Time since last vaccine dose in PCR-positive and PCR-negative children with suspected pertussis to monitor pertussis vaccine effectiveness.

We evaluated whether the results of diagnostic polymerase chain reaction (PCR) testing combined with time since last vaccine dose could be used to monitor the effectiveness of acellular pertussis vaccines. In 258 consecutive nasopharyngeal swabs from children and adolescents with typical pertussis symptoms, 80 were positive and 178 were negative in PCR for Bordetella pertussis DNA (IS 481). Time since last vaccine dose was available for 152 patients, of which 120 were fully immunised. Among the fully vaccinated patients, the median age of 41 PCR-positive patients was 8.4 years (range 0.9-12.3) and that of 79 PCR-negative cases was 3.3 years (range 0.4-14.1) (p < 0.01). The median time since last pertussis vaccine dose was 6.05 years [95 % confidence interval (CI): 0.5-10.9] in PCR-positive cases and 2.22 years (95 % CI: 0.04-9.23) in PCR-negative cases (p < 0.001). The use of diagnostic PCR results from pertussis cases together with time since last vaccine dose permits estimates of the duration of protection after vaccination with acellular pertussis vaccines that are in keeping with more complex studies.

[Important vector-borne infectious diseases among humans in Germany. Epidemiological aspects]. / Wichtige, durch Vektoren übertragene Infektionskrankheiten beim Menschen in Deutschland. Epidemiologische Aspekte.

Vector-borne infections pathogenic to humans play an important role in Germany. The relevant zoonotic pathogens are either endemic throughout Germany (e.g. Borrelia burgdorferi sensu latu) or only in specific regions, e.g. tick-borne encephalitis (TBE) virus and hantavirus. They cause a substantial burden of disease. Prevention and control largely rely on public advice and the application of personal protective measures (e.g. TBE virus vaccination and protection against vectors). High quality surveillance and targeted epidemiological studies are fundamental for the evaluation of temporal and spatial risks of infection and the effectiveness of preventive measures. Aside from endemic pathogens, vector-borne infections acquired abroad, mostly transmitted by mosquitoes, have to be systematically and intensively monitored as well, to assess the risk of infection for German residents traveling abroad and to adequately evaluate the risk of autochthonous transmission. Related issues, such as invasive species of mosquitoes in Germany and climate change, have to be taken into consideration. Such pathogens include West Nile, dengue and chikungunya viruses, as well as malaria parasites (Plasmodium species). The article presents an overview of the epidemiological situation of selected relevant vector-borne infections in Germany.

A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013.

Between October 2012 and May 2013, five cases of invasive meningococcal disease in young men who have sex with men (MSM) living in Berlin were notified to local health authorities in Germany. Three of the five cases died. All were caused by serogroup C variants with the finetype P1.5-1,10-8:F3-6. Awareness was increased through the use of community networks; an extension of the existing vaccination recommendation to all MSM is currently being considered.

Comparative hepatitis A seroepidemiology in 10 European countries.

The WHO recommends hepatitis A virus (HAV) immunization according to level of transmission and disease burden. We aimed to identify susceptible age groups by standardized serosurveys to inform HAV vaccination policy in participating countries: Belgium, Czech Republic, England, Finland, Germany, Italy, Lithuania, Malta, Romania, and Slovakia. Each country tested national serum banks (n = 1854-6748), collected during 1996-2004, for anti-HAV antibodies. Local laboratory results were standardized to common units. Forty-one per cent of those aged <30 years and 6% of those aged ≥30 years were susceptible to HAV in Romania; compared to 70-94% and 26-71%, respectively, elsewhere. Romania reported high HAV incidence in children and young adults. Other countries reported HAV disease primarily in older risk groups. The results suggest low level of HAV transmission in most of Europe. Romania, however, appeared as an area with intermediate transmission. Vaccination of risk groups in countries with high susceptibility of young and middle-aged adults needs to be continued.

[Infections with pneumococci, menigococci, H. influenzae and diphtheria in Germany: the RKI Reference Network for Invasive Bacterial Infections (IBI) at the 5th Würzburg Workshop on Epidemiology, Prevention and Therapy for Invasive Meningococcal Diseases 2010 (meeting report)]. / Infektionen mit Pneumokokken, Meningokokken, H. influenzae und Diphtherie in Deutschland: das RKI Referenznetzwerk für Invasive Bakterielle Infektionen (IBI) beim 5. Würzburger Workshop zur Epidemiologie, Prävention und Therapie von invasiven Meningokokkenerkrankung 2010 (Tagungsbericht).

The surveillance and prevention of invasive bacterial infections requires flexible strategic coordination of all involved health-care professionals. For this purpose, the German National Reference Centres for Meningococci, Streptococci and the Consultant Laboratories for Haemophilus influenzae and diphtheria have formed the Reference Network for Invasive bacterial infections (IBI). The 5th Würzburg Workshop on Meningococcal Diseases 2010 provided the network with a forum for the interdisciplinary exchange between scientists, public health professionals, medical microbiologists and clinicians. The topics covered the analysis of surveillance data for meningococcal disease in the last decade, as well as methods to control for antibody response following vaccination, including a serum bactericidal antibody (SBA) assay, and the development of new vaccines that also include the most common serogroup B. The presentation on diphtheria showed that this rare disease in Germany has become a diagnostic challenge, and that apart from the classical pathogen also toxigenic C. ulcerans strains must be considered. Due to the successful vaccination against Hib, H. influenzae disease has changed from a classical childhood disease to an infection of elderly people mainly caused by unencapsulated strains. Following the introduction of vaccines, changes in the serotype distribution and antibiotic resistance profiles have become apparent for S. pneumoniae infections. The epidemiological data were complemented by clinical aspects concerning the vaccination of immunocompromised children.

What is the evidence for giving chemoprophylaxis to children or students attending the same preschool, school or college as a case of meningococcal disease?

We performed a systematic literature review to assess the effectiveness of chemoprophylaxis for contacts of sporadic cases of invasive meningococcal disease (IMD) in educational settings. No studies directly compared IMD risk in contacts with/without chemoprophylaxis. However, compared to the background incidence, an elevated IMD risk was identified in settings without a general recommendation for chemoprophylaxis in pre-schools [pooled risk difference (RD) 58·2/105, 95% confidence interval (CI) 27·3-89·0] and primary schools (pooled RD 4·9/105, 95% CI 2·9-6·9) in the ~30 days after contact with a sporadic IMD case, but not in other educational settings. Thus, limited but consistent evidence suggests the risk of IMD in pre-school contacts of sporadic IMD cases is significantly increased above the background risk, but lower than in household contacts (pooled RD for household contacts with no chemoprophylaxis vs. background incidence: 480·1/105, 95% CI 321·5-639·9). We recommend chemoprophylaxis for pre-school contacts depending on an assessment of duration and closeness of contact.

Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011.

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/ verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency.

Low hepatitis B immunogenicity of a hexavalent vaccine widely used in Germany: results of the German Health Survey for Children and Adolescents, 2003-2006.

The success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac, Infanrix hexa) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection. We compared hepatitis B surface antibody (anti-HBs) levels in children fully vaccinated with Hexavac or Infanrix hexa (n=477) in a secondary data analysis of a large cross-sectional health survey in Germany. On average 2.4 years after vaccination, 25.3% of Hexavac vaccinees had anti-HBs levels <10 mIU/ml (95% CI 19.0-32.8) compared to 4.7% of Infanrix hexa vaccinees (95% CI 2.4-8.9). These findings suggest that short-term hepatitis B immunogenicity in Hexavac vaccinees may also be weaker. Further studies are warranted to assess whether Hexavac vaccinees should be re-vaccinated or receive a booster vaccination before these birth cohorts reach adolescence.

Changes to the varicella and pertussis immunisation schedule in Germany 2009: background, rationale and implementation.

In July 2009, the German Standing Committee on Vaccination (STIKO) modified its recommendations for varicella and pertussis vaccination, based on newly available data on disease epidemiology, vaccine effectiveness (VE) and safety, and an evaluation of the feasibility of the recommended immunisation strategy. The recommendation for varicella vaccine now includes a routine two-dose schedule with the administration of the first dose at the age of 11 to 14 months and the second dose at the age of 15 to 23 months, with a minimum interval of four weeks between these doses. Furthermore, STIKO recommended adding a one-time pertussis booster to the adult vaccination schedule to expand the cocoon strategy in place since 2004. The recommendation of a booster vaccination with an acellular pertussis vaccine every 10 years for persons employed in the care of pre-school children and for healthcare personnel in paediatric, gynaecologic and obstetric health facilities was extended to persons employed in schools and in other institutions caring for older children, and to all healthcare personnel. These recommendations were based on available epidemiological data showing an increase in incidence from 7-10 cases per 100,000 inhabitants in 2002-2004 to over 30 by 2007. Moreover, the high burden of pertussis in infants at 94 hospitalised cases per 100,000 infants in 2007 suggested that the previous cocoon strategy was insufficient.

Pandemic influenza A(H1N1) 2009 breakthrough infections and estimates of vaccine effectiveness in Germany 2009-2010.

During the 2009 influenza pandemic, a monovalent AS03-adjuvanted vaccine was almost exclusively used in Germany for immunisation against the 2009 pandemic influenza A(H1N1) virus. One-dose vaccination was recommended for all age groups. We applied the screening method for the rapid assessment of vaccine effectiveness (VE) based on reported data of vaccinated and unvaccinated pandemic influenza cases and vaccination coverage estimates. Preliminary results demonstrate excellent VE in persons aged 14-59 years (96.8%; 95% confidence interval (CI): 95.2-97.9) and moderately high VE in those 60 years or older (83.3%; 95% CI: 71.0-90.5).

Invasive meningococcal disease with fatal outcome in a Swiss student visiting Berlin.

Following the fatal invasive meningococcal disease in a Swiss student who had been visiting Berlin, several public health institutions on local, regional and national level cooperated to ensure that the appropriate measures such as contact tracing and post exposure prophylaxis were taken to prevent further cases. The incidence highlighted the importance of early disease notification and showed that if an infectious disease requiring public health action occurs in an international context, it is vital that relevant information is communicated to all levels of the public health systems of the countries involved.

[3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease in Würzburg 2006]. / 3. Würzburger Workshop zur Epidemiologie, Prävention und Therapie der invasiven Meningokokkenerkrankung 2006.

On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with the German Society for Hygiene and Microbiology (DGHM). Given the recent recommendation of the German Standing Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all children in the second year of life, observations from meningococcal C conjugate vaccination campaigns in other European countries were presented and compared to the German situation. Moreover, the newly implemented cluster detection routines employed at the NRZM and their integration into the interactive geographical information system EpiScanGIS were shown. Based on recent experiences from regional outbreaks in Oberallgäu, Sangerhausen, and Greater Aachen, examples for public health intervention were given at the conference. In addition, current developments in the area of meningococcal research, as well as trends in antimicrobial susceptibility were covered. Finally, the latest evidence concerning the clinical management and chemoprophylaxis of this invasive bacterial disease was discussed.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD)--mainly meningitis and septicaemia--and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100,000 in the general population, with a total of 23,470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD) - mainly meningitis and septicaemia - and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100 000 in the general population, with a total of 23 470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

[Meningococcal carriers in high school students and possible risk factors]. / Meningokokken-Trägerstatus von Gymnasiasten und mögliche Risikofaktoren.

From August 2004 to January 2005 a cluster of 7 cases of serogroup B meningococcal disease occurred in the state of Saxony-Anhalt in the town of Sangerhausen and the surrounding area. This led to an investigation of meningococcal carriage in 816 high school students (grades 9 to 13). The students were also asked to fill out a questionnaire regarding possible risk factors for carriage. The goal of the study was the evaluation of a possibly persistently increased risk for further cases in the region. Results of the study were to be used for a comprehensive and targeted education of the public. The percentage of students found harbouring N. meningitidis in the nasopharynx in Sangerhausen (9.0 %) was not elevated compared to that found in the two control regions of Kelbra, County of Sangerhausen (8.2 %) and Jessen, County of Wittenberg (9.9 %). The serogroup B fine type responsible for the cluster (P1.7-2,16:F3-3:PorB3-24) was found only in one student each in Sangerhausen and Kelbra. Thus, there was no evidence of an increased risk for further cases at the time of the study at the end of January, 2005. This may have been due to intensive contact tracing and provision of chemoprophylaxis in Sangerhausen. Visiting a disco or bar and smoking were identified as risk factors for meningococcal carriage. However, these factors were associated with carriage only in boys but not in girls. This may be explained by sex-specific differences in physical interaction with others. Efforts to prevent further cases during clusters of meningococcal disease should consider sex-specific risk behaviour.

Balloon angioplasty of postsurgical recoarctation in infants: the risk of restenosis and long-term follow-up.

OBJECTIVES: This study was undertaken to evaluate the long-term results of balloon angioplasty (BA) for postsurgical recoarctation in infants. BACKGROUND: Balloon angioplasty is a well-accepted modality for the treatment of recoarctation. However, infants remain a group of concern because of their size, risk for complications and the potential for restenosis with growth. Age <12 months has been determined to be a risk factor for the development of recoarctation after angioplasty for native coarctation. Although studies on postsurgical coarctation have found no relationship between age at angioplasty and the development of recoarctation, few studies specifically addressing infants have been performed. METHODS: Clinical, echocardiographic, hemodynamic and angiographic data on 22 consecutive children <1 year of age who underwent BA between 1986 and 1996 were reviewed. RESULTS: A successful result, defined as a postprocedure gradient of < or =20 mm Hg, was achieved in 20 of 22 (91%) infants with a reduction in the systolic peak pressure gradient from 48 +/- 27 to 9 +/- 10 mm Hg (p < 0.001) and an increase in coarctation diameter from 2.7 +/- 1.1 to 5.2 +/- 1.5 mm (p < 0.001). At long-term follow-up of a median of 56 months (0.6 to 12 years), the restenosis rate after an initial optimal result was 16% (3 of 19). Five (24%) infants required reintervention (2 initially unsuccessful; 3 recoarctation), with a success rate of 95% after two procedures. Suboptimal long-term outcome correlated with a lower infant weight. CONCLUSIONS: Balloon angioplasty can be safely performed in infants, with good long-term results. The risk of restenosis is low and can be successfully managed with repeat angioplasty.

Endovascular stents for coarctation of the aorta: initial results and intermediate-term follow-up.

OBJECTIVES: The aim of this study was to evaluate the use of endovascular stents in native and recurrent coarctation of the aorta (CoA). BACKGROUND: Stents have been used successfully in various locations. Their use in CoA can be an alternative to surgery or balloon angioplasty (BA). METHODS: Thirty-four patients with CoA (13 native and 21 re-coarctation after surgery or BA) with a mean age of 16 +/- 8 years (range 4 to 36 years) underwent attempted stent implantation between 1993 and 1999. Successful outcome was defined as peak systolic pressure gradient after stent implantation < 20 mm Hg. RESULTS: Stents were implanted in 33/34 patients, and successful outcome occurred in 32/33 patients. Peak systolic pressure gradient decreased from 32 +/- 12 mm Hg to 4 +/- 11 mm Hg (p < 0.001). Coarctation site to descending aorta diameter ratio increased from 0.46 +/- 0.16 to 0.92 +/- 0.16 (p < 0.001). Two patients underwent successful stent re-dilation 16 and 21 months after initial implantation. Six patients (18%) developed complications, including two patients who underwent surgery. Follow-up for 29 +/- 17 months (range: 5 to 81 months) demonstrated no evidence of re-coarctation, aneurysm formation, stent displacement or fracture. Systolic blood pressure (SBP) decreased from 136 +/- 21 mm Hg before stent placement to 122 +/- 19 mm Hg at follow-up (p = 0.002). The SBP gradient decreased from 39 +/- 18 mm Hg to 4 +/- 6 mm Hg, and peak Doppler gradient decreased from 51 +/- 26 mm Hg to 13 +/- 11 mm Hg at follow-up (p < 0.001). CONCLUSIONS: Intravascular stent placement for native and recurrent CoA has excellent results in the short and intermediate terms. Long-term outcome remains to be evaluated.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany.

In a case-control study, we investigated the possible etiologic relevance to Parkinson's disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case-control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.