Micha Löbermann

Immunization in the adult immunocompromised host

The number of patients with impaired immune response has been steadily increasing within the last years, not only with the onset of the AIDS epidemic, but also due to increasing numbers of subjects on immunosuppressive therapies. These patients are at an increased risk for infections, many of which are preventable by immunization. Inactivated vaccines are generally safe in subjects with underlying immunosuppression. However, immune response and protection may be hampered, depending on the extent of immunosuppression. In contrast, live vaccines such as yellow fever, measles, rubella, herpes zoster, and cholera may lead to severe reactions in immunocompromised patients and have been shown to deteriorate some immune-mediated diseases such as multiple sclerosis. Data on the efficacy of vaccines in biological therapies is scarce. Where necessary vaccines should be updated before immunosuppressive therapies are started. To improve the vaccination status several guidelines exist for immunosuppressed patients at risk such as those with rheumatic diseases, asplenia or solid organ and hematopoietic stem cell transplantation.

Human cowpox virus infection acquired from a circus elephant in Germany

A 40-year-old Asian circus elephant developed mouth and trunk ulcers. Three weeks later, her 19-year-old animal warden noticed a vesicle on his forearm, evolving into a scab. Identical cowpox strains were isolated from lesions of the elephant and the warden. Cowpox virus could no longer be isolated after the scab disappeared, but PCR still revealed orthopox DNA. Healing was complete seven weeks later, leaving a 1 cm scar.

Tickborne Meningoencephalitis, First Case after 19 Years in Northeastern Germany

To the Editor: Tickborne encephalitis virus (TBEV) is focally distributed in Europe and Asia (between 42° and 63° north latitude). Recently, 5 human tickborne encephalitis cases have been reported, and anti-tickborne encephalitis antibody prevalence in dogs has been observed in southern Norway (1). In the last 2 decades, mild winters may have favored a northbound spread and increased tickborne encephalitis incidence (2). Tickborne encephalitis is endemic in southern Germany, but no cases had been reported in northeast Germany since 1985 (3,4). A 61-year-old man was bitten by a tick at Lake Woblitz, near the town of Neustrelitz in former East Germany, on May 31, 2004, between 8:00 a.m. and 4:00 p.m. The patients history showed no other tick bites, no stays in tickborne encephalitis–endemic areas, and no tickborne encephalitis vaccination. On June 9, transient fever and headache developed in the patient, followed 6 days later by difficulty in concentrating, apathy, and a strong urge to sleep. On June 23, the patient was hospitalized with fever (temperature 39.2°C) and mental confusion. Because he had cruised the Nile in December 2003, he was transferred to the Tropical Medicine Division of Rostock University to exclude a diagnosis of malaria. Somnolence, slurred speech, amnestic dysphasia, and impaired fine motor control, but no meningism, focal signs, pyramidal tract, or sensation impairment, were observed. Results of magnetic resonance imaging brain scan and electroencephalogram were normal. Laboratory tests showed leukocytosis of 9,400 leukocytes/µL and lymphocytopenia of 12%. Alpha-amylase was 254 U/L, lipase 84 U/L, sodium 131 mmol/L, and fibrinogen 4.4 g/L. C-reactive protein and all other routine laboratory parameters were normal. In the serum, immunoglobulin (Ig)G, but not IgM, was detected against Borrelia burgdorferi. Tests of cerebrospinal fluid (CSF) specimens, including polymerase chain reaction (PCR) for herpes simplex virus types 1 and 2, varicella zoster virus, Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were negative. Antibody tests for Borrelia burgdorferi, Mycoplasma pneumoniae, Bartonella, Brucella, Leptospira interrogans, HIV, EBV, and arboviruses were negative. VDRL (Venereal Disease Research Laboratory) tests, Gram stains, and routine bacterial cultures for common pathogens were also negative (5). Tests on CSF showed mild pleocytosis (9 leukocytes/µL) and high protein concentration (1,322 g/L). Most cells were lymphocytes (89%) and monocytes (10%). Protein analysis showed blood-brain barrier impairment and intrathecal IgM synthesis. Anti-tickborne encephalitis virus IgG and IgM antibodies were detectable in the serum by enzyme-linked immunosorbent assay 29 days after the tick bite; corresponding CSF titers were borderline. One week later, IgG and IgM antibodies were positive in serum and CSF, while CSF leukocyte count and protein concentration were normal. The anti-tickborne encephalitis serum immunofluorescence titer rose from 1:80 (June 29) to 1:640 (July 14); titers against dengue, West Nile, yellow fever, and Japan B encephalitis were not elevated. Even though CSF specimens were negative for TBEV genome on 2 occasions, a confirmed tickborne encephalitis case had to be reported to the health authorities. With symptomatic therapy, the patients condition improved, and he was discharged on July 7 with slight mental slowing. By July 14, he had recovered completely. Our patient had acquired tickborne encephalitis at a popular tourist site (Figure), where no human cases had occurred for 19 years. From 1959 to 1983, numerous TBEV foci existed in northeastern Germany (3). From 1960 to 1985, a total of 4 human cases were seen 10 km east of Neustrelitz. From 1983 to 1989, numerous attempts to cultivate TBEV from ticks or small mammals failed (3). In 1992, TBEV genome was detected by PCR in 3 tick pools from the island of Usedom, and in 2 pools from the Darss peninsula, 100 km northeast of Neustrelitz. From 1993 to July 2004, TBEV genome was not detected in 16,098 ticks collected from 275 regions of northeastern Germany, including the county where Lake Woblitz is situated, as part of a statewide surveillance program (State Health Services, unpub. data). However, during 2004, this county reported 24 cases of Lyme disease (2003: 10 cases; 2002: 8 cases; 2001: 1 case). Therefore, our tickborne encephalitis case might represent intensified amplification cycles of tickborne infectious agents in 2004. Figure European tickborne encephalitis–endemic areas (in red) and new infection site of case in northeastern Germany (arrow). Map provided by Baxter Germany GmbH. The absence of tickborne encephalitis cases for 20 years does not likely represent a lack of data before or a lack of interest after the reunification of Germany. Tickborne encephalitis was a reportable disease under East German regulations, and tickborne encephalitis surveillance was intensified after reunification (3). Eight weeks after our patients tick bite, 160 Ixodes ricinus ticks were collected from 10 pools near Lake Woblitz. RNA was isolated in 5 mol/L guanidium isothiocyanate solution, extracted by phenolchloroform, and precipitated with ethanol. cDNA was amplified by nested reverse transcription–PCR and detected by electrophoresis (6). In 2 of these pools, PCR directed towards the 5´ terminal noncoding region of the TBEV genome yielded a 104-bp fragment, but the sequence was not specific for flaviviruses. This case does not prove a northbound spread of tickborne encephalitis in northeastern Germany. Rather, it shows that after years of negative tickborne encephalitis test results in ticks, old tickborne encephalitis foci may retain activity. Thus, tickborne encephalitis should be included in the differential diagnosis of meningoencephalitis in northeastern Germany, even if the patient has not been in tickborne encephalitis–endemic areas.

Impfen bei Immundefekten oder medikamentöser Immunsuppression

Patients with immunodeficiency and patients under immunosuppressive therapy have an increased risk of infectious diseases. Vaccination strategies are needed to protect them from preventable diseases. The underlying disease and severity of the immune impairment may have influence on indications and contra-indications of vaccines. Inactivated vaccines can be administered safely according to the current recommendations of the Permanent Commission on Vaccinations of the Robert-Koch-Institut in Berlin, Germany (STIKO). Depending on the severity of the immune dysfunction, antibody response to vaccinations varies. Where possible, the antibody response following vaccinations should be tested. Previously, attenuated live vaccines were considered to be strictly contra-indicated in immunocompromised patients. Today, the administration of attenuated live vaccines is thought to be possible, depending on the degree and type of immunodeficiency or immunosuppression of the individual.

[Tick-borne encephalitis virus in humans and ticks in Northeastern Germany].

Tick-borne encephalitis (TBE) was known to have occurred in humans in the area of Mecklenburg-Western Pomerania in Germany, until 1985. Between 1992 and 2004 more than 16,000 ticks were tested and found to be negative for TBE virus in that area of Germany, wich was therefore thought to be free of TBE. But after 19 years three autochthonous cases of human TBE-infections were identified between 2004 and 2006. We subsequently collected ticks from the three areas where the infection had been acquired and tested them for the presence of TBE-virus RNA with a nested reverse transcription polymerase chain reaction (RT-PCR). Since there is evidence that a blood-meal leads to an increase of FSME-RNA in ticks, we tested both, unfed ticks and ticks after a blood-meal. Three unfed and one fed nymph from the area around Lake Woblitz and one unfed and one fed nymph from Thiessow were positive for TBE-virus RNA. A total of six of 250 (2.4%) ticks tested positive for TBE-virus. The emerging of human TBE infections in three regions in Mecklenburg-Western Pomerania shows that the activity of natural TBE virus foci does not cease even after decades, or that TBE-infected ticks could have recolonized these regions.

Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis

Objective  In malaria and sepsis, apoptotic endothelial damage is preventable in vitro by antioxidants and protease inhibitors. Activated protein C, which has anti‐apoptotic effects, improves survival in sepsis. Therefore, we studied whether activated protein C prevents endothelial cell apoptosis, induced by serum from patients with malaria or sepsis.

BCGitis mit Lungen-, Leber- und Knochenmarksbeteiligung nach Immuntherapie eines Urothelkarzinoms

Medical history A 77-year-old patient with transurethral resection of a bladder tumor was transferred due to persistent fever and progressive dyspnea despite antibiotic therapy for suspected urinary tract infection. Repeating the medical history revealed that a BCG immunotherapy of his non-muscle-invasive bladder carcinoma was performed the day before fever developed. Therefore, BCGitis was suspected. Examinations Laboratory parameters showed pancytopenia, elevated liver enzymes, eleveated C-reactive protein and hypoxemia. The CT scan showed multiple miliary lesions of the lung, the bone marrow biopsy revealed granuloma. Diagnosis M. bovis BCG was cultured from urine and bronchoalveolar lavage fluid. Therapy and course Therapy with isoniazide, rifampine, ethambutol and initially prednisolone caused rapid improvement. Conclusion BCGitis is a rare complication of BCG immunotherapy of non-muscle-invasive bladder carcinoma.

Frühsommer-Meningoenzephalitis-Virus bei Menschen und Zecken in Mecklenburg-Vorpommern

Tick-borne encephalitis (TBE) was known to have occurred in humans in the area of Mecklenburg-Western Pomerania in Germany, until 1985. Between 1992 and 2004 more than 16,000 ticks were tested and found to be negative for TBE virus in that area of Germany, wich was therefore thought to be free of TBE. But after 19 years three autochthonous cases of human TBE-infections were identified between 2004 and 2006. We subsequently collected ticks from the three areas where the infection had been acquired and tested them for the presence of TBE-virus RNA with a nested reverse transcription polymerase chain reaction (RT-PCR). Since there is evidence that a blood-meal leads to an increase of FSME-RNA in ticks, we tested both, unfed ticks and ticks after a blood-meal. Three unfed and one fed nymph from the area around Lake Woblitz and one unfed and one fed nymph from Thiessow were positive for TBE-virus RNA. A total of six of 250 (2.4%) ticks tested positive for TBE-virus. The emerging of human TBE infections in three regions in Mecklenburg-Western Pomerania shows that the activity of natural TBE virus foci does not cease even after decades, or that TBE-infected ticks could have recolonized these regions.

Bilateral deafness two days following influenza vaccination: a case report

ABSTRACT Objective: We report a case of deafness occurring in a temporal context of an influenza vaccination in a 79-year-old woman. Methods: Case report and review of the literature on influenza causing deafness. Results: A 79-year-old woman with normal hearing developed acute bilateral sensorineural hearing loss two days after a seasonal influenza vaccination, other obvious reasons for acute hearing loss were excluded. Conclusion: This patient appears to be the first reported case of bilateral deafness following a trivalent seasonal influenza vaccination.

Posttraumatic Aneurysm of a Patent Umbilical Vein: Diagnosis and Specific Treatment

A patent umbilical vein is a rare condition in healthy volunteers, but can be detected in up to 11% of patients with liver cirrhosis as a consequence of portal hypertension. We report the case of a 52-year-old woman who was admitted to our department with acute abdominal pain after blunt trauma to her forehead and abdomen. She had a history of alcohol abuse with liver cirrhosis that had been classified as Child-Pugh stage C 5 years earlier. Signs of portosystemic shunting had been present at an earlier endoscopy, and esophageal varices were found. Clinical examination revealed typical signs of liver cirrhosis, and ultrasound examination showed an aneurysm of 6 cm of the umbilical vein, which had not been present at earlier examinations. After lowering portal hypertension by inserting a transjugular intrahepatic portosystemic shunt, an open surgical resection of the aneurysmal umbilical vein was performed without complications. The patient recovered well and was discharged from the hospital 10 days later. We hypothesize that the abdominal trauma prompted or aggravated umbilical vein aneurysm in this patient with liver cirrhosis and portal hypertension. Due to the risk of rupture, a surgery-based resection is a valuable treatment option.