Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.

BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

Evaluating the implementation of nurse-initiated HIV rapid testing in three Veterans Health Administration substance use disorder clinics.

Individuals with substance use disorders (SUDs) are at higher risk of HIV infection, yet recent studies show rates of HIV testing are low among this population. We implemented and evaluated a nurse-initiated HIV oral rapid testing (NRT) strategy at three Veterans Health Administration SUD clinics. Implementation of NRT includes streamlined nurse training and a computerized clinical reminder. The evaluation employed qualitative interviews with staff and a quantitative evaluation of HIV testing rates. Barriers to testing included lack of laboratory support and SUD nursing resistance to performing medical procedures. Facilitators included the ease of NRT integration into workflow, engaged management and an existing culture of disease prevention. Six-months post intervention, rapid testing rates at SUD clinics in sites 1, 2, and 3 were 5.0%, 1.1% and 24.0%, respectively. Findings indicate that NRT can be successfully incorporated into some types of SUD subclinics with minimal perceived impact on workflow and time.

Evaluating frequency, diagnostic quality, and cost of Lyme borreliosis testing in Germany: a retrospective model analysis.

BACKGROUND: Data on the economic impact of Lyme borreliosis (LB) on European health care systems is scarce. This project focused on the epidemiology and costs for laboratory testing in LB patients in Germany. MATERIALS AND METHODS: We performed a sentinel analysis of epidemiological and medicoeconomic data for 2007 and 2008. Data was provided by a German statutory health insurance (DAK) company covering approx. 6.04 million members. In addition, the quality of diagnostic testing for LB in Germany was studied. RESULTS: In 2007 and 2008, the incident diagnosis LB was coded on average for 15,742 out of 6.04 million insured members (0.26%). 20,986 EIAs and 12,558 immunoblots were ordered annually for these patients. For all insured members in the outpatient sector, a total of 174,820 EIAs and 52,280 immunoblots were reimbursed annually to health care providers (cost: 2,600,850€). For Germany, the overall expected cost is estimated at 51,215,105€. However, proficiency testing data questioned test quality and standardization of diagnostic assays used. CONCLUSION: Findings from this study suggest ongoing issues related to care for LB and may help to improve future LB disease management.

Detection of Treponema pallidum in the vitreous by PCR.

BACKGROUND: Ocular involvement of syphilis still poses a clinical challenge due to the chameleonic behaviour of the disease. As the serodiagnosis has significant limitations, the direct detection of Treponema pallidum (TP) in the vitreous represents a desirable diagnostic tool. METHODS: Real-time polymerase chain reaction (PCR) for the detection of TP was applied in diagnostic vitrectomies of two patients with acute chorioretinitis. Qualitative verification of TP by real-time PCR and melting point analysis according to a modified protocol was ruled out. Patients underwent complete ophthalmological examination with fundus photographs, fluorescein angiography, serological examination, antibiotic treatment and follow-up. RESULTS: In two cases of acute chorioretinitis of unknown origin, real-time PCR of vitreous specimens of both patients provided evidence of TP and was 100% specific. Initial diagnosis of presumed viral retinitis was ruled out by PCR of vitreous specimen. Patients were treated with systemic antibiotics and showed prompt improvement in visual function and resolution of fundus lesions. CONCLUSIONS: With real-time PCR, detection of TP in the vitreous was possible and delivered a sensitive, quick and inexpensive answer to a disease rather difficult to assess. In cases of acute chorioretinitis, the use of PCR-based assays of vitreous specimens in the diagnostic evaluation of patients is advisable. Although syphilitic chorioretinitis is a rare disease, PCR should include search for TP, as diagnostic dilemmas prolong definitive treatment in a sight-threatening disease.

[Congenital syphilis despite prenatal screening? An evaluation of 14 cases]. / Konnatale Syphilis trotz Mutterschaftsvorsorge? Eine Evaluierung von 14 Fällen.

BACKGROUND: Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. PATIENTS AND METHODS: Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. RESULTS: All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. CONCLUSIONS: Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS.

[Syphilis in pregnancy]. / Syphilis in der Schwangerschaft.

Syphilis, a sexually transmitted infection, has a major impact on the disease burden worldwide. Globally, an estimated 12 million new cases of sexually acquired syphilis occurred in 1997. Developing countries in Africa, Southeast Asia and regions of the former Soviet Union are mainly affected. With rising numbers of human immunodeficiency virus-infected pregnant women and an increase in gonorrhoea in some areas, the incidence of syphilis is expected to increase again. As a consequence of migration from Eastern bloc countries to Europe after the breakdown of the former Soviet Union, the resurgence of syphilis will also affect Germany. Therefore, we present the clinical picture of syphilis as well as review the current recommendations of the German STD Society, the Centers of Disease Control (CDC), USA, and the Clinical Effectiveness Group (CEG), England, for diagnosis and treatment of syphilis with special emphasis on pregnancy. Considering the current epidemiological situation, physicians should include syphilis in their differential diagnosis. Although recommended therapy regimens differ, penicillin is the treatment of choice. Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin. Early recognition and timely treatment of syphilis are essential to prevent or treat potentially fatal fetal infection.

Rapid DNA typing of HLA-B27 allele by real-time PCR using lightcycler technology.

For clinical diagnostic routine we developed a fast DNA typing of HLA-B27 by PCR and real-time detection using LightCycler technology. The method combines the sensitivity and specificity of PCR with the swiftness of the LightCycler system. The amplification step was performed with a primer set coding for a region in the third exon common to B*2701 to B*2705. The PCR cycles were monitored continuously using the SYBR Green I dye. Beta-globin was used as an internal control. An analysis of 32 samples with one PCR run was completed within 40 minutes. After amplification a melting curve analysis permitted the accurate identification of the PCR amplicons. The mean melting temperatures (Tm) were 90.5 degrees C and 87.3 degrees C, which are characteristic for HLA-B27 and beta-globin, respectively. A comparison of 300 samples which were typed for HLA-B27 with a conventional sequence-specific polymerase chain reaction (SSP-PCR) and with the new method demonstrated a perfect correlation (specificity 100%). In summary, the method described is fast, reliable, cost-effective and well adapted for routine laboratory testing.

DNA fingerprinting by pulsed-field gel electrophoresis to investigate a nosocomial pneumonia caused by Legionella bozemanii serogroup 1.

We typed 18 isolates of Legionella bozemanii obtained from clinical and environmental sources by pulsed-field gel electrophoresis. Each of the unrelated strains showed individual restriction patterns of the genomic DNA when either the SfiI or NotI restriction enzyme was used. One strain isolated from a patient with nosocomial legionellosis and two strains from the corresponding hospital water supply were indistinguishable, arguing for a transmission of L. bozemanii from the water supply to the patient. In conclusion, macrorestriction analysis is a valuable tool for studies of the molecular epidemiology of L. bozemanii.

[Current aspects in the diagnosis of syphilis]. / Aktuelle Aspekte der Syphilisdiagnostik.

In order to present the diagnostic possibilities of treponemal infections, syphilis can be chosen as an example. The direct detection of the pathogen is limited mainly to the early stages of the disease. The diagnostic significance of the PCR as a possible alternative method cannot yet be estimated. The concept for the serodiagnosis of syphilis which includes the TPHA assay as a screening test, the FTA-ABS as the confirmatory test, and the detection of T. pallidum specific IgM antibodies and lipoidal antibodies for the estimation of the disease activity has proven to be very successful. Whether the enzyme immunoassays can replace or supplement the conventional methods has yet to be evaluated critically. There is no possibility for a general statement on the symptomatology of syphilis and the pattern of serological reactions in HIV-infected persons, since the immune system function of each individual is of great importance.

Bacteriological and serological study of pertussis in Abeokuta, Nigeria.

Charcoal horse blood agar is the medium of choice for isolation of Bordetella pertussis from patients with early whooping cough. Since sterile animal blood often is not available in developing countries, a field study in Nigeria was undertaken to evaluate donated human blood as supplement to charcoal agar. Out of 209 children with suspected early pertussis, 33 were culture-positive (isolation rate 16%). Out of 188 children studied serologically by enzyme immunoassay, 36 (19%) were seropositive. The satisfactory isolation rate of 16% shows that culturing for B. pertussis on charcoal human blood agar can be tried in countries, where there is no regular supply of bacteriological media with animal blood.

Comparison of erythromycin ethylsuccinate and co-trimoxazole for treatment of pertussis.

Fifty-five ambulatory children with early culture-proven pertussis were treated for two weeks either with erythromycin ethylsuccinate (n = 28) (50-80 mg/kg/day in three doses during meals) or with co-trimoxazole (n = 27) (6-10 mg trimethoprim/kg/day in two doses after meals). After completion of treatment, all patients in the erythromycin group were culture-negative, while in the co-trimoxazole group one child was still culture-positive. In this case vomiting may have played a role. Both agents appear to be able to eradicate Bordetella pertussis from the nasopharynx of patients with early whooping cough.

[Cryptosporidiosis in immunocompetent patients. Epidemiology and clinical picture]. / Kryptosporidiose bei immunkompetenten Patienten. Epidemiologie und Klinik.

Cryptosporidiosis species were demonstrated in stool of 1.9% of 1600 unselected patients with enteritis (practically evenly divided between children and adults). Further investigations revealed seven cases of enteritis among family members. In eight patients there was a double infection with Cryptosporidium plus another enteritis pathogen. The most frequent clinical symptoms were diarrhea, vomiting, cramp-like abdominal pain, fever and headache. The mean period of parasite excretion was 14 days. Spontaneous cure occurred in all patients. Since cryptosporidiosis is relatively common not only in those with lowered resistance but also those who are immune-competent, search for Cryptosporidium should be included in all tests for etiologically uncertain cases of enteritis.

[Incidence and diagnostic significance of reactive syphilis antibodies in systemic lupus erythematodes and other immunologic diseases]. / Häufigkeit und diagnostische Bedeutung reaktiver Syphilisantikörper bei systemischem Lupus erythematodes und anderen Immunerkrankungen.

Serum samples of 78 patients with systemic lupus erythematosus, systemic sclerosis and other immunological diseases were tested for antibodies to syphilis. Reactive or weak reactive results were observed in 10% by means of the treponema pallidum hemagglutination (TPHA) test, in 27% by the FTA-Abs test, in 40% applying the IgM-FTA-Abs test, in 10% by the VDRL test and in 3% of the cases using the cardiolipin CF test. Only in 3 patients (4%) we found an antibody pattern characteristic of syphilitic patients (TPHA and FTA-Abs test simultaneously undoubtedly reactive). Neither the comparative qualitative and quantitative determination of antibodies to ANA, nDNS and ENA (extractable salinesoluble nuclear antigen) nor elimination of nDNS and ENA antibodies, or incubation of the treponemal test antigen with DNase lead to a conclusion whether the reactive results of the TPHA, FTA-Abs, and IgM-FTA-Abs tests specifically indicate a syphilitic infection. The low incidence of reactive syphilis tests in SLE and the presence of syphilitic antibodies in other immunological diseases limitate the significance for the criterium in the diagnosis of SLE.

[Comparison of 4 methods (immunofluorescence of antinuclear antibodies, indirect hemagglutination, immunodiffusion, counterimmunoelectrophoresis) for the differentiation and identification of nuclear antigen]. / Vergleich der Eignung von vier Methoden (Immunfluoreszenz antinukleärer Antikörper, indirekte Hämagglutination, Immundiffusion, Gegenstromimmunelektrophorese) zur Differenzierung und Identifizierung von nukleäres Antigen.

The performance of four methods (immunofluorescence of antinucleic antibodies (ANA), indirect haemagglutination, immunodiffusion and counterimmunoelectrophoresis) in the detection and differentiation of the antibodies against extractable nucleic antigen (ENA) was analysed with the aid of sera from 197 patients suffering from inflammatory diseases. Counterimmunoelectrophoresis showed the highest sensitivity and specificity for the detection and differentiation of antibodies against ribonucleoproteins (RNP), nuclear glycoprotein (Sm) and antibodies, which occur in Sicca (Sjögren) syndrome (SS-B, Ha). This method, like immunodiffusion, is suitable for demonstrating the common immunological identity of the ENA-antibody sera and the reference sera. The proof of immunological identity using the counterimmunoelectrophoresis was performed with the newly developed test system (pool procedure). This method, as compared to the procedure of Kurata & Tan ((1976) Arthritis Rheum. 19, 574-580) has certain technical advantages, and gives better identification.

[Diphtheria immunity and its epidemiological significance]. / Diphtherie-Immunität und ihre epidemiologische Bedeutung.

Indirect haemagglutination test for antitoxic diphtheria antibodies was performed on 3503 sera of persons of all age groups. The results demonstrate that a high percentage of juveniles and adults with less than 0.01 IU/ml has either no (48.9% for juveniles, 35.6% for adults) or at 0.01-0.09 IU/ml only insufficient immunological protection (30% and 41%, respectively) against diphtheria and its toxic effects. But even among children up to 14 years of age, 28.5% are completely without and 20.5% without reliably protective antitoxic immunity, despite a high rate of immunization. There is thus a dangerously high epidemic potential of susceptible persons in the population of the Federal Republic of Germany. To erect a barrier of immunity against epidemic spread requires not only immunization of all children, but also re-immunization every five to six years, plus immunization of juveniles and young adults among a selected group with, at present, highest risk of infection. For this purpose there is a diphtheria toxoid of Behringwerke for adults with only 5 IU toxoid/0.5 ml, which, however, after single application produced an antitoxic immunity (greater than or equal to 0.1 IU/ml) in previously sensitized subjects (17 of 49). Of 32 primary seronegative persons 14 reacted to two injections, while a further 18 (36.7%) had no immune response within six weeks even after second injection.