Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report.

BACKGROUND: Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in the USA linked to a bone graft product containing live cells derived from a single deceased donor. METHODS: In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis. FINDINGS: The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24-87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8-99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56-81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical. INTERPRETATION: Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered. FUNDING: None.

Risk of Transmissibility From Neurodegenerative Disease-Associated Proteins: Experimental Knowns and Unknowns.

Recent studies in animal models demonstrate that certain misfolded proteins associated with neurodegenerative diseases can support templated misfolding of cognate native proteins, to propagate across neural systems, and to therefore have some of the properties of classical prion diseases like Creutzfeldt-Jakob disease. The National Institute of Aging convened a meeting to discuss the implications of these observations for research priorities. A summary of the discussion is presented here, with a focus on limitations of current knowledge, highlighting areas that appear to require further investigation in order to guide scientific practice while minimizing potential exposure or risk in the laboratory setting. The committee concluded that, based on all currently available data, although neurodegenerative disease-associated aggregates of several different non-prion proteins can be propagated from humans to experimental animals, there is currently insufficient evidence to suggest more than a negligible risk, if any, of a direct infectious etiology for the human neurodegenerative disorders defined in part by these proteins. Given the importance of this question, the potential for noninvasive human transmission of proteopathic disorders is deserving of further investigation.

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults.

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/µL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change -0.04 (±0.18) log(10) copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination.

Case-control study of armadillo contact and Hansen's disease.

Hansen's disease (HD) continues to have worldwide impact despite efforts to eradicate the disease. Although a definitive transmission mode has not been identified, data supports an association between HD and contact with the nine-banded armadillo. We conducted a case-control study of 28 HD patients to determine if there is an association between armadillo exposure and HD. There was no association between HD and place of birth or having hunted, consumed, or had direct or indirect contact with deer, birds, or squirrels. Univariate analysis showed that residence in Mexico (P = 0.001), hunting rabbits (P = 0.04), cleaning rabbits (P < 0.001), and armadillo exposure from hunting (P = 0.005), cleaning (P = 0.004), consuming (P = 0.002) them, or having direct armadillo contact (P = 0.017) were associated with HD. Multivariate analysis showed that eating armadillos (P = 0.039, odds ratio [OR] = 3.65, 95% confidence interval [CI] = 1.07-12.4), cleaning rabbits (P = 0.018, OR = 4.08, 95% CI = 1.27-13.1), and having lived in Mexico (P = 0.006, OR = 24.9, 95% CI = 2.52-245) were associated with HD.

Clindamycin-induced Sweet's syndrome.

Drug-induced acute febrile neutrophilic dermatosis, or Sweet's syndrome, is rare and, to our knowledge, has not previously been associated with clindamycin therapy. We describe a 47-year-old woman with type 2 diabetes mellitus and end-stage renal disease requiring hemodialysis who developed Sweet's syndrome after receiving oral and intravenous clindamycin for a tooth infection. After the clindamycin was discontinued, the patient's clinical symptoms resolved over several days. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of Sweet's syndrome and clindamycin therapy. Clinicians should be aware that Sweet's syndrome can occur with clindamycin treatment. Early recognition of this condition in conjunction with cessation of drug exposure, with or without antiinflammatory therapy, can produce complete recovery.

Severe serum sickness reaction to oral and intramuscular penicillin.

Serum sickness is a type III hypersensitivity reaction mediated by immune complex deposition with subsequent complement activation, small-vessel vasculitis, and tissue inflammation. Although the overall incidence of serum sickness is declining because of decreased use of heterologous sera and improved vaccinations, rare sporadic cases of serum sickness from nonprotein drugs such as penicillins continue to occur. Drug-induced serum sickness is usually self-limited, with symptoms lasting only 1-2 weeks before resolving. We report an unusual case of a severe and prolonged serum sickness reaction that occurred after exposure to an intramuscular penicillin depot injection (probable relationship by Naranjo score) and discuss how pharmacokinetics may have played a role. Clinicians should be familiar with serum sickness reactions particularly as they relate to long-acting penicillin preparations. Accurate diagnosis in conjunction with cessation of drug exposure and prompt initiation of antiinflammatory treatment with corticosteroids can produce complete recovery

Dilated cardiomyopathy and acute liver injury associated with combined use of ephedra, gamma-hydroxybutyrate, and anabolic steroids.

Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used gamma-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of gamma-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury.