Multidrug-resistant Mycobacterium tuberculosis in HIV-infected persons, Peru.During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima, Peru, and a random sample of other Lima residents with TB. Multidrug-resistant (MDR MDR,
n See multidrug resistance.
n the abbreviation for minimum daily requirement, specifically the Minimum Daily Requirements for Specific Nutrients compiled by the United States Food and Drug Administration. )-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%) of 965 patients who were HIV-negative or of unknown HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. status (p < 0.001). HIV-positive patients with MDR-TB MDR-TB Multi-Drug Resistant Tuberculosis were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis prophylaxis (prō'fĭlăk`sĭs), measures designed to prevent the occurrence of disease or its dissemination. Some examples of prophylaxis are immunization against serious diseases such as smallpox or diphtheria; quarantine to confine . However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel sentinel /sen·ti·nel/ (sen´ti-n'l) one who gives a warning or indicates danger.
a recording mechanism, such as an animal, a farm or a veterinarian, posted explicitly to record a possible occurrence or series of cases for a potentially larger epidemic of nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.
1. Of or relating to a hospital.
Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control and has been identified in almost all surveyed countries. During 1994 to 1997, the World Health Organization (WHO)-International Union against Tuberculosis and Lung Disease lung disease Pulmonary disease Pulmonology Any condition causing or indicating impaired lung function Types of LD Obstructive lung disease–↓ in air flow caused by a narrowing or blockage of airways–eg, asthma, emphysema, chronic bronchitis; identified high prevalences of MDR-TB in the former Soviet Union, Asia, the Dominican Republic Dominican Republic (dəmĭn`ĭkən), republic (2005 est. pop. 8,950,000), 18,700 sq mi (48,442 sq km), West Indies, on the eastern two thirds of the island of Hispaniola. The capital and largest city is Santo Domingo. , and Argentina (1).
MDR-TB has been associated with inadequate treatment regimens, poor adherence to treatment adherence to treatment Compliance Therapeutics The following of a recommended course of treatment by taking all prescribed medications for the length of time necessary , poorly managed TB-control programs, and unenforced hospital infection control programs, as well as HIV infection (2). HIV infection influences the natural history of TB in several ways: active TB occurs within 6 months of acquiring Mycobacterium tuberculosis Mycobacterium tuberculosis
Mycobacterium tuberculosis infection in 37% of persons with HIV-induced immunosuppression immunosuppression
Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects. (3) but occurs in 2% of immunocompetent im·mu·no·com·pe·tent
Having the normal bodily capacity to develop an immune response following exposure to an antigen.
im adults during the first year after acquiring M. tuberculosis M. tuberculosis,
n the bacterium responsible for tuberculosis, generally a respiratory infection in man; nonrespiratory tuberculosis is considered an indicator disease for AIDS. See also tuberculosis. infection (4). HIV-infected persons with TB also have increased frequency of disseminated and meningeal me·nin·ge·al
Of, relating to, or affecting the meninges.
pertaining to the meninges.
meningeal hemorrhage disease, other extrapulmonary diseases, atypical atypical /atyp·i·cal/ (-i-k'l) irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type.
adj. clinical signs and symptoms, drug-related adverse events, and negative sputum smears Noun 1. sputum smear - any of several cytologic smears obtained from different parts of the lower respiratory tract; used for cytologic study of cancer and other diseases of the lungs
bronchoscopic smear, lower respiratory tract smear for acid-fast bacilli bacilli /ba·cil·li/ (bah-sil´i) plural of bacillus.
see bacillus. (5).
Nosocomial outbreaks of MDR-TB involving HIV-infected persons have occurred in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. and other industrialized in·dus·tri·al·ize
v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es
1. To develop industry in (a country or society, for example).
2. countries (6-9), but improved treatment and hospital infection control programs have contained these initial outbreaks of MDR-TB. However, such outbreaks are increasingly recognized in countries with more limited resources (10, 11).
In Peru, the National TB Control Program received reports of 35,685 new TB cases in 1999 (incidence 141.4/100,000) (12). Passive reporting to the National TB Control Program showed HIV prevalences from 1% to 1.5% in TB patients during 1996 to 1999 (12), but prospective testing of 1,043 patients with a new event of TB in Lima and Callao from September to October 1999 found HIV seropositivity Seropositivity is the presence of a certain antibody in a blood sample. A patient with seropositivity for a particular antigen or agent is termed seropositive. in 2.3% (EE. Campos Campos (käm`ps), city (1996 pop. 391,299), Rio de Janeiro state, SE Brazil, on the Paraíba River near its mouth. , unpub. data). Furthermore, TB was the AIDS-defining illness in 10,939 (28%) AIDS cases in Peru (13), and 50% of persons with AIDS in Peru develop TB at some point in their disease.
A National TB Control Program survey during 1999 found MDR-TB in 57 (3%) of 1,879 Peruvians with a first episode of TB and in 32 (12.3%) of 260 with previously treated TB (14). Of 2,101 TB patients in that survey, 8 had a previous diagnosis of HIV infection. In 1997, at the Dos de Mayo Hospital The Mayo Hospital is located in Lahore, Punjab, Pakistan. It is a teaching hospital of King Edward Medical College. The college is located in Old Anarkali in Lahore city. in Lima, which provides care to the largest number of HIV-infected persons, 9 (34.6%) of 26 HIV-infected patients with TB had MDR-TB (15).
Mortality rates during TB treatment of Peruvian HIV-infected patients has been high; 63%, 51%, 49%, and 39% of patients with a first episode of TB died during treatment that was started in 1996, 1997, 1998, and 1999, respectively (12,16). These rates contrast with a mortality rate of 9% in HIV-infected persons with pulmonary TB pulmonary TB Pulmonary tuberculosis, see there in Haiti (17). Treatment regimens prescribed for TB in developing countries are rarely based on susceptibility testing susceptibility test Antimicrobial susceptibility test, see there , and since 1987, HIV-infected patients with a first episode of TB in Peru have received a standard course of rifampin rifampin (rĭfăm`pĭn), antibiotic used in the treatment of tuberculosis. It is also used to eliminate the meningococcus microorganism from carriers and to treat leprosy, or Hansen's disease. , isoniazid isoniazid (ī'sōnī`əzĭd), drug used to treat tuberculosis. Also known as isonicotinic acid hydrazide, isoniazid is the most effective antituberculosis drug currently available. , pyrazinamide, and ethambutol ethambutol /etham·bu·tol/ (e-tham´bu-tol) an antibacterial, specifically effective against Mycobacterium; used with one or more other antituberculous drugs in the treatment of pulmonary tuberculosis, administered as the in compliance with WHO recommendations (18). Therefore, MDR-TB might contribute to the high mortality rate for TB in HIV-infected Peruvians.
We performed this study to further characterize the prevalence and pattern of MDR-TB in HIV-infected adults in Lima and the adjacent port of Callao in Peru and to explore preventable risk factors that could be used to design, implement, and evaluate better preventive and therapeutic interventions.
Study Design and Population
This study was designed to evaluate the prevalence of MDR-TB in HIV-infected patients [greater than or equal to] 18 years of age and to assess potential risk factors for MDR-TB in HIV-infected persons with TB. The study was carried out from February 1999 to January 2000 in Lima and Callao. Lima is the capital city of Peru, and Callao is the adjacent main port; together they have a population of 8,239,891, representing 32% of the national population. Lima and Callao accounted for 78% of all Peruvian AIDS cases reported from 1983 to September 2000 (13) and for 56% of all TB cases reported in 1999 (12). The research protocol for using human participants in this study has been reviewed and approved by the Human Subject Review Committee of the University of Washington and the Ethical Committee of the Scientific Research Office at the Cayetano Heredia Cayetano Heredia (August 5, 1797 – June 11, 1861) was a Peruvian physician, born in Catacaos, Piura (Peru). Together with Hipolito Unanue he was one of the two greater Peruvian physicians of the 19th century. University. Informed consent was obtained from the participants.
From February 1999 to January 2000, we introduced an active surveillance system to identify HIV-infected adults with a new event of TB, defined as a first episode of TB or a relapse, at the 10 public hospitals that provide care for most HIV-infected persons living in Lima and Callao. Each of these 10 hospitals has a unit of the National TB Control Program where every patient with a suspected or confirmed diagnosis of TB is referred for further work-up, treatment, follow-up, or referral. To identify HIV-infected patients with a new episode of TB, one trained interviewer periodically visited each of these units. In addition, we encouraged all clinicians to send clinical specimens for isolation of M. tuberculosis, and all laboratories to submit such isolates to TB control program reference laboratories for susceptibility testing.
MDR-TB was defined as resistance to both isoniazid and rifampin, with or without resistance to other drugs. Case-patients were adults with previously diagnosed HIV infection and with a new episode of TB, whose isolates of M. tuberculosis were MDR-TB. HIV-seropositive controls were adults with previously diagnosed HIV infection and a new event of TB, whose isolates of M. tuberculosis were susceptible to isoniazid or rifampin, HIV-positive status was defined by previous, repeatedly positive enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses. (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. ) confirmed by immunofluorescence Immunofluorescence
A technique that uses a fluorochrome to indicate the occurrence of a specific antigen-antibody reaction. The fluorochrome labels either an antigen or an antibody. or Western blot Western blot
A technique developed in 1979 that is used to confirm ELISA results. HIV antigen is purified by electrophoresis and attached by blotting to a nylon or nitrocellulose filter. .
From February trough September 1999, a total of 972 adult patients with a new episode of smear-positive TB in Lima and Callao who received care at Ministry of Health facilities were included in the National TB Control Program's surveillance of resistance to anti-TB drugs. Of these 972, a total of 116 had been previously tested for HIV: 7 (6%) were HIV seropositive seropositive /se·ro·pos·i·tive/ (-poz´i-tiv) showing positive results on serological examination; showing a high level of antibody.
adj. . From the remaining 965 participants who were HIV seronegative seronegative /se·ro·neg·a·tive/ (-neg´ah-tiv) showing negative results on serological examination; showing a lack of antibody.
adj. or not tested for HIV infection, we randomly selected a second control group of 153 participants.
Enrollment, Interview, and Treatment
Both trained interviewers periodically visited each of the 10 hospitals to identify, enroll, and interview HIV-infected patients with a new episode of TB. Because classification as "case" or "control" for HIV-infected patients was determined by drug susceptibility-test results, which became available after 3 or 4 months, each HIV-infected adult with a new episode of TB was eligible to participate, and interviewers were blinded to susceptibility test results. One member of the local TB team introduced the interviewer, who explained the study and invited the patient to participate. Interviewers contacted adults with TB who were HIV seronegative or of unknown HIV status belonging to the HIV seronegative control group at their homes, where they were invited to participate, enrolled, and interviewed. Patients giving written informed consent underwent a standardized standardized
pertaining to data that have been submitted to standardization procedures.
standardized morbidity rate
see morbidity rate.
standardized mortality rate
see mortality rate. face-to-face interview concerning demographic characteristics, past and current medical history, and potential exposures to M. tuberculosis during the 12 months before onset of TB symptoms. Healthcare workers at each facility followed national guidelines of the TB and the AIDS control programs in providing further treatment and follow up of study participants. Data collected were handled exclusively by the study team, ensuring confidentiality.
Primary isolations were attempted by using Lowenstein-Jensen or Ogawa medium at each hospital laboratory and at local reference laboratories serving the national surveillance study. Susceptibility testing was carried out at the Mycobacteria mycobacteria
members of the genus Mycobacterium.
see opportunist (atypical) mycobacteria (below).
see opportunist (atypical) mycobacteria (below). Laboratory of the Peruvian National Institute of Health, the national reference laboratory for susceptibility testing, or at one of three local mycobacterium mycobacterium
Any of the rod-shaped bacteria that make up the genus Mycobacterium. The two most important species cause tuberculosis and leprosy in humans; another species causes tuberculosis in both cattle and humans. reference laboratories. These laboratories used the proportion method to determine the sensitivity profile of each strain (19), using the following critical concentrations ([micro]g/mL): isoniazid, 0.2; rifampin, 40; streptomycin streptomycin (strĕp'tōmī`sĭn), antibiotic produced by soil bacteria of the genus Streptomyces and active against both gram-positive and gram-negative bacteria (see Gram's stain), including species resistant to other , 4; ethambutol, 2; and pyrazinamide, 100. The National Reference Laboratory underwent external quality control by the Pan American Health American Health Inc. is a company that manufactures health supplements. It is located in Holbrook, New York. One of its products is labeled the "Chewable Original Papaya Enzyme" with the attached registered trademark, "The 'After Meal Supplement'". Organization/WHO Instituto Panamericano de Proteccion de Alimentos y Zoonosis Zoonosis Definition
Zoonosis, also called zoonotic disease refers to diseases that can be passed from animals, whether wild or domesticated, to humans. (INPPAZ) and performed quality control for the three local reference laboratories (20).
SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. 10.0 software (SPSS, Inc., Chicago, IL) was used for data entry and analyses. Percentages of MDR-TB were compared in HIV-positive and HIV-negative patients with TB, and risk factors for MDR-TB in HIV-infected patients were explored by calculation of odds ratios (OR) for dichotomous di·chot·o·mous
1. Divided or dividing into two parts or classifications.
2. Characterized by dichotomy.
di·chot variables. Medians of continuos variables were compared by using Student t test for independent samples.
Characteristics of Patients with TB
Of 415 HIV-seropositive patients diagnosed and reported with a new episode of TB (on the basis of acid-fast smear or culture results or on clinical characteristics) at the 10 hospitals during the study period, 157 (38%) were not interviewed: 87 had already left the hospital and could not be located at referral health centers, 67 were in poor clinical condition and unable to answer the questionnaire, and 3 declined to participate. The remaining 258 seropositive participants interviewed averaged 32 years of age (range 18 to 62) and reported 9.8 years of education; 77% were men, 57% single, and 20% had had at least one previous episode of TB. Isolation of M. tuberculosis was attempted in 239 (93%); 135 were culture-positive, 61 were smear positive for acid-fast bacilli, and 62 were diagnosed on the basis of clinical criteria. Drug-susceptibility testing was requested for all positive cultures and completed on 81, who were the focus of subsequent analyses; the remaining strains were lost before or during transport to the National Reference Laboratory for susceptibility testing.
Of the 153 TB patients randomly selected as controls without known HIV infection, we located 110; 108 agreed to participate. They averaged 29.3 years of age (range 18 to 80) and reported 10.3 years of education; 57% were men, 52% single, and 9.3% had had at least one previous episode of TB.
Table 1 presents characteristics of participants with and without known HIV infection for whom drug-susceptibility testing was completed. Because HIV infection in Peru disproportionately affects men who have sex with men Men who have sex with men (MSM) is a term used mostly in the United States to classify men who engage in sex with other men, regardless of whether they self-identify as gay, bisexual, or heterosexual. , HIV-seropositive persons were more often men and less often married, divorced, or widowed; family income and family ownership of the home were more common among those not known to have HIV infection. More importantly, previous history of TB or TB prophylaxis was significantly more common in HIV-infected participants, as was history of contact with hospitals.
Drug-Susceptibility Test Results
The prevalence of MDR-TB was 43% in the 81 HIV-seropositive patients with available susceptibility test results and 3.9% in the 965 patients whose HIV status was negative or unknown (p < 0.001); only 1 (0.9%) of 108 patients whom we randomly selected and interviewed from this group of 965 TB patients had an MDR-TB isolate (Table 2). The prevalence of resistance to any drug was also higher in M. tuberculosis isolates from HIV-positive patients than in isolates from the 965 without known HIV infection.
Drug-susceptibility test results were available for 26 (16.6%) of the 157 HIV-seropositive patients we did not interview; 35% of these patients had MDR-TB, not significantly different from the 43% of those we did interview (p = 0.44).
HIV Patients with MDR-TB and with Non-MDR-TB
Of HIV-seropositive participants with TB (Table 3), MDR-TB was significantly associated with TB diagnosed at hospital A (OR 3.7, 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [CI] 1.3 to 10), with employment during the 12 months before the onset of symptoms, and with exposure to TB at work, but not with age, sex, marital status marital status,
n the legal standing of a person in regard to his or her marriage state. , education level, crowding in the home, or low income. MDR-TB was not significantly associated with previous episodes of TB or with TB prophylaxis; the proportion who had received TB prophylaxis or had a previous episode of treatment for TB was 17 (49%) of 35 with MDR-TB versus 20 (43%) of 46 without MDR-TB (OR 1.2, 95% CI 0.5 to 3.0).
Table 4 lists the 10 major public hospitals in Lima and Callao by number of persons with newly diagnosed AIDS reported during 1999, number with TB diagnosed during 1999, number of HIV-infected patients with a new event of TB during the study, and percentage of isolates of M. tuberculosis identified as MDR-TB. All but one of the MDR-TB cases were identified in the three hospitals reporting the largest number of HIV-seropositive patients with a new event of TB during 1999.
Assessment of Possible Bias
Interviewed patients with (N = 81) or without (N = 177) susceptibility results were similar with respect to age, years of education, family income, symptom duration, time since previous TB, TB prophylaxis in the past, crowding in the home, gender, marital status, home ownership, and employment; and during the past 12 months, exposure to TB at work, exposure at home, ambulatory care ambulatory care
Medical care provided to outpatients.
n the health services provided on an outpatient basis to those who can visit a health care facility and return home the same day. at health centers, ambulatory care at hospitals, inpatient hospital care, and participation in HIV or TB support groups. History of previous TB was somewhat more frequent in those tested (27%) than in those not tested (17%, p = 0.09), and history of Pneumocystis carinii pneumonia Pneumocystis carinii pneumonia (PCP)
A lung infection that affects people with weakened immune systems, such as people with AIDS or people taking medicines that weaken the immune system.
Mentioned in: AIDS, Antiprotozoal Drugs, Sulfonamides (PCP PCP
2. primary care physician
Pneumocystis carinii pneumonia (PCP) ) prophylaxis was more frequent among those tested (50%) than in those not tested (32%, p < 0.01).
This study documents high rates of MDR-TB in HIV-infected persons with TB receiving care at public hospitals in Lima and Callao; MDR-TB was 11 times more common in these patients than in 965 TB patients without known HIV infection in Lima and Callao. In comparison to persons having TB without known HIV infection, the HIV-infected patients with TB had higher frequency of contact with health centers and hospitals, and MDR-TB was found mainly in patients receiving care at the three hospitals serving the largest number of HIV-infected patients with TB. Although participants with HIV infection more often had had previous episodes of TB, and presumably pre·sum·a·ble
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. , only the HIV-infected persons had received TB prophylaxis, these factors were not significantly associated with MDR-TB in the HIV-infected patients with TB.
The 43% prevalence of MDR-TB among HIV-infected persons with TB found in this study is higher than the 36% previously found in Italy (21), and the 28.3% found in Argentina, both during epidemics of nosocomial MDR-TB (1).
Because early clinical manifestations of TB often develop in HIV-infected persons (3,5), they mark sentinel cases that first indicate outbreaks of nosocomial transmission of TB and may represent a larger number of nosocomial transmission of TB.
Three factors drive TB transmission: the rate of exposure of susceptible to infectious persons, the efficiency of transmission per exposure, and the average duration of infectiousness once infection has occurred (22). For HIV-infected persons, higher exposure to TB in general could easily result from routine periodic visits to clinical settings also frequented by patients with TB (as occurs in Lima and Callao, where most persons with HIV infection attend HIV/AIDS HIV/AIDS Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome clinics located at large hospitals); or from the mixing of HIV-infected patients with TB patients in these settings because of the archaic practice of mixing patients who have communicable diseases communicable diseases, illnesses caused by microorganisms and transmitted from an infected person or animal to another person or animal. Some diseases are passed on by direct or indirect contact with infected persons or with their excretions. (like TB and HIV infection) in large multiple-bed wards. MDR-TB case-patients tend to be selectively hospitalized because they do not respond to routine therapy.
Conditions that increase exposure to TB, such as overcrowding overcrowding
overcrowding of animal accommodation. Many countries now publish codes of practice which define what the appropriate volumetric allowances should be for each species of animal when they are housed indoors. Breaches of these codes is overcrowding. , long waiting times in clinics, sharing of facilities, and large open multiple-bed wards, are common in medical institutions in the developing world. Increased efficiency of transmission per exposure could occur if HIV-related immunosuppression increases host susceptibility to acquisition of infection by M. tuberculosis" in general or by MDR-TB strains of TB in particular.
Several factors could prolong the duration of infectiousness of MDR-TB in HIV-immunosuppressed persons, including continued use of isoniazid- and rifampin-based regimens as initial therapy for TB in HIV-infected persons, even during ongoing outbreaks of MDR-TB transmission. Patients receiving ineffective treatment will not improve and will more often use clinical services as outpatients and as inpatients, increasing the exposure to MDR-TB of other patients. In addition, increased frequency of atypical clinical pictures and smear-negative results, relatively common features in HIV-infected patients with TB, can contribute to delayed diagnosis and prolonged infectivity infectivity
ability of an agent to infect. .
Evidence suggests that HIV infection favors the emergence of acquired drug resistance in individual patients during treatment (23,24). HIV-infected persons have a higher risk for acquisition of isolated rifampin resistance (25,26), and once- or twice-weekly rifamycin-based regimens increase the risk for acquired rifamycin rifamycin /rif·a·my·cin/ (rif?ah-mi´sin) any of a family of antibiotics biosynthesized by a strain of Streptomyces mediterranei, resistance in TB patients with advanced HIV disease (27-29). MDR-TB is more often a consequence of addition of rifampin resistance than of addition of isoniazid resistance (22).
Limitations of this study included the fact that TB cases with HIV infection were recruited from hospitals where patients with known HIV infection receive care in Lima, whereas HIV-negative controls were recruited from non-hospital clinics. However, methodologic features and results of this evaluation suggest that results may be generalizable gen·er·al·ize
v. gen·er·al·ized, gen·er·al·iz·ing, gen·er·al·iz·es
a. To reduce to a general form, class, or law.
b. To render indefinite or unspecific.
2. to all HIV-infected patients with TB receiving care within the Ministry of Health system in Lima and Callao. Of 457 new episodes of TB in HIV-infected persons [greater than or equal to] 18 years in Lima and Callao during 1999 (12), we identified 415 cases (91%) through the TB units at each of these 10 hospitals during the 12-month study. We systematically interviewed HIV-infected patients well in advance of knowing whether they had MDR-TB, and we systematically interviewed a random sample of TB patients without known HIV infection from a larger representative sample of TB patients from Lima and Callao. Participants with known HIV infection were selected consecutively and patients without known HIV infection were selected randomly from all case-patients of TB receiving care at public health services health services Managed care The benefits covered under a health contract . Comparisons of those interviewed versus not interviewed, and those tested and not tested for drug susceptibility suggested no bias, except that those tested had somewhat higher frequencies of previous TB and of PCP prophylaxis. The latter could reflect greater immunosuppression or greater contact with the medical care system. Although both could have biased results toward higher estimates of MDR-TB prevalence among HIV-seropositive patients, a previous history of TB or of TB prophylaxis was not associated with MDR-TB.
We were unable to interview all HIV-positive patients with TB diagnosed during the study, raising the question of whether the prevalence of MDR-TB was higher in those we interviewed than in those not interviewed. However, the 43% frequency of MDR-TB in those we interviewed did not differ significantly from the 35% prevalence of MDR-TB in the 26 patients who we did not interview for whom susceptibility testing was performed. Finally, concerning the fact that we did not obtain HIV serologic se·rol·o·gy
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.
2. finding from all of the 108 controls with negative or unknown HIV status, if the prevalence of HIV had been higher than the 2.3% prevalence observed during prospective testing in Lima in 1999, such misclassification bias would only have reduced the differences observed between groups.
Community-based studies throughout the United States have documented increased prevalence of MDR-TB in HIV-infected people (2), and in a recent report of several surveys (30), MDR-TB was found more often in HIV-infected patients than in HIV-uninfected patients, but after adjustment for previous treatment for TB the difference between HIV-infected and HIV-uninfected patients was no longer statistically significance. However, in our survey, even after eliminating patients with history of prior episodes of TB or TB prophylaxis, MDR-TB was still seen in 18 (43%) of 44 isolates from HIV-infected persons versus 24 (3%) of 814 HIV-negative controls (p < 0.001).
Although rigorous compliance with infection control recommendations (31), particularly those related to engineering control, is difficult in developing countries, the combined epidemics of TB, MDR-TB, and HIV/AIDS make infection control measures essential. WHO guidelines recommend a hierarchy of controls (administrative, environmental, and personal respiratory protection), many of which entail little or no cost (32). Minimal measures must include strict respiratory isolation for patients with confirmed or suspected TB and mandatory wearing of appropriate masks for persons entering all patient rooms, for patients leaving their rooms when unavoidable, and for patients with cough when seen in clinics. The efficacy of these essential measures to avert TB transmission in healthcare settings have been demonstrated (33). Segregating persons with TB from those with HIV in individual rooms with negative air flow, establishing safer sputum sputum /spu·tum/ (spu´tum) [L.] expectoration; matter ejected from the trachea, bronchi, and lungs through the mouth.
sputum cruen´tum bloody sputum. sampling collection procedures, improving the laboratory support for early identification of TB and of MDR-TB, and providing more effective treatment regimens to patients at increased risk for MDR-TB are necessary. HIV testing HIV test Various tests have been used to detect HIV and production of antibodies thereto; some HTs shown below are no longer actively used, but are listed for completeness and context. See HIV, Immunoblot. of patients with TB and susceptibility testing of M. tuberculosis isolates from HIV-infected patients should be routine in settings where outbreaks or endemic transmission of MDR-TB is occurring in HIV-infected patients.
Nosocomial MDR-TB transmission at hospital A has been ongoing since 1997. Recently published IS6110 restriction fragment length polymorphism restriction fragment length polymorphism
n. Abbr. RFLP
Intraspecies variations in the length of DNA fragments generated by the action of restriction enzymes and caused by mutations that alter the sites at which these enzymes act, changing analysis of M. tuberculosis strains collected between July 1997 and April 1999 and belonging to HIV-positive inpatients clearly implicate im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. nosocomial transmission of MDR-TB in this hospital (34). Similarly, outbreaks of nosocomial MDR-TB in HIV-infected persons have emerged first in New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , Buenos Aires Buenos Aires (bwā`nəs ī`rēz, âr`ēz, Span. bwā`nōs ī`rās), city and federal district (1991 pop. , and Lima (settings providing hospital-based care, including antiretroviral antiretroviral /an·ti·ret·ro·vi·ral/ (-ret´ro-vi?ral) effective against retroviruses, or an agent with this quality.
adj. therapy, for HIV-infected persons). Unrecognized MDR-TB outbreaks in other developing countries are likely. As delivery of antiretroviral therapy for HIV in developing countries proceeds, nosocomial exposure of HIV-infected persons to TB must be minimized. More effective surveillance, prevention, and treatment for MDR-TB are essential.
Table 1. Demographic characteristics, past medical history, and potential exposures to tuberculosis (TB) of participants with and without known HIV infection (a) Negative or HIV-infected unknown HIV (n = 81) status (n = 108) Mean [+ or -] Mean [+ or -] p value or OR Variable SD, or % SD, or % (95% CI) (b) Age 31.6 [+ or -] 29.3 [+ or -] 0.13 7.0 11.9 Male 80 57 3.0 (1.6 to 5.9) Marital status Single 59 52 0.42 Married 9 20 0.05 Divorced/widowed 11 28 <0.01 Cohabitant 21 0 <0.01 Y of education 9.6 [+ or -] 2.8 10.3 [+ or -] 0.08 2.1 No. residents/no. 3.0 [+ or -] 2.0 2.8 [+ or -] 1.4 0.48 bedrooms Family income 603 [+ or -] 333 845 [+ or -] 404 <0.01 Family owns home 75 88 0.4 (0.2 to 0.9) Employed (d) 63 28 4.4 (2.4 to 8.2) Exposure to TB at 17 3 7.3 (2.0 to work (c) 26.4) Exposure to TB at 16 1 20 (2.6 to home (c) 160) Previously treated 27 9 3.6 (1.6 to TB (c) 8.3) Ambulatory care at 21 5 5.5 (1.9 to health centers (d) 16) Ambulatory care at 40 1 70 (9.3 to hospitals (d) 526) Inpatient care (d) 14 0 <0.001 Inpatient MoH 11 0 <0.001 hospitals (d) Any exposure to 44 1 86 (11.4 to hospital (d) 644) TB prophylaxis (e) 22 0 <0.001 (a) OR, odds ratio; CI, confidence interval; MoH, Ministry of Health. (b) p values proved when comparing means or when one column had a value of 0. (c) Exposure to someone with TB at work or at home during the 12 months before onset of symptoms. (d) Variable reported by patients to have occurred during the 12 months before onset of symptoms. (e) Ever in the past. Table 2. Drug-susceptibility profiles of Mycobacterium tuberculosis isolates from participants with and without known HIV infection HIV negative or unknown status HIV positive Interviewed patients patients All patients Characteristic N (%) N (%) N (%) Total no. tested for drug resistance 81 (100) 108 (100) 965 (100) Fully susceptible isolates 28 (35) 92 (85) 789 (82) Any resistance 52 (65) 16 (15) 76 (18) Any H resistance 42 (52) 11 (10) 110 (10) Any R resistance 39 (48) 2 (2) 53 (6) Any E resistance 19 (24) 0 (0) 27 (3) Any S resistance 39 (48) 12 (11) 88 (9) Any Z resistance 28 (35) NA NA Multidrug resistance 35 (43) 1 (1) 38 (3.9) Only HR resistance 3 (4) NA NA HRZ resistance 25 (32) NA NA HRESZ resistance 11 (14) NA NA (a) NA, not available; H, isoniazid; R, rifampin; E, ethambutol; S, streptomycin; Z, pyrazinamide; HRZ resistance includes any strain resistant at least to H and R and Z. Table 3. Demographic characteristics, past medical history, and potential exposures to TB of HIV-infected participants with MDR-TB and without MDR-TB (a) HIV-infected with HIV-infected without MDR-TB (n = 35); MDR-TB (n = 46); Mean [+ or -] Mean [+ or -] Variable SD or % SD or % Employed (b) 46 76 Exposure to TB at work (c) 6 26 Exposure to TB at home (c) 20 13 Previously treated TB (d) 29 26 Duration of symptoms 6.7 [+ or -] 5.4 7.8 [+ or -] 6.6 Ambulatory care at health centers (b) 14 26 Ambulatory care at hospitals (b) 43 37 Ambulatory care at hospitals 3924 [+ or -] (c) 5749 2737 [+ or -] 3361 Inpatient care (b) 17 11 Inpatient MoH hospitals (b) 11 11 Days of hospitalization (b) 18 [+ or -] 11 30 [+ or -] 26 Diagnosed at hospital "A" 80 52 Any exposure to hospital (b) 51 39 HIV support group (b) 11 7 TB prophylaxis (d) 26 2 Mo. of TB prophylaxis 6.7 [+ or -] 5 4.4 [+ or -] 3.3 PCP prophylaxis (d) 57 44 Extrapulmonary TB 29 44 Variable p value OR (95% CI) Employed (b) 0.3 (0.1 to 0.7) Exposure to TB at work (c) 0.2 (0.04 to 0.8) Exposure to TB at home (c) 1.7 (0.5 to 5.5) Previously treated TB (d) 1.1 (0.4 to 3.0) Duration of symptoms 0.44 Ambulatory care at health centers (b) 0.5 (0.2 to 1.5) Ambulatory care at hospitals (b) 1.3 (0.5 to 3.1) Ambulatory care at hospitals (c) 0.48 Inpatient care (b) 1.7 (0.5 to 6.1) Inpatient MoH hospitals (b) 1.1 (0.3 to 4.3) Days of hospitalization (b) 0.36 Diagnosed at hospital "A" 3.7 (1.3 to 10) Any exposure to hospital (b) 1.6 (0.7 to 4.0) HIV support group (b) 1.9 (0.4 to 8.9) TB prophylaxis (d) 1.4 (0.5 to 4.1) Mo. of TB prophylaxis 0.27 PCP prophylaxis (d) 1.7 (0.7 to 4.2) Extrapulmonary TB 0.5 (0.2 to 1.3) (a) MDR-TB, too multidrug-resistant tuberculosis; OR, odds ratio; CI, confidence interval; MoH, Ministry of Health; PCP, Pneumocystis carinii pneumonia. (b) Variables reported by patients to have occurred 12 months before onset of symptoms. (c) Exposure to someone with TB at work or at home 12 months before onset of symptoms. (d) Ever in the past. (e) As a continuous variable: total minutes of exposure 12 months before onset of symptoms. Table 4. Ranking of hospitals by number of newly diagnosed cases of AIDS, tuberculosis (TB), HIV, and TB co-infection, February 1999-January 2000 (a,b) Total no. No. (%) HIV- HIV- infected infected No. AIDS No. TB patients patients No. MDR-TB / patients patients with a with a new total drug reported diagnosed new diagnosis susceptibility during during diagnosis of TB test results Hospital 1999 (c) 1999 of TB interviewed available (%) A 154 1,985 204 116 (57) 28/52 (54) B 60 723 49 40 (82) 4/9 (44) C 139 1,068 41 24 (59) 2/7 (29) D 10 891 37 29 (78) 0/4 (0) E 33 635 33 21 (64) 0/5 (0) F 95 608 29 11 (38) 0/1 (0) G 9 425 12 11 (92) 0/1 (0) H 30 169 6 4 (67) 0/1 (0) I 4 130 3 1 (33) 0/0 (NA) J 2 131 1 1 (100) 1/1 (100) Total 554 6,765 415 258 35/81 (43) (a) Among those co-infected with TB and HIV, the number (%) with MDR-TB. (b) MDR-TB; multidrug-resistant tuberculosis. (c) Number of AIDS cases reported to the National AIDS and STD Control Program.
These authors were supported by Fogarty International Center, International AIDS Research and Training Program grant NIH "Not invented here." See digispeak.
NIH - The United States National Institutes of Health. T22TW00001 ; and the University of Washington Center for AIDS Research Grant NIAID NIAID National Institute of Allergy and Infectious Diseases. AI-27757.
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Pablo E. Campos, * ([dagger]) Pedro G. Suarez, ([double dagger double dagger
A reference mark () used in printing and writing. Also called diesis.
Noun 1. ]) Jorge Sanchez, ([dagger]) ([section]) David Zavala, ([double dagger]) Jorge Arevalo, ([double dagger]) Eduardo Ticona, ([double dagger]) Charles M. Nolan, * ([paragraph]) Thomas M. Hooton, * and King K. Holmes *
* University of Washington, Seattle, Washington This page is protected from moves until disputes have been resolved on the .
The reason for its protection is listed on the protection policy page. , USA; ([dagger]) Cayetano Heredia University, Lima, Peru; ([double dagger]) Peruvian Ministry of Health, Lima-Peru; ([section]) Asociacion Civil Impacta Salud y Educacion (IMPACTA), Lima, Peru; and ([paragraph]) Public Health Seattle-King County, Seattle, Washington, USA
Dr. Campos is an associate professor at the Cayetano Heredia School of Public Health. He has worked in HIV prevention and care since 1990.
Address for correspondence: King K. Holmes, Center for AIDS and STD (Subscriber Trunk Dialing) Long distance dialing outside of the U.S. that does not require operator intervention. STD prefix codes are required and billing is based on call units, which are a fixed amount of money in the currency of that country. , University of Washington, Box-359931, 325 9th Ave. Seattle, WA 98104, USA; fax: 206-731-3694; email:email@example.com