The emergence of strains of Myco-bacterium tuberculosis that are resistant to antituberculosis agents, although not a novel phenomenon, has recently received increased attention, largely owing to dramatic outbreaks of multidrug-resistant (MDR) TB in HIV-infected patients in New York and Florida.2 These outbreaks have been characterized by delayed diagnoses, inadequate treatment regimens, high mortality, and significant rates of nosocomial transmission.3 MDR TB, however, is a worldwide problem in both immunocompetent and HIV-infected populations. Both primary and acquired drug resistance may occur, the latter as a result either of inappropriate regimens prescribed by providers or of nonadherence by patients.4
Early diagnosis of TB–especially pulmonary TB–is one of the most important factors in preventing its transmission and in allowing prompt initiation of effective treatment. TB, however, must be suspected by the clinician if there is to be prompt diagnosis. The definitive diagnosis of TB depends on isolation and identification of the etiologic agent, M tuberculosis, while design of an appropriate therapeutic regimen depends on the results of antituberculosis drug-susceptibility testing. Highly infectious patients with acid-fast bacilli (AFB)-positive sputum smears deserve Fast Track procedures5 to ensure the most rapid microbiological results. Anti-tuberculosis drug-susceptibility testing results should be available within 2 to 3 weeks (versus 2 to 3 months) after a specimen has been obtained from the patient.
To reverse the TB epidemic in the 1990s (Figure 1), it was vital to establish directly observed therapy (DOT) as the standard of care and primary means of increasing the completion rate of treatment in TB patients.6,7 The effective management of TB cases depends on timely and well-coordinated interaction among medical care providers, the staff, and public health officials. The following case studies illustrate the importance of the partnership between these key players in controlling TB.
CASE 1
The patient was a 9-year-old autistic child living with his grandmother, who was his legal guardian. Other family members included his mother (a homeless drug addict) and his aunt, who had MDR pulmonary TB. The aunt had AFB-positive sputum smears and M tuberculosis-positive cultures from January 1995 to November 1996. The original isolate was susceptible to all antituberculosis drugs, but subsequent isolates demonstrated some resistance. Specifically, a report of April 4, 1997, indicated resistance to isoniazid, rifampin, rifabutin, pyrazinamide, and streptomycin with susceptibility to ethambutol, ethionamide, capreomycin, cycloserine, kanamycin, ciprofloxacin, ofloxacin, and para-aminosalicylic acid.
The patient was referred to a department of health chest clinic after a positive tuberculin skin test (TST) of 16 mm on April 4, 1997. His significant medical history included congenital syphilis, otitis media, and behavioral problems. Upon initial evaluation, he was without constitutional symptoms of TB; however, a chest radiograph revealed a lesion in the right lower lobe. Because of concern about potential TB, he was sent to a hospital. His grandmother, however, removed him from the hospital against medical advice.
On April 24, the patient presented at the emergency department of a second hospital. A chest radiograph was interpreted as showing possible pneumonia in the right lower lobe and fibrotic changes in the left lung. On the basis of this radiograph, clinicians at a pediatric pulmonary clinic to which the patient was referred diagnosed resolving pneumonia (on May 1) and discharged him to a developmental clinic for follow-up treatment; the family refused further care. Subsequently, the patient was seen at the second hospital’s outpatient clinic, but his grandmother did not reveal some of the pertinent recent medical history.
In July, she was informed that the case was being evaluated by the legal unit of the department of health because of her noncompliance with evaluation for potential TB and the possible need for treatment for this child. On August 5, the grandmother agreed to have the child evaluated at the second hospital. Specimens from a gastric aspirate were obtained and sent to the laboratory for culture. Meanwhile, because of potential exposure to an index case of MDR TB, the patient’s therapy was initiated with isoniazid, ethambutol, ethionamide, and capreomycin, and he was referred to the department of health clinic for DOT.
A repeat chest radiograph on August 14 revealed a persistent infiltrate in the right lower lobe and fibrosis on the left, unchanged from April. An expert in pediatric TB from the first hospital was consulted and advised holding anti-MDR TB therapy pending culture results. The grandmother discontinued the patient’s medications as advised but refused to return to the department of health for his follow-up care.
On October 1, culture of the gastric aspirate from August 7 grew fully susceptible M tuberculosis. Reinitiation of treatment was ordered, but, once again, the patient’s grandmother declined. She insisted that she had been instructed to stop the medications and that, furthermore, she doubted the diagnosis of TB altogether. On October 14, a conference was held by the department of health physician, outreach workers, a pulmonary specialist, a pediatrician from the second hospital, and two family members to formulate a plan of action to return the child to care. This was accomplished, and he returned to the department of health to restart treatment with isoniazid, rifampin, and pyrazinamide. With constant interaction and support of the family, the patient completed 6 months of treatment. A follow-up chest radiograph was declined by the grandmother.
A source case and contact investigation was conducted, and 18 household members were identified. Of these, 10 were examined; eight were not infected and two were infected without disease. The primary caretaker (the grandmother) refused a TST, but her chest radiograph was normal and she was asymptomatic for TB. Because a drug-susceptible TB strain had been diagnosed in the patient, and because he was in school, the case was referred for an epidemiological consultation to assess the need for an expanded contact investigation. The possibility of another source case was also being considered because the isolate from the patient was susceptible to anti-TB drugs, whereas the most recent isolate from the identified potential source case, his aunt, was MDR. DNA fingerprints for both the susceptible and drug-resistant isolates from the aunt were compared with that of the susceptible isolate from the patient. It was found that the susceptible isolates from both the patient and his aunt matched, and this supported the hypothesis that the patient had been infected by her. Because she was then considered the likely source of disease, a source-case investigation in the school was not deemed necessary.
The following was accomplished:
- The patient did not receive a full course of highly toxic second-line TB drugs.
- The TB status of the patient was confirmed by bacteriology reports and the patient was placed on the correct regimen.
- A coordination of effort and consistent interaction helped provide a unified plan to the family. Despite reluctance from the family, the patient was maintained on treatment once restarted.
- The involvement of the laboratory and the epidemiology units averted unnecessary public health panic in a school setting. The availability of the laboratory to perform DNA fingerprinting and to provide information about the source of the isolate was crucial in the management of this case.
It is important to seek expert consultation in the following events: when a nonstandardized drug regimen is initiated, when a first-line drug is dropped because of adverse reaction(s), when the laboratory is reporting drug resistance, and when the patient is not becoming culture negative by the end of the third month of treatment.
CASE 2
The patient was a 47-year-old male who was hospitalized for diarrhea and suspected food poisoning in May 1997. He had a history of heavy alcohol use. The diarrhea resolved, but during his evaluation he was found to have cavitary TB. He was started on daily isoniazid (300 mg), rifampin (600 mg), pyrazinamide (1 g), and ethambutol (800 mg). Upon discharge, he was referred to a department of health clinic for TB follow-up treatment. His treatment was changed to twice weekly oral doses of isoniazid (900 mg), rifampin (600 mg), pyrazinamide (3 g), and ethambutol (3 g) all by DOT. Ethambutol was discontinued after laboratory results showed full susceptibility to first-line drugs.
In August, the patient’s HIV test was positive. Ten weeks after the start of TB treatment, sputum smears were still positive for AFB, he continued to lose weight (10 lb), and radiographic improvement was slow despite 100 percent adherence to treatment with DOT. Because of the slow clinical progress, therapeutic-drug-level monitoring was performed to rule out the possibility of low drug levels as the cause of his poor response to therapy. The first therapeutic-drug-level monitoring specimen, collected in September, showed the rifampin level to be subtherapeutic. On the basis of the drug level, the dosage of rifampin was increased to 900 mg biweekly; isoniazid and pyrazinamide were continued at the previous dosages.
In November 1997, therapeutic-drug-level monitoring was repeated. Isoniazid and pyrazinamide were above therapeutic levels but the rifampin level was reported as a trace. Sputum conversion occurred after 3 months. Based on the subtherapeutic level of the rifampin, the decision was made to continue the three drugs, to monitor liver enzymes, and to repeat the therapeutic-drug-level monitoring for rifampin. The treating physician observed the ingestion of 900 mg of rifampin and the specimen was collected 2 hours later. The result was reported as zero.
In January 1998, specimens were collected for therapeutic-drug-level monitoring 1 and 2 hours after drug ingestion. The rifampin level remained subtherapeutic on this biweekly regimen: isoniazid (900 mg), rifampin (900 mg), and pyrazinamide (3 g).
The patient improved clinically and the cavity noted on his chest radiograph resolved but continued to show some infiltrate. He gained weight, and the sputum smear and culture remained negative. Because of the subtherapeutic level of the rifampin in his regimen, the treatment will need to be prolonged (4 months after sputum conversion).
Therapeutic-drug-level monitoring was valuable for the management of this patient. Without knowledge of the therapeutic-drug levels, pyrazinamide would probably have been stopped after 2 months, leaving him on monotherapy with isoniazid.
Therapeutic-drug-level monitoring may be useful in MDR-TB patients, drug-susceptible-TB patients who fail to respond to treatment despite adherence to DOT, active-TB patients who are suspected of having malabsorption of medication because of HIV-related or gastrointestinal disease, and patients who have relapsed with active TB despite appropriate treatment.
In other clinical situations, such as when protease inhibitors or other medications are being used, therapeutic-drug-level monitoring may be crucial to prevent drug toxicity because of the interactions between anti-TB drugs and other medications.
HISTORY OF TB CONTROL IN NEW YORK CITY
In 1979, the Bureau of Tuberculosis Control (BTBC) was formed, comprising approximately 52 staff members (primarily outreach workers).7,8 The major function of the bureau was to perform surveillance to identify TB cases. Active case management was performed on a priority basis and consisted of assigning patients with an AFB-positive smear or positive culture for M tuberculosis to an outreach worker who would follow up on their treatment plan and perform contact investigations. The medical management of the TB patient was the responsibility of the physician who provided the treatment. This responsibility shifted whenever the TB patient changed his/her medical care provider. This often resulted in long breaks in treatment, and nonadherent patients were reported to the bureau long after they had been lost to supervision.
By 1992, TB patients were cared for by hospitals, outpatient clinics, and many private physicians (who would sometimes care for only two or three patients with TB per year). TB care was not standardized, and the coordination of case management activities was challenging because providers’ responsibilities were not clearly defined. In 1993, the BTBC established specialized units in its outreach services to carry out the various activities involved and implemented a refined case management model for chest-clinic patients.8
CURRENT CASE MANAGEMENT
Case management is the comprehensive follow-up treatment of a suspected or confirmed TB case. This includes the monitoring of an appropriate regimen to ensure completion of treatment and avoid acquisition of resistance, as well as the timely identification, evaluation, and treatment of each case’s contacts to avoid the emergence of secondary cases. The responsibility for case management of TB patients is shared by various units within the BTBC in a network of activities. The specialized units responsible for case management of patients with TB in New York City are the initial evaluation unit, the case management unit, the DOT unit, the return-to-service unit, the regulatory affairs unit, the contact investigation unit, and the clinical services unit.
Initial Evaluation Unit
Outreach workers in this unit interview all hospitalized patients with confirmed or suspected TB. These patients are identified through active surveillance such as reviewing hospital laboratory records, meeting with the hospital infection control nurse on a regular basis to inquire about newly admitted patients suspected or known to have TB, reviewing hospital isolation listings, and reviewing pharmacy lists to identify patients on TB medications.
Patients are interviewed on a priority basis to ensure proper management. Patients with positive AFB sputum smears and/or cavitary lesions on chest radiographs are the first priority. Special attention is given to collecting information that will assist workers in locating the patient after discharge. The interview must be performed within 3 working days of identifying the patient. At this time, patient education is given about TB and the interaction between TB and HIV, DOT is offered, the importance of medical follow-up care is stressed, and the availability of free care at the clinics is discussed.
A very important function of this unit is to elicit names of contacts and to perform informational source-case investigations for children with significant TST reactions. The outreach workers are involved in the hospital discharge-planning process to ensure that referrals for TB treatment and DOT are made and that TB care is not interrupted. Once the patient leaves the hospital, management of the case is transferred to the case management unit and the contacts identified are forwarded to the contact investigation unit.
Case Management Unit
This unit is responsible for monitoring–until completion of treatment–all confirmed and suspected TB cases who have cavitary lesions on their chest radiographs or a positive AFB sputum smear. This unit also monitors the contacts of cases who are receiving their medical follow-up care from a private physician or a non-BTBC clinic. The activities of this unit include ensuring that medical follow-up visits occur, updating the central TB registry system with information on the latest prescribed treatment and bacteriology findings, and ensuring that suspected cases are evaluated for final TB status within 3 months of identification. The public health advisers in this unit serve as a safety net for patients and medical care providers by bringing to the latter’s attention issues of concern such as lack of follow-up specimens to document sputum conversion, lack of rifampin in the treatment regimen, inappropriate dosages, and nonstandardized regimens. The outreach worker collaborates with each medical care provider to form a partnership for care that is beneficial to the medical care provider and the patient.
A small percentage (20 percent) of the TB patients are on self-administered medication. The assessment of treatment adherence of patients on self-administered therapy is done through (1) consultations with the medical provider to check the patient’s adherence to follow-up medical evaluation; (2) pharmacy checks to verify that the prescribed medications are picked up; and (3) review of bacteriology findings to evaluate progress or relapse. Any anomaly identified through this process is promptly communicated to and discussed with the medical provider.
The outreach workers serve as facilitators in the resolution of various constraints to TB treatment adherence. They develop a close rapport with the patients and assess patient needs (and any obstacles to treatment adherence). They often become the patient’s advocates for access to community services for homelessness, substance abuse, and illnesses such as AIDS and diabetes.
DOT Unit
One of the goals of the BTBC is to identify all individuals with suspected or confirmed TB disease and ensure appropriate treatment, ideally on a regimen of DOT. In 1993, the BTBC made DOT the standard of care for TB patients in New York City. This service is made available to every TB patient in the city. The DOT unit provides support to private physicians and other providers by ensuring that their patients adhere to their treatment and medical visits. The major characteristic of this unit is the flexibility to provide DOT to patients at their convenience and preferred locations (home, work, park bench, or the like).
Return-to-Service Unit
This unit locates patients who are nonadherent to treatment and lost to follow-up care and returns them to service–and, if needed, evaluates them for legal action. This unit is best described as a “SWAT team” of public health workers specializing in finding patients when no one else can.
Regulatory Affairs Unit
In 1993, New York City’s Board of Health amended the city’s health code to allow the commissioner of health to issue orders for DOT and for the detention of patients with pulmonary TB who were persistently nonadherent to treatment. The regulatory affairs unit coordinates the bureau’s work with these patients. This includes reviewing the appropriateness of documentation supporting efforts to address patient constraints to treatment adherence, drafting legal orders, and coordinating legal and medical issues while the patient is under an order.
Contact Investigation Unit
This unit ensures that the contacts of infectious TB patients are located, tested, and evaluated for preventive treatment, if indicated. The primary sources of referral to this unit are other bureau units, but private physicians or the staffs of hospitals, outpatient clinics, work sites, and schools can also refer contacts for evaluation. The investigation and evaluation of contacts are done on a priority basis, with highest priority given to the contacts of pulmonary and laryngeal cases with a positive AFB smear, cavitary radiograph, or MDR TB; to contacts who are known to be HIV-positive or at risk for HIV; and to children, especially those less than 5 years old.
This part of case management demands intensive interaction and nurturing of the relationships among public health workers, source cases, the medical community, and contacts. Fear of the breaching of confidentiality often interferes with the identification of significant contacts. Reassurance and education remain key factors throughout the contact investigation process.
An expanded contact investigation team was developed to assess the need for expanded investigations whenever transmission of TB infection is suspected. This may occur in common settings such as schools, nursing homes, job sites, and the like. This addition represents a cross-unit team effort involving epidemiologists, educators, outreach workers, and medical care providers.
Clinical Services Unit
This unit comprises 10 chest clinics and provides complete TB treatment and management to approximately 33 percent of the cases confirmed per year in New York City. With the influx of resources, TB medical subspecialists, additional nurses, social workers, and clinic-based outreach workers were hired to provide quality care; the environment was upgraded to provide a more patient-friendly atmosphere; and state-of-the-art equipment, including x-ray machines and sputum booths equipped with high-efficiency particulate air filters, was installed. These changes increased the public’s confidence in the bureau’s ability to provide the best care to the TB patient. These clinics provide extended evening and Saturday hours, as well as multilingual services not readily available at hospitals or other outpatient clinics.
Every confirmed TB patient managed by the clinics is offered DOT on-site or at a location of his/her choice. Although DOT is the standard of care in the clinics, some patients still refuse this service and prefer to self-administer their medications. Approximately 75 percent of the patients managed in these clinics, however, receive DOT.
In addition, this unit interacts closely with all of the outreach units and serves as a primary referral site for uninsured and difficult-to-treat TB patients and their contacts. The team approach to case management is the norm, and every TB patient seen at the clinics is assigned a primary physician, nurse, and outreach worker. The clinics’ medical staff members also provide expert consultation to private physicians.
EVALUATION OF CASE MANAGEMENT ACTIVITIES
The bureau has established several methods to evaluate the effectiveness of the case management of all confirmed TB patients in New York City. They include case management meetings, caseload review, medical review of all verified cases, and quarterly cohort presentations.
Weekly case management meetings are conducted by the physicians in charge of patients who attend department of health chest clinics; these patients are reviewed for adherence to DOT and medical visits. New patients are presented, difficult cases are discussed, and a plan is made for timely follow-up care.
A systematic review of the caseload of each outreach worker is conducted by a senior outreach worker at least every 2 weeks. At the time of this review, adherence issues are addressed and follow-up activities are identified. This caseload review method is used in every unit and serves as a means of providing continuous supervision of cases and of ensuring that nonadherent cases are identified and dealt with in a timely fashion.
At the beginning of each month, a list of all cases confirmed during the previous month is submitted to the assigned units. A medical consultant reviews each newly counted case for appropriateness of treatment and contact investigation. Through this process, improper or nonstandardized treatments are identified and addressed by a TB medical expert early in the course of treatment.
TB cases verified during a 3-month period are reported to the medical director of the bureau 6 months after the end of the period, using a medical-case-presentation format. Information such as patient adherence and progress toward completion of treatment, actions taken to address social issues that interfered with adherence, contact investigation, and treatment outcomes is presented. These quarterly cohort presentations provide a focus for staff accountability and a vehicle for staff teaching. They also provide opportunities to identify and respond to TB caregivers’ needs.
Unique program resources
1)TB reporting hotline
The BTBC maintains a centralized registry of all suspected and confirmed cases of TB. Included for each record are:
- demographic and social information,
- TST and chest radiograph results,
- the name of the hospital or clinic reporting the TB case,
- the date and location of each medical visit,
- the anti-TB drugs and dosages being used,
- the percentage of adherence to DOT,
- AFB-smear results,
- nucleic acid amplification results,
- culture and susceptibility results,
- the site of disease, and
- names and TST results for the contacts of the case.
Physicians who call for information using the hotline can–upon having their medical license numbers verified by the hotline’s staff–obtain registry information on patients for whom they are providing care. For example, should a patient present at the emergency department of a hospital stating he/she has a history of TB treatment or diagnosis at another hospital, a physician would be able to access the patient’s complete TB-related history. In this way, the physician could discover whether the patient had been previously treated for TB, the date of the last positive AFB smear and culture, whether the strain of TB was resistant to any medications, and where the patient had previously received medical attention.
2) Fast Track Program
The Fast Track Program for TB testing was initiated in late 1993 to prioritize specimens from highly infectious patients for the most rapid identification and susceptibility testing of tubercle bacilli. This program is available to all health care providers and clinical laboratories caring for highly infectious smear-positive patients in the state of New York. In April 1996, nucleic acid amplification testing was added to the Fast Track Program, providing immediate benefits to all enrolled hospitals, clinics, and medical centers. As of May 1998, there were more than 160 institutions enrolled.
The Fast Track Program allows broader accessibility to state-of-the-art laboratory procedures. It enhances infection control, allowing public health officials to stay focused on highly infectious TB patients for DOT and contact investigations, both of which demand substantial resources. For patients infected with nontuberculous mycobacteria, it dramatically shortens the period of exposure to potentially toxic and unnecessary anti-TB drugs, allowing these patients to be released from respiratory isolation earlier and conserving health care resources. The mailed report is accompanied by current information on case management to increase the likelihood of appropriate care.
CONCLUSION
The case management model currently being used in New York City was established to handle the large number of confirmed TB cases identified per year. Although this model may not be applicable in its entirety to other TB programs, it can be adapted based on individual program caseloads and available resources. DOT, as a specific element of this case management model, played a very important part in its success.
In addition, the development and maintenance of partnerships among patients, medical care providers, and the department of health (including its Public Health Laboratory), and the ensuring of accountability for every aspect of case management of the TB patient by establishing performance indicators, are very important measures.
Marie Dorsinville, RN, is director of clinical services, and Klaus D. Lessnau, MD, is a clinician, both at the Bureau of Tuberculosis Control, New York City Department of Health, New York. Max Salfinger, MD, is director of the Clinical Mycobacteriology Laboratory at the Wadsworth Center, New York State Department of Health, in Albany.
Acknowledgment
This article benefited from the comments and suggestions of Paula I. Fujiwara, MD, MPH.
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