The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs.

Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes.

Contexte : Les Centers for Disease Control and Prevention des Etats Unis recommandent de consulter un expert en cas de tuberculose multirésistante (TB-MDR). En 2002, le California MDR-TB Service a été créé afin de fournir une consultation d'experts en TB-MDR. Nous décrivons les caractéristiques, les résultats du traitement et la prise en charge des patients référés vers ce service.Méthode : Les données de surveillance ont été utilisées pour une analyse descriptive des cas ayant eu une consultation entre juillet 2002 et décembre 2012. Les données de consultation clinique et les indicateurs modifiés de l'Organisation Mondiale de la Santé ont été utilisés afin d'évaluer la prise en charge des cas qui ont bénéficié d'une consultation entre janvier 2009 et décembre 2012.Résultats : Sur 339 patients TB-MDR, 140 ont bénéficié d'une consultation. Cette proportion est passée de 12% en 2002 à 63% en 2012. Il y a eu 24 patients TB pré-ultrarésistante et 5 patients TB ultrarésistante. La majorité (n = 123 ; 88%) a achevé le traitement, 5 (4%) sont décédés, 7 (5%) ont déménagé avant la fin du traitement, 4 (3%) ont arrêté le traitement à cause d'un effet secondaire et 1 (1%) a eu un résultat inconnu. Les indicateurs ont montré que 86% avaient bénéficié d'un test de pharmacosensibilité moléculaire rapide, que 98% avaient reçu au moins quatre médicaments avec une sensibilité connue ou présumée et que 93% ont eu une conversion de culture dans les 6 mois.Conclusion : Les consultations au service de TB-MDR ont augmenté dans le temps. Nous avons mis en lumière les bons résultats du traitement et des indicateurs.

Marco de referencia: Los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos recomiendan que se recurra a la consulta con expertos en los casos de tuberculosis multirresistente (TB-MDR). En el 2002, se creó el California MDR-TB Service en California, con el objeto de proveer consultas de expertos en la materia. En el presente estudio se describen las características, los desenlaces terapéuticos y el tratamiento de los pacientes remitidos a este servicio.Métodos: Se utilizaron los datos de la vigilancia en el análisis descriptivo de los casos que consultaron el Servicio de julio del 2002 a diciembre del 2012. A partir de la base de datos de la consulta y los indicadores modificados de la Organización Mundial de la Salud se evaluó la atención y el tratamiento de los casos que consultaron de enero del 2009 a diciembre del 2012.Resultados: De los 339 pacientes con diagnóstico de TB-MDR, 140 obtuvieron la consulta de expertos. La proporción de pacientes con una consulta aumentó de un 12% en el 2002 al 63% en el 2012. Se atendieron 24 pacientes con TB pre-ultrarresistente y cinco pacientes con TB ultrarresistente. La mayoría completó el tratamiento (n = 123; 88%), 5 pacientes fallecieron (4%), 7 se mudaron antes de haber completado el tratamiento (5%), 4 interrumpieron el tratamiento debido a una reacción adversa (3%) y se desconoció el desenlace de 1 paciente (1%). Según los datos de los indicadores, en 86% de los casos se practicaron pruebas moleculares rápidas de sensibilidad a los medicamentos, el 98% de pacientes recibió como mínimo cuatro fármacos con sensibilidad confirmada o supuesta y el 93% de los pacientes había convertido el cultivo en un lapso de 6 meses.Conclusión: Las consultas al Servicio de expertos en TB-MDR han aumentado con el transcurso del tiempo. Los resultados del estudio ponen de manifiesto la eficacia del tratamiento y revelan indicadores de evolución muy favorables.

Reduced importation of tuberculosis after the implementation of an enhanced pre-immigration screening protocol.

SETTING: Importation of infectious tuberculosis (TB) threatens TB control in California and the United States. OBJECTIVE: To assess the effectiveness of an enhanced pre-immigration screening and treatment protocol to prevent the importation of infectious TB. DESIGN: Retrospective analysis of immigrants ≥ 15 years of age with TB suspect classifications who were screened for TB in their countries of origin before (pre-intervention cohort) and after (post-intervention cohort) implementation of enhanced pre-immigration screening. Enhanced pre-immigration screening added sputum cultures to the existing screening system based on sputum smears for persons with abnormal chest radiographs. RESULTS: The pre- and post-intervention cohorts included respectively 2049 and 1430 immigrants. The occurrence of tuberculosis ≤ 6 months after US arrival in this population decreased following the intervention, from 4.2% (86 cases) to 1.5% (22 cases, P < 0.001). Among pre-intervention cohort cases, 14% were sputum acid-fast bacilli (AFB) smear-positive and 81% were sputum culture-positive for TB, compared with 5% sputum AFB smear-positive (P = 0.46) and 68% sputum culture-positive (P = 0.18) among the post-intervention cohort cases. CONCLUSION: The enhanced pre-immigration screening was associated with a decline in the proportion of immigrants with TB suspect classifications identified with TB within 6 months of arrival in the United States. Continued state and national surveillance is critical to monitor the effectiveness of the revised pre-immigration screening as it is implemented in additional countries.

Progress and problems in achieving the United States national target for completion of antituberculosis treatment.

SETTING: The target for antituberculosis treatment in the United States is for 90% of patients to complete therapy within 12 months. OBJECTIVE: To assess progress in achieving the US national target for tuberculosis treatment. DESIGN: A comparison of treatment outcome in two cohorts of patients with drug-susceptible tuberculosis in California-those reported in 1993-1994 (8488 patients) and 1995-1996 (7823 patients). Risk factors for delay in treatment completion (more than 12 months) were assessed. RESULTS: The percentage of cases completing treatment within 12 months increased in the 1995-1996 cohort (to 68.2%), primarily due to concomitant reductions in delays in treatment completion (to 11.1%) and defaulting (to 2.4%). Disparities in timely treatment completion narrowed over time and in nearly all subpopulations, especially in groups with lowest treatment completion in the 1993-1994 cohort. Remaining risk factors for delay in treatment completion included AIDS and older ages. A substantial percentage of patients died or moved before treatment completion. CONCLUSIONS: Despite recent improvements, completion of antituberculosis treatment in California has not reached the national target. Reaching this target will require further reductions in delays in treatment completion and deaths during treatment, and ensuring that patients who move eventually complete treatment.

HIV-related oral manifestations in two cohorts of women in San Francisco.

The goals of this study were to compare the prevalence of oral lesions in women infected with human immunodeficiency virus (HIV) and HIV-negative women, and to determine the association of oral lesions with route of HIV transmission and with level of immunosuppression in infected women. As part of a prospective 4-year study, oral examinations and blood tests were performed, at 6-month intervals, on 176 HIV-infected women and on 117 HIV-negative women at risk for HIV infection. We evaluated participants for the following oral conditions: hairy leukoplakia, candidiasis, ulcers, warts, non-Hodgkin's lymphoma, Kaposi's sarcoma, and parotid enlargement. As previously reported in men, the prevalence of oral lesions was significantly higher among HIV-infected (22%) than HIV-negative women (3%) [odds ratio (OR) = 8.2; 95% confidence interval (CI) 2.8, 23.5], particularly candidiasis (14%) and hairy leukoplakia (10%). Among HIV-infected women with CD4 cell count nadir > or = 200 cells/microliters, the prevalence of hairy leukoplakia was higher among those infected heterosexually than among injection drug users (OR = 5.5; 95% CI: 1.5; 19). The OR for the association between oral lesions and CD4 cell count nadir (< 200 vs. > 500 cells/microliters) was 8.9 (95% CI: 2.6, 30), indicating a strong positive association with level of immunosuppression.

The diagnosis of periodontal conditions associated with HIV infection.

Objective, reliable, and valid diagnostic criteria are required for studies of HIV-associated periodontal conditions. A set of diagnostic criteria were devised based on a literature review and the clinical experience of the authors. Validity was assessed by comparison with clinical photographs and the criteria were evaluated and refined for ease of use and objectivity. To assess the reliability of the criteria, 9 experienced examiners were shown 20 clinical photographs accompanied by brief vignettes of clinical information. Each examiner was asked to identify signs evident in a particular area of the photograph and to record a diagnosis. Five examiners were then trained and calibrated in the use of the criteria. Finally, all 9 examiners were shown the original 20 photographs and asked to identify signs and record diagnoses. The examiners showed only fair reliability in the recognition of clinical signs, made diagnoses intuitively, and had only fair agreement on the diagnosis of periodontal diseases. The inter-examiner reliability of examiners trained and calibrated in the use of the criteria increased and was greater than among untrained examiners. Rigid diagnostic criteria are essential in epidemiologic studies. Inter-examiner reliability will be increased if examiners are trained in their use and calibrated in the recognition of clinical signs. Diagnostic criteria should be modified as understanding of the diseases they classify increases. The proposed criteria will enhance the value of studies of HIV-associated periodontal changes and will contribute to that understanding.

Time from HIV seroconversion to oral candidiasis or hairy leukoplakia among homosexual and bisexual men enrolled in three prospective cohorts.

OBJECTIVES: We evaluated time from HIV seroconversion to diagnosis of two common oral lesions associated with HIV infection and disease progression. DESIGN: Oral examinations were performed on homosexual and bisexual men enrolled in prospective cohorts. SETTING: Homosexual and bisexual men were followed in three epidemiologic cohort studies in San Francisco, California, USA. PARTICIPANTS: Data were evaluated from 80 men with well-defined dates of HIV seroconversion from 1984 through 1991. MAIN OUTCOME MEASURES: We determined the cumulative incidence of oral candidiasis and hairy leukoplakia after HIV seroconversion. RESULTS: Four per cent of men developed oral candidiasis within 1 year after HIV seroconversion, 8% within 2, 15% within 3, 18% within 4, and 26% within 5 years. Nine per cent developed hairy leukoplakia within 1 year, 16% within 2, 25% within 3, 35% within 4, and 42% within 5 years. The median CD4+ count was 391 x 10(6)/l when oral candidiasis was first reported and 468 x 10(6)/l when hairy leukoplakia was first reported. CONCLUSIONS: Oral candidiasis or hairy leukoplakia appeared in a significant proportion of HIV-infected homosexual and bisexual men. These lesions occurred relatively soon after HIV seroconversion, typically before AIDS. Evaluation of HIV-infected individuals for these lesions has many potential clinical and research benefits, including the possible use of oral lesions as primary end-points in clinical trials.

Prognostic significance of oral lesions in children with perinatally acquired human immunodeficiency virus infection.

OBJECTIVE: To assess the prevalence and prognostic significance of oral lesions in children with human immunodeficiency virus infection. DESIGN: Clinical cohort study. SETTING: Children's Hospital Center at Jackson Memorial Hospital, Miami, Fla. PARTICIPANTS: Ninety-nine children with perinatally acquired human immunodeficiency virus infection examined longitudinally for oral lesions. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Presence of oral lesions was determined by a pediatrician who had been trained in the diagnosis of oral lesions. The cumulative prevalence of lesions was 72% for oral candidiasis, 47% for parotid enlargement, and 24% for herpes simplex. The median time from birth to development of a lesion was 2.4 years for candidiasis, 4.6 years for parotid enlargement, and 5 years for herpes simplex. The median time from lesion to death was 3.4 years for patients with candidiasis, 5.4 years for patients with parotid enlargement, and 4.3 years for patients with herpes simplex. In a time-dependent proportional-hazards model, oral candidiasis was associated with a more rapid rate of progression to death (relative hazard, 14.2; 95% confidence interval, 4.8 to 41.8), while parotid enlargement was associated with a less rapid rate of progression to death (relative hazard, 0.38; 95% confidence interval, 0.16 to 0.88) and herpes simplex was unrelated to the rate of progression (relative hazard, 1.3; 95% confidence interval, 0.5 to 3.1). CONCLUSIONS: The presence of oral candidiasis and parotid enlargement confer important prognostic information and should be incorporated into decisions regarding therapy for HIV-infected children.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

OBJECTIVE: This study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DESIGN: Cohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions. SETTING: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. PARTICIPANTS: Of the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. MAIN OUTCOME MEASURES: We determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. RESULTS: Using proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CI), 1.2-2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1-17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6-6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. CONCLUSION: The presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.

What if Americans ate less fat? A quantitative estimate of the effect on mortality.

Americans consume an average of 37% of their energy intake as fat. Many authorities recommend restricting fat intake to 30% of energy intake to reduce the rates of coronary heart disease and perhaps of cancers of the breast, colon, and prostate. Based on the assumptions that underlie those recommendations, we estimated the effect of this dietary change on mortality. If all Americans restricted their intake of dietary fat by reducing consumption of saturated fat and accompanying dietary cholesterol, the corresponding reductions in serum cholesterol levels could reduce coronary heart disease mortality rates by 5% to 20%, depending on age. If the relationship between dietary fat and cancer is as strong as has been observed in some studies, the proportional effects on mortality from fat-related cancers could be even greater, although the absolute effects--given the lower mortality rates--would be smaller. Overall, if the assumptions are correct, about 42,000 of the 2.3 million deaths that would have occurred in adults each year in the United States could be deferred. This 2% benefit, equivalent to an increase in average life expectancy of 3 to 4 months, would accrue chiefly to people over the age of 65 years. If recent concerns about the possibly harmful effects of cholesterol lowering on mortality from noncardiovascular causes--which mainly affect younger persons--are valid, these relatively modest benefits would be overestimates of the actual effect.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts.

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Use of drugs and alcohol by homosexually active men in relation to sexual practices.

The use of alcohol and recreational drugs in relationship to sexual practices was investigated longitudinally and cross-sectionally in a cohort of homosexually active men at a Boston community health center. Use of marijuana, nitrite inhalants, and cocaine decreased by approximately 25-48% during 42 months of follow-up, whereas use of alcohol showed little change. Men who initially reported both high-risk sexual practices and some use of alcohol or marijuana and who subsequently stopped using marijuana or reduced their frequency of alcohol use were significantly more likely to stop those unsafe sexual practices than were those who continued to use these substances. Men who at their most recent visit reported impaired judgement during sexual activity due to substance use, and particularly due to drug use, had significantly higher levels of perceived susceptibility to AIDS and barriers to behavior change, and lower levels of self-efficacy, which were independent of their unsafe sexual practices.