[Oculogyric crisis as an isolated extrapyramidal symptom of auto-intoxication with risperidone]. / Oculogyre crisis als enige extrapiramidaal symptoom bij auto-intoxicatie met risperidon.

A 19-year-old female was seen at the emergency department following an auto-intoxication. An oculogyric crisis (ogc) was observed, in the absence of other extrapyramidal symptoms (eps). In a second anamnesis, patient indicated that she had taken risperidone 3 mg (an atypical antipsychotic). This particular case description of an isolated ogc shows that care providers should be attentive to the occurrence of ogc, even if the most frequent eps are absent. This case also emphasizes the importance of a complete history in order to efficiently and timely guide the care provider to the correct diagnosis.

Prediction of recurrent disease by cytology and HPV testing after treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To assess the role of human papillomavirus (HPV) testing and cytology as predictors of residual/recurrent disease after treatment of high-grade cervical intraepithelial lesions. METHODS: One hundred and thirty-eight women with cervical intraepithelial neoplasia (CIN) grade 2/3 lesion on biopsy were included in a prospective follow-up study in Belgium and Nicaragua. All women were treated with loop electrosurgical excision procedure (LEEP) and follow-up visits took place at 6 weeks, 6 months, 1 year and 2 years. During these visits, a Papanicolaou (Pap) smear test was taken, colposcopy was performed and specimens were collected for HPV testing. Cytology, high-risk (HR) HPV presence, persistent HR HPV infection and combinations of these tests at different time points during follow-up were correlated with histologically confirmed residual/recurrent disease. RESULTS: Thirteen patients (9%) developed residual/recurrent disease during follow-up. Abnormal cytology at 6 weeks after treatment was significantly correlated with residual/recurrent disease. Nine of thirty-seven patients with abnormal cytology at 6 weeks had recurrent disease versus three of seventy with a normal cytology [odds ratio (OR): 7.2; 95% confidence interval (CI): 1.8-28.5; P = 0.003). Sensitivity of this test was 75.0%, specificity 70.5%. Combining abnormal cytology and the presence of HR HPV within the first 6 months after treatment gave the best correlation with residual/recurrent disease: of the 54 women with abnormal cytology and/or HR HPV presence within the first 6 months, 11 developed residual/recurrent disease (OR 10.2; 95% CI: 2.2-48.3). Sensitivity of this combination was 84.6% and specificity 65.0%. CONCLUSION: Cytology remains the cornerstone in the early follow-up after LEEP for CIN lesions of the cervix. HPV testing can add value as it increases the sensitivity of cytology in concomitant testing within the first 6 months.

[Human papillomavirus genotype profile in Kinshasa, Democratic Republic of the Congo: implications for vaccination]. / Profil génotypique du papillomavirus humain rencontré dans l'environnement de Kinshasa: intérêt vaccinal.

UNLABELLED: Proposed anti-human papillomavirus (HPV) vaccines, i.e., Cervarix (Glaxomith-Kline) and Gardasil (Merck), are designed to prevent infection by two high-risk HPV types, i.e., 16 and 18, for which estimation mainly in Western Europe and North America have demonstrated a prevalence 60 to 70%. OBJECTIVE: The purpose of this study was to determine the genotype profile of HPV strains encountered in the women of childbearing age in Kinshasa, Democratic Republic of the Congo and discuss the implications of this profile for anti-HPV vaccination. METHODS: Data and specimen collection was carried out at a voluntary HIV screening and treatment facility. Genotyping of HPV was performed in 55 patients presenting dysplastic lesions of the uterine cervix including 47 (85.5%) who were HIV-seropositive. Detection and typing of HPV were performed using the Inno-Lipa technique (Innogenetics Line Probe Assay) from Glaxo-Smith-Kline. RESULTS: Tests for HPV were positive in 54 patients (98.2%). A total of 153 HPV strains were isolated. Twenty-three HPV types were identified including 83.0% with high oncogenic activity. In order of frequency the oncogenic types were as follows: 68, 35, 51, 52, 16, 31, 18, 17, 33, 45, 56, 58 and 59. Strain frequency per patient ranged from 1 to 8 (mean +/- standard deviation, 2.8 +/- 2,0). Types 16 and 18 accounted for 11.8% of the isolated strains (18/153) and were observed in 33.3% of patients (18/54). CONCLUSION: The findings of this study suggest that the HPV genotype profile in Kinshasa differs from the profile observed in Western Europe and North America. If confirmed by larger-scale studies, this result bodes poorly for the efficacy of anti-HPV vaccines in Kinshasa.

Surveillance of cytomegalovirus (CMV) DNAemia in pediatric allogeneic stem cell transplantation: incidence and outcome of CMV infection and disease.

Cytomegalovirus (CMV) remains a serious problem after hematopoietic stem cell transplantation (HSCT). To investigate the incidence of CMV infection and outcome we retrospectively analyzed 70 consecutive pediatric allogeneic HSCTs monitored by CMV polymerase chain reaction (PCR), with at least 1-year follow-up or until death. All patients at risk for CMV infection (CMV-seropositive patients and CMV-seronegative recipients transplanted from CMV-seropositive donors) received hyperimmune anti-CMV globulins whereas in the group of HSCT patients with both donor and recipient CMV negativity, polyvalent immunoglobulins were given, both at a dose of 400 mg/kg. All patients received acyclovir at prophylactic doses for at least 6 months. Patients were monitored twice a week by CMV PCR. Patients with 2 positive results for CMV DNAemia received ganciclovir for 14 days and continued until 2 consecutive negative results were obtained. The incidence of CMV DNAemia was 12.8% (9/70) in the whole group, with significant higher risk for patients with CMV-seropositive recipient status, 8 out of 22 (36%), vs. patients with seronegative status, 1 out of 48 (2%) (P=0.0002). Three out of 9 patients with DNAemia developed CMV disease despite adequate preemptive treatment. The transplant-related mortality was higher in the CMV-seropositive recipient group (P=0.05). Age, use of hyperimmune anti-CMV globulins at a high dose, and the low incidence of graft-versus-host disease might be contributing factors to this low incidence.

Prevalence of high risk human papillomavirus types among Nicaraguan women with histological proved pre-neoplastic and neoplastic lesions of the cervix.

OBJECTIVES: To determine the prevalence of high risk human papillomavirus (HPV) types in Nicaraguan women with histological proved pre-neoplastic and neoplastic cervical lesions, and to assess its potential impact on preventive strategies. METHODS: 206 women with histopathological confirmed cervical lesions (CIN I or worse) were screened for HPV DNA on a liquid based cytology sample, using an HPV short fragment polymerase chain reaction based assay. HPV positive samples were genotyped with a reverse hybridisation line probe assay (Lipa). HPV negative samples were re-analysed using type specific real time polymerase chain reaction. RESULTS: Of all lesions CIN II or worse, 12% tested negative. Prevalence of high risk HPV increased from 48.1% in cervical intraepithelial neoplasia I (CIN I) to 94.7% in invasive squamous cervical carcinoma (SCC). The most prevalent high risk HPV types were, in order of prevalence rate, HPV 16, 58, 31 and 52. HPV 16 and/or HPV 31 were present in 63.2% of SCC cases. CONCLUSION: Targeting HPV 16 and 31 with prophylactic vaccines could possibly have an important impact on the incidence of invasive cervical carcinoma in Nicaragua. Further research is needed to define the oncogenic potential of other high prevalent HPV genotypes. Meanwhile, primary prevention and cervical cancer screening programmes should be optimised.

Human papillomavirus DNA detection in women with primary abnormal cytology of the cervix: prevalence and distribution of HPV genotypes.

OBJECTIVES: In this study, we focus on the prevalence and occurrence of different anogenital human papillomavirus (HPV) genotypes in a first abnormal cervical screening test, and correlate HPV genotyping with the cytological diagnosis on thin-layer liquid-based preparations in routine gynaecological screening. METHODS: Out of 780 abnormal smears, 513 tested positive for HPV. All 25 different HPV types were identified by Line Probe Assay. RESULTS: The prevalence of high-risk HPV types increased from 72% in atypical squamous cell of undetermined significance to 94.5% in high-grade intra-epithelial lesion (HSIL). Co-infection with multiple HPV types was predominantly found in HSIL (35.8%). In the HSIL group the most common HPV types were 16, 52, 51 and 31; type 18 was rarely present. CONCLUSION: The role of types 31, 51 and 52 should be considered in future studies on vaccine development.

Chlamydia trachomatis in female sex workers in Belgium: 1998-2003.

OBJECTIVE: We analysed the results of a 6 year screening period for Chlamydia trachomatis in a group of female sex workers (FSW) of all ages in Ghent, Belgium. METHODS: They were tested in the context of an outreach health programme for sex workers. C trachomatis was tested by Cobas Amplicor CT/NG PCR. RESULTS: In the 6 year period, 1643 tests were performed on 950 different sex workers (nationality: Belgian 60.3%, other western European (mostly French) 21.0%, African 12.4%, eastern European 3.0%, other 3.3%; workplace: bar/sauna 49.0%, private homes 31.8%, windows 18.2%, and escorts 1.0%). Baseline prevalence (only considering results of first test) was 70/950 or 7.4% (95% CI 5.7 to 9.0). The incidence rate was 98 episodes in 1347 person years or 7.3/100 person years (95% CI 5.9 to 8.7). There was a strong age effect. There was no clear relation with nationality or the workplace. CONCLUSIONS: The prevalence was higher than in general populations selected in Belgium, Britain, and the Netherlands. Since younger age is a risk factor for C trachomatis, it is very important to contact these women as soon as possible when they enter the trade. General screening for C trachomatis in young women is not common practice in Belgium. Sex workers often do not tell doctors about their work and will therefore not be screened unless in the context of specific outreach projects.

Cervical smears and human papillomavirus typing in sex workers.

OBJECTIVES: Sex workers are at increased risk for sexually transmitted infections (STI), human papillomavirus (HPV) and hence cervical cancer. In Belgium screening for cervical cancer starts at the age of 25, and is at 3 yearly intervals. The aim of this study is to assess risks for abnormal cervical smears and HPV in sex workers and decide whether the current screening policy is sufficient for them. METHODS: In an outreach programme for sex workers results of 653 smears sampled between 1992 and 2001 were analysed, and compared to a control group matched for age from the general population in 2001. Separately, 99 consecutive samples were typed for HPV and compared to an equal control group, matched for age. Smears and typing were performed according to current techniques. RESULTS: In the sex worker group 2.6% were diagnosed with atypical glandular cells of undetermined significance (AGUS)/atypical squamous cells of undetermined significance (ASCUS), 15.6% with low grade squamous intraepithelial lesion (LSIL), and 2.9% with high grade squamous intraepithelial lesion (HSIL), and in the control group results were 1.4%, 2.9% (p<0.001) and 0.6% (p<0.001) respectively. When considering only those under 25 years, 24.4% should have further follow up. Of the sex workers, 77.4% were positive for one or more types of HPV (55.9% for high risk HPV), in comparison with 27.6% of the control group (14.3% for high risk HPV) (p<0.001). In high risk HPV samples more LSIL and HSIL were found. CONCLUSION: Abnormal smears and high risk HPV were significantly more prevalent in sex workers than in controls. Current screening policy would miss many sex workers with an abnormal smear who should be referred for further follow up. It is proposed to screen sex workers when they enter prostitution regardless of their age.

Importance of methodology in determination of Chlamydia pneumoniae seropositivity in healthy subjects and in patients with coronary atherosclerosis.

Enzyme immunoassays (EIAs) for the detection of Chlamydia pneumoniae antibodies were compared to the microimmunofluorescence (MIF) test, the reference method. Furthermore, we assessed the hypothesis that a possible relationship between Chlamydia pneumoniae immunoglobulin G (IgG) antibodies and coronary artery disease is dependent on the type of EIA. Sera from 112 healthy men (mean age, 50.1 years) were tested for antibodies against Chlamydia pneumoniae by five commercial test kits: Focus Chlamydia MIF IgG test, Labsystems Chlamydia pneumoniae IgG EIA (LS EIA), R-Biopharm Elegance Chlamydia pneumoniae IgG EIA (RB EIA), Medac Chlamydia pneumoniae IgG sandwich enzyme-linked immunosorbent assay ELISA (MCp sELISA) and Medac Chlamydia IgG recombinant enzyme-linked immunosorbent assay ELISA (MC rELISA). Sera from 106 consecutive male patients (mean age, 63.6 years) undergoing diagnostic coronary angiography were also examined using the Focus MIF, LS EIA, MCp sELISA, and MC rELISA techniques. The agreement between LS EIA (65 to 83% [controls-patients]) or MC rELISA (49 to 61%) and Focus MIF (78 to 83%) was average to fair (kappa = 0.597 and 0.234, respectively). MCp sELISA and RB EIA showed good agreement with MIF (kappa = 0.686 and 0.665, respectively), with 80 to 89 and 79% of individuals reacting positively. A significant difference in seroprevalence between patients and healthy subjects was observed with the LS EIA, while seropositivities in the two study groups appeared equal when the Focus MIF assay was applied. The MC rELISA and MCp sELISA gave statistically significant differences in antibody seroprevalence in patients with two-vessel disease or when the patient group combined individuals with a two- or a three-vessel disease, respectively. The concordance between MIF and other commonly used serological assays for C. pneumoniae IgG antibody detection is good to fair. The choice of serological assay has important implications for C. pneumoniae antibody seroprevalence, as well as for the relationship between C. pneumoniae seropositivity and coronary artery disease.

Hepatitis B vaccination for sex workers: do outreach programmes perform better?

OBJECTIVES: To assess to what extent hepatitis B vaccination of sex workers in Ghent, Belgium, is successful within the context of the existing health services and to compare this with alternative approaches such as outreach programmes; to compare two hepatitis B vaccination schemes in the outreach programme for sex workers. METHODS: Testing all first contacts (n = 1096) in the outreach programme for hepatitis B virus (HBV) markers assessed success of hepatitis B vaccination in routine services. The performance of the outreach service was measured by counting the number of sex workers who started hepatitis B vaccination in the programme. The hepatitis B vaccination schemes were assessed by analysing the number of people completing the vaccination. RESULTS: Naturally acquired HBV was found in 11.9% of 1096 sex workers (0.6% HBsAg), and 7% were vaccinated in existing services. In contrast, hepatitis B vaccination using outreach methodology was able to achieve higher vaccination rates: among non-immune sex workers 82.8% received the first dose of vaccine, and 71.5% the second. If given 1 month later, 67.9% received the third dose, in contrast with 47.9%, when given 6 months later. CONCLUSIONS: Existing services are not successful in vaccinating sex workers for HBV, in contrast with specifically targeted outreach services. Shorter intervals between vaccine doses gave better compliance.

Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women's health clinics in Nicaragua.

OBJECTIVES: To determine prevalence and risk factors of sexually transmitted infections (STIs), HIV, and cervical neoplasia in women attending women's health clinics in Nicaragua, and to assess the potential impact of screening for these diseases. METHODS: Consecutive women attending women's health clinics in different regions were interviewed and examined for STI, HIV, and cervical neoplasia. RESULTS: Whereas only 30.4% of the 1185 participating women attended the clinics because of STI related complaints, 77.0% reported symptoms after probing. Clinical cervicitis was diagnosed in 32.8%, Chlamydia trachomatis in 4.1%, gonorrhoea in 0.4%, trichomoniasis in 10.2%. Antibodies for syphilis were found in 0.7%, for hepatitis B in 3.7%, and none were HIV seropositive. The STI prevalence was 21.8% in women offending with complaints, 17.3% in symptomatic women after probing, and 14.8% in asymptomatic women. Abnormal Papanicolaou (Pap) smears were found in 7.7%, with high risk human papilloma virus (HPV) types in almost 60%. Male promiscuity was associated with high grade squamous intraepithelial lesions (HSIL) and reported former screening was not shown to be protective. Young age and being employed were risk factors for C. trachomatis. CONCLUSION: Nearly one out of five women attending women's health clinics in Nicaragua had an STI, and one out of 13 a precancerous lesion of the cervix. These clinics provide an opportunity to improve the reproductive health of women by probing for STI symptoms, especially in young women, and by offering cervical screening to casual attendees. Of concern is the high rate of cervical lesions in women with a screening history, underlining the need for proper quality control.

Parameters of inflammation and infection in a community based case-control study of coronary heart disease.

BACKGROUND: increased levels of systemic inflammatory markers appear to be related to coronary heart disease (CHD) both in asymptomatic individuals and in subjects with established CHD. Whether these associations are related to confounding coronary risk factors or are explicable through chronic infectious conditions is not clear. OBJECTIVES: (1) to determine whether subjects with stable CHD differ from normal controls in inflammatory markers (CRP, SAA and fibrinogen) and/or in serostatus of four infectious agents (Helicobacter pylori, Chlamydia pneumoniae, CMV and EBV), independent of classical coronary risk factors. (2) To determine whether these inflammatory markers are related to the serostatus against these four infectious agents either in patients with CHD or in normal subjects. METHODS: in a large epidemiologic survey, 446 out of 16307 men at work, aged 35-59 years, had antecedents of myocardial infarction, CABG or PTCA or had prominent Q/QS waves on their resting ECG. They were compared with double the number (n=892) of men, matched for age, educational level and industry. Inflammatory biomarkers (CRP, fibrinogen and SAA) and antibodies against H. pylori, C. pneumoniae, CMV and EBV were measured, besides classical coronary risk factors. RESULTS: in univariate analyses, cases had higher CRP, fibrinogen and SAA levels than controls, but no differences were observed in serumantibody levels to any of the infectious agents. Markers of previous infections were not related to inflammatory biomarkers. In multivariate analyses CRP was significantly different between cases and controls independent of differences in other coronary risk factors and in the use of lipid lowering drugs and antiplatelet aggregants. CONCLUSIONS: in men at work with CHD, CRP levels are significantly different from controls, independent of known risk factors. No association was found between inflammatory biomarkers and positive serostatus against four infectious agents, neither in the patients nor in the healthy controls.

Coupled particle light scattering: a new technique for serodiagnosis of Epstein-Barr virus infection.

The Coupled Particle Light Scattering technique was evaluated for serological diagnosis of Epstein-Barr Virus (EBV) infection. Two hundred ninety-six patient sera selected from several clinical categories (acute infection, non-primary infection, interfering non-EBV infection, non-infected) were tested for IgM and IgG antibodies (anti-VCA, anti-EBNA and anti-EA). Determination of EBV IgG with Copalis multiplex was accurate when compared with Enzygnost Anti-EBV/IgG ELISA. Although the sensitivity of Copalis IgM for acute infections was 100% a positive IgM result did not always indicate an acute infection. Strong reactivity to IgG EA (ratio 3, 1) and IgG VCA (ratio 13, 3) correlated with persistent infection or reactivation. The CopalisI has many advantages over the existing methods, such as the possibility to measure three semi-quantitative IgG responses to three different EBV antigens simultaneously.

Effect of a syphilis control programme on pregnancy outcome in Nairobi, Kenya.

OBJECTIVES: To assess the impact of a syphilis control programme of pregnant women on pregnancy outcome in Kenya. METHOD: Women who came to deliver to Pumwani Maternity Hospital (PMH) between April 1997 and March 1998 were tested for syphilis. Reactive rapid plasma reagin (RPR) tests were titrated and confirmed with treponema haemagglutination test (TPHA). Equal numbers of RPR and TPHA negative women were enrolled. Antenatal syphilis screening and treatment history were examined from the antenatal cards. RESULTS: Of 22,466 women giving birth, 12,414 (55%) were tested for syphilis. Out of these, 377 (3%) were RPR reactive of whom 296 were confirmed by TPHA. Syphilis sero-reactive women had a more risky sexual behaviour and coexistent HIV antibody positivity; 26% were HIV seropositive compared with 11% among syphilis negative mothers. The incidence of adverse obstetric outcome defined as low birth weight and stillbirth, was 9.5%. Syphilis seropositive women had a higher risk for adverse obstetric outcome (OR 4.1, 95% CI 2.4-7.2). Antenatal treatment of RPR reactive women significantly improved pregnancy outcome but the risk of adverse outcome remained 2.5-fold higher than the risk observed in uninfected mothers. CONCLUSIONS: These data confirm the adverse effect of syphilis on pregnancy outcome. This study also shows the efficacy of antenatal testing and prompt treatment of RPR reactive mothers on pregnancy outcome.

Epstein-Barr virus infection in sixty pediatric liver graft recipients: diagnosis of primary infection and virologic follow-up.

BACKGROUND: Epstein-Barr virus (EBV) is an important cause of infection after pediatric liver transplantation. Earlier detection of EBV could result in shortening the delay in diagnosis and allow better management of a pediatric high risk population. OBJECTIVES: To determine the timing of EBV primary infection after graft and to compare the performances of different assays for an early detection of the virus. METHODS: Sixty pediatric liver graft recipients were followed. Kinetics of appearance of different EBV serologic parameters (anti-EBV-IgG, -IgM and -IgA, and anti-EBV nuclear antigen-IgG) and of the viral DNA in peripheral blood lymphocytes by PCR were compared. RESULTS: Thirty-six patients had a primary EBV infection. The first PCR and IgM positive result appeared after a mean delay of 56 and 61 days, respectively, and preceded the IgG response (mean delay, 143 days). Most of the studied patients (13 of 16) developed anti-EBV-IgA and only 3 developed anti-EBNA-IgG during the follow-up period. CONCLUSIONS: EBV primary infection occurred in most cases during the first 2 months after graft. The IgG response was delayed. The best performance was obtained by PCR. However, the IgM test compared well with the PCR and could be a more widely accessible measure to follow regularly.

Significance of qualitative polymerase chain reaction combined with quantitation of viral load in the diagnosis and follow-up of cytomegalovirus infection after solid-organ transplantation.

Quantitative PCR was evaluated in the monitoring of patients with ongoing posttransplantation cytomegalovirus (CMV) infection and antiviral therapy, compared to leukoDNAemia and serology. From January 1998 until May 1999, 61 patients were followed up weekly during 3 months after transplantation by a qualitative PCR. The quantitative PCR was performed on plasma samples from 21 selected patients, of whom 12 had a primary infection and 9 a reactivation or reinfection. Analysis of the viral load differences showed that the viral loads in patients with a primary infection were significantly higher than viral loads in patients with a reactivation (p < 0.01). Based on the results of our study, we can state that qualitative PCR is a good marker for initiating preemptive therapy. In addition, viral quantitation is clinically useful for accurate diagnosis of established CMV disease, and monitoring of antiviral therapy.

Passive particle agglutination test for screening of Treponema Pallidum antibodies in blood bank routine.

In most laboratories and blood banks, the TP.PA test has replaced the TPHA test for the screening of Treponema pallidum antibodies. In this study we show that the 1:20 serum dilution should be used to discriminate between negative and positive samples instead of the recommended 1:40 dilution, thus increasing sensitivity without a significant loss of specificity.

Lyme borreliosis--a review of the late stages and treatment of four cases.

Difficulties in diagnosis of late stages of Lyme disease include low sensitivity of serological testing and late inclusion of Lyme disease in the differential diagnosis. Longer treatment modalities may have to be considered in order to improve clinical outcome of late disease stages. These difficulties clinical cases of Lyme borreliosis. The different clinical cases illustrate several aspects of late borreliosis: false negative serology due to narrow antigen composition of the used ELISA format, the need for prolonged antibiotic treatment in chronic or recurrent forms and typical presentations of late Lyme disease, such as lymphocytic meningo-encephalitis and polyradiculoneuritis.

Coxsackie B virus epidemiology and neonatal infection in Belgium.

Outbreaks of Coxsackie B virus infection occur mainly in the warm spring and summer when enteroviruses are most prevalent. A study of five Coxsackie B virus serotypes was made over the last decade by collecting and typing nearly all enteroviruses isolated in Belgium. The study showed that Coxsackie B virus infection appeared in waves. We describe two outbreaks of Coxsackie B virus infection in our maternity unit. The first took place in 1988, when Coxsackie B 2 virus was the most prevalent serotype in the general population. One baby fell ill 6 days after birth and developed signs of meningitis. In a second baby the infection showed a diphasic pattern. The first phase was relatively mild but, after a period of recovery the child developed signs of myocarditis. After a period of low prevalence or complete absence from 1982 to 1988, Coxsackie B I virus reappeared in the summer of 1989. That summer, a small outbreak was seen in our maternity unit where one baby was infected from his mother and the infection spread from that baby to another one. Both babies developed meningitis but their convalescence was uncomplicated. A higher risk of outbreaks in nurseries was observed in summer when viruses are most prevalent. Measures to prevent such infections are discussed.