The mycobacteriology laboratory. Past, present, and future

The role of the mycobacteriology laboratory in tuberculosis control programs has been underestimated in the past, but now laboratory services are proven to play an essential role if properly implemented. The importance and reliability of these services in the future will depend on their centralization in specialized mycobacteriology laboratories that will be able to put new technologies into practice. The shortest turnaround time and the greatest cost effectiveness can be achieved by direct submission of raw specimens to such laboratories, especially for the management of new tuberculosis patients.     

Prevention of perinatal transmission of HIV in Arkansas

In 1994, the Centers for Disease Control and Prevention (CDC) recommended zidovudine (ZDV) prophylaxis to reduce perinatal transmission of HIV. Caregivers at the University of Arkansas for Medical Sciences (UAMS) instituted a program of universal voluntary HIV testing of pregnant females combined with maternal education regarding ZDV prophylaxis in October 1994. Since that time, 7 of 39 (18%) infants referred to Arkansas Children's Hospital (ACH) for evaluation of perinatal HIV exposure have been infected compared to 21 of 53 (40%) referred prior to October 1994, (p = 0.042). Unfortunately, of the 39 infants referred to ACH after October 1994, 21 were born to HIV-infected mothers who did not comply with prophylaxis. Fifteen of these mothers were not offered intravenous ZDV during delivery; five have children infected with HIV. These data indicate the need for increased efforts by health officials in Arkansas to institute nationally recommended methods of prevention of perinatal HIV.     

Prevention of nosocomial transmission of Mycobacterium tuberculosis

The recent resurgence of TB together with the ongoing HIV epidemic has resulted in a larger number of infectious TB patients being admitted to US health care facilities. These patients have become a source for both nosocomial (patient-to-patient) and occupational (patient-to-health care worker) M. tuberculosis transmission. Infectious MDR-TB patients serve as even greater potential infectious sources because they often remain AFB smear and culture positive for months to years. The keys to the prevention of nosocomial and occupational transmission of M. tuberculosis is conducting a risk assessment for each area of the facility and instituting appropriate control measures, having a high index of suspicion by clinicians for infectious TB in those who present with consistent signs and symptoms, rapid triage of such patients to isolation areas and their appropriate clinical work-up, and the institution of effective antituberculous therapy. Infection control personnel should ensure that infectious TB patients are isolated in appropriate isolation rooms (i.e., negative pressure, greater than or equal to 6 ACH, and direct external exhaust of the room air). Health care workers with infectious TB patient contact should be instructed in the epidemiology of M. tuberculosis transmission, the role of respirators in protecting the health care worker from airborne inoculation, and the importance of periodic health care worker TST. The nosocomial TB outbreaks in the 1980s and 1990s document that M. tuberculosis can be transmitted to both patients and health care workers in US health care facilities when appropriate infection control measures are not fully implemented. Follow-up studies at some of these institutions, however, document that when infection control measures similar to the 1990 or 1994 CDC TB Guidelines are fully implemented, M. tuberculosis transmission to both patients and health care workers can be reduced or eliminated. Protection of both patients and health care workers from M. tuberculosis infection is dependent on an understanding and full implementation of the 1994 CDC TB Guidelines.     

Laboratory diagnosis of tuberculosis: past, present, and future

Resurgence of tuberculosis justifies extraordinary efforts to expedite TB diagnosis and susceptibility testing. This demands that laboratory support expand to a "second generation" of methods and procedures, including rapid availability of fluorochrome smears of concentrated specimens, faster techniques for detection (e.g., the BACTEC radiometric broth system and microcolony detection), quicker identification (e.g., high-pressure liquid chromatography, nonisotopic genetic probes), more rapid susceptibility testing methods (e.g., BACTEC), and reporting of these results as critical values. Guidelines have been established for turnaround time for results of smears, TB organism identification, and susceptibility testing to usual first-line drugs. A "third generation" of laboratory techniques soon will make testing not only more effective but also more efficient. These methods include direct testing of respiratory specimens through nonisotopic genetic probes as well as nucleic acid amplification techniques utilizing polymerase chain reaction (PCR) and other molecular procedures. These new procedures and protocols place heavy demands on laboratory test volume, technologist time and costs. For the healthcare system or clinical laboratory without the resources to deal with these new demands, referral of TB specimens represents a reasonable alternative, as long as transport is adequate to meet current CDC and other guidelines for turnaround time.     

Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer''s disease

With funding from the Administration on Aging, the National Resource Center: Diversity and Long-Term Care surveyed state administrators of programs serving elders in 24 states in 1994. This survey sought to document what written guidelines and training case managers receive in promoting client autonomy in care planning. In discussions with respondents and review of written materials provided by the states, surveyors explored whether clients received written information about services, the structure for seeking client input into care planning, and the structure for soliciting client feedback once the care plan was in place. Of the states included in this survey, few have developed and implemented guidelines or provide case managers training to promote client autonomy in the care-planning process. After reviewing the survey findings, the authors make two policy recommendations for states to consider in this area.     

Evaluation of mycobacteria growth indicator tube for recovery and drug susceptibility testing of Mycobacterium tuberculosis isolates from respiratory specimens

The new BBL mycobacteria growth indicator tube (MGIT) was evaluated for its ability to detect mycobacteria directly from patient specimens and to determine the drug susceptibility of Mycobacterium tuberculosis isolates. A total of 85 respiratory specimens were tested. Specimens were digested, concentrated, examined microscopically for acid-fast bacilli, and inoculated into MGITs and onto Lowenstein-Jensen slants by standard procedures. The tubes were incubated at 37 degrees C and were examined daily for fluorescence to 365-nm UV light. All 25 specimens smear positive for acid-fast bacilli were tested for drug susceptibility in MGITs containing 1.0 mu g of rifampin per ml, 0.1 mu g of isoniazid per ml, 2.0 mu g of streptomycin per ml, and 2.0 mu g of ofloxacin per ml. These results were compared with those obtained by testing the same M. tuberculosis isolates by the indirect proportion method at drug concentrations of 4.0 mu g of rifampin per ml, 0.2 mu g of isoniazid per ml, 2.0 mu g of ethambutol per ml. 4.0 mu g of streptomycin per ml, and 2.0 mu g of ofloxacin per ml. No significant difference in the sensitivity of detection of M. tuberculosis isolates was found between the two methods. However, the time to detection was significantly shorter in MGITs. Drug susceptibility test results for M. tuberculosis isolates by the two methods demonstrated an excellent correlation. The mean time to reporting of drug susceptibility results was 5 days for MGITs versus 16 days for Lowenstein-Jensen slants. The results of this preliminary study indicate that the MGIT system appears to have potential for routine use in mycobacteriology for both the detection and the drug susceptibility testing of M. tuberculosis isolates. However, it is important to emphasize that simple nonautomated equipment should be developed to improve the accuracy of fluorescence detection.     

Randomized controlled trials in cancer: improving the quality of their reports will also facilitate better conduct

BACKGROUND: The 1994 Centers for Disease Control and Prevention draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities did not exempt pediatric facilities from instituting controls to prevent nosocomial tuberculosis (TB) transmission. Many researchers contend that TB disease in children does not require such rigid controls. We surveyed acute-care pediatric facilities in the United States to determine adherence to environmental and administrative control recommendations. METHODS: The study included 4 mailings of a survey to infection control professionals at 284 US children's hospitals and adult acute-care hospitals with > 30 pediatric beds. RESULTS: Isolation rooms (IRs) generally conformed to recommended guidelines; 92% of respondents reported IRs with > or = 6 air changes per hour, 90% reported 1-pass air and negative pressure, and 89% reported that IRs were private rooms. A sufficient number of inpatient IRs were reported by 88%, but only 42% had IRs in outpatient areas, and 19% had IRs in off-site clinics. Employee tuberculin skin-test programs were in place at 98% of facilities, but policies pertaining to implementation varied. Employees' use of personal respirators increased at respondent hospitals from 1991 to 1994, but as late as 1994, nearly one third still used surgical masks for high-risk procedures. CONCLUSIONS: Environmental and administrative controls used by respondent hospitals largely conformed to published guidelines. Because definitive studies that quantify the risk of nosocomial M tuberculosis transmission in pediatric settings have yet to be performed, pediatric facilities are required to have the same protections in place as do their adult counterparts.     

Malaria surveillance -- United States, 1994

PROBLEM/CONDITION: Malaria is caused by infection with one of four species of Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, and P. malariae ), which are transmitted by the bite of an infective female Anopheles sp. mosquito. Most malarial infections in the United States occur in persons who have traveled to areas (i.e., other countries) in which disease transmission is ongoing. However, cases are transmitted occasionally through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to adapt prevention recommendations. REPORTING PERIOD COVERED: Cases with onset of symptoms during 1994. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood smear are reported to local and/or state health departments by health-care providers and/or laboratories. Case investigations are conducted by local and/or state health departments, and the reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), which was the source of data for this report. Numbers of cases reported through NMSS may differ from those reported through other passive surveillance systems because of differences in the collection and transmission of data. RESULTS: CDC received reports of 1,014 cases of malaria with onset of symptoms during 1994 among persons in the United States or one of its territories. This number represented a 20% decrease from the 1,275 cases reported for 1993. P. vivax, P. falciparum, P. malariae, and P. ovale accounted for 44%, 44%, 4%, and 3% of cases, respectively. More than one species was present in five persons (<1% of the total number of patients). The infecting species was not determined in 50 (5%) cases. The number of reported malaria cases in U.S. military personnel decreased by 86% (i.e., from 278 cases in 1993 to 38 cases in 1994). Of the U.S. civilians who acquired malaria during travel to foreign countries, 18% had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Five persons became infected while in the United States; the infection was transmitted to two of these persons through transfusion of infected blood products. The remaining three cases, which occurred in Houston, Texas, were probably locally acquired mosquitoborne infections. Four deaths were attributed to malaria. INTERPRETATION: The 20% decrease in the number of malaria cases from 1993 to 1994 resulted primarily from an 86% decrease in cases among U.S. military personnel after withdrawal from Somalia. Because most malaria cases acquired in Somalia during 1993 resulted from infection with P. vivax, there was a proportionately greater decrease during 1994 in the number of cases caused by P. vivax relative to those caused by P. falciparum. ACTIONS TAKEN: Additional information was obtained concerning the four fatal cases and the five cases acquired in the United States. Malaria prevention guidelines were updated and distributed to health-care providers. Persons traveling to a geographic area in which malaria is endemic should take the recommended chemoprophylactic regimen and should use protective measures to prevent mosquito bites. Persons who have a fever or influenza-like illness after returning from a malarious area should seek medical care; medical evaluation should include a blood smear examination for malaria. Malarial infections can be fatal if not promptly diagnosed and treated. Recommendations concerning prevention and treatment of malaria can be obtained from CDC.     

Constant low rate of fungemia in norway, 1991 to 1996. The Norwegian Yeast Study Group

Since 1991 information on yeast isolates from blood cultures has been recorded prospectively from all microbiological laboratories (5 university and 16 county or local hospital laboratories) in Norway (population, 4.3 million). From 1991 to 1996 a total of 571 episodes of fungemia in 552 patients occurred (1991, 109 episodes; 1992, 81 episodes; 1993, 93 episodes; 1994, 89 episodes; 1995, 98 episodes; and 1996, 101 episodes). The fungemia rates per 10,000 patient days were 0.29 in 1991 and 0.27 in 1996. The average rates for the years 1991 to 1996 were 0.37 for the university laboratories and 0.20 for the other laboratories. These rates are low compared to the rate (0. 76) in five Dutch university hospitals in 1995 and the rate (2.0) in Iowa in 1991. The four most frequently isolated species were Candida albicans (66%), Candida glabrata (12.5%), Candida parapsilosis (7.6%), and Candida tropicalis (6.4%). The incidences of both C. albicans (range, 63 to 73%) and C. glabrata (range, 8.4 to 15.7%) varied somewhat throughout this period, but no significant increase or decrease was noted. MICs of amphotericin B, flucytosine, and fluconazole were determined for 89% of the isolates. All were susceptible to amphotericin B, and only 29 (5.6%) strains had decreased susceptibility to flucytosine. All C. albicans isolates were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs, >/=16 microgram/ml) did increase, from 9.6% in 1991 and 1992 to 12.2% in 1994, 16.1% in 1995, and 18.6% in 1996. This was largely due to increases in the percentages of resistant C. glabrata and Candida krusei strains in the last 2 years. Compared to the incidence in other countries, it is remarkable that Norway has such a low and constant incidence of fungemia. A possible reason for this difference might be a restricted antibiotic use policy in Norway.     

On the need for standardization in panic disorder treatment research: survey of the literature, 1980-1992

A retrospective literature survey (1980-1992) was conducted to chronicle the development of panic disorder treatment research. Based on a National Institute of Mental Health conference on assessment standardization in this area (Shear and Maser, 1994), the results and implications of the survey are presented in terms of eight domains of measurement recommended as essential for high quality research.     

External Quality Assessment of stat test intralaboratory turnaround times. Pilot study from the Members of the Working Group for the Standardization and Promotion of Turnaround Time Control under the Auspices of the Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio

We describe procedures, results and prospects of a pilot program in External Quality Assessment (EQA) of the stat test intralaboratory turnaround times. Our goals are to promote quality by systematic monitoring and comparison of performances by laboratories, continuous investigation into the state of the art of the processes from receipt of sample to transmission of results and creation of a data base for standardization of measures and definition of consensus values for turnaround time. Of 30 laboratories invited to participate, 25 took part, agreeing to record times of arrival and transmission for all determinations of three analytes (blood hemoglobin, serum/plasma potassium and plasma prothrombin time) for seven consecutive days and to continue for one or more further periods of seven days as necessary if there were less than 300 determinations for each analyte. Within a preset time limit, data were sent by e-mail on an Excel file and we sent back two reports per analyte, showing: i) the graph for time vs. percentage of tests completed and several measures of turnaround time; ii) results of all laboratories in graph form, allowing each laboratory to identify only its own data. The high proportion of participating laboratories among those invited (83%) encourages us to implement the EQA program systematically, on a half-yearly basis, extending it to all laboratories wishing to participate in Italy or elsewhere in Europe.     

Intestinal absorption and biliary secretion of cholesterol in rats with nephrotic syndrome

STUDY OBJECTIVE: To evaluate physician prescribing practices for the initial therapy for tuberculosis (TB) according to the recommendations of the Centers for Disease Control and Prevention (CDC) and American Thoracic Society (ATS). DESIGN: Cross-sectional study. SETTING: Statewide TB surveillance system in New Jersey, 1994 to 1995. PATIENTS: We studied 1,230 culture-positive TB patients who were alive at diagnosis and whose isolates were tested for isoniazid susceptibility. RESULTS: Almost all TB patients (98%) were reported from counties with an isoniazid-resistant proportion of 4% or more, which is the minimum level for implementation of an initial four-drug regimen recommended by CDC/ATS. Overall, 36% of the 1,230 patients were not initially treated with four or more drugs. Multivariate analyses found that non-Hispanic white patients were more likely to be treated with fewer than four drugs than were non-Hispanic black patients. Private practitioners and physicians at chest clinics were about five times more likely to prescribe fewer than four drugs initially than were physicians at the hospital where a national TB center is located. CONCLUSION: A substantial proportion of physicians did not initially treat their TB patients according to the CDC/ATS recommendations. The results suggest that New Jersey physicians should be better informed about the recommendation and the high level of drug resistance in the communities they serve to assure that TB patients receive appropriate initial therapy.     

Population parameters, sample statistics, and individual observations: A lesson in the law of small numbers.

Comments on the original article "Predoctoral internship training in Canada--I: Internship settings and supervisory issues," by J. L. Howes, T. M. Vallis, A. Wilson, M. Ross, and H. Louisy (see record 1996-06731-004). It has come to our attention that the data presented for Manitoba are misleading. It is stated (p. 175) that the average stipend in Manitoba decreased from 1992-93 to 1996-97. However, this is a statistical artifact due to the addition of a second program which paid less than the existing program. Rather than a reduction, the program participating in the 1992-93 survey actually increased its funding by $1,746 (from $28,671 to $30,417). A second program opened between '92-3 and '96-7 (with a stipend of $19,000). As well, on page 174 of our paper Manitoba's stipend is listed as $27,671 when it in fact was $28,671. We regret any confusion that reporting provincial averages may have caused. To clarify the funding issue, we reanalyzed our data on a program basis, not provincial basis (i.e., programs are the unit of measurement). We included only those 30 funded programs operating in 1992-93 in this re-analysis, the results of which are presented here. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

E-test for susceptibility testing of Mycobacterium tuberculosis

SETTING: Initial isolates should be tested for drug susceptibility to confirm the anticipated effectiveness of chemotherapy. OBJECTIVE: To evaluate E-test strips for susceptibility testing of Mycobacterium tuberculosis. DESIGN: A proportion method using Lowenstein-Jensen medium and the Bactec radiometric system were compared with the E-test (isoniazid [INH], rifampicin [RMP], ethambutol [EMB] and streptomycin [SM]). RESULTS: For 73 of the 81 M. tuberculosis isolates (90.1%) the proportion and E-test methods yielded concordant susceptibility results against all four antimicrobial agents tested. Of these 73 strains, 69 were fully susceptible; the four isolates showing resistance to antimicrobial drugs by both methods were also resistant when tested by Bactec 460TB. While the proportion method indicated susceptibility for the eight remaining strains, E-test results showed mono EMB resistance in five strains, INH resistance for two isolates (including one isolate resistant to EMB plus INH), and for one strain E-test yielded resistance to EMB and SM. Using Bactec as the reference method, the E-test resulted in false resistance in eight strains and no false susceptibility. CONCLUSION: Due to a substantial rate of false resistance, this method cannot be recommended at present for practical use in clinical laboratories.     

Passive surveillance for Kawasaki disease in San Diego County

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. Epidemiologic surveillance is conducted to monitor baseline incidence of the disease and to identify epidemics. The aim of this study was to evaluate a passive surveillance system for reporting cases of KD in San Diego County to the local, state and national health authorities. METHODS: We performed a retrospective review of a 2-year period to identify the number of patients who met criteria of the Centers for Disease Control and Prevention for diagnosis of KD and who were successfully reported to the county, state and national databases. RESULTS: The total number of KD patients for 1994 and 1995 was determined by retrospective review of medical record discharge diagnosis codes. Of the 28 San Diego County residents diagnosed with KD in 1994, 24 (86%) met CDC criteria and 15 (63%) of these eligible patients were reported to the county and state health authorities. Of the 41 residents in 1995, 34 (83%) met CDC criteria and 22 (65%) were reported to the above agencies. No patient in either 1994 or 1995 was reported by local or state health authorities to the CDC. CONCLUSION: Passive surveillance for KD in San Diego County resulted in the reporting of approximately two-thirds of the eligible patients at the county and state levels but completely failed to report any documented cases to the CDC. Implementation of a sentinel hospital reporting system should be considered as a preferred alternative to national passive surveillance in the effort to track total numbers of patients and to follow disease trends over time.     

Resistance of Mycobacterium tuberculosis to antituberculosis drugs in the Central Region of Thailand, 1996

OBJECTIVE: To determine the proportion and profile of antituberculosis drug resistance among Mycobacterium tuberculosis isolates in Thailand. SETTING: A 500-bed cardiothoracic centre. DESIGN: From January to December 1996, isolates of M. tuberculosis from consecutive patients with pulmonary tuberculosis underwent susceptibility testing to isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S), kanamycin (K), and ofloxacin (O). RESULTS: In all, 1861 strains were tested, 1738 from new cases and 123 from previously treated cases. Overall initial and acquired resistance were 20.9% and 53.6%, respectively. The percentages of initial resistance to R, H, S, O, K and E were 12.6, 8.3, 6.6, 1.8, 1.1 and 0.8, respectively, whereas those of acquired resistance were 43.0, 29.2, 21.1, 9.7, 8.1 and 4.8, respectively. Multidrug resistance was observed in 4.2% of new patients and 25.2% of previously treated patients. CONCLUSION: The overall drug resistance of M. tuberculosis in the central region of Thailand is high, and acquired multidrug resistance has reached an ominous level. The results have serious implications for tuberculosis control in Thailand. Urgent measures are needed to control the spread of drug resistance, and supervised treatment of standard protocol should be adhered to more strictly.     

Hospitalization of patients infected with active TB in New York State, 1987-1992: the effect of the HIV epidemic

Hospital discharge records were used to study the relationship between human immunodeficiency virus (HIV) epidemic and hospitalized patients with tuberculosis in New York State from 1987 through 1992. The discharges of patients coinfected with HIV and tuberculosis increased by 270%, rising from 1,573 in 1987 to 5,825 in 1992. This constitutes an increase from 19.8 to 49.1% of all discharges of patients with tuberculosis. Discharges of tuberculosis patients who were not infected with HIV decreased slightly during this time, going from 6,359 to 6,039. Postdischarge treatment plans, HIV prevention, HIV testing, and HIV educational programs for the tuberculosis population require special consideration, given the significant rise of HIV in the tuberculosis-infected population.     

The costs of healthcare worker respiratory protection and fit-testing programs

OBJECTIVE: We studied hospital costs associated with healthcare worker (HCW) respiratory protection and respirator fit-testing programs recommended by the Centers for Disease Control and Prevention (CDC) and mandated by the Occupational Safety and Health Administration to decrease nosocomial or occupational Mycobacterium tuberculosis (TB). DESIGN: The number and cost of high-efficiency particulate air (HEPA)-filter and dust-mist (DM) respirators for 1989 to 1994 were obtained from study hospital purchasing departments, and the costs of HCW fit-testing and education programs for 1994 were estimated from information provided by infection control practitioners. Costs of N-class respirator programs were estimated for study hospitals using retrospective cost analysis and an observational study. SETtING: Four urban hospitals with, and one rural community hospital without, documented nosocomial or occupational transmission of multidrug-resistant TB. RESULTS: During the study period, four of five hospitals introduced HEPA and DM respirators and respirator education and fit-testing programs. Median costs in 1994 were $83,900 (range, $2,000-$223,000) for respirators and $17,187 (range, $8,736-$26,175) for respiratory fit-testing programs. The projected median annual cost of N95 respirators was $62,023 (range, $270-$422,526). CONCLUSIONS: Compliance with CDC TB guidelines may require a substantial investment. However, outlays for respirators and education and fit-testing programs are more reasonable than would be suggested by analyses that estimated the costs of preventing one case of nosocomial TB.