Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy.

Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes presented by recipient HLA class II (predicted indirectly recognizable HLA epitopes presented by HLA class II [PIRCHE-II]). In the present study, we evaluated the role of PIRCHE-II in child-specific HLA antibody formation during pregnancy. A total of 229 mother-child pairs were HLA typed. For all mismatched HLA class I molecules of the child, we subsequently predicted the number of HLA epitopes that could be presented by maternal HLA class II molecules. Child-specific antigens were classified as either immunogenic or nonimmunogenic HLA based on the presence of specific antibodies and correlated to PIRCHE-II numbers. Immunogenic HLA contained higher PIRCHE-II numbers than nonimmunogenic HLA. Moreover, the probability of antibody production during pregnancy increased with the number of PIRCHE-II. In conclusion, our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. Present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests the PIRCHE-II concept is universal.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Summary of the Dutch S3-guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatology and Venereology.

This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.

[HIV-test policy for tuberculosis patients in the Netherlands]. / Hiv-testbeleid bij tuberculosepatiënten in Nederland.

OBJECTIVE: To compare the proportion of tuberculosis patients tested for HIV infection, before and after introduction of highly active antiretroviral therapy (HAART) in the Netherlands, and to analyse predictive factors for performing an HTV-test in this population. DESIGN: Retrospective. METHOD: Whether patients had been tested for HIV, was investigated in random samples consisting of 200 patients, who were registered in the Netherlands Tuberculosis Register (NTR) in the years 1995 and 2001 respectively. RESULTS: The number of patients tested for HIV was 29 out of 84 (16%) in 1995, and 39 out of 190 (21%) in 2001 (not significant). HIV-tests had been carried out most frequently among homeless patients (71%), drug addicts (56%) and alcohol-abusing patients (60%). Significant predictive factors for HIV testing were place of residence (city), localisation of disease (pulmonary tuberculosis in combination with extrapulmonary tuberculosis) and place of origin (sub-Saharan Africa). CONCLUSION: Despite introduction of HAART during this period, in the Netherlands the proportion of tuberculosis patients tested for HIV did not significantly increase between 1995 and 2001. HIV testing was mainly limited to tuberculosis patients from risk groups.

HIV prevalence among tuberculosis patients in The Netherlands, 1993-2001: trends and risk factors.

OBJECTIVES: To describe the prevalence and predictive factors of human immunodeficiency virus (HIV) infection among tuberculosis (TB) patients in The Netherlands during the period 1993-2001. DESIGN: Data were obtained from the national surveillance register of all patients notified with TB (all forms) during the period of the study. In addition, records or discharge notes were checked of a random sample of 200 TB patients notified in 1995 and another 200 in 2001. RESULTS: Of 13 269 patients diagnosed with TB, 542 were HIV-positive (4.1%). Prevalence was 4.1% in 1993-1995, 3.8% in 1996-1998 and 4.4% in 1999-2001. The highest prevalence was observed among drug users (29.2%), homeless patients (20.1%) and patients residing illegally in the country (9.1%). Compared with the period 1993-1995, the relative risk of HIV infection in the periods 1996-1998 and 1999-2001 decreased significantly for drug using patients (P = 0.006), and increased for patients from African countries (P < 0.001). According to patient records, 29/184 (16%) had been tested for HIV in 1995 and 39/190 (21%) in 2001 (P = 0.289); 18 patients tested positive (4.8%). CONCLUSION: Although the prevalence of HIV among TB patients in The Netherlands remained stable between 1993 and 2001, the distribution of risk groups changed over this period.

Screening for pulmonary tuberculosis in a Tanzanian prison and computer-aided interpretation of chest X-rays.

SETTING: Tanzania is a high-burden country for tuberculosis (TB), and prisoners are a high-risk group that should be screened actively, as recommended by the World Health Organization. Screening algorithms, starting with chest X-rays (CXRs), can detect asymptomatic cases, but depend on experienced readers, who are scarce in the penitentiary setting. Recent studies with patients seeking health care for TB-related symptoms showed good diagnostic performance of the computer software CAD4TB. OBJECTIVE: To assess the potential of computer-assisted screening using CAD4TB in a predominantly asymptomatic prison population. DESIGN: Cross-sectional study. RESULTS: CAD4TB and seven health care professionals reading CXRs in local tuberculosis wards evaluated a set of 511 CXRs from the Ukonga prison in Dar es Salaam. Performance was compared using a radiological reference. Two readers performed significantly better than CAD4TB, three were comparable, and two performed significantly worse (area under the curve 0.75 in receiver operating characteristics analysis). On a superset of 1321 CXRs, CAD4TB successfully interpreted >99%, with a predictably short time to detection, while 160 (12.2%) reports were delayed by over 24 h with conventional CXR reading. CONCLUSION: CAD4TB reliably evaluates CXRs from a mostly asymptomatic prison population, with a diagnostic performance inferior to that of expert readers but comparable to local readers.

Contexte : La Tanzanie est lourdement frappée par la tuberculose (TB) et les prisonniers sont un groupe à haut risque qui devrait bénéficier d'un dépistage actif, comme le recommande l'Organisation Mondiale de la Santé. Les algorithmes de dépistage qui débutent par une radiographie pulmonaire peuvent détecter des cas asymptomatiques, mais ils requièrent des lecteurs de radiographies expérimentés, qui sont rares dans le contexte pénitentiaire. Des études récentes sur des patients sollicitant des soins pour des symptômes liés à la TB ont mis en évidence une bonne performance diagnostique du logiciel CAD4TB.Objectif : Evaluer le potentiel d'un dépistage assisté par ordinateur en utilisant CAD4TB au sein d'une population carcérale en majorité asymptomatique.Schéma : Étude transversale.Résultats : CAD4TB et sept professionnels de santé lisant des radiographies dans des services de TB locaux ont évalué un ensemble de 511 radiographies pulmonaires provenant de la prison d'Ukonga à Dar es Salaam et les performances ont été comparées grâce à une radiographie de référence. Deux lecteurs ont été significativement plus performants que CAD4TB, trois ont été comparables et deux ont été significativement moins bons (zone sous la courbe de 0,75 dans l'analyse ROC ­fonction d'efficacité du receveur). Sur un ensemble de 1321 radiographies pulmonaires, CAD4TB en a interprété avec succès plus de 99% avec un délai de détection prévisible court, tandis que 160 (12,2%) réponses ont été retardées de plus de 24 h avec la méthode de lecture conventionnelle.Conclusion : CAD4TB évalue de manière fiable les radiographies pulmonaires dans une population en majorité asymptomatique de détenus, avec une performance diagnostique inférieure à celle de lecteurs experts mais comparable à celle des lecteurs locaux.

Marco de referencia: Tanzania es un país con una alta tasa de morbilidad por tuberculosis (TB) y las personas en los establecimientos penitenciarios constituyen un grupo de alto riesgo de contraer la enfermedad; en esta población se debe practicar la detección sistemática activa como lo recomienda la Organización Mundial de la Salud. Los algoritmos de detección cuya etapa inicial es la radiografía de tórax pueden detectar los casos asintomáticos, pero su eficacia depende de la experiencia del profesional que interpreta las imágenes y esta competencia es escasa en los entornos penitenciarios. Algunos estudios recientes de pacientes que buscan atención sanitaria por síntomas asociados con la TB han revelado un buen rendimiento diagnóstico con la utilización del programa informático CAD4TB. Objetivo: Evaluar la utilidad de la detección sistemática de la TB asistida por el programa CAD4TB, en una población penitenciaria en su mayoría asintomática.Método: Fue este un estudio de tipo transversal.Resultados: Siete profesionales de atención sanitaria de los servicios locales de TB analizaron 511 radiografías de tórax provenientes de la prisión de Ukonga, en Dar es-Salam, con la ayuda del programa CAD4TB; se preparó un conjunto de referencia radiográfica de lectura con el fin de evaluar el rendimiento diagnóstico. El desempeño de dos de los lectores fue significativamente superior al resultado del programa CAD4TB, tres lectores obtuvieron una puntuación comparable al programa y en dos lectores se observó un rendimiento significativamente inferior (área bajo la curva: 0,75 en el análisis de eficacia diagnóstica). En un conjunto especial de 1321 radiografías de tórax el programa CAD4TB interpretó eficazmente más del 99%, con un corto lapso previsible hasta la detección, en contraste con la lectura clásica de las radiografías que dio lugar a un retraso superior a 24 horas en 160 informes (12,2%).Conclusión: El programa CAD4TB realizó una evaluación fiable de las radiografías provenientes de una población penitenciaria en su mayor parte asintomática. El rendimiento diagnóstico del programa fue inferior al rendimiento de los lectores expertos, pero comparable con el rendimiento de los lectores locales.

Phase II trial of combined radiotherapy and daily low-dose cisplatin for inoperable, locally advanced non-small cell lung cancer (NSCLC).

With the use of cis-diamminedichloroplatinum(II), cisplatin, to enhance the effect of radiation a combined modality approach was designed to treat patients with inoperable, locally advanced NSCLC. The regimen consisted of radiation doses of 300 cGy for 4 days every week for 4 weeks with a 2 week split in between. Each radiation dose was followed by an i.v. injection of cisplatin 6 mg/m2 within 30 min. Hydration consisted on an oral fluid intake of 2 L only, enabling the patient to receive the treatment on an outpatient basis. Of 40 patients entered into the study, 37 were evaluable for toxicity and 33 for response. Overall response rate was 65% and complete response rate 22%. Median duration of local control was 7 months. The majority of all patients (76%) eventually progressed at the primary tumor site, while in 16 patients relapse occurred in distant sites first. Median duration of overall survival was 10.5 months, whereas that of complete responders was 29.5 months. Generally, acute side effects were transient and did not require discontinuation of treatment. One patient presented with thrombocytopenia 4 weeks after treatment had been finished. His death of cerebral bleeding was likely to be related with his therapy-resistant malignancy. Of late side effects three patients showed disabling symptoms consisting of uncontrollable pulmonary infections in the presence of tumor in two patients, one patient had radiation myelopathy and another experienced vertebral collapse with distal paresis. The combination of radiation and daily low-dose cisplatin is a tolerable treatment modality with most benefit for patients reaching a complete remission. Intensification of the regimen is being planned in those patients with inoperable, locally advanced squamous cell lung cancer to reach a complete remission.

Tuberculin skin test reactions by time of reading among Dutch travellers.

SETTING: Five travel and TB control clinics in The Netherlands. OBJECTIVE: To assess the variation of skin test reactions between different days of reading. DESIGN: Cohort study of non-BCG-vaccinated travellers. Mantoux skin test data were analysed for associations between time interval between administration and reading and reaction size. RESULTS: There were no significant differences in reaction size to 1 TU PPD between readings at day 3 or 4, either for pre-travel (n = 1004) or post-travel (n = 577) tests, before (P = 0.990 and 0.210, respectively) or after exclusion of 0 mm reactions (P = 0.330 and 0.474). Time intervals were not different for reaction sizes of 0, 1-9 or > or = 10 mm (P = 0.826 and 0.306). There were also no significant associations for simultaneous tests with a sensitin of Mycobacterium scrofulaceum. CONCLUSIONS: Tuberculin skin tests can be read on day 3 or 4, without compromising their validity.

How does tuberculosis relate to HIV positive and HIV negative drug users?

OBJECTIVES: (1) To compare the incidence of active tuberculosis in HIV positive and HIV negative drug users. (2) To describe the main characteristics of the tuberculosis cases. DESIGN: A prospective study was performed from 1986 to 1996 as part of an ongoing cohort study of HIV infection in Amsterdam drug users. METHODS: Data from the cohort study, including HIV serostatus and CD4-cell numbers, were completed with data from the tuberculosis registration of the tuberculosis department of the Amsterdam Municipal Health Service. Analyses were carried out with person time and survival methods. RESULTS: Of 872 participants, 24 persons developed culture confirmed tuberculosis during a total follow up period of 4000 person years (0.60 per 100 py, 95% CI: 0.40, 0.90). Nineteen cases were HIV positive (1.54 per 100 py, 95% CI: 0.86, 2.11) and five HIV negative (0.18 per 100 py, 95% CI: 0.08, 0.43). Multivariately HIV infection (relative risk: 12.9; 95% CI: 3.4, 48.8) and age above 33 years (RR: 6.8; 95% CI: 1.3, 35.0, as compared with age below 27) increased the risk for tuberculosis substantially. Additional findings were: (1) 13 of 22 pulmonary tuberculosis cases (59%) were detected by half yearly radiographic screening of the chest; (2) tuberculosis occurred relatively early in the course of HIV infection at a mean CD4 cell number of 390/microliter; (3) an estimated two thirds of the incidence of tuberculosis observed among HIV positive cases was caused by reactivation; (4) all but one patient completed the tuberculosis treatment. CONCLUSION: HIV infection increases the risk for active tuberculosis in Amsterdam drug users 13-fold. The incidence of tuberculosis in HIV negative drug users is still six times higher than in the overall Amsterdam population. In the absence of contact tracing and screening with tuberculin skin tests, periodic chest radiographic screening contributes substantially to early casefinding of active tuberculosis in Amsterdam drug users.

[Exogenous reinfection with Mycobacterium tuberculosis caused by nosocomial transmission by a patient with AIDS]. / Exogene reïnfectie met Mycobacterium tuberculosis door nosocomiale transmissie bij een patiënt met AIDS.

A 55-year-old AIDS patient relapsed with tuberculosis as a result of exogenous reinfection, 1.5 years after a prior diagnosis of tuberculosis, for which he had been treated. He was reinfected after exposure to another AIDS patient, a 25-year-old man with tuberculosis, when they were hospitalized together during 5 days. The diagnosis of tuberculosis in the latter patient was delayed because the clinical picture was obscured by another infection. Reinfection and nosocomial transmission were demonstrated by analysis of the restriction-fragment-length polymorphism patterns on serial isolates of Mycobacterium tuberculosis. Increased alertness to tuberculosis, especially among HIV-infected persons, and implementation of effective infection control precautions are important in the prevention of nosocomial transmission.

[Tuberculosis in HIV-positive and HIV-negative drug users in Amsterdam]. / Tuberculose bij HIV-positieve en HIV-negatieve drugsgebruikers in Amsterdam.

OBJECTIVE: To determine and to compare the incidences of active tuberculosis in HIV positive and HIV negative drug users and to describe the main characteristics of the tuberculosis cases. DESIGN: Prospective. SETTING: Municipal Health Service, Amsterdam, the Netherlands. METHOD: Data of the ongoing cohort study of HIV infection in Amsterdam drug users, including HIV serostatus and CD4 cell counts, from 1986 until 1996 were completed with data from the tuberculosis registration of the tuberculosis department of the Amsterdam Municipal Health Service and analysed statistically. RESULTS: Of 872 participants 24 persons developed culture confirmed tuberculosis during a total follow-up period of 4000 person years (py) (0.6 per 100 py). Nineteen persons were HIV positive (1.54 per 100 py) and 5 HIV negative (0.18 per 100 py). Multivariately, HIV infection and higher age increased the risk of tuberculosis substantially (relative risks 12.9; 95% confidence interval (CI): 3.4-48.8 and 6.8: 95% CI: 1.3-35.0 respectively). Thirteen of 22 pulmonary tuberculosis cases (59%) were detected by half-yearly X-ray screening of the chest. Tuberculosis occurred relatively early in the course of HIV infection at a mean CD4 cell number of 390/microliter. All but one patient completed the tuberculosis treatment. CONCLUSION: HIV infection increases the risk of active tuberculosis in Amsterdam drug users 13-fold. The incidence of tuberculosis in HIV negative drug users in 6 times higher than that in the overall Amsterdam population. Periodic chest X-ray screening contributes substantially to case-finding of active tuberculosis in Amsterdam drug users.

[AIDS and tuberculosis; a retrospective study in 225 patients with AIDS]. / AIDS en tuberculose; een retrospectief onderzoek bij 225 patiënten met AIDS.

Of 225 patients in whom AIDS was diagnosed in the period January 1982 to March 1988 at the Academic Medical Centre, Amsterdam, the tuberculosis incidence and the clinical and demographic characteristics were recorded retrospectively. Tuberculosis was diagnosed in 18 patients (8%). The most frequent risk factor of AIDS-tuberculosis patients was intravenous drug abuse. The chest X-ray was frequently atypical and there were more extrapulmonary locations in comparison to patients with tuberculosis without AIDS. On September 1, 1988, 13 of the 18 patients had died. The response to tuberculostatic therapy was good. Our results are in agreement with comparable studies elsewhere. The expectation is that the tuberculosis incidence among AIDS patients will increase as more intravenous drug users become part of the whole AIDS patient population.

[Limited tuberculin screening participation amongst travellers to countries with high tuberculosis incidence; reason to consider BCG vaccination for some travellers]. / Beperkte deelname aan tuberculinescreening onder reizigers naar landen met hoge tuberculose-incidentie; reden om voor sommigen BCG-vaccinatie te overwegen.

OBJECTIVE: To determine the compliance amongst Dutch travellers to high tuberculosis-incidence countries with a screening procedure involving a tuberculin skin test before and after the trip. DESIGN: Prospective study. METHOD: Nine hundred and eighty-eight tuberculin-negative Dutch people who travelled to high tuberculosis-incidence countries for 3 to 12 months were studied for their compliance with an advised screening procedure of repeat tuberculin skin testing 2 to 4 months after return. At 2 of the 4 participating health services, data were also collected on extra calls made and the pertinent time investments. RESULTS: Five hundred and ninety-nine travellers (61%) were compliant with the screening procedure. Of those for whom the data was available (n = 417), 33% (98/300) of the compliant travellers required extra calls. These took an average of 30 min per extra traveller tested as a result. Compliance varied according to health service and was better amongst travellers to Africa. In addition, non-compliance was independently associated with male sex, work being the main travel purpose, and an undecided duration of travel on departure. CONCLUSIONS: Compliance of Dutch travellers with tuberculin skin-test screening is limited, particularly if no extra calls are issued. Bacillus Calmette-Guérin vaccination appears to be preferable for travellers with undecided travel duration and persons travelling for work on a frequent basis.

High sensitivity of chest radiograph reading by clinical officers in a tuberculosis prevalence survey.

BACKGROUND: Chest radiographs (CXRs) are used in tuberculosis (TB) prevalence surveys to identify participants for bacteriological examination. Expert readers are rare in most African countries. In our survey, clinical officers scored CXRs of 19 216 participants once. We assessed to what extent missed CXR abnormalities affected our TB prevalence estimate. METHODS: Two experts, a radiologist and pulmonologist, independently reviewed 1031 randomly selected CXRs, mixed with lms of confirmed TB cases. CXRs with disagreement on 'any abnormality' or 'abnormality consistent with TB' were jointly reviewed during a consensus panel. We compared the nal expert and clinical of cer classifications with bacteriologically confirmed TB as the gold standard. RESULTS: After the panel, 199 (19%) randomly selected CXRs were considered abnormal by both expert reviewers and another 82 (8%) by one reviewer. Agreement was good among the experts (κ 0.78, 95%CI 0.73-0.82) and moderate between the clinical officers and experts (κ range 0.50-0.62). The sensitivity of 'any abnormality' was 95% for the clinical officers and 83% and 81% for the respective experts. The specificities were respectively 73%, 74% and 80%. TB prevalence was underestimated by 1.5-5.0%. CONCLUSIONS: Acceptable CXR screening can be achieved with clinical officers. Reviewing a sample of CXRs by two experts allows an assessment of prevalence underestimation.

Coverage and yield of tuberculosis contact investigations in the Netherlands.

SETTING: An increasing proportion of tuberculosis (TB) patients in low-incidence countries are immigrants. It is unclear whether contact investigations among immigrant patients are adequate. OBJECTIVE: To determine whether ethnicity of pulmonary TB patients was associated with coverage and yield of contact investigations in the Netherlands. DESIGN: Contact investigation results were extracted from records of patients reported in the nationwide surveillance register in 2006 and 2007. Prevalence odds ratios (PORs) with 95% confidence intervals (CIs) were calculated to determine the association between patient ethnicity and coverage of contact investigations and the yield of individuals with Mycobacterium tuberculosis infection or TB. RESULTS: Of the 1040 pulmonary TB patients reported, 642 (62%) were eligible for analysis. Compared to close contacts of Dutch patients, close contacts of immigrant patients were significantly less likely to be examined for TB (89% vs. 93%, POR 0.6, 95%CI 0.5-0.7) and infection (50% vs. 75%, POR 0.3, 95%CI 0.3-0.4), whereas the yield was significantly higher for disease (1.5% vs. 0.4%, POR 3.4, 95%CI 1.8-6.4) and infection (13% vs. 10%, POR 1.2, 95%CI 1.0-1.5). CONCLUSION: The effectiveness of contact investigations in the Netherlands can be optimised by expanding the investigation of contacts of immigrant patients.

The value of 99mTc macroaggregated albumin lung perfusion scanning in the prediction of postpneumonectomy function and pulmonary artery pressure.

99mTc macroaggregated albumin lung perfusion scans were performed with assessment of pulmonary hemodynamics in 14 male patients with a centrally located lung tumor, subjected to pneumonectomy. In 7 patients perfusion of the affected lung was less than one third of total perfusion. However, all tumors were resectable. Results show that predictive value of the perfusion scan was significant (p less than 0.02) with regard to forced expiratory volume in the first second (FEV1, r = 0.80). A fair but not significant correlation existed in the prediction of vital capacity (VC, r = 0.64) and total lung capacity (TLC, r = 0.71). No correlation was found between perioperative change in mean pulmonary artery pressure (MPAP) and either relative radionuclide uptake of the affected lung or predicted FEV1. So, the lung perfusion scan cannot be used in preoperative estimation of postoperative MPAP.

Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment.

During TB cytokines play a role in host defence. To determine the cytokine pattern during various disease stages of TB, serum levels of IL-12, interferon-gamma (IFN-gamma), IL-4, IL-6 and IL-10 were measured in 81 patients with active TB, 15 patients during therapy and 26 patients after anti-tuberculous therapy as well as in 16 persons who had been in close contact with smear-positive TB and in 17 healthy controls. IFN-gamma was elevated during active TB when compared with healthy controls, declining during and after treatment. IL-12 (p40 and p70) serum levels were not significantly higher in patients with active TB compared with any of the other groups. IL-4 levels were low in all groups. IL-6 and IL-10 serum levels were elevated in patients with active TB and during treatment. In patients with active TB serum levels of IFN-gamma and IL-6 were higher in patients with fever, anorexia and malaise. IL-12 levels were higher in patients with a positive smear. Cytokine levels did not correlate with localization of TB (pulmonary versus extrapulmonary), or skin test positivity. Cytokines directing a Th1 response (IL-12) or a Th2 response (IL-4) were not elevated in sera of this large group of patients with pulmonary and extrapulmonary TB. In patients with active TB, cytokines that were elevated in serum were IFN-gamma, IL-6 and IL-10.