Barriers to Receipt of Prenatal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine Among Mothers of Infants Aged <4 Months with Pertussis - California, 2016.

Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended for all pregnant women to protect infants who are too young for vaccination from severe pertussis-related outcomes (1-3). However, Tdap vaccine coverage among pregnant women remains suboptimal in California (4). California mothers whose infants developed pertussis in 2016 and their prenatal care providers were interviewed to ascertain possible reasons for low Tdap vaccine coverage. Mothers who were offered Tdap vaccination on-site during a routine prenatal visit were more likely to be vaccinated than were mothers who were referred off-site for vaccination. Mothers insured by Medicaid were less likely to receive Tdap vaccine than were mothers with private insurance, even when the vaccine was stocked on-site. Nearly all vaccinated mothers received Tdap vaccine in their prenatal clinic. Incorporating Tdap vaccination into routine prenatal care visits is an effective means to increase prenatal Tdap vaccination coverage.

Developing and using performance measures based on surveillance data for program improvement in tuberculosis control.

California state and local tuberculosis (TB) programs used a systematic process to develop a set of indicators to measure and improve program performance in controlling TB. These indicators were the basis for a quality improvement process known as the TB Indicators Project. Indicators were derived from guidelines and legal mandates for clinical, case management, and surveillance standards and were assessed using established criteria. The indicators were calculated using existing surveillance data. The indicator set was field tested by local programs with high TB morbidity and subsequently revised. Collaboration with key stakeholders at all stages was crucial to developing useful and accepted indicators. Data accessibility was a critical requirement for indicator implementation. Indicators most frequently targeted for performance improvement were those perceived to be amenable to intervention. Indicators based on surveillance data can complement other public health program improvement efforts by identifying program gaps and successes and monitoring performance trends.

Treatment of active tuberculosis in HIV-coinfected patients: a systematic review and meta-analysis.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse. METHODS: A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression. RESULTS: After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase (n=3352 patients from 35 study arms), thrice-weekly therapy (n=211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with > or =8 months, or if antiretroviral therapy was not used. CONCLUSIONS: This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.

Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis.

BACKGROUND: Treatment regimens for active tuberculosis (TB) that are intermittent, or use rifampin during only the initial phase, offer practical advantages, but their efficacy has been questioned. We conducted a systematic review of treatment regimens for active TB, to assess the effect of duration and intermittency of rifampin use on TB treatment outcomes. METHODS AND FINDINGS: PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were searched for randomized controlled trials, published in English, French, or Spanish, between 1965 and June 2008. Selected studies utilized standardized treatment with rifampin-containing regimens. Studies reported bacteriologically confirmed failure and/or relapse in previously untreated patients with bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of treatment outcomes and association with risk factors were computed with stratified random effects meta-analyses. Meta-regression was performed using a negative binomial regression model. A total of 57 trials with 312 arms and 21,472 participants were included in the analysis. Regimens utilizing rifampin only for the first 1-2 mo had significantly higher rates of failure, relapse, and acquired drug resistance, as compared to regimens that used rifampin for 6 mo. This was particularly evident when there was initial drug resistance to isoniazid, streptomycin, or both. On the other hand, there was little evidence of difference in failure or relapse with daily or intermittent schedules of treatment administration, although there was insufficient published evidence of the efficacy of twice-weekly rifampin administration throughout therapy. CONCLUSIONS: TB treatment outcomes were significantly worse with shorter duration of rifampin, or with initial drug resistance to isoniazid and/or streptomycin. Treatment outcomes were similar with all intermittent schedules evaluated, but there is insufficient evidence to support administration of treatment twice weekly throughout therapy.

Extensively drug-resistant tuberculosis in california, 1993-2006.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. METHODS: XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. RESULTS: Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. CONCLUSIONS: XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants.

BACKGROUND: Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. METHODS: Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. RESULTS: Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6-26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than hospitalization of passively detected cases. CONCLUSION: While the current immigration screening program is unlikely to result in a large change in case rates, domestic follow-up of B-notification patients, including LTBI treatment, is highly cost-effective. If as many as three percent of screened individuals have active TB, and early detection reduces the rate of hospitalization, net savings may be expected.

Improved outcomes found after implementing a systematic evaluation and program improvement process for tuberculosis.

California's state and local tuberculosis (TB) programs collaborated to develop the Tuberculosis Indicators Project (TIP), a program evaluation and improvement process. In TIP, local and state staff review data, identify program gaps, implement plans to improve local TB program performance, and evaluate outcomes. After 10 years of project implementation, indicator performance changes and patient outcomes were measured. Eighty-seven percent of participating programs showed a performance increase in targeted indicators after three years compared with 57% of comparison groups. Statistically significant performance change was more common in the intervention local health departments (LHDs) than in comparison groups. The most notable performance changes were in the contact investigation and case management indicators. These results indicate that this systematic evaluation and program improvement project was associated with improved LHD TB control performance and may be useful to inform improvement projects in other public health programs.

Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

INTRODUCTION: Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. METHODS: We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. RESULTS: Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6-7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3) and less than 50 cells/mm(3), and when correcting for drug resistance pattern. LIMITATIONS: We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. DISCUSSION: While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

Sputum monitoring during tuberculosis treatment for predicting outcome: systematic review and meta-analysis.

WHO has previously recommended sputum-smear examination at the end of the second month of treatment in patients with recently diagnosed pulmonary tuberculosis, and, if positive, extension of the intensive therapy phase. We did a systematic review and meta-analysis to assess the accuracy of a positive sputum smear or culture during treatment for predicting failure or relapse in pulmonary tuberculosis. We searched PubMed, Embase, and the Cochrane Library for studies published in English through December, 2009. We included randomised controlled trials, cohort, and case-control studies of previously untreated pulmonary tuberculosis patients who had received a standardised regimen with rifampicin in the initial phase. Accuracy results were summarised in forest plots and pooled by use of a hierarchical regression approach. 15 papers (28 studies) met the inclusion criteria. The pooled sensitivities for both 2-month smear (24% [95% CI 12-42%], six studies) and culture (40% [95% CI 25-56%], four studies) to predict relapse were low. Corresponding specificities (85% [95% CI 72-90%] and 85% [95% CI 77-91%]) were higher, but modest. For failure, 2-month smear (seven studies) had low sensitivity (57% [95% CI 41-73%]) and higher, although modest, specificity (81% [95% CI 72-87%]). Both sputum-smear microscopy and mycobacterial culture during tuberculosis treatment have low sensitivity and modest specificity for predicting failure and relapse. Although we pooled a diverse group of patients, the individual studies had similar performance characteristics. Better predictive markers are needed.

Effect of ring strain on nucleophilic substitution at selenium: a computational study of cyclic diselenides and selenenyl sulfides.

Nucleophilic substitution reactions of small rings incorporating selenium are examined using computational methods. The potential energy surfaces of HS- and HSe- with 1,2-diselenirane, 1,2-diselenetane, 1,2-diselenolane, and 1,2-diselenane were computed at B3LYP/6-31+G(d) and MP2/6-31+G(d). The reactions of three-, four-, five-, and six-membered rings incorporating the S-Se bond with HS- were computed at B3LYP/6-31+G(d). The strained three- and four-membered diselenides and selenenyl sulfide rings undergo SN2 reactions, while the five- and six-membered rings react via the addition-elimination pathway, a path that invokes a hypercoordinate selenium intermediate. The strain in the small rings precludes the addition of a further ligand to either heteroatom. Substitution at selenium is both kinetically and thermodynamically favored over attack at sulfur.

Cost-effectiveness of alternative strategies for tuberculosis screening before kindergarten entry.

OBJECTIVE: We undertook a decision analysis to evaluate the economic and health effects and incremental cost-effectiveness of using targeted tuberculin skin testing, compared with universal screening or no screening, before kindergarten. METHODS: We constructed a decision tree to determine the costs and clinical outcomes of using targeted testing compared with universal screening or no screening. Baseline estimates for input parameters were taken from the medical literature and from California health jurisdiction data. Sensitivity analyses were performed to determine plausible ranges of associated outcomes and costs. We surveyed California health jurisdictions to determine the prevalence of mandatory universal tuberculin skin testing. RESULTS: In our base-case scenario, the cost to prevent an additional case of tuberculosis by using targeted testing, compared with no screening, was $524,897. The cost to prevent an additional case by using universal screening, compared with targeted testing, was $671,398. The incremental cost of preventing a case through screening remained above $100,000 unless the prevalence of tuberculin skin testing positivity increased to >10%. More than 51% of children entering kindergarten in California live where tuberculin skin testing is mandatory. CONCLUSIONS: The cost to prevent a case of tuberculosis by using either universal screening or targeted testing of kindergarteners is high. If targeted testing replaced universal tuberculin skin testing in California, then $1.27 million savings per year would be generated for more cost-effective strategies to prevent tuberculosis. Improving the positive predictive value of the risk factor tool or applying it to groups with higher prevalence of latent tuberculosis would make its use more cost-effective. Universal tuberculin skin testing should be discontinued, and targeted testing should be considered only when the prevalence of risk factor positivity and the prevalence of tuberculin skin testing positivity among risk factor-positive individuals are high enough to meet acceptable thresholds for cost-effectiveness.

Laboratory reporting of tuberculosis test results and patient treatment initiation in California.

Prompt laboratory reporting of tuberculosis (TB) test results is necessary for TB control. To understand the extent of and factors contributing to laboratory reporting delays and the impact of reporting delays on initiation of treatment of TB patients, we analyzed data from 300 consecutive culture-positive TB cases reported in four California counties in 1998. Laboratory reporting to the specimen submitter was delayed for 26.9% of smear-positive patients and 46.8% of smear-negative patients. Delays were associated with the type of laboratory that performed the testing and with delayed transport of specimens. Referral laboratories (public health and commercial) had longer median reporting time frames than hospital and health maintenance organization laboratories. Among patients whose treatment was not started until specimens were collected, those with delayed laboratory reporting were more likely to have delayed treatment than patients with no laboratory reporting delays (odds ratio [OR] of 3.9 and 95% confidence interval [CI] of 1.6 to 9.7 for smear-positive patients and OR of 13.1 and CI of 5.3 to 32.2 for smear-negative patients). This relation remained after adjustment in a multivariate model for other factors associated with treatment delays (adjusted OR of 25.64 and CI of 7.81 to 83.33 for smear-negative patients). These findings emphasize the need to reduce times of specimen transfer between institutions and to ensure rapid communication among laboratories, health care providers, and health departments serving TB patients.