Acute ulcerative proctocolitis associated with primary cytomegalovirus infection.

The case is reported of a 39-year-old pregnant woman who presented with fever, abdominal complaints, and diarrhea. Laboratory investigation revealed mononucleosis in the peripheral blood. All microbiological studies were negative, with the exception of finding cytomegalovirus (CMV). Seroconversion was documented; the virus was cultured from urine and subsequently was demonstrated to be present in the inflamed mucosa of the rectum and distal sigmoid, which was found at sigmoidoscopy. This woman was delivered of a neonate with congenital CMV infection but without apparent malformations. The patient experienced recurrences of the bowel disease, in the first of which CMV could still be cultured from a biopsy specimen. In the follow-up period, an otherwise aspecific chronic inflammatory bowel disease remained present. No immunological abnormalities were found, and antibodies to human immunodeficiency virus were negative. This case demonstrates that inflammatory bowel disease can develop as a result of primary infection with CMV.

The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.

OBJECTIVE: To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS). BACKGROUND: Infections with many agents have been reported preceding GBS. Some infections are related to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear. METHOD: A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same. RESULTS: Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns. CONCLUSIONS: Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.

Identification of rosette-forming cells in permanent preparations.

A method is described for the identification of leucocytes in permanent cytocentrifuge rosette preparations made with the fluorescent methyl green pyronin-SITS (MPS) staining technique. The percentages of rosettes in stained slides agree well with the results obtained with the conventional haemocytometer method. Application of the MPS staining to cytocentrifuge preparations permits reliable morphological differentiation between free and rosetting leucocytes, and should be particularly valuable in studies on lymphocyte subpopulations in patients.

Immunofluorescence studies with 4-acetamido-4'-isothiocyanato stilbene-2,2'-disulphonic acid (SITS).

The application of the fluorochrome 4-acetamido-4'-isothiocyanato stilbene-2,2'-disulphonic acid (SITS) in immunofluorescence was studied. The optimal excitation wave length is 350 nm, and optimal fluorescence is obtained at 420 nm. After purification of the commercial compound, conjugation is performed in a strong buffer at pH 9.0-9.5. SITS conjugates were very satisfactory for immunofluorescence studies of the cytoplasmic antigens of cell preparations, but their blue emission was difficult to distinguish from autofluorescence in sections of human tissues. Good results with immunofluorescence on membrane bound antigens were obtained by using an ultra-violet laser beam as light source. SITS can be used simultaneously with FITC and TRITC conjugates thus making it possible to show three antigens in one preparation.

The significance of complete serological testing for hepatitis B in heart valve banking.

Allograft heart valves obtained from donor hearts have been cryopreserved in the Heart Valve Bank in Rotterdam for transplantation purposes. In contrast to hepatitis B screening of organ donors, which consists of only a rapid HBV surface antigen (HBsAg) assay, tissue donors can be screened more completely for hepatitis B virus (HBV) by HBsAg and antibodies against HBV core antigen (anti-HBc) tests, and when necessary, anti-HBs and HBV-DNA tests. The value of this complete HBV screening was investigated by evaluation of the HBV screening results of 676 donor sera. HBsAg was positive in 1 serum. Anti-HBc was positive in 63 sera, of which 52 also had positive antibodies against HBV surface antigen (anti-HBs) tests (no risk of transmission) and 10 had negative anti-HBs tests. In 3 cases with a negative anti-HBs test the HBV-DNA test was positive (risk of transmission). In 3 cases not enough serum was available to perform all tests, resulting in a total of 7 rejected donors. Single HBsAg testing would have resulted in the rejection of only 1 donor. In the presented group of selected donors, approximately 0.5% of the HBsAg-negative donors were lower-level chronic carriers of hepatitis B. Complete HBV screening decreases the risk of transmission of hepatitis B in allograft heart valve transplantation.

Prevention of cytomegalovirus-related death by passive immunization. A double-blind placebo-controlled study in kidney transplant recipients treated for rejection.

In a double-blind placebo-controlled study, the value of prophylactic anti-CMV immunoglobulin administration was evaluated in 39 kidney transplant recipients treated for rejection with rabbit antithymocyte globulin. Passive immunization completely prevented CMV-related death, although it did not reduce the incidence of CMV isolation, viremia, or disease. The effect of passive immunization was exclusively observed in CMV-seronegative recipients of a CMV-seropositive kidney donor. It could be demonstrated even when instituted when antirejection therapy was started. Seropositive recipients did not benefit from immunoglobulin treatment. Moreover, CMV-seronegative recipients of a kidney from a seronegative donor were not at risk for CMV infection at all. Therefore passive immunization should be restricted to seronegative recipients of seropositive allograft donors treated for rejection.

Cytomegalovirus seronegative heart transplant recipients. Prophylactic use of anti-CMV immunoglobulin.

Thirty-two CMV seronegative heart transplant patients received prophylactic anti-CMV immunoglobulin during the first three posttransplant months. One of the 16 recipients of a heart from a seronegative donor acquired CMV infection and developed CMV disease. In eight of the 16 recipients of a heart from a seropositive donor, CMV infection was observed. Viremia was diagnosed in seven of them, but only two of these patients developed CMV disease. The incidence of CMV infection and of CMV disease in the globulin-treated CMV seronegative recipients of a heart from a seropositive donor was comparable to the incidence of CMV infection and of CMV disease in 31 nonglobulin-treated CMV seropositive recipients. This was significantly lower (percentage difference 69 percent, 95 percent CI 42-97 percent, p less than 0.001) than expected on the basis of the data from the literature and indicates that passive immunization with anti-CMV immunoglobulins induces the same protection against CMV disease as natural acquired anti-CMV resistance. This protective effect was temporary, as one patient developed symptomatic CMV infection four months after transplantation at a time when the anti-CMV immunoglobulin levels had decreased to pretransplantation values.

Successful treatment with ganciclovir of presumed Epstein-Barr meningo-encephalitis following bone marrow transplant.

Epstein-Barr virus-specific polymerase chain reaction was used to diagnose EBV-meningo-encephalitis in a bone marrow transplant recipient. The patient made complete recovery with ganciclovir treatment. Pitfalls in diagnosis with EBV-PCR and the potential therapeutic efficacy of ganciclovir in EBV infections are discussed.

Transmission of hepatitis B virus among heart transplant recipients during endomyocardial biopsy procedures.

BACKGROUND: The unexpected conversion to HBsAg seropositivity of three cardiac allograft recipients prompted us to conduct a multidisciplinary study to identify the source, transmission mode, and extent of the hepatitis B virus (HBV) infection among the 256 cardiac allograft recipients of our hospital. METHODS: All recipients were retrospectively screened for serum markers of HBV infection. A selected genomic region defining subtypes of the viruses involved was amplified and sequenced. An epidemiologic case-control study for possible risk factors was conducted to identify the mode of transmission. RESULTS: Eighteen additional HBV-infected patients were identified, none of whom had shown symptoms of HBV infection. The involvement of one virus (subtype ayw 3) was shown in 20 of the 21 HBV-infected patients. This virus is found in less than 10% of HBV-infected individuals in The Netherlands. The demonstration of a common source of infection, combined with results of the epidemiologic study, identified posttransplantation endomyocardial biopsy procedures as the most likely mode of transmission. However, we also found evidence of secondary virus transmission by cardiac catheterization procedures to nonallograft recipients. CONCLUSIONS: The immunosuppressive therapy practiced in these patients to prevent allograft rejection may have not only facilitated virus transmission by causing high levels of viremia but also left the spreading of HBV undetected by causing a subclinical course of the infection. These findings stress the necessity of strict hygienic precautions during intravascular diagnostic procedures and indicate that vaccination against and routine monitoring for certain bloodborne infections in cardiac allograft recipients should be considered.

Influenza virus serology--a comparative study.

Virus isolation or influenza virus antigen detection are the most rapid tests for diagnosis in the acute stage of influenza virus infection. As serology is easier to carry out, the synthesis of serum IgM, IgA and IgG was studied in two well-defined patient groups, infected with influenza B virus (cohort 1, n = 37) and influenza A virus (cohort 2, n = 40), diagnosed by antigen detection and/or virus isolation within 36 h after onset of symptoms. IgM was found in 13 influenza B patients (35%), IgA in 12 patients (32%), whereas a significant antibody rise was found in 33 patients (92%) by enzyme-linked immunosorbent assay (ELISA) and 74% by haemagglutination inhibition assay (HAI). For the influenza A cohort these numbers were respectively 18 (45%), 27 (68%) and 24 (62%) HAI (72%). In age-matched controls, who were bled on the first day of illness of the enrolled patient low prevalence was found for IgA and IgG, for influenza B respectively in 2 and 18%, and for influenza A in 4 and 39%. Studying the kinetics of the antibody response, we found that virus specific IgA and the bulk of IgG is synthesised within the first week of the infection. It is concluded that the finding of a specific serum IgA is highly indicative of an acute influenza infection.

Diagnostic assays in cytomegalovirus retinitis: detection of herpesvirus by simultaneous application of the polymerase chain reaction and local antibody analysis on ocular fluid.

AIM: To determine the value of the polymerase chain reaction (PCR) technique and the analysis of intraocularly produced antibodies by calculating a Goldmann-Witmer quotient (GWq) as diagnostic assays in the confirmation of a clinically diagnosed cytomegalovirus (CMV) retinitis in a group of unselected AIDS patients. METHODS: Eleven samples of undiluted ocular fluid, obtained from nine AIDS patients with a clinically diagnosed CMV retinitis were analysed for the presence of genomic DNA from CMV, HSV-1, VZV, and EBV by PCR. Nine of these samples were analysed for the presence of locally produced IgG antibodies against these herpesviruses by calculating a GWq. Ten samples obtained from patients with various entities of clinical non-herpetic uveitis and 17 samples of aqueous humour obtained at cataract surgery were used as controls. RESULTS: In 10 out of 11 samples from AIDS patients (91%) the presence of CMV DNA was demonstrated. In four out of nine (44%) patients this was accompanied by CMV DNA in the blood indicating a CMV viraemia. In one sample, VZV DNA was detected and in another sample both CMV and VZV DNA were detected. No HSV-1 or EBV DNA could be demonstrated in these 11 samples. In contrast, simultaneous analysis of locally produced IgG antibodies against herpesviruses could not confirm the initial diagnosis of CMV retinitis. Ocular fluid samples obtained from 10 control uveitis patients were negative for DNA from CMV, VZV, and EBV by PCR. In one of 10 uveitis control samples HSV-1 DNA was detected; antibody analysis did not confirm this. In the uveitis control group, a significant GWq was calculated in one sample for HSV-1 and in another sample for VZV. The cataract control samples were all herpesvirus DNA negative by PCR. CONCLUSIONS: To establish the diagnosis of CMV retinitis in AIDS patients, ophthalmoscopic examination is a sensitive method. In confirming a diagnosis in indistinctive cases, application of a PCR assay detecting CMV DNA is a more sensitive method than analysis of locally produced antibodies by calculating a GWq. In clinical non-herpetic uveitis, secondary release of HSV-1 and VZV should be considered requiring additional therapeutic anticipation.

Selection of asymptomatic HIV carriers for antiviral therapy.

In order to find suitable markers for selection and monitoring of antiviral therapy in asymptomatic HIV-infected patients, we evaluated 18 anti-HIV positive individuals at three monthly intervals by HIV culture, HIV antigen, and core (p24) antibody testing as well as by measurement of lymphocyte subsets. Consistent results were obtained with HIV antigen, p24 antibody testing and T4 cell enumeration, whereas results of virus detection were variable. Therefore cumbersome and expensive virus culture is not of use in selecting patients for antiviral therapy. On the basis of our results and recent literature we currently propose using absence of p24 antibodies, presence of HIV antigen and low or falling T4 cells as eligibility criteria for antiviral therapy in asymptomatic infected individuals.

[Indications for influenza vaccination in children with lung disorders. Dutch Association for Pediatric Medicine]. / Indicaties voor influenzavaccinatie bij kinderen met longaandoeningen. Nederlandse Vereniging voor Kindergeneeskunde.

The Dutch Association for Paediatric Medicine has formulated guidelines regarding influenza vaccination of children with pulmonary disease. Influenza virus is the most frequent cause of airway infections in humans over two years of age. It may lead to serious morbidity in children with pulmonary disease: exacerbations, (transient) disturbances in pulmonary function, and symptoms lasting weeks, but mortality is probably very low. The effects of influenza vaccination of children with pulmonary disease are similar to those in normal healthy children. A positive long-term effect on the asthma has never been demonstrated. It is advised that children with moderate to severe asthma who require treatment to be vaccinated against influenza every year. If the first vaccination ever occurs before the age of six years, it should be followed by a booster vaccination after four weeks. In both instances, a full vaccination dose should be administered.

[Hepatitis B in children in 4 university centers in The Netherlands]. / Hepatitis B bij kinderen in vier universitaire centra in Nederland.

OBJECTIVE: To evaluate the prevalence and the natural course of hepatitis B infection in children. DESIGN: Retrospective longitudinal. SETTING: Four university pediatric centres. METHOD: To explore the possibility of starting a trial with interferon alpha, data of viral and biochemical tests and biopsies of children younger than 16 years were studied. RESULTS: In a period of 10 years (1980-1990) 145 patients, of whom 74% were not of original Dutch descent, were found positive for HBsAg. The data of 142 patients could be analysed. Seroconversion was seen in 27 patients and 42 were already anti-HBe positive at the time of presentation. Chronic hepatitis, representing the category which could benefit from interferon alpha treatment, was found in 24 patients. Severe complications of the hepatitis were found in 4% of the children, including hepatocellular carcinoma and cirrhosis. Follow-up was insufficient so the seroconversion rate could only be estimated at 12% for the first year following the diagnosis. CONCLUSION: As a result of this study the authors present a proposal for a therapeutic trial with interferon alpha. This is a national protocol under the auspices of the section for pediatric gastroenterology of the Nederlandse Vereniging voor Kindergeneeskunde (Netherlands Pediatric Association).

[Non-Hodgkin lymphoma in patients with an HIV-infection]. / Non-Hodgkin-lymfomen bij patiënten met een HIV-infectie.

In the period 1985-1990, 111 patients with AIDS were treated in the University Hospital Rotterdam-Dijkzigt. In 8 out of 111 patients malignant non-Hodgkin lymphoma developed. The unusual and bizarre representation is highlighted by several clinical histories and a review of literature. HIV-related non-Hodgkin lymphoma is characterized by widespread extranodal disease, often at unusual sites, and high grade B-cell malignancy. The therapeutic outcome and survival in these cases has been disappointing. Prognosis is better for patients without a prior AIDS diagnosis, higher total CD4 cell counts, good performance score and absence of an extranodal site of disease. Treatment should be tailored to individual patients based upon a variety of prognostic features.

[Respiratory syncytial virus infections and preventive options]. / Infectie met respiratoir syncytieel virus en mogelijkheden voor preventie.

Respiratory syncytial virus (RSV) is the most prominent pathogen found in respiratory tract infections in children and the most important cause of bronchiolitis in the first two years of life. In the Netherlands approximately 2000 children are admitted each winter season. A serious course is mostly seen in children younger than 3 months, (ex-)prematures, children with bronchopulmonary dysplasia or congenital cardiac anomalies, children with cystic fibrosis younger then 2 years and children with impaired T cell immunity; such cases not rarely require intensive care. Treatment (fluid, nutrition, bronchodilator agents, corticosteroids, oxygen and ventilation) is usually symptomatic. Antiviral therapy is only indicated in immunodeficient patients. For prevention by passive immunization palivizumab was recently registered in the Netherlands, a monoclonal antibody against RSV that has to be administered intramuscularly from the start of the RSV season (15 mg per kg bodyweight once a month during five months). In a number of large-scale American multicenter studies both the number of hospital admissions related to RSV infection and the mean duration of hospital stay showed a statistically significant reduction in high-risk children who had been treated with palivizumab. Palivizumab appears to be indicated in children from the categories with an increased risk for serious RSV disease.

[An infant with AIDS]. / Een zuigeling met AIDS.

A four-month-old girl was hospitalized with pneumococcal sepsis from which she recovered. Subsequently she developed various other infectious diseases, including chronic diarrhoea caused by Cryptosporidium. After a period with neurological symptoms, later sagittal sinus thrombosis and cerebral atrophy, she died at age 13 months. It was found that the child suffered from AIDS. The mother was seropositive and the virus had probably been transmitted via the placenta. Rapid recognition of infants and young children with AIDS is necessary, for in the near future more cases of this disease will occur. Antiviral treatment may bring about improvement in children as well.

[Hepatitis B in children]. / Hepatitis B bij kinderen.

Central to immunization programmes is that hepatitis B virus infection in infancy is much more likely to result in the chronic carrier state than if infection occurs in adulthood. In areas of high endemicity like south-eastern Asia most infections occur when chronically infected women transmit hepatitis B virus to their newborns or when chronically infected children transmit the virus to other children. In the Netherlands, the endemicity is considered low; seroprevalence studies showed that 0.8% of the pregnant women are HBsAg-positive. To prevent mother to child transmission of hepatitis B a national immunization program has recently been implemented to prevent perinatal infection in approximately 450 neonates each year. Horizontal transmission of hepatitis B virus also seems possible in children since persistent carriers are found in (medical) centres and institutions for mentally handicapped. Since hepatitis B infections acquired during early childhood are likely to progress to chronicity and liver disease in adult life some risk factors for children in the Netherlands to contract hepatitis B infection are described and the immunization strategy is discussed.

[HIV infections in childhood]. / Infecties met HIV op de kinderleeftijd.

After the presentation of 3 case histories of children who became infected with HIV through different modes of transmission the disease is further discussed. Special attention is paid on epidemiology, transmission pathways, pathophysiology, making the diagnosis, clinical symptoms, therapy and prognosis of HIV infected children.

[Congenital cytomegalovirus infection]. / Congenitale cytomegalovirus-infectie.

Until recently, prevention and treatment of congenital cytomegalovirus infection was not possible. However, several studies on the epidemiology of congenital CMV infection and the development of vaccines, diagnostic tests and antiviral drugs such as ganciclovir may improve the perspectives for patients with congenital CMV disease. In this article we will discuss several of those developments that may offer new approaches for prevention and treatment of congenital CMV disease.