Altruism, Scepticism, and collective decision-making in foreign-born U.S. residents in a tuberculosis vaccine trial.

BACKGROUND: The current vaccine against tuberculosis, BCG, is effective when given in most TB-endemic countries at birth but has diminished efficacy against pulmonary TB after 15-20 years. As a result, new booster vaccines for adolescents and adults are being developed to realize the World Health Organization target of global elimination of TB by 2035. Multiple TB candidates thus are in active clinical development. METHODS: One of these, DAR-901, is advancing in human clinical trials. These clinical trials are conducted in BCG immunized adults with and without HIV infection in order to assess safety and efficacy among the people most in need of a new vaccine. A Phase I dose escalation trial of DAR-901 in BCG-immunized adults with or without HIV infection was conducted between 2014 and 2016. This offered an unusual opportunity to qualitatively examine why foreign-born adults living in the United States - a poorly studied population - decide to participate, or not, in clinical trials. RESULTS: We conducted a qualitative study of individuals who were recruited to participate in this Phase I vaccine trial, interviewing those who agreed and declined to participate. We found diverse motivations for participation or refusal; varied understandings of tuberculosis and vaccines; and complex views about how 'informed consent' can be at odds with cultural understandings of power, authority, and medical decision-making. These dynamics included: knowledge (direct or indirect) of tuberculosis, a desire to be altruistic and simultaneous hopes for personal gain as well as concerns over what remuneration for participation could mean, the importance of personal relationships with care providers in shaping volunteerism, concerns over privacy, and evidence of how culture and history shape medical decision-making. CONCLUSIONS: This US-based trial, aimed at addressing a crucible global health issue, raises productive questions about the interface between altruism and scepticism regarding clinical research participation. TRIAL REGISTRATION: NCT02063555 .

Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants.

This document outlines the consensus agreement from the Union's BCG Working Group regarding BCG vaccination in HIV-infected infants, in response to recently revised World Health Organization (WHO) guidelines, which make HIV infection in infants a full contraindication to bacille Calmette-Guérin (BCG) vaccination. BCG is one of the most widely given vaccines globally and is safe in immunocompetent individuals. Recent evidence shows that HIV-infected infants who were routinely vaccinated with BCG at birth, when asymptomatic, and who later developed AIDS, are at high risk of developing disseminated BCG disease (estimated incidence 407-1300 per 100 000). The document outlines requirements to implement selective BCG vaccination strategies in infants born to HIV-infected women and strategies to reduce the risk of vertical HIV transmission and disseminated BCG disease in infants.

Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania.

SETTING: Isoniazid preventive therapy (IPT) has not been widely implemented due to questions about acceptance, adherence and side effects. OBJECTIVE: To examine factors related to completion of IPT among human immunodeficiency virus (HIV) infected subjects in Tanzania. DESIGN: HIV-infected subjects in the DarDar TB vaccine trial with CD4 cell counts >or=200 cells/mm(3) and a positive tuberculin skin test (TST) were counseled, offered IPT for 6 months and seen monthly. RESULTS: Among 1932 subjects, TST results were positive in 631 (33%): 568 (90%) were offered IPT, 565 (99%) accepted and three (<1%) refused. Of the 565 subjects who accepted IPT, 493 (87%) completed treatment and 72 (13%) did not. Non-completion was physician-initiated in 24 (33%, due to active TB or side effects), patient-initiated in 42 (58%, due to self-cessation or loss to follow-up) and due to death in 6 (8%, unrelated to IPT). Interviews were conducted among 109 completers and 20 non-completers (12 physician- and 8 patient-initiated). Completers were motivated by fear of TB (44%), understanding the importance of IPT (32%) and counseling (22%). Patient-initiated non-completers were dissuaded by stigma (58%), side effects (14%) and travel distance (1%). CONCLUSIONS: HIV-infected subjects provided with counseling, monthly follow-up and travel reimbursement have high rates of IPT completion with minimal side effects.

Fatal hemoptysis from invasive Aspergillus niger in a patient with cavitary lung disease and Mycobacterium avium complex infection.

Invasive aspergillosis typically afflicts immunocompromised patients, whereas pulmonary aspergilloma is a recognized complication of pre-existing cavitary lung disease in immunocompetent hosts. In both cases, the most prevalent pathogens are Aspergillus fumigatus and Aspergillus flavus. We describe a case of fatal hemoptysis from invasive Aspergillus niger infection in the setting of bullous lung disease, steroid-treated sarcoidosis, and Mycobacterium avium complex infection. This report highlights the potential for A. niger to cause invasive disease in conjunction with other pathologic processes in the lung.

A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guérin in Finland.

SETTING: Mycobacterium bovis bacille Calmette-Guerin (BCG) is provided to all infants born in Finland. OBJECTIVE: To analyze the cost-effectiveness of universal versus selective BCG immunization. DESIGN: A Markov model was developed to simulate rates of tuberculosis (TB) and non-tuberculous mycobacterial disease (NTM), and to examine the cost-effectiveness in terms of cost per case averted of three different strategies: universal BCG, selective BCG (10% of infants at higher TB risk than other infants) or no BCG immunization. RESULTS: In a cohort of 60,000 infants over 15 years, the model predicts five cases each of TB and NTM disease with universal immunization, 8-21 TB and 31 NTM cases with various strategies of selective immunization, and 25 TB and 34 NTM cases with no BCG immunization. BCG side-effects are predicted in 5, 0.5 and 0 infants, respectively. The cost per case averted for immunization strategies ranges from a cost of 38,311 US dollars to a savings of 323 dollars as selective immunization becomes more efficient at targeting infants at highest risk of TB. CONCLUSIONS: In a country with a low incidence of pediatric tuberculosis, selective BCG immunization is a more cost-effective strategy than universal BCG immunization for the prevention of tuberculosis, but results in an increase in NTM cases.

Detection of latent tuberculosis among HIV-infected patients after initiation of highly active antiretroviral therapy.

This cross-sectional study of 110 individuals examined skin testing for latent tuberculosis infection (LTBI) after the initiation of highly active antiretroviral therapy. Skin test reactivity to one or more of four antigens was found in 98 out of 110 subjects (89%), and was maximal in those whose CD4 cell counts recovered to >= 100 cells/mm3. Skin testing is reliable for the identification or exclusion of LTBI once the CD4 cell count recovers to >= 100 cells/mm3.

Similar serovar and drug susceptibility profiles among AIDS-related Mycobacterium avium isolates from diverse geographic locations.

Serotyping was performed on Mycobacterium avium isolates from 40 AIDS patients from 5 geographic sites: Boston (17 patients), New Hampshire (4 patients), Finland (12 patients), Trinidad (3 patients), and Kenya (4 patients). Serovars were similar from the five sites. Serovars 4 and 8 were the most common. In addition, minimal inhibitory concentrations to 8 antimicrobial agents were determined for 31 of these isolates and for 21 additional patient isolates from these sites. Minimal inhibitory concentration90 values for clarithromycin, azithromycin, clofazimine, amikacin, ethambutol, ciprofloxacin, sparfloxacin, and rifabutin were similar for isolates from the five geographic sites. Antimicrobial susceptibility patterns did not differ by serovar.

Immunization of HIV-infected adults with a three-dose series of inactivated Mycobacterium vaccae.

Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to 12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic side effects were monitored. Delayed-type hypersensitivity to purified protein derivative and Mycobacterium avium sensitin was measured at baseline and after the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a short-term culture filtrate of Mycobacterium tuberculosis were also measured. Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no systemic side effects were noted. Purified protein derivative skin test conversions did not occur. Changes in CD4 counts and HIV viral load were not significant. Three (27%) of 11 subjects who completed the trial showed either M avium skin test (n = 1) or short-term culture filtrate antibody (n = 2) responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated in adults with early HIV infection and produces detectable immunologic responses in a subset of these subjects.

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.