Nosocomial transmission of tuberculosis among mentally-handicapped patients in a long-term care facility

Tubercle and Lung Disease (1996) 77, 531-536 © 1996 PearsonProfessionalLtd

Nosocomial transmission of tuberculosis among mentally-handicapped patients in a long-term care facility N. Lemaltre*, W. Sougakoff*, D. Co~tmeur t, J. VauceF, V. Jarlier*, J. Grosset* *Laboratoire de Bactdriologie, Centre National de R~fdrence de la TubercuIose et des Infections g~Mycobactdries Atypiques, Groupe Hospitalier Pitid-SalpOtriOre, Paris, France, tCentre Hospitalier, Saint-Brieuc, France S U M M A R Y Setting: A long-term care facility at Saint-Brieuc hospital, France. Objective: To investigate a nosocomial outbreak of culture-positive pulmonary tuberculosis in 6 (40%) of 15 mentally handicapped HIV-seronegative patients. Design: The factors contributing to the outbreak were analyzed and the restriction fragment length polymorphism (RFLP) patterns of the six Mycobacterium tuberculosis strains were compared. Results: RFLP analysis of the six strains demonstrated an identical banding pattern, thus confirming the spread of a unique strain. A prolonged period of contagiousness due to a delay in diagnosis of the source patient, as well as crowded living conditions in the facility, probably contributed to the outbreak. Surveillance of residents and staff in contact with the source patient resulted in the detection of five secondary cases. Because effective isolation of mentally handicapped patients in the long-term care facility turned out to be difficult, the six case-patients were transferred to the pneumology department, thus limiting the spread of tuberculosis to other residents and staff. Conclusions: The present outbreak emphasizes the difficulties of implementing control measures for preventing the nosocomial transmission of tuberculosis in long-term care facilities for mentally handicapped patients. R J~ S U M E. Cadre: Service de long s~jour h l'h6pital de Saint Brieuc, France. Objectif: Etudier une micro~pid~mie nosocomiale de tuberculose pulmonaire, bact~riologiquement prouv~e, chez 6 (40%) des 15 sujets VIH-s~ron~gatifs handicap~s mentaux. Schgma: Les facteurs ayant contribu~s h la micro~pid~mie ont ~t~ analys~s et les profils R F L P des 6 souches de Mycobacterium tuberculosis ont ~t~ compares. R~sultats: L'analyse par RFLP des 6 souches a mis en ~vidence des profils RFLP identiques, confirmant ainsi la transmission d'une souche unique. La dur~e prolong~e de contagiosit~ due au d~lai de diagnostic du patient index ainsi que la promiscuit~ des patients dans le service de long s~jour ont contribu~ h la micro~pid~mie. La surveillance des r~sidents et du personnel au contact avec le patient index ont permis la d~tection de 5 cas secondaires. Comme l'isolement efficace de ces patients handicap~s mentaux dans le service de long s~jour s'av~rait difficile, les 6 patients ont ~t~ transforms dans le d~partement de pneumologie, ce qui a limit~ la diffusion de la tuberculose parmi les autres r~sidents et parmi le personnel. Conclusion: La micro~pid~mie actuelle fait ressortir les difficult~s de mise en oeuvre des mesures de contr61e pour pr~venir la transmission nosocomiale de la tuberculose dans les services de long s~jour pour les patients handicap~s mentaux. R E S U M E N. Marco de referencia: Centro de atenci6n prolongada del Hospital Saint-Brieuc, Francia. Objetivo: Investigar un foco nosocomial de tuberculosis pulmonar con cultivo positivo en seis (40%) de quince pacientes con insuficiencia mental, VIH seronegativos. M~todo: Los factores que contribuyeron a la aparici6n de este foco fueron analizados y se compararon los patrones de R F L P (restriction fragment length polymorphism) de las seis cepas de Mycobacterium tuberculosis. Resultados: E1 anfilisis del R F L P de las seis cepas mostr6 un patr6n de bandas id~ntico, confirmando asi que se Correspondenceto: W. Sougakoff,Laboratoirede Bact6fiologie, Facult6 de M6decinePifi6-Salp&ribre,Universit6Pierre et Marie Curie, 91, boulevardde l'H6pital, 75634 Paris cedex 13, France. Paper received 7 December 1995. Finalversion accepted20 June 1996. 531

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trat6 de un eontagio a partir de una cepa dnica. Una duracirn prolongada de la fase de contagio debido a un retardo del diagnrstico en el paciente iudice, asi como un cierto hacinamiento del ceutro, probablemente contribuyeron a la aparicirn del foco. El control de los residentes y del personal en contacto con el paciente indice signific6 la deteccirn de cinco casos secundarios. Debido a que un aislamiento eficaz de estos pacientes con insuficiencia mental era m u y dificil dadas ias condiciones del centro de atencirn prolongada, los seis pacientes fueron trasladados al departamento de neumologla, evitando asi la propagacirn de la tuberculosis a otros residentes y al personal del centro. Conclusiones: La existeucia de este foco subraya las dificultades para la puesta en prfictica de medidas de control para prevenir la transmisirn nosocomial de la tuberculosis en las estructuras de hospitalizaci6n prolongada para los pacientes con insuficiencia mental.

INTRODUCTION The risk of nosocomial transmission of tuberculosis, particularly with multidmg-resistant bacilli, among patients infected with human immunodeficiency virus (HIV), is well recognizedJ -v Such outbreaks have been extensively studied these last years by using DNA typing methods such as restriction fragment length polymorphism (RFLP). 8,9 Conversely, nosocomial transmission of drug-susceptible bacilli in immunocompetent patients has been less frequently described ~°-~s and, to our knowledge, has not been investigated by RFLP analysis. In this report, we describe an outbreak of six cases of pulmonary tuberculosis with a streptomycin resistant strain of Mycobacterium tuberculosis among mentally handicapped patients in a long-term care facility. Conventional epidemiologic investigation and RFLP analysis demonstrated that these cases were related and resulted from a nosocomial transmission of a single strain of M. tuberculosis.

MATERIALS AND METHODS

For RFLP analysis, DNA was prepared and treated according to the standardized protocol of Van Soolingen et al. 9 Briefly, chromosomal DNA was digested with the restriction endonuclease PvuII and DNA blots were hybridized to the mycobacterial IS6110 probe prepared as previously described. TM

Epidemiologic investigation

Case-patient medical records were reviewed for admission dates, room assignments, HIV infection status, potential proximity to other case-patients and infection control practices.

RESULTS Description of the outbreak and characterization of cases

The long-term care facility of Saint-Brieuc hospital is divided into three units, each including 15 single-bed rooms and separate lounge and canteen (Fig. 1). The three units are connected by a large central lounge where

Case defnition

A case was defined as a patient with culture-positive pulmonary tuberculosis diagnosed in the long-term care facility of Saint-Brieuc hospital from April 1992 to November 1994.

unit 1

Laboratory methods

Culture, identification and antimicrobial susceptibility testing of M. tuberculosis isolates were performed at Saint-Brieuc hospital. Standard RFLP analysis was undertaken when the sixth case of tuberculosis was reported, and was carried out at the National Reference Center for Tuberculosis Surveillance, Pitir-Salp~tri~re hospital. Reference strain Mt1432314 and four epidemiologically unrelated Mo tuberculosis strains from the community were also analyzed. These strains were isolated from four patients who were hospitalized for tuberculosis, two of them in Saint-Brieuc hospital and the two others in Pitir-Salp~tribre hospital.

unit 3

A

unit 2

Fig. l ~ c h e m a t i c drawing of the long-term care facility. *Indicates rooms in which the case-patients were hospitalized. L1, C1; L2, C2; L3, C3: lounge and canteen of units 1, 2 and 3, respectively. A: central lounge.

Tuberculosis in a long-term care facility 533 all the residents of the three units can share part of their social activities. In units 2 and 3, residents were elderly persons present for several years. In unit 1, 15 patients, transferred from a hospital for the mentally handicapped in the Saint-Brieuc area, were hospitalized in April 1992. In February 1993, one of these patients, a 40-yearold man with infantile psychosis, developed cough and fever. His symptoms persisted despite administration of broad spectrum antibiotic therapy (macrolides and ~-lactam antibiotics). In May 1993, pulmonary tuberculosis was diagnosed on the basis of abnormal chest shadows with cavity and the presence of acid-fast bacilli in the sputum smears. The patient, who had never been previously treated for tuberculosis and was HIV seronegative, was transferred to the pneumology department where he received standard antituberculosis treatment. In May 1993, when the results of sputum smears of the first patient (case no. 1) were known, active tuberculosis case-finding, based on medical examination and chest radiograph, was undertaken among residents and staff. At this stage there was no evidence of other cases of tuberculosis. Tuberculin skin tests were positive (induration size ___5 mm) for almost all the residents and staff, but no strongly positive reaction (i.e. induration size _ 10 m m with blistering) was observed. Because BCG vaccination is compulsory in France, the results of tuberculin testing were not an indication of recent infection, and residents and staff were not given preventive chemotherapy but were carefully monitored during the following months. In August 1993, 3 months after the

initial tuberculin test, a second test was performed, as recommended. ~5No tuberculin conversion, defined as an increase of the induration size _> 10 m m from the last reaction, was detected among staff and residents. However, at the same time one patient (case no. 2) developed anorexia, and his chest radiograph showed a pleural effusion (Fig. 2). In October 1993, systematic chest radiograph led to the identification of two other new patients (cases no. 3 and 4) who had alveolar infiltrates. One of them (case no. 4) was sputum smearpositive. Finally, two other patients (cases no. 5 and 6) developed clinical symptoms which alerted staff members in January 1994. Case-patient no. 5 suffered from weight loss from December 1993 and his chest radiograph revealed a pleural effusion. Case no. 6 had cough, fever and minimal radiographic infiltrates. All five secondary cases diagnosed between September 1993 and January 1994 belonged to unit 1, i.e. were mentally handicapped patients transferred to this unit in April 1992. For a period of 11 months, the proportion of nosocomial tuberculosis was 40% among patients of unit 1 and 11% among all patients of the long-term care facility. After the transfer of the six case-patients to the pneumology department, no additional cases occurred among elderly patients or among health care workers, either in unit 1 or in the two other units.

Antibiotic susceptibilities and R F L P analysis The M. tuberculosis isolates obtained from the six case-

Transfer to the long-term care facility Case-patients 6

5

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I I I

2

I

I

J Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan 1992

~

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1993

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1994

Fig. 2---Time course of patients with streptomycin-resistanttuberculosis in the long-term care facility of Saint-Brieuc hospital, between April 1992 and January 1994 (all six case-patients were admitted to the facility in April 1992). The length of stay in the facility is represented by open boxes. Dark circles and triangles indicate onset of clinical symptomsand first specimen culture-positive for Mycobacterium tuberculosis, respectively. Patients who were sputum smear-positive are indicated by an asterisk.

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Tubercle and Lung Disease 1

2

3

4

5

6

7

8

9

10

11

14.4

7.2

7.0

3.6

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3,0

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Fig. 3--Restriction fragment length polymorphism typing of Mycobacterium tuberculosis isolates from case-patients and epidemiologically unrelated patients. Lanes 1~: isolates from case-patients; lanes 7-10: isolates from epidemiologically unrelated patients; lane l l : reference strain Mt14323. Molecular sizes of bands obtained from the Mt14323 reference strain are indicated in kb on the right.

patients were susceptible to the first line antituberculosis drugs, but resistant to streptomycin. The genomic DNA extracted from the six isolates was studied by RFLP analysis. An identical DNA fingerprint, with eight fragments hybridizing with the IS6110 probe, was observed for the six isolates (Fig. 3). In contrast, each of the strains obtained from patients who were epidemiologically unrelated had a different and unique hybridization pattern.

DISCUSSION Several lines of evidence suggest a nosocomial outbreak of tuberculosis caused by a unique strain of M. tuberculosis in the unit for mentally handicapped patients in the long-term care facility of Saint-Brieuc hospital. Since tuberculosis was uncommon in this institution, the temporal clustering of six tuberculosis cases was striking. Five of the six patients developed the disease within the 7-11 months following the apparition of the first patient's symptoms, a period of time which corresponds

to the average time of tuberculosis incubation in HIV seronegative patients. 16 Moreover, the probable source and the secondary cases were detected in the same unit, a relatively enclosed space where the residents shared the same facilities and were truly 'home contacts', at high risk of being infected by the source patient whose tuberculosis remained undiagnosed during 3 months. The six case-patients had pulmonary tuberculosis caused by strains which were susceptible to the first line antituberculosis drugs, but were resistant to streptomycin. This special feature suggested the spread of a single strain since only 5% of the strains isolated from patients with no previous history of tuberculosis are resistant to this drug alone, in France. However, only genotypic analysis could provide definite proof of crosscontamination, particularly because the six isolates were not multidrug resistant strains. Using RFLP typing, the six related M. tuberculosis isolates had identical DNA fingerprints, thus confirming the transmission of a single strain in the long-term care facility. Until recently, classical typing methods, such as phage and antibiotic resistance typing, were used for investigating tuberculosis transmission but, because of

Tuberculosis in a long-term care facility 535 limited reproducibility and discriminatory power, such methods did not allow a good differentiation of isolatesJ 7 In contrast, R F L P analysis is a reliable epidemiological tool that is particularly useful when there are no distinctive drug resistance patterns, and can simplify outbreak investigation by identifying the sources of transmission and thus the starting point for contact investigations. 17 Two factors facilitated the outbreak in the long-term care facility. The first factor was the significant delay in diagnosis and, as a consequence, in treatment and isolation of the probable source patient. Indeed, as clearly indicated in recommendations published by the Centers for Disease Control, early identification, treatment and isolation of persons with active tuberculosis are basic actions for preventing the nosocomial transmission of tuberculosisJ 82° However, in the present situation, where the first case of tuberculosis was diagnosed in a psychotic patient, the diagnosis was delayed because communication with this patient was almost impossible and medical examination was difficult. Moreover, the limited number of health care workers in the unit probably contributed to the delay in the recognition o f tuberculosis in this patient. Consequently, the duration of contagiousness of this patient lasted 3 months, favoring transmission of tuberculosis. A similar situation has been previously reported in an outbreak of tuberculosis affecting non-HIV patients in a long-term care facility, s° The second factor that clearly facilitated the spread of a single strain of M. tuberculosis among the mentally handicapped patients was the enclosed space where they were hospitalized. In the past, many outbreaks of tuberculosis have been reported in 'closed communities' such as schools, nurseries and asylums. 2~ In schools and nurseries, the source was often an adult with contagious pulmonary tuberculosis who had close contact with the children. It has also been reported that the overcrowding in 'closed institutions', such as hospitals for the mentally handicapped and nursing homes, increases the risk of tuberculosis transmissionJ °,1~,~3 Therefore, it is likely that repeated contact between the probable source case and other patients hospitalized in the same unit facilitated the transmission of tuberculosis in the long-term care facility of Saint-Brieuc hospital. W h e n the source case was eventually identified, active surveillance of residents and staff members was undertaken, resulting in the identification of five secondary cases between September 1993 and January 1994. Measures of isolation were taken in order to protect the other residents and staff" members in the facility. However, since this implementation turned out to be difficult in the unit for the mentally handicapped, the case-patients were transferred to the pneumology department of the hospital where they were more efficiently isolated, leading to the cessation of the outbreak. It m a y seem surprising that isoniazid prophylaxis was not prescribed to exposed patients and staff members after the discovery of case no. 1. The measure was con-

sidered but two reasons countered the use of isoniazid prophylaxis: 1. Ahnost all exposed residents had had B C G vaccination in the past and were tuberculin-positive, but none of them had a tuberculin induration of more than 10 ram, thus there was no evidence of recent tuberculous superinfection. 2. Because a majority of the mentally handicapped patients were already receiving other medications (neuroleptics and anti-convulsant drugs), the prescription of isoniazid prophylaxis was not without risk. It was finally decided not to give preventive chemotherapy but to keep residents under close supervision. In conclusion, the difficulties in implementing a routine infection-control policy in a long-term care facility for mentally handicapped patients can lead to a high rate of tuberculosis in a short period of time.

Acknowledgements We are grateful to J. D. A. van Embden for the gift of strain Mt14323 and his help in performing RFLP analysis.

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