Study design and participants
This observational, retrospective population-based cohort study was based on data obtained from the electronic medical records of Clalit Health Services (CHS), a large healthcare organization that covers approximately 52% of the entire Israeli population. The study commenced on July 31, 2022, when the MVA vaccination campaign was initiated in CHS. Participants were followed until September 12, 2022, and for at least 25 days after vaccination. Participants vaccinated after August 18, 2022, were excluded to allow sufficient follow-up time.
The primary endpoint was MPXV infection diagnosis, determined by a laboratory-confirmed real-time polymerase chain reaction (RT-PCR) test. The estimated date of infection was defined as the earlier of the following dates: five days before the PCR test or five days before a suspected diagnosis of MPXV was documented.
The cohort included all CHS members eligible for the MVA vaccine per the Israeli MOH guidelines when the study commenced. The MVA eligibility criteria were: (a) Males aged 18 – 42 who were dispensed HIV-PrEP at least for one month since January 1, 2022, or (b) Males aged 18 – 42 who were diagnosed with HIV and also were diagnosed with one or more of the following STIs since January 1, 2022: active Syphilis, Chlamydia, or Gonorrhea. Subjects who were infected with MPXV prior to the study period were excluded.
The following data were extracted for each participant: age, geographical district of primary healthcare clinic, population sector, the score for socioeconomic status, utilization of primary healthcare services, vaccines utilization, history of HIV/AIDS, STIs detected in rectal, pharyngeal, or urine PCR tests, blood test for Syphilis screening (TPHA), and dispense of HIV-PrEP therapy and PDE5-inhibitors (sildenafil, tadalafil, or vardenafil).
The CHS data repositories and the definition of the sociodemographic variables were previously described in Covid-19 studies (7). The data extraction date was September 19, 2022.
Descriptive statistics were used to characterize the study participants. The geographical district was classified as Tel Aviv versus other districts, as Tel Aviv is the Israeli epicenter of the LGTBQ+ community. The population sector was classified as the general Jewish sector versus two minority sectors: Arabs and Jewish-Ultraorthodox, and the sociodemographic status score was categorized as below the median versus median score or higher.
In order to avoid immortal time bias (8), we performed a time-dependent analysis in which a time-varying covariate was used to indicate the initiation of vaccination for each vaccinated patient. participants were transferred from the 'unvaccinated' risk set to the 'vaccinated' risk set when vaccinated, modifying their vaccination status from unvaccinated to vaccinated. Consequently, the follow-up of vaccinated patients started at the end of the immortal period.
The association between MVA vaccination and MPXV infection was estimated as follows: first, a univariate Kaplan-Meier analysis with a log-rank test was applied to test the associations of each independent candidate variable with the primary outcome. The threshold for the first testing criteria was set at p<0.2. Then the proportional hazard assumption was validated for those variables using Schoenfeld's global test. Variates that met these two testing criteria served as inputs for multivariate Cox proportional-hazards analysis. Vaccine effectiveness was defined as 1 minus the hazard ratio.
Analyses were conducted in R statistical software version 3.5.0 (R Project for Statistical Computing). All reported p-values are two-tailed.