Late onset of fatal cytomegalovirus infection after renal transplantation. Primary or reactivation infection?

Cytomegaloviurs (CMV) infections are a recognized problem in the first six months after renal transplantation. Studies have suggested that primary infections produce symptomatic disease, whereas reactivation infections are usually asymptomatic. Two patients are described who developed fatal CMV infections in the second year after transplantation. Both patients had typical CMV disease with fever, pneumonitis, and hepatitis. Results of serologic studies in one patient were characteristic of primary infection, with seroconversion at the time of disease and appearance of specific IgM antibodies. The other patient had a similar antibody response at the time of his illness, but serial antibody tests showed that he had had a transient seroconversion earlier, in the second month after transplanation, that was not associated with clinical symptoms. These patients indicate that CMV infection must be considered in the differential diagnosis of serious febrile illnesses even in the late posttransplantation period and may occur either as the result of primary or reactivation infection. Serologic studies at the time of illness may not allow distinction between the types of infection.

Isolation and characterization of mouse nasal lymphocytes.

A method for isolation of mouse nasal lymphocytes is described. Lymphocyte-enriched suspensions are examined for their morphologic, surface immune staining and mitogenic characteristics. This method will allow testing of immune function in the upper respiratory tract of the mouse.

Herpesvirus hominis type 2 meningoencephalitis following renal transplantation.

Herpesvirus hominis (HVH) type 2 meningoencephalitis, confirmed by isolation of the virus from cerebrospinal fluid and brain biopsy specimens, is described in a 44 year old man following renal transplantation. An HVH type 2 genital infection developed two weeks after renal transplantation, which was followed by meningoencephalitis 10 days later. Subsequently an intracerebral hemorrhage developed with evidence of diffuse vasculitis on arteriography. In a second transplant patient a similar clinical syndrome also developed after an HVH type 2 genital infection, but viral studies were not made to confirm the etiology of the meningoencephalitis. HVH has been recognized as a cause ot mucocutaneous diseases in recipients of renal transplants, but involvement of the central nervous system has not been reported.

Detection of viremia by a one step polymerase chain reaction method in hepatitis C virus infection.

A simple, sensitive, and specific one step polymerase chain reaction (PCR) method for the detection of hepatitis C virus (HCV) RNA in infected patients' serum or plasma samples is described. We performed the one step PCR amplification in combination with the initial step of reverse transcription by using oligonucleotide primers derived from the conserved 5'-untranslated region (5'-UTR) of the HCV genome. By utilizing this strategy, there was no need for nested or second stage PCR amplification. The PCR products (cDNAs) were easily visualized by agarose gel electrophoresis and ethidium bromide staining. Furthermore, the PCR products were characterized by Southern blot hybridization and DNA sequencing. We then used the one step PCR amplification method to detect the presence of HCV RNA in several infected patients' samples with acute and chronic infections. There was a 100% concordance between the results of PCR and second generation recombinant immunoblot assay (RIBA II). In addition, this method was found to be useful in determining viremia in HCV infected patients with indeterminate RIBA II results. The 5'-UTR of the HCV genome, being the most conserved region among different viral isolates, could be amplified by PCR for the detection of HCV RNA, as shown here, as well as serving as a potential target for antiviral agents.

Comparison of acellular pertussis vaccine with whole cell vaccine as a booster in children 15 to 18 months and 4 to 6 years of age.

The safety and immunogenicity of a booster dose of a new acellular pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTaP) were compared with whole cell pertussis component diphtheria-tetanus toxoids-pertussis vaccine (DTwP). Fifty children ages 15 to 18 months and 50 children ages 4 to 6 years were studied. The incidence of adverse reactions observed during the first 72 hours after vaccination in the DTaP/DTwP vaccinees were: pain, 32%/92% (P < 0.001); redness, 14%/24% (P = 0.2); swelling, 2%/14% (P < 0.03); fever, 52%/90% (P < 0.001); drowsiness, 14%/34% (P < 0.05); fussiness, 32%/88% (P < 0.001); and unusually poor appetite, 6%/42% (P < 0.001). The geometric mean titers of anti-pertussis toxin and anti-filamentous hemagglutinin antibody were also significantly (P < 0.001) higher in the DTaP compared to the DTwP recipients. When administered as a booster dose this DTaP vaccine, which has been chosen by the NIH for the second pertussis vaccine clinical efficacy trial, was more immunogenic for pertussis toxin and filamentous hemagglutinin and caused fewer and less severe adverse reactions compared with the Connaught DTwP vaccine used in this study.

Local and systemic antibody response to rotavirus WC3 vaccine in adult volunteers.

An evaluation of the safety and immunogenicity of WC3 rotavirus vaccine was evaluated in adult volunteers. Pre- and post-vaccination titers of neutralizing antibody to WC3 and to the four human rotavirus serotypes as well as serum and stool rotavirus IgA levels were measured. Vaccination was safe and did not induce elevation of liver enzymes. None of the 12 volunteers receiving WC3 vaccine shed detectable amounts of virus although antibody rises were detected in 11 of 12 vaccines. Nine developed and increase in WC3 neutralizing antibody, one additional subject had a rise in Wa (human serotype 1) neutralizing antibody while another subject only developed a rise in stool rotavirus IgA. All of the vaccine recipients with a rise in WC3 neutralizing antibody also developed a rise in neutralizing antibody against at least one of the four most common human rotavirus serotypes. A stool IgA rotavirus antibody response was detected in 6 of 9 WC3 recipients with measurable stool antibody. None of the control subjects developed significant rises in any of the antibody titers measured. WC3 rotavirus vaccine appears to be safe and induces systemic and local immune responses in adults suggesting that further evaluation of WC3 should be considered in infants.

Influenza-specific ELISA IgA and IgG predict severity of influenza disease in subjects prescreened with hemagglutination inhibition.

Four influenza A challenge studies were performed over a period of three years using the same dose of one virus pool. The first three studies were conducted two influenza seasons apart from the last study. In all four studies only subjects with screening hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8 in sera were accepted as study subjects. The rate of infection after influenza challenge was 96% (25 of 26) in the first three studies, and only 73% (8 of 11) in the last study (P less than 0.04). The rate of influenza illness in the first three studies was 62% (16 of 26), and only 9% (1 of 11) in the last study (all subjects: P = 0.003; infected subjects: P = 0.01). Even though screening HAI titers were comparable between groups, prechallenge serum influenza-specific IgG titers correlated inversely with respiratory symptoms (P = 0.04). Prechallenge nasal wash influenza-specific IgA titers were lower in subjects who developed influenza illness (P = 0.03). Prechallenge influenza-specific nasal wash ELISA-IgA titers and serum ELISA-IgG titers predicted influenza severity in patients prescreened by HAI during influenza challenge studies.

Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A.

The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind, placebo-controlled, randomized studies. In a study of 476 subjects aged 18 to 55 years, adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day (P less than 0.009). The influenza attack rate in this study was too low to assess efficacy. In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg, 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness (P less than 0.02, 66, 74 and 82% protection, respectively), and in suppressing viral replication (P = 0.02). There was no significant difference between amantadine groups in influenza illness or viral shedding. Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate (100 mg: 40% protection: P = 0.012; 200 mg: 32% protection: P = 0.045) whereas the 50 mg group did not (20% protection: P = 0.187). These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day.

Screening hospital patients for hepatitis B surface antigen.

A survey of adult patients admitted to a general hospital showed that 1.5% had hepatitis B surface antigen in the blood and 22% had hepatitis antibody. The majority of patients with hepatitis B did not have clinical hepatitis and would not have been recognized without screening all hospital admissions for hepatitis B antigen. The question of routine screening is discussed in relation to the risk of acquiring hepatitis.

Assessment of signs of influenza illness in the ferret model.

The ferret model of influenza A infection was evaluated to determine whether physical signs of influenza illness in addition to fever could be adequately followed. Ferrets were evaluated for nasal and systemic signs of influenza infection in a blinded, randomized protocol. Nasal signs were scored depending on the degree of nasal discharge and congestion. Systemic signs were evaluated on the basis of the activity level of ferrets. Nasal and systemic signs in ferrets challenged with influenza began to rise at peak virus shedding. This rise was coincident with the onset of the nasal inflammatory cell response. Nasal and systemic signs were statistically higher in challenged ferrets as compared with controls from 28 to 52 h after infection [P = 0.002 except at 28 h (P = 0.01)]. Despite precautions against influenza transmission, controls shed influenza virus associated with mild increases in nasal and systemic signs late in the course of the study. Our results suggest that severity of influenza illness can be adequately assessed in the ferret model using collective measurements of nasal and systemic signs, temperatures, and nasal cellular infiltration.

Comparative study of the immunogenicity and safety of two doses of recombinant hepatitis B vaccine in healthy adolescents.

PURPOSE: A prospective, two-armed, open-label, randomized trial was performed to compare the geometric mean titers (GMT), seroprotection (SP) and seroconversion (SC) rates found after administration of two doses of recombinant hepatitis B vaccine. METHODS: Recombinant hepatitis B vaccine 10 or 20 micrograms was administered IM at 0, 1, and 6 months in healthy adolescents. RESULTS: Volunteers who received either dose of the vaccine had similarly high seroconversion and seroprotection rates at all visits. At Month 8, both doses of the vaccine were highly immunogenic with GMTs of 1989 mIU/mL (10 micrograms dose) and 7672 mIU/mL (20 micrograms dose) and nearly equivalent SP rates (97% and 99% in the 10 and 20 micrograms dose groups, respectively). The geometric mean titers of seroconverters at Months 3, 6 and 8 were significantly greater in the 20 micrograms group as compared to the 10 micrograms group (p < or = 0.003). Both doses were well-tolerated, with injection site pain the most common reported adverse event. Injection site pain was reported significantly (p = 0.004) more by volunteers who received the 20 micrograms dose (10.7%) compared with volunteers who received the 10 micrograms dose (3.8%). CONCLUSION: Vaccination with 10 micrograms of recombinant hepatitis B vaccine may provide a clinically effective and economical alternative to the use of the 20 micrograms dose in healthy adolescents.

Coxsackievirus B epidemic at a boys' camp.

An epidemic of coxsackievirus B2 infections occured at a boys summer camp. The resulting illness was characterized by malaise, headache, muscle pain, and high fever that persisted for four to six days. The boy in the index case arrived at the camp the first day of the season. The attack rate was 89% among campers and 47% among counselors. The spread of infections appeared to be on a person-to-person basis and in a disorderly fashion. Unusual features of the epidemic included the high attack rate, restriction of infection to the camp residents, and evidence of prolonged pharyngeal viral shedding. Conditions at camps are ripe for similar epidemic and the potential problem is greater than is generally realized.

Clinical activity of pleconaril in an experimentally induced coxsackievirus A21 respiratory infection.

A randomized, double-blind study assessed the efficacy and safety of pleconaril, a novel antiviral drug with broad-spectrum activity against picornaviruses, in the treatment of 33 adults with an experimentally induced viral respiratory infection. Subjects received either pleconaril 200 mg twice daily (initial dose of 400 mg) or placebo for 7 days. Fourteen hours after receiving the initial dose of either pleconaril or placebo, subjects were inoculated intranasally with 100 plaque-forming units of coxsackievirus A21. Results revealed statistically significant reductions in viral shedding in nasal secretions (P<.001), nasal mucus production (P=.004), and total respiratory illness symptom scores (P=.013) in pleconaril-treated as compared with placebo-treated subjects. The most common adverse events were nausea and abdominal pain. These data support the safety and efficacy of pleconaril in decreasing the signs and symptoms and viral shedding associated with a viral respiratory infection.

Widespread cutaneous angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (AHE) is classically characterized by benign vascular tumors on the head and neck of young adults. An unusual case of widespread cutaneous AHE that clinically mimicked prurigo nodularis is presented and illustrated. The relationship of AHE to the recently described entity, histiocytoid hemangioma, is discussed.

Rubella control--1984.

The incidence of rubella and the congenital rubella syndrome has decreased dramatically in the United States since rubella vaccine became available in 1969. A marked shift in susceptibility rate has occurred so that 70% of current rubella cases involve teenagers and young adults. The history of rubella control is reviewed. Future research as well as altered public health strategies are suggested to optimize rubella control.

Similar subclass antibody responses after intranasal immunization with UV-inactivated RSV mixed with cholera toxin or live RSV.

To determine the effect of cholera toxin as a mucosal adjuvant on the class and subclass antibody response to RSV, mice were immunized intranasally with different doses of live RSV or UV-inactivated RSV mixed with cholera toxin. A single 10(6) pfu dose of live RSV and a single 50 micrograms dose of UV-inactivated RSV mixed with cholera toxin produced comparable serum IgG and respiratory secretion IgG and IgA antibody titers. Subclass antibody titers to whole RSV were also comparable between these two immunizing regimens. A predominance of IgG2a subclass to whole RSV was found for both regimens. The quantity of serum total IgG antibody to glycoprotein F or glycoprotein G did not differ between these regimens. The serum IgG subclass antibody response to both glycoprotein F and G was also not significantly different between regimens. Cholera toxin as a mucosal adjuvant can stimulate class and subclass antibody responses to UV-inactivated RSV that are similar in quantity and distribution to those after live RSV infection.

Comparison of class and subclass antibody response to live and UV-inactivated RSV administered intranasally in mice.

To determine the effect of viral dose and replication on the subclass antibody response to RSV, mice were immunized intranasally with different doses of live RSV (10(4)-10(6) pfu) and compared to mice given an immunizing regimen of UV-inactivated RSV. Mice given the 10(6) pfu dose of live RSV and mice given the 40 micrograms dose of UV-inactivated RSV had comparable class specific antibody responses to whole RSV in serum and respiratory secretions. Serum from these two groups of mice were then compared for IgG subclass response to whole RSV. A predominance of IgG2a subclass antibody was found for both immunizing regimens, and no significant differences in subclass proportions were noted between regimens. These two regimens were then compared for serum total IgG response to RSV surface glycoproteins F and G. The serum IgG response to these glycoproteins was lower after immunization with UV-inactivated RSV than after live-RSV immunization (F: P = 0.03; G: P less than 0.05), even though the serum IgG response of the two groups to whole RSV was comparable. The IgG subclass response to surface glycoproteins was evaluated for live RSV immunization. The proportions of subclass antibody responses to glycoprotein F were comparable to the subclass response proportions to whole RSV and were not characteristic of a T-dependent response pattern. The subclass profile for glycoprotein G was not comparable to that of whole RSV but was suggestive of a T-independent response pattern.

Rapid recovery in mice after combined nasal/oral immunization with killed respiratory syncytial virus.

Based on the concept of a common mucosal immune system, the murine gastrointestinal tract was inoculated (oral) with three doses (5, 20, and 40 micrograms) of UV-inactivated respiratory syncytial virus (RSV) in order to elicit a virus-specific immune response in the respiratory tract. Only the 40 micrograms dose induced significant (P less than 0.01) anti-RSV-IgG rises in serum and lung wash compared to controls. To improve the immune response, mice were immunized intranasally under light anesthesia with the same 40 micrograms dosage regimen of killed RSV so that each dose passed through the nose and was swallowed. This combined nasal/oral immunization stimulated anti-RSV-IgG in serum, lung wash and nasal wash (P less than 0.001) and anti-RSV-IgA in lung and nasal wash (P less than 0.001) that were comparable to levels after infection with live RSV. Three days after challenge with live RSV, mice given combined nasal/oral immunization showed suppressed nasal virus shedding (P = 0.025). Nasal virus shedding correlated inversely with concentrations of anti-RSV-Ig in nasal secretions but did not correlate with concentrations in serum.