Shama D. Ahuja

Risk Factors for Sporadic Campylobacter Infection in the United States: A Case-Control Study in FoodNet Sites

Campylobacter is a common cause of gastroenteritis in the United States. We conducted a population-based case-control study to determine risk factors for sporadic Campylobacter infection. During a 12-month study, we enrolled 1316 patients with culture-confirmed Campylobacter infections from 7 states, collecting demographic, clinical, and exposure data using a standardized questionnaire. We interviewed 1 matched control subject for each case patient. Thirteen percent of patients had traveled abroad. In multivariate analysis of persons who had not traveled, the largest population attributable fraction (PAF) of 24% was related to consumption of chicken prepared at a restaurant. The PAF for consumption of nonpoultry meat that was prepared at a restaurant was also large (21%); smaller proportions of illness were associated with other food and nonfood exposures. Efforts to reduce contamination of poultry with Campylobacter should benefit public health. Restaurants should improve food-handling practices, ensure adequate cooking of meat and poultry, and consider purchasing poultry that has been treated to reduce Campylobacter contamination.

Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

The broadest pattern of tuberculosis drug resistance for which a consensus definition exists is extensively drug-resistant tuberculosis (XDR-TB). It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR-alone and three non-mutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) capreomycin and kanamycin/amikacin (XDR+2sli); XDR plus resistance to second-line injectables and to ≥1 Group 4 drug, i.e. : ethionamide/prothionamide, cycloserine/terizidone or PAS (XDR+sliG4); and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR-alone; 68 XDR+2sli; 48 XDR+sliG4; and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted Odds Ratio (aOR): 0.4; 95% Confidence Interval: 0.2–0.8) compared to XDR-alone, while odds of failure+death were higher in all XDR patients with additional resistance (aOR range: 2.6–2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current DST methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2–0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6–2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

Farm Visits and Undercooked Hamburgers as Major Risk Factors for Sporadic Escherichia coli O157:H7 Infection: Data from a Case-Control Study in 5 FoodNet Sites

In 1996, active surveillance in 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites revealed up to a 9-fold difference in Escherichia coli O157:H7 (O157) infection incidence between sites. A matched case-control study of sporadic O157 cases was conducted in these sites from March 1996 through April 1997. Case subjects were patients with non-outbreak-related diarrheal illness who had O157 isolated from their stool samples. Control subjects were healthy persons matched by age and telephone number exchange. Overall, 196 case patients and 372 controls were enrolled. O157 infections were associated with farm exposure, cattle exposure, eating a pink hamburger (both at home and away from home), eating at a table-service restaurant, using immunosuppressive medication, and obtaining beef through a private slaughter arrangement. Variations in cattle exposures may explain a part of the regional variability of O157 infection incidence. O157 control measures should focus on reducing risks associated with eating undercooked hamburger, dining at table-service restaurants, and farm exposures.

Egg Consumption is the Principal Risk Factor for Sporadic Salmonella Serotype Heidelberg Infections: A Case-Control Study in FoodNet Sites

To determine risk factors for sporadic Salmonella serotype Heidelberg diarrheal disease, we conducted a population-based case-control study in 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas in 1996-1997. Forty-four case patients and 83 control subjects matched by age and telephone exchange were asked about exposures during the 5-day period before onset of illness in the case patient. Risk factors for infection were evaluated using conditional logistic regression analysis. Eating eggs prepared outside the home remained the only significant risk factor for illness (matched odds ratio [MOR], 6.0; 95% confidence interval [CI], 1.2-29.6). The population-attributable fraction of S. Heidelberg infections associated with eating eggs prepared outside the home was 37%. Eliminating the risk associated with out-of-home egg consumption could substantially reduce the incidence of S. Heidelberg infections. Control measures to prevent S. Heidelberg infection should include advising consumers to avoid eating undercooked eggs and educating food handlers about proper egg handling and cooking.

Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000–06

UNLABELLED Rationale Linezolid may be effective for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious adverse events are common and there is little information on the management of these toxicities. METHODS We retrospectively reviewed public health and medical records of 16 MDR TB patients, including 10 patients with XDR TB, who were treated with linezolid in New York City between January 2000 and December 2006, to determine treatment outcomes and describe the incidence, management and predictors of adverse events. RESULTS Linezolid was added to MDR TB regimens for a median duration of 16 months (range: 1-29). Eleven patients (69%) completed treatment, four (25%) died and one (6%) discontinued treatment without relapse. Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11) after starting linezolid, gastrointestinal adverse events occurred in 13 (81%) patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events were managed by combinations of temporary suspension of linezolid, linezolid dose reduction and symptom management. Five (31%) patients required eventual discontinuation of linezolid. Myelosuppression was more responsive to clinical management strategies than was neurotoxicity. Leucopenia and neuropathy occurred more often in males and older age was associated with thrombocytopenia (P < 0.05). CONCLUSIONS The majority of MDR TB patients on linezolid had favourable treatment outcomes, although treatment was complicated by adverse events that required extensive clinical management.

Active Case Finding and Prevention of Tuberculosis Among a Cohort of Contacts Exposed to Infectious Tuberculosis Cases in New York City

BACKGROUND Tuberculosis contact investigation identifies individuals who may be recently infected with tuberculosis and are thus at increased risk for disease. Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis to prevent active disease; however, the effectiveness of this intervention is unclear as treatment completion is generally low. METHODS A retrospective cohort study of 30 561 contacts identified during investigation of 5182 cases of tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched the NYC tuberculosis registry to identify contacts developing active tuberculosis within 4 years of follow-up. We estimated the following: number of contacts undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per prevalent case diagnosed; number of contacts with LTBI that need to be treated with standard chemoprophylaxis to prevent 1 active case. RESULTS Of 30 561 contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102 contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90-115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who did not complete treatment. During 4 years of follow-up, active tuberculosis was diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI, .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis case (95% CI, 53-164). CONCLUSIONS Contact investigation facilitates active case finding and tuberculosis prevention, even when completion rates of chemoprophylaxis are suboptimal.

Rifapentine for the Treatment of Pulmonary Tuberculosis

Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.

Distinct clinical and epidemiological features of tuberculosis in New York City caused by the RD Rio Mycobacterium tuberculosis sublineage

BACKGROUND Genetic tracking of Mycobacterium tuberculosis is a cornerstone of tuberculosis (TB) control programs. The RD(Rio) M. tuberculosis sublineage was previously associated with TB in Brazil. We investigated 3847 M. tuberculosis isolates and registry data from New York City (NYC) (2001-2005) to: (1) affirm the position of RD(Rio) strains within the M. tuberculosis phylogenetic structure, (2) determine its prevalence, and (3) define transmission, demographic, and clinical characteristics associated with RD(Rio) TB. METHODS Isolates classified as RD(Rio) or non-RD(Rio) M. tuberculosis by multiplex PCR were further classified as clustered (≥2 isolates) or unique based primarily upon IS6110-RFLP patterns and lineage-specific cluster proportions were calculated. The secondary case rate of RD(Rio) was compared with other prevalent M. tuberculosis lineages. Genotype data were merged with the data from the NYC TB Registry to assess demographic and clinical characteristics. RESULTS RD(Rio) strains were found to: (1) be restricted to the Latin American-Mediterranean family, (2) cause approximately 8% of TB cases in NYC, and (3) be associated with heightened transmission as shown by: (i) a higher cluster proportion compared to other prevalent lineages, (ii) a higher secondary case rate, and (iii) cases in children. Furthermore, RD(Rio) strains were significantly associated with US-born Black or Hispanic race, birth in Latin American and Caribbean countries, and isoniazid resistance. CONCLUSIONS The RD(Rio) genotype is a single M. tuberculosis strain population that is emerging in NYC. The findings suggest that expanded RD(Rio) case and exposure identification could be of benefit due to its association with heightened transmission.

Mycobacterium tuberculosis cluster with developing drug resistance, New York, New York, USA, 2003-2009.

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003–2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.