Subsequent Surveillance Research Articles

Spatial Ecology of Raccoons Related to Cattle and Bovine Tuberculosis in Northeastern Michigan

ABSTRACT In 1995, Mycobacterium bovis, the causative bacterium of bovine tuberculosis (bTB), was detected in 5 beef cattle operations in Alcona County, Michigan, USA. In accordance with Federal law, the operations were depopulated to prevent the spread of bTB. Subsequent wildlife surveillance programs identified high prevalence of M. bovis in mesocarnivores, including raccoons (Procyon lotor), which suggested that raccoons may be complicit in vectoring the pathogen among livestock operations. Our goal was to develop an empirical basis for generating hypotheses about the likelihood for raccoons to mediate the transmission of bTB to livestock. We found intersexual differences in scale‐dependent resource selection and probability of spatial interaction that, under certain circumstances, may form the foundation for a sex‐bias in disease transmission. Spatial dispersion of mixed‐forest patches facilitated overlap of adjacent males, whereas female overlap zones included pastures. Within overlap zones, probabilities of interaction for male‐male and male‐female dyads were greater than for female‐female dyads, although we documented an elevated likelihood of spatial interaction between raccoons and livestock around cattle‐feeding troughs and water sources, regardless of sex. Partial regressions generated by linear models indicated that distance between nearest‐neighbor mixed‐forest patches explained most of this observed variation. These results supported our prediction that forest patches juxtaposed with anthropogenic features fostered social tolerance between males and, thus, facilitated spatial interaction and exploitation of anthropogenic features. In raccoons, sex and landscape composition influenced pathogen transmission potential. We suggest that livestock producers locate livestock feeding and watering features away from forest patches to mitigate future outbreaks of bTB in endemic areas.

INDOOR RESIDUAL SPRAYING OF DDT FOR MALARIA CONTROL

We wish to comment on O'Shaughnessy's article1 on the use of DDT to control malaria from our years of malaria eradication experience.2 From 1948 to 1958, H. H. C. participated in Taiwan's malaria program. In 1950, there were 1.2 million cases of malaria out of a population of 7.5 million.3,4 After a period of DDT indoor residual spraying from 1953 to 1957,3,5–7 the number of cases dropped to 533. Subsequent surveillance, case detection, treatment, and focal indoor residual spraying resulted in only 19 cases in 1965 (out of a population of 12.4 million) and the World Health Organization (WHO) declared that malaria has been eradicated on the island. Remarkably, the total program cost per capita from 1953 to 1957 was NT $3 (US $0.10 at the current exchange rate).6 The story of parachuting cats into malaria-infested areas to counteract the increasing rodent populations after the DDT spraying program killed the native cats is cited as a parable of ecosystem meddling and has become an urban legend. In Taiwan, we knew indoor residual spraying killed cats and other animals, so we asked villagers to keep them out of the house for several days after the spraying. Surveillance of 682 houses sprayed (264 with cats) found that 43 cats died, along with many mice and chickens.3 Some animals died in a day, suggesting that direct toxicity was the issue, not biomagnification. We are skeptical about the validity of the reports of cats being parachuted into Sarawak in 1960. An airdrop of DDT supplies in 1954 during the pilot project is mentioned in another source,8 but supplies were always transported via speedboats during H. H.C.'s tenure as the malaria advisory team leader in Sarawak from 1962 to 1968. Colbourne et al. never mentioned parachuting cats to us or in their article, which focused on the Sarawak malaria epidemic from 1955 to 1958.9 Similarly, we heard no mention of such an incident from the WHO Senior Malaria Advisor from 1959 to 1961. In Sarawak, Malaysia, we heard complaints about spoiled thatch roofs of farm huts10 in the neighboring area of Sabah (North Borneo), but never Sarawak. Longhouses—the typical indigenous abode in Sarawak at the time—have roofs of billian (extremely hard wood impervious to moth larvae)8; thatching was not used so longhouses were unaffected. Despite claims to the contrary, we do not believe that there were any major typhus epidemics or outbreaks of sylvatic plague in Sarawak due to increased vector populations. In fact, in Taiwan, we experienced a positive consequence of the spraying program: head lice disappeared. Today's reader might cringe, but villagers often asked to have their heads sprayed with DDT! Indoor residual spraying is controversial, but it is appealing for a variety of reasons. It contaminates the environment less than larviciding or aerial spraying. It is economical. Spraying can be done once or twice a year for 3 to 5 years followed by focal spraying. Malaria eradication has failed for multiple reasons: drug resistance, continuous mosquito exposure, geographical challenges, and political instability. Although restarting indoor residual spraying alone is insufficient to control malaria, fears of environmental destruction are overblown. It is time to retire the cat story and reconsider DDT's role in the fight against malaria.

Sensitivity of PillCam ESO for Detection of Esophageal Varices; A Meta Analysis

Introduction: Current guidelines recommend screening for esophageal varices at diagnosis of cirrhosis and depending on the findings, treatment and subsequent surveillance is indicated. Esophago-gastro-duodenoscopy (EGD) is the current gold standard for evaluation of esophageal varices. Recently numerous studies have evaluated the role of esophageal capsule endoscopy (ECE) as an alternative to EGD for screening of varices. Aim: To perform a Meta analysis to evaluate the overall pooled sensitivity and specificity of ECE in detecting esophageal varices when compared to traditional EGD.

Optical Biopsy At Colonoscopy: Are We Ready? DISCARD Study: Early Results

Background: 90% of polyps removed at colonoscopy are <10mm in size and only 50% of these are neoplastic. The number of neoplastic polyps is the key determinant of future surveillance intervals and small adenomas, especially those less than 5 mm in size, rarely contain advanced pathology. Accurate characterisation of small polyps in vivo could reduce the number of unnecessary polypectomies, reduce the need for polyp retrieval and greatly reduce histopathology costs. Accurate characterisation of small polyps in vivo is feasible, with a number of studies reporting accuracy around 90% when using magnification, chromoendoscopy or narrow band imaging (NBI). However the ability to make clinical decisions based on optical biopsy has not been investigated. Aims and Methods: This prospective study examined whether colonoscopists could accurately assess small polyps in vivo and determine appropriate surveillance intervals based on real time optical biopsy. Consecutive patients attending for colonoscopy (FOBT positive or adenoma surveillance) were included. Four endoscopists with varying experience of optical biopsy performed all the colonoscopies. Once a polyp < 10 mm was encountered the endoscopist predicted polyp histology using one or a combination of optical modalities (high definition white light alone, NBI or indigocarmine chromoendoscopy). At the end of the procedure, future surveillance intervals based on optical biopsies were determined according to BSG guidelines. Optical diagnosis was compared to histopathology findings. The primary outcome measure was the accuracy of optical polyp characterisation and clinical decision making (ie to resect or leave polyps in situ). A secondary outcome was any change in surveillance interval following histopathological assessment. Results: 168 (out of 296 planned) polyps smaller than 10 mm (mean size 3.5 mm, range 1-9 mm SD 2.2) were found in 57 patients. Histology was available for 141 lesions - 85 adenomas, 38 hyperplastic polyps, 1 inflammatory, 3 lymphoid follicles and 14 normal. 92% (78/85) of adenomas and 95% (36/38) of hyperplastic polyps were correctly diagnosed by optical biopsy. In 82/86 (95%) cases the decision to resect and discard the polyp could be considered correct. Two adenomas contained high-grade dysplasia - in both of these cases, the colonoscopist predicted the diagnosis of adenoma and elected to resect and discard but the subsequent colonoscopy surveillance interval was unaffected. There were no cancers smaller than 10mm. Following BSG Guidelines for polyp surveillance, 0/57 patients had their predicted surveillance interval changed after formal histopathology.

The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter

The shuttling of substrates across a cellular membrane frequently requires a specialized ATP-binding cassette (ABC) transporter, which couples the energy of ATP binding and hydrolysis to substrate transport. Due to its importance in immunity, the ABC transporter associated with antigen processing (TAP) has been studied extensively and is an excellent model for other ABC transporters. The TAP protein pumps cytosolic peptides into the endoplasmic reticulum for loading onto class I major histocompatibility complex (MHC) for subsequent immune surveillance. Here, we outline a potential mechanism for the TAP protein with supporting evidence from bacterial transporter structures. The similarities and differences between TAP and other transporters support the notion that ABC transporters in general have adapted around a universal transport mechanism.

Surveillance FDG-PET detection of asymptomatic recurrences in patients with cervical cancer

Objectives To evaluate survival after detection of recurrent cervical cancer by FDG-PET in symptomatic versus asymptomatic patients. Methods This is a prospective registry study of 103 patients treated with definitive chemoradiation for advanced cervical cancer who demonstrated no abnormal FDG uptake (a complete metabolic response, CMR) on their 3-month posttherapy FDG-PET. Their median age was 48 years (range 26–84). The clinical stages were Ib in 38, IIa in 1, IIb in 39, and IIIb in 25. All patients underwent subsequent surveillance FDG-PET. Patients were grouped according to symptom status at the time of the surveillance FDG-PET. Recurrence sites and survival data were analyzed. Results The median time from the 3-month posttherapy FDG-PET to the first surveillance FDG-PET was 13 months. 25 patients (25/103; 24%) were symptomatic at the time of surveillance FDG-PET and 21 of these had FDG-PET findings indicative of recurrence. 78 patients (78/103; 76%) were asymptomatic and 9 of these had tumor recurrence detected by PET. All recurrences were confirmed by biopsy or radiologic progression. The recurrences in the 21 symptomatic patients were loco regional in 4 and distant in 17. The 9 asymptomatic patients had isolated loco regional disease in 8 and distant disease in 1. All patients received treatment for recurrence. The three-year cause-specific survival for symptomatic recurrences was 19% versus 59% for asymptomatic recurrences ( p = 0.09). Conclusions Surveillance FDG-PET can detect asymptomatic recurrent disease that is potentially amenable to salvage therapy. Prospective investigation of surveillance PET is warranted.

Cohort study of the association of antibody levels to AMA1, MSP119, MSP3 and GLURP with protection from clinical malaria in Ghanaian children

BackgroundAntigen-specific antibody-mediated immune responses play an important role in natural protection against clinical malaria, but conflicting estimates of this association have emerged from immuno-epidemiological studies in different geographical settings. This study was aimed at assessing in a standardized manner the relationship between the antibody responses to four malaria vaccine candidate antigens and protection from clinical malaria, in a cohort of Ghanaian children.MethodsStandardized ELISA protocols were used to measure isotype and IgG subclass levels to Apical Membrane Antigen 1 (AMA1), Merozoite Surface Protein 1–19 (MSP119), Merozoite Surface Protein 3 (MSP3) and Glutamate Rich Protein (GLURP) antigens in plasma samples from 352 Ghanaian children, aged three to 10 years with subsequent malaria surveillance for nine months. This is one of a series of studies in different epidemiological settings using the same standardized ELISA protocols to permit comparisons of results from different laboratories.ResultsThe incidence rate of malaria was 0.35 episodes per child per year. Isotype and IgG subclasses for all antigens investigated increased with age, while the risk of malaria decreased with age. After adjusting for age, higher levels of IgG to GLURP, MSP119, MSP3 and IgM to MSP119, MSP3 and AMA1 were associated with decreased malaria incidence. Of the IgG subclasses, only IgG1 to MSP119 was associated with reduced incidence of clinical malaria. A previous study in the same location failed to find an association of antibodies to MSP119 with clinical malaria. The disagreement may be due to differences in reagents, ELISA and analytical procedures used in the two studies. When IgG, IgM and IgG subclass levels for all four antigens were included in a combined model, only IgG1 [(0.80 (0.67–0.97), p = 0.018)] and IgM [(0.48 (0.32–0.72), p < 0.001)] to MSP119 were independently associated with protection from malaria.ConclusionUsing standardized procedures, the study has confirmed the importance of antibodies to MSP119 in reducing the risk of clinical malaria in Ghanaian children, thus substantiating its potential as a malaria vaccine candidate.

The Yield of Surveillance Colonoscopy by Adenoma History and Time to Examination

Surveillance colonoscopy is recommended for subjects with a history of adenomas but there is limited information on the yield of surveillance. A sample of subjects in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial with abnormal flexible sigmoidoscopy and follow-up colonoscopy were queried about subsequent surveillance colonoscopy over a 10-year period. Medical records were obtained to verify procedure dates and histologic findings. Subjects with advanced adenomas, nonadvanced adenoma, nonadenomatous polyps, and no polyps at baseline were included. At the first surveillance, 10.5% had advanced adenoma and 37% had any adenoma in the advanced adenoma group (n = 1057), compared with rates of 6.8% and 32% (nonadvanced adenoma: n = 765), 4.9% and 22% (nonadenomatous polyps: n = 658), and 3.1% and 16% (no polyps: n = 127) (P < .0001, linear trend test). Mean (SD) time intervals (years) from baseline colonoscopy to first surveillance were 3.4 (2.0) for advanced adenoma, 4.3 (2.0) for nonadvanced adenoma, 4.5 (2.0) for nonadenomatous polyps, and 4.7 (2.0) for no polyps. There were no increasing (or decreasing) trends in the observed rate of advanced adenoma or any adenoma with time to the initial surveillance examination in any baseline group. Among subjects with a second surveillance examination, adenoma findings at both baseline and first surveillance influenced the rates of advanced adenoma and any adenoma at second surveillance. Subjects with baseline advanced adenomas are more likely to have recurrent advanced adenomas at initial surveillance. The lack of association between recurrence rates and time to surveillance suggests limitations in our understanding of the biology of adenoma development.

Multifocal High-Grade Dysplasia (MFHGD) in Barrett's Esophagus Is Associated with Adenocarcinoma in Patients Undergoing Endoscopic Mucosal Resection (EMR) for Barrett's Esophagus

Background: Risk of undetected adenocarcinoma in patients with high-grade dysplasia (HGD) is considered high. The extent of HGD has been suggested to be a risk factor for the development of cancer, but the predictive value of MFHGD as a marker for adenocarcinoma remains controversial. EMR can completely eradicate areas of Barrett's esophagus and it enables a complete pathologic evaluation of the Barrett's segment. Aim: To examine the extent of HGD in association with co-existing carcinoma in Barrett's esophagus in endoscopically resected specimens. Methods: Twenty-eight patients with Barrett's HGD or adenocarcinoma who underwent EMR between May 2005 and October 2006 were included in the analysis. All patients with HGD were planned for 2-staged complete eradication EMR. Two patients did not complete the eradication due to multifocal cancer in one and lymphovascular invasion (LVI) in another found at the first EMR. They subsequently underwent surgery, thus full pathology is available. One patient did not have subsequent follow up. All EMR specimens were retrieved and pinned on the corkboard, oriented, serially sectioned and submitted entirely for microscopic examination. Slides were independently reviewed by experienced gastrointestinal pathologists for presence and degree of dysplasia, carcinoma, and depth of invasion. MFHGD was defined as the presence of HGD at multiple levels of esophagus. Results: Fourteen pts were diagnosis with HGD and 14 with adenocarcinoma at surveillance biopsies prior to referral to the institution. Among the 14 pts with HGD, 4 pts had MFHGD. A total of 19 pts were confirmed with adenocarcinoma after EMR. Eight pts with adenocarcinoma (42%) had coexisting MFHGD. Three pts with a diagnosis of adenocarcinoma by biopsy (21%) did not have an evidence of cancer in EMR specimens and subsequent surveillance biopsy. Among the 14 pts who went to eradication EMR with a diagnosis of HGD, 7 (50%) had evidence of unsuspected adenocarcinoma in EMR specimens. All 4 pts with MFHGD (100%) had a focus of adenocarcinoma whereas 3 of 10 pts with focal HGD (30%) had adenocarcinoma. All adenocarcinoma in HGD group was diagnosed as intramucosal carcinoma. One patient in MFHGD group had intramucosal carcinoma with an evidence of LVI and underwent surgical resection. Conclusions: Adenocarcinoma is highly associated with co-existing MFHGD. MFHGD by surveillance biopsy suggested higher probability of undetected adenocarcinoma in this cohort of patients. Although larger studies are needed to confirm this finding, MFHGD may be used for risk stratification of patients with Barrett's esophagus, especially when choosing resection versus ablation therapy.

Aggressive pediatric meningioma with soft tissue and lymph node metastases: a case report

Metastatic meningioma is extremely rare, occurring in an estimated 0.1% of cases. We report a case of pediatric meningioma metastatic to cervical soft tissue and lymph nodes. An 8‐year‐old boy presented with headaches, dizziness, involuntary eye flickering, and 3‐year history of cervical lymphadenopathy. MRI revealed a 7.5 cm parasagittal dural‐based mass with venous sinus encasement. Therapeutic embolization was followed by bilateral craniotomy, achieving subtotal resection. Histopathologic examination revealed an atypical meningioma (WHO grade II) with regions of hypercellularity, small cell morphology, sheeting architecture, increased mitoses, and brain invasion. Deletions of NF2 and DAL1 (protein 4.1B) were documented by fluorescence in situ hybridization. Subsequent surveillance MRI studies showed growth of residual intracranial tumor, large extra‐axial and subgaleal CSF collections, and enlarging cervical soft tissue masses with posterior triangle lymphadenopathy. Gamma knife and surgical resection were employed for the intracranial tumor burden; resection of the soft tissue masses revealed metastatic meningioma, with diffuse soft tissue infiltration, extensive lymphatic invasion, and metastasis to 8 lymph nodes. This case demonstrates the aggressive biologic potential of pediatric meningiomas, with potential for distant spread via CSF leakage and lymphatic invasion.

Implementing a Survivorship Care Plan for Patients With Breast Cancer

Breast cancer survivors account for 23% of the more than 10 million cancer survivors in the United States today. The treatments for breast cancer are complex and extend over a long period of time. The post-treatment period is characterized by gradual recovery from many adverse effects from treatment; however, many symptoms and problems persist as late effects (eg, infertility, menopausal symptoms, fatigue), and there may be less frequent long-term effects (eg, second cancers, lymphedema, osteoporosis). There is increasing recognition of the need to summarize the patient's course of treatment into a formal document, called the cancer treatment summary, that also includes recommendations for subsequent cancer surveillance, management of late effects, and strategies for health promotion. This article provides guidance on how oncologists can implement a cancer treatment summary and survivorship care plan for breast cancer survivors, with examples and linkage to useful resources. Providing the breast cancer treatment summary and survivorship care plan is being recognized as a key component of coordination of care that will foster the delivery of high-quality cancer care.

Johne's Disease in a Free-Ranging White-tailed Deer from Virginia and Subsequent Surveillance for Mycobacterium avium subspecies paratuberculosis

Johne's disease (paratuberculosis) was diagnosed in a 2-yr-old, male, free-ranging white-tailed deer (Odocoileus virginianus) from Fauquier County, Virginia, USA, based on histopathology and culture for Mycobacterium avium subspecies paratuberculosis. Clinical and pathologic findings included emaciation; loss of body fat; chronic diarrhea; severe, chronic, diffuse granulomatous colitis with intrahistiocytic acid-fast bacilli; moderate, chronic granulomatous lymphadenitis with intrahistiocytic acid-fast bacilli; as well as moderate chronic, multifocal, lymphoplasmacytic hepatitis. These findings are consistent with previous reports of Johne's disease in cervids. Subsequent targeted surveillance of 10 emaciated deer with diarrhea, as well as sampling of 72 asymptomatic deer for M. avium subsp. paratuberculosis using culture of multiple tissue types, as well as serology using an enzyme-linked immunosorbent assay (ELISA) optimized for cervid antibody detection, did not reveal any additional cases of infection in this geographic region. To date, this appears to be an isolated case of Johne's disease in a free-ranging white-tailed deer, and infection with the causative agent for Johne's disease appears to be an infrequent occurrence in deer from this region. The origin of infection was most likely domestic ruminants. This is the first report of clinical Johne's disease in a free-ranging white-tailed deer outside of the Florida Keys, USA. Stressors, such as high deer population density and low selenium levels, may have contributed to the development of clinical disease in this case and warrant further investigation.

Impact of Prophylaxis with Aerosolized Amphotericin-B Deoxycholate (d-AmB) on Respiratory Tract Invasive Fungal Infections (IFIs) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables.Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis.Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

Polypes gastriques

Gastric polyps exist in a wide variety of types, most often benign. Endoscopic discovery of gastric polyps necessitates biopsies - not only of the lesion but also of the antral and fundic mucosa to determine the therapeutic strategy and subsequent surveillance. Fundic gland polyps are the most frequent type; they are asymptomatic with no malignant potential. They require neither treatment nor surveillance. Hyperplastic polyps, adenomas and tumors must be totally resected. Biopsies alone are insufficient to assess the extent of malignancy of adenomas and of hyperplastic polyps more than 5 mm in diameter. These polyps are associated with an elevated frequency of precancerous alterations of the gastric mucosa and consequently by an elevated risk of synchronous or metachronous cancer. Eradication of Helicobacter pylorus may reduce the risk of metachronous gastric cancer and recurrence after resection. Carcinoid tumors of the fundus most often occur in patients with hypergastrinemia during atrophic gastritis of autoimmune origin; they are not serious. The advantages and procedures for endoscopic surveillance of patients with a precancerous condition of the gastric mucosa have not yet been clearly established in populations with a low incidence of cancer.

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In this issue

Duplex scan surveillance after carotid angioplasty and stenting: A rational definition of stent stenosis

A duplex ultrasound (DUS) surveillance algorithm used after carotid endarterectomy (CEA) was applied to patients after carotid stenting and angioplasty (CAS) to determine the incidence of high-grade stent stenosis, its relationship to clinical symptoms, and the outcome of reintervention. In 111 patients who underwent 114 CAS procedures for symptomatic (n = 62) or asymptomatic (n = 52) atherosclerotic or recurrent stenosis after CEA involving the internal carotid artery (ICA), DUS surveillance was performed <or=30 days and every 6 months thereafter. High-grade stenosis (peak systolic velocity [PSV] >300 cm/s, diastolic velocity >125 cm/s, internal carotid artery stent/proximal common carotid artery ratio >4) involving the stented arterial segment prompted diagnostic angiography and repair when >75% diameter-reduction stenosis was confirmed. Criteria for >50% CAS stenosis was a PSV >150 cm/s with a PSV stent ratio >2. All 114 carotid stents were patent on initial DUS imaging, including 90 (79%) with PSV <150 cm/s (94 +/- 24 cm/s), 23 (20%) with PSV >150 cm/s (183 +/- 34 cm/s), and one with high-grade, residual stenosis (PSV = 355). During subsequent surveillance, 81 CAS sites (71%) exhibited no change in stenosis severity, nine sites demonstrated stenosis regression to <50% diameter reduction, and five sites developed velocity spectra of a high-grade stenosis. Angiography confirmed >75% diameter reduction in all six CASs with DUS-detected high-grade stenosis, all patients were asymptomatic, and treatment consisted of endovascular (n = 5) or surgical (n = 1) repair. During the mean 33-month follow-up period, three patients experienced ipsilateral, reversible neurologic events at 30, 45, and 120 days after CAS; none was associated with severe stent stenosis. No stent occlusions occurred, and no patient with >50% CAS stenosis on initial or subsequent testing developed a permanent ipsilateral permanent neurologic deficit or stroke-related death. DUS surveillance after CAS identified a 5% procedural failure rate due to the development of high-grade in-stent stenosis. Both progression and regression of stent stenosis severity was observed on serial testing, but 70% of CAS sites demonstrated velocity spectra consistent with <50% diameter reduction. The surveillance algorithm used, including reintervention for asymptomatic high-grade CAS stenosis, was associated with stent patency and the absence of disabling stroke.

Hypermethylation of p14 ARF May Be Predictive of Colitic Cancer in Patients with Ulcerative Colitis

The microsatellite instability and CpG island hypermethylation of p14 ( ARF ) and p16 ( INK4a ) are related to the pathogenesis of neoplasia in ulcerative colitis. This study was designed to assess the significance of those genetic or epigenetic alterations for cancer surveillance in ulcerative colitis. During surveillance colonoscopy in 39 patients with ulcerative colitis, biopsy specimens were obtained from the cecum and the rectum as well as from any other areas suspected of being neoplasia by chromoscopy. Using DNA extracts, the methylation status of p14 ( ARF ) and p16 ( INK4a ) and the microsatellite status were determined. Microsatellite instability was positive in one of five dysplasias, but it was negative in the cecum and the rectum. The incidence of hypermethylation of p14 ( ARF ) was 0 percent in the cecum, 26 percent in the rectum, and 100 percent in dysplasia, whereas that of p16 ( INK4a ) was 10, 10, and 0 percent, respectively. Patients who were positive for the hypermethylation of p14 ( ARF )in the rectum had a longer duration of ulcerative colitis than those who were negative for such hypermethylation. Two of 10 patients who were positive for p14 ( ARF ) hypermethylation in the rectum and 1 of 29 patients who were negative for the hypermethylation had dysplasia. During the subsequent surveillance of 36 patients, dysplasia was detected in 2 of 8 patients with p14 ( ARF ) hypermethylation and in none of 28 patients without hypermethylation (P = 0.044). In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia. The hypermethylation may be one of candidates for potential biomarker to identify patients at a high risk of dysplasia.

Coyotes as Sentinels for Monitoring Bovine Tuberculosis Prevalence in White‐Tailed Deer

Abstract: Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), is endemic in free‐ranging white‐tailed deer (Odocoileus virginianus) in 5 counties (Alcona, Alpena, Montmorency, Oscoda, and Presque Isle) in the northeastern Lower Peninsula of Michigan, USA. The presence of a wildlife reservoir of tuberculosis in Michigan and the incidence of bTB in cattle (Bos taurus) resulted in Michigan losing its bTB accredited‐free status. Subsequent wildlife surveillance programs identified relatively high disease prevalence in coyotes (Canis latrans), generating interest in their potential to serve as a sentinel species to detect bTB prevalence in white‐tailed deer. Our goal was to develop an empirical basis for generating hypotheses about the spatial epidemiology of bTB infection in coyotes for future surveillance, management, and modeling efforts. Though variation in coyote home‐range size may confound attempts to spatially correlate the incidence of disease in the sentinel and host species at a fine scale, overlap zones (OZs) between adjacent coyote home ranges may be the appropriate sample unit for spatially correlating disease prevalence in coyotes and white‐tailed deer. Because overlapping home ranges are generally configured around resource rich (e.g., small mammals and white‐tailed deer) timber management patches, the OZ concentrates spatial interaction between adjacent groups in a relatively small area. Furthermore, there is a direct relationship between interaction probabilities and the spatial dispersion of those patches. The latter finding provides a useful metric to incorporate into future efforts to develop spatially explicit models of bTB dynamics. Modeling efforts can then be used as a foundation to predict the epidemiological ramifications of alterations in intensively managed forested landscapes. (JOURNAL OF WILDLIFE MANAGEMENT 71(5):1545‐1554; 2007)

Role of Radioactive Iodine for Adjuvant Therapy and Treatment of Metastases

Normal thyrocytes and thyroid cancer cells are characterized by possession of a sodium iodide symporter. Radioiodine administration is a unique and powerful means of treating differentiated thyroid cancer because of the ability of thyroid cancer cells to concentrate beta-emitting radiolabeled iodine. Several manipulations, such as iodine depletion and thyroid hormone-stimulating hormone elevation, are used to enhance uptake of radiolabeled iodine by tumor cells. Adjuvant radioiodine therapy, given to patients without evidence of residual disease, enhances the sensitivity of subsequent surveillance and may decrease recurrence rates and mortality. However, its exact role in the management of low-risk patients merits further investigation. In contrast, radioactive iodine therapy used in patients with residual or metastatic disease clearly improves outcomes. Several studies show decreased recurrence and mortality rates in patients treated with radioiodine compared with those not receiving radioactive iodine. Adverse events from radioiodine therapy include salivary gland dysfunction, bone marrow suppression, and reproductive disturbances. Side effects of radioiodine therapy are generally greater when higher activities of radioiodine are used and may be transient or permanent. Secondary malignancies also may occur after radioiodine therapy. These side effects must be weighed against potential benefits, especially when radioactive iodine is used as adjuvant therapy. Stimulation of the expression of the sodium iodide symporter, or its introduction de novo into nonthyroid cells, is promising in treating poorly differentiated thyroid cancer and nonthyroid malignancies, respectively.

Serogroup X in Meningococcal Disease, Western Kenya

To the Editor: Although >12 different serogroups of Neisseria meningitidis exist, most disease outbreaks across the African meningitis epidemic belt are caused by serogroup A and, less frequently, by serogroups C and W135 (1). N. meningitidis serogroup X was first described in the 1960s and has been found to cause a few cases of invasive disease across North America, Europe, and Africa (2). In Africa, small serogroup X outbreaks have been described in Ghana (9 cases over a 2-year period) and in Niger (134 cases between 1995 and 2000) (3,4). In 2006, however, 51% of 1,139 confirmed cases of meningococcal meningitis in Niger were found to be caused by serogroup X (5). Before the 2005-06 meningococcal epidemic season, no published reports had described serogroup X isolates in East Africa. We report the involvement of N. meningitidis serogroup X in an outbreak of meningococcal disease in Western Kenya. In January 2006, the Ministry of Health of Kenya and Medecins sans Frontieres were notified of a suspected meningococcal disease outbreak in West Pokot District, bordering Uganda, in Western Kenya. On the basis of the initial outbreak investigation, the outbreak was assessed to have begun in late December 2005. Subsequent active surveillance, using the same clinical case definition of sudden fever onset with stiff neck, altered mental status, or both, showed 74 suspected cases through mid-March 2006, with a case-fatality rate of 20%. No cases were reported after March 2006. Over the course of the outbreak, cerebrospinal fluid samples were obtained from 18 patients. Due to low population density, poor access to seminomadic populations, and the limited nature of the outbreak (relatively small numbers dispersed over a wide geographic region), obtaining specimens from untreated patients in West Pokot proved difficult. Three of the 5 first samples were found to show gram-negative diplococci on staining, the next 2 were negative on Pastorex rapid latex agglutination test (Bio-Rad Laboratories, Hercules, CA, USA) (during the outbreak investigation), and a subsequent 13 were sent to the African Medical and Research Foundation (AMREF) laboratory in Nairobi, Kenya, for culture and susceptibility testing. From these 13 specimens, 2 yielded a pure growth of N. meningitidis serogroup X, while no growth was observed for the remaining 11 specimens. These 2 cultures were subsequently confirmed as serogroup X by the World Health Organization Collaborating Centre for Meningococci in Oslo, Norway. Multilocus sequence typing and sequencing of the porA and fetA genes as described (http://pubmlst.org/neisseria/), showed that the infecting strain belonged to a new sequence type, ST-5403, and that it was subtype P1.19,26 and FetA type F3-27. This sequence type is unrelated to other serogroup X isolates from Africa, including those from the latest serogroup X outbreak in Niger, but it resembles a sequence type isolated in the United States in the 1970s. In addition to the testing at AMREF and in the Oslo laboratory, the 13 samples were also analyzed by PCR at the US Naval Medical Research Unit No. 3 in Cairo, Egypt. Overall, 5 of these 13 specimens were positive for serogroup X (including the 2 samples found to be serogroup X at AMREF and confirmed by PCR in Oslo) and 1 each was positive for serogroups C, W135, and Y. At the same time as this outbreak in Western Kenya, a meningococcal meningitis outbreak was being monitored across the border in the Karamoja region of northeastern Uganda. Seminomadic populations move freely across the 2 countries, and we can assume that there was 1 meningitis outbreak that started in eastern Uganda and spread to Western Kenya. Although initial laboratory testing in Uganda suggested the presence of serogroup A, among 23 specimens subsequently sent to the Oslo laboratory, 11 were identified as serogroup X by PCR and 3 were serogroup W135 (6). Therefore, the outbreaks in both Kenya and Uganda involved multiple N. meningitidis serogroups. In West Pokot, Kenya, the Ministry of Health and Medecins sans Frontieres conducted a vaccination campaign using the trivalent polysaccharide vaccine against serogroups A, C, and W135. Before 2006, previous disease outbreaks caused by serogroup X had not reached the magnitude of those caused by serogroups A, C, or W135; they tended to evolve independently of the occurrence of both serogroups A and C and to be self-limited (3,4). Although most of Kenya is not included in the African meningitis belt, large epidemics of meningococcal disease have been reported previously (7). In conclusion, we would like to highlight the presence of N. meningitidis serogroup X in East Africa, its potential involvement in disease outbreaks, and the difficulties it may cause for laboratory confirmation and, consequently, for making an appropriate epidemic response.