Determining a sampling regime for PCR detection of respiratory tract viral infection at coronial post-mortem examinations.

Death due to respiratory infection is commonly encountered at autopsy. With only one opportunity to obtain samples for identification of a causative agent, it is important to ensure that sampling regimes are optimized to provide the greatest detection, without the expense and redundancy that can arise from over-sampling. This study was performed retrospectively using data from Coronial autopsies over the period 2012-2019 from which swabs from the nasopharyngeal region, trachea and lung parenchyma, in addition to samples of lung tissue, had been submitted for multiplex PCR detection of respiratory pathogens. From 97 cases with all four samples, there were 24 with at least one positive result for viral infection. Some cases had multiple positive results and a total of 27 respiratory tract viruses were identified, of which rhinovirus, influenza A virus and respiratory syncytial virus were the most common. Seventeen of the 27 viral infections (63%) were identified in all four samples. However, in nearly all cases (96%) the nasopharyngeal swab detected the infective agent when the multiplex PCR panel had detected infection in any of the four sample types. A nasopharyngeal swab is considered to be an optimal sample for detection of respiratory tract viral infection. As the samples analyzed were acquired before the appearance of the COVID-19 virus, the applicability of this finding for COVID-19 screening is not established.

Complications of tuberculosis.

PURPOSE OF REVIEW: Diagnosis and management of tuberculosis (TB) remains challenging and complex because of the heterogeneity of disease presentations. Despite effective treatment, TB disease can lead to significant short-and long-term health consequences. We review potential acute and chronic complications of TB disease and current management approaches. RECENT FINDINGS: Acute and subacute complications of TB disease are attributable to structural damage or vascular compromise caused by Mycobacterium tuberculosis, as well as metabolic abnormalities and host inflammatory responses. TB-related sepsis is a life-threatening acute complication for which current diagnostic and management approaches are likely inadequate. Therapeutic intensification and usage of immunomodulators are areas of ongoing research. Paradoxical reaction or symptom worsening during TB treatment may benefit from corticosteroids. Despite successful cure of TB, chronic complications can arise from anatomic alterations at disease sites. Examples include mycetomas developing within residual TB cavities, impaired pulmonary function, or focal neurologic deficits from tuberculomas. SUMMARY: Effective management of TB requires attention to potential structural, metabolic, vascular, and infectious complications. In some instances, individualizing treatment regimens may be necessary. Imunosuppression and other host factors predispose to complications; others occur despite adequate treatment. Public health TB programs and health systems require additional resources to provide comprehensive TB and post-TB care.

Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis.

BACKGROUND: It has been axiomatic that echinocandins (e.g., caspofungin) are ineffective against mucormycosis. However, on the basis of preclinical data, we recently began treating rhino-orbital-cerebral mucormycosis (ROCM) with combination polyene-caspofungin therapy. METHODS: To determine the impact of polyene-caspofungin therapy, ROCM cases identified by an International Classification of Diseases, Ninth Revision search were retrospectively reviewed to gather data on demographic characteristics, clinical history, and outcomes. The predefined primary end point was success (i.e., the patients was alive and not in hospice care) at 30 days after hospital discharge. RESULTS: Forty-one patients with biopsy-proven ROCM were identified over 12 years; 23 (56%) of these patients were Hispanic, and 34 (83%) were diabetic. Patients treated with polyene-caspofungin therapy (6 evaluable patients) had superior success (100% vs. 45%; Pp.02) and Kaplan-Meier survival time (Pp.02), compared with patients treated with polyene monotherapy. Patients treated with amphotericin B lipid complex had inferior success (37% vs. 72%; Pp.03) and a higher clinical failure rate (45% vs. 21%; Pp.04), compared with patients who received other polyenes. However, patients treated with amphotericin B lipid complex plus caspofungin had superior success (100% vs. 20%; Pp.009) and survival time (Pp.01), compared with patients who received amphotericin B lipid complex alone. The benefit of combination therapy, compared with monotherapy, was most pronounced in patients with cerebral involvement (success rate, 100% vs. 25%; Pp.01). In multivariate analysis, only receipt of combination therapy was significantly associated with improved outcomes (odds ratio, 10.9; 95% confidence interval, 1.3- ;Pp.02). CONCLUSIONS: Combination polyene-caspofungin therapy represents a promising potential alternative to polyene monotherapy for patients with ROCM. Randomized, prospective investigation of these findings is warranted.

A prospective multicenter study of written action plans among emergency department patients with acute asthma.

BACKGROUND: The prevalence of written "action plans" (APs) among emergency department (ED) patients with acute asthma is unknown. OBJECTIVE: To determine the prevalence of APs among ED patients, to describe the demographic and clinical profile of patients with and without APs, and to examine the appropriateness of response to an asthma exacerbation scenario. METHODS: Using a standard protocol, 49 North American EDs performed a prospective cohort study involving interviews of 1,756 patients, ages 2-54, with acute asthma. Among children only, a random sample was contacted two years after the index ED visit to assess current AP status and parents' self-management knowledge. RESULTS: The overall prevalence of APs was 32% (95% confidence interval [CI], 30%-34%), and was higher among children than adults (34% vs. 26%, respectively; p = 0.001). Patients with APs had worse measures of chronic asthma severity (p < 0.05) and were more likely to be hospitalized (multivariate odds ratio, 1.5; 95%CI, 1.1-2.1). After 2 years, most children with an AP at the index ED visit still had one but only 20% of those without an AP had obtained one; moreover, many of the APs appeared inadequate. Parents of children with a current AP performed slightly better on the asthma scenario, but both groups overestimated their asthma knowledge. CONCLUSION: The prevalence of APs among ED patients with acute asthma is unacceptably low, and many of these APs appear inadequate. "Confounding by severity" will complicate any non-randomized analysis of the potential impact of APs on asthma outcomes in ED patients.

Access to new medications for the treatment of drug-resistant tuberculosis: patient, provider and community perspectives.

Multidrug-resistant tuberculosis (MDR-TB) is on the rise, and is difficult to treat. The approval of two new drugs, bedaquiline and delamanid, and growing evidence for the use of linezolid, offer renewed hope for addressing MDR-TB. However, access to these medicines remains a significant challenge. These drugs have not been registered for TB in most settings; barriers to preapproval access persist; and high pricing and intellectual property restrictions limit access. Many unanswered research questions about optimal use of these drugs also limit access, particularly for vulnerable populations. This review outlines challenges in accessing drugs encountered from the perspective of clinicians, patients and affected communities, and offers potential solutions.

West nile virus prevalence across landscapes is mediated by local effects of agriculture on vector and host communities.

Arthropod-borne viruses (arboviruses) threaten the health of humans, livestock, and wildlife. West Nile virus (WNV), the world's most widespread arbovirus, invaded the United States in 1999 and rapidly spread across the county. Although the ecology of vectors and hosts are key determinants of WNV prevalence across landscapes, the factors shaping local vector and host populations remain unclear. Here, we used spatially-explicit models to evaluate how three land-use types (orchards, vegetable/forage crops, natural) and two climatic variables (temperature, precipitation) influence the prevalence of WNV infections and vector/host distributions at landscape and local spatial scales. Across landscapes, we show that orchard habitats were associated with greater prevalence of WNV infections in reservoirs (birds) and incidental hosts (horses), while increased precipitation was associated with fewer infections. At local scales, orchard habitats increased the prevalence of WNV infections in vectors (mosquitoes) and the abundance of mosquitoes and two key reservoir species, the American robin and the house sparrow. Thus, orchard habitats benefitted WNV vectors and reservoir hosts locally, creating focal points for the transmission of WNV at landscape scales in the presence of suitable climatic conditions.

Benign esophagobronchial fistula with and without esophageal obstruction: two ends of the surgical spectrum.

Acquired esophagobronchial fistula (EBF) is uncommon and its surgical remediation is challenging. Management depends on the cause, degree of pulmonary involvement, and existence of esophageal obstruction. We report management of two EBF cases representing extremes of the surgical spectrum. One patient with EBF secondary to mediastinal fungal infection underwent pulmonary resection and esophageal repair. Another, who was positive for human immunodeficiency virus, required esophageal resection and fistula closure, but no pulmonary resection. Successful outcome was achieved in both patients.

Novel antiretroviral agents in HIV therapy.

There are many promising new agents in development for the treatment of HIV type 1 (HIV-1). The targets of antiretroviral drugs include the three major HIV-1 enzymes (reverse transcriptase, protease, and integrase), final packaging and export of mature virions, and entry mediated by the CD4 receptor and the CCR5 and CXCR4 coreceptors. Drugs in development in existing classes are primarily designed to provide new options for those with resistance to existing agents. Novel agents such as those targeting integrase, entry inhibitors, and those targeting viral processing likely will be useful the treatment of antiretroviral-experienced patients. Depending on safety, efficacy, tolerability, and convenience of dosing, new agents may also alter the current treatment paradigms for first-line therapy. This review summarizes data on several drugs that could move forward into the clinical arena and affect the lives of those infected with HIV-1.