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Streptococcal meningitis in Qatar: A secondary analysis of a hospital-based study

Dr. Fahmi Yousef Ahmed Khan

By Dr. Fahmi Yousef Ahmed Khan

Dr. Fahmi Yousef Khan is currently a consultant physician in internal medicine at Hamad General Hospital. He received his undergraduate degree from Faculty of medicine, Aden University (Yemen) in 1992. He obtained his Arab board certificate in internal medicine (CABMS) in 2000. Dr. Khan started his academic medical career as assistant professor of medicine at faculty of medicine, University of science and technology, Yemen. He is currently assistant professor of clinical medicine at Weill Cornell medical college in Qatar. He is interested in medical research (especially neurology, endocrinology and infectious diseases) and evidence based medicine. He published his first of many research papers in 2005 and currently has more than ninety publications and two book chapters.

Citation: Khan, Fahmi Yousef. “Streptococcal meningitis in Qatar: A secondary analysis of a hospital-based study”. International Journal of Medical Science and Research, 1.4: 01-05.

Abstract

Background and Objectives: Streptococcal meningitis is a recognized medical condition that confronts physicians in Qatar. The aim of this study was to describe the demographic, clinical characteristics, underlying conditions, and treatment outcome of streptococcal meningitis.

Patients and Methods: This was a secondary post hoc analysis of our previous study entitled “Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013”. It involved only patient with streptococcal meningitis.

Results: We identified 27 cases of streptococcal meningitis. The study sample comprised 16 (59.3%) male and 11 (40.7%) female patients. All episodes were community acquired and fever was the most frequent symptom 24 (88.9%), whereas bacteremia was found in 18(66.7%) cases. S. pneumoniae was the most frequent pathogen found in this study 19 (70.4%). The main affected age group was neonates under one year of age and the mortality was 3 (11.1%) cases

Conclusion: Streptococcal meningitis is a recognized clinical entity in Qatar that was caused by several species of streptococci, with S. pneumoniae being the most common. Despite vaccination, infants were the most affected group with high mortality from pneumococcal meningitis, suggesting that pneumococcal meningitis prevention strategies may need to be re-evaluated in this country

Keywords: streptococcal meningitis, pneumococcal meningitis, pneumococcal vaccine

Introduction

Streptococcal meningitis can be caused by certain streptococci species, which are spherical Gram-positive bacteria with Streptococcus (S.) pneumoniae being the most important causative pathogen in adults and children [1]. Other streptococcal species that have been reported to cause meningitis include S. agalactiae [2], S. bovis [3], S. milleri [4], S. mitis [5], and S. salivarius [6], however, these species are an infrequent cause of bacterial meningitis in adults and children.

Meningitis caused by S. pneumoniae is described widely, however, there is lack of information on meningitis caused by streptococcal species other than S. pneumoniae. Few studies have been described meningitis caused by well-identified Streptococcus species [1, 8]. This post hoc analysis was performed to describe the demographic, clinical characteristics, underlying conditions, and treatment outcome of streptococcal meningitis.

Patients and methods

We performed a secondary post hoc analysis of collected data from our previous study entitled “Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013” [7]. We retrieved patients with streptococcal meningitis from the primary study, which was a retrospective descriptive study that involved all in-patients with acute bacterial meningitis at Hamad General Hospital between January 1, 2009, and December 31, 2013.

Diagnostic criteria

Streptococcal meningitis was considered if at least one of the following compatible clinical pictures were met with no other apparent cause: fever (38°C), headache, meningeal signs, cranial nerve signs, and impaired mental status, plus one of the following [9, 10]: 1. Positive cerebrospinal fluid (CSF) culture; 2. Positive CSF bacterial antigen test (with latex agglutination counterimmunoelectrophoresis) associated with pleocytosis mainly neutrophilic, defined as absolute WBC ≥ 100 cells/mm [3], with a decreased glucose level ≤ 2.2 mmol/L and an increased protein concentration ≥ 60 mg/dL.

Definitions

Streptococcal meningitis was considered nosocomial if the diagnosis was made after more than 48 hours of hospitalization or within a short period of time (i.e., usually within one month after discharge from the hospital where the patient had received an invasive procedure, especially a neurosurgical procedure). On the other hand, ABM was considered as community-acquired if the diagnosis was made within the first 48 hours of hospitalization and the patient was not hospitalized in the preceding month [7].

Identifications of cases

We selected cases of streptococcal meningitis from the primary study. We described the demographic and clinical characteristics, of these patients as well as the underlying conditions, name of species, appropriateness and outcome of therapy.

Ethical consideration

The original study was approved by Medical Research Ethical Committee at HMC, Qatar. Since this was a secondary post-hoc analysis of collected data from our previous study, no ethics committee approval or informed consent was required.

Data analysis

Data analysis was performed with SPSS software (v 23.0; IBM Corp, Armonk, NY, USA). The results of analyses of continuous variables are expressed as means and standard deviations (SD) unless otherwise specified.

Results

Demographic and clinical data

During the study period, we identified 27 cases of streptococcal meningitis. The study sample comprised 16 (59.3%) male and 11 (40.7%) female patients. Their mean age was 20± 23.1 (range: 0.01–74 years), and 12 (44.4%) patients were Qatari. The peak frequency of streptococcal meningitis episodes was noted among infants <1 year old, 6 (22.2%). Clinically, fever was the most frequent symptom 24 (88.9%), followed by headache 14 (51.9%), mental alteration 12 (44.4%), and vomiting 10 (37.0%). Meningismus was detected in 13 (48.1%) patients. S. pneumoniae and S. agalctiae were the two most frequent pathogens found in this study (see Table 2). The frequency of pneumococcal meningitis per year is described in figure 1.

Fig 1: Number of pneumococcal cases meningitis and mortalities per year

Associated Medical conditions

Bacteremia was found in 18 (66.7%) cases, while otitis media and pneumonia were found in 3 (11.1%) cases each (see table 1).

Table 1: Demographic and clinical data of the involved patients

Variable
Age, mean±SD (range) years 20± 23.1 (0.01-74)
Age group
<1 6(22.2%)
1-5 4(14.8%)
6-14 3(11.1%)
15-24 3(11.1%)
25-34 3(11.1%)
35-44 3(11.1%)
45-54 3(11.1%)
≥55 2(7.5%)
Sex
M 16(59.3%)
F 11(40.7%)
Nationality
Qatari 12(44.4%)
Non-Qatari 15(55.6%)
Associated medical conditions
DM 2(7.5%)
HTN 1(3.7%)
Alcohol 1(3.7%)
Prematurity 1(3.7%)
Bacteremia 18(66.7%)
Otitis media 3(11.1%)
Immunosuppression 1(3.7%)
Chronic kidney disease 1(3.7%)
Pneumonia 3(11.1%)
Sinusitis 2(7.5%)
Clinical presentations
Fever 24(88.9%)
Seizure 9(33.3%)
Headache 14(51.9%)
Anorexia 4(14.8%)
Vomiting 10(37.0%)
Photophobia 3(11.1%)
Focal signs 1(3.7%)
Meningism 13(48.1%)
Mental alteration 12(44.4%)
Acquisition of Infection
Community acquired 27(100%)
Mortality (%) 3(11.5%)

Diagnostic work up

Cerebrospinal fluid (CSF) was obtained from all patients. Gram stain was positive in 88.8% of the cases. Table 3, summarizes the results of CSF analysis.

Trends of Antimicrobial Susceptibility

Among the Streptococcus pneumoniae, 3 (15.8%) episodes were resistant to ceftriaxone, while all are sensitive to vancomycin. Details of antimicrobial susceptibility are shown in table 2.

Table 2: Species distribution with their drug resistance to common antimicrobials

Streptococci species
n (%)
Pen
Cefr
cotr
Van
Mer
streptococcus agalactiae 3 (11.1%) 0 0 0 0 0
streptococcus bovis II 1 (3.7%) 1(100%) 1(100%) 1(100%) 0 0
streptococcus milleri 2 (7.4%) 2(100%) 2(100%) 2(100%) 0 0
streptococcus mitis 1 (3.7%) 1(100%) 1(100%) 1(100%) 0 0
streptococcus pneumoniae 19 (70.4%) 6(31.6%) 3(15.8%) 3(15.8%) 0 0
streptococcus salivarius 1 (3.7%) 0 0 0 0 0

TNP: total number of patients; pen: penicillin; cotr: cotrimoxazole; cefr: ceftriaxone; van: vancomycin; Mer: meropenem; NT: not tested

Table 3: Results of spinocerebral fluid study

Cerebrospinal fluid
Value
WBCs/µL, mean±SD (range) 5424.3±8966.4 (48-38575)
Neutrophils (%) 83.8±17.3 (12-98%)
Lymphocytes (%) 14.5±17.2 (2-88%)
Protein (g/dl) 300±249.9 (60-840 g/dl)
Glucose (mmol/l) 1.7±1.7 (1-6.3 mmol/l)
Positive gram stain 24(88.8%)
Positive culture 27(100%)
Positive latex agglutination 12(44.4%)

Treatment & outcome

Antimicrobial treatment was initiated for all patients. Ceftriaxone plus vancomycin combination were used most frequently followed by meropenem. The mean duration of therapy was 18.4±13.9 (1-27 days). Central nervous system complications include brain abscess 3 (11.1%), hydrocephalus 3 (11.1%) and stroke 3 (11.1%). The in-hospital mortality was 3 (11.1%) and all cases were infants with pneumococcal meningitis.

Table 4: Distribution of streptococcal species in relation to different age groups, complications and mortality

Variables
S. agalactiae
S. bovis II
S. milleri
S. mitis
S. pneumoniae
S. salivarius
<1 2 1 0 0 3 0
1-5 0 0 0 1 2 1
6-14 0 0 0 0 3 0
15-24 0 0 1 0 2 0
25-34 0 0 0 0 3 0
35-44 0 0 1 0 2 0
45-54 0 0 0 0 3 0
≥55 1 0 0 0 1 0
Complications
Hydrocephalus 0 0 0 0 3 0
Brain abscess 0 0 2 0 1 0
Cerebral infarction 1 0 0 0 2 0
Mortality 0 0 0 0 3 0

Discussion

To our knowledge, this is the first report from Qatar and the Arab countries that describes clinical and epidemiologic features of streptococcal meningitis in different age groups, which will help to approach such cases properly and initiate appropriate empirical treatment as early as possible. Since the introduction of the seven-valent then 13-valent pneumococcal conjugated vaccines (PCVs), there was a decline in the number of reported cases of pneumococcal disease, including pneumococcal meningitis in both adults and children [11, 12]. PCV-7 was licensed in Qatar in August 2005, and PCV-13, in November 2010, nevertheless, the effectiveness of such preventive measures in Qatar and the actual disease burden have not been investigated. Similar to other reports, our study showed a reduction in the overall number of the cases of streptococcal meningitis that were reported before and after vaccine initiation (see figure 1). In addition to the implementation of vaccine programs, this decline can be attributed to several factors, including improved living conditions, easy access to healthcare facilities, the development of diagnostic facilities and improved prevention and control strategies by the Qatar health authorities against all types of meningitis including streptococcal meningitis.

The current study showed a predominance of male sex, similar to the previous two studies [1, 8], and the main affected age group was neonates under one year of age. It is interesting to note that despite the availability of the S. pneumoniae vaccine in Qatar, meningitis among 50% of this age group was due to S. pneumoniae, which is similar to reports from Northern America that show S. pneumoniae as an important cause of bacterial meningitis among neonates despite high vaccine coverage [13-15]. It is worth noting that despite the overall decrease in the number of pneumococcal cases in our study, the number of cases increased slightly in 2013 (see figure1). This may be due in part to the fact that a shift in disease causing strains towards non- vaccine serotypes may occur naturally with time in response to vaccine pressure that may eventually limit the effect of vaccination with currently available vaccines [12, 16]. Moreover, the heterogeneity of the society in Qatar due to the multinationals may affect the impact of the vaccine on the prevalence of pneumococcal meningitis.

In our study, we also found that S. agalactiae was the second most common causative pathogen of infant meningitis, which contradicts reports from European countries where S. agalactiae is the most common pathogen for neonatal meningitis [12, 17]. All of our cases of neonatal meningitis due to S. agalactiae were community acquired as they occurred one month after delivery, therefore, transmission from colonized mothers is unlikely. In many centers, the prevention of S. agalactiae meningitis is practiced by the implementation of intrapartum antibiotic prophylaxis in pregnant women with high risk for neonatal S. agalactiae disease, because there is currently no vaccine against S. agalactiae [12, 13, 17, 18].

As noted in this and other reports [1, 8], the most consistent clinical features of streptococcal meningitis were fever, headache and mental alteration, which are non-specific and can be found in other infections such as septicemia. Moreover, meningism was found in 48% of our cases, which makes diagnosis a challenge requiring high index of suspicion especially among neonates.

The susceptibility profile of streptococcal species isolates to various antimicrobials in our series showed a 100% resistance to penicillin and ceftriaxone among S. bovis II, S. milleri, S. mitis species, while the resistance to these antibiotics among S. pneumoniae was 31.6% and 15.8% respectively. This finding is in line with many reports [19-21], that showed resistance of pneumococci to penicillin and cephalosporins, and support the guidelines that recommend initiating ceftriaxone and vancomycin as an empirical therapy of choice for suspected community acquired bacterial meningitis until the results of the sensitivity are available.

The mortality among our patients was 11.1%, and all were infants less than one-year-old infected with S. pneumoniae. Our finding is similar to findings from other countries which showed acute bacterial meningitis in childhood has considerable mortality and complications.

There are several limitations to our study. Firstly, it was a retrospective study, therefore we were unable to study many variables, such as the immunization status of the patients and the complications. Secondly, Streptococcus pneumoniae serotypes were not identified thus we lost the opportunity to be sure of the phenomenon of serotype replacement. Thirdly, it was hospital- based, thus we cannot generalized our results.

In conclusion, streptococcal meningitis is a recognized clinical entity in Qatar caused by various species of streptococci, with S. pneumoniae being the most common. Despite vaccination, infants were the most affected group with high mortality from pneumococcal meningitis, suggesting that pneumococcal meningitis prevention strategies may need to be re-evaluated in this country.

References

  1. Lu CH, Chang WN, Chang Streptococcal meningitis in adults: therapeutic outcomes and prognostic factors. Clin Neurol Neurosurg. 2001; 103(3):137-42.
  2. Khan FY. Streptococcus agalactiae Meningitis in Adult Patient: A Case Report and Literature Review. Case Rep Infect Dis. 2016; 2016:6183602.
  3. Smith AH, Sra HK, Bawa S, Stevens Streptococcus bovis meningitis and hemorrhoids. J Clin Microbiol. 2010; 48(7):2654–2655.
  4. Padhi S, Mahapatra A, Pattnaik D, Chayani N, Mishra S, Mahapatra A. Bacterial meningitis due to Streptococcus milleri. Indian J Med Microbiol. 2004; 22:130.
  5. Kutlu SS, Sacar S, Cevahir N, Turgut H. Community- acquired Streptococcus mitis meningitis: a case report. Int J Infect Dis. 2008; 12(6):e107-9.
  6. Wilson M, Martin R, Walk ST, et al. Clinical and laboratory features of Streptococcus salivarius meningitis: a case report and literature review. Clin Med Res. 2012; 10(1):15–25. doi:10.3121/cmr.2011.1001
  7. Khan FY, Abu-Khattab M, Almaslamani EA, et al. Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013. Biomed Res Int. 2017; 2017:2975610. doi:10.1155/2017/2975610
  8. Cabello C, Viladrich PF, Corredoira J, Verdaguer R, Ariza J, Gudiol F. Streptococcal meningitis in adult patients: current epidemiology and clinical spectrum. Clin Infect Dis. 1999; 28:1104–8.
  9. Durand ML, Calderwood SB, Weber DJ. Acute bacterial meningitis in adults: a review of 493 episodes. The New England Journal of Medicine. 1993; 328(1):21–28. doi: 1056/NEJM199301073280104
  10. Sigurdardóttir B, Björnsson ÓM, Jónsdóttir KE, Erlendsdóttir H, Gudmundsson Acute bacterial meningitis in adults: a 20-year overview. Archives of Internal Medicine. 1997; 157(4):425–430. doi:10.1001/archinte.199 7.00440250077009
  11. Ouldali N, Levy C, Varon E, Bonacorsi S, Béchet S, Cohen R, et al. Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis. 2018; 18(9):983-991. doi: 1016/S1473-3099(18)30349-9.
  12. Van Ettekoven CN, Van de Beek D, Brouwer MC. Update on community-acquired bacterial meningitis: guidance and challenges. Clin Microbiol Infect. 2017; 23(9):601-606. doi: 1016/j.cmi.2017.04.019.
  13. Oordt-Speets AM, Bolijn R, Van Hoorn RC, Bhavsar A, Kyaw MH. Global etiology of bacterial meningitis: A systematic review and meta-analysis. PLoS One. 2018; 13(6):e0198772. doi:10.1371/journal.pone.0198772
  14. Castelblanco RL, Lee M, Hasbun R. Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study. The Lancet Infectious diseases. 2014; 14(9):813-9. https://doi.org/10.1016/S1473- 3099(14)70805-9
  15. Gounder PP, Zulz T, Desai S, Stenz F, Rudolph K, Tsang R, et al. Epidemiology of bacterial meningitis in the North American Arctic, 2000±2010. The Journal of infection. 2015; 71(2):179-87. https://doi.org/10.1016/j.jinf.2015.04.0 01
  16. Elshafie S, Taj-Aldeen SJ. Emerging resistant serotypes of invasive Streptococcus pneumoniae. Infect Drug Resist. 2016; 9:153–160. doi:10.2147/IDR.S102410
  17. Brimil N, Barthell  E, Heindrichs  U, Kuhn  M, Lütticken R, Spellerberg B. Epidemiology of Streptococcus agalactiae colonization in Germany. Int J Med Microbiol. 2006; 296(1):39-44.
  18. Bekker V, Bijlsma MW, Van de Beek D, Kuijpers TW, Van der Ende A. Incidence of invasive group B streptococcal disease and pathogen genotype distribution in newborn babies in the Netherlands over 25 years: a nationwide surveillance study. Lancet Infect Dis. 2014; 14:1083e9.
  19. Dash N, Ameen AS, Sheek-Hussein MM, Smego RA Jr. Epidemiology of meningitis in Al-Ain, United Arab Emirates, 2000-2005. Int J Infect Dis. 2007; 11(4):309-12.
  20. Quagliarello VJ, Scheld WM. Treatment of bacterial N Engl J Med. 1997; 336:708-16.
  21. Weisfelt M, de Gans J, Van der Poll T, Van de Beek D. Pneumococcal meningitis in adults: new approaches to management and Lancet Neurol. 2006; 5:332-42.