Sex: M
Vaccine: MNQ, MNQ
Symptoms: Meningococcal infection, Vaccination failure
Clinical narrative: This case was reported in a literature article and described the occurrence of suspected vaccination failure in a male patient who received Men ACWY-CRM NVS (Menveo) for prophylaxis. Co-suspect products included MENINGOCOCCAL A, C, Y, W135 CONJUGATE VACCINE (DIPHTHERIA) (MENACTRA (MENACWY-D)) for prophylaxis. On an unknown date, the patient received Menveo and MENACTRA (MENACWY-D). On an unknown date, 7 years after receiving Menveo, the patient experienced vaccination failure (serious criteria GSK medically significant) and meningococcal infection (serious criteria GSK medically significant). On an unknown date, the outcome of the vaccination failure and meningococcal infection were unknown. The reporter considered the vaccination failure and meningococcal infection to be related to Menveo. Additional details were reported as follows: This case was reported in a literature article and described the suspected vaccination failure in a male patient aged between 12 to 62 years, who was vaccinated with Menveo (MenACWY-CRM) vaccine (GlaxoSmithKline) for prophylaxis. The patient was a part of the report which described recent cases of serogroup A, C, W, and Y meningococcal disease in persons previously vaccinated with a MenACWY vaccine. [The authors analyzed cases of serogroup A, C, W, and Y meningococcal disease reported through the Regulatory Authority database from 2014 through 2018. State health departments submitted additional information on risk factors and clinical course. Confirmed and probable cases of serogroup A, C, W and Y meningococcal disease reported from 2014 through 2018 were reviewed for this analysis. Meningococcal vaccine history was collected through interview and review of vaccine registries. All cases in patients who had previously received one or more doses of MenACWY vaccine were reviewed and additional information was collected on risk factors and clinical course of illness. Additional data collected included symptoms; whether the patient had a documented complement deficiency, functional or anatomic asplenia, HIV or other underlying conditions or chronic illness; medications and treatments at time of disease onset, including complement inhibitor use; dates of hospitalization and ICU admission; prior history of meningococcal disease; and family history of meningococcal disease. Species and serogroup of the infecting strain were determined by state public health laboratories and confirmed by the CDC laboratory using slide agglutination and/or polymerase chain reaction (PCR) when an isolate was available. Sequence type and clonal complex were determined by whole genome sequencing at CDC]. The patient had no prior history of meningococcal disease nor family history of meningococcal disease. The patient's immunosuppressive condition was not known. No information on patient's concomitant medication was provided. On an unspecified date, 7 years prior to onset, the patient received 1 (one) dose of MenACWY-CRM (Menveo) (Route and site of administration unknown; batch number not provided). On an unspecified date, 1 year before onset, the patient received 1 (one) dose of MenACWY-D (Menactra) (Route and site of administration unknown; batch number not provided). [Two quadrivalent meningococcal conjugate serogroup A, C, W, Y (MenACWY) vaccines were used in 2018: MenACWY-D (Menactra) (licensed in 2005) and MenACWY-CRM (Menveo) (licensed in 2010). A polysaccharide vaccine, MPSV4 (Menomune), was also in use through 2017. In 2005, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination with MenACWY vaccines at 11 to 12 years of age and added a booster dose recommendation in 2010 for adolescents at 16 years of age. ACIP also recommended meningococcal vaccination for persons aged 2 months and older who were at increased risk of meningococcal disease, including a 2-dose primary series and booster doses every 3-5 years for persons at increased risk for meningococcal disease because of certain underlying medical conditions (e.g., complement deficiency, asplenia, HIV infection)]. The age at vaccination was not provided. On an unspecified date, between 2014 to 2018, 7 years after Menveo vaccination and 1 year after Menactra vaccination, the patient had Serogroup Y Meningococcal disease. [From 2014 through 2018, 822 cases of serogroup A, C, W, and Y meningococcal disease were reported. Of these, 34 cases (4%) were in patients who were reported to have previously received one or more doses of a MenACWY vaccine. Of the remaining 788 cases, 470 were in unvaccinated patients and 318 were missing information on vaccination history. Vaccinated patients were significantly younger than unvaccinated patients. No significant differences were seen between vaccinated and unvaccinated cases in terms of patient sex, serogroup distribution, syndrome, or association with an outbreak. None of the previously vaccinated patients reported a prior history of meningococcal disease or a family history of meningococcal disease. A significantly higher proportion of vaccinated patients were people living with HIV (PLWH) compared to unvaccinated patient. The five cases in PLWH who had previously received MenACWY vaccine were all in men who had sex with men (MSM); all five cases were caused by serogroup C, and three were part of meningococcal disease outbreaks in MSM populations. Of the 34 vaccinated patients, 21 (62%) received one dose, nine (26%) received two doses, and four were missing information on the number of doses received. Based on patient age and year of vaccination, 23 vaccinated patients (68%) were up-to-date on MenACWY vaccination per recommendations, and seven (21%) were not up-to-date. Of the seven patients who were not up-to-date, three individuals had received one dose of MenACWY vaccine and were overdue for the ACIP-recommended booster dose, and four were at increased risk for meningococcal disease because of underlying medical conditions, including 3 PLWH, but had not completed the recommended 2-dose primary series. No significant differences were seen between fully vaccinated and partially vaccinated cases in terms of patient age, patient sex, serogroup distribution, syndrome, association with an outbreak, time since most recent MenACWY vaccine dose, whether patients were admitted to the intensive care unit (ICU), or the case fatality ratio. Vaccine type was known for 22 of the 34 vaccinated patients. Of those with known vaccine type for the first dose, 73% of patients were vaccinated with MenACWY-D, 18% with MenACWY-CRM, and 9% with MPSV4. Three cases occurred less than one year after vaccination, 10 occurred one to three years after vaccination, and 17 occurred more than three years after vaccination. Four cases were missing information on timing of vaccination. The three cases that occurred within one year of vaccination were one serogroup Y case in a patient with no known immunosuppressive conditions and two serogroup C clonal complex 11 cases in PLWH. Of the two PLWH, one had received the ACIP-recommended 2-dose series and was not yet due for a booster dose; the other had not completed the recommended 2-dose series. Eight of the 34 vaccinated patients were immunosuppressed, including the five PLWH, while the remaining 26 were not known to be immunosuppressed. The additional three immunosuppressed patients included one patient taking eculizumab and two patients taking other immunosuppressive medications (adalimumab and corticosteroids). Immunosuppressed patients previously vaccinated with MenACWY were significantly older than patients who were previously vaccinated and were not known to be immunosuppressed. No significant differences were seen between previously vaccinated immunosuppressed patients and patients not known to be immunosuppressed in number of MenACWY doses received, time since most recent MenACWY dose, whether patients were admitted to the ICU, or the case fatality ratio. The case fatality ratio also did not differ between vaccinated patients and unvaccinated patients. Of the five fatal vaccinated cases, three were caused by serogroup C and two by serogroup Y. The fatal vaccinated cases occurred in patients who ranged in age from 14 to 36 years with a median age of 21 years. Only one of the five patients had a known immunosuppressive condition; this PLWH developed disease caused by serogroup C. All five fatal cases were in patients who had only received one dose of MenACWY vaccine. Time since vaccination was available for four of the five patients; meningococcal disease onset occurred one to three years after vaccination in one patient, and more than three years after vaccination in the other three patients. Serogroup Y male case with no known immunosuppressive conditions that received one dose of MenACWY-CRM and one dose of MenACWY-D]. This case has been considered as suspected vaccination failure since laboratory confirmation was not provided. This case has been considered as serious due to suspected vaccination failure. Treatment was unknown. The outcome of the event was not reported.  The authors commented, "From 2014 to 2018, 34 cases of serogroup A, C, W, and Y meningococcal disease were reported that had previously received at least one dose of MenACWY vaccine. Vaccinated patients were significantly younger than unvaccinated patients, likely because of the age groups routinely recommended to receive MenACWY vaccine and the timing of the implementation of this recommendation. Half of the cases in vaccinated patients occurred more than three years after their most recent dose, consistent with previously observed waning effectiveness over time. Of the 34 patients previously vaccinated with MenACWY, 24% were immunosuppressed. Information was not available for unvaccinated patients to compare the proportion who were immunosuppressed but given that meningococcal vaccination is specifically recommended for some immunosuppressed patients, it is expected that there would be a higher proportion of immunosuppressed patients among cases in the vaccinated group. The proportion of immunosuppressed patients is higher than the 12% identified in 14 breakthrough cases identified from 2005 to 2008. This difference might be because of small numbers of immunosuppressed patients and breakthrough cases in each analysis, or it might be a result of the changing epidemiology of meningococcal disease between the two time periods, with fewer total cases reported each year in this analysis compared to the previous analysis. It has been shown previously that as fewer meningococcal disease cases are reported, the proportion occurring in people with complement deficiencies is higher, and it is plausible that there would be similar trends among individuals with other immunosuppressive conditions. Five of the 34 breakthrough cases were in PLWH, including two of the three cases occurring within one year after vaccination. This finding is in line with findings of reduced immunogenicity of meningococcal vaccines among PLWH. A significantly larger proportion of vaccinated versus unvaccinated serogroup A, C, W, or Y meningococcal disease patients were PLWH, but this is to be expected because PLWH are specifically recommended to receive meningococcal vaccine, whereas the majority of the population, outside of the adolescent age group, is not. Additionally, ACIP recommends that PLWH receive a 2-dose primary series of MenACWY; however, only two of the five breakthrough cases in PLWH were in people who received the recommended 2-dose series. It is unclear if implementation of the recommended 2-dose primary series in this population is poor or if 2-dose coverage is only low among patients with breakthrough disease. Further evaluation would be helpful to understand implementation of ACIP meningococcal vaccine recommendations in PLWH. There are limitations to this analysis. Vaccination status for patients reported not to be vaccinated may be misclassified depending on how vaccination status was verified. Misclassification or underreporting of MenACWY receipt in patients may have led to the under-ascertainment of breakthrough disease. Also, retrospective collection of some clinical and risk factor information may have impacted the completeness of information obtained and limited which variables could be collected. No data were available to compare severity between vaccinated and unvaccinated patients, with the exception of outcome; however, the small number of cases in vaccinated people limited power to detect differences in outcome. Additionally, information is not available on adherence to ACIP meningococcal vaccine recommendations outside of adolescence (e.g., data on coverage among PLWH) so vaccination status among individuals who have not developed meningococcal disease cannot be compared to that among cases. Overall, immunosuppression, incomplete vaccination, and waning immunity likely contributed to the breakthrough cases of meningococcal disease reported here. These findings highlight the importance of following ACIP-recommended vaccination schedules, including the 2-dose primary series recommended in PLWH. Additional data on the implementation of these recommendations will be helpful to inform efforts to effectively prevent meningococcal disease". The authors concluded, "Immunosuppression, incomplete vaccination, and waning immunity likely contributed to breakthrough cases of meningococcal disease among people who received MenACWY vaccine. Continued monitoring of serogroup A, C, W, and Y meningococcal disease in previously vaccinated persons will help inform meningococcal disease prevention efforts". This case is 1 of the 4 cases reported in the literature article.; Sender's Comments: US-GLAXOSMITHKLINE-US2021GSK244767:Same reporter.