Faculty Bibliography

The [Bhagwan Shree Rajneesh] outbreak and the multiple murders are likely to raise suspicions among public-health investigators. The idea that criminal activity is responsible 'needs to be in the back of our mind in an investigation when things do not add up,' says Dr. [Thomas J. Torok]. 'But usually it should be at the bottom of the list.'

One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacterial pathogens. The lack of neutral mutations in structural genes indicates that M. tuberculosis is evolutionarily young and has recently spread globally. Species diversity is largely caused by rapidly evolving insertion sequences, which means that mobile element movement is a fundamental process generating genomic variation in this pathogen. Three genetic groups of M. tuberculosis were identified based on two polymorphisms that occur at high frequency in the genes encoding catalase-peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old and allied with M. bovis, the cause of bovine tuberculosis. A subset of several distinct insertion sequence IS6110 subtypes of this genetic group have IS6110 integrated at the identical chromosomal insertion site, located between dnaA and dnaN in the region containing the origin of replication. Remarkably, study of approximately 6,000 isolates from patients in Houston and the New York City area discovered that 47 of 48 relatively large case clusters were caused by genotypic group 1 and 2 but not group 3 organisms. The observation that the newly emergent group 3 organisms are associated with sporadic rather than clustered cases suggests that the pathogen is evolving toward a state of reduced transmissability or virulence

Using the latest computer tomography (CT) and X-ray (DEXA) technology to measure body fat in 224 Caucasian women, researchers confirmed that abdominal fat, particularly internal fat wrapped around the liver and other internal organs, is linked to heart disease. According to their report in the American Journal of Clinical Nutrition, leg fat was actually associated with better cardiovascular health

Consider two outbreaks that were initially attributed to an unusual natural accident and a hereditary disorder. Later they were found to have been caused by criminal acts, something that doctors generally have little reason to consider in most cases of disease, as opposed to cases of physical violence, long recognized as a public health problem. And even when doctors do find a criminal cause for a medical problem, they have tended not to report the cases in medical journals, partly, they say, to avoid further incidents. That attitude has begun to change, albeit slowly. Last week Federal health officials focused new attention on one such criminal outbreak 13 years after it happened. They published a report in The Journal of the American Medical Association about 751 cases of salmonella infection that occurred in 1984 among the 10,500 residents of The Dalles, Ore., because followers of Bhagwan Shree Rajneesh had deliberately contaminated restaurant salad bars there. ''The possibility of deliberate contamination has been on every investigator's list since the Rajneesh incident and it has greatly influenced how we approach outbreaks of illness,'' said Dr. Thomas J. Torok, an epidemiologist at the Federal Centers for Disease Control and Prevention in Atlanta who participated in the Oregon investigation

Shigella pathogenesis involves bacterial invasion of colonic epithelial cells and movement of bacteria through the cytoplasm and into adjacent cells by means of actin-based motility. The Shigella protein IcsA (VirG) is unipolar on the bacterial surface and is both necessary and sufficient for actin-based motility. IcsA is inserted into the outer membrane as a 120-kDa polypeptide that is subsequently slowly cleaved, thereby releasing the 95-kDa amino-terminal portion into the culture supernatant. IcsP, the major Shigella protease that cleaves IcsA, was identified and cloned. It has significant sequence similarity to the E. coli serine proteases, OmpP and OmpT. Disruption of icsP in serotype 2a S. flexneri leads to a marked reduction in IcsA cleavage, increased amounts of IcsA associated with the bacterium and altered distribution of IcsA on the bacterial surface. The icsP mutant displays significantly increased rates of actin-based motility, with a mean speed 27% faster than the wild-type strain; moreover, a significantly greater percentage of the icsP mutant moves in the cytoplasm. Yet, plaque formation on epithelial monolayers by the mutant was not altered detectably. These data suggest that IcsA, and not a host protein, is limiting in the rate of actin-based motility of wild-type serotype 2a S. flexneri.

OBJECTIVE:To determine whether IV pyelography (IVP) is required routinely for all patients presenting to the ED with ureteral colic. METHODS:A randomized prospective study was conducted with 2 patient groups-a routine IVP group, in which all patients underwent IVP, and a selective IVP group, in which patients were treated, observed, and released without undergoing IVP unless they experienced continued symptoms. The study was performed in a large university-affiliated, community hospital ED. Participants were patients aged 18-65 years with signs and symptoms consistent with ureteral colic. RESULTS:Among the 40 patients enrolled in the routine IVP group, 26 had positive studies, 8 of which necessitated hospitalization. Among the 41 patients randomized to the selective IVP group, there were only 19 IVPs performed, of which 6 were positive and 4 necessitated hospitalization. Compared with the routine IVP group, there were 54% fewer FVPs performed and a 51 % lower admission rate in the selective IVP group. Despite the fact that fewer IVPs were performed in the selective IVP group, clinical outcomes in the 2 groups were similar, without significant complication in either group. CONCLUSIONS:IVPs do not need to be routinely performed for all patients presenting to the ED with ureteral colic. The decision to perform an IVP may be dictated by symptoms that persist after initial evaluation and treatment.

In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city

STUDY OBJECTIVE: To test the hypothesis that individuals chronically noncompliant with antituberculous chemotherapy are vectors for ongoing transmission of the disease in the community. DESIGN: Cohort study. SETTING: A large public hospital with a tuberculosis detention unit for patients with repeated and prolonged nonadherence to therapy. PATIENTS: Mycobacterium tuberculosis isolates from patients confined on the detention unit were obtained from the hospital's mycobacteriology laboratory. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A standardized IS6110-based Southern blot hybridization protocol was used to genotype M tuberculosis isolates recovered from patients confined on the detention unit at the hospital. Each DNA fingerprint pattern was compared with the IS6110-fingerprint database at the Public Health Research Institute Tuberculosis Center, which has archived fingerprint patterns from over 2,500 M tuberculosis isolates collected from New York City patients in the past 5 years. Eighty percent of available isolates from detained patients belonged to an identifiable DNA fingerprint cluster, suggesting an epidemiologic link between the detainees and other New York City tuberculosis patients. CONCLUSIONS: Chronic noncompliance with therapy is associated with ongoing spread of tuberculosis in the community. Aggressive measures, including detention, for the small number of recalcitrant, noncompliant patients may interrupt a chain of transmission and contribute to a decline in the spread of tuberculosis in urban areas

Ethambutol [(S,S')-2,2'-(ethylenediimino)di-1-butanol; EMB], is a first-line drug used to treat tuberculosis. To gain insight into the molecular basis of EMB resistance, we characterized the 10-kb embCAB locus in 16 EMB-resistant and 3 EMB-susceptible genetically distinct Mycobacterium tuberculosis strains from diverse localities by automated DNA sequencing and single-stranded conformation polymorphism analysis. All 19 organisms had virtually identical sequences for the entire 10-kb region. Eight EMB-resistant organisms had mutations located in codon 306 of embB that resulted in the replacement of the wild-type Met residue with Ile or Val. Automated sequence analysis of the 5' region (1,892 bp) of embB in an additional 69 EMB-resistant and 30 EMB-susceptible M. tuberculosis isolates from diverse geographic localities and representing 70 distinct IS6110 fingerprints confirmed the unique association of substitutions in amino acid residue 306 of EmbB with EMB resistance. Six other embB nucleotide substitutions resulting in four amino acid replacements were uniquely found in resistant strains. Sixty-nine percent of epidemiologically unassociated EMB-resistant organisms had an amino acid substitution not found in susceptible strains, and most (89%) replacements occurred at amino acid residue 306 of EmbB. For strains with the Met306Leu or Met306Val replacements EMB MICs were generally higher (40 microg/ml) than those for organisms with Met306Ile substitutions (20 microg/ml). The data are consistent with the idea that amino acid substitutions in EmbB alter the drug-protein interaction and thereby cause EMB resistance

OBJECTIVES: This study evaluated the efficacy of radiographic screening for tuberculosis in correctional facilities. METHODS: Inmates at an admission facility in New York, NY, were screened for tuberculosis by registry cross-match, symptom interviews, tuberculin testing, and chest radiography. RESULTS: Thirty-two cases of tuberculosis were detected among 4172 inmate admissions (767 cases per 100,000). Twenty-five inmates (78%) were previously diagnosed but incompletely treated; all were identified by registry cross-match. Seven inmates (22%) were newly diagnosed, of whom four (57%) were asymptomatic, had negative skin tests, and were detected only by their abnormal radiographs. CONCLUSIONS: Screening strategies that limit radiographic testing to inmates with either positive skin tests or symptoms may result in missed opportunities for diagnosing active tuberculosis.