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BACKGROUND: Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy.METHODS: Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation.RESULTS: People who smoked drugs (PWSD) comprised 54.8% (n = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10–1.97; P = 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22–4.34; P = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62–1.87; P = 0.799) was not associated with increased cavitation.CONCLUSIONS: PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.

BACKGROUND: The continued development of new anti-TB agents brings with it a demand for accompanying treatment regimens to prevent the development of resistance. Effectively meeting this demand requires an understanding of the pathogen´s susceptibility to various treatment options, which in turn makes access to antibiotic susceptibility testing (AST) a paramount consideration in the global treatment of TB.METHODS: A 12-question, quantitative and qualitative survey was developed to gauge global capacity and access to AST. The survey was disseminated to members of the Global Laboratory Initiative, Global Drug-resistant TB Initiative, and the TB section of the International Union Against Tuberculosis and Lung Disease to solicit responses from pertinent stakeholders.RESULTS: A total of 323 complete responses representing 84 countries and all WHO Regions were collected. AST capacity for fluoroquinolones and second-line injectables was high in all WHO Regions. AST capacity for the new and repurposed drugs is highest in the European Region, Region of the Americas and the Western Pacific Region, but quite limited in the African and Eastern Mediterranean Regions. The AST turnaround time for second-line drugs was delayed compared to that for first-line drugs as samples needed to be sent farther for analysis. Common barriers to AST for second-line drugs were lack of specimen transportation infrastructure, high costs, and lack of specialised laboratory workers and specialised laboratory facilities.CONCLUSION: Without expanding global access to AST, the growing availability of new treatment options will likely be threatened by accompanying increase in resistance. There is an earnest and pressing need to improve capacity and access to AST alongside treatment options.

SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.

SETTING: The global multidrug-resistant tuberculosis (MDR-TB) epidemic has grown over the past decade and continues to be difficult to manage. In response, new drugs and treatment regimens have been recommended.OBJECTIVE: In 2017 and again in 2018, the International Union Against Tuberculosis and Lung Disease (The Union) drug-resistant (DR) TB Working Group collaborated with RESIST-TB to implement an internet survey to members of The Union around the world to assess access to these new treatment strategies.DESIGN: A nine-question survey was developed using SurveyMonkey®. The survey was open for participation to all members of The Union registered under the TB Section. Two reminders were sent during each survey. The responses were analyzed taking into account the WHO Region to which the respondent belonged.RESULTS: The 2018 survey showed a global increase in implementation of the shorter (9-month) MDR-TB regimen (from 33% to 56% of respondents, P < 0.001) and an increase in the use of bedaquiline and/or delamanid (from 25% to 41% of respondents, P < 0.001) compared to 2017. There were substantial variations in roll-out between WHO regions.CONCLUSION: These results demonstrate improvement in global implementation of the new treatment strategies over a 1-year period.

Setting Ethiopia has a high prevalence of tuberculosis (TB) and is one of the countries with the highest burden of multidrug-resistant TB (MDR-TB). Objective To understand the costs that patients incur in obtaining diagnosis and treatment for MDR-TB. Design In March 2013, interviews were conducted with 169 MDR-TB patients at three hospitals in Ethiopia to identify the cost to patients and the impact on employment and family income. Results The average MDR-TB patient incurred a total cost of US$1378, which represented 25 months of a mid-treatment household income of US$54. The impact on the patient's employment and on overall patient and family income was generally catastrophic: 74% of all respondents reported losing their jobs, 66% of patients lost household income, and household income was reduced by 38%. To help cover the costs, 38% of patients sold some type of property, while 7% leased out property and 41% took out loans, any of which could jeopardize their future financial situation even further. Conclusion Despite services being officially free of charge, most patients incurred catastrophic costs and suffered significant income loss as a result of obtaining diagnosis and treatment for MDR-TB.

BackgroundComorbid mental disorders in patients with tuberculosis (TB) may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.MethodsWe searched eight databases for studies published from 1990-2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (OR) with 95% confidence intervals (CI).FindingsOf 7,687 studies identified, ten were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95% CI: 0.85-5.37), 1.90 (0.33-10.91), and 1.60 (0.81-3.02), respectively. High statistical heterogeneity was present.InterpretationOur review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

BACKGROUND: Tuberculosis incidence varies seasonally in many settings. However, the role of seasonal variation in reactivation vs. transmission is unclear.METHODS: We reviewed data on TB notifications in Cape Town, South Africa, from 1903 to 2017 (exclusive of 1995–2002, which were unavailable). Data from 2003 onward were stratified by HIV status, age and notification status (new vs. retreatment). We performed seasonal decomposition and time-dependent spectral analysis using wavelets to assess periodicity over time. We estimated monthly peak-to-peak seasonal amplitude of notifications as a percentage of the annual notification rate.RESULTS: A seasonal trend was intermittently detected between 1904 and 1994, particularly during periods of high notification rates, but was consistently and strongly evident between 2003 and 2017, with peaks in September through November, following winter. Among young children, a second, higher seasonal peak was observed in March. Seasonal variation was greater in children (CONCLUSIONS: Stronger seasonal effects were seen in children, in whom progression following recent infection is known to be the predominant driver of disease. These findings may support increased transmission in the winter as an important driver of TB in Cape Town.

BACKGROUND The well-documented association between underweight and increased incidence of active tuberculosis (TB) has not been extended to incidence or prevalence of latent tuberculous infection (LTBI). DESIGN After identifying studies that reported a categorical measure of body mass index (BMI) and used the tuberculin skin test (TST) or QuantiFERON®-TB Gold In-Tube (QFT) to measure LTBI, a maximum likelihood random-effects model was used to examine the pooled association between LTBI and low BMI (

Setting A post-hoc exploratory analysis of a randomized, open-label clinical trial that enrolled 8053 participants from the United States, Canada, Brazil, and Spain. Objective To assess factors associated with non-completion of study follow-up (NCF) in a 33-month latent tuberculous infection treatment trial, PREVENT TB. Design Participants were randomized to receive 3 months of weekly directly observed therapy vs. 9 months of daily self-administered therapy. NCF was defined as failing to be followed for at least 993 days (33 months) from enrollment. Possible factors associated with NCF were analyzed using univariate and multivariate regression via Cox proportional hazard model. Results Of 7061 adults selected for analysis, 841 (11.9%) did not complete study follow-up. Homelessness, young age, low education, history of incarceration, smoking, missing an early clinic visit, receiving isoniazid only, and male sex were significantly associated with NCF. Similar results were found in the North American region (United States and Canada) only. In Brazil and Spain, the only significant factor was missing an early clinic visit. Conclusions Study subjects at higher risk for NCF were identified by characteristics known at enrollment or in early follow-up. Evaluation of follow-up in other trials might help determine whether the identified factors consistently correlate with retention.

On June 17, 2016, RESIST-TB, IMPAACT, Vital Strategies, and New Ventures jointly hosted the Pediatric Multidrug Resistant Tuberculosis Clinical Trials Landscape Meeting in Arlington, Virginia, USA. The meeting provided updates on current multidrug-resistant tuberculosis (MDR-TB) trials targeting pediatric populations and adult trials that have included pediatric patients. A series of presentations were given that discussed site capacity needs, community engagement, and additional interventions necessary for clinical trials to improve the treatment of pediatric MDR-TB. This article presents a summary of topics discussed, including the following: current trials ongoing and planned; the global burden of MDR-TB in children; current regimens for MDR-TB treatment in children; pharmacokinetics of second-line anti-tuberculosis medications in children; design, sample size, and statistical considerations for MDR-TB trials in children; selection of study population, design, and treatment arms for a trial of novel pediatric MDR-TB regimens; practical aspects of pediatric MDR-TB treatment trials; and strategies for integrating children into adult tuberculosis trials. These discussions elucidated barriers to pediatric MDR-TB clinical trials and provided insight into necessary next steps for progress in this field. Investigators and funding agencies need to respond to these recommendations so that important studies can be implemented, leading to improved treatment for children with MDR-TB.

SETTING: Xpert® MTB/RIF is the first-line diagnostic test for Mycobacterium tuberculosis and rifampicin (RIF) resistance in South Africa. OBJECTIVE: To describe the rates of Xpert RIF resistance not confirmed on follow-up testing, as well as the patient and test characteristics associated with discordant results. DESIGN: Retrospective review of patients with isolates showing Xpert RIF resistance. Line-probe assay, phenotypic drug susceptibility testing or repeat Xpert were all considered confirmatory tests of RIF resistance. ‘Discordance’ was defined as a patient with RIF resistance identified on initial Xpert testing, with a subsequent confirmatory test indicating RIF susceptibility. Associations were analysed using Pearson χ(2) difference of proportions and modified Poisson regression. RESULTS: RIF discordance occurred in 22/263 subjects and was associated with Xpert probe B, probe binding delay, as opposed to probe dropout, and probe binding delays (ΔCt) of between 4 and 4.9. CONCLUSION: Discordant RIF resistance was common in our cohort and was associated with Xpert probe delay and use of probe B.

Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.

Ethiopia has a high prevalence of tuberculosis (TB) and is one of the countries with the highest burden of multidrug-resistant TB (MDR-TB).To understand the costs that patients incur in obtaining diagnosis and treatment for MDR-TB.In March 2013, interviews were conducted with 169 MDR-TB patients at three hospitals in Ethiopia to identify the cost to patients and the impact on employment and family income.The average MDR-TB patient incurred a total cost of US$1378, which represented 25 months of a mid-treatment household income of US$54. The impact on the patient's employment and on overall patient and family income was generally catastrophic: 74% of all respondents reported losing their jobs, 66% of patients lost household income, and household income was reduced by 38%. To help cover the costs, 38% of patients sold some type of property, while 7% leased out property and 41% took out loans, any of which could jeopardize their future financial situation even further.Despite services being officially free of charge, most patients incurred catastrophic costs and suffered significant income loss as a result of obtaining diagnosis and treatment for MDR-TB.

The past 4 years have seen the introduction of new regimens and new drugs to treat multidrug-resistant tuberculosis (MDR-TB). To identify implementation trends over time, the DR-TB Working Group of the International Union Against Tuberculosis and Lung Disease (The Union), in collaboration with RESIST-TB, launched an online survey to Union members around the world. Survey results showed substantial diversity in treatment roll-out: 36% of respondents stated that their country is using the 9-month regimen for MDR-TB treatment; 41% are using bedaquiline and delamanid, but not the 9-month regimen; 28% are using both; and 22% of respondents indicated that their country does not currently offer either of these treatment options. Survey respondents also identified specific challenges to the introduction of shorter MDR-TB regimens and new drugs, including access to rapid diagnosis of fluoroquinolone resistance and case management. The results of this survey are intended to help identify research and implementation gaps while highlighting the importance of global implementation of scalable regimens for the treatment of MDR-TB.Les quatre dernières années ont vu l'introduction de nouveaux protocoles et de nouveaux médicaments dans le traitement de la tuberculose multirésistante (TB-MDR). Dans le but d'identifier les tendances de la mise en œuvre dans le temps, le groupe de travail sur la TB résistante de l'Union Internationale contre la tuberculose et les maladies respiratoires (L'Union), en collaboration avec RESIST-TB, a lancé une enquête en ligne auprès des membres de l'Union autour du monde. Les résultats de l'enquête ont montré une grande diversité dans le lancement du traitement : 36% des répondants ont affirmé que leur pays utilisait le protocole de 9 mois pour le traitement de la TB-MDR ; 41% utilisent la bédaquiline et le délamanide, mais pas le protocole de 9 mois ; 28% utilisent les deux ; et 22% des répondants ont indiqué que leur pays n'offrait actuellement aucune de ces options de traitement. Les répondants ont également identifié les défis spécifiques à l'introduction de protocoles plus courts et de nouveaux médicaments de TB-MDR, notamment l'accès à un diagnostic rapide de la résistance aux fluoroquinolones et la prise en charge des cas. Les résultats de cette enquête sont destinés à contribuer à identifier les lacunes en matière de recherche et de mise en œuvre, tout en mettant en lumière l'importance de la mise en œuvre mondiale de protocoles évolutifs pour le traitement de la TB-MDR.En los últimos 4 años ha tenido lugar la introducción de nuevos esquemas terapéuticos y nuevos fármacos para el tratamiento de la tuberculosis multirresistente (TB-MDR). Con el propósito de evaluar las tendencias de su aplicación en el transcurso del tiempo, el grupo de trabajo sobre TB farmacorresistente de la Unión Internacional Contra la Tuberculosis y Enfermedades Respiratorias (La Unión), en colaboración con la iniciativa RESIST-TB, emprendió una encuesta en línea dirigida a los miembros de La Unión en todo el mundo. Los resultados pusieron de manifiesto una gran diversidad del despliegue del tratamiento. El 36% de quienes respondieron afirmaba que en su país se utiliza el esquema de 9 meses para el tratamiento de la TB-MDR; el 41% utiliza bedaquilina y delamanid, pero no el esquema de 9 meses; el 28% utilizan ambos; y el 22% de quienes respondieron indicaba que en su país no se ofrece en la actualidad ninguna de estas opciones terapéuticas. Las respuestas a la encuesta revelan también dificultades específicas con la introducción de los esquemas más cortos de tratamiento de la TB-MDR y con los nuevos medicamentos, entre ellas el acceso al diagnóstico rápido de la resistencia a las fluoroquinolonas y el manejo de los casos. Los resultados de esta encuesta tienen por finalidad contribuir a reconocer las lagunas en la investigación y en la ejecución y al mismo tiempo destacar la importancia de la introducción mundial de esquemas ampliables de tratamiento de la TB-MDR.

Hepatitis C virus (HCV) infection incidence among 18- to 30-year-olds is increasing and guidelines recommend treatment of active injection drug users to limit transmission. We aimed to : measure linkage to HCV care among 18- to 30-year-olds and identify factors associated with linkage; compare linkage among 18- to 30-year-olds to that of patients >30 years. We used the electronic medical record at an urban safety net hospital to create a retrospective cohort with reactive HCV antibody between 2005 and 2010. We report seroprevalence and demographics of seropositive patients, and used multivariable logistic regression to identify factors associated with linkage to HCV care. We defined linkage as having evidence of HCV RNA testing after reactive antibody. Thirty two thousand four hundred and eighteen individuals were tested, including 8873 between 18 and 30 years. The seropositivity rate among those ages 18-30 was 10%. In multivariate analysis, among those 18-30, diagnosis location (Outpatient vs Inpatient/ED) (OR 1.78, 95% CI 1.28-2.49) and number of visits after diagnosis (OR 5.30, 95% CI 3.91-7.19) were associated with higher odds of linking to care. When we compared linkage in patients ages 18-30 to that among those older than 30, patients in the 18-30 years age group were more likely to link to HCV care than those in the older cohort even when controlling for gender, ethnicity, socioeconomic status, birthplace, diagnosis location and duration of follow-up. Eighteen- to 30-year-olds are more likely to link to HCV care than their older counterparts. During the interferon-free treatment era, there is an opportunity to prevent further HCV transmission in this population.

OBJECTIVES To assess latent tuberculous infection (LTBI) treatment completion rates in a large prospective US/Canada multisite cohort and identify associated risk factors. METHODS This prospective cohort study assessed factors associated with LTBI treatment completion through interviews with persons who initiated treatment at 12 sites. Interviews were conducted at treatment initiation and completion/cessation. Participants received usual care according to each clinic's procedure. Multivariable models were constructed based on stepwise assessment of potential predictors and interactions. RESULTS Of 1515 participants initiating LTBI treatment, 1323 had information available on treatment completion; 617 (46.6%) completed treatment. Baseline predictors of completion included male sex, foreign birth, not thinking it would be a problem to take anti-tuberculosis medication, and having health insurance. Participants in stable housing who received monthly appointment reminders were more likely to complete treatment than those without stable housing or without monthly reminders. End-of-treatment predictors of non-completion included severe symptoms and the inconvenience of clinic/pharmacy schedules, barriers to care and changes of residence. Common reasons for treatment non-completion were patient concerns about tolerability/toxicity, appointment conflicts, low prioritization of TB, and forgetfulness. CONCLUSIONS Less than half of treatment initiators completed treatment in our multisite study. Addressing tangible issues such as not having health insurance, toxicity concerns, and clinic accessibility could help to improve treatment completion rates.

Setting An estimated 300 000 individuals are treated for latent tuberculosis infection (LTBI) in the United States and Canada annually. Little is known about the proportion or characteristics of those who decline treatment. Objective To define the proportion of individuals in various groups who accept LTBI treatment and to identify factors associated with non-acceptance of treatment. Design Persons offered LTBI treatment at 30 clinics in 12 Tuberculosis Epidemiologic Studies Consortium sites were prospectively enrolled. Multivariate regression models were constructed based on manual stepwise assessment of potential predictors. Results Of 1692 participants enrolled from March 2007 to September 2008, 1515 (89.5%) accepted treatment and 177 (10.5%) declined. Predictors of acceptance included believing one could personally spread TB germs, having greater TB knowledge, finding clinic schedules convenient and having low acculturation. Predictors of non-acceptance included being a health care worker, being previously recommended for treatment and believing that taking medicines would be problematic. Conclusion This is the first prospective multisite study to examine predictors of LTBI treatment acceptance in general clinic populations. Greater efforts should be made to increase acceptance among health care workers, those previously recommended for treatment and those who expect problems with LTBI medicines. Ensuring convenient clinic schedules and TB education to increase knowledge could be important for ensuring acceptance.

Several new classes of anti-tuberculosis agents are likely to become available in the coming decade. Ensuring prompt access to these drugs for patients without other treatment options is an important medical and public health issue. This article reviews the current state of ‘compassionate use’ and ‘expanded access’ programs for these new drugs, and identifies several shortcomings that will limit patient access to the drugs. A series of five steps is outlined that will need to be taken by national health bodies, international agencies and non-governmental organizations to prevent undue delays in access to new tuberculosis drugs for patients who could benefit from them. Following these steps can ensure that patients will be able to benefit from access to these drugs, while minimizing the risk of emergence of resistance to the drug.

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.To describe a community-based participatory intervention for improving the detection and treatment of LTBI and TB and reducing TB incidence.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.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.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.Les taux d’infection tuberculeuse latente (LTBI) et de maladie tuberculeuse (TB) sont élevés dans le Sud-Est rural des Etats-Unis ainsi que chez les résidents Noirs nés aux Etats-Unis ou à l’étranger. Pour prévenir la TB et réduire la transmission de la maladie, des stratégies basées sur la collectivité sont essentielles. Nous décrivons une intervention de participation basée sur la collectivité en vue d’améliorer la détection et le traitement de la LTBI et de la TB et de réduire l’incidence de la TB.En Floride rurale, nous avons mené entre 1997 et 2000 une campagne d’éducation de la collectivité au sujet de la TB, comportant des présentations lors d’événements de la collectivité, une campagne dans les média et le travail avec des groupes locaux de la collectivité pour élaborer des messages de prévention appropriés au niveau culturel. La campagne a été menée parallèlement à une enquête sur la LTBI basée sur la population.Le taux d’incidence annuel de la TB dans la zone d’intervention a diminué de 81/100 000 en 1994–1997 à 42/100 000 en 1998–2001 et à 25/100 000 en 2002–2005 (La participation de la collectivité au dépistage de la LTBI et à la formation en matière de TB est en association avec une réduction substantielle des taux de TB. Bien que le ratio de taux d’incidence de la TB n’ait pas été réduit entre les Noirs et les non-Noirs, on a noté une décroissance de l’incidence de la TB dans tous les groupes raciaux.Las tasas de infección tuberculosa latente (LTBI) y de enfermedad tuberculosa son altas en las regiones rurales del sureste de los Estados Unidos y en los residentes de etnia negra nacidos en el país o en el extranjero. Es primordial introducir estrategias comunitarias con el fin de prevenir la tuberculosis (TB) y disminuir su transmisión. En el presente artículo se describe una intervención comunitaria participativa encaminada a mejorar la detección y el tratamiento de la LTBI y la TB y a disminuir la incidencia de la TB.Entre 1997 y el año 2000 se llevó a cabo en zonas rurales del estado de Florida una actividad educativa comunitaria que consistió en presentaciones en los eventos de la comunidad, una campaña en los medios de comunicación y el trabajo con grupos comunitarios locales con el propósito de elaborar mensajes de prevención culturalmente adaptados. La campaña tuvo lugar en forma concomitante con una encuesta poblacional sobre la LTBI.La tasa de incidencia anual de TB en la zona de la intervención disminuyó de 81 por 100 000 habitantes entre 1994 y 1997 a 42/100 000 entre 1998 y el 2001 y a 25/100 000 del 2002 al 2005 (Se concluye que la participación comunitaria en la detección de la LTBI y la educación en materia de TB se asocian con una disminución considerable de la incidencia de TB. Aunque no hubo una disminución en el cociente de la tasa de incidencia entre personas de etnia negra y de otras etnias, sí se observó una disminución de la incidencia de TB en todos los grupos étnicos.

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.

Background A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). Objectives To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. Methods In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Results Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. Conclusions A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

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/mul and bacille Calmette-Guerin 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/mul (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.

Massachusetts is one of five states that mandate the reporting of latent tuberculous infection (LTBI). We assessed 2006-2008 Massachusetts surveillance data for LTBI to describe the system and examine the characteristics of persons with LTBI. Over 3 years, 15 301 LTBI cases were reported (4742-5398/year). Among those with known country of birth (n = 11 655), 9983 (85.7%) were foreign-born. Substantial under-ascertainment and/or under-reporting appear likely; mandatory reporting does not appear sufficient for LTBI detection. Enhanced targeted testing, active LTBI surveillance, or laboratory-based surveillance may be needed to eliminate tuberculosis disease in the United States.Le Massachusetts est l'un des cinq états qui exige la déclaration de l'infection tuberculeuse latente (LTBI). Nous avons évalué les données de surveillance de la LTBI au Massachusetts de 2006 à 2008 afin de décrire le système et d'étudier les caractéristiques des patients. En trois ans, 15 301 cas ont été rapportés (4742 à 5398 par an). Parmi les 11 655 patients dont le pays d'origine était connu, 9983 (85,7%) étaient nés à l'étranger. Il est probable que ce système de déclaration et de surveillance est déficient, car la déclaration obligatoire ne parait pas suffire à la détection de la LTBI. L'élimination de la tuberculose aux Etats-Unis pourrait nécessiter de mettre l'accent sur le dépistage ciblé, la surveillance active de la LTBI ou une surveillance basée sur les examens de laboratoire.Massachusetts es uno de los cinco estados en los cuales la notificación de la infección tuberculosa latente (LTBI) es obligatoria. En el presente estudio se evaluaron los datos de la vigilancia de esta afección entre el 2006 y el 2008, con el objeto de describir el sistema de vigilancia y examinar las características de las personas con diagnóstico de LTBI en Massachusetts. Durante el período de 3 años del estudio se notificaron 15 301 casos (de 474 a 5398 por año). De los casos en los cuales se conocía el país de origen (

To identify the sources of disseminated Mycobacterium avium complex (MAC) infection in AIDS.HIV positive subjects with CD4 counts100/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.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 CD425, 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).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.

OBJECTIVES: To investigate the short- and long-term risk of cancer in patients with active tuberculosis (TB).DESIGN: Using Danish nationwide databases, we quantified cancer risk in TB patients during 1978-2011 compared with the general population.RESULTS: We observed 1747 cancers in 15 024 TB patients (median follow-up 8.5 years), reflecting a standardised incidence ratio (SIR) of 1.52 (95%CI 1.45-1.59). All-time SIR for extra-pulmonary cancer was 1.29 (95%CI 1.22-1.36) and for lung cancer it was 3.40 (95%CI 3.09-3.74). Absolute cancer risk 3 months after TB was 1.83% (SIR 11.09, 95%CI 9.82-12.48), with highly increased SIRs for malignant pleural mesothelioma (368.4), lung cancer (40.9), Hodgkin's lymphoma (30.6), ovarian cancer (26.4) and non-Hodgkin's malignant lymphoma (23.8). Between the 3-month and 5-year follow-up, the SIR for any cancer was 1.59 (95%CI 1.46-1.72), including 19- and 3-fold increases for malignant pleural mesothelioma and lung cancer. Beyond 5 years, the SIR of cancer was 1.17 (95%CI 1.10-1.25). Elevated long-term risks persisted for haematological (SIR 1.34, 95%CI 1.01-1.74) and tobacco-related cancers (SIR 1.78, 95%CI 1.60-1.97).CONCLUSION: TB is a marker of occult lung cancer and several extra-pulmonary cancers. TB also predicts increased long-term risk of cancer, possibly related to chronic inflammation and shared risk factors, including immunosuppression and smoking.

Buruli ulcer (BU) is an emerging necrotic skin disease caused by Mycobacterium ulcerans. To assess the potential for a serodiagnostic test, we measured the humoral immune response of BU patients to M. ulcerans antigens and compared this response with delayed-type hypersensitivity responses to both Burulin and PPD. The delayed-type hypersensitivity response generally supported the diagnosis of BU, with overall reactivity to Burulin in 28 (71.8%) of 39 patients tested, compared with 3 (14%) of 21 healthy controls. However, this positive skin test response was observed primarily in patients with healed or active disease, and rarely in patients with early disease (p=0.009). When tested for a serologic response to M. ulcerans culture filtrate, 43 (70.5%) of 61 BU patients had antibodies to these antigens, compared with 10 (37.0%) of 27 controls and 4 (30. 8%) of 13 tuberculosis patients. There was no correlation between disease stage and the onset of this serum antibody response. Our findings suggest that serologic testing may be useful in the diagnosis and surveillance of BU.

Although most diseases due to pathogenic mycobacteria are caused by Mycobacterium tuberculosis, several other mycobacterial diseases-caused by M. ulcerans (Buruli ulcer), M. marinum, and M. haemophilum-have begun to emerge. We review the emergence of diseases caused by these three pathogens in the United States and around the world in the last decade. We examine the pathophysiologic similarities of the diseases (all three cause necrotizing skin lesions) and common reservoirs of infection (stagnant or slow-flowing water). Examination of the histologic and pathogenic characteristics of these mycobacteria suggests differences in the modes of transmission and pathogenesis, though no singular mechanism for either characteristic has been definitively described for any of these mycobacteria.

Objective: Infection with HIV adversely affects survival in patients with tuberculosis (TB), even when TB is effectively treated. The aim of this study was to identify the determinants of survival in HIV-associated TB. Design: Retrospective cohort study. Setting: Four US academic medical centers. Patients: An inception cohort of 112 HIV-infected patients (mean age 41 years, 96% men, 46% African American) with their first episode of culture-proven TB. Outcome measures: Observed survival from the date of diagnosis of TB to the date of death or censoring. Independent variables included demographics, HIV-related conditions, risk behavior for HIV, absolute CD4+ counts, and site of disease with Mycobacterium tuberculosis. Results: Of the 112 patients, 54 (48%) had pulmonary TB alone, 36 (32%) had both pulmonary and extra-pulmonary TB and 22 (20%) had extrapulmonary TB alone. Median CD4+ count was 95 x 10 6 /l (range, 2-767 x 10 6 /l). During follow-up, 45 patients (40%) died. Median survival was shortest in patients with both pulmonary and extrapulmonary disease (8.4 months), followed by extrapulmonary disease alone (15.6 months), then pulmonary disease (30.4 months; P < 0.001, log-rank test). Median survival was also reduced in patients with previous opportunistic infection and in those with CD4+ < 200 x 10 6 /l. In a proportional hazards regression analysis, which adjusted for CD4+ count, extrapulmonary disease and previous opportunistic infection were the only factors independently associated with shorter survival. Of the extrapulmonary sites of disease, TB meningitis was associated with the greatest risk of death. Conclusion: The site of culture-proven TB at presentation and the history of previous opportunistic infection are important predictors of survival in HlV-infected patients with TB.

To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.

Several new classes of anti-tuberculosis agents are likely to become available in the coming decade. Ensuring prompt access to these drugs for patients without other treatment options is an important medical and public health issue. This article reviews the current state of 'compassionate use' and 'expanded access' programs for these new drugs, and identifies several shortcomings that will limit patient access to the drugs. A series of five steps is outlined that will need to be taken by national health bodies, international agencies and non-governmental organizations to prevent undue delays in access to new tuberculosis drugs for patients who could benefit from them. Following these steps can ensure that patients will be able to benefit from access to these drugs, while minimizing the risk of emergence of resistance to the drug.

This study aimed to examine racial discrimination and relation to sexual risk for HIV among a sample of urban Black and African American men. Participants of this cross-sectional study were Black and African American men (N = 703) between the ages of 18 and 65 years, recruited from four urban clinical sites in the northeast. Multivariate logistic regression models were used to analyze the relation of reported racial discrimination to the following: (1) sex trade involvement, (2) recent unprotected sex, and (3) reporting a number of sex partners in the past 12 months greater than the sample average. The majority of the sample (96 %) reported racial discrimination. In adjusted analyses, men reporting high levels of discrimination were significantly more likely to report recent sex trade involvement (buying and/or selling) (adjusted odds ratio (AOR) range = 1.7–2.3), having recent unprotected vaginal sex with a female partner (AOR = 1.4, 95 % confidence interval (CI), 1.1–2.0), and reporting more than four sex partners in the past year (AOR = 1.4, 95 % CI, 1.1–1.9). Findings highlight the link between experiences of racial discrimination and men's sexual risk for HIV.

In settings with high tuberculosis (TB) prevalence, 15-30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity.To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART.We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities - in all patients or only symptomatic patients - for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/μl; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective.Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient.Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective.

To describe the natural history of Mycobacterium avium complex (MAC) in the respiratory or gastrointestinal tract of persons with human immunodeficiency virus (HIV) infection, 67 HIV-infected patients with CD4+ cell counts < 200/mm3 and initial negative MAC blood cultures were followed prospectively. Patients were screened every 3 months with cultures and smears of sputum, rectal swab, and blood for mycobacteria. Fourteen patients (20.9%) developed positive blood cultures for MAC (23.4%/year). Sputum cultures revealed MAC in 3 (21%) of the 14 patients at 1, 2, and 8 months before dissemination; no smears were positive. No rectal swab cultures or smears were positive before dissemination. Colonization of the respiratory and gastrointestinal tracts in persons with HIV infection and < 200/mm3 CD4+ cells is infrequently detected with currently available techniques. Screening cultures and smears of sputum and stool do not appear to be sensitive methods for detection of early MAC infection.

The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible.The 171 patients (median age, 46 years) had previously received a median of six drugs and shed bacilli that were resistant to a median of six drugs. Thus, their regimens were frequently not optimal. Of 134 patients with sufficient follow-up data, 87 (65 percent) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 47 patients (35 percent) had no response, as shown by continually positive cultures. The median stay in the hospital was more than seven months. In a multivariate analysis, an unfavorable response was significantly associated with a greater number of drugs received before the current course of therapy (odds ratio, 4.0; 95 percent confidence interval, 1.6 to 9.9; P0.001) and with male sex (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 6.2; P0.03). Twelve of the patients with responses subsequently had relapses. The overall response rate was 56 percent over a mean period of 51 months. Of the 171 patients, 63 (37 percent) died, and 37 of these deaths were attributed to tuberculosis.For patients with pulmonary tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. Only about half of such patients eventually have negative sputum cultures despite carefully selected regimens administered for extended periods. Failure to control this resistant infection is associated with high mortality and ominous implications for the public health.

The presence of Mycobacterium avium complex (MAC) in stool specimens may be a predictor of disseminated MAC infection, yet the methods for decontaminating stools have not been evaluated for their usefulness in recovering MAC organisms. In the present study, four decontamination methods commonly used to recover acid-fast bacteria from respiratory specimens were compared for their utility in recovering MAC from stool specimens. Ten strains of MAC were used at a level of 10(4) to 10(6) CFU to seed the stool specimens. Specimens were divided into four portions and were decontaminated by using the following treatments: (i) N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH), (ii) cetylpyridinium chloride-sodium chloride (CPC-NaCl), (iii) oxalic acid, or (iv) benzalkonium chloride-trisodium phosphate (BC-TSP). The specimens were then plated onto a total of five pieces of selective and nonselective egg- and agar-based media. The oxalic acid method yielded the greatest number of MAC CFU from seeded stool samples; this was followed by NALC-NaOH, BC-TSP, and CPC-NaCl. The difference between the oxalic acid method and each of the other methods was statistically significant (analysis of variance at the 95% significance level). Although more MAC CFU was recovered from seeded stool samples by using oxalic acid than NALC-NaOH, no difference in culture positivity rates was observed when the two methods were used to test 368 clinical stool specimens processed with either oxalic acid (164 specimens) or NALC-NaOH (204 specimens) (P = 0.07) or 67 specimens processed by both methods (P = 0.77). The oxalic acid and NALC-NaOH decontamination methods both appear to be useful for the recovery of MAC organisms from stool specimens.

A rural section of a county in central Florida.Racial disparities in tuberculosis disease (TB) are substantial in the United States.To determine if TB was attributable to primary infection, reactivation or both.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.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).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.

Total hemolytic complement activity and serum complement protein concentrations were compared in 17 hospitalized patients with normal hepatic function and 16 patients with liver disease due to alcohol (15 patients) or acetaminophen toxicity (one patient). In contrast to the control patients, individuals with hepatic dysfunction had decreased total CH50 levels and low concentrations of total C3, C4, C5, factor B, and the regulatory proteins factor I and beta-1H. These patients also had increased C4d/C4 ratios, indicating classical pathway activation. The level of complement deficiency appears to correlate with either prolongation of the prothrombin time or depression of serum albumin concentration. These results indicate that patients with hepatic disease have severe complement depletion that is probably multifactorial in origin. This impairment in complement function will contribute to the impaired antibacterial host defense of the patient with chronic hepatic disease.

Mycobacterium avium complex disease is the third most common opportunistic disease affecting patients with AIDS. In a nationwide survey, it occurred in 22 percent of such patients1; only Pneumocystis carinii pneumonia and Kaposi's sarcoma were more frequent, occurring in 58 percent and 28 percent of patients, respectively. M. avium disease is associated with debilitating symptoms and shortened survival.2 Thus, the reports in this issue of the Journal that document improved regimens for the prevention3,4 and treatment5 of this disease are welcome news. Clarithromycin and azithromycin both have good in vitro activity against M. avium, and it is . . .

Health care workers and medical students in the United States subject to annual tuberculin skin testing.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).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 wereor = 5 mm and alsoor = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM.MAS reactions wereor = 5 mm in 40% andor = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P0.001). PPD reactions wereor = 15 mm in 3% of subjects. PPD reactionsor = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P0.001). 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).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.

The contribution of disseminated Mycobacterium avium complex (DMAC) infection to the morbidity and mortality of patients with acquired immune deficiency syndrome (AIDS) is unclear. Previous studies that suggested the decreased survival of patients with AIDS and DMAC had incomplete information on patient immunologic status and follow-up. We studied patients with AIDS and DMAC and compared their survival with that of AIDS patients without DMAC but with other comparable risk factors for survival. Case and control subjects were similar in terms of CD4 cell count, prior AIDS status, history of antiretroviral therapy, history of Pneumocystis carinii prophylaxis, and year of diagnosis. A group of 39 patients with untreated DMAC had significantly shorter survival, mean of 5.6 +/- 1.1 months (median 4 months), than 39 matched patients with AIDS but without DMAC, mean 10.8 +/- 1.3 months (median 11 months, p less than 0.0001). The survival of 16 additional patients with DMAC who received antimycobacterial therapy, mean of 9.5 +/- 1.4 months (median 8 months), was not significantly shorter than that of an additional 16 matched control subjects, mean 11.7 +/- 1.9 months (median 11 months, p = 0.58). Patients with treated DMAC survived significantly longer than those with untreated DMAC (p less than 0.01). We conclude that untreated DMAC significantly shortens survival. Moreover, these results indicate that patients with DMAC who receive antimycobacterial therapy do not experience the shortened survival seen in untreated DMAC.

The optimal regimen for treatment of Mycobacterium avium complex (MAC) disease has not been established. Eighty-five AIDS patients with disseminated MAC disease were randomized to receive a three-drug regimen of clarithromycin, rifabutin or clofazimine, and ethambutol. Two dosages of clarithromycin, 500 or 1,000 mg twice daily (b.i.d.), were compared. The Data and Safety Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison. After a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarithromycin at 500 mg b.i.d. had died (70 deaths per 100 person-years) compared with 17 (43%) of 40 patients receiving clarithromycin at 1,000 mg b.i.d. (158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence interval, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiving rifabutin had died (81 deaths per 100 person-years) compared with 23 (52%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) (relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacteriologic outcomes were similar among treatment groups. In treating MAC disease in AIDS patients, the maximum dose of clarithromycin should be 500 mg b.i.d.

The clinically important nontuberculous mycobacteria include M. kansasii, M. genavense, M. marinum, M. simiae, M. scrofulaceum and M. szulgai, M. avium, M. haemophilum, M. intracellulare, M. malmoense, M. ulcerans, and M. xenopi, M. abscessus, M. chelonae, M. fortuitum, and (rarely) M. smegmatis. Four clinical syndromes account for nearly all cases: pulmonary disease, lymphadenitis, skin or soft tissue disease, and disseminated disease in AIDS. M. avium and M. intracellulare (known together as M. avium complex), are the most common causes of pulmonary disease, lymphadenitis, and disseminated disease. All four clinical syndromes seem to be increasing in frequency, particularly in immunosuppressed hosts. Nontuberculous mycobacteria are acquired from the environment, but specific reservoirs of these organisms leading to human disease have not been defined.

As part of an epidemiologic study of Mycobacterium avium complex (MAC) infection in San Francisco, water, food and soil samples were collected from the home environment of 290 persons with human immunodeficiency virus (HIV) infection and cultured for mycobacteria. Isolates recovered from the environment were compared with isolates cultured from study patients. Although mycobacteria were recovered from numerous environmental samples, isolates reactive with MAC-specific DNA probes were recovered from only four of 528 (0.76%) water samples and one of 397 (0.25%) food samples. The species M. avium was recovered from one water (0.19%) and one food sample. In contrast, MAC was recovered from 55% and M. avium from 27% of soil samples taken from potted plants in patients' home. Speciation of 76 MAC isolates from study patients showed all isolates belonged to the species M. avium. With use of serotype and multilocus enzyme electrophoresis analysis, some of the soil isolates were found to be similar to isolates recovered from study patients. The results of this study suggest that soil, rather than water, may be a significant reservoir of organisms causing MAC infection in San Francisco.