Allan Hornsleth

Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection

BACKGROUND little is known about inflammatory mediators (IM); like cytokines, chemokines and receptors; in respiratory secretion as possible indicators of the severity of respiratory syncytial virus (RSV) disease. Nor have systematic studies been published on the ratios between IM as such indicators. OBJECTIVE to define the role of IM ratios as possible indicators of the severity of RSV disease. STUDY DESIGN about 46 infants aged 0-9 months with acute RSV infections were studied. Prematurity (PM) and/or underlying disease (UD) were present in 11 of them. The concentrations of seven different IM were measured by ELISA in samples of nasopharyngeal secretions (NPS), four cytokines; IL-1, IL-6, IL-10 and TNF-alpha; the cytokine receptor TNF-R1 and the chemokines; IL-8 and RANTES. 21 IM ratios were calculated from these concentrations. The patients were assigned a clinical score (CS) ranging from 0 to 3 according to the severity of disease. RESULTS when 25 patients with severe disease (CS 2-3) and 21 patients with mild disease (CS 0-1) were compared with respect to different IM ratios, three ratios were related to severity of disease: IL-1/RANTES, IL-8/RANTES and TNF-R1/RANTES. When 12 patients with mild disease were compared with 16 patients with severe disease, omitting patients more than 5 months of age and patients with PM and/or UD, the following IM ratios were related to severity of disease: TNF-R1/RANTES, IL-8/RANTES and RANTES/IL-10. CONCLUSION of 21 IM ratios studied, TNF-R1/RANTES was related to severity of disease with greatest consistency.

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

BACKGROUND Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Prevalence of Parvovirus B19 and Parvovirus V9 DNA and Antibodies in Paired Bone Marrow and Serum Samples from Healthy Individuals

ABSTRACT Parvovirus B19 (hereafter referred to as B19) exhibits a marked tropism to human bone marrow (BM), and infection may lead to erythema infectiosum, arthropathy, hydrops fetalis, and various hematologic disorders. Recently, a distinct parvovirus isolate termed V9 with an unknown clinical spectrum was discovered. In contrast to the many studies of B19 serology and viremia, valid information on the frequency of B19 or V9 DNA in the BM of healthy individuals is limited. To develop a reference value, paired BM and serum samples from healthy subjects were tested for the presence of B19 and V9 DNA and specific antibodies. Immunoglobulin M (IgM) was not found in any of the serum samples. The prevalence of IgG showed a gradual and steady increase from 37% in children aged 1 to 5 years to 87% in people aged >50 years. When 190 well-characterized subjects were examined, B19 DNA was detected in the BM of 4 individuals (2.1%; 95% confidence interval, 0.58 to 5.3%) while none of the paired serum samples showed evidence of circulating viral DNA. V9 DNA was not found in any of the BM or serum samples. The finding of B19 DNA probably indicated a primary infection in one 7-year-old individual and reinfection or reactivation of persistent infection in the remaining three persons, aged 47 to 58 years. Serving as a benchmark for future studies, these findings are useful when interpreting epidemiologic data, performing BM transplantation, or considering clinical implications of parvovirus infection.

Occurrence of herpes‐ and adenovirus antibodies in patients with carcinoma of the cervix uteri.Measurement of antibodies to herpesvirus hominis (types 1 and 2), cytomegalovirus, EB‐virus, and adenovirus

One hundred thirty‐five sera from patients with newly diagnosed, untreated cervical cancer and 115 sera from healthy women matched for age and socioeconomic background have been examined for antibodies to Herpesvirus hominis (types 1 and 2), cytomegalovirus, EB‐virus and adenovirus. Eighty‐five per cent of the patients with cervical cancer had antibodies to Herpesvirus hominis type 2 compared to 47% in the control group. The incidences of antibodies to cytomegalovirus and EB‐virus were significantly greater in the sera from patients with cervical cancer than in control sera. The incidence of antibodies to adenovirus was the same for both groups. The incidences of antibodies were not correlated to the clinical stages of the disease. In the control group, antibodies to Herpesvirus hominis type 2 and EB‐virus were found with higher incidence among women with low socioeconomic background than in women from higher social classes. Such a correlation was not seen in patients with cervical cancer.

Parvovirus B19 Infection Associated with Myocarditis Following Adult Cardiac Transplantation

A 56-year-old woman underwent an uneventful cardiac transplantation due to dilated cardiomyopathy. One week later the patient developed clinical and histological signs of myocarditis. We report for the first time a case of myocarditis in an adult heart transplant recipient, possibly induced by parvovirus B19, as evidenced by the finding of specific IgM in serum and specific DNA in the myocardial cells. Furthermore, this is the first time parvovirus B19 DNA has been observed in the myocardium of an adult. In conclusion, parvovirus B19 should be recognized as a potential pathogen causing myocarditis in heart transplant recipients. In order to establish a definite and rapid diagnosis, a search for specific IgM should be supplemented with PCR investigations of serum and myocardial biopsies when available.

Estimation of serum concentration of parvovirus B19 DNA by PCR in patients with chronic anaemia.

Parvovirus B19 DNA was detected in serum samples from 10 out of 42 patients with chronic anaemia, the majority of whom suffered from aplastic anaemia, haemolytic anaemia, pure red cell anaemia or myelodysplastic syndrome. Nested PCR methods with sensitivities of 0.005-0.05 fg DNA were developed. In nine patients, B19 DNA could only be detected by nested PCR. Conventional PCR with a sensitivity of 50 fg B19 DNA could only detect B19 DNA in one patient. In the majority of B19-DNA-positive patients, the DNA concentration was estimated at 0.005-0.05 fg per 5 microliters serum.

THE ROLE OF PARVOVIRUS B19 INFECTION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

The authors hypothesized that parvovirus B19 with its hematotropic effects has the potential to precipitate varying forms of cytopenia in patients prior to or at the diagnosis of acute lymphoblastic leukemia (ALL). Consequently, and in view of the increasing number of cases reported, this retrospective study evaluated, for the first time, the possible role of parvovirus B19 infection in pediatric patients suffering from ALL, by investigating the frequency and clinical relevance of this infection at the time of the malignant diagnosis or, when applicable, during a phase of pre-ALL. Furthermore, a review of reported parvovirus B19 infections in pediatric ALL patients is presented. The serum of 65 consecutive pediatric patients with a diagnosis of ALL was examined for possible parvovirus B19 infection employing the polymerase chain reaction and ELISA techniques. Specific IgG was demonstrated in 30% of the patients. One patient diagnosed with pre-ALL had evidence of parvovirus B19 DNA in the serum during pancytopenia 5 months prior to the onset of ALL. The results suggest that there is an insignificant chance of finding a parvovirus B19 infection in pediatric patients with ALL at the time of diagnosis. However, parvovirus B19 infection may infrequently serve as a prodrome to ALL.

Restriction pattern variability of respiratory syncytial virus during three consecutive epidemics in Denmark

A PCR‐based assay was used to distinguish between respiratory syncytial virus (RSV) group A and B in order to analyze their prevalence in Denmark in three consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total of 96 RSV strains isolated from hospitalized children were examined, showing alternation of group prevalence. Furthermore, the genetic variability of the RSV isolates was illustrated by restriction enzyme analysis of PCR products originating from a part of the F and G proteins that has been reported to be highly variable. We found that, in general, different genome types predominated each year, some types being present in consecutive epidemics, indicating a contribution of strains circulating unattended between outbreak seasons, while others seemed to disappear or became undetectable, being replaced by emerging types. Some of the genome types found seemed related to strains isolated up to more than two decades ago in other parts of the world. This indicates that the temporal fluctuation in predominance of genome types presumably caused by selective pressure exerted by host immunity is due to the favoring of strains from a pool of globally circulating, genetically relatively stable genome types, rather than a molecular evolution in strains induced or directed by immunoselective pressure.

Parvovirus B19 Infection Associated with Encephalitis in a Patient Suffering from Malignant Lymphoma

A parvovirus B19 infection was established in a 58-year-old woman undergoing treatment for malignant lymphoma. Clinically, the patient displayed a variety of neurologic symptoms that could not readily be explained by the mere presence of lymphoblastic cells within the central nervous system. This is the first time parvovirus B19 DNA has been detected in the cerebrospinal fluid of a patient suffering from encephalitis.

Parvovirus B19 infection and Diamond-Blackfan anaemia.

It is the purpose of the study to report the frequency of parvovirus in children with a diagnosis of Diamond‐Blackfan anaemia and to discuss the possible aetiological role of parvovirus in Diamond‐Blackfan anaemia. We found parvovirus DNA in 3 of 11 bone marrow smears. Giant pronormoblasts showed low sensitivity (33%) and poor specificity (75%). The presence of giant pronormoblasts was associated with a very high myeloid: erythroid ratio, and may not be specific for parvovirus infection, but a feature of severely suppressed erythropoiesis. The three parvovirus‐positive patients were the only children who experienced a remission, and who are free of medication. The seven surviving parvovirus‐negative patients are all currently on steroid treatment.