Faculty Bibliography

BACKGROUND: A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. METHODOLOGY/PRINCIPAL FINDINGS: We monitored the response to 48-week ART in 100 treatment-naive Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. CONCLUSION: The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure

BACKGROUND: S-adenosylmethionine (AdoMet) is a key molecule involved in methylation reactions and polyamine synthesis. Pneumocystis carinii are unable to synthesize this molecule and have been shown to scavenge this metabolic intermediate from the plasma of rats during active infection. A prior study involving humans strongly suggested that low levels of plasma AdoMet are sensitive and specific indicators of acute infection. METHODS: From March 2004 through January 2006, we collected plasma AdoMet levels from patients with human immunodeficiency virus (HIV) infection and either confirmed Pneumocystis carinii pneumonia (PCP), confirmed pulmonary tuberculosis, or confirmed bacterial pneumonia. We compared levels in patients with PCP with those in patients with other diseases and also monitored changes in levels during treatment of PCP. RESULTS: Initial AdoMet levels were significantly lower in patients with PCP, and there was no overlap between the groups. Among patients with PCP, levels of AdoMet increased with successful treatment. CONCLUSIONS: Measurement of plasma AdoMet levels in patients with HIV infection who have pulmonary infections can identify those with PCP

BACKGROUND: Most cases of tuberculosis (TB) in the United States are diagnosed in foreign-born persons, and undocumented foreign-born persons may face particular barriers to timely access to health care services. This study investigates whether differences in clinical presentations among persons with pulmonary TB are associated with foreign birth or documentation status. METHODS: In this cross-sectional study, we reviewed the medical records of patients who had received a diagnosis of microbiologically proven pulmonary TB at a New York City public hospital during the period April 1999 through March 2005. Three groups of patients with pulmonary TB (US-born persons, foreign-born persons with documents, and undocumented, foreign-born persons) were defined and compared at presentation. Odds ratios (ORs) for a symptom duration >or=8 weeks before hospital admission for each group were estimated using logistic regression. RESULTS: Among 194 subjects with newly diagnosed pulmonary TB, 61 (31%) were US born, 62 (32%) were documented foreign-born persons, and 71 (37%) were undocumented foreign-born persons. Undocumented foreign-born persons presented with significantly higher frequencies of cough (P = .020) and hemoptysis P = .012 and had a significantly longer median duration of symptoms, compared with US-born persons (8 vs. 4 weeks; P = .023). No statistically significant differences between documented foreign-born and US-born persons were observed. Multivariate analysis revealed that undocumented status (compared with being US born; adjusted OR, 4.1; 95% confidence interval, 1.7-10.2; P = .0002) and being unemployed (adjusted OR, 2.2; 95% CI, 1.1-4.5; P = .023) were independently associated with a prolonged symptom duration (i.e., >or=8 weeks). CONCLUSIONS: Undocumented status was associated with an increased frequency of cough and hemoptysis and a longer duration of symptoms before medical evaluation for pulmonary TB. Whether reducing barriers to health services for undocumented foreign-born persons could enhance TB control deserves additional study

OBJECTIVE: The authors conducted a retrospective cohort study to determine the incidence, bacteriological features, and risk factors for postcraniotomy meningitis. METHODS: Patients older than 18 years who underwent nonstereotactic craniotomies between January 1996 and March 2000 and who survived for more than 7 days were included. Operations for placement of burr holes and shunts were excluded. Records of the first 30 postoperative days were abstracted. Host factors, types of craniotomy, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTS: Among 453 patients, there were 25 cases of meningitis. Eight out of 12 culture-positive cases were the result of gram-positive cocci. Four hundred twenty (92%) patients received antibiotic prophylaxis, most commonly a first-generation cephalosporin. In multivariate analysis, the risk of meningitis was increased by surgery that entered a sinus (odds ratio [OR], 4.49; P = 0.018), an increase in the American Society of Anesthesiologists score (OR, 1.72; P = 0.023), and increases in the number of days of external ventricular drainage (OR, 1.21; P = 0.049) and intracranial pressure monitoring (OR, 1.24; P = 0.002). CONCLUSION: Access of upper airway bacteria to the surgical wound, host factors as expressed by the American Society of Anesthesiologists score, and duration of device-related postoperative communication of the cerebrospinal fluid and the environment are major risk factors for postoperative meningitis after craniotomy

The 81-kDa malate synthase (MS; Rv 1837c) and the 27-kDa MPT51 (Rv 3803c) of Mycobacterium tuberculosis are immunodominant antigens recognized by serum antibodies from approximately 80% of human immunodeficiency virus-negative smear-positive tuberculosis patients from India. We now provide evidence that the use of the MS/MPT51-based serodiagnostic assay can serve as an adjunct to sputum microscopy in the rapid diagnosis of pulmonary tuberculosis

Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2+/-14.7 years), the mean period of residence in the United States was 11.9+/-7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR) =2.3, 95% confidence interval (95% CI) =1.05-5.0] and inverse associations with period in the United States (OR per year of residency in the United States =0.95, 95% CI =0.91-0.99) and with a history of dyspepsia (OR for a history of stomach pain =0.52, 95% CI =0.3-1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.