Leonard Mukasa

The Road to Tuberculosis (Mycobacterium tuberculosis) Elimination in Arkansas; a Re-Examination of Risk Groups

Objectives This study was conducted to generate knowledge useful for developing public health interventions for more effective tuberculosis control in Arkansas. Methods The study population included 429 culture-confirmed reported cases (January 1, 2004–December 31, 2010). Mycobacterium tuberculosis genotyping data were used to identify cases likely due to recent transmission (clustered) versus reactivation (non-clustered). Poisson regression models estimated average decline rate in incidence over time and assessed the significance of differences between subpopulations. A multinomial logistic model examined differences between clustered and non-clustered incidence. Results A significant average annual percent decline was found for the overall incidence of culture-confirmed (9%; 95% CI: 5.5%, 16.9%), clustered (6%; 95% CI: 0.5%, 11.6%), and non-clustered tuberculosis cases (12%; 95% CI: 7.6%, 15.9%). However, declines varied among demographic groups. Significant declines in clustered incidence were only observed in males, non-Hispanic blacks, 65 years and older, and the rural population. Conclusions These findings suggest that the Arkansas tuberculosis control program must target both traditional and non-traditional risk groups for successful tuberculosis elimination. The present study also demonstrates that a thorough analysis of TB trends in different population subgroups of a given geographic region or state can lead to the identification of non-traditional risk factors for TB transmission. Similar studies in other low incidence populations would provide beneficial data for how to control and eventually eliminate TB in the U.S.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection

Background Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Identification of factors for tuberculosis transmission via an integrated multidisciplinary approach

It was reported previously that the major fraction of the recent decrease of tuberculosis incident cases in Arkansas had been due to a decrease in the reactivated infections. Preventing transmission of Mycobacterium tuberculosis is the key to a continued decline in tuberculosis cases. In this study, we integrated epidemiological data analysis and comparative genomics to identify host and microbial factors important to tuberculosis transmission. A significantly higher proportion of cases in large clusters (containing >10 cases) were non-Hispanic black, homeless, less than 65 years old, male sex, smear-positive sputum, excessive use of alcohol, and HIV sero-positive, compared to cases in small clusters (containing 2-5 cases) diagnosed within one year. However, being non-Hispanic black and homeless within the past year were the only two host characteristics that were identified as independent risk factors for being in large clusters. This finding suggests that social behavioral factors have a more important role in transmission of tuberculosis than does the infectiousness of the source. Comparing the genomic content of one of the large cluster strains to that of a non-clustered strain from the same community identified 25 genes that differed between the two strains, potentially contributing to the observed differences in transmission.

Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.

BACKGROUND Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical specimens. In 2012, the Arkansas Tuberculosis Control Program introduced GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium Tuberculosis Direct (MTD) assay. AIMS To rapidly diagnose TB within two hours and to simultaneously detect RIF resistance. OBJECTIVES Describe the procedure used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.Characterise the current gap in rapid M. tuberculosis diagnosis in Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but culture-positive cases in Arkansas.Illustrate, with two case reports, the role of GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis diagnosis in the first year of implementation. METHOD Between June 2012 and June 2013, all AFB sputum smearpositive cases and any others, on request by the physician, had GeneXpert MTB/RIF assay performed as well as traditional M. tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator Tube (MGIT) 960 and Löwenstein-Jensen (LJ) slants. Surveillance data for January 2009-June 2013 was analysed to characterise sputum smear-negative but culture-positive cases. RESULTS Seventy-one TB cases were reported from June 2012- June 2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as three cases that were negative on culture. Also, this rapid assay identified all six smear-negative but M. tuberculosis culture-positive cases; two of these cases are described as case reports. CONCLUSION GeneXpert MTB/RIF assay has made rapid TB diagnosis possible, with tremendous potential in determining isolation of TB suspects on one hand, and quickly ruling out TB whenever suspected.

Pulmonary Tuberculosis in a Patient with Cystic Fibrosis

Context: Mycobacterium tuberculosis (MTB) infection is rarely seen in cystic fibrosis (CF) patients. Case Report: We report a 24-year-old CF patient with fever, cough, hemoptysis, and weight loss of 1week duration prior to admission. Past sputum cultures grew methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The patient was treated with broad spectrum antibiotics based on previous culture data, but failed to improve. Chest radiograph and computed tomography (CT) chest revealed chronic collapse of the anterior subsegment of right upper lobe and multiple bilateral cavitary lesions which were worse compared to prior films. MTB was suspected and was confirmed by positive acid-fast bacilli (AFB) smears and cultures. After receiving first-line antituberculous drugs, the patient′s condition markedly improved. Conclusion: MTB is an infrequent finding, but considered a potential pathogen in CF patients, and may lead to serious pulmonary complications if there is a delay in diagnosis and treatment.

Tuberculosis reinfection in a pregnant cystic fibrosis patient

Cystic Fibrosis (CF) is a multisystem disease predominantly affecting the airways and predisposing patients to recurrent infections with various multidrug resistant organisms. Mycobacterium tuberculosis (MTB) infection is rarely seen, but considered a potential pathogen in CF patients. We report a 26 year old pregnant CF patient on Ivacaftor who was admitted with symptoms suggestive of tuberculosis. Three years prior to the current admission, she had completed four drug anti- MTB therapy for pulmonary tuberculosis and was considered cured as her sputum cultures after six months of treatment were negative. Genotype analysis revealed the current MTB strain to be different from the strain causing the previous infection. After receiving first line anti-tuberculous regimen for nine months, the patients condition markedly improved culminating in an uneventful pregnancy and delivery. To our knowledge, this is the only reported case of reinfection tuberculosis in a CF patient.

Effectiveness of contact investigations for tuberculosis control in Arkansas.

Comprehensive assessment of the effectiveness of contact investigations for tuberculosis (TB) control is still lacking. In this study, we use a computational model, calibrated against notification data from Arkansas during the period 2001-2011, that reproduces independent data on key features of TB transmission and epidemiology. The model estimates that the Arkansas contact investigations program has avoided 18.6% (12.1-25.9%) of TB cases and 23.7% (16.4-30.6%) of TB deaths that would have occurred during 2001-2014 if passive diagnosis alone were implemented. If contacts of sputum smear-negative cases had not been included in the program, the percentage reduction would have been remarkably lower. In addition, we predict that achieving national targets for performance indicators of contact investigation programs has strong potential to further reduce TB transmission and burden. However, contact investigations are expected to have limited effectiveness on avoiding reactivation cases of latent infections over the next 60 years.

Integration of Tuberculosis (TB) Screening in The Ryan White Program in Arkansas

Abstract Background Globally, TB remains the most common cause of death among people with HIV (killing 1 in 4 patients). In the US, the conservative estimate of HIV-LTBI burden is 48,000. Population-based TB-HIV data are not available due to inadequate TB screening among the HIV-infected. In the previous study we found that recommendation for TB screening is missing in HIV guidelines in 36 out of 50 (72%) US states, and TB screening data are missing in half of the Ryan White Programs. Methods We aim to assess the current surveillance structure and prevalence of TB screening among Ryan White clients in Arkansas, and inform revisions of guidelines. We interviewed ADH staff (including Ryan White program manager, data specialist, Infectious Disease branch manager, and TB epidemiologist) to map out how TB screening is supposed to be reported in the Ryan White Program. We also assessed data availability and quality in both CAREWare and electronic client dossiers. After evaluation, we created a user-defined data field in CAREWare for pilot testing. Then we had meetings involving both the Ryan White Program and the TB Program for discussion. Results The data flow is shown in Figures 1 and 2. We found no TB screening files in Ryan White client dossiers. The existing TB data structure in CAREWare is confusing, with duplicate variables (both active and inactivate) in multiple sub-tabs. We proposed a user-friendly data field for TB screening (date, type of tests, result, and interpretation). We made three policy changes at the ADH: a memorandum of understanding between the Ryan White Program and the TB Program to improve communications, a modified contract (effective March 2017) with Ryan White providers that mandates annual TB screening for all clients, and an official letter to all physicians in Arkansas addressing the importance of TB screening among HIV-infected people. Conclusion We believe that program collaboration and service integration between TB and HIV is the key in eliminating missed opportunities in TB-AIDS diagnoses. In our next steps, we want to evaluate the data captured in CAREWare between 2016 and 2017. We also want to question why individual level data, which should include TB screenings, are not reported to the HRSA.Figure 1. TB and HIV reporting system in the USA.Figure 2. Information flow in the Ryan White Program Disclosures All authors: No reported disclosures.