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Biomedical subjects

A C Kroes

Publications and source records attributed to A C Kroes.

At least 19 recordsLinked to original sources

[From fowl plague to influenza pandemic; a reason for taking precaution].

Throughout Eastern Asia, there is currently an epidemic of fowl plague or highly pathogenic avian influenza, on an unprecedented scale. The prospects for rapid containment are poor. The causative virus, influenza A of the H5N1 subtype, is of limited infectivity for humans. If infection occurs, however, then the consequences are serious and even fatal in a majority of cases. In view of the receptor specificity of avian influenza viruses, this may be related to individually increased susceptibility, which does not lead to further spread. However, it is known that influenza A viruses can readily adapt to replication in the human host by the acquisition of specific gene segments or even by mutations of the avian virus. The extreme scale of human contact with influenza virus of the H5N1 subtype at present engenders fear that there is a high risk of such adaptation and a subsequent pandemic spread. Adequate precautions are necessary, not only in terms of an acceleration of vaccine production but primarily in arranging for sufficient availability of the new antiviral drugs.

Animals↗

[Duration of follow-up after contact with HIV: 3 or 6 months].

The revised Netherlands guideline 'Sexually transmitted diseases and neonatal herpes' recommends shortening of the follow-up period from 6 to 3 months for HIV-testing after a risky contact and a period of 6 months in case of post-exposure prophylaxis. The newly adopted follow-up period has a precedent in Sweden, where, based on the same scientific arguments, the follow-up period has been reduced to 3 months. There is little scientific information on which to base the optimal duration of the follow-up period. Therefore, two different periods are used in the Netherlands: 3 months for medical practice in the field of sexually transmitted diseases and 6 months for occupational exposure of health care workers and for blood products.

Anti-HIV Agents↗

[HIV-1 therapy in the Netherlands; virological and immunological response to antiretroviral therapy].

OBJECTIVE: To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of since 1996 in the Netherlands available protease and reverse transcriptase inhibitors. DESIGN: Prospective cohort study. METHODS: In an observational clinical cohort of HIV-1-infected individuals, the short-term successful treatment end point of antiviral therapy including at least one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels < or = 500 copies/ml (virological success). Cox proportional hazard models were used to identify prognostic markers for therapy success. The study included 2,148 infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had been pre-treated with antiretroviral drugs before starting their new regimen and 1,099 were treatment naive. RESULTS: Plasma HIV-1 RNA levels < or = 500 copies/ml at 24 weeks of treatment were seen in 61% of all patients. The chance of therapy success for naive patients was twice that for pre-treated patients (relative risk: 1.8; p < or = 0.001). Following the first 24 weeks, the chance of virological success was higher in the naive group (78% versus 63%; p < or = 0.001), and the number of naive patients failing therapy after initial success was smaller compared to pre-treated patients (22% versus 45%; p < or = 0.001). In the naive group, the CD4+ T-cell number increased from 239 to 440 (x 10(6) cells/l) in case of success, and decreased from 150 to 320 in case of treatment failure. HIV-1 related morbidity declined from 0.26 to 0.05 and mortality dropped from 0.07 to 0.03 per person-year of follow-up. Regimens were changed at least once in 76% of patients. Toxicity and therapy failure were the main reasons for regimen changes in naive and pre-treated patients, respectively. CONCLUSION: A combination of antiretroviral drugs, including at least one of the drugs licensed since 1996, led to a drop in HIV-1 plasma concentrations. Morbidity and mortality also decreased. The chance of a better immunological and virological response to the new drug regimens was greatest in therapy-naive patients.

Acquired Immunodeficiency Syndrome↗

Prediction of severe disseminated adenovirus infection by serum PCR.

Adenoviruses are increasingly recognised as viral pathogens that can cause fatal infections in immunocompromised patients, particularly recipients of haematopoietic stem-cell grafts. Adenovirus infections are not easily diagnosed and the development of a severe infection cannot be predicted by standard culture techniques. In a pilot study, we investigated the value of adenovirus DNA detection in serum as a marker of disseminated disease in 14 patients with defined patterns of adenovirus infections. The results show that the appearance of adenoviral DNA in serum preceded the development of a severe or fatal adenovirus infection. Because proper management is dependent on early diagnosis and differentiation from other conditions, this test may be a valuable tool in the management of adenovirus infection.

Adenovirus Infections, Human↗

[Virus quantification in peripheral blood as a reflection of the clinical course].

Quantitative determination of viral nucleic acid in peripheral blood appears to be important for nearly all viral infections with a chronic and reactivating course, as this provides relevant information on the clinical consequences, the level of infectivity and the response to antiviral treatment or other interventions. The practical application of this principle in clinical virology has benefited from the availability of new techniques, particularly those in which amplification of viral nucleic acid can be followed in real time. In addition, the potential value of quantitative virology was clearly demonstrated by the experience gained from viral load monitoring in HIV-infected patients. This approach will probably be widely applicable in clinical microbiology in general.

Chronic Disease↗

Monitoring response during a randomised controlled trial of escalating interferon dose for chronic hepatitis C infection: predictive value of quantitative and qualitative HCV RNA assays.

BACKGROUND: In chronic hepatitis C infection, raising the interferon dose in initial non-responders may increase the generally poor sustained response rates. Monitoring virological response is essential in this kind of individual patient based approach. Quantitative HCV RNA assays are increasingly used for this purpose. However, their additional value as compared to strictly qualitative HCV RNA assays should be evaluated before they are implemented as a routine measurement, since these assays are more expensive and time consuming than qualitative assays. OBJECTIVES: Goals of this study were (1) to test the hypothesis that increasing interferon dose in initial non-responders results in permanent viral clearance in more patients and (2) evaluation of the predictive value of quantitative versus qualitative HCV RNA assays before and during treatment. STUDY DESIGN: 63 patients were treated in a randomised controlled trial of escalating interferon dose. In the standard treatment group patients received 6 MU alpha-2a thrice weekly for 3 months followed by 3 MU thrice weekly for 3 months. In the experimental group interferon dose was escalated at 6 weeks to 9 MU if HCV RNA was still detectable at 4 weeks. Predictors of response were analyzed at various time points before and during treatment and the predictive value of quantitative HCV RNA measurements was compared to that of qualitative HCV RNA assays. RESULTS: No significant difference in sustained response rate was found between the treatment groups at the end of follow-up. At baseline, the strongest independent predictor for a sustained response was a viral load level below 10(6) copies/ml and age younger than 40 years. During treatment a negative HCV RNA status at week 4 was the strongest predictor of a sustained response. Viral load levels during treatment did not independently predict a sustained response. CONCLUSIONS: While on treatment, qualitative HCV RNA assays should be used to monitor response.

Adult↗

Efficient extraction of virus DNA by NucliSens Extractor allows sensitive detection of hepatitis B virus by PCR.

The NucliSens Extractor is an automated nucleic acid isolation system based on guanidinium thiocyanate (GuSCN)-silica extraction technology. The system has been validated for the isolation of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNAs from human samples in combination with nucleic acid sequence-based amplification- and reverse transcription-PCR-based methods. We evaluated the extractor for hepatitis B virus (HBV) DNA extraction from human samples using a noncommercial HBV DNA PCR. Several sample pretreatment procedures in combination with the extractor were compared with the Qiagen extraction method, and the impact of the sample volume used in the extraction on the sensitivity was investigated. Heating of the lysed sample prior to extractor isolation and the use of a large sample volume resulted in highly sensitive detection of HBV DNA. Incubation of a 1-ml sample in GuSCN at 80 degrees C (10 min) and at 37 degrees C (30 min) allowed detection of 4 and 40 HBV genome equivalents/ml, respectively, in standard dilution panels. Sample lysis in GuSCN at room temperature and proteinase K treatment prior to use of the extractor were less efficient procedures. All clinical samples that were PCR positive after Qiagen extraction and/or that were HBsAg positive were also PCR positive after extractor isolation. HBV DNA, HCV RNA, and HIV type 1 RNA were efficiently coextracted from a single sample, allowing reliable detection of viral genomes.

DNA, Viral↗

First experiences with an accelerated CMV antigenemia test: CMV Brite Turbo assay.

BACKGROUND: Cytomegalovirus disease is still a major problem in immunocompromised patients, such as bone marrow or kidney transplantation patients. The detection of viral antigen in leukocytes (antigenemia) has proven to be a clinically relevant marker of CMV activity and has found widespread application. Because most existing assays are rather time-consuming and laborious, an accelerated version (Brite Turbo) of an existing method (Brite) has been developed. The major modification is in the direct lysis of erythrocytes instead of separation by sedimentation. OBJECTIVE: In this study the Brite Turbo method has been compared with the conventional Brite method to detect CMV antigen pp65 in peripheral blood leukocytes of 107 consecutive immunocompromised patients. RESULTS: Both tests produced similar results. Discrepancies were limited to the lowest positive range and sensitivity and specificity were comparable for both tests. CONCLUSIONS: Two major advantages of the Brite Turbo method could be observed in comparison to the original method: assay-time was reduced by more than 50% and only 2 ml of blood was required. An additional advantage was the higher number of positive nuclei in the Brite Turbo method attributable to the increased number of granulocytes in the assay. Early detection of CMV infection or reactivation has become faster and easier with this modified assay.

Cytomegalovirus↗

Evaluation of automated nucleic acid extraction devices for application in HCV NAT.

BACKGROUND: To further improve the safety of the blood supply, various national blood transfusion organizations presently use or are in the process of implementing routine HCV NAT in minipools. According to the Committee for Proprietary Medicinal Products (CPMP) of the European Union, the HCV NAT detection limit of the assay should be 100 IU per mL (270 geq/mL) for testing initial plasma pools. Paul Ehrlich Institute (PEI) regulations stipulate that 5000 IU per mL (13,500 geq/mL) must be detected to calculate the amount contributed by individual donations composing the minipool. The sensitivity for HCV RNA extraction achieved by three commercially available laboratory kits was compared. STUDY DESIGN AND METHODS: Nucleic acids from 1-in-3 serial dilutions of an HCV RNA run control (Pelispy, CLB) were extracted with three kits (Cobas Amplicor, Roche Diagnostic Systems; BioRobot 9604, Qiagen; and NucliSens Extractor, Organon Teknika). HCV PCR of all extracts was performed using a second-generation Cobas Amplicor HCV test and the Cobas Amplicor analyzer. RESULTS: The manual Cobas Amplicor, the BioRobot 9604, and the NucliSens Extractor setups allow a 95-percent HCV RNA detection limit of 129, 82, and 12 geq per mL, respectively. The maximal pool size for the manual Cobas Amplicor, the BioRobot 9604, and the NucliSens Extractor kits that would still meet the PEI criteria for HCV NAT in minipools was calculated at 104, 164, and 1125 donations, respectively. CONCLUSION: All three HCV NAT kits evaluated meet the criteria set by CPMP and PEI. The highest sensitivity for HCV NAT screening can be achieved with the high-volume NucliSens Extractor method in combination with the Cobas Amplicor HCV v2.0 test on the Cobas Amplicor analyzer.

Blood Donors↗

Human parvovirus B19: relevance in internal medicine.

Infection by the human parvovirus B19 can lead to several clinical manifestations which are relevant in internal medicine. These include aplastic crisis in chronic haemolytic anaemias, exanthemathous disease and arthropathy, mainly in women, and chronic anaemia in the immunocompromised host. After initial replication, probably in the respiratory tract, the virus enters its target cells in the bone marrow, erythroid precursor cells, through its receptor, the blood group P antigen. Viral replication in these cells leads to an arrest in erythropoiesis, normally lasting approximately 1 week. In this stage, an aplastic crisis can be produced in all patients under 'erythropoietic stress'. The viraemia disappears as specific antibodies to the virus become detectable in serum, which may give rise to a rash or arthralgia, symptoms that are probably immune-mediated. In immunologically normal individuals the infection is cleared by the humoral immune system within several weeks, whereafter detectable specific IgG confers lifelong immunity to reinfection. In patients with absent or dysfunctional humoral immunity to this virus, however, persistent infection can occur, which results in chronic suppression of erythropoiesis with chronic anaemia. Passive immunization, by means of normal immunoglobulin preparations has been reported to be effective in treating this condition. Diagnosis of parvovirus infection is usually possible by the detection of specific antibodies of IgM class in cases of recent infection. In patients with aplastic crisis and patients with chronic anaemia diagnosis rests upon the detection of parvovirus B19 DNA in serum by polymerase chain reaction. Parvovirus B19 is a ubiquitous virus. By the age of 15, about 50% of individuals have serologic evidence of a past infection, which may present as the common childhood disease erythema infectiosum. At the age of 70, seroprevalence reaches 80 to 100%. A vaccine against this virus is currently being developed.

Adolescent↗

Hepatitis B and hemodialysis: the impact of universal precautions in preventing the transmission of bloodborne viruses.

A detailed description is presented of the hemodialysis treatment for 6 weeks of a patient strongly positive for hepatitis B virus ([HBV], hepatitis B surface antigen, hepatitis B e antigen, HBV DNA), which was performed without any special precautions. All 59 patients potentially exposed to the HBV-positive patient, of whom 29 appeared fully unprotected by antibody, were followed for at least 9 months but remained negative. This illustrates the feasibility of following Universal Precautions instead of using exceptional procedures for one single agent.

Adult↗

Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects.

Exhaled nitric oxide (NO) is elevated in asthmatics, and varies with disease severity. We postulated that a respiratory virus infection increases exhaled NO levels in asthma, and examined the relationship between the virus-induced changes in exhaled NO and in airway hyperresponsiveness to histamine. In a parallel study, seven patients underwent experimental rhinovirus 16 (RV16) inoculation at days 0 and 1, whilst seven patients received placebo. Exhaled NO was measured at baseline (day 0) and at days 1, 2 and 3 after inoculation. Histamine challenges were performed prior to (day -7) and after inoculation (day 3), and were expressed as provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). Following RV16 infection there was a significant increase in NO at days 2 and 3 as compared to baseline (median change (range): 4.2 (7.5) parts per billion (ppb), p=0.03, and 3.0 (10.1) ppb, p=0.02, respectively). Furthermore, PC20 decreased significantly following RV16 infection (mean+/-SD change in doubling dose: -0.65+/-0.54, p=0.02), whereas PC20 did not change in the placebo group (p=0.1). There was a significant correlation between the RV16-induced changes in exhaled NO levels at day 2 and the accompanying changes in PC20 at day 3 (rank correlation coefficient (rs): 0.86, p=0.01). Hence, the greater the increase in exhaled NO, the smaller the decrease in PC20. We conclude that rhinovirus infection increases exhaled nitric oxide levels in asthmatics, and that this increase is inversely associated with worsening of airway hyperresponsiveness to histamine. These results suggest that viral induction of nitric oxide synthase within the airways may play a protective role in exacerbations of asthma.

Adult↗

[Vaccination against hepatitis B possibly indicated for elderly institutionalized mentally handicapped persons with isolated anti-HBc positivity of the prevaccination serum].

OBJECTIVE: To determine whether vaccination against hepatitis B may be omitted in persons with isolated positive anti-HBc. DESIGN: Prospective study using control groups. SETTING'S: Heeren Loo-Lozenoord, Ermelo, the Netherlands. METHOD: Twenty-six older residents (group P) with isolated anti-HBc positivity (HBsAg negative and anti-HBs < 10 IU/l) were given hepatitis B vaccine (3 doses); 16 matched controls (group C1) lacking hepatitis B markers, received a primary vaccination (3 doses), 8 controls (group C2) with a immune status based on infection in the past received vaccination (3 doses) and 27 controls (group C3) were given a booster vaccination (1 dose) after vaccination 7 years earlier. The anti-HBs response was measured 0, 1 and 7 months after the first vaccine dose. An anamnestic response was defined as a fourfold rise of anti-HBs after one dose of vaccine or--in the absence of an anti-HBs titer in the prevaccination serum--a response > or = 10 IU/l after one dose of vaccine. A primary response was defined as an anti-HBs response > or = 10 IU/l after giving 3 vaccines, while the criteria for an anamnestic response were not met. RESULTS: In the isolated anti-HBc group (P) and in the corresponding control group (C2) 15 and 12.5%, respectively, showed an anamnestic response; the majority reacted with a primary response or did not respond at all. The subjects given a primary vaccination (C1) responded in 62.5% with a primary response while those vaccinated earlier (C3) responded in 92.6% with a fourfold rise of anti-HBs. CONCLUSIONS: The anti-HBs response to vaccination in older mentally handicapped persons is delayed and there is a reduced chance of development of a protective anti-HBs titer. The majority of individuals with isolated anti-HBc showed a primary response. In these persons vaccination should not be omitted, especially if there is a risk of hepatitis B.

Aged↗