Vaccine Preventable Infection in Two Siblings: One Healthy and the Other With Risk Factor for Meningococcal Disease

Dear Editor,

Meningococcal disease is a vaccine-preventable, fatal disease that usually manifests as bacterial meningitis and sepsis. Here, we report two siblings diagnosed with meningococcal meningitis, one of whom had a predisposing factor, to draw attention to meningococcal infections and risk factors and to emphasize the importance of meningococcal vaccination.

A 13-year-old female patient diagnosed with monogenic systemic lupus erythematosus (SLE) with C1S complement deficiency, with the clinical phenotype of systemic lupus erythematosus, who had not been taking her medication and had not attended follow-up appointments for 3 years, presented with complaints of fever and altered consciousness.

Hemogram revealed that white blood cell (WBC): 15.2 (10³/μL), neutrophil (NEU): 13.1 (10³/μL), lymphocyte (LYM): 1200 (10³/μL), monocyte (MON): 500 (10³/μL), hemoglobin (HB): 11.2 (10³/μL), and platelet (PLT): 214.000 (10³/μL).

Due to the patient’s cardiovascular instability, empirical treatment with vancomycin, ceftriaxone, and acyclovir was initiated for pre-diagnosed meningitis without lumbar puncture (LP). When her clinical condition stabilized, contrast-enhanced cranial magnetic resonance imaging was performed, which was interpreted as normal, and LP was performed.

Cerebrospinal fluid examination revealed a white blood cell count of 180 cells/mm³, with neutrophilia (normal value: max. 0-3 cells/mm³); CSF protein level, 20 mg/dL; CSF glucose level, 64 mg/dL; with a concurrent blood glucose level, 94 mg/dL. Polymerase chain reaction (PCR) of the cerebrospinal fluid was negative for herpes simplex virus (HSV). Based on these findings, the patient was diagnosed with meningococcal meningitis.

Three days after the onset of symptoms, the patient’s 5.5-year-old previously healthy sister was admitted to an external center with fever, petechiae on the lower trunk and proximal thigh, and arthritis (Figure 1).

Figure 1.

Petechiae on the lateral side of the leg

Hemogram revealed that WBC: 13.9 (10³/μL), NEU: 8.5 (10³/μL), LYM: 2.9 (10³/μL), MON: 1.2 (10³/μL), HB: 11.4 (g/dL), and PLT: 280 000 (10³/μL). In addition to these results, complement values were c3: 2.08 g/L (0.9-1.8 g/L) and c4: 0.57 g/L (0.1-0.4 g/L). Lumbar puncture was performed, and an empirical combination of vancomycin, ceftriaxone, and acyclovir was initiated after the puncture. During follow-up, she was transferred to the pediatric intensive care unit because of the development of confusion and hypotension with a diagnosis of septic shock. PCR of the CSF was positive for Neisseria meningitidis, and meningococcal infection was diagnosed.

When the patient’s general condition improved, she was transferred to our department to continue treatment with her sister. Because her sister has a complement mutation, genetic testing was also performed on her younger sibling, but the test results are not yet available.

Based on clinical presentation and laboratory results, the siblings were diagnosed with meningococcal meningitis and septic shock. Two siblings underwent two weeks of antibiotic therapy with ceftriaxone until they responded clinically. Treatment with acyclovir and vancomycin was discontinued in both after the PCR was negative for HSV and the CSF cultures did not reveal any other microorganisms.

For prophylaxis, the three siblings of the family members were given a single dose of ceftriaxone intramuscularly, and the mother and father were given a single dose of ciprofloxacin orally.

When the family was interviewed, it was discovered that neither sibling had been vaccinated according to the vaccination schedule set by the Ministry of Health. The plan was to administer the missing vaccinations to the patients as part of the Ministry’s expanded vaccination program. The family was educated on the importance of vaccines that protect against the serogroups that cause meningococcal disease (ACYW and B vaccines). The sister, who was diagnosed with SLE and C1 complement deficiency, received both serotypes of meningococcal vaccine free of charge and was started on penicillin prophylaxis.

Meningococcal disease (MD) is a serious bacterial infection caused by the bacterium N. meningitidis.^1,2 N. meningitidis is a gram-negative diplococcus that is divided into 13 serogroups according to the structure of the capsular polysaccharides. Serogroups A, B, C, Y, and W135 are the most common causes of invasive disease. Transmission occurs via droplet aerosols or secretions from the nasopharynx of colonized individuals.³

Invasive MD usually manifests as meningitis, septicemia, or a combination of these; in our case, the older sibling had only had meningitis, while the younger one had both. Arthritis, which is usually immune-mediated and transient, occurs less frequently and was also present in the younger sibling.³ There are a number of environmental and host factors that have been associated with an increased risk of invasive MD. There is an increased risk of disease in certain populations, including infants, adolescents, and people living in overcrowded dormitories, such as college dormitories.⁴,⁵ Immunosuppression, asplenia, deficiency of the terminal complement cascade (factors C5 to C9) and properdin are some of the risk factors.⁴ Even meningococcal poisoning can be the first symptom in a child or young adult with complement deficiency.⁶ The complement system plays an important role in defense mechanisms by promoting the adherence of microorganisms to phagocytic cells and the lysis of foreign organisms. Deficiency of the first complement component, C1r/C1s, frequently causes systemic lupus erythematosus-like syndromes and recurrent infections since childhood, including pneumococcal and meningococcal meningitis.⁷ Our first case is a typical example of a C1-deficient patient diagnosed with SLE who developed a meningococcal infection.⁸

The microorganism is capable of infecting all age groups of the population, leading to both endemic and epidemic infections.⁸ Children younger than 1 year and adolescents are the most commonly affected age group for MD, and previously healthy individuals may experience rapid progression with a high mortality rate. Early diagnosis and appropriate antibiotic treatment determine the outcome of the disease.

In addition to treatment, the most important measure to prevent MD and its serious complications is vaccination. Although effective vaccines are available, the vaccination rate is low in many countries owing to financial reasons. MD itself is associated with high financial costs for the treatment and rehabilitation of patients. Improving the availability of vaccines for children and adolescents by supporting reimbursement will reduce the burden of the disease and the associated economic costs. In addition, vaccination may help to reduce nasopharyngeal infection and transmission and thus achieve herd protection.⁹,¹⁰ In summary, meningococcal infection is a devastating, contagious disease that can progress rapidly. However, vaccination can prevent this global threat. Therefore, vaccination should be the most important public health strategy for meningococcal disease.

Funding Statement

This study received no funding.

Availability of Data and Materials:

The data that support the findings of this study are available on request from the corresponding author.