Family outbreak of an infection with a recombinant Coxsackie A virus in eastern Switzerland.

PURPOSE: We report on an unusual familial outbreak of a coxsackie virus infection in Switzerland in which five family members were affected. Most of the patients presented with signs of meningitis, and four were hospitalized. METHODS: In three individuals, the virus was detected in the cerebrospinal fluid, pharynx, and stool, respectively. The genome was sequenced in specimens of two patients. RESULTS: The nucleotide sequences of both virus strains were identical. Blast search revealed that the first half of the sequence was 88 % homologous to Enterovirus 75 (EV-75), 87 % with Echovirus 11 (E-11), and 84 % homologous to Coxsackie virus A9 (CV-A9). The second half of the sequence was 77 % homologous to EV-75, 75 % to E-11, and 91 % to CV-A9. CONCLUSION: We propose that the isolated virus strain is a recombinant strain with a 5' untranslated region and with the start of the VP4 sequence originating from E-11/EV-75 and the rest of the genome originating from CV-A9. Interestingly, this novel virus strain showed an exceptional virulence and rapid spread. Two weeks after the initial outbreak in this family, a similar outbreak was observed in a second geographic area roughly 100 km distant to the primary identification site, and another 2 months later this virus strain was found to circulate in the western part of Switzerland some 250 km distant to the primary locus. These findings suggest that genetic recombination has resulted in a novel enterovirus with features of high virulence, contagiosity, and spreading.

Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has been associated with a marked decrease in the prevalence of opportunistic infections in HIV-infected patients. However, chronic mucocutaneous herpes simplex virus (HSV) infection remains a difficult clinical challenge. OBJECTIVE: The aim of the study was to optimize the diagnosis and follow-up of chronic HSV-2 infection in HIV-infected patients and to correlate clinical data with CD4 cell count, in vitro HSV virological resistance and histology. METHODS: A retrospective case series was collected from a specialist out-patient clinic providing consultations to patients with infectious skin diseases. Clinical, biological, virological and histological data were analysed. RESULTS: Seven HIV-infected patients with genital and perianal herpes simplex infection were followed over 10 years. Ulcerative and pseudo-tumoral forms were observed. Lesions occurred at various stages of immune suppression (CD4 counts from 1 to 449 cells/µL). Clinical resistance to conventional anti-herpetic drugs was correlated with the in vitro resistance of HSV in 70% of cases. CONCLUSIONS: Chronic mucocutaneous HSV infection in AIDS patients remains a rare but regularly observed infection in very immunosuppressed patients or those with unstable immunity during HAART. Virological results obtained from mucocutaneous samples were in most cases found to be correlated with clinical evolution and should therefore be used in making decisions on treatment. Despite efficient antiviral therapy, mucocutaneous healing is slow in the majority of cases.

False serologic evidence for acute primary toxoplasmosis during liver transplantation for fulminant hepatitis B: a case report.

Acute primary Toxoplasma gondii infection is usually considered to be a contraindication for solid organ transplantation. Recent reports of acute T. gondii infection have highlighted the need to include T. gondii serology in the pretransplant screening of solid-organ transplant recipients. However such serology might be misleading. We describe the case of a 25-year-old woman who received a liver transplantation for life-threatening liver failure due to hepatitis B virus infection. The presence of high IgM titers against T. gondii, as detected by membrane immunoassay, immunofluorescence, and mu-capture ELISA tests, together with the absence of IgG antibodies in the immediate pretransplant serology screening suggested acute primary T. gondii infection at the time of transplantation. We initiated a preemptive therapy with intravenous clindamycin and cotrimoxazole. However, negative PCR and IgA capture assays, together with the absence of a sustained IgG response finally excluded the initial diagnosis of primary toxoplasmosis, leading to discontinuation of antitoxoplasmosis therapy. This case illustrates the problem that, in the context of fulminant hepatitis B, serologic markers for acute primary toxoplasmosis can be falsely positive. Confirmation by PCR and IgA antibody determinations is required to confirm this diagnosis.

Swiss recommendations for the management of varicella zoster virus infections.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

[Will avian influenza virus become a human virus?]. / Le viruS de la grippe aviaire sera-t-il humain ?

Since 1997, an Influenza virus of avian origin appears regularly in human causing severe respiratory infections leading to death in half cases. This Influenza A (H5N I) virus which is at the origin of this illness circulates in wild birds and in domestic birds. Million poultry have been regularly infected or slaughtered on 3 continents: Asia, Africa and Europe. H5NI virus, like any other Influenza virus, has the ability to adapt its genome and theoretically could easily jump from the avian animals to human directly. On the other hand, since 10 years it still did not acquire this capacity. This paper summarise our knowledge on the risk of a future pandemic.

[Emerging viral infections]. / Infections virales émergentes.

Emerging, re-emerging, rare or dangerous viruses are regularly citated in news. Most of theses viruses belong to the class 3 and 4. Clinical specimens must be handled with appropriate bio-security conditions, and, for some of them, high security facilities are required. In Geneva, a new P4D facility aiming to conduct diagnostic procedures targeting these viruses, fills a gap in Switzerland in this field. The goal of this review is to present some examples of past and ongoing viral outbreaks around the world, to present the virus classification according to the biological risk and to summarise basic knowledge concerning class 4 viruses.

[From diagnosis to the detection of avian influenza virus]. / Von der Diagnose zum Nachweis der Vogelgrippe beim Menschen.

Until now the avian influenza A (H5N1) virus is only adapted to birds. But even so infections in man are observed sporadically. Why is this possible and how big is the risk that the virus becomes fully adapted to man so that he can be transmitted easily from man to man. Two major mechanisms for the adaptation to a new host have been described: Adaptation by the accumulation of mutations in important places of the genome and adaptation through the exchange of genome segments between two different types of viruses. But there are indications that the adaptation is not linked to only one event. It is probably a multifactor event where its requirements are not all known or understood. Until now avian influenza is not adapted to man. Infection is primarily observed after close contact with infected birds or their contaminated secretions. It seems that the virus needs to reach the lower respiratory tract in order to be able to infect. The disease starts with the clinical symptoms of influenza but progresses rapidly involving primarily the lower respiratory tract causing sometimes live threatening complications. Because of the similarity of symptoms with normal flu laboratory testing is necessary to clarify the situation. Ideally a rapid test would give in a short time a result. Unfortunately this type of test shows insufficient sensitivity and for this reason is not recommended to screen suspect cases for avian influenza. For this reason the detection of the avian virus by RT-PCR in throat swabs is the method of choice in order to be able to confirm or exclude a suspect case.

[Respiratory tract viruses]. / Respiratorische Viren.

The respiratory tract is the site of entrance of many viruses. However, not all of them cause symptomatic respiratory infections. In the past the clinical significance of some viruses was underestimated. Viruses leading to population-wide epidemics like influenzavirus or to nosocomial outbreaks like respiratory syncytial virus or SARS-associated coronavirus have a great impact on public health and the respective preventive measures are of paramount importance. The advent of new diagnostic tools led to discoveries and additional information about some "banal" viruses causing severe diseases in special hosts such as infants and immunosuppressed patients. In addition new viral pathogens were discovered and found to cause respiratory infections, metapneumovirus and SARS-associated coronavirus being the most important ones.

Rapid antigen testing for the surveillance of influenza epidemics.

OBJECTIVE: To assess the use of a 'near patient' test for rapid antigen detection to obtain the more timely acquisition of data for the surveillance of influenza epidemics. METHODS: To the classical cell culture system used for the surveillance of influenza, a 'near patient' test was added. The cell culture method was applied for the detection of influenza virus in specimens sent to our laboratory. In contrast, the 'near patient' test was used directly by practitioners in their practices to screen patients for the presence of influenza virus antigen. RESULTS: The results for two seasons are presented. The 'near patient' test was able to detect a developing influenza epidemic with the same reliability as clinical consultation reports for influenza-like illness or the conventional culture method. However, the results obtained were available 9 days earlier on average, compared with cell culture. Because of this, results concerning the epidemics could be announced via the internet more rapidly. Although the 'near patient' test demonstrated a lower sensitivity than detection by conventional cell culture, the sensitivity was still sufficiently high to reveal the characteristics of the epidemics in the community. CONCLUSIONS: Rapid influenza testing is a reliable tool for influenza surveillance and, compared with traditional methods (virus detection on cell culture and monitoring of influenza-like illness), provides faster results. Although the 'near patient' test has limited sensitivity compared with cell culture, results were consistent over two seasons, and suggest that rapid testing should be part of a surveillance program.

Human infection by a swine influenza A (H1N1) virus in Switzerland.

The isolation of A/Switzerland/8808/2002 provides further evidence of sporadic human infection by contemporary swine influenza A H1N1 viruses, antigenically and genetically distinct from H1N1 viruses circulating in the human population. Together with the recent emergence of human-swine-avian reassortant viruses in pig populations in Europe and North America, frequent transmission between swine and human populations emphasises the potential for the emergence in pigs of novel subtypes with the capacity to cause major human epidemics.

The use of near patient tests in influenza surveillance: Swiss experience and EISS recommendations.

Surveillance requires time for analysis and for the communication to physicians. In order to reduce this delay, a new surveillance system based on the use of a near patient test (NPT) has been evaluated. The high specificity of NPT together with the rapidity in obtaining the results, make these tests attractive for surveillance of influenza epidemic in community practice. Such surveillance has been used in several countries including Switzerland. Four different seasons - between 1999 and 2003 - of this type of surveillance experienced in Switzerland have been analysed. The heterogeneity in terms of intensity and type of strains detected during these four epidemics seasons allowed an efficient evaluation. The average gain of time with NPT compared to cell culture was nine days. Furthermore, training of participants appeared to be essential to assure the quality of the surveillance system. A statement on the use of NPTs for influenza surveillance has finally been endorsed by EISS members. Included are recommendations that the network should use the NPTs data, which provides additional information to the classical surveillance systems, as an "early warning" system of a change in influenza activity.

Evaluation of an optical immunoassay for the rapid detection of influenza A and B viral antigens.

An optical immunoassay for the rapid detection of influenza types A and B viral antigens, FLU OIA (Biostar, USA), was prospectively compared with antigen detection methods and cell culture on 400 respiratory specimens during an influenza outbreak that occurred in Switzerland in 1998/1999. The FLU OIA had an overall sensitivity of 64.4% (95%CI, 56.3-71.7%) and a specificity of 94.9% (95%CI, 89.8-97.7%). Using specimens from pediatric and adolescent patients, the sensitivity obtained (71.8%; 95%CI, 61.7-80%) was different than that achieved with specimens from adult patients (51.4%; 95%CI, 36.5-65%) (P=0.004). The results show that rapid diagnostic tests with higher sensitivity and specificity for the detection of influenza virus are needed.

Detection of enteroviruses in the cerebrospinal fluid by polymerase chain reaction: prospective study of impact on the management of hospitalized children.

A polymerase chain reaction kit (AMPLICOR EV) for the detection of enteroviruses (EV-PCR) in the cerebrospinal fluid (CSF) was evaluated in clinical conditions in a prospective blinded-intention study. Forty-three children (mean age 2.7 years) hospitalized for suspected meningitis or fever of unclear etiology were enrolled. EV-PCR was performed on a daily basis. Results were available in less than 2 days in 72% of cases. EV-PCR was positive in nine (21%) children, including three infants without CSF pleocytosis. Knowing their EV-PCR result would have allowed a saving of 18 hospital days and 12 days of antibiotic therapy. The EV-PCR in the CSF can thus be practically useful for children hospitalized for meningitis or fever if available on-site on a daily basis.

Costs and outcomes of prolonged cytomegalovirus prophylaxis to cover the enhanced immunosuppression phase following lung transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is one of the major challenges of lung transplantation that may determine outcome. The benefits of ganciclovir prophylaxis seem indisputable, but no consensus has been reached on the optimal duration of therapy. Results with different protocols suggest that efficacy is related to the duration of treatment. MATERIALS AND METHODS: To evaluate the additional effect of a prolonged regimen throughout the maximal immunosuppression phase, we conceived a protocol administering ganciclovir, 5 mg/kg/d for 20 weeks from the first postoperative day, to all CMV-seropositive patients undergoing lung transplantation or receiving the lung from a seropositive donor. Virus shedding was routinely measured in body fluids including through BAL. Costs and outcomes are compared with those in shorter prophylaxis protocols from previous reported studies. RESULTS: Of 30 lung transplant recipients, 22 patients at risk for CMV reactivations were observed for (mean SD) 22.9 +/- 13.2 months. CMV infections were detected in eight patients 8.6 +/- 5.1 months after transplantation. CMV pneumonitis developed in one patient 9 months following the transplant event. Prolonged IV ganciclovir prophylaxis was, in general, well tolerated. However, five patients had bacteremia and one had a local thrombosis, with no long-term consequences. A prescription for 8 additional weeks of prophylaxis to cover the whole period of enhanced immunosuppression decreased the cumulative incidence of first CMV infections by 29% 1 year after transplantation compared to 12-week regimens reported in other studies that indicated a 50% reduction in the incidence of first CMV infection. The total cost of 20 weeks of IV ganciclovir prophylaxis was $6,010 (US dollars) per patient more expensive than 12 weeks of IV ganciclovir therapy. This was not offset by the reduced requirement for treatment of infections. Indeed, extrapolating to our cohort of patients, the additional cost per patient was seven times greater than the treatment for the infections that were reported after the 12-week prophylaxis protocol. CONCLUSION: Prolonging ganciclovir prophylaxis to 20 weeks decreased by half the rates of CMV infection when compared to reports from centers using a shorter protocol of 12 weeks for ganciclovir prophylaxis. Additionally, a delay in the onset of the first infection was observed. Nevertheless, the increase in costs and the discomfort of long-term use of venous catheters are important factors that may favor a shorter regimen of 12 weeks followed by preemptive therapies each time CMV infections occur.

Treatment of acyclovir-resistant herpetic ulceration with topical foscarnet and antiviral sensitivity analysis.

BACKGROUND: Herpes simplex virus (HSV) can produce persistent mucocutaneous disease in patients with the acquired immunodeficiency syndrome (AIDS). In this case report, we evaluate the efficacy, safety and viral resistance after topical foscarnet in severe genital ulceration due to acyclovir-resistant HSV-2. CASE REPORT: A 45-year-old African woman was known for an HIV infection with severe immunosuppression (CD4 <100/mm3). She had received a long-term prophylaxis with acyclovir (400 mg b.i.d.) for a recurrent genital herpes. Few weeks after stopping this prophylaxis, she developed large genital ulcerations progressing despite valacyclovir treatment (1,000 mg t.i.d.). Cultures were positive for HSV-2, resistance to acyclovir was shown by the plaque reduction assay and topical foscarnet was tried. Treatment consisted of a 20-min application of topical foscarnet 2.4% twice a day. Dramatic improvement was observed with rapid antalgia, and cicatrization of the genital ulcerations was observed after 50 days. HSV could not be detected on the mucosal surface. Initially, HSV-2 was resistant to acyclovir but sensitive to foscarnet. After 1 month of topical treatment, HSV-2 became sensitive to acyclovir and was still sensitive to foscarnet. Finally, after 6 weeks of treatment, no virus could be detected by culture. CONCLUSION: Topical foscarnet (2.4%) is a convenient treatment for chronic genital herpes. Resistance to acyclovir disappears few weeks after stopping this drug and sensitivity to foscarnet persists during the 50 days of treatment.

Influenza immunization: improving compliance of healthcare workers.

OBJECTIVE: In spite of yearly recalls, influenza immunization rates of healthcare workers (HCWs) remained low (10%) at the University Hospitals of Geneva. This study was conducted to identify HCWs' reasons for rejection of immunization, to design specific intervention methods based on these reasons, and to evaluate the impact of such interventions. METHODS: Three departments with high-risk patients (geriatrics, obstetrics, and pediatrics) were selected as main targets. Questionnaires were distributed in these units. Based on HCWs' perceptions, different intervention methods were designed and used either in these departments only (educational conferences, on-site availability of a vaccination nurse) or in the whole institution (posters, personal letters). Immunization rates were collected throughout the institution. RESULTS: 797 completed questionnaires from 1,092 HCWs (73%) were returned. Major reasons for immunization rejection were confidence that their bodies' self-defense mechanisms would ward off infection (32%), perception of low exposure risk (23%), and doubts concerning vaccine efficacy (19%). The use of intervention methods designed to address these factors increased influenza immunization rates in the three targeted departments from 13% (95% confidence interval [CI95], 11.4-15.6) in 1995 and 1996 to 37% (CI95, 34.5-40.3) in the following season (P<.001). In all other departments, immunization rates rose from 9% (CI95, 8.5-10.3) to 23% (CI95, 21.6-24.1; P<.001). Nurses were, and remained, more reluctant to be immunized compared to other HCWs. CONCLUSIONS: Influenza immunization rates can be increased significantly by specific interventions based on local concerns of HCWs, among which educational conferences and the on-site availability of a vaccination nurse appeared important.

Surveillance of cytomegalovirus after solid-organ transplantation: comparison of pp65 antigenemia assay with a quantitative DNA hybridization assay.

In a multicenter study, 113 blood samples from 19 organ transplant patients were analyzed for cytomegalovirus by the pp65 antigenemia assay and a quantitative DNA hybridization assay. Overall, there was 84% agreement among the results obtained by the two tests. Fifteen of 16 episodes of active infection were detected by both assays. One episode was missed by the pp65 assay, and one patient showed significant DNA-emia but only low-level antigenemia.

ARDS caused by herpes simplex virus pneumonia in a patient with Crohn's disease: a case report.

Pneumonia caused by herpes simplex virus type 1 (HSV1) is rare and occurs in severely immunosuppressed patients. HSV1 can be detected in bronchoalveolar lavage (BAL) from patients presenting with respiratory failure, but its direct effect on disease is difficult to prove. We demonstrate the causative role of HSV1 in the case of a 44-year-old male with Crohn's disease who presented to the intensive care unit with the acute respiratory distress syndrome after surgery. BAL cells were cultured and immunofluorescence confirmed the presence of HSV1 during the first weeks of illness. Increased IgG titers confirmed the diagnosis of a recurrent HSV1 infection. A lung biposy specimen showed fibroproliferation without pathogens. Immunosuppressive therapy had been stopped and acyclovir was introduced at this time. The diagnostic difficulties in this patient underline the importance of early recognition of viral infection as a potential cause of severe pneumonia in severely ill, immunocompromised patients.

World-wide surveillance of influenza.

Influenza epidemics and pandemics resulting in excess mortality are due to various influenza viruses, in which through the accumulation of mutations the structure changes. A world-wide surveillance has been set up for early detection of new influenza virus strains and of epidemics or pandemics resulting thereof. Basing on such data the World Health Organisation (WHO) issues recommendations to Public Health authorities on the most efficient means for prevention.