Susan A. Maloney

Efficacy of Control Measures in Preventing Nosocomial Transmission of Multidrug-Resistant Tuberculosis to Patients and Health Care Workers

Nosocomial transmission of Mycobacterium tuberculosis, particularly transmission of multidrug-resistant strains, to patients and health care workers is a major public health problem [1-12]. From 1990 through 1992, the Centers for Disease Control and Prevention (CDC) investigated eight outbreaks of multidrug-resistant tuberculosis in U.S. hospitals (1-6; CDC, unpublished data). More than 300 patients with multidrug-resistant tuberculosis were identified during these investigations; most (87%) were infected with human immunodeficiency virus (HIV). Their clinical course was characterized by rapid progression from infection to active tuberculosis and their mortality rate was high [9]. Additionally, more than 100 health care workers at hospitals where outbreaks of multidrug-resistant tuberculosis had occurred had conversion of their tuberculin skin tests, suggesting recently acquired M. tuberculosis infection. At least 17 of these newly infected health care workers developed active multidrug-resistant M. tuberculosis, and at least 7 of them died with multidrug-resistant tuberculosis [10]. Because of the explosive and fatal nature of these recent nosocomial outbreaks of multidrug-resistant tuberculosis, questions have been raised about the most effective interventions and control measures necessary to prevent institutional transmission of tuberculosis [13-15]. We evaluated the efficacy of control measures for decreasing the transmission of these multidrug-resistant M. tuberculosis strains in one of the hospitals that had had an outbreak. Methods In May 1991, we investigated an outbreak of multidrug-resistant tuberculosis at Cabrini Medical Center, a teaching hospital in New York City. In that investigation, epidemiologic and laboratory data showed the occurrence of nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers [5]. Risk factors for acquisition of multidrug-resistant tuberculosis by patients included age, HIV seropositivity, and hospital admission to Cabrini Medical Center within 7 months before onset of multidrug-resistant tuberculosis. Additionally, health care workers assigned to the medical or HIV wards (primary wards housing patients with tuberculosis) were identified as being at increased risk for tuberculin skin test conversion. Conditions facilitating tuberculosis transmission included delayed identification, isolation, or treatment of patients with infectious tuberculosis; lapses in tuberculosis isolation practices; and inadequate isolation facilities for patients with tuberculosis. In response to the outbreak, control measures similar to those recommended in the CDCs 1990 tuberculosis guidelines were instituted to prevent further nosocomial transmission of tuberculosis [16]. Control Measures Numerous measures were introduced to decrease transmission of multidrug-resistant tuberculosis, including source controls, environmental controls, and respiratory protection for health care workers (Table 1). Source control measures included improved isolation precautions and expanded treatment regimens for patients with suspected or confirmed tuberculosis and included routine use of acid-fast bacilli smears to determine length of isolation and to establish treatment efficacy. To expedite the identification of patients with infectious tuberculosis and the determination of the antimicrobial susceptibility of M. tuberculosis isolates, laboratory procedures were also modified. Thus, personnel and workday hours devoted to processing of mycobacterial isolates were expanded; a hospital-wide computerized database of patients with tuberculosis was developed; a gene probe was introduced; and the reporting of acid-fast bacilli smear results to requesting physicians was standardized. Table 1. Infection Control Measures* Environmental modifications included installing exhaust fans in isolation rooms to increase the number of acid-fast bacilli isolation rooms with negative pressure and included using portable Aeroguard (HR Incorporated, Bellevue, Washington) chambers to do cough-inducing procedures, such as sputum induction or aerosolized pentamidine administration. Finally, to further decrease the risk for occupational acquisition of tuberculosis, the respiratory protection worn by health care workers was changed from nonmolded to molded surgical masks (3M 1800+ Aseptex, 3M Incorporated, St. Paul, Minnesota). To assess compliance with these control measures, we examined the hospitals isolation facilities, reviewed patient charts for documentation of initiation and discontinuation of acid-fast bacilli isolation precautions, interviewed infection control and laboratory personnel, observed isolation practices on hospital wards containing patients with tuberculosis, and evaluated the ventilation system in acid-fast bacilli isolation rooms by testing air-flow direction using smoke tubes. Epidemiologic Studies A case-patient was defined as any Cabrini Medical Center patient whose M. tuberculosis isolate was resistant to at least isoniazid and rifampin and as any patient whose clinical course was consistent with active tuberculosis during the study period (1 January 1990 to 11 August 1992). Case-patients and all other patients with tuberculosis were identified by reviewing Cabrini Medical Center laboratory and infection control records during the study period. Medical records of all potential case-patients were reviewed to verify a clinical course consistent with tuberculosis. To determine whether a decrease had occurred in the incidence of multidrug-resistant tuberculosis after the institution of control measures, we compared the proportion of patients with tuberculosis who had multidrug-resistant strains before (preintervention period) and after (intervention period) the implementation of control measures. The preintervention period (January 1990 to June 1991) was defined as the time from the onset of the outbreak until the formal institution of recommended control measures; the intervention period (July 1991 to 11 August 1992) was defined as the time during and after the institution of recommended control measures until our follow-up study. Patient-to-Patient Transmission To investigate possible patient-to-patient transmission of multidrug-resistant tuberculosis, we evaluated case-patient medical records to determine if case-patients had been hospitalized at Cabrini Medical Center within 7 months before onset of tuberculosis. For those case-patients who had been previously hospitalized, we determined whether they had been hospitalized on the same ward at the same time or whether they had a documented nosocomial exposure to another patient with culture-confirmed multidrug-resistant tuberculosis during a previous hospitalization. Data collected included age, sex, race, HIV serologic status, previous opportunistic infections, dates and results of acid-fast bacilli smears and mycobacterial cultures, M. tuberculosis antimicrobial susceptibilities, dates of admission and discharge, hospital room assignments, dates of isolation for tuberculosis, nursing documentation of proper application of isolation precautions, antituberculous medications prescribed, clinical course, and outcome. Patient-to-Health Care Worker Transmission To evaluate whether the risk for transmission of multidrug-resistant tuberculosis from patients to health care workers had been reduced, we compared conversion rates of tuberculin skin tests in health care workers during the preintervention and intervention periods. During both periods, the tuberculin skin testing program at Cabrini Medical Center required annual testing of all hospital employees and additional testing of health care workers after a known tuberculosis exposure. A tuberculin skin test conversion was defined as induration of 10 mm or more to purified protein derivative in a Cabrini Medical Center employee with a documented tuberculin skin test result that was negative within the previous 24 months. Employees without negative skin test results at baseline were excluded from our analyses. Conversion rates were compared by period, by job category (frequent direct patient contact compared with infrequent or no direct patient contact), and by ward assignment (primary wards housing patients with tuberculosis [medical and HIV wards] compared with wards infrequently housing patients with tuberculosis). Health care workers with direct patient contact included physicians, nurses, nursing aides, respiratory therapists, and social workers; workers without direct patient contact included administrative staff, clerks, dieticians, housekeepers, engineers, and laboratory personnel. Health care workers with tuberculin skin-test conversions or active tuberculosis or both were identified by reviewing employee health and infection control records during the study period. Data collected included age, sex, race, history of bacille CalmetteGurin (BCG) vaccination or tuberculosis exposure or both, country of origin, job title, duration of employment, and work location at time of tuberculin skin-test conversion. Statistical Analysis Data were collected on standardized forms, entered into Epi Info Version 5.01b software, and analyzed [17]. Categorical variables were compared by the Fisher exact or chi-square test, and relative risks (RRs) were calculated. Continuous variables were compared by the Student t-test or the Kruskal-Wallis rank-sum test. Results Case-Patients Forty patients met the case definition (Figure 1). Case-patients in the preintervention and intervention periods were similar in age, race, sex, HIV serologic status, and diagnosis of AIDS (data not shown). However, case-patient mortality decreased in the intervention compared with the preintervention period (4 of 10 [40%] compared with 25 of 30 [83%] deaths; P = 0.01). Further, in the preintervention period, 20 of 25 (80%) case-patient deaths were attributed to tuberculosis, whereas in the intervention period, only

Incidence, Seasonality and Mortality Associated with Influenza Pneumonia in Thailand: 2005–2008

Background Data on the incidence, seasonality and mortality associated with influenza in subtropical low and middle income countries are limited. Prospective data from multiple years are needed to develop vaccine policy and treatment guidelines, and improve pandemic preparedness. Methods During January 2005 through December 2008, we used an active, population-based surveillance system to prospectively identify hospitalized pneumonia cases with influenza confirmed by reverse transcriptase–polymerase chain reaction or cell culture in 20 hospitals in two provinces in Thailand. Age-specific incidence was calculated and extrapolated to estimate national annual influenza pneumonia hospital admissions and in-hospital deaths. Results Influenza was identified in 1,346 (10.4%) of pneumonia patients of all ages, and 10 influenza pneumonia patients died while in the hospital. 702 (52%) influenza pneumonia patients were less than 15 years of age. The average annual incidence of influenza pneumonia was greatest in children less than 5 years of age (236 per 100,000) and in those age 75 or older (375 per 100,000). During 2005, 2006 and 2008 influenza A virus detection among pneumonia cases peaked during June through October. In 2007 a sharp increase was observed during the months of January through April. Influenza B virus infections did not demonstrate a consistent seasonal pattern. Influenza pneumonia incidence was high in 2005, a year when influenza A(H3N2) subtype virus strains predominated, low in 2006 when A(H1N1) viruses were more common, moderate in 2007 when H3N2 and influenza B co-predominated, and high again in 2008 when influenza B viruses were most common. During 2005–2008, influenza pneumonia resulted in an estimated annual average 36,413 hospital admissions and 322 in-hospital pneumonia deaths in Thailand. Conclusion Influenza virus infection is an important cause of hospitalized pneumonia in Thailand. Young children and the elderly are most affected and in-hospital deaths are more common than previously appreciated. Influenza occurs year-round and tends to follow a bimodal seasonal pattern with substantial variability. The disease burden varies significantly from year to year. Our findings support a recent Thailand Ministry of Public Health (MOPH) decision to extend annual influenza vaccination to older adults and suggest that children should also be targeted for routine vaccination.

The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study

The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.

Bartonella tamiae sp. nov., a Newly Recognized Pathogen Isolated from Three Human Patients from Thailand

ABSTRACT Three strains of a novel Bartonella species (Bartonella tamiae) were isolated from human patients from Thailand. Sequence analysis of six chromosomal regions (16S rRNA, gltA, groEL, ftsZ, rpoB, and the intergenic spacer region) and phenotypical analysis supported the similarity of the three strains and placed them within the genus Bartonella separately from previously described species.

SARS in Healthcare Facilities, Toronto and Taiwan

The healthcare setting was important in the early spread of severe acute respiratory syndrome (SARS) in both Toronto and Taiwan. Healthcare workers, patients, and visitors were at increased risk for infection. Nonetheless, the ability of individual SARS patients to transmit disease was quite variable. Unrecognized SARS case-patients were a primary source of transmission and early detection and intervention were important to limit spread. Strict adherence to infection control precautions was essential in containing outbreaks. In addition, grouping patients into cohorts and limiting access to SARS patients minimized exposure opportunities. Given the difficulty in implementing several of these measures, controls were frequently adapted to the acuity of SARS care and level of transmission within facilities. Although these conclusions are based only on a retrospective analysis of events, applying the experiences of Toronto and Taiwan to SARS preparedness planning efforts will likely minimize future transmission within healthcare facilities.

Overseas Screening for Tuberculosis in U.S.-Bound Immigrants and Refugees

BACKGROUND In 2007, a total of 57.8% of the 13,293 new cases of tuberculosis in the United States were diagnosed in foreign-born persons, and the tuberculosis rate among foreign-born persons was 9.8 times as high as that among U.S.-born persons (20.6 vs. 2.1 cases per 100,000 population). Annual arrivals of approximately 400,000 immigrants and 50,000 to 70,000 refugees from overseas are likely to contribute substantially to the tuberculosis burden among foreign-born persons in the United States. METHODS The Centers for Disease Control and Prevention (CDC) collects information on overseas screening for tuberculosis among U.S.-bound immigrants and refugees, along with follow-up evaluation after their arrival in the United States. We analyzed screening and follow-up data from the CDC to study the epidemiology of tuberculosis in these populations. RESULTS From 1999 through 2005, a total of 26,075 smear-negative cases of tuberculosis (i.e., cases in which a chest radiograph was suggestive of active tuberculosis but sputum smears were negative for acid-fast bacilli on 3 consecutive days) and 22,716 cases of inactive tuberculosis (i.e., cases in which a chest radiograph was suggestive of tuberculosis that was no longer clinically active) were diagnosed by overseas medical screening of 2,714,223 U.S.-bound immigrants, representing prevalences of 961 cases per 100,000 persons (95% confidence interval [CI], 949 to 973) and 837 cases per 100,000 persons (95% CI, 826 to 848), respectively. Among 378,506 U.S.-bound refugees, smear-negative tuberculosis was diagnosed in 3923 and inactive tuberculosis in 10,743, representing prevalences of 1036 cases per 100,000 persons (95% CI, 1004 to 1068) and 2838 cases per 100,000 persons (95% CI, 2785 to 2891), respectively. Active pulmonary tuberculosis was diagnosed in the United States in 7.0% of immigrants and refugees with an overseas diagnosis of smear-negative tuberculosis and in 1.6% of those with an overseas diagnosis of inactive tuberculosis. CONCLUSIONS Overseas screening for tuberculosis with follow-up evaluation after arrival in the United States is a high-yield intervention for identifying tuberculosis in U.S.-bound immigrants and refugees and could reduce the number of tuberculosis cases among foreign-born persons in the United States.

Identification of Bartonella Infections in Febrile Human Patients from Thailand and Their Potential Animal Reservoirs

To determine the role of Bartonella species as causes of acute febrile illness in humans from Thailand, we used a novel strategy of co-cultivation of blood with eukaryotic cells and subsequent phylogenetic analysis of Bartonella-specific DNA products. Bartonella species were identified in 14 blood clots from febrile patients. Sequence analysis showed that more than one-half of the genotypes identified in human patients were similar or identical to homologous sequences identified in rodents from Asia and were closely related to B. elizabethae, B. rattimassiliensis, and B. tribocorum. The remaining genotypes belonged to B. henselae, B. vinsonii, and B. tamiae. Among the positive febrile patients, animal exposure was common: 36% reported owning either dogs or cats and 71% reported rat exposure during the 2 weeks before illness onset. The findings suggest that rodents are likely reservoirs for a substantial portion of cases of human Bartonella infections in Thailand.

The burden of hospitalized lower respiratory tract infection due to respiratory syncytial virus in rural Thailand.

Background We describe the epidemiology of hospitalized RSV infections for all age groups from population-based surveillance in two rural provinces in Thailand. Methods From September 1, 2003 through December 31, 2007, we enrolled hospitalized patients with acute lower respiratory tract illness, who had a chest radiograph ordered by the physician, from all hospitals in SaKaeo and Nakhom Phanom Provinces. We tested nasopharyngeal specimens for RSV with reverse transcriptase polymerase chain reaction (RT-PCR) assays and paired-sera from a subset of patients with IgG enzyme immunoassay. Rates were adjusted for enrollment. Results Among 11,097 enrolled patients, 987 (8.9%) had RSV infection. Rates of hospitalized RSV infection overall (and radiographically-confirmed pneumonia) were highest among children aged <1 year: 1,067/100,000 (534/100,000 radiographically-confirmed pneumonia) and 1–4 year: 403/100,000 (222/100,000), but low among enrolled adults aged ≥65 years: 42/100,000. Age <1 year (adjusted odds ratio [aOR]  = 13.2, 95% confidence interval [CI] 7.7, 22.5) and 1–4 year (aOR = 8.3, 95% CI 5.0, 13.9) were independent predictors of hospitalized RSV infection. Conclusions The incidence of hospitalized RSV lower respiratory tract illness among children <5 years was high in rural Thailand. Efforts to prevent RSV infection could substantially reduce the pneumonia burden in children aged <5 years.

Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.

Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand

Please cite this paper as: Simmerman et al. (2011) Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand. Influenza and Other Respiratory Viruses 5(4), 256–267