Real-World Effectiveness of Zamerovimab and Mazorelvimab and Vaccine for Rabies Grade III Exposure in Nanyang

Post-Exposure Prophylaxis Outcome of Zamerovimab and Mazorelvimab Injection and Rabies Vaccine in Grade III Rabies Exposure Cases From Single-Dog Multiple-Bite Incidents: A Real-World Prospective Study

The objective of this real-world, prospective observational study is to evaluate the clinical effectiveness of zamerovimab and mazorelvimab injection (a human rabies monoclonal antibody cocktail) administered in combination with a standard rabies vaccine for post-exposure prophylaxis (PEP) in individuals with WHO Grade III rabies exposure in Nanyang City, China.

1. The study primarily aims to assess:
2. The 3-month rabies-free survival rate following PEP initiation.
3. The 1-year long-term rabies-free survival rate.

The rabies virus (RABV) carrying rate and genomic epidemiology among offending dogs involved in single-dog multiple-bite incidents.

Eligible participants aged 18 years or older who have sustained a Grade III exposure from a tracked multi-person canine attack event, and have completed wound debridement and initial passive/active immunization within 24 hours prior to screening, will be followed for up to 1 year via telephone or clinic visits to monitor clinical survival.

This prospective, multicenter registry study evaluates the real-world deployment, clinical protection, and safety profile of zamerovimab and mazorelvimab injection (ZM cocktail)- containing two non-overlapping human monoclonal antibodies-in community emergency settings. Rabies presents a near 100% case-fatality rate upon symptom onset, making immediate and high-potency passive immunization essential during the active-vaccine immunity window (Days 0-7). Recent regional epidemic resurgences underscore the public health urgency of handling single-dog multiple-bite clusters, where furious rabid animals carry high viral loads and inflict multiple deep lesions.Approximately 80 patients receiving routine post-exposure care will be enrolled. Participants will receive standard-of-care wound debridement, anatomical infiltration of the ZM cocktail, and a full rabies vaccine regimen. Joining this registry involves no additional clinical interventions beyond standard medical care; investigators will actively maintain follow-up contacts at 3 months and 1 year to document survival outcomes. Concurrently, trapped offending dogs will undergo molecular verification via reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) to map localized viral ecology, providing crucial real-world data to optimize outbreak emergency response frameworks.

Inclusion Criteria:

1. Adults aged ≥18 years at the time of screening.
2. Sustained a verified WHO Grade III rabies exposure from a traceable offending dog involved in a multi-person canine attack incident (defined as a single animal attacking multiple individuals within a clustered timeframe/location) in Nanyang City.
3. Time interval from Grade III exposure to post-exposure prophylaxis (PEP) initiation is less than 7 days.
4. Successfully completed standard wound debridement, anatomical infiltration of zamerovimab/mazorelvimab injection (0.3 mg/kg single full dose), and the first dose of rabies vaccine within 24 hours prior to screening.
5. Voluntarily provides signed written informed consent.
6. Patient is willing and able to comply with all sequential follow-up procedures (including serum collections if applicable) and intends to reside locally for the full 1-year study duration.

Exclusion Criteria:

1. Documented history of any separate animal bite or scratch (e.g., dog, cat, bat, or wild carnivore) within the past 12 months prior to the current exposure.
2. Documented complete pre-exposure or post-exposure rabies vaccination history within the past 12 months.
3. Concurrent presentation with life-threatening traumatic injuries requiring intensive care, or severe systemic immunodeficiency disorders that could impede immunogenicity or follow-up compliance.
4. Any other clinical or psychological condition deemed by the investigator as unsuitable for safe participation or reliable data registry.