Public Health Response to Tuberculosis Outbreak among Persons Experiencing Homelessness, Minneapolis, Minnesota, USA, 2017-2018.

Tuberculosis (TB) is a greater risk for populations experiencing homelessness. When a TB exposure occurs in a homeless shelter, evaluation of contacts is both urgent and challenging. In 2017, local public health workers initiated a response to a TB outbreak in homeless shelters in Minneapolis, Minnesota, USA. In this contact investigation, we incorporated multiple techniques to identify, evaluate, and manage patients, including the concentric-circle method to characterize amount of contact, identifying the most frequent sites of sporadic medical care, using electronic medical records, and engaging with medical providers treating this population. Of 298 contacts evaluated, 41 (14%) had latent TB infection and 2 had active TB disease. Our analysis indicated a significant relationship between duration of exposure and positive TB test result (p = 0.001). We encourage local public health departments to expand beyond traditional contact tracing techniques by leveraging partnerships and existing systems to reach contacts exposed in shelters.

Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management.

Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed.

Acinetobacter baumannii is not associated with osteomyelitis in a rat model: a pilot study.

BACKGROUND: Multidrug resistant Acinetobacter baumannii (MDR AB) with and without Staphylococcus aureus (SA) is a commonly isolated organism in infected segmental bone defects in combat-related trauma in Iraq and Afghanistan. Although MDR AB in visceral infections is a therapeutic challenge, control of infection appears more common for combat-related osteomyelitis. QUESTIONS/PURPOSES: Using a rat model, we explored the virulence of MDR AB in segmental bone defects alone and in combination with SA. METHODS: Segmental defects in 60 rat femurs were created, stabilized, and inoculated with MDR AB alone and 60 with MDR AB and SA. We performed qualitative and quantitative bacteriology and radiographic assessments at 2, 4, and 8 weeks for MDR AB and at 1, 2, and 3 weeks for MDR AB and SA. RESULTS: Quantitative bacteriology revealed a 3- to 5-log decrease in MDR AB from the initial inoculum. After polymicrobial inoculation, only 10 of 60 animals had positive cultures for MDR AB, whereas 59 of 60 animals had positive cultures for SA. Recovered SA were 2 to 5 log greater than the initial inoculum, while there again was a 3- to 5-log decrease in MDR AB. MDR AB alone did not cause bony lysis, but there was radiographic evidence of new bone formation in 67% of the segmental defects. Osteolysis was noted with MDR AB and SA. CONCLUSIONS: MDR AB did not appear to cause or contribute to clinically apparent osteomyelitis in this pilot study. CLINICAL RELEVANCE: Resolution of infections in combat-related segmental bone defects inoculated with MDR AB may be attributable to low virulence. Additional studies are needed to confirm low virulence and bone formation with MDR AB.

Serial testing of refugees for latent tuberculosis using the QuantiFERON-gold in-tube: effects of an antecedent tuberculin skin test.

Screening for latent tuberculosis infection (LTBI) in refugee populations immigrating to low-incidence countries remains a challenge. We assessed the characteristics of the QuantiFERON-Gold In-Tube (QFT-GIT) compared with the tuberculin skin test (TST) in 198 refugees of all ages from tuberculosis-endemic countries. Diagnostic agreement between the first QFT-GIT and simultaneous TST was 78% (kappa = 0.56) and between serial QFT-GITs was 89% (kappa = 0.76). In serial QFT-GIT testing, 70% of subjects had an increased QFT-GIT value, perhaps the result of an antecedent TST in the setting of previous TB exposure. This boosting seemed to become less prevalent with time from TST and occurred less frequently in those with negative first QFT-GIT readings. Despite small changes in the quantitative results caused by nonspecific variation and boosting, the diagnostic result of the QFT-GIT was reliable. The QFT-GIT shows the potential to replace the TST for LTBI screening in refugees from tuberculosis-endemic areas.

Evaluation of malaria screening in newly arrived refugees to the United States by microscopy and rapid antigen capture enzyme assay.

Before an empiric malaria treatment program, >60% of Liberian refugees had malaria on arrival to Minnesota. We compared microscopy with rapid antigen testing for detecting asymptomatic parasitemia. Nine of 103 (8.7%) had malaria by polymerase chain reaction (blood smear and rapid testing had a sensitivity of 22%). The empiric treatment program has decreased the rate of imported asymptomatic malaria. Blood film and rapid antigen testing are poor screening tests.

Recombinant human osteogenic protein-1 induces bone formation in a chronically infected, internally stabilized segmental defect in the rat femur.

BACKGROUND: Recombinant human osteogenic protein-1 (rhOP-1), combined with a collagen carrier, has been shown to induce new-bone formation in a variety of animal models. The purpose of the present investigation was to test the hypotheses that rhOP-1 would accelerate bone formation in an internally stabilized, chronically infected, critical-size defect in the rat femur and that this effect would be enhanced by the administration of systemic antibiotic. METHODS: A 6-mm segmental defect was created surgically, stabilized with a polyacetyl plate and six Kirschner wires, and contaminated with 10(4) colony-forming units of Staphylococcus aureus in one femur in each of 168 Sprague-Dawley rats. After two weeks, these infected defects were débrided surgically and were assigned to one of six treatment groups. The defects in the thirty animals in the first group received lyophilized collagen carrier mixed with 200 microg of rhOP-1 dissolved in buffer, the defects in the thirty animals in the second group received carrier with 20 microg of rhOP-1 in buffer, and the defects in the twenty-four control animals in the third group received carrier mixed with buffer without rhOP-1. The last three groups were treated identically to the first three groups, except that the animals also received the antibiotic ceftriaxone for twenty-eight days after débridement. The animals were killed at two, four, eight, or twelve weeks after débridement. Newly mineralized callus within the defect, and adjacent to and bridging the outside of the defect, was assessed with use of quantitative high-resolution radiography, microcomputed tomography, torsional failure testing, and histological analysis of undecalcified sections. RESULTS: Bacterial cultures confirmed the presence of a chronic infection during the study period in all animals. At the later time-points, significantly more newly mineralized callus was present within and adjacent to the débrided defects that had been treated with 200 microg of rhOP-1, whereas minimal amounts of callus were present within and adjacent to the defects that had been treated without rhOP-1 and with 20 microg of rhOP-1. At eight and twelve weeks after débridement, there was significantly more newly mineralized callus in the group that had been treated with 200 microg of rhOP-1 with antibiotic than in the group that had been treated with 200 microg of rhOP-1 without antibiotic (p < 0.05). At twelve weeks, the values for torque, energy to failure, and linear stiffness for femora that had been treated with 200 microg of rhOP-1 with antibiotic were not significantly different from the values for intact, contralateral control femora, whereas the values for femora that had been treated with 200 microg of rhOP-1 without antibiotic remained significantly lower than those for the intact, contralateral controls (p < 0.05). CONCLUSIONS: Recombinant human osteogenic protein-1 maintained its osteoinductive capability in the presence of chronic infection, and this property was enhanced by antibiotic therapy. No substantial callus formed in the infected defects without a sufficiently high dose of rhOP-1. CLINICAL RELEVANCE: The treatment of an infection at the site of a fracture often necessitates removal of internal fixation. However, internal fixation is needed for fracture stability. This study presents an intervention that may accelerate fracture-healing in the presence of infection and colonized hardware, thereby permitting earlier removal of the hardware and more timely and effective treatment of the infection.

Characterization of a chronic infection in an internally-stabilized segmental defect in the rat femur.

The aim of this study was to characterize a new model of chronic osteomyelitis with clinically relevant features. A segmental defect of critical size was surgically created in the rat femur, stabilized with a polyacetyl plate and Kirschner wires, and contaminated with bacteria. The animals were allowed to recover while the contamination progressed to a chronic infection. At a later point in time, the defect was surgically débrided without removing the implant. Further treatments of interest, such as antibiotic therapy or application of an osteogenic agent, could be introduced at this time. To implement this model, an initial experiment was performed to determine the bacterial inoculum and time from contamination that would reliably result in an infected defect without causing excessive bone damage by the time débridement surgery was performed. The number of recovered bacteria, degree of radiographic bony lysis, and torsional stiffness of the defect fixation were measured in 192 rats as a function of 4 inocula of Staphylococcus aureus (10(3), 10(4), 10(5) or 10(6) CFUs) and 4 times from contamination (1, 2, 3 or 4 weeks). A 10(4) CFU inoculum over 2 weeks was found to consistently create an infection without severe lysis and loss of fixation stability. Based on these values, a second experiment was performed in 96 rats to characterize the débrided defect over time (2, 4, 8 and 12 weeks after débridement), with and without 4 weeks of the antibiotic ceftriaxone, in terms of the same outcome variables. Infection was persistent in all animals in spite of débridement and antibiotic therapy. Antibiotic therapy did not reduce the degree of bony lysis. Compared with animals not given antibiotic, bacterial counts significantly decreased during the period of antibiotic therapy, but then rebounded to significantly higher levels at 12 weeks. This model allows us to perform further studies on differing regimens of antibiotic therapy and their relationship to surgical débridement, and on the efficacy of osteogenic agents in the presence of infection.

Horses and the risk of zoonotic infections.

Infectious agents are insidious, often changing to adapt to host defenses or treatment advances. Because these challenges will continue, the need to apply standard and transmission-based precautions is important not only in the human hospital setting but in the veterinary clinic setting. In addition, to prevent human infection and potential liability, clinics need to establish program algorithms to prevent disease spread for specific agents or planned procedures to respond to potential nosocomial and zoonotic disease events. These need to be done proactively. Furthermore, more money needs to be dedicated to establish infection control programs and to improve the science of infection control in the veterinary setting.