Extrapulmonary tuberculosis in high prevalence of tuberculosis and low prevalence of HIV

The authors' data show a higher rate of pleural and meningeal involvement among extrapulmonary TB cases than expected by previous works. Special attention should be given to tuberculous meningitis cases among all extrapulmonary TB cases because of its high mortality rate. The most common extrapulmonary involvement is pleural. Pleural involvement is most common among the young male military service personnel. These data underscore the importance of determining pleural involvement among extrapulmonary TB cases and emphasize the need to consider clinic and epidemiologic differences in the diagnosis and evaluation of extrapulmonary TB. Finally, it seems unlikely that HIV infection currently has a role in the cause of extrapulmonary TB in the authors' region.     

Unusual presentation of renal tuberculosis

Urogenital tuberculosis (TB) is a common late manifestation of an earlier symptomatic or asymptomatic pulmonary TB infection. A latency period ranging from 5 to 40 years between the time of the initial infection and the expression of urogenital TB frequently occurs. As one of the most common sites of involvement of extrapulmonary TB, urogenital TB accounts for 15% to 20% of the infections. We present a patient who had culture-negative active tubercular kidney disease due to silent tuberculous infection. Our case demonstrates the limitations of noninvasive testing in establishing the diagnosis of renal tuberculosis.     

Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection

The annual number of cases of culture-proven extrapulmonary tuberculosis (TB) at our hospital increased from 47 cases in 1983 to 113 cases in 1988. At least 43% (199) of 464 consecutive patients with extrapulmonary TB during this 6-year period were infected with the human immunodeficiency virus (HIV); since HIV serologic testing was not performed routinely the true HIV prevalence is likely to be higher. Of the HIV-infected patients, 59% were intravenous drug users, 31% were Haitian, 3% were homosexual males, 1% were perinatally-infected infants, and 6% did not have a known risk factor for HIV infection. Ninety-eight percent of the HIV-infected patients were black (84%) or hispanic (14%). The HIV-infected patients were more likely than the control patients to have either disseminated, genitourinary, intra-abdominal, mediastinal, or concurrent pulmonary TB. Fever was nearly universal among the HIV-infected patients, but was absent in about one-third of the control patients. Among untreated HIV-infected patients, disease progression was rapid and nearly always fatal. Among HIV-infected patients who received treatment, the response to therapy, as judged by hospital survival and time to defervescence, was similar to that of the control patients. Despite the extensive tuberculous dissemination among the HIV-infected patients, the diagnosis of TB was difficult and often delayed. In addition to the decrease in tuberculin reactivity and the atypical chest radiograph patterns, there was a need to consider other HIV-related infections in the differential diagnosis. Although sputum specimens grew M. tuberculosis in greater than 90% of the HIV-infected patients in whom they were obtained, sputum AFB stains were positive in less than 50%. Blood and urine specimen cultures were positive in 56% and 77% of the HIV-infected patients in whom these specimens were obtained, but did not provide a means of early diagnosis. Cerebrospinal fluid and pleural fluid were abnormal in nearly all patients with involvement of these sites but were rarely AFB-positive and were, therefore, only suggestive of TB. Procedures such as biopsies and aspirates of peripheral lymph nodes, visceral lymph nodes, liver, and bone marrow provided the highest immediate diagnostic yields with rates between 50% and 90%. These procedures must be considered early in the course of illness in HIV-infected patients with suspected extrapulmonary TB due to the rapidly progressive nature of this often fatal but usually treatable infection.     

Disseminated tuberculosis in the acquired immunodeficiency syndrome era

To assess the influence of human immunodeficiency virus type 1 (HIV)-induced immunodeficiency on the clinical, radiographic, and pathologic features of disseminated tuberculosis (TB), we studied 79 patients presenting in 1984 through 1987 with miliary or focal disseminated disease due to Mycobacterium tuberculosis, as well as 4 additional non-HIV patients diagnosed after 1987. Clinically defined acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) was present in 51 (Group 1). A total of 20 had TB unrelated to HIV disease (Group 2). The remaining 12 were excluded because the role of HIV could not be determined. Clinical features were similar between groups aside from younger age; lower hemoglobin, total leukocyte, lymphocyte, and platelet counts; and more frequent tuberculin anergy (90 versus 40%) in AIDS/ARC patients (p less than or equal to 0.03). Chest radiographs showed a miliary pattern in about half of each group. Pleural effusion occurred only in AIDS/ARC patients (24%, p = 0.02), but intrathoracic lymphadenopathy was present in about a third of each group. Tissue biopsies (n = 70) usually revealed necrotizing granulomatous inflammation in each group, with a tendency to greater necrosis and more numerous acid-fast bacilli in Group 1. Granulomas were usually poorly formed in AIDS/ARC patients (59 versus 18%, p = 0.01). Autopsy of 9 AIDS/ARC patients with overwhelming miliary TB revealed a "nonreactive" histologic pattern with poorly organized or absent granulomas, extensive necrosis, and numerous bacilli. HIV-related disseminated TB causes a major constitutional illness with a high short-term mortality (25%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycobacterial disease associated with HIV infection

Mycobacterial disease is a major part of the spectrum of opportunistic infections (OIs) associated with HIV infection.Mycobacterium avium intracellulare (MAI) andMycobacterium tuberculosis are the most common mycobacterial pathogens afflicting HIV-positive patients. Infection with MAI tends to be an OI of advanced AIDS, and the results of treatment are frequently unsatisfactory.M. tuberculosis tends to attack patients much earlier in the course of their HIV disease, responds to standard treatment, and is the most contagious of the life-threatening HIV-related pathogens. This article provides concise information about the management of mycobacteriosis in the context of HIV infection. It is directed especially at primary care physicians. Emphasis is on clinical manifestation, diagnosis, therapy, and prevention.     

Mycobacterial disease associated with HIV infection

Mycobacterial disease is a major part of the spectrum of opportunistic infections (OIs) associated with HIV infection.Mycobacterium avium intracellulare (MAI) andMycobacterium tuberculosis are the most common mycobacterial pathogens afflicting HIV-positive patients. Infection with MAI tends to be an OI of advanced AIDS, and the results of treatment are frequently unsatisfactory.M. tuberculosis tends to attack patients much earlier in the course of their HIV disease, responds to standard treatment, and is the most contagious of the life-threatening HIV-related pathogens. This article provides concise information about the management of mycobacteriosis in the context of HIV infection. It is directed especially at primary care physicians. Emphasis is on clinical manifestation, diagnosis, therapy, and prevention. Received from the Division of Allergy and Clinical Immunology, Harbor-UCLA Medical Center, F-10, 1000 West Carson Street, Torrance, CA 90509.     

Long-term follow-up of tuberculoma of the brain in an AIDS patient.

Human immunodeficiency virus infection and extrapulmonary TB are defined as AIDS. The clinical manifestations of the TB are related to the interplay of the organism and the host's immune system. A seven-year follow-up of a woman successfully treated for biopsy- and culture-documented tuberculous brain abscess is described. Antibodies to HIV have been positive on repeated testing, yet CD4 counts remain over 500. Aggressive diagnostic and therapeutic maneuvers for all forms of TB in AIDS are warranted since long-term prognosis may be good.     

AIDS合并结核病患者HIV RNA定量和CD4+T淋巴细胞计数特点分析

目的 总结AIDS合并结核病的临床特点,进一步提高对AIDS合并结核病的认识.方法 将AIDS合并结核病患者分为肺内结核组、肺内结核并肺外结核组和肺外结核组,比较和分析3组之间HIV RNA定量、CD4+T淋巴细胞计数的差异.结果 肺内结核组的HIV RNA定量明显低于肺内并肺外结核组和肺外结核组(P均＜0.05).肺内结核组的CD4+T淋巴细胞计数明显高于肺内并肺外结核组和肺外结核组(P均＜ 0.05).结论 患者的HIV RNA载量越高、CD4+T淋巴细胞计数越低,免疫功能越差,越易发生肺外结核和肺内并肺外结核,越易导致结核分枝杆菌播散性传播.     

T lymphocyte responses to mycobacterial antigen in AIDS patients with disseminated Mycobacterium avium-Mycobacterium intracellulare infection

Patients with acquired immunodeficiency syndrome (AIDS) who have Mycobacterium avium-Mycobacterium intracellulare (MAI) infection typically have widely disseminated disease, often fail to respond to multi-drug chemotherapeutic regimens, and show little or no inflammatory tissue response. To determine if this clinicopathologic state correlates with in vitro lymphocyte responses to specific antigen, peripheral blood mononuclear cells from 18 patients with AIDS who had MAI bacillemia were stimulated with either particulate (heat-killed bacille Calmette Guérin [BCG]) or soluble (M intracellulare) mycobacterial antigens. In comparison to reactive cells from healthy control subjects testing positive with purified protein derivative of tuberculin (PPD) or from MAI-colonized (non-AIDS) control subjects, cells from 16 (89 percent) patients with AIDS essentially failed to show any antigen-induced proliferative activity or secretion of gamma-interferon; however, in two patients, antigen-stimulated proliferation of gamma-interferon production was modest but within the range of responses of normal healthy control subjects. Thus, although an occasional patient with AIDS can develop disseminated MAI infection despite the presence of antigen-reactive cells in vitro, most MAI-infected patients with AIDS display a striking defect in responsiveness to both particulate and soluble mycobacterial antigens. Since treatment with gamma-interferon activates the mononuclear phagocyte in vivo, these results suggest a rationale for a trial of gamma-interferon therapy in patients with AIDS who have disseminated MAI infection.     

Primary sternal tuberculosis osteomyelitis: A case report and discussion

As immigration to the United States from countries endemic for tuberculosis (TB) increases, the incidence of pulmonary and extrapulmonary TB disease may increase. Primary tuberculous sternal osteomyelitis is one form of extrapulmonary TB that is exceedingly rare throughout the world, and falls under the differential diagnosis for chest wall masses. Management involves standard antituberculous therapy with antibiotics similar to treating other forms of extrapulmonary TB, as well as consideration of surgical intervention depending on the extent of osteomyelitis. A typical case of primary sternal TB osteomyelitis is reported, and the epidemiology, differential diagnosis, clinical manifestations and management are reviewed.     

Tuberculosis in patients with human immunodeficiency virus infection

Tuberculosis (TB) is the major opportunistic infection of human immunodeficiency virus (HIV)-infected persons worldwide. Human immunodeficiency virus infection is the most potent known risk factor for reactivation of latent Mycobacterium tuberculosis infection, and TB disease appears to increase the rate of HIV progression. Pulmonary disease is seen in most patients, including a large proportion of those with extrapulmonary disease. Failure to suspect TB and to order the appropriate diagnostic tests is the most common reason for diagnostic delays. With advancing HIV infection, tuberculin skin test reactivity decreases along with reactivity to nonspecific antigens such as mumps, tetanus toxoid, and Candida; anergy testing need not be a routine component of tuberculosis screening of HIV-infected persons. The diagnosis depends on identifying the organism on smears or cultures; direct amplification tests may facilitate rapid identification of M. tuberculosis, but the relatively low sensitivity in smear-negative specimens limits their use. Also, these tests must be used in conjunction with the clinical assessment, and they must always be performed in conjunction with microscopy and standard culture. Shorter courses of combination preventive therapy of patients with latent tuberculous infection are effective, but the potential advantages of improved adherence and reduced costs of shorter courses should be balanced with an increased risk secondary to ongoing TB exposure in areas with a high TB prevalence. Six months of treatment for active tuberculosis is recommended, unless the response of a particular patient is slow or otherwise suboptimal. The use of highly active antiretroviral therapy (HAART) made a remarkable impact on the course or HIV disease, but raises several issues with respect to HIV-related TB. Drug interactions necessitate either a non-rifamycin-based regimen or a rifabutin-based regimen in patients on HAART treated for TB.     

Epidemiology of extrapulmonary tuberculosis. A comparative analysis with pre-AIDS era

To study the changes in the epidemiology of extrapulmonary tuberculosis in Tennessee, we compared the 454 cases of extrapulmonary tuberculosis reported between 1977 and 1981 with 356 cases encountered between 1982 and 1986. The data were analyzed by age, sex, race and site of the disease which were compared with the national statistics during the periods. We observed that 11.3 percent of the total TB cases were extrapulmonary. Unlike national statistics, the proportion of extrapulmonary tuberculosis had remained unchanged between the two study periods. Except for a significant decline (p less than 0.001) in genitourinary tuberculosis, the incidence of other extrapulmonary TB had remained the same. The higher incidences of lymphatic, miliary, and meningeal TB were noted in nonwhites, particularly in the younger population, during both study periods. While the national trend showed a steady increase in the percentage of extrapulmonary TB cases, there was no change in Tennessee. The reason for a continued decline of GU TB remains unclear. Although AIDS may have contributed toward the increase nationally, fewer cases of AIDS in the state have not influenced the proportion of extrapulmonary TB. Awareness of such regional differences in the epidemiology of TB, and the impact of HIV infection, will be very useful to physicians and other health care providers involved in the diagnosis, treatment, and prevention of tuberculosis.     

Extrapulmonary pneumocystosis: the first 50 cases

Over the last 35 years, 50 cases of extrapulmonary infection with Pneumocystis carinii have been reported in the literature throughout the world. Use of prophylactic aerosolized pentamidine may have facilitated the relative prevalence of extrapulmonary disease because of its inadequate systemic distribution. An increase in reported cases of infections due to P. carinii has been seen in conjunction with AIDS, but extrapulmonary pneumocystosis represents less than 1% of all cases of infection with P. carinii. Several organs or tissues may be involved, but the most common sites are lymph nodes, spleen, liver, and bone marrow. Extrapulmonary spread of P. carinii infection occurs via both lymphatic and hematogenous routes. While all patients with disseminated forms of this infection die rapidly, survival for patients with AIDS is possible if systemic treatment is provided, if a single extrapulmonary site is involved, and if no concomitant pneumonia is present. Because of the increasing frequency of this condition in patients who do not have pneumonia due to P. carinii, extrapulmonary pneumocystosis should be included among the AIDS-defining criteria.     

Tuberculosis in HIV infection.

Persons with AIDS (PWAs) are 100 times more likely to develop tuberculosis (TB) than the general population. The TB incidence rates in PWAs in the US range from 4-21%, especially among intravenous drug users and Haitians. In Florida, 60% of Haitian AIDS patients also had TB compared to 2.7% of non-Haitian AIDS patients. At a hospital in London, England, 25% of PWAs also had TB and 42% of all AIDS patients at this hospital were members of racial groups with a high prevalence of TB. In developed countries, reactivation of a latent TB infection is generally what occurs in AIDS patients. The absolute number of AIDS patients with TB in these countries is low and unlikely that it will spread to non-HIV seropositive patients. On the other hand, 30-60% of adults have been infected with Mycobacterium tuberculosis in central Africa and HIV seroprevalence is also high. So many AIDS patients here can develop TB through reactivation or exogenous primary infection. This situation significantly increases the risk of TB for HIV seronegative persons. In fact, TB is 1 of the most frequent opportunistic infections in PWAs in developing countries, such as central Africa. In patients at an early stage of HIV infection, TB manifests itself classically. The clinical presentation in patients in the late stages includes fever, weight loss, malaise, productive cough accompanied with labored breathing, an atypical chest radiograph, and extrapulmonary TB. This atypical pattern often results in delays of diagnosis and treatment. Many sputum samples do not test positive for M. tuberculosis therefore if a physician suspects TB, treatment should begin immediately. Some studies demonstrate that isoniazid prophylaxis substantially decreases the incidence of TB in HIV seropositive patients in Zambia. There is no conclusive evidence of the harm or effectiveness of the BCG vaccine in HIV children and adults.     

Tuberculous cardiac tamponade and AIDS

Tuberculosis, usually extrapulmonary, is often associated withAIDS but ruberculous pericarditis is a rare manifestation inthis group. We report three patients with tuberculous pericarditisas the first manifestation of AIDS.     

Assessment of tuberculosis infection during treatment with biologic agents in a BCG-vaccinated pediatric population

Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early.     

Disseminated extrapulmonary tuberculosis with skin, lymph node and bone involvement

Disseminated extrapulmonary tuberculosis is uncommon in no immunocompromised hosts. We described the case of a 68-year-old HIV seronegative man, who presented with a 5 months history of constitutional symptoms, generalized lymphadenopathy, evening fever, osteomyelitis of the left fibula and cutaneous lesions (papules and pustules). There was neither clinical nor radiological evidence of pulmonary involvement. On the basis of bacteriological and pathological findings the diagnosis of disseminated extrapulmonary tuberculous was made.     

Disseminated infection with Mycobacterium avium-intracellulare. A report of 13 cases and a review of the literature

Thirteen cases of disseminated infection with Mycobacterium avium-intracellulare (MAI) seen at the National Jewish Hospital and Research Center and 24 cases from the literature were analyzed to define clinical and therapeutic features of the disease. Disseminated MAI infection was a disease of immunocompromised and apparently normal hosts. It was acquired from the environment by unknown mechanisms, usually entering the body through the lungs and spreading to include the reticuloendothelial system, bones, and less commonly, the skin. Diagnosis was often delayed and required culture of tissue or secretions. Medical personnel must maintain a high index of suspicion for MAI disease, especially in immunocompromised hosts. These patients should be monitored carefully for evidence of MAI with frequent cultures of blood and bone marrow. Blood culture systems able to recover MAI promptly and reliably should be employed (52, 64). New diagnostic aids, such as the standardized preparation of PPD-B currently being prepared or tests for antibody to MAI, will help in differentiating MAI from other processes. If MAI is recovered, broad-spectrum therapy should be instituted. Response to combination antimicrobial chemotherapy in the patients surveyed in this report was gratifying. Over two-thirds of treated patients responded to therapy. New antimycobacterial agents such as ansamycin and thienamycin have been shown to have activity against MAI in vitro (40, 81, 92) and may further improve therapeutic efficacy. Studies of in vitro synergy, currently in progress in our laboratory, will also help define the optimal therapeutic regimen for each individual patient. While the patients presented in this report had a reassuring response to therapy, those who had many bacilli in the tissues had a poorer outcome. Patients with AIDS often have this lepromatous histology (37) and thus may respond more poorly than the patients in this report even when optimal therapy is employed. Careful monitoring of AIDS patients for MAI infection may permit earlier institution of therapy and improve the chances for control of the infection. Studies to assess the relationship of in vitro sensitivity to therapeutic response in these patients are currently underway in our laboratory. It is hoped that early institution of therapy and optimization of regimens according to in vitro sensitivity data will lead to decreased morbidity and mortality in all patients with MAI infection.     

A case of hepatic tuberculosis: A tuberculoma

Tuberculosis (TB) is a common cause of morbidity and mortality worldwide and its eradication in the United States has stalled for the first time in decades. Isolated hepatic TB is an extremely uncommon form of extrapulmonary TB. Here we present a case of a tuberculous liver abscess and suggest that TB should be considered in patients who fail to respond to antibiotics and prompt diagnostic intervention.