Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States.

SETTING: Health care workers and medical students in the United States subject to annual tuberculin skin testing. OBJECTIVE: To use skin testing with Mycobacterium avium sensitin (MAS) to determine contemporary rates of infection with non-tuberculous mycobacteria (NTM) and their effect on reactions to M. tuberculosis purified protein derivative (PPD). DESIGN: Dual skin testing was performed with PPD and MAS on 784 health care workers and medical students in the northern and southern US. MAS reactions that were > or = 5 mm and also > or = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM. RESULTS: MAS reactions were > or = 5 mm in 40% and > or = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P < 0.001). PPD reactions were > or = 15 mm in 3% of subjects. PPD reactions > or = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P < 0.001). MAS dominant reactions were found in 82% of subjects with 5-9 mm PPD reactions and 50% with 10-14 mm PPD reactions; these reactions were more common among whites (P = 0.046), US-born (P = 0.038) and subjects without BCG immunization (P = 0.004). CONCLUSIONS: Infections with NTM are responsible for the majority of 5-14 mm PPD reactions among US-born health care workers and medical students subject to annual tuberculin testing.     

Tuberculin skin test reactivity among adults infected with human immunodeficiency virus.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults.     

Self-assessment of tuberculin skin test reactions by drug users with or at risk for human immunodeficiency virus infection.

SETTING: Self-assessment of tuberculin test results, if accurate, could enhance tuberculosis screening efforts by reducing the need for follow-up visits for skin test reading. We investigated tuberculin test self-assessment in a longitudinal study of tuberculosis infection among drug users. OBJECTIVE: To determine the accuracy of tuberculin reaction self-assessment by drug users at high risk for tuberculosis infection. DESIGN: Two readings were compared of the same skin test, performed 48-72 hours after placement: 1) self-assessment using a simple yes-no approach to induration, versus 2) trained examiner reading. Self-assessments were performed immediately prior to trained examiner readings. RESULTS: Participants were 137 human immunodeficiency virus (HIV) seropositive and 344 HIV-seronegative current and former drug users. Ten per cent (35/344) of reactions read by participants as 'flat' were read by trained examiners as > or =5 mm (54% of which were > or =10 mm). Twenty-three per cent (19/82) of reactions read by trained examiners as > or =10 mm and 32% (35/110) of reactions read by trained examiners as being > or =5 mm were self-read by participants as 'flat'. Sensitivity (0.68) and specificity (0.83) of self-read tuberculin reactions were sub-optimal. Inter-reader reliability was poorer between participants and trained examiners than between trained examiners. CONCLUSION: Self-assessments of tuberculin skin test responses by drug users with or at risk for HIV infection are not reliable.     

Humoral response to Mycobacterium tuberculosis in patients with human immunodeficiency virus infection.

The effect of the human immunodeficiency virus (HIV) on mycobacterial antibody production was investigated. Using an enzyme-linked immunosorbent assay (ELISA) for detecting IgG against Mycobacterium tuberculosis PPD, it was observed that individuals at risk of HIV infection show a pattern of humoral response to the tubercle bacillus similar to that previously found in the immunocompetent population not exposed to risk factors: 6 of 12 (50.0%) tuberculosis cases had elevated levels of antibodies to PPD and 27 of 30 (90.0%) asymptomatic individuals had antibody levels within the normal range. In an HIV-seropositive group without AIDS indicator diseases, 8 of 22 (36.4%) tuberculous patients had detectable mycobacterial antibodies whereas 156 of 164 (95.1%) non-tuberculous subjects did not. Among AIDS cases, only 1 of 20 (5.0%) patients with tuberculosis and none of 53 non-tuberculous subjects showed a positive result. The study evidenced an increasing humoral unresponsiveness to PPD in the progression of HIV infection to AIDS. Thus, a serodiagnostic method for detecting tuberculosis such as the ELISA here employed noticeably decreases its utility in the latency stage of the HIV infection, and it is practically useless in clinical AIDS.     

Surfactant protein a promotes attachment of Mycobacterium tuberculosis to alveolar macrophages during infection with human immunodeficiency virus.

The incidence of tuberculosis is increasing on a global scale, in part due to its strong association with human immunodeficiency virus (HIV) infection. Attachment of Mycobacterium tuberculosis to its host cell, the alveolar macrophage (AM), is an important early step in the pathogenesis of infection. Bronchoalveolar lavage of HIV-infected individuals demonstrated the presence of a factor which significantly enhances the attachment of tubercle bacilli to AMs 3-fold relative to a normal control population. This factor is surfactant protein A (SP-A). SP-A levels are increased in the lungs of HIV-infected individuals. SP-A levels and attachment of M. tuberculosis to AMs inversely correlate with peripheral blood CD4 lymphocyte counts. Elevated concentrations of SP-A during the progression of HIV infection may represent an important nonimmune risk factor for acquiring tuberculosis, even before significant depletion of CD4 lymphocytes in the peripheral blood occurs.     

Efficacy of a cell-mediated reaction to the purified protein derivative of tuberculin in the disposal of Mycobacterium leprae from human skin.

The purpose of this study was to evaluate the effects of a delayed-type cell-mediated immune response to Mycobacterium tuberculosis antigen on the Mycobacterium leprae load in the skin of leprosy patients. Twelve patients with the lepromatous form of leprosy have been injected intradermally with 5 units of the purified protein derivative of tuberculin (PPD). Ten individuals responded with areas of induration ranging from 12 to 21 mm in diameter, and two were unresponsive (less than 10 mm). Twenty-one days thereafter, the injected and control sites were biopsied, and the histology, number of acid-fast bacilli, nature and phenotype of the emigrant cells, and ultrastructural characteristics of the lesions were evaluated. Eight of the 10 responding patients showed reductions in the number of acid-fast bacilli by factors ranging from 5 to 10,000. Two responders and both nonresponders exhibited no discernible decline in the number of organisms. The reduction in bacillary load was correlated with an intense mononuclear cell infiltrate, the maintenance of a high CD4+ T-cell/CD8+ T-cell ratio, the formation of granulomata, and the extensive destruction of previously parasitized macrophages.     

Association of human immunodeficiency virus and anal human papillomavirus infection among homosexual men.

BACKGROUND--A previous study of men with proctitis, proctocolitis, or enteritis showed an association of anal human papillomavirus (HPV) infection with human immunodeficiency virus (HIV) infection. Because anorectal abnormalities may confound an observed association between anal HPV DNA and HIV seropositivity, the present study was undertaken among consecutive homosexual men seeking HIV serologic testing who were unselected for anorectal symptoms. METHODS--Consecutive homosexual men underwent a standardized interview, physical examination, and collection of specimens for HIV serologic testing and detection of anal HPV DNA. RESULTS--Anal HPV DNA was detected in eight (31%) of 26 HIV-seropositive men and in 10 (8%) of 119 HIV-seronegative men (odds ratio, 5.8; 95% confidence interval, 1.1 to 30.1, adjusted for history of sexually transmitted disease, current anorectal symptoms, and age). When men with anorectal symptoms were excluded from the analysis, anal HPV DNA was detected in 27% of seropositive men compared with 8% of seronegative men (odds ratio, 4.4; 95% confidence interval, 1.4 to 13.4). There was no difference between HIV-seropositive and HIV-seronegative men with respect to distribution of type of HPV DNA. Men with group II or III and group IV HIV disease were 4.1 and 10.9 times, respectively, more likely than HIV-seronegative men to have anal HPV DNA detected. CONCLUSIONS--Because HIV-seropositive men appear to be at increased risk for the detection of anal HPV DNA, the natural course of anal HPV infection should be compared among HIV-seropositive and HIV-seronegative homosexual men.     

Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease.

The epidemiology and natural history of bacterial infections among ambulatory patients with advanced human immunodeficiency virus (HIV) disease has not been well described. In this prospective study, 394 subjects were enrolled and followed at 8-week intervals for a median of 21 months. During follow-up, 164 (42%) of 394 patients developed at least 1 bacterial infection. The most common infections were sinusitis, bacterial pneumonia, skin and soft tissue infection, and bronchitis. Serious bacterial infections (defined as bacterial pneumonia, bacteremia, or deep visceral abscess) were reported by 56 subjects (14%). Female sex, age of <40 years, and Karnofsky score of < or =80 were independent risk factors for bacterial infections. Prophylaxis with clarithromycin, trimethoprim and sulfamethoxazole, or both had significant protective effect. The occurrence of any confirmed bacterial infection was associated with a significantly increased risk of mortality. This study documents that bacterial infections are common among patients with advanced HIV disease, especially among women.     

Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection.

Hepatitis C virus (HCV) has emerged as a major pathogen among patients with human immunodeficiency virus (HIV). Morbidity and mortality were compared among 263 patients with HIV alone, 166 patients with HIV and HCV, and 60 patients with HCV alone (mean duration of follow-up, 2 years and 10 months). No differences in HIV loads and CD4 cells counts were observed between the HIV and HIV/HCV groups. Alanine aminotransferase levels were higher (52 U/L versus 35 U/L; P<.05) and albumin levels were lower (3.5 g/dL versus 3.8 g/dL; P <.02) among coinfected patients than they were among patients with HIV alone. Liver decompensation developed in 10% of patients with HIV/HCV coinfection. In contrast, no liver-related deaths or decompensation occurred in patients without coinfection (P<.05). Of the patients with HIV alone, 7% died, compared with 11% of the coinfected patients (P<.02); 47% of the deaths in the latter group were due to liver-related causes. In summary, HCV infection causes increased morbidity and mortality in patients with HIV infection.     

A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.

Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.     

Positive Kveim test in patients with coexisting sarcoidosis and human immunodeficiency virus infection.

We present two cases of sarcoidosis complicated by HIV infection. Each case had a different level of sarcoidosis activity and coexisted with either an AIDS-related infection or a HIV-positive state. Manifestations of sarcoidosis were not apparent in the patient with the AIDS-defining opportunistic infection, but were active in the patient with asymptomatic HIV infection. Both patients had granulomatous reactions to Kveim antigen, and one had such a reaction following an AIDS-defining infection. These findings suggest that non-T-cell mechanisms may be involved in granuloma formation in sarcoidosis.     

人类免疫缺陷病毒感染/艾滋病合并结核分枝杆菌感染诊治专家共识

2017年, 中华医学会感染病学分会艾滋病学组和中华医学会热带病与寄生虫学分会艾滋病学组共同制订并发布了第1版《HIV合并结核分枝杆菌感染诊治专家共识》。2021年, 中国性病艾滋病防治协会HIV合并结核病专业委员会组织相关专家对第1版共识进行了修订和更新。新版共识更新了人类免疫缺陷病毒感染/艾滋病患者的结核病预防性治疗、结核病的分子诊断、耐药结核病的治疗、抗反转录病毒治疗启动时机与方案、结核相关免疫重建炎症综合征的诊断及处理、不良反应等方面的进展。本共识将根据最新临床研究证据定期进行更新。     

Combined intra- and extracellular immunization against human immunodeficiency virus type 1 infection with a human anti-gp120 antibody.

In this study, a human CD4+ T lymphocyte line was transduced to secrete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency virus type 1 (HIV-1) envelope protein. In the transduced cells infected with HIV-1, the nascent Fab fragments bind intracellularly to the HIV-1 envelope protein and inhibit HIV-1 production. The secreted Fab fragments are able to neutralize cell-free HIV-1. In addition, the nascent Fab fragments can inhibit HIV-1 production by binding intracellularly to envelope mutants that escape neutralization by extracellular F105 antibody. The combined intra- and extracellular binding activities of the expressed Fab fragments result in the efficient blocking of cytopathic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infection but also can protect surrounding lymphocytes by secreting neutralizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases.     

A comparison of dual skin test with mycobacterial antigens and tuberculin skin test alone in estimating prevalence of Mycobacterium tuberculosis infection from population surveys.

SETTING: City of Manaus, Amazonas, Brazil. OBJECTIVE: To compare estimates of Mycobacterium tuberculosis infection prevalence obtained using traditional tuberculin skin test (TST) criteria and dual skin test (DST) data. METHODS: A total of 1070 schoolchildren received DST with tuberculin and four environmental mycobacteria sensitins. Responses were classified as sensitin-dominant, tuberculin-dominant or non-dominant. Positive predictive values (PPV) were defined using 'narrow' and 'wide' standards based on DST responses. These predictive values were derived for each category of tuberculin indurations, and were used to calculate the prevalence estimates. RESULTS: Using DST data, the estimates of M. tuberculosis prevalence for scar-negative children were 7.4% (M. avium) and 7.8% (M. scrofulaceum) using the 'narrow' standard, and 16.9% (M. avium) and 15.2% (M. scrofulaceum) using the 'wide' standard. The percentage with TST > or =10 mm was 11.5%. Scar-positive children had higher estimates using both the 10 mm cut-off and DST data. CONCLUSION: In settings with a relatively low prevalence of M. tuberculosis infection and high cross-reactivity with environmental mycobacteria, DST can help to assess the validity of traditional thresholds for estimating the prevalence of M. tuberculosis infection. DST data with environmental antigens and tuberculin do not distinguish BCG-induced cross-reactivity.     

Induction of antibodies to the envelope protein of the human immunodeficiency virus by immunization with monoclonal anti-idiotypes.

Anti-idiotypes that possess the internal image of antigen can induce protective humoral immunity toward microbes. Herein we demonstrate antigen mimicry by monoclonal anti-idiotypes of a distinct epitope of the human immunodeficiency virus (HIV) envelope protein that is defined by a synthetic peptide. This peptide, corresponding to amino acid residues 503-535 (peptide 503-535) of HIV-1 IIIB gp160, induced antibodies in three mammalian species that interacted with HIV-1 gp120 and inhibited in vitro syncytium formation caused by HIV-1, IIIB and MN isolates. Three monoclonal anti-idiotypes were generated against rabbit anti-gp120 antibodies specific for peptide 503-535. These anti-idiotypes recognize an interspecies cross-reactive idiotype expressed on mouse, chimpanzee, baboon, rabbit, and human anti-gp120 antibodies specific for peptide 503-535. The interaction with the cross-reactive idiotype is inhibited by synthetic peptide and HIV-1 gp160. Furthermore, rabbits immunized with the monoclonal anti-idiotypes produced antibodies that also bind HIV-1 gp120 and gp160 and recognized the epitope defined by peptide 503-535.     

The detection of antibodies to Mycobacterium tuberculosis and its reactivity to three different purified protein derivative by ELISA]

The specific PPD IgG antibodies in serum of patients with pulmonary tuberculosis and its reactivity to PPD of Mycobacterium tuberculosis M. bovis and M. avium were detected by ELISA. The results showed that the antibody level and positive rate of patients with pulmonary tuberculosis significantly increased than those of normal subjects. Specific antibody level and its positive rate were higher in hospitalized patients than those treated in clinic and both were higher in sputum positive cases than in sputum negative one. There was cross-reactivity among three different PPD. Absorption black test indicated that M. tuberculosis PPD had good specificity. PPD should be further purified in order to make ELISA as a useful serodiagnostic tool.     

Impact of human immunodeficiency virus infection on women and infants.

Infection with HIV is a problem of growing magnitude among women and children in the United States. During 1991, AIDS will be among the five leading causes of death for women of childbearing age. Over 80% of children with HIV have acquired the infection vertically, and AIDS is now a leading cause of death of children in many urban areas of the United States. Gender and age have important influences on the progression of HIV disease and on the occurrence of complicating illnesses. Zidovudine can slow HIV disease progression, and several regimens of prophylaxis are effective against P. carinii pneumonia, which is the leading cause of death among adults and children with AIDS. Intravenous immunoglobulin may be effective for prevention of serious infections in some children with symptomatic HIV infection. Ultimately, prevention of HIV infection among women and children depends on targeted education and, possibly, the development of medical strategies for interruption of vertical transmission.     

Dual pulmonary infection with Mycobacterium tuberculosis and Pneumocystis carinii in patients infected with human immunodeficiency virus.

During a 22-month period, we identified 39 patients with human immunodeficiency virus (HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with pneumonia and who had sputum and/or other specimens that tested concurrently positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most common chest x-ray abnormality was a reticulonodular pattern or bilateral infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17 (85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%]) received both antituberculous and anti-PCP therapy (17 with steroids), and 22 improved. All ten patients who received no treatment for PCP improved and were discharged from the hospital, whereas 4 (80%) of the 5 persons who received no antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with HIV or acquired immune deficiency syndrome may present with both TB and PCP; of the 2, TB seems to account for the most severe features of disease.