Ban Mishu

Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome

The Guillain-Barre syndrome, sometimes called acute inflammatory polyneuropathy, is an inflammatory demyelinating disease of peripheral nerves characterized by various degrees of weakness, sensory abnormalities, and autonomic dysfunction [1, 2]. Since the marked decline in poliomyelitis, the Guillain-Barre syndrome has become the most common cause of acute neuromuscular paralysis in adults and children in the United States and has an annual incidence of 1.7 per 100 000 people [3, 4]. Epidemiologic studies in all parts of the world have confirmed the association between the Guillain-Barre syndrome and previous acute infection, especially of the respiratory or gastrointestinal tracts [4-8]. Most report that between 50% and 75% of patients have an infectious illness 1 to 3 weeks before onset of neurologic symptoms; previous diarrheal illness occurs in 10% to 30% of patients [4-6]. Bacteria of the genus Campylobacter are important human pathogens and are common causes of gastrointestinal illness in both developed and developing countries [9]. Extraintestinal complications of Campylobacter jejuni infection such as reactive arthritis, pancreatitis, and carditis are well described [10], and in the last decade, clinical and epidemiologic evidence has suggested that infection with C. jejuni may be a precipitating factor for development of the Guillain-Barre syndrome. In small serologic studies of patients with the Guillain-Barre syndrome, as many as one third to one half of patients had increased levels of C. jejuni antibodies at the time of onset of neurologic symptoms [11-13]. Routine stool cultures of eight patients with the Guillain-Barre syndrome in Japan yielded C. jejuni in seven (88%) patients [14]. In an important U.S. investigation of 106 patients with the Guillain-Barre syndrome, C. jejuni was isolated from 4 (44%) of 9 patients who had antecedent clear-cut diarrheal illness; however, cultures had not been obtained from 97 other patients [15]. To assess the extent to which the Guillain-Barre syndrome is associated with recent C. jejuni infection, we did serologic screening with defined assays to determine the frequency of C. jejuni antibodies in a large group of patients with the syndrome and in two control groups. Methods Study Population Case Patients Case patients included 126 persons with the Guillain-Barre syndrome admitted to the University of Maryland Medical Center, the University of Medicine and Dentistry of New Jersey, or to one of several hospitals in St. Louis between 1983 and 1990. A consecutive sample was used. All patients met the National Institute of Neurologic and Communicative Disorders and Stroke [16] criteria for diagnosis of the Guillain-Barre syndrome; none had any exclusion criteria. Most of the patients had demyelinating polyneuropathy, although some had axonal damage. All had a monophasic illness that progressed during 1 to 4 weeks, plateaued, and almost all patients recovered to some extent; one patient died. Blood samples were collected within 3 weeks after the onset of neurologic symptoms from 118 of the patients; 8 patients had blood samples collected from 24 days to more than 3 months after onset of neurologic symptoms (median, 10 weeks). Because antibody response to C. jejuni infection is usually transient [17], specimens from these eight patients are not included in the analysis. Histories of symptoms of gastrointestinal or respiratory infections before onset of the Guillain-Barre syndrome were not available. Controls Two groups of controls were studied. One control group, a convenience sample, consisted of 56 patients with neurologic diseases other than the Guillain-Barre syndrome who were admitted to the neurology services at the University of Maryland, the University of Medicine and Dentistry of New Jersey, or one of the St. Louis hospitals. Diagnoses of these patients included optic neuritis, multiple sclerosis, amyotrophic lateral sclerosis, polyneuropathy associated with IgM paraproteinemia, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, unexplained peripheral neuropathy, ischemic neuropathy, neuropathy associated with diabetes, and drug-induced neuropathy. The second control group, a voluntary sample, included 18 healthy employees of the neurology departments of the three universities and 29 healthy family members of case patients and of disease controls. Medical histories of healthy controls were not obtained. Sera and Data Collection Sera from case patients and controls was stored frozen at the collection sites until the serologic assays were done. Data collected included disease severity of case patients, sex, age, and date of sera collection. Information about race was available only from the patients at the University of Medicine and Dentistry of New Jersey. Serologic Methods Presence of serum IgA, IgG, and IgM antibodies specific for C. jejuni was determined by enzyme-linked immunosorbent assay (ELISA) as previously described [17]. Antigens from three C. jejuni strains of Penner (O-) types 1, 2, and 3, which are commonly isolated from humans, were prepared as described by McCoy and colleagues [18]; they contained a mixture of acid-extracted proteins common to C. jejuni strains [17, 19, 20]. The serum dilutions used were as follows: 1:50 for IgA, 1:200 for IgG, and 1:400 for IgM. The class-specific second antibody used (and the use dilution) was peroxidase-conjugated goat anti-human IgA (1:2000), IgG (1:2500), or IgM (1:1000) (Tago Inc; Burlingame, California). The plates were read at 414 nm on a Dynatech ELISA reader (Alexandria, Virginia), and results were expressed as an optical density value for each well. All sera had been coded and were assayed blindly three times on different days in duplicate wells for each run. Calculation of Optical Density Ratios The assays were standardized using sera from a patient with the Guillain-Barre syndrome and culture-proven C. jejuni infection (positive control) and sera from 38 healthy children in New York who had had no recent history of diarrheal illness (negative controls). Optical density values were determined serially for plates containing these sera, and the mean optical density of the positive control was plotted versus the mean optical density + 1 SD of the negative controls. For each immunoglobulin class, a regression line was calculated and then used each day the assay was done (using the same positive control serum) to generate a threshold value for determination of the optical density ratio. (Regression analysis for IgA assay, r = 0.973, P < 0.001; regression analysis for the IgG assay, r = 0.998, P < 0.001; regression analysis for the IgM assay, r = 0.981, P < 0.001.) To control for day-to-day assay variation, the optical density ratio was defined as the ratio of the optical density of each unknown serum sample to the observed threshold on that day. A similar method has been used to standardize Helicobacter ELISA determination [21]. Case Definitions and Statistical Methods A positive serologic response was defined as an optical density ratio greater than or equal to a specified threshold in one or more immunoglobulin classes. Differences in the proportion of positive responses among case patients and controls were ascertained using an optical density ratio 1, 2, or 3 as the threshold. Statistical analyses were done in a univariate manner using the Mantel Haenszel Chi-squared analysis or the Fisher exact test when indicated and by the calculation of odds ratios. The sensitivity and specificity of the assays were determined as follows. Optical density ratios were determined as described above for 17 patients in the convalescent phase of culture-proven C. jejuni infection. These were U.S. soldiers who had become infected while on military exercise in Thailand in 1988; convalescent sera were obtained 4 weeks after onset of diarrhea. The comparison group comprised 19 healthy adults who were employees of or visitors to the Infectious Diseases Division of Vanderbilt University and included 20 healthy children in Nashville who had no recent history of diarrheal illness. Results Patients Demographic characteristics of the 118 case patients and 103 controls are shown in (Table 1). Age was known for 112 (95%) case patients and 93 (90%) controls; gender was known for 116 (98%) case patients and for 99 (96%) controls. Information about the month blood was drawn was available for 116 (98%) case patients and 80 (78%) controls. The groups were similar except that controls were somewhat younger (median age, 33 years compared with 41 years for case patients) and were more likely to have had their blood drawn during the summer months. Race of patients and controls (from the University of Medicine and Dentistry of New Jersey only) also was similar in the two groups. In both groups there were more male patients. Table 1. Demographic Characteristics of 118 Patients with the Guillain-Barre Syndrome and of 103 Controls, Including 56 Controls with Disease and 47 Healthy Controls Serologic Assays in Persons with Campylobacter jejuni Infection and in Controls Among 17 persons with culture-proven C. jejuni infections, in the IgA assay, 15 (88%) had an optical density ratio 1. Increasing the threshold for defining a positive serologic response to an optical density ratio 2 and 3 decreased the sensitivity of the test (Table 2). The specificity of the test was evaluated by the serologic responses in the control group. Defining a positive serologic response as an optical density ratio 1, the IgA assay was 85% specific (specificity determined by subtracting the percentage of controls exceeding threshold from 100%) (Table 2). Increasing the threshold to an optical density ratio 2 or 3 improved the specificity of the test. The sensitivity and specificity of the IgG and IgM assays are also shown in Table 2. As expected, raising the stringency by increasing the optical density ratios or numbers of positive classes

Salmonella enteritidis Gastroenteritis Transmitted by Intact Chicken Eggs

OBJECTIVE To determine the source and to describe the clinical importance of a large outbreak of Salmonella enteritidis gastroenteritis in Tennessee, which is outside the geographic focus of the S. enteritidis pandemic. DESIGN A case-control study and tracing of the source eggs. SETTING A Tennessee community and a large layer farm in Indiana. PATIENTS Case patients ate at the implicated restaurant and subsequently developed S. enteritidis gastroenteritis; controls ate with the case patients, but did not develop gastroenteritis. MEASUREMENTS Eighty-one case patients were identified; 73 (90%) had eaten egg-containing sauces at a local restaurant on a given evening. The eggs were traced to their farm of origin in Indiana. The farm was inspected 5 weeks after the outbreak. MAIN RESULTS Of 24 patients with culture-proved cases, 11 were hospitalized. Hollandaise and bernaise sauces prepared with intact, extra-large, grade-A eggs were strongly associated with illness (P less than 0.001). Salmonella enteritidis was isolated from specimens collected from chickens and the farm. Antimicrobial susceptibility patterns, phage typing, and plasmid profiles of isolates from the farm and from patients were indistinguishable. CONCLUSIONS Salmonella enteritidis infection is a large and growing public health problem that is spreading beyond the northeastern United States. This study shows a direct link between infected poultry flocks and an outbreak of human illness.

HIV transmission from surgeons and dentists to patients: can models predict the risk?

acquiring H1V infection in the operating room or the dentists chair? Analysis of related data and public sentiment suggest this model will provide limited reassurance; however, it cannot explain a critical event: the clustering of HIV transmission from a Florida dentist to six patients. Since the early days of the acquired immunodeficiency syndrome (AIDS) era, this disease has engendered intense anxiety (some have described it as near-hysteria) in the general population. As more was learned about HIV and its transmission, the general public came to understand that, with the exception of infants born to infected mothers, individuals became infected with HIV only by sexual intercourse with an infected person, intravenous drug use, or transfusion of contaminated blood products. Gradually, it became accepted that acquisition of infection did not occur through casual contact with infected persons2; the public was reassured that sharing an office, a taxi, a classroom, or a dormitory room with an HIV-infected person did not pose a risk. Even the chance of acquiring HIV infection from transfused blood products became increasingly remote as blood donor sources were limited to low-risk populations, routine screening of blood for HIV antibodies became standard, and opportunities for directed donations became more widely available. Thus, as information about routes of HIV transmission was disseminated to the public, a more calm and rational approach to AIDS emerged.2 In 1990, the Centers for Disease Control announced that a dentist with AIDS had transmitted