Sex: M
Vaccine: UNK
Symptoms: Cytogenetic analysis, Gene sequencing, Gram stain, Heterosexuality, Meningococcal infection
Clinical narrative: Suspected vaccination failure; Neisseria meningitidis urethritis clade; urethritis clade; This case was reported in a literature article and described the occurrence of vaccination failure in a adult male patient who received Men ACWY-CRM NVS (Meningocococcal ACWY vaccine) for prophylaxis.   On an unknown date, the patient received Meningocococcal ACWY vaccine at an unknown dose. On an unknown date, unknown after receiving Meningocococcal ACWY vaccine and an unknown time after starting ceftriaxone, the patient experienced vaccination failure (serious criteria GSK medically significant), neisseria meningitidis infection nos (serious criteria GSK medically significant) and urethritis. The subject was treated with ceftriaxone. On an unknown date, the outcome of the vaccination failure, neisseria meningitidis infection nos and urethritis were unknown.   It was unknown if the reporter considered the vaccination failure, neisseria meningitidis infection nos and urethritis to be related to Meningocococcal ACWY vaccine.  Additional details were provided as follows: This case was reported in a literature article and described the suspected vaccination failure in a male aged between 23 and 39 years who was vaccinated with unspecified meningococcal vaccine (quadrivalent MenACWY) vaccine (manufacturer unknown) for prophylaxis.   The patient was the part of the study that aimed to determine whether the same phenomenon occurs with the US_NmUC (non-groupable and monophyletic urethritis clade (UC) of Neisseria meningitidis (Nm) [the US_NmUC], they examined men who presented for care at the sexually transmitted diseases (STD) clinic over a 40-month period to see if they experienced repeat episodes of urethritis due to the US_NmUC. [In this study, they extracted demographic and clinical data from electronic medical records for men diagnosed with urethritis confirmed to be caused by the US_NmUC between 1st January 2015, and 30th April 2018. They extracted demographic and clinical data from electronic medical records for diagnosed with urethritis confirmed to be caused by the US_NmUC between 1st January 2015, and 30th April 2018. During study period, they identified 133 episodes of urethritis caused by the US_NmUC among 128 unique men seeking STD care. More than half 73 men, returned at least once to the STD clinic during the follow-up period. Four of the men with repeat infections. 4 of the men were marital status were single and 1 was married. All reported heterosexual orientation. All 5 reported had oral sex on the last 12 months. Out of 5, 2 always used condom and 3 used sometimes 5 reported oral-genital contact (2 received fellatio; the remaining 3 reported "oral sex" but the type of contact was not defined) with at least 1 sex partner prior to the first episode of urethritis due to the US_NmUC; 4 of 5 also reported oral-genital contact (3 fellatio; 1 not defined) in the period before the second episode]. No information on patient's medical or family history or concurrent condition or concomitant condition was provided. On unspecified date, the patient had received unspecified meningococcal vaccine (quadrivalent MenACWY) vaccine (administration route and site unspecified, dosage unknown; batch number not provided). The age of vaccination was not provided. On unspecified date between 1st January 2015, and 30th April 2018, unknown period after vaccination, the patient's urethral swab for gram stain were analysised who was screened at the STD clinics, regardless of reported symptoms or behavioral risks. Culture growth was confirmed to be Nm by Analytical Profile Index (API NH) and Nmspecific PCR. The patient's US_NmUC identification and characterization was performed by clade-specific Polymerase chain reaction (PCR), whole-genome sequencing (WGS) analysis, and phylogenetic analysis. The US_NmUC isolates from patient underwent genomic analysis to determine sequence similarity between the first and second isolate. The patient repeat episode of symptomatic urethritis in which US_NmUC was confirmed to be the cause. [In this study, The median duration of time between the onset of symptoms and presentation to the STD clinic, for both the first and second episodes of urethritis due to the US_NmUC, was 3 days (range, 1- 6 days). The median duration of time between the first and second episode was 273 days (range, 83-576 days). Only 1 patient had an STD clinic visit in between his first and second episodes of urethritis. Phylogenetic analysis of WGS data demonstrated a high degree of sequence homology between all urethral US_NmUC isolates (A-1, A-2 to E-1, E-2) from the men with repeat infections . Sex partner information was available only for 1 patient. During his clinical interview, this patient reported receiving fellatio from the same female partner prior to both his first (D-1 urethral isolate) and second (D-2 urethral isolate) episodes of symptomatic urethritis; 83 days elapsed between the 2 episodes. The female partner screened positive at the oropharynx for the US_NmUC [female (oropharyngeal) isolate]. No vaginal or rectal screening for Nm was performed. She was treated with intramuscular ceftriaxone (250 mg) and oral azithromycin (1 gram) shortly before the male patient presented with his second episode of symptomatic urethritis due to the US_NmUC. Neither the male patient nor his female sex partner returned to the STD clinic for evaluation during the remainder of the study period after both received treatment. Finally, the core genome sequence identity between the US_NmUC isolates (10 urethral and 1 oropharyngeal) and the cc11 reference isolate FAM18]. This case has been considered as suspected vaccine failure because time to onset was unknown. This case has been considered as serious due to suspected vaccination failure. The patient received effective treatment with intramuscular ceftriaxone (250 mg) and oral. The outcome of the event was not provided.  The author commented, "The US_NmUC has primarily been associated with episodes of symptomatic urethritis that mimics gonorrhea. We provide evidence that, similar to gonococcal urethritis, repeat episodes of symptomatic urethritis caused by the US_NmUC are possible. These findings suggest that infection with the US_NmUC may not fully protect against future reinfection, even with isolates that show a very high degree of sequence identity. Furthermore, the short median duration of time between onset of symptoms and presentation to the STD clinic (3 days) and long median duration of time between episodes (273 days), suggest that subsequent infections were most likely due to reinfection rather than persistent infection. Additionally, while immune correlates of protection are well-described for invasive meningococcal infection,16 we do not have data on the type of immune response elicited by urethral infection with the US_NmUC or whether vaccination impacts the risk of urethral infection. Finally, the number of men with repeat urethral infection due to the US_NmUC is small, and the patterns they observed may not be replicated in larger samples". The author concluded, "In summary, we find that similar to N. gonorrhoeae, symptomatic urethral reinfection with the US_NmUC can and does occur. Studies should evaluate not only the type of immune responses elicited by urethral US_NmUC infection, but also the risk of infection and reinfection following exposure to untreated sex partners.      Lab Comments: Lab test was done on an unspecified date between 1st January 2015, and 30th April 2018. The patient's urethral swab for gram stain were analysised who was screened at the STD clinics, regardless of reported symptoms or behavioral risks. Culture growth was confirmed to be Nm by Analytical Profile Index (API NH) and Nmspecific PCR. The patient's US_NmUC identification and characterization was performed by clade-specific Polymerase chain reaction (PCR), whole-genome sequencing (WGS) analysis, and phylogenetic analysis. The US_NmUC isolates from patient underwent genomic analysis to determine sequence similarity between the first and second isolate. The patient repeat episode of symptomatic urethritis in which US_NmUC was confirmed to be the cause.