Protein-calorie malnutrition, macronutrient supplements, and tuberculosis.

BACKGROUND: Protein-calorie malnutrition (PCM) is a risk factor for tuberculosis (TB) disease and may affect treatment outcomes. There is currently no recommended macronutrient intervention for improving the outcome of anti-tuberculosis treatment. METHODS: We reviewed current literature on PCM and low body mass index (BMI) as risk factors for tuberculous infection and TB disease, and their effects on anti-tuberculosis treatment. We summarize clinical trials of macronutrient supplementation in the treatment of TB. RESULTS: PCM is a well-established risk factor for TB disease; however, data on malnutrition and the risk of tuberculous infection are limited. Malnutrition is associated with an increased risk of mortality and relapse of active TB. Clinical trials of macronutrient supplementation during treatment confirm a 2-3 kg improvement in weight gain at 2 months, and may result in improvement in physical function, sputum conversion and treatment completion, but they have not been powered to assess effects on mortality or relapse. CONCLUSION: Assessment of dietary intake, food security, and baseline BMI should be standard practice in anti-tuberculosis treatment, along with dietary counselling. As macronutrient supplementation may have modest benefits and is not associated with adverse events, patients with BMI values <18.5 kg/m(2) should be provided with balanced macronutrient supplementation whenever possible.

Nutritional status of HIV-infected women with tuberculosis in Dar es Salaam, Tanzania.

SETTING: Tuberculosis (TB) treatment clinics in Dar es Salaam, Tanzania. OBJECTIVE: To quantify anthropometrics and intake of en-ergy and protein among human immunodeficiency virus (HIV) positive women with TB. DESIGN: HIV-positive women with newly diagnosed TB were assessed on their anthropometric characteristics and dietary intake. Energy and protein intake were determined using Tanzania food composition tables and compared with standard recommendations. Patients were re-evaluated after 4-6 months of anti-tuberculosis treatment. RESULTS: Among 43 women, the baseline median CD4 count was 209 cells/µl (range 8-721); 19 (44%) had a CD4 count of <200; 20 (47%) were on antiretroviral therapy. Body mass index was <18.5 kg/m(2) in 25 (58%); the median food insecurity score was 6. The median level of kcal/day was 1693 (range 1290-2633) compared to an estimated need of 2658; the median deficit was 875 kcal (range -65-1278). The median level of protein/day was 42 g (range 27-67) compared to 77 g estimated need; the median protein deficit was 35 g (range 10-50). The median weight gain among 29 patients after 4-6 months was 6 kg. CONCLUSION: HIV-positive women with TB have substantial 24-h deficits in energy and protein intake, report significant food insecurity and gain minimal weight on anti-tuberculosis treatment. Enhanced dietary education together with daily supplementation of 1000 kcal with 40 g protein may be required.

New vaccines for the prevention of tuberculosis in human immunodeficiency virus infection.

The prevention of human immunodeficiency virus (HIV) associated tuberculosis (TB) remains challenging. Several vaccines against TB have advanced to clinical trials in patients with HIV infection. The DarDar Trial, a large, randomized, placebo-controlled efficacy trial conducted in Tanzania, has demonstrated that a multiple dose series of an inactivated whole cell mycobacterial vaccine is safe in HIV and can prevent HIV-associated TB in patients with childhood bacille Calmette-Guérin vaccination and CD4 counts of ≥200 cells/mm(3). These developments offer promise that in the not too distant future immunization with an effective vaccine against TB can be added to other strategies for the prevention of HIV-associated TB. This expanded approach is referred to as the Five 'I's': intensified case finding, infection control, isoniazid preventive therapy (IPT), initiation of antiretroviral therapy (ART), and immunization against TB. We encourage additional studies of new TB vaccines in HIV, and propose a strategy to reduce the risk of TB by integrating IPT, ART and immunization into routine HIV care. At the time of HIV diagnosis, patients with CD4 counts of ≥200 cells/mm(3) could receive immunization, IPT and, as appropriate, ART. In patients presenting with lower CD4 counts or already on ART, immunization could be initiated at CD4 counts of ≥200 cells/mm(3) to add to the protection afforded by IPT and ART.

Sustained reduction in tuberculosis incidence following a community-based participatory intervention.

BACKGROUND: Rates of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease are elevated in the rural southeastern United States and among US- and foreign-born Black residents. To prevent TB and reduce TB transmission, community-based strategies are essential. OBJECTIVE: To describe a community-based participatory intervention for improving the detection and treatment of LTBI and TB and reducing TB incidence. DESIGN: In rural Florida, we carried out a community educational TB campaign from 1997 to 2000, including presentations at community events, a media campaign and working with local community groups to develop culturally appropriate prevention messages. The campaign was implemented concurrently with a population-based LTBI survey. RESULTS: The annual TB incidence rate in the intervention area decreased from 81 per 100 000 in 1994-1997, to 42/ 100 000 in 1998-2001, and to 25/100 000 in 2002-2005 (P = 0.001). This decrease was not observed in communities where the intervention was not implemented. There was no decrease in the TB incidence rate ratio between Blacks and non-Blacks in either region during the study period. CONCLUSIONS: We conclude that community participation in LTBI screening and TB education was associated with a substantial reduction in TB rates. Although the TB incidence rate ratio did not decrease between Blacks and non-Blacks, TB incidence fell in all racial groups.

Completion of isoniazid preventive therapy and survival in HIV-infected, TST-positive adults in Tanzania.

SETTING: The World Health Organization recommends the use of isoniazid preventive therapy (IPT) for human immunodeficiency virus (HIV) infected patients with a positive tuberculin skin test (TST). However, due to concerns about the effectiveness of IPT in community health care settings and the development of drug resistance, these recommendations have not been widely implemented in countries where tuberculosis (TB) and HIV co-infection is common. OBJECTIVE: To evaluate the effectiveness of IPT on survival and TB incidence among HIV-infected patients in Tanzania. DESIGN: A cohort study nested within a randomized trial of HIV-infected adults with baseline CD4 counts of ≥ 200 cells/µ l was conducted to compare survival and incidence of active TB between TST-positive subjects who did or did not complete 6 months of IPT in the period 2001-2008. RESULTS: Of 558 TST-positive subjects in the analytic cohort, 488 completed 6 months of IPT and 70 did not. Completers had a decrease in mortality compared to non-completers (HR 0.4, 95%CI 0.2-0.8). However, the protective effect of IPT on the incidence of active TB was non-significant (HR 0.6, 95%CI 0.3-1.3). CONCLUSION: Completion of IPT is associated with increased survival in HIV-infected adults with CD4 counts ≥ 200 cells/µ l and a positive TST.

Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality.

BACKGROUND: Disseminated tuberculosis (TB) is a major cause of death in patients with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and clinical features have not been defined prospectively. METHODS: Human immunodeficiency virus (HIV) infected adults with a CD4 count ≥ 200 cells/µl and bacille Calmette-Guérin scar underwent immunologic evaluation and subsequent follow-up. RESULTS: Among 20 subjects who developed disseminated TB, baseline tuberculin skin tests were ≥15 mm in 14 (70%) and lymphocyte proliferative responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of diagnosis, fever ≥2 weeks plus ≥5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/µl (range 1-122). By insertion sequence (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%) concurrent sputum isolates represented a different strain (polyclonal disease). Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a month. CONCLUSIONS: Disseminated TB in HIV occurs with cellular immune responses indicating prior mycobacterial infection, and IS6110 analysis suggests an often lethal combination of reactivation and newly acquired infection. Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever.

Low BMI and falling BMI predict HIV-associated tuberculosis: a prospective study in Tanzania.

BACKGROUND: Low body mass index (BMI) is a known risk factor for tuberculosis (TB) in people without human immunodeficiency virus (HIV), but there are no prospective studies linking BMI to the risk of HIV-associated TB. DESIGN: In HIV-infected adults with CD4 counts ≥ 200 cells/µl receiving placebo in a TB booster vaccine trial in Dar es Salaam, Tanzania, we measured BMI at baseline and Year 1, and related baseline BMI and change in BMI to the risk of developing TB. RESULTS: We documented 92 cases of TB among 979 subjects followed for a mean of 3.2 years. Compared to subjects who did not develop TB, subjects who developed TB had a lower baseline BMI (23.2 vs. 24.6 kg/m(2), P = 0.006), and a greater BMI decline from baseline to Year 1 (-0.4 vs. 0.6 kg/m(2), P < 0.001). In multivariate analyses, baseline BMI was associated with the risk of developing TB (hazard ratio [HR] per kg/m(2) 0.94, 95%CI 0.90-0.99, P = 0.028), as was the change in BMI from baseline to Year 1 (HR per kg/m(2) 0.79, 95%CI 0.71-0.87, P < 0.001). Subjects with a baseline BMI < 17 kg/m(2) were more likely to develop TB (HR 3.72, 95%CI 1.16-12.0, P = 0.028). CONCLUSION: Low and falling BMI predict HIV-associated TB.

Racial disparities in primary and reactivation tuberculosis in a rural community in the southeastern United States.

SETTING: A rural section of a county in central Florida. BACKGROUND: Racial disparities in tuberculosis disease (TB) are substantial in the United States. OBJECTIVE: To determine if TB was attributable to primary infection, reactivation or both. DESIGN: A population-based survey of latent tuberculosis infection (LTBI), a case-control analysis of TB, and a cluster analysis of TB isolates were performed between 1997 and 2001. RESULTS: Of 447 survey participants, 135 (30%) had LTBI. Black race was strongly associated with LTBI among US-born (OR 2.6, 95%CI 1.3-5.5) and foreign-born subjects (OR 4.3, 95%CI 2.2-8.4). Risk factors for TB included human immunodeficiency virus (HIV; OR 27.4, 95%CI 10.1-74.1), drug use (OR 4.6, 95%CI 1.7-12.4) and Black race (OR 3.4, 95%CI 1.2-9.6). The population risk of TB attributable to Black race was 64%, while that attributable to HIV was 46%. Cluster analysis showed 67% of TB cases were clustered, but Blacks were not at a significantly increased risk of having a clustered isolate (OR 2.1, 95%CI 0.12-36.0). CONCLUSION: Both reactivation TB and recent TB transmission were increased among Blacks in this community. Therefore, LTBI screening and intensive contact tracing, both followed by LTBI treatment, will be needed to reduce TB in Blacks.

Sources of disseminated Mycobacterium avium infection in AIDS.

OBJECTIVES: To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS. METHODS: HIV positive subjects with CD4 counts <100/mm(3) in Atlanta, Boston, New Hampshire and Finland were entered in a prospective cohort study. Subjects were interviewed about potential MAC exposures, had phlebotomy performed for determination of antibody to mycobacterial lipoarabinomannin and for culture. Patient-directed water samples were collected from places of residence, work and recreation. Patients were followed for the development of disseminated MAC. Univariate and multivariate risk factors for MAC were analyzed. RESULTS: Disseminated MAC was identified in 31 (9%) subjects. Significant risks in univariate analysis included prior Pneumocystis carinii pneumonia (PCP) (hazard ratio 1.821), consumption of spring water (4.909), consumption of raw seafood (34.3), gastrointestinal endoscopy (2.894), and showering outside the home (0.388). PCP, showering and endoscopy remained significant in a Cox proportional hazards model. There was no association between M. avium colonization of home water and risk of MAC. In patients with CD4<25, median OD antibody levels to lipoarabinomannin at baseline were 0.054 among patients who did not develop MAC and 0.021 among patients who did develop MAC (P=0.077). CONCLUSIONS: MAC infection results from diverse and likely undetectable environmental and nosocomial exposures. Mycobacterial infection before HIV infection may confer protection against disseminated MAC in advanced AIDS.

Skin test reactivity and cellular immune responses to Mycobacterium avium sensitin in AIDS patients at risk for disseminated M. avium infection.

Skin tests and lymphocyte proliferation assays (LPA) were performed with Mycobacterium avium sensitin on patients with AIDS. Among 139 subjects, 13% had positive skin test results and 32% had positive LPA results. The LPA may be a more sensitive indicator of prior M. avium infection in this population.

Nosocomial infections due to nontuberculous mycobacteria.

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and cause colonization, infection, and pseudo-outbreaks in health care settings. Data suggest that the frequency of nosocomial outbreaks due to NTM may be increasing, and reduced hot water temperatures may be partly responsible for this phenomenon. Attention to adequate high-level disinfection of medical devices and the use of sterile reagents and biologicals will prevent most outbreaks. Because NTM cannot be eliminated from the hospital environment, and because they present an ongoing potential for infection, NTM should be considered in all cases of nosocomial infection, and careful surveillance must be used to identify potential outbreaks. Analysis of the species of NTM and the specimen source may assist in determining the significance of a cluster of isolates. Once an outbreak or pseudo-outbreak is suspected, molecular techniques should be applied promptly to determine the source and identify appropriate control measures.

Patient selection criteria and management guidelines for outpatient parenteral antibiotic therapy for native valve infective endocarditis.

Outpatient parenteral antibiotic therapy (OPAT) for infective endocarditis (IE) is being applied widely, despite the absence of controlled data that demonstrates that outcomes are equivalent to those with standard inpatient antibiotic therapy. We review existing OPAT guidelines, published data on the timing of complications from IE, and data on risk factors that can be used to predict complications. These data are used to propose more stringent criteria for patient selection and clinical management of OPAT for native valve IE. We recommend a conservative approach (inpatient or daily outpatient follow-up) during the critical phase (weeks 0-2 of treatment), when complications are most likely, and we recommend consideration of OPAT for the continuation phase (weeks 2-4 or 2-6 of treatment) when life-threatening complications are less likely.

Bacteremia due to Mycobacterium tuberculosis or M. bovis, Bacille Calmette-Guérin (BCG) among HIV- positive children and adults in Zambia.

BACKGROUND: Among adults with advanced HIV infection in developing countries, bacteremia due to Mycobacterium tuberculosis (MTB) is common and bacteremia due to M. bovis (bacille Calmette-Guérin; BCG) is rare. Comparable data are not available for children with HIV. OBJECTIVE: To compare the prevalence of bacteremia due to M. tuberculosis or M. bovis BCG in hospitalized children and adults with HIV infection in a developing country with a high prevalence of tuberculosis and HIV and > 95% BCG immunization coverage. DESIGN: Descriptive cross-sectional study. METHODS: Prospectively hospitalized patients in Lusaka, Zambia who were suspected to have HIV infection underwent phlebotomy for HIV ELISA, HIV viral load, and lysis-centrifugation blood culture for mycobacteria. Histories were obtained and patients were examined for BCG scars. Mycobacterial isolates were identified using DNA probes for MTB complex (MTBC), multiplex PCR and IS6110 typing. RESULTS: The median age of 387 HIV-positive children was 15 months; 98% were BCG immunized. The median age of 344 HIV-positive adults was 32 years; 44% were BCG immunized. Blood cultures were positive for mycobacteria in six children (2%) and 38 adults(11%) (P < 0.001). The six pediatric isolates included five MTBC (40% clustered) and one BCG. The 38 adult isolates included 36 MTBC (16% clustered) and two M. avium complex. CONCLUSION: Bacteremia due to MTB is less common among children than adults with advanced HIV infection in Zambia. Bacteremia due to M. bovis BCG is rare even among children with recent BCG immunization and symptomatic HIV infection.

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.

Safety and immunogenicity of a five-dose series of inactivated Mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis.

Five doses of inactivated Mycobacterium vaccae vaccine were administered intradermally to 22 human immunodeficiency virus (HIV)-infected patients (11 bacille Calmette-Guérin [BCG]-positive and 11 BCG-negative) in Zambia whose CD4 lymphocyte counts were >/=200 cells/mm(3). HIV viral load and lymphocyte proliferation responses were compared for vaccine recipients and 22 HIV-infected control patients (11 BCG-positive and 11 BCG-negative). Immunization was safe and well tolerated in all patients, and induration at the vaccine site decreased from dose 1 to dose 5. A transient decrease in HIV viral load was observed in BCG-positive vaccine recipients after dose 3 but not after subsequent doses. Median lymphocyte stimulation indices to M. vaccae were 6.0 in vaccine recipients and 2.3 in control patients (P<.001). Stimulation indices were >/=3.0 in 19 vaccine recipients (86%) and 7 control patients (32%; P=.001). A 5-dose series of vaccination with inactivated M. vaccae is safe in HIV-infected patients and induces lymphocyte proliferation responses to the vaccine antigen. M. vaccae vaccine is a candidate for the prevention of tuberculosis in HIV infection.