Early emergence of anti-HCV antibody implicates donor origin in recipients of an HCV-infected organ.

Hepatitis C virus (HCV) seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti-HCV antibody at any point during follow-up. The majority of antibody-positive individuals became positive within 1-3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti-HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%-25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti-HCV antibody is common in HCV-uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti-HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.

Transplanting hepatitis C virus-infected hearts into uninfected recipients: A single-arm trial.

The advent of direct-acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV-infected donors. We conducted a single-arm trial of orthotopic heart transplantation (OHT) from HCV-infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40-65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV-genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt-in for HCV nucleic-acid-test (NAT)+ donor offers to OHT was 39 days (interquartile range [IQR] 17-57). The median donor age was 34 years (IQR 31-37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR-12). The 10th recipient had a positive cross-match, experienced antibody-mediated rejection and multi-organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short-term results suggest that HCV-negative candidates transplanted with HCV-infected hearts have acceptable outcomes.

The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients.

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA+ donors and none have reported quality of life (QOL). Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.

Notional Spread of Cholera in Haiti Following a Natural Disaster: Considerations for Military and Disaster Relief Personnel.

INTRODUCTION: Cholera remains a significant public health threat for many countries, and the severity largely varies by the population and local conditions that drive disease spread, especially in endemic areas prone to natural disasters and flooding. Epidemiological models can provide useful information to military planners for understanding disease spread within populations and the effectiveness of response options for preventing the transmission among deployed and stationed personnel. This study demonstrates the use of epidemiological modeling to understand the dynamics of cholera transmission to inform emergency planning and military preparedness in areas with highly communicable diseases. MATERIALS AND METHODS: Areas with higher probability for a potential cholera outbreak in Haiti followed by a natural disaster were identified. The hotspots were then used to seed an extended compartmental model, EpiGrid, to simulate notional spread scenarios of cholera originating in three distinct areas in Haiti. Disease parameters were derived from the 2010 cholera outbreak in Haiti, and disease spread was simulated over a 12-week period under uncontrolled and controlled spread. RESULTS: For each model location, scenarios of mitigated (intervention with 30% transmission reduction via international aid) and unmitigated (without intervention) are simulated. The results depict the geographical spread and estimate the cumulative cholera infection for each notional scenario over the course of 3 months. Disease transmission differs considerably across origin site with an outbreak originating in the department of Nippes spanning the largest geographic area and resulting in the largest number of cumulative cases after 12 weeks under unmitigated (79,518 cases) and mitigated (35,667 cases) spread scenarios. CONCLUSIONS: We modeled the notional re-emergence and spread of cholera following the August 2021 earthquake in Haiti while in the midst of the global COVID-19 pandemic. This information can help guide military and emergency response decision-making during an infectious disease outbreak and considerations for protecting military personnel in the midst of a humanitarian response. Military planners should consider the use of epidemiological models to assess the health risk posed to deployed and stationed personnel in high-risk areas.

A Universal Travel Risk Assessment Questionnaire: Travel Assessment During COVID-19 Pandemic and Endemicity.

INTRODUCTION: Throughout the Coronavirus Disease 2019 (COVID-19) pandemic, military commanders have been challenged with providing appropriate travel guidance for their military and civilian personnel and dependents. This guidance, where promulgated, lacks uniformity. Travel aids and computer applications similarly differ and are not updated as often as jurisdictional travel health guidance is changed. Given the ever-evolving Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants with differing degrees of infectivity, COVID-19 travel guidance will remain relevant for military travelers during the transition from pandemic to endemic phases and for the foreseeable future. MATERIALS AND METHODS: We reviewed all germane travel guidance promulgated by the U.S, Department of Defense; the U.S. Centers for Disease Control and Prevention; and other federal, state, and international agencies. From these materials, we identified and delineated applicable universal components for COVID-19 travel risk and created a universal Travel Risk Assessment Questionnaire (TRAQ). RESULTS: We present a universal TRAQ that identifies and allows for a graded most-appropriate response to known travel risk assessment factors including travel restrictions, travel mode, travel time, travel party size, trip duration, COVID-19 incidence rate at travel destination, lodging, planned activities, personal interaction level, vaccination coverage at destination, travel location, traveler's vaccination status, previous COVID-19 infection, mask wear compliance, mask type, and work environment, along with additional considerations and post-travel COVID-19 questions. We provide examples of the use of this questionnaire that describe low, medium, and high risk to the traveler for contracting COVID-19. CONCLUSION: Our TRAQ provides an easy-to-use format that can enable military, business, or personal travelers to more completely assess their likelihood of COVID-19 exposure and help them to reduce their potential for contracting COVID-19 during travel and subsequently transmitting it to others upon return. It should help commanders and traveling personnel to better assess COVID-19 travel risks through application of known travel risk factors.