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.

Factors associated with recently transmitted Mycobacterium tuberculosis strain MS0006 in Hinds County, Mississippi.

OBJECTIVE: The objective of this study was to investigate risk factors associated with tuberculosis (TB) transmission that was caused by Mycobacterium tuberculosis strain MS0006 from 2004 to 2009 in Hinds County, Mississippi. METHODS: DNA fingerprinting using spoligotyping, mycobacterial interspersed repetitive unit, and IS6110-based restriction fragment length polymorphism of culture-confirmed cases of TB was performed. Clinical and demographic factors associated with strain MS0006 were analyzed by univariate and multivariate analysis. RESULTS: Of the 144 cases of TB diagnosed during the study period, 117 were culture positive with fingerprints available. There were 48 different strains, of which 6 clustered strains were distributed among 74 patients. The MS0006 strain accounted for 46.2% of all culture-confirmed cases. Risk factors for having the MS0006 strain in a univariate analysis included homelessness, HIV co-infection, sputum smear negativity, tuberculin skin test negativity, and noninjectable drug use. Multivariate analysis identified homelessness (odds ratio 7.88, 95% confidence interval 2.90-21.35) and African American race (odds ratio 5.80, 95% confidence interval 1.37-24.55) as independent predictors of having TB caused by the MS0006 strain of M. tuberculosis. CONCLUSIONS: Our findings suggest that a majority of recently transmitted TB in the studied county was caused by the MS0006 strain. African American race and homelessness were significant risk factors for inclusion in the cluster. Molecular epidemiology techniques continue to provide in-depth analysis of disease transmission and play a vital role in effective contact tracing and interruption of ongoing transmission.

Seizures in an Immunocompetent Adult From Treatment of Latent Tuberculosis Infection: Is Isoniazid to Blame?

Isoniazid-induced seizures are a rare adverse reaction especially in immunocompetent adults. We report a case of a healthy man with seizures shortly after ingestion of his first therapeutic dose of isoniazid with rifapentine therapy for treatment of latent tuberculosis infection. Only 6 other similar cases are reported in the literature.

Three indigenous cases of leprosy in the Mississippi delta.

Three native-born patients from the Mississippi Delta presented with leprosy over a 13-month period. None had a history of foreign travel, contact with each other, or known leprosy patients. Two patients' lesions lacked anesthesia, and all had a history of armadillo exposure. These cases add to the association of armadillo exposure and the subsequent development of leprosy.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Chemotherapy of Tuberculosis.

The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months. The loss of first-line agents, due to resistance or intolerance, necessitates lengthy treatment courses, frequently 12-18 months or longer. Due to the long treatment times and the implications of missed doses, directly-observed therapy (DOT) is considered the standard of care. Drugs used for the treatment of TB have serious potential toxicities that require close monitoring and prompt response. A strong public health infrastructure and robust social supports are important elements to assure successful treatment. These numerous factors compel public health entities to take a lead role in the management of TB, either through the direct management of TB treatment or by assuring the activities of partner organizations.

Multiclonal methicillin-resistant Staphylococcus aureus (MRSA) outbreak and its control after use of the Veterans Affairs (VA) MRSA bundle in a VA long-term care facility, 2004-2014.

A multiclonal methicillin-resistant Staphylococcus aureus (MRSA) outbreak with 91 infections occurred in our Veterans Affairs (VA) community living center over 46 months. Both similar and unique strains were shown by repetitive polymerase chain reaction to contribute to the outbreak, including 1 strain causing infections over a 33-month period. Most infections were soft tissue infections (67%). For 21 months after the initiation of the VA MRSA bundle, no infections were identified, and low rates of infection have been sustained an additional 4 years. The average annual rate of MRSA infection decreased by 62% (P < .001) from 0.6 per 1,000 resident days for 4 years prior to the bundle implementation to 0.09 per 1,000 resident days for 4 years after the bundle implementation.

Clinical spectrum of muscle weakness in human West Nile virus infection.

Poliomyelitis has recently been identified as a cause of muscle weakness in patients with West Nile virus (WNV) infection. However, the clinical spectrum of WNV-associated weakness has not been described. We reviewed data on 13 patients with WNV infection. Patients with muscle weakness were classified into one of three distinct groups based on clinical features. Group 1 comprised five patients who developed acute flaccid paralysis, four with meningoencephalitis and one without fever or other signs of infection. Paralysis was asymmetric, and involved from one to four limbs in individual patients. Electrodiagnostic studies confirmed involvement of anterior horn cells or motor axons. Group 2 involved two patients without meningoencephalitis who developed severe but reversible muscle weakness that recovered completely within weeks. Muscle weakness involved both lower limbs in one patient and one upper limb in the other. Group 3 consisted of two patients who experienced subjective weakness and disabling fatigue, but had no objective muscle weakness on examination. In addition to the three distinct groups, two other patients developed exaggerated weakness in the distribution of preexisting lower motor neuron dysfunction. We conclude that the clinical spectrum of WNV-associated muscle weakness ranges from acute flaccid paralysis, with or without fever or meningoencephalitis, to disabling fatigue. Also, preexisting dysfunction may predispose anterior horn cells to additional injury from WNV. Awareness of this spectrum will help to avoid erroneous diagnoses and inappropriate treatment.

Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital.

Candida parapsilosis is an important cause of bloodstream infections in the health care setting. We investigated a large C. parapsilosis outbreak occurring in a community hospital and conducted a case-control study to determine the risk factors for infection. We identified 22 cases of bloodstream infection with C. parapsilosis: 15 confirmed and 7 possible. The factors associated with an increased risk of infection included hospitalization in the intensive care unit (adjusted odds ratio, 16.4; 95% confidence interval, 1.8 to 148.1) and receipt of total parenteral nutrition (adjusted odds ratio, 9.2; 95% confidence interval, 0.9 to 98.1). Samples for surveillance cultures were obtained from health care worker hands, central venous catheter insertion sites, and medical devices. Twenty-six percent of the health care workers surveyed demonstrated hand colonization with C. parapsilosis, and one hand isolate was highly related to all case-patient isolates by tests with the DNA probe Cp3-13. Outbreak strain isolates also demonstrated reduced susceptibilities to fluconazole and voriconazole. This largest known reported outbreak of C. parapsilosis bloodstream infections in adults resulted from an interplay of host, environment, and pathogen factors. Recommendations for control measures focused on improving hand hygiene compliance.

Acute flaccid paralysis and West Nile virus infection.

Acute weakness associated with West Nile virus (WNV) infection has previously been attributed to a peripheral demyelinating process (Guillain-Barré syndrome); however, the exact etiology of this acute flaccid paralysis has not been systematically assessed. To thoroughly describe the clinical, laboratory, and electrodiagnostic features of this paralysis syndrome, we evaluated acute flaccid paralysis that developed in seven patients in the setting of acute WNV infection, consecutively identified in four hospitals in St. Tammany Parish and New Orleans, Louisiana, and Jackson, Mississippi. All patients had acute onset of asymmetric weakness and areflexia but no sensory abnormalities. Clinical and electrodiagnostic data suggested the involvement of spinal anterior horn cells, resulting in a poliomyelitis-like syndrome. In areas in which transmission is occurring, WNV infection should be considered in patients with acute flaccid paralysis. Recognition that such weakness may be of spinal origin may prevent inappropriate treatment and diagnostic testing.