Twins with Meningitis Due to Neisseria meningitidis

Abstract

Introduction The incidence of invasive meningococcal disease is highest in infants and young children. Case report Twin infants diagnosed two days apart with meningitis due to N. meningitidis serogroup B are presented. Conclusions There has never been a report of concurrent meningococcal meningitis in twin brothers. We wanted to highlight the high likelihood of meningococcal transmission through household contacts and the importance of antibiotic prophylaxis and meningococcal vaccination recommendations for close contacts of these cases.

Introduction

Neisseria meningitidis, which is solely pathogenic in humans, can cause meningitis or rapidly fatal sepsis in previously healthy individuals and is associated with high mortality and morbidity. The incidence of invasive meningococcal disease is highest in infants and young children, with a small second peak in adolescents and young adults in some countries.[1] Twelve capsular serogroups of Neisseria meningitidis have been identified: MenA, MenB, MenC, MenE, MenH, MenI, MenK, MenL, MenW, MenX, MenY, and MenZ. Although the distribution of serogroups varies between geographic regions at any given time and within the same geographic region over time, serogroups A, B, C, W, X, and Y have caused the majority of invasive meningococcal disease worldwide.[1,2] According to surveillance studies conducted between 2005 and 2018, the most common causative agent of bacterial meningitis in Turkey is N. meningitidis, and the most common strain is MenB.[3,4] The current national immunization schedule in Turkey does not include meningococcal vaccination. Men A, B, C, W vaccines and Men B vaccine are licensed in Turkey and can be easily accessed by families who wish to receive these vaccines. Here, twin infants diagnosed two days apart with meningitis due to N. meningitidis serogroup B are presented.

Case reports

Case 1

A 46-day-old male baby, born at 35 weeks of gestation, presented to the pediatric emergency department because of feeding aversion for the last three days, along with restlessness and fever of 37.5°C for one day. His twin brother and other people in the house had no symptoms. Laboratory evaluation showed a hemoglobin of 9.4 g/dL, WBC of 5,320 × 10⁹/L, platelet count of 370,000/µL, and CRP of 132 mg/L (0-5 mg/L). Lumbar puncture was performed because the patient had a weak sucking reflex and was lethargic on examination. Following the lumbar puncture, he was started on cefotaxime and ampicillin. The direct examination of the cerebrospinal fluid (CSF) with the Thoma cell counting chamber showed numerous leukocytes while the biochemistry of the CSF showed a glucose level of 19 mg/dL and a protein level of 294 mg/dL. Vancomycin was added to the existing antibiotic regimen for acute bacterial meningitis. Transfontanelle ultrasound (US) revealed that the leptomeninges were mildly hyperechogenic, consistent with meningitis. On the 3^rd day of hospitalization, the CSF PCR panel was positive for N. meningitidis. Ciprofloxacin chemoprophylaxis was prescribed for the close contacts of the patients immediately following the PCR result. N. meningitidis growth (sensitive to ciprofloxacin, meropenem, and ceftriaxone) was detected in blood culture while there was no growth in CSF culture. Treatment with vancomycin and ampicillin was stopped, and treatment with ceftriaxone was continued. The blood culture isolate was sent to the reference laboratory for confirmation and serotyping. The isolate was freshly passaged on sheep blood agar and chocolate agar media and incubated for 1824 hours. After incubation, catalase- and oxidasepositive Gram-negative diplococci were grown on the plates. The isolate was identified as N. meningitidis by the MALDI-TOF MS system (Bruker Daltonics, Germany). In order to determine the serogroup, polyvalent and then monovalent antisera were applied to the bacterial suspensions with no spontaneous agglutination taking place. The isolate was identified as N. meningitidis serogroup B using commercially available polyvalent (Poly: A-D and Poly 2: X,Y,Z) and monovalent (A, B, C, D, X, Y, Z, W135, Z) antisera (BD DIFCO™, Becton, Dickinson and Company, USA). The isolate was also molecularly identified as serogroup B by PCR. Immunological evaluation of the patient showed that immunoglobulin levels, lymphocyte subgroup distribution and number, and the C3, C4 and CH50 complement levels were normal. He was discharged after completing the antibiotic treatment. Vaccination with meningococcal B vaccines was recommended for the family members.

Case 2

The twin of the patient detailed above was admitted two days after the presentation of his twin, with fever and redness and swelling over the left ankle. On physical examination, he was restless and there was a 2 × 2 cm hyperemic lesion on the lateral aspect of the left ankle, compatible with cellulitis. Laboratory evaluation showed a hemoglobin of 9.9 g/dL, WBC of 5,970 × 10⁹/L, platelet count of 375,000/µL, and CRP of 301 mg/L. The patient underwent lumbar puncture immediately after admission because he was prone to sleeping and he was then started on cefotaxime. Direct examination of CSF with a Thoma cell counting chamber showed a large number of leukocytes. CSF biochemistry revealed glucose <4 mg/dL and protein 64.5 mg/dL. Following the lumbar puncture, ampicillin, vancomycin, and iv dexamethasone at 0.15 mg/kg/dose (for a total of 8 doses) were added to the treatment. On the 12^th hour of the patient's admission to the inpatient unit, the results of the PCR tests of his twin had just been reported. The other antibiotics were discontinued and treatment was continued with ceftriaxone. The lesion on the ankle disappeared on the second day of hospitalization. CSF multiplex PCR panel was positive for N. meningitidis. There was no growth in CSF or blood cultures. Transfontanelle US showed increased echogenicity in bilateral periventricular white matter. On contrast-enhanced cranial magnetic resonance imaging (MRI) diffusionweighted imaging showed diffusion restriction within the occipital horns of the lateral ventricles consistent with infected-purulent content. Slightly increased contrast enhancement was observed in the wall of the occipital horns of both lateral ventricles in the series after intravenous contrast material administration.

The appearance was consistent with ventriculitis and the duration of antibiotic treatment was extended due to this development. Immunological evaluation showed that the immunoglobulin levels, distribution and number of lymphocyte subgroups, and C3, C4 and CH50 complement levels were normal with no immunodeficiency detected. Ceftriaxone treatment was extended to 6 weeks due to the ventriculitis. He was discharged after the completion of the antibiotic treatment.

Discussion

Invasive meningococcal disease occurs in all age groups but it is most common in infants under 1 year of age, with the second most common age group being 1-4 years of age. In some countries, it has a second peak in adolescents and young adults.[2] Increased socialization with behavioral changes in this age group is thought to be responsible for this second peak in adolescence. [1,2] The patients presented here were in the age group in which invasive meningococcal disease is most common. Adults in the household were not affected but two young infants were infected.

Meningitis is the most common manifestation of meningococcal disease and this form occurs in about 60% of the infected patients. Shock or fulminant sepsis with or without meningitis develops in 10-20% of cases. Approximately 30% of the patients have only fever and rash without meningitis or shock at presentation. Although bacterial load, endotoxin concentrations, and inflammatory mediators are low in these patients, meningitis and sepsis may develop if not treated in time.[5] Intensive care hospitalization has been reported in 31.3-67% of children with invasive meningococcal disease, mechanical ventilation in 37%, need for inotropic support in 30%, multiple organ failure in 18%, and mortality in 4.1-9.9%.[6,7,8] A quarter of survivors recover with sequelae.[6,8] One of the most important features of meningococcal disease is the rash. The rash is typically purpuric or petechial, but maculopapular and other rashes may also be present.[9] Hemorrhagic cutaneous lesions are present on admission in 28-77% of patients with invasive meningococcal disease.[5] Meningococcal disease can therefore occur without petechiae and other hemorrhagic cutaneous lesions. It has been reported that N. meningitidis is the causative agent in 92% of the meningitis cases that are accompanied by a rash. A rash can also accompany meningococcal sepsis.[9] The first patient presented here did not have a rash, but the second patient had a cellulitis-like rash on the foot that disappeared rapidly with antibiotic treatment.

Invasive meningococcal disease is usually sporadic with no history of contact. It can lead to clusters of cases and epidemics among people living in the same house, school, or communal area.[10] In particular, household contacts of the index case have increased risk for invasive meningococcal disease.[11] Although the risk of invasive meningococcal disease in family members continues for 14 to 365 days after contact, most infections seem to occur within the first 14 days according to Hoek et al.[12] In a review of 58 clusters, it was reported that the majority of clusters (91%) contained two or three cases while the cluster with the highest number of cases contained 12 cases. Secondary cases following the index case occurred predominantly within the first week.[13] The attack rate is 1.1/1000 in household contacts that have received chemoprophylaxis.[12] If chemoprophylaxis is not used, the risk of invasive meningococcal disease in household contacts is 1000 times higher than in the general population.[14] Chemoprophylaxis is recommended for close contacts of the patient and aims to eliminate carriage of N. meningitidis and prevent transmission of the bacteria to others.[5] The patients presented here are examples of how easily meningococcus is transmitted through close contact. Timely initiation of chemoprophylaxis in close contacts within 24 hours of presentation, rather than waiting for culture confirmation and serogrouping is very important. As the meningococcal test results of case 1 were not available at the time of the onset of fever in the second case, case 2 did not receive chemoprophylaxis. However, other close contacts were prescribed prophylaxis immediately following the meningococcal test results and no further cases of meningococcal disease occurred.

The UK and German guidelines recommend vaccination for vaccine-preventable non-B serogroups for the contacts of patients who have experienced meningococcal disease, and such vaccination should begin as soon as possible after the contact.[9,14] If a second Men B case occurs in the household, Men B vaccination should be considered together with chemoprophylaxis for all of the household contacts, even in the situations where the time between the two cases is more than 30 days.[9] With regard to the recommendation to vaccinate all cases after exposure to a non-B meningococcal case, this recommendation is consistent with countryspecific recommendations. Vaccination of household contacts following a sporadic case of meningococcal disease is not a universal recommendation. The benefit of vaccination of contacts for the purpose of post-exposure prophylaxis has been poorly documented.[15] In situations where the incidence of invasive meningococcal disease is low and cases are sporadic, the impact of vaccination may be relatively small. However, where there are persistent clusters of cases with the same serogroup, vaccination of a defined population at risk may be quite effective. There is no recommendation for post-exposure vaccination of contacts of invasive meningococcal disease patients in Turkey. Bexsero is licensed in Turkey for the vaccination against Men B. The Men B vaccine was recommended for the household contacts of the presented cases.

Invasive meningococcal disease can occur following close contact with a colonized individual.[16] Although carriage can occur in all age groups, the rates are age dependent. Less than 2% of children under 5 years of age are carriers, and carriage rates in older adolescents and young adults have been reported to range from 9.1% to 33%.[9,11,16] Carriage can last from days to months.[5] Previous tonsillectomy, upper respiratory tract infection in the previous month, high number of household members, antibiotic use in the last month, daily cigarette smoking, drinking alcohol in the past week, and frequent visits to bars or clubs were associated with higher rates of meningococcal carriage.[11,17] In contrast, age ≥22 years, female sex, and living in a household with children aged 0-9 years were associated with lower rates of meningococcal carriage. Fortunately, about half of the colonizing N. meningitidis were of the serotype that does not cause invasive disease.[11] The possible source of infection in the first case of the twins is unknown. Considering that the patients presented here were two days apart, it is highly likely that they were infected by the same carrier. A carriage study was not conducted among the close family contacts. It is also possible that the transmission to the second infant occurred from the first infected infant.

Conclusions

We wanted to highlight the high likelihood of meningococcal transmission through household contacts and the importance of antibiotic prophylaxis and meningococcal vaccination recommendations for close contacts of these cases.