative assay has been used to measure titres of infectious HIV in peripheral blood of symptomatic and asymptomatic patients. Viral titres were assessed in conjunction with virological and immunological status of patients including measurement of p24 antigen, antibody responses to structural (gp41, p24) and regulatory gene products (NEF, REV, TAT, and VIF), determination of beta 2 microglobulin levels and enumeration of lymphocyte subsets. Titres of HIV were significantly higher among symptomatic than asymptomatic patients. Viral load was closely associated with the number of CD4+ cells, the proportion of these cells harbouring HIV increasing with disease progression. Higher titres of infectious HIV among symptomatic patients was also associated with p24 antigenaemia and decreased antibody responses to NEF.     

Dengue-2 vaccine: virological, immunological, and clinical responses of six yellow fever-immune recipients.

Six male volunteers, previously immunized with yellow fever vaccine, were inoculated subcutaneously with a live, attenuated dengue-2 virus (PR-159/S-1) candidate vaccine. Five recipients developed viremia 8 or 9 days after vaccination, which lasted 1 to 10 days. The onset of viremia was followed by fever in three people, transient leukopenia in four, and an erythematous rash in one. One volunteer developed an oral temperature of 38.8 degrees C with headache, myalgia, fatigue, and photophobia suggestive of mild dengue fever. All five viremic volunteers developed fourfold or greater rises in serum neutralizing antibody. The sixth volunteer, who had a low titer of preexisting dengue-2 neutralizing antibody, had no viremia, no symptoms, and a modest rise in hemagglutination inhibiting antibody. Virus isolates obtained from plasma retained the small-plaque and temperature-sensitive growth characteristics of the vaccine virus in vitro. In this study, the vaccine virus genetically stable and immunogenic and seemed sufficiently attenuated for additional testing in humans.     

Performance of medical students in a nontraditional rural clinical program, 1998-99 through 2003-04.

PURPOSE: To compare knowledge acquisition as measured by test scores for students in nontraditional clinical clerkships to scores for students in traditional urban hospital-based clerkships. Interdisciplinary and continuity-of-care clerkships in rural areas are the focus of the study. METHOD: All the students' Medical College Admission Test (MCAT) scores, National Board of Medical Examiners (NBME) subject exam scores, and United States Medical Licensing Examination (USMLE) Step 1 and Step 2 scores over a six-year period, 1998-99 to 2003-04, were compared for third-year students in nontraditional and traditional clerkships at the University of North Dakota School of Medicine and Health Sciences. Cohorts were 29 students in our Rural Opportunities in Medical Education (ROME) program and 296 students in traditional third-year clerkships. NBME subject exam scores were those in pediatrics, internal medicine, surgery, and obstetrics and gynecology. The exam used for family medicine is not standardized to national standards, but controlled within the Department of Family Medicine. MCAT and USMLE Step 1 scores were used as a means of controlling for prior academic achievement and ability. RESULTS: There were no significant differences (p > or = .05) in MCAT scores, Step 1 scores, subject exam scores, or Step 2 scores between the two groups. In contrast, students from ROME scored higher (p < or = .05) on the internal medicine clinical preceptor assessments than did students from the traditional track. CONCLUSIONS: These findings suggest that students in remote, rural, longitudinal, integrated learning environments can attain fund-of-knowledge scores comparable to the scores of students in traditional clerkships, and may, as in this study, receive higher ratings for clinical proficiency.     

Evidence of Rickettsia spp. infection in Sweden: a clinical, ultrastructural and serological study

Sweden is an area potentially endemic for spotted fever rickettsioses. Rickettsia helvetica has been isolated from its tick vector Ixodes ricinus, and in a handful of cases linked to human disease. This study demonstrates for the first time in Sweden the transmission of rickettsial infection after a tick bite and the attack rate in an endemic area. We present three cases of documented rickettsial infection and a prospective serological study of Swedish recruits who were trained in the area where the patients lived and showed seroconversion to spotted fever rickettsiae. All patients showed a four-fold increase in antibody titer to the spotted fever rickettsia, R. helvetica, and immunohistochemical examination revealed rickettsia-like organisms in the walls of skin capillaries and veins. Electron microscopy showed organisms resembling R. helvetica and immunogold labeling with two anti-rickettsial antibodies demonstrated specific labeling of the rickettsial organisms in the skin biopsy specimens. Eight of the thirty-five recruits showed a four-fold increase in IgG titer reflecting a high rate of exposure. The results of this study demonstrate that spotted fever rickettsioses should be taken into consideration in the diagnosis of tick-transmitted infections in Sweden.     

Comparative evaluation of virological and serological methods in prenatal diagnosis of parvovirus B19 fetal hydrops.

Human parvovirus B19 infection in pregnancy represents a potential hazard to the fetus since fetal loss or fetal hydrops can occur. The risk of fetal loss due to transplacental B19 transmission has been evaluated in several studies using different diagnostic methods on maternal and fetal specimens. We analyzed the diagnostic value of virological and serological techniques on maternal serum, fetal cord blood, and amniotic fluid specimens obtained at the time of clinical diagnosis of fetal hydrops in 18 cases of B19 fetal hydrops. B19 DNA was detected by nested PCR, dot blot hybridization, and in situ hybridization assay. Anti-B19 immunoglobulin M and G antibodies were detected by immunoassays using recombinant B19 antigens. Our data suggest that for maternal sera, virological and serological methods have a complementary role in diagnosis, while for fetal specimens the in situ detection of B19 DNA in fetal cord blood is the most sensitive diagnostic system.     

The significance of rhinovirus detection in hospitalized children: clinical,epidemiological and virological features

Recent developments in molecular diagnostic tools have led to the easy and rapid detection of a large number of rhinovirus (HRV) strains. However, the lack of clinical and epidemiological data hampers the interpretation of these diagnostic findings. From October 2009 to January 2011, we conducted a prospective study in hospitalized children from whom samples were taken for the detection of respiratory viruses. Clinical, epidemiological and microbiological data from 644 patients with 904 disease episodes were collected. When HRV tested positive, strains were further characterized by sequencing the VP4/VP2 region of the HRV genome. HRV was the single respiratory virus detected in 254 disease episodes (28%). Overall, 99 different serotypes were detected (47% HRV-A, 12% HRV-B, 39% HRV-C). Patients with HRV had more underlying pulmonary illness compared with patients with no virus (p 0.01), or patients with another respiratory virus besides HRV (p 0.007). Furthermore, cough, shortness of breath and a need for oxygen were significantly more present in patients with HRV infection. Particularly, patients with HRV-B required extra oxygen. No respiratory symptom, except for oxygen need, was predictive of the presence of HRV. In 22% of HRV-positive disease episodes, HRV infection was hospital acquired. Phylogenetic analysis revealed several clusters of HRV; in more than 25% of these clusters epidemiological information was suggestive of transmission within specific wards. In conclusion, the detection of HRV may help in explaining respiratory illness, particular in patients with pulmonary co-morbidities. Identifying HRV provides opportunities for timely implementation of infection control measures to prevent intra-hospital transmission.