Epidemiologic Studies of HMPXV Infection among PWID in the US-Mexico Border Region to Inform Prevention Responses

In response to NOT-OD-22-159, this project will leverage an ongoing cohort of people who inject drugs (PWID) in the U.S.-Mexico border region to study the epidemiology of monkeypox virus (HMPXV) to inform prevention interventions to diagnose and treat HMPXV and curtail transmission. Although it is well known that PWID face numerous health disparities including higher rates of HIV, HCV and sexually transmitted infections (STIs) than the general population, experts are concerned that the ongoing outbreak of HMPXV, which is the largest international outbreak recorded since this virus first emerged in the 1970’s, will soon disproportionately affect people experiencing homelessness (PEH), which includes a high proportion of PWID. Our team includes epidemiologists, prevention interventionists, molecular virologists and infectious disease physicians to address these aims: Aim 1. To determine the prevalence and correlates of subclinical and symptomatic HMPXV infection among PWID in the San Diego/Tijuana (SD/TJ) border region to inform the development of prevention interventions. H1. PWID who are unstably housed (H1.1), Latinx (H1.2) or living with HIV and not receiving ART (H1.3) will be significantly more likely to test positive for HMPXV infection. Aim 2. To estimate incidence and risk factors of HMPXV infection among PWID over a one-year period. H2.1 PWID who report recently having abscesses associated with injection drug use, STIs or open sores will be more likely to acquire HMPXV during follow-up. H2.2. PWID who report engaging in sex work and those with higher numbers of sex partners will be more likely to acquire HMPXV during follow-up. Aim 3. To determine network features associated with cross-border transmission of HMPXV among PWID. H3.1 Cross-border drug tourism between SD and TJ (by participants & their network contacts) will be associated with HMPXV infection. H3.2. Network-level risk factors such as total number of contacts and number of contacts who are MSM, sex workers, unstably housed, or have a history of incarceration will be independently associated with HMPXV infection after controlling for individual-level risk factors. Aim 4: To conduct phylogenomic characterization of circulating HMPXV variants in the SD/TJ region including mutation signatures (e.g., APOBEC3). H4.1 Circulating HMPXV will have a single origin (lineage B.1) followed by local dispersal. We will leverage the binational infrastructure of our NIDA- funded binational cohort of PWID, and support from a new pandemic preparedness institute at UCSD to conduct HMPXV PCR testing and sequencing on swabs collected from any suspect lesions/vesicles as well as oral and anal swabs. Serologic HMPXV testing will be done in-kind by the CDC. Findings will inform potential interventions and policies, including whether PWID and/or PEH should be recommended for routine vaccination and whether subsequent interventions to increase HMPXV testing, vaccination and treatment in this vulnerable population should be network or venue-based, following NIMHD’s conceptual model for structural interventions.